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John P Dunbar - One of the best experts on this subject based on the ideXlab platform.

  • Synanthropic spiders, including the global invasive noble false widow Steatoda nobilis, are reservoirs for medically important and antibiotic resistant bacteria
    Scientific Reports, 2020
    Co-Authors: John P Dunbar, Sam Afoullouss, Michel M Dugon, Neyaz A. Khan, Cathy L. Abberton, Pearce Brosnan, Jennifer Murphy, Vincent O’flaherty, Aoife Boyd
    Abstract:

    The false widow spider Steatoda nobilis is associated with bites which develop bacterial infections that are sometimes unresponsive to antibiotics. These could be secondary infections derived from opportunistic bacteria on the skin or infections directly vectored by the spider. In this study, we investigated whether it is plausible for S. nobilis and other synanthropic European spiders to vector bacteria during a bite, by seeking to identify bacteria with pathogenic potential on the spiders. 11 genera of bacteria were identified through 16S rRNA sequencing from the body surfaces and chelicerae of S. nobilis , and two native spiders: Amaurobius similis and Eratigena atrica . Out of 22 bacterial species isolated from S. nobilis , 12 were related to human pathogenicity among which Staphylococcus epidermidis , Kluyvera intermedia , Rothia mucilaginosa and Pseudomonas putida are recognized as class 2 pathogens. The isolates varied in their antibiotic susceptibility: Pseudomonas putida, Staphylococcus capitis and Staphylococcus edaphicus showed the highest extent of resistance, to three antibiotics in total. On the other hand, all bacteria recovered from S . nobilis were susceptible to ciprofloxacin. Our study demonstrates that S. nobilis does carry opportunistic pathogenic bacteria on its body surfaces and chelicerae. Therefore, some post-bite infections could be the result of vector-borne bacterial zoonoses that may be antibiotic resistant.

  • Venomics Approach Reveals a High Proportion of Lactrodectus-Like Toxins in the Venom of the Noble False Widow Spider Steatoda nobilis.
    Toxins, 2020
    Co-Authors: John P Dunbar, Ronan Sulpice, Michel M Dugon, Antoine Fort, Damien Redureau, Loïc Quinton
    Abstract:

    The noble false widow spider Steatoda nobilis originates from the Macaronesian archipelago and has expanded its range globally. Outside of its natural range, it may have a negative impact on native wildlife, and in temperate regions it lives in synanthropic environments where it frequently encounters humans, subsequently leading to envenomations. S. nobilis is the only medically significant spider in Ireland and the UK, and envenomations have resulted in local and systemic neurotoxic symptoms similar to true black widows (genus Latrodectus). S. nobilis is a sister group to Latrodectus which possesses the highly potent neurotoxins called α-latrotoxins that can induce neuromuscular paralysis and is responsible for human fatalities. However, and despite this close relationship, the venom composition of S. nobilis has never been investigated. In this context, a combination of transcriptomic and proteomic cutting-edge approaches has been used to deeply characterise S. nobilis venom. Mining of transcriptome data for the peptides identified by proteomics revealed 240 annotated sequences, of which 118 are related to toxins, 37 as enzymes, 43 as proteins involved in various biological functions, and 42 proteins without any identified function to date. Among the toxins, the most represented in numbers are α-latrotoxins (61), δ-latroinsectotoxins (44) and latrodectins (6), all of which were first characterised from black widow venoms. Transcriptomics alone provided a similar representation to proteomics, thus demonstrating that our approach is highly sensitive and accurate. More precisely, a relative quantification approach revealed that latrodectins are the most concentrated toxin (28%), followed by α-latrotoxins (11%), δ-latroinsectotoxins (11%) and α-latrocrustotoxins (11%). Approximately two-thirds of the venom is composed of Latrodectus-like toxins. Such toxins are highly potent towards the nervous system of vertebrates and likely responsible for the array of symptoms occurring after envenomation by black widows and false widows. Thus, caution should be taken in dismissing S. nobilis as harmless. This work paves the way towards a better understanding of the competitiveness of S. nobilis and its potential medical importance.

  • envenomation by the noble false widow spider Steatoda nobilis thorell 1875 five new cases of steatodism from ireland and great britain
    Clinical Toxicology, 2018
    Co-Authors: John P Dunbar, Sam Afoullouss, Ronan Sulpice, Michel M Dugon
    Abstract:

    Objective: The noble false widow Steatoda nobilis is the only medically significant spider known to occur in the British Isles and Ireland, with a single case of steatodism ever reported from Great...

  • Envenomation by the noble false widow spider Steatoda nobilis (Thorell, 1875) – five new cases of steatodism from Ireland and Great Britain
    Clinical toxicology (Philadelphia Pa.), 2017
    Co-Authors: John P Dunbar, Sam Afoullouss, Ronan Sulpice, Michel M Dugon
    Abstract:

    AbstractObjective: The noble false widow Steatoda nobilis is the only medically significant spider known to occur in the British Isles and Ireland, with a single case of steatodism ever reported from Great Britain. We present here five new cases of envenomations by S. nobilis, three from Ireland and two from Great Britain and describe symptoms not previously reported for the genus Steatoda.Case presentation: Four adult males and one adult female with confirmed S. nobilis bites reported their symptoms to the authors. General practitioner chart was obtained for case #3. In all five cases, envenomations were immediately followed by a sharp and prolonged onset of pain, mild to extensive erythema and localised to extensive swelling around the bite site. Additional symptoms include moderate to intense pruritus, vasodilation of the capillaries around the bite site and a possible minor necrotic wound.Conclusion: In all cases, symptoms subsided within 48–72 h and no further complications were reported. Envenomatio...

Michel M Dugon - One of the best experts on this subject based on the ideXlab platform.

  • Synanthropic spiders, including the global invasive noble false widow Steatoda nobilis, are reservoirs for medically important and antibiotic resistant bacteria
    Scientific Reports, 2020
    Co-Authors: John P Dunbar, Sam Afoullouss, Michel M Dugon, Neyaz A. Khan, Cathy L. Abberton, Pearce Brosnan, Jennifer Murphy, Vincent O’flaherty, Aoife Boyd
    Abstract:

    The false widow spider Steatoda nobilis is associated with bites which develop bacterial infections that are sometimes unresponsive to antibiotics. These could be secondary infections derived from opportunistic bacteria on the skin or infections directly vectored by the spider. In this study, we investigated whether it is plausible for S. nobilis and other synanthropic European spiders to vector bacteria during a bite, by seeking to identify bacteria with pathogenic potential on the spiders. 11 genera of bacteria were identified through 16S rRNA sequencing from the body surfaces and chelicerae of S. nobilis , and two native spiders: Amaurobius similis and Eratigena atrica . Out of 22 bacterial species isolated from S. nobilis , 12 were related to human pathogenicity among which Staphylococcus epidermidis , Kluyvera intermedia , Rothia mucilaginosa and Pseudomonas putida are recognized as class 2 pathogens. The isolates varied in their antibiotic susceptibility: Pseudomonas putida, Staphylococcus capitis and Staphylococcus edaphicus showed the highest extent of resistance, to three antibiotics in total. On the other hand, all bacteria recovered from S . nobilis were susceptible to ciprofloxacin. Our study demonstrates that S. nobilis does carry opportunistic pathogenic bacteria on its body surfaces and chelicerae. Therefore, some post-bite infections could be the result of vector-borne bacterial zoonoses that may be antibiotic resistant.

  • Venomics Approach Reveals a High Proportion of Lactrodectus-Like Toxins in the Venom of the Noble False Widow Spider Steatoda nobilis.
    Toxins, 2020
    Co-Authors: John P Dunbar, Ronan Sulpice, Michel M Dugon, Antoine Fort, Damien Redureau, Loïc Quinton
    Abstract:

    The noble false widow spider Steatoda nobilis originates from the Macaronesian archipelago and has expanded its range globally. Outside of its natural range, it may have a negative impact on native wildlife, and in temperate regions it lives in synanthropic environments where it frequently encounters humans, subsequently leading to envenomations. S. nobilis is the only medically significant spider in Ireland and the UK, and envenomations have resulted in local and systemic neurotoxic symptoms similar to true black widows (genus Latrodectus). S. nobilis is a sister group to Latrodectus which possesses the highly potent neurotoxins called α-latrotoxins that can induce neuromuscular paralysis and is responsible for human fatalities. However, and despite this close relationship, the venom composition of S. nobilis has never been investigated. In this context, a combination of transcriptomic and proteomic cutting-edge approaches has been used to deeply characterise S. nobilis venom. Mining of transcriptome data for the peptides identified by proteomics revealed 240 annotated sequences, of which 118 are related to toxins, 37 as enzymes, 43 as proteins involved in various biological functions, and 42 proteins without any identified function to date. Among the toxins, the most represented in numbers are α-latrotoxins (61), δ-latroinsectotoxins (44) and latrodectins (6), all of which were first characterised from black widow venoms. Transcriptomics alone provided a similar representation to proteomics, thus demonstrating that our approach is highly sensitive and accurate. More precisely, a relative quantification approach revealed that latrodectins are the most concentrated toxin (28%), followed by α-latrotoxins (11%), δ-latroinsectotoxins (11%) and α-latrocrustotoxins (11%). Approximately two-thirds of the venom is composed of Latrodectus-like toxins. Such toxins are highly potent towards the nervous system of vertebrates and likely responsible for the array of symptoms occurring after envenomation by black widows and false widows. Thus, caution should be taken in dismissing S. nobilis as harmless. This work paves the way towards a better understanding of the competitiveness of S. nobilis and its potential medical importance.

  • envenomation by the noble false widow spider Steatoda nobilis thorell 1875 five new cases of steatodism from ireland and great britain
    Clinical Toxicology, 2018
    Co-Authors: John P Dunbar, Sam Afoullouss, Ronan Sulpice, Michel M Dugon
    Abstract:

    Objective: The noble false widow Steatoda nobilis is the only medically significant spider known to occur in the British Isles and Ireland, with a single case of steatodism ever reported from Great...

  • Envenomation by the noble false widow spider Steatoda nobilis (Thorell, 1875) – five new cases of steatodism from Ireland and Great Britain
    Clinical toxicology (Philadelphia Pa.), 2017
    Co-Authors: John P Dunbar, Sam Afoullouss, Ronan Sulpice, Michel M Dugon
    Abstract:

    AbstractObjective: The noble false widow Steatoda nobilis is the only medically significant spider known to occur in the British Isles and Ireland, with a single case of steatodism ever reported from Great Britain. We present here five new cases of envenomations by S. nobilis, three from Ireland and two from Great Britain and describe symptoms not previously reported for the genus Steatoda.Case presentation: Four adult males and one adult female with confirmed S. nobilis bites reported their symptoms to the authors. General practitioner chart was obtained for case #3. In all five cases, envenomations were immediately followed by a sharp and prolonged onset of pain, mild to extensive erythema and localised to extensive swelling around the bite site. Additional symptoms include moderate to intense pruritus, vasodilation of the capillaries around the bite site and a possible minor necrotic wound.Conclusion: In all cases, symptoms subsided within 48–72 h and no further complications were reported. Envenomatio...

Grażyna Wilczek - One of the best experts on this subject based on the ideXlab platform.

  • Effect of long-term cadmium and copper intoxication on the efficiency of ampullate silk glands in false black widow Steatoda grossa (Theridiidae) spiders
    Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 2019
    Co-Authors: Grażyna Wilczek, Teresa Kowalska, Mieczysław Sajewicz, Kamila Wiśniewska, Kinga Surmiak, Beata Wawszczak, Piotr Sindera, Elżbieta Szulińska
    Abstract:

    The aim of the study was to compare cellular effects of xenobiotic cadmium and biogenic copper in ampullate silk glands of false black widow Steatoda grossa spider after long-term exposure via ingestion under laboratory conditions. Both the level of selected detoxification parameters (glutathione S-transferase, catalase, and the level of total antioxidant capacity) and degree of genotoxic changes (comet assay) were determined in the silk glands. Additionally the contents of selected amino acids (L-Ala, L-Pro, L-His, L-Phe, DL-Ile, and DL-Asn) in the hunting webs produced by spiders of this species were assessed. The ability of S. grossa females to accumulate cadmium was higher than that for copper. Long-term exposure of spiders to copper did not change the level of detoxification parameters, and the level of DNA damage in the cells of ampullate silk glands was also low. Cadmium had a stronger prooxidative and genotoxic effect than copper in the cells of the analyzed silk glands. However, regardless of the type of metal used, no significant changes in the level of amino acids in silk were found. The obtained results confirmed the effectiveness of metal neutralization mechanisms in the body of the studied spider species, which results in the protection of the function of ampullate silk glands.

  • Evaluation of selected biological properties of the hunting web spider (Steatoda grossa, Theridiidae) in the aspect of short- and long-term exposure to cadmium
    The Science of the total environment, 2018
    Co-Authors: Grażyna Wilczek, Jagna Karcz, Magdalena Rost-roszkowska, Andrzej Kędziorski, Piotr Wilczek, Magdalena Skowronek, Kamila Wiśniewska, Florentyna Kaszuba, Kinga Surmiak
    Abstract:

    The study aimed at comparing the effects of short- and long-term exposure of Steatoda grossa female spiders to cadmium on the web's architecture, its energy content, and ultrastructure of ampullate glands. Simple food chain model (medium with 0.25 mM CdCl2 → Drosophila hydei flies → spider (for 4 weeks or 12 months) was used for the exposure. Analysis of Cd content provided evidence that silk fibers of the web are well protected against its incorporation irrespectively of the exposure period. Long-term exposure to cadmium resulted in the occurrence of numerous autophagosomes with degenerated organelles as well as apoptotic and necrotic cells in the ampullate glands. Concurrently, the individual silk fibers building double and multiple combination complexes were significantly thinner than in the control threads. Moreover, exposed spiders spun net with smaller mean calorific value than did the control individuals. Hence, evaluation of both the diameter of silk fibers and calorific value of the web can serve as biomarkers of the effects caused by exposure of these predators to cadmium.

  • Application of Thin-Layer Chromatography to Ecotoxicological Study with the Steatoda grossa Spider Web
    JPC – Journal of Planar Chromatography – Modern TLC, 2018
    Co-Authors: Magda Michalik, Maja Surmacka, Monika Stalmach, Grażyna Wilczek, Teresa Kowalska, Mieczysław Sajewicz
    Abstract:

    In the search for biocompatible and biodegradable natural products, much attention of biomedical engineering experts is attracted by spider web (also known as spider silk). Apart from its biocompatibility and biodegradability, the key feature of spider silk is its extraordinary tensile strength, in many cases surpassing that of steel or Kevlar. Although spider silk (unlike that produced by the silk worms) cannot be produced on a mass scale, it can serve as a structural template to be imitated by the organic chemists. The main building blocks of the spider silk proteins, spidroins, are the non-polar and hydrophobic α-amino acids, and the most abundant among them are l -glycine and l -alanine. In this study, we investigated an impact of cadmium chloride (CdCl_2) as a toxic anthropogenic environmental pollutant on quantitative levels of glycine, alanine, histidine, and phenylalanine in spider silk produced by the female Steatoda grossa spider kept for the periods of 4 weeks and 12 months, respectively, on cadmium-enriched diet. Quantification of this dietary effect was carried out with the aid of thin-layer chromatography, using silica gel as the stationary phase and 2-butanol- acetone-glacial acetic acid—water, 7:7:2:4 (v/v) as the mobile phase. First, the calibration curves were established for the standards of the four α-amino acids of interest (for glycine, y = 369.8 x + 175.9 [ r = 0.990]; for alanine, y = 725.8 x + 175.3 [ r = 0.985]; for histidine, y = 117.7 x + 272.4 [ r = 0.990]; for phenylalanine, y = 198.0 x + 143.0 [ r = 0.995]). Then, these four α-amino acids were quantified in the spider webs of the control spiders and those held on the cadmium- enriched diet. With all four α-amino acids of interest, their respective levels were in the range of 100 to 200 μg α-amino acid per 1 mg spider silk. The observed differences between the α-amino acid contents in the control web silk and in those produced by the cadmium fed spiders were rather insignificant and, in most cases, within the range of the experimental error. Thus, a general conclusion was drawn as to an apparent resistance of the S. grossa spider species to the environmental cadmium pollution.

  • Application of thin-layer chromatography to ecotoxicological study with the Steatoda grossa spider web
    JPC - Journal of Planar Chromatography - Modern TLC, 2018
    Co-Authors: Magda Michalik, Maja Surmacka, Monika Stalmach, Grażyna Wilczek, Teresa Kowalska, Mieczysław Sajewicz
    Abstract:

    In the search for biocompatible and biodegradable natural products, much attention of biomedical engineering experts is attracted by spider web (also known as spider silk). Apart from its biocompatibility and biodegradability, the key feature of spider silk is its extraordinary tensile strength, in many cases surpassing that of steel or Kevlar. Although spider silk (unlike that produced by the silk worms) cannot be produced on a mass scale, it can serve as a structural template to be imitated by the organic chemists. The main building blocks of the spider silk proteins, spidroins, are the non-polar and hydrophobic α-amino acids, and the most abundant among them are l-glycine and l-alanine. In this study, we investigated an impact of cadmium chloride (CdCl2) as a toxic anthropogenic environmental pollutant on quantitative levels of glycine, alanine, histidine, and phenylalanine in spider silk produced by the female Steatoda grossa spider kept for the periods of 4 weeks and 12 months, respectively, on cadmi...

  • Effects of food contaminated with cadmium and copper on hemocytes of Steatoda grossa (Araneae: Theridiidae).
    Ecotoxicology and environmental safety, 2017
    Co-Authors: Grażyna Wilczek, Monika Stalmach, Magdalena Rost-roszkowska, Piotr Wilczek, Magdalena Skowronek, Kamila Wiśniewska, Bartosz Kozina, Florentyna Kaszuba
    Abstract:

    The aim of this study was to evaluate the metabolic condition of Steatoda grossa (Theridiidae) spider, from their hemocytes, after a short-term (four-week) exposure to cadmium and copper in sublethal doses by administering them into the body of the preys. The ultrastructure of the dominant types of hemocytes, such as granulocytes, plasmatocytes and prohemocytes, was evaluated using transmission electron microscope (TEM). Quantitative evaluation of apoptotic and necrotic cells, as well as the ones with depolarized mitochondria in hemolymph, was performed using flow cytometry, while ATP concentration and ADP/ATP ratio in hemocytes were measured by luminescent methods. Cadmium, unlike copper, demonstrated proapoptotic and pronecrotic activity. Low ATP levels and high ADP/ATP ratio in hemocytes indicate a disturbance in the energy metabolism of cells and may account for their qualitative and quantitative degenerative changes. The intensification of death processes in hemocytes after an exposure to cadmium-contaminated food may impair the ability of these cells to fight infectious diseases. Copper at the applied dosage was safe for the spiders without causing visible changes in the hemocyte ultrastructure and in the level of analyzed cell death indices.

Loïc Quinton - One of the best experts on this subject based on the ideXlab platform.

  • Venomics Approach Reveals a High Proportion of Lactrodectus-Like Toxins in the Venom of the Noble False Widow Spider Steatoda nobilis.
    Toxins, 2020
    Co-Authors: John P Dunbar, Ronan Sulpice, Michel M Dugon, Antoine Fort, Damien Redureau, Loïc Quinton
    Abstract:

    The noble false widow spider Steatoda nobilis originates from the Macaronesian archipelago and has expanded its range globally. Outside of its natural range, it may have a negative impact on native wildlife, and in temperate regions it lives in synanthropic environments where it frequently encounters humans, subsequently leading to envenomations. S. nobilis is the only medically significant spider in Ireland and the UK, and envenomations have resulted in local and systemic neurotoxic symptoms similar to true black widows (genus Latrodectus). S. nobilis is a sister group to Latrodectus which possesses the highly potent neurotoxins called α-latrotoxins that can induce neuromuscular paralysis and is responsible for human fatalities. However, and despite this close relationship, the venom composition of S. nobilis has never been investigated. In this context, a combination of transcriptomic and proteomic cutting-edge approaches has been used to deeply characterise S. nobilis venom. Mining of transcriptome data for the peptides identified by proteomics revealed 240 annotated sequences, of which 118 are related to toxins, 37 as enzymes, 43 as proteins involved in various biological functions, and 42 proteins without any identified function to date. Among the toxins, the most represented in numbers are α-latrotoxins (61), δ-latroinsectotoxins (44) and latrodectins (6), all of which were first characterised from black widow venoms. Transcriptomics alone provided a similar representation to proteomics, thus demonstrating that our approach is highly sensitive and accurate. More precisely, a relative quantification approach revealed that latrodectins are the most concentrated toxin (28%), followed by α-latrotoxins (11%), δ-latroinsectotoxins (11%) and α-latrocrustotoxins (11%). Approximately two-thirds of the venom is composed of Latrodectus-like toxins. Such toxins are highly potent towards the nervous system of vertebrates and likely responsible for the array of symptoms occurring after envenomation by black widows and false widows. Thus, caution should be taken in dismissing S. nobilis as harmless. This work paves the way towards a better understanding of the competitiveness of S. nobilis and its potential medical importance.

Ronan Sulpice - One of the best experts on this subject based on the ideXlab platform.

  • Venomics Approach Reveals a High Proportion of Lactrodectus-Like Toxins in the Venom of the Noble False Widow Spider Steatoda nobilis.
    Toxins, 2020
    Co-Authors: John P Dunbar, Ronan Sulpice, Michel M Dugon, Antoine Fort, Damien Redureau, Loïc Quinton
    Abstract:

    The noble false widow spider Steatoda nobilis originates from the Macaronesian archipelago and has expanded its range globally. Outside of its natural range, it may have a negative impact on native wildlife, and in temperate regions it lives in synanthropic environments where it frequently encounters humans, subsequently leading to envenomations. S. nobilis is the only medically significant spider in Ireland and the UK, and envenomations have resulted in local and systemic neurotoxic symptoms similar to true black widows (genus Latrodectus). S. nobilis is a sister group to Latrodectus which possesses the highly potent neurotoxins called α-latrotoxins that can induce neuromuscular paralysis and is responsible for human fatalities. However, and despite this close relationship, the venom composition of S. nobilis has never been investigated. In this context, a combination of transcriptomic and proteomic cutting-edge approaches has been used to deeply characterise S. nobilis venom. Mining of transcriptome data for the peptides identified by proteomics revealed 240 annotated sequences, of which 118 are related to toxins, 37 as enzymes, 43 as proteins involved in various biological functions, and 42 proteins without any identified function to date. Among the toxins, the most represented in numbers are α-latrotoxins (61), δ-latroinsectotoxins (44) and latrodectins (6), all of which were first characterised from black widow venoms. Transcriptomics alone provided a similar representation to proteomics, thus demonstrating that our approach is highly sensitive and accurate. More precisely, a relative quantification approach revealed that latrodectins are the most concentrated toxin (28%), followed by α-latrotoxins (11%), δ-latroinsectotoxins (11%) and α-latrocrustotoxins (11%). Approximately two-thirds of the venom is composed of Latrodectus-like toxins. Such toxins are highly potent towards the nervous system of vertebrates and likely responsible for the array of symptoms occurring after envenomation by black widows and false widows. Thus, caution should be taken in dismissing S. nobilis as harmless. This work paves the way towards a better understanding of the competitiveness of S. nobilis and its potential medical importance.

  • envenomation by the noble false widow spider Steatoda nobilis thorell 1875 five new cases of steatodism from ireland and great britain
    Clinical Toxicology, 2018
    Co-Authors: John P Dunbar, Sam Afoullouss, Ronan Sulpice, Michel M Dugon
    Abstract:

    Objective: The noble false widow Steatoda nobilis is the only medically significant spider known to occur in the British Isles and Ireland, with a single case of steatodism ever reported from Great...

  • Envenomation by the noble false widow spider Steatoda nobilis (Thorell, 1875) – five new cases of steatodism from Ireland and Great Britain
    Clinical toxicology (Philadelphia Pa.), 2017
    Co-Authors: John P Dunbar, Sam Afoullouss, Ronan Sulpice, Michel M Dugon
    Abstract:

    AbstractObjective: The noble false widow Steatoda nobilis is the only medically significant spider known to occur in the British Isles and Ireland, with a single case of steatodism ever reported from Great Britain. We present here five new cases of envenomations by S. nobilis, three from Ireland and two from Great Britain and describe symptoms not previously reported for the genus Steatoda.Case presentation: Four adult males and one adult female with confirmed S. nobilis bites reported their symptoms to the authors. General practitioner chart was obtained for case #3. In all five cases, envenomations were immediately followed by a sharp and prolonged onset of pain, mild to extensive erythema and localised to extensive swelling around the bite site. Additional symptoms include moderate to intense pruritus, vasodilation of the capillaries around the bite site and a possible minor necrotic wound.Conclusion: In all cases, symptoms subsided within 48–72 h and no further complications were reported. Envenomatio...