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Caterpillars of the Neotropical genus Lonomia (Lepidoptera: Saturniidae) are responsible for some fatal envenomation of humans in South America inducing hemostatic disturbances in patients upon skin contact with the caterpillars' spines. Currently, only two species have been reported to cause hemorrhagic syndromes in humans: Lonomia achelous and Lonomia obliqua. However, species identifications have remained largely unchallenged despite improved knowledge of venom diversity and growing evidence that the taxonomy used over past decades misrepresents and underestimates species diversity. Here, we revisit the taxonomic diversity and distribution of Lonomia species using the most extensive dataset assembled to date, combining DNA barcodes, morphological comparisons, and geographical information. Considering new evidence for seven undescribed species as well as three newly proposed nomenclatural changes, our integrative approach leads to the recognition of 60 species, of which seven are known or strongly suspected to cause severe envenomation in humans. From a newly compiled synthesis of epidemiological data, we also examine the consequences of our results for understanding Lonomia envenomation risks and call for further investigations of other species' venom activities. This is required and necessary to improve alertness in areas at risk, and to define adequate treatment strategies for envenomed patients, including performing species identification and assessing the efficacy of anti-Lonomia serums against a broader diversity of species., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 González et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Linear cationic venom peptides are antimicrobial peptides (AMPs) that exert their effects by damaging cell membranes. These peptides can be highly specific, and for some, a significant therapeutic value was proposed, in particular for treatment of bacterial infections. A prolific source of novel AMPs are arthropod venoms, especially those of hitherto neglected groups such as pseudoscorpions. In this study, we describe for the first time pharmacological effects of AMPs discovered in pseudoscorpion venom. We examined the antimicrobial, cytotoxic, and insecticidal activity of full-length Checacin1, a major component of the Chelifer cancroides venom, and three truncated forms of this peptide. The antimicrobial tests revealed a potent inhibitory activity of Checacin1 against several bacteria and fungi, including methicillin resistant Staphylococcus aureus (MRSA) and even Gram-negative pathogens. All peptides reduced survival rates of aphids, with Checacin1 and the C-terminally truncated Checacin1 1-21 exhibiting effects comparable to Spinosad, a commercially used pesticide. Cytotoxic effects on mammalian cells were observed mainly for the full-length Checacin1. All tested peptides might be potential candidates for developing lead structures for aphid pest treatment. However, as these peptides were not yet tested on other insects, aphid specificity has not been proven. The N- and C-terminal fragments of Checacin1 are less potent against aphids but exhibit no cytotoxicity on mammalian cells at the tested concentration of 100 µM.

The significant incidence of deforestation in South America culminates in the contact of humans with typical forests species. Among these species, one may highlight Lonomia obliqua caterpillar, which, when touched by humans, can poison them through their bristles. Therefore, better acknowledging the mechanisms involved in envenomation caused by Lonomia obliqua caterpillar bristle extract (LOCBE) may contribute to further treatments. Recently, we demonstrated that LOCBE induces a pro-inflammatory profile in endothelial cells; thus, we decided to investigate the effects of LOCBE on human polymorphonuclear neutrophils (PMN), which are the first leukocytes that migrate to the inflammatory focus. Our results showed that treatment with LOCBE induced PMN chemotaxis together with alterations in actin cytoskeleton and focal adhesion kinase (FAK) activation, favoring migration. Concurrently, LOCBE induced PMN adhesion to matrix proteins, such as collagen IV, fibronectin, and fibrinogen. Moreover, we observed that LOCBE attenuated PMN apoptosis and increased reactive oxygen species (ROS) production together with nuclear factor kB (NF-κB) activation-a redox-sensitive transcription factor-as well as interleukin (IL)-1β and IL-8 release. We call attention to the ROS-dependent effect of LOCBE on increased cell migration once an antioxidant treatment reverted it. In summary, we report that LOCBE activates PMN, inducing pro-inflammatory responses modulated by ROS.

Among the Chilopoda class of centipede, the Cryptops genus is one of the most associated with envenomation in humans in the metropolitan region of the state of São Paulo. To date, there is no study in the literature about the toxins present in its venom. Thus, in this work, a transcriptomic characterization of the Cryptops iheringi venom gland, as well as a proteomic analysis of its venom, were performed to obtain a toxin profile of this species. These methods indicated that 57.9% of the sequences showed to be putative toxins unknown in public databases; among them, we pointed out a novel putative toxin named Cryptoxin-1. The recombinant form of this new toxin was able to promote edema in mice footpads with massive neutrophils infiltration, linking this toxin to envenomation symptoms observed in accidents with humans. Our findings may elucidate the role of this toxin in the venom, as well as the possibility to explore other proteins found in this work.

As a tribute to Butantan Institute in its 120th anniversary, this review describes some of the scientific research efforts carried out in the study of Lonomia envenoming in Brazil, a country where accidents with caterpillars reach over 42,000 individuals per year (especially in South and Southeast Brazil). Thus, the promising data regarding the studies with Lonomia 's toxins contributed to the creation of new research centers specialized in toxinology based at Butantan Institute, as well as to the production of the antilonomic serum (ALS), actions which are in line with the Butantan Institute mission "to research, develop, manufacture, and provide products and services for the health of the population". In addition, the study of the components of the Lonomia obliqua bristle extract led to the discovery of new molecules with peculiar properties, opening a field of knowledge that could lead to the development and innovation of new drugs aimed at cell regeneration and inflammatory diseases.

Background: Envenomation by the South American Lonomia saturniid caterpillars, named lonomism, constitutes an emerging and somewhat neglected public health issue in Argentina and neighboring countries. Considering that there is an intricate relationship between environment and human health in such cases, this study aimed to analyze the eco-epidemiological profile of 40 accidents and 33 occurrences of Lonomia spp. in Misiones (Argentina) between January 2014 and May 2020., Methodology/principal Findings: We described the eco-epidemiological variables and characterized the abiotic scenario of such cases. Additionally, we obtained a density map that shows the punctual intensity of Lonomia records throughout Misiones. Most of the accidents occurred in the Department of Guaraní and involved male victims younger than 20 years old. The accidental/occasional occurrence of Lonomia spp. (considering both adult and caterpillar stages together) was significantly higher in the rural area, whereas only adult specimens were found in urban areas. We determined that the presence of this insect in Misiones is positively related to higher temperatures and solar radiation, and larger precipitation and evapotranspiration throughout the year., Conclusion/significance: This study represents an initial step towards the global understanding of lonomism as a public health problem in Argentina. It provides a map of the risk level for this envenomation in Misiones, which could help authorities address public health policy efforts to implement sustainable strategies for prevention and response to this threat in Northeastern Argentina and neighboring regions., Competing Interests: The authors have declared that no competing interests exist.

Envenomation caused by contact with Lonomia obliqua bristles is characterized by pain, an intense systemic proinflammatory reaction and disturbances in the coagulation cascade that can cause severe clinical manifestations and death. However, the role of immune system components in these effects is still poorly understood. In this study, we evaluated the cytotoxic effect of L. obliqua venom on THP-1-derived macrophages and its ability to modulate inflammatory markers, as well as the cytokine and chemokine release profile. Our results show that L. obliqua venom is able to directly exert a potent pro-inflammatory reaction in macrophages, characterized by the activation of the NF-κB transcription factor pathway, the expression of CD80 and CD83, and the release of pro-inflammatory mediators such as TNF-α, IL-1β, IL-6, IL-8 and CXCL10. These results suggest that macrophages can play an important role during the orchestration of the inflammatory response present in envenomation caused by Lonomia obliqua caterpillars., Competing Interests: The authors declare that they have no conflict of interest related to this study and the publication of this manuscript.

Velvet ants (Hymenoptera: Mutillidae) are a family of solitary parasitoid wasps that are renowned for their painful stings. We explored the chemistry underlying the stings of mutillid wasps of the genus Dasymutilla Ashmead. Detailed analyses of the venom composition of five species revealed that they are composed primarily of peptides. We found that two kinds of mutillid venom peptide appear to be primarily responsible for the painful effects of envenomation. These same peptides also have defensive utility against invertebrates, since they were able to incapacitate and kill honeybees. Both act directly on cell membranes where they directly increase ion conductivity. The defensive venom peptides of Dasymutilla bear a striking similarity, in structure and mode of action, to those of the ant Myrmecia gulosa (Fabricius), suggesting either retention of ancestral toxins, or convergence driven by similar life histories and defensive selection pressures. Finally, we propose that other highly expressed Dasymutilla venom peptides may play a role in parasitisation, possible in delay or arrest of host development. This study represents the first detailed account of the composition and function of the venoms of the Mutillidae.

Chagas disease is an important disease affecting millions of patients in the New World and is caused by a protozoan transmitted by haematophagous kissing bugs. It can be treated with drugs during the early acute phase; however, effective therapy against the chronic form of Chagas disease has yet to be discovered and developed. We herein tested the activity of solenopsin alkaloids extracted from two species of fire ants against the protozoan parasite Trypanosoma cruzi, the aetiologic agent of Chagas disease. Although IC 50 determinations showed that solenopsins are more toxic to the parasite than benznidazole, the drug of choice for Chagas disease treatment, the ant alkaloids presented a lower selectivity index. As a result of exposure to the alkaloids, the parasites became swollen and rounded in shape, with hypertrophied contractile vacuoles and intense cytoplasmic vacuolization, possibly resulting in osmotic stress; no accumulation of multiple kinetoplasts and/or nuclei was detected. Overexpressing phosphatidylinositol 3-kinase-an enzyme essential for osmoregulation that is a known target of solenopsins in mammalian cells-did not prevent swelling and vacuolization, nor did it counteract the toxic effects of alkaloids on the parasites. Additional experimental results suggested that solenopsins induced a type of autophagic and programmed cell death in T. cruzi. Solenopsins also reduced the intracellular proliferation of T. cruzi amastigotes in infected macrophages in a concentration-dependent manner and demonstrated activity against Trypanosoma brucei rhodesiense bloodstream forms, which is another important aetiological kinetoplastid parasite. The results suggest the potential of solenopsins as novel natural drugs against neglected parasitic diseases caused by kinetoplastids.

Calcium entry is central to the functional processes in mast cells and basophils that contribute to the induction and maintenance of inflammatory responses. Mast cells and basophils express an array of calcium channels, which mediate responses to diverse stimuli triggered by small bioactive molecules, physicochemical stimuli and immunological inputs including antigens and direct immune cell interactions. These cells are also highly responsive to certain venoms (such as Hymenoptera envenomations), which cause histamine secretion, cytokine release and an array of pro-inflammatory functional responses. There are gaps in our understanding of the coupling of venom exposure to specific signaling pathways such as activation of calcium channels. In the present study, we performed a current survey of a model mast cell line selected for its pleiotropic responsiveness to multiple pro-inflammatory inputs. As a heterogenous stimulus, Hymenoptera venom activates multiple classes of conductance at the population level but tend to lead to the measurement of only one type of conductance per cell, despite the cell co-expressing multiple channel types. The data show that I CRAC , I ARC, and TRPV-like currents are present in the model mast cell populations and respond to venom exposure. We further assessed individual venom components, specifically secretagogues and arachidonic acid, and identified the conductances associated with these stimuli in mast cells. Single-cell calcium assays and immunofluorescence analysis show that there is heterogeneity of channel expression across the cell population, but this heterogeneity does not explain the apparent selectivity for specific channels in response to exposure to venom as a composite stimulus.

Accidental contact with caterpillar bristles causes local symptoms such as severe pain, intense heat, edema, erythema, and pruritus. However, there is little functional evidence to indicate a potential mechanism. In this study, we analyzed the biological characteristics of the crude venom from the larval stage of Latoia consocia living in South-West China. Intraplantar injection of the venom into the hind paws of mice induced severe acute pain behaviors in wild type (WT) mice; the responses were much reduced in TRPV1-deficit (TRPV1 KO) mice. The TRPV1-specific inhibitor, capsazepine, significantly attenuated the pain behaviors. Furthermore, the crude venom evoked strong calcium signals in the dorsal root ganglion (DRG) neurons of WT mice but not those of TRPV1 KO mice. Among the pain-related ion channels we tested, the crude venom only activated the TRPV1 channel. To better understand the venom components, we analyzed the transcriptome of the L. consocia sebaceous gland region. Our study suggests that TRPV1 serves as a primary nociceptor in caterpillar-induced pain and forms the foundation for elucidating the pain-producing mechanism.

Assassin bugs (Reduviidae) produce venoms that are insecticidal, and which induce pain in predators, but the composition and function of their individual venom components is poorly understood. We report findings on the venom system of the red-spotted assassin bug Platymeris rhadamanthus , a large species of African origin that is unique in propelling venom as a projectile weapon when threatened. We performed RNA sequencing experiments on venom glands (separate transcriptomes of the posterior main gland, PMG, and the anterior main gland, AMG), and proteomic experiments on venom that was either defensively propelled or collected from the proboscis in response to electrostimulation. We resolved a venom proteome comprising 166 polypeptides. Both defensively propelled venom and most venom samples collected in response to electrostimulation show a protein profile similar to the predicted secretory products of the PMG, with a smaller contribution from the AMG. Pooled venom samples induce calcium influx via membrane lysis when applied to mammalian neuronal cells, consistent with their ability to cause pain when propelled into the eyes or mucus membranes of potential predators. The same venom induces rapid paralysis and death when injected into fruit flies. These data suggest that the cytolytic, insecticidal venom used by reduviids to capture prey is also a highly effective defensive weapon when propelled at predators., Competing Interests: The authors declare no conflict of interest.

Pain is a natural bioassay for detecting and quantifying biological activities of venoms. The painfulness of stings delivered by ants, wasps, and bees can be easily measured in the field or lab using the stinging insect pain scale that rates the pain intensity from 1 to 4, with 1 being minor pain, and 4 being extreme, debilitating, excruciating pain. The painfulness of stings of 96 species of stinging insects and the lethalities of the venoms of 90 species was determined and utilized for pinpointing future directions for investigating venoms having pharmaceutically active principles that could benefit humanity. The findings suggest several under- or unexplored insect venoms worthy of future investigations, including: those that have exceedingly painful venoms, yet with extremely low lethality-tarantula hawk wasps ( Pepsis ) and velvet ants (Mutillidae); those that have extremely lethal venoms, yet induce very little pain-the ants, Daceton and Tetraponera ; and those that have venomous stings and are both painful and lethal-the ants Pogonomyrmex , Paraponera , Myrmecia , Neoponera , and the social wasps Synoeca , Agelaia , and Brachygastra . Taken together, and separately, sting pain and venom lethality point to promising directions for mining of pharmaceutically active components derived from insect venoms.

Background: Lonomia obliqua venom is nephrotoxic and acute kidney injury (AKI) is the main cause of death among envenomed victims. Mechanism underlying L. obliqua-induced AKI involves renal hypoperfusion, inflammation, tubular necrosis and loss of glomerular filtration and tubular reabsorption capacities. In the present study, we aimed to investigate the contribution of kallikrein to the hemodynamic instability, inflammation and consequent renal and vascular impairment., Methodology/principal Findings: Addition of L. obliqua venom to purified prekallikrein and human plasma in vitro or to vascular smooth muscle cells (VSMC) in culture, was able to generate kallikrein in a dose-dependent manner. Injected in rats, the venom induced AKI and increased kallikrein levels in plasma and kidney. Kallikrein inhibition by aprotinin prevented glomerular injury and the decrease in glomerular filtration rate, restoring fluid and electrolyte homeostasis. The mechanism underlying these effects was associated to lowering renal inflammation, with decrease in pro-inflammatory cytokines and matrix metalloproteinase expression, reduced tubular degeneration, and protection against oxidative stress. Supporting the key role of kallikrein, we demonstrated that aprotinin inhibited effects directly associated with vascular injury, such as the generation of intracellular reactive oxygen species (ROS) and migration of VSMC induced by L. obliqua venom or by diluted plasma obtained from envenomed rats. In addition, kallikrein inhibition also ameliorated venom-induced blood incoagulability and decreased kidney tissue factor expression., Conclusions/significance: These data indicated that kallikrein and consequently kinin release have a key role in kidney injury and vascular remodeling. Thus, blocking kallikrein may be a therapeutic alternative to control the progression of venom-induced AKI and vascular disturbances., Competing Interests: The authors have declared that no competing interests exist.

Assassin flies (Diptera: Asilidae) inject paralysing venom into insect prey during hunting, but their venoms are poorly characterised in comparison to those produced by spiders, scorpions, or hymenopteran insects. Here we investigated the composition of the venom of the giant Australian assassin fly Dolopus genitalis using a combination of insect microinjection assays, calcium imaging assays of mammalian sensory neurons, proteomics and transcriptomics. Injection of venom into blowflies ( Lucilia cuprina ) produced rapid contractile paralysis (PD 50 at 1 min = 3.1 μg per fly) followed by death, and also caused immediate activation of mouse dorsal root ganglion neurons (at 50 ng/μL). These results are consistent with venom use for both prey capture and predator deterrence. Paragon searches of tandem mass spectra of venom against a translated thoracic gland RNA-Seq database identified 122 polypeptides present in the venom, including six linear and 21 disulfide-rich peptides. Some of these disulfide-rich peptides display sequence homology to peptide families independently recruited into other animal venoms, including inhibitor cystine knots, cystine-stabilised α/β defensins, Kazal peptides, and von Willebrand factors. Numerous enzymes are present in the venom, including 35 proteases of the S1 family, proteases of the S10, C1A, M12A, M14, and M17 families, and phosphatase, amylase, hydrolase, nuclease, and dehydrogenase-like proteins. These results highlight convergent molecular evolution between the assassin flies and other venomous animals, as well as the unique and rich molecular composition of assassin fly venom.

Background: Poisonings constitute a significant medical, social and economic problem worldwide. In Poland there is no nationwide registry of poisonings, which results in a lack of accurate epidemiological data. Few publications dealing with the problem are based on data obtained from toxicology units and therefore do not include information about cases treated at emergency departments and other non-toxicology units., Methods: We analyzed all admissions due to poisonings reported to the Polish National Health Fund by all hospital units in Poland in the 2009-2011 period. Diagnoses were encoded according to the ICD-10 classification., Results: A total of 254,425 admissions were reported, 85,398 in 2009, 85,230 in 2010 and 83,797 in 2011. The male to female ratios were 1.88, 1.75 and 1.80 respectively. The most frequent causes of admissions were poisonings with ethanol (n = 121,874; 47.9%), carbon monoxide (n = 17,179; 6.8%) and benzodiazepines (n = 10,340; 4.1%). Alcohols were the reason for 104,680 admissions in men (63.2%) and 22,612 admissions in women (25.5%; p < 0.01). Poisonings with pharmaceuticals and other drugs were reported in 34,616 men (20.9%) and 45,238 women (51%; p < 0.01). There were 1680 cases of fatal poisonings in the analyzed period. The hospital mortality due to poisonings increased from 1.1% in 2009 to 1.5% in 2011 (p < 0.01). The mortality in general Intensive Care Units increased from 14.4% in 2009 to 22.3% in 2011 (p < 0.01). The etiology of fatal poisonings was highly dependent on the type of hospital unit., Conclusions: The overall number of admissions due to poisonings decreased slightly during the study period, but they remained a significant cause of morbidity and mortality. Alcohols were the main cause of admissions in the analyzed period. Alcohol intoxications were more frequent in men while poisonings with pharmaceuticals were more frequent in women. Carbon monoxide exposures were a significant cause of morbidity and mortality in the studied period in Poland. A national poison information and toxicovigilance system should be created in Poland, ideally allowing for near real-time monitoring of cases of poisonings.

In South America, accidental contact with Lepidoptera larvae can produce a diversity of reactions that vary from dermatological problems to severe hemorrhagic syndromes, such as those caused by contact with caterpillars of the genus Lonomia (Saturniidae). Lonomia venom can alter the hemostatic system and lead to renal failure, internal and brain bleeding, and in severe cases, death. The only specific treatment available for these envenomations is the Lonomia Antivenom (LAV) produced by the Butantan Institute, in Brazil, using an extract of Lonomia obliqua scoli as the antigen. LAV has been used to treat exposure to other Lonomia species across South America. However, no experimental studies have been performed to test the efficacy of LAV in neutralizing the venom of species other than L. obliqua found in Southern Brazil. In this study, we tested the effectiveness of LAV in reversing the hemostatic disturbances induced by injecting Lonomia casanarensis (Lca) and Lonomia orientoandensis (Lor) scolus extracts into rats and compared the effects to the case of L. obliqua (Lob) scolus extract-induced envenomation. Lca and Lor caterpillars were collected in Colombia, and some of them were reared to adults for identification. The Minimum Defibrinating Doses (MDD) of Lca and Lor were estimated. Rats were injected (i.d.) with a dose of 3 MDD per rat of each scolus extract and treated (i.v.) with 1.5 mL of LAV or 1.5 mL of saline. Twenty-four hours after the treatment, the fibrinogen levels and platelet counts had recovered to the hemostatic levels in the groups treated with LAV. The groups treated with the saline solution had fibrinogen levels and platelet counts at non-hemostatic levels. Thromboelastometric analyses confirmed these results. In conclusion, the results showed that LAV is effective at neutralizing the envenomation induced by Lca and Lor spine extracts in rats and restoring hemostasis., Competing Interests: The authors have declared that no competing interests exist.

Latrodectism following Black Widow envenomation is rare in Canada. We present the case of a previously healthy 50 year old male who presented with an acute abdomen, hypertension, and urinary retention. After a thorough work up it was determined to be as a result of a Black Widow spider bite. Due to climate change we may see more cases of Latrodectism in the future and it should be considered as a differential diagnosis in anyone presenting with an acute abdomen after an insect bite.

The assassin bug venom system plays diverse roles in prey capture, defence and extra-oral digestion, but it is poorly characterised, partly due to its anatomical complexity. Here we demonstrate that this complexity results from numerous adaptations that enable assassin bugs to modulate the composition of their venom in a context-dependent manner. Gland reconstructions from multimodal imaging reveal three distinct venom gland lumens: the anterior main gland (AMG); posterior main gland (PMG); and accessory gland (AG). Transcriptomic and proteomic experiments demonstrate that the AMG and PMG produce and accumulate distinct sets of venom proteins and peptides. PMG venom, which can be elicited by electrostimulation, potently paralyses and kills prey insects. In contrast, AMG venom elicited by harassment does not paralyse prey insects, suggesting a defensive role. Our data suggest that assassin bugs produce offensive and defensive venoms in anatomically distinct glands, an evolutionary adaptation that, to our knowledge, has not been described for any other venomous animal.

Centipedes can subdue giant prey by using venom, which is metabolically expensive to synthesize and thus used frugally through efficiently disrupting essential physiological systems. Here, we show that a centipede ( Scolopendra subspinipes mutilans , ∼3 g) can subdue a mouse (∼45 g) within 30 seconds. We found that this observation is largely due to a peptide toxin in the venom, SsTx, and further established that SsTx blocks KCNQ potassium channels to exert the lethal toxicity. We also demonstrated that a KCNQ opener, retigabine, neutralizes the toxicity of a centipede's venom. The study indicates that centipedes' venom has evolved to simultaneously disrupt cardiovascular, respiratory, muscular, and nervous systems by targeting the broadly distributed KCNQ channels, thus providing a therapeutic strategy for centipede envenomation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Envenomation caused by human contact with the caterpillar Lonomia is characterized by deleterious effects on coagulation and patency of blood vessels. The cellular effects induced by Lonomia obliqua venom highlights its capacity to activate endothelial cells, leading to a proinflammatory phenotype. Having more knowledge about the mechanisms involved in envenomation may contribute to better treatment. We aimed to evaluate the effects of Lonomia obliqua caterpillar bristle extract (LOCBE) on vascular smooth muscle cells (VSMC). We observed that LOCBE induced VSMC migration, which was preceded by alterations in actin cytoskeleton dynamics and Focal Adhesion Kinase activation. LOCBE also induced Extracellular Signal-Regulated Kinase (ERK) phosphorylation in VSMC, and the inhibition of this pathway impaired cell proliferation. Stimulation of VSMC with LOCBE triggered reactive oxygen species (ROS) production through the activation of NADPH oxidase. The rapid increase in these ROS further induced mitochondrial ROS production, however only NADPH oxidase-derived ROS were involved in ERK activation in VSMC. We that demonstrated the chemotactic and proliferative effects of LOCBE on VSMC were dependent on ROS production, mainly through NADPH oxidase. Together, the data show that Lonomia obliqua venom can interact with and activate VSMC. These effects rely on ROS production, suggesting new potential targets for treatment against vascular damage during envenomation., Competing Interests: The authors report no conflict of interest.

Members of arachnida, such as spiders and scorpions, commonly produce venom with specialized venom glands, paralyzing their prey with neurotoxins that specifically target ion channels. Two well-studied motifs, the disulfide-directed hairpin (DDH) and the inhibitor cystine knot motif (ICK), are both found in scorpion and spider toxins. As arachnids, ticks inject a neurotoxin-containing cocktail from their salivary glands into the host to acquire a blood meal, but peptide toxins acting on ion channels have not been observed in ticks. Here, a new neurotoxin (ISTX-I) that acts on sodium channels was identified from the hard tick Ixodes scapularis and characterized. ISTX-I exhibits a potent inhibitory function with an IC50 of 1.6 μM for sodium channel Nav1.7 but not other sodium channel subtypes. ISTX-I adopts a novel structural fold and is distinct from the canonical ICK motif. Analysis of the ISTX-I, DDH and ICK motifs reveals that the new ISTX-I motif might be an intermediate scaffold between DDH and ICK, and ISTX-I is a clue to the evolutionary link between the DDH and ICK motifs. These results provide a glimpse into the convergent evolution of neurotoxins from predatory and blood-sucking arthropods.

Ticks are important vectors of pathogens and secreted neurotoxins with approximately 69 out of 692 tick species having the ability to induce severe toxicoses in their hosts. The Australian paralysis tick (Ixodes holocyclus) is known to be one of the most virulent tick species producing a flaccid paralysis and fatalities caused by a family of neurotoxins known as holocyclotoxins (HTs). The paralysis mechanism of these toxins is temperature dependent and is thought to involve inhibition of acetylcholine levels at the neuromuscular junction. However, the target and mechanism of this inhibition remain uncharacterised. Here, we report that three members of the holocyclotoxin family; HT-1 (GenBank AY766147), HT-3 (GenBank KP096303) and HT-12 (GenBank KP963967) induce muscle paralysis by inhibiting the dependence of transmitter release on extracellular calcium. Previous study was conducted using extracts from tick salivary glands, while the present study is the first to use pure toxins from I. holocyclus. Our findings provide greater insight into the mechanisms by which these toxins act to induce paralysis.

The capsaicin receptor TRPV1 ion channel is a polymodal nociceptor that responds to heat with exquisite sensitivity through an unknown mechanism. Here we report the identification of a novel toxin, RhTx, from the venom of the Chinese red-headed centipede that potently activates TRPV1 to produce excruciating pain. RhTx is a 27-amino-acid small peptide that forms a compact polarized molecule with very rapid binding kinetics and high affinity for TRPV1. We show that RhTx targets the channel's heat activation machinery to cause powerful heat activation at body temperature. The RhTx-TRPV1 interaction is mediated by the toxin's highly charged C terminus, which associates tightly to the charge-rich outer pore region of the channel where it can directly interact with the pore helix and turret. These findings demonstrate that RhTx binding to the outer pore can induce TRPV1 heat activation, therefore providing crucial new structural information on the heat activation machinery.

Scolopendra subspinipes is the only clinically significant centipede found in Hawai'i. Envenomation typically leads to extreme localized pain, erythema, induration, and tissue necrosis and possible lymphedema or lymphangitis. Mortality is uncommon and results from secondary infection or anaphylaxis. Management is supportive and includes wound care, pain control, and treatment with topical or oral antihistamines and anti-inflammatory medications.

The present article aimed to show the distribution of accidents involving the caterpillar Lonomia obliqua, Walker, 1855, in the State of Paraná between 1989 and 2001. The data were obtained from the Environmental Health Department of Paraná. The information collected was mapped using the Arcview program, and maps of the seasonal occurrence of accidents were generated. This seasonality was correlated with the insects life cycle and summer was shown to be the period with greatest incidence of accidents. The greatest concentrations occurred in the central-southern, southeastern and southwestern regions of the State.

The case of a 70 year-old, previously healthy woman who developed a severe bleeding diathesis shortly after touching a Lonomia obliqua caterpillar and finally died from multiple intracerebral hemorrhages is described. Brain hemorrhages are the leading cause of death in patients envenomed by the Lonomia species. The pertinent literature is reviewed and the most relevant clinical features highlighted, with emphasis on diagnosis. The use of new therapeutic options such as anti-Lonomia serum is discussed.

Contact with a caterpillar of the genus Lonomia can result in a hemorrhagic syndrome. Lonomia obliqua venom activates prothrombin and factor X and promotes fibrinogenolytic activity. Although crude L. obliqua bristle extract can induce hemolytic activity in human and rat erythrocytes, there have been no reports of hemolysis in the cases of human contact. We report a confirmed human case of Lonomia venom-induced hemolysis.

Background: Anaphylactic sting reactions in patients with Hymenoptera venom allergy are prevented by venom immunotherapy (VIT) in most patients., Objective: The aim of this study was to investigate re-sting reactions in the field during VIT or during an observation period of up to 13 years after cessation of treatment. Furthermore we sought to identify patients at higher risk of developing a systemic allergic reaction (SAR) and to assess possible correlations with basal serum tryptase concentration., Methods: The clinical data of 192 patients with a recorded field sting during VIT were evaluated and the patients were questioned regarding possible re-stings after cessation of VIT. Baseline mast-cell tryptase concentrations and specific IgE were analyzed in patients with a reported SAR., Results: Of 192 patients with reported re-stings in the field, 27 developed SARs (14.1%). A SAR occurred in 11.9% of the stings delivered during VIT, whereas 9.7% of the stings resulted in a SAR after VIT. The majority of SARs in response to a field sting during VIT were mild, whereas severe SARs occurred more often after VIT and repeated reexposure. Out of 23 patients with reported SARs, 2 (8.7%) had elevated basal serum tryptase., Conclusions: VIT lasting for at least 3 years is effective in protecting the vast majority of patients. The individual predictability of the response of patients to a field sting is low. SARs of increased severity mainly occur after therapy and after tolerating consecutive stings.

Background: Although rapid venom immunotherapy (VIT) protocols have been shown to be safe and effective, this issue has not yet been clarified in Turkey., Objective: The aim of this study was to evaluate the side effects of rush VIT as well as early clinical and immunological responses in patients with a venom allergy., Methods: Eighteen patients who had a history of severe systemic reactions after Hymenoptera sting were included in the study. The diagnosis was made on the basis of positive skin test reactivity and the presence of specific IgE in serum to either bee or vespid venoms. Fourteen patients underwent an average 7-day rush VIT regimen under careful monitoring in our clinic. Among them 7 patients were treated with Vespula species and 7 with Apis mellifera venom extracts. Four patients were followed up as a control group. Skin test response, specific IgE and IgG4 levels were determined before and after a year of VIT. Local and systemic reactions due to injections were monitored during the induction and maintenance phases of VIT., Results: Specific IgG4 levels significantly increased after 1 year compared with levels before VIT (mean concentration before and after; 13.04 vs 21.85 mg/L, respectively; P < .05) whereas specific IgE levels did not change (11.54 vs. 13.32 kU/L). No significant differences were observed before and after one year of VIT in skin prick (2.34 vs 3.66 mm) and intradermal (0.12-0.11 microg/mL) test reactivities (P > .05). A single patient treated with bee venom developed 4 mild systemic reactions (4/469 injections, 0.85%) during the course of VIT. More local reactions occurred in patients receiving bee venom extract (3.33%) than in those receiving yellow jacket venom (1.33%). Two patients tolerated field stings without reactions., Conclusion: Our experience confirms that rush VIT is safe and has a low systemic reaction. It can be considered for patients requiring rapid protection.

Caterpillars are the wormlike larval forms of butterflies and moths of the insect order Lepidoptera. Next to flies, lepidopterans are the most abundant arthropods with over 165,000 species worldwide, over 11,000 species in the United States alone, and with most species posing no human threats. Caterpillar species from several families of moths in the South can inflict serious human injuries ranging from urticarial dermatitis and conjunctivitis to atopic asthma and pan-uveitis. Since the 1970s, there have been increasing reports of dermatolgic, pulmonary, and systemic reactions following caterpillar encounters throughout the South.

Caterpillars are the wormlike, larval forms of butterflies and moths of the insect order Lepidoptera. Next to flies, lepidopterans are the most abundant arthropods with more than 165,000 species worldwide, and with most species posing no human threats. However, caterpillar species from approximately 12 families of moths or butterflies worldwide can inflict serious human injuries ranging from urticarial dermatitis and atopic asthma to osteochondritis, consumption coagulopathy, renal failure, and intracerebral hemorrhage. Unlike bees and wasps, envenoming or stinging caterpillars do not possess stingers or modified ovipositors attached to venom glands, but instead bear highly specialized external nettling or urticating hairs and breakaway spines or setae to defend against attacks by predators and enemies. Since the 1970s, there have been increasing reports of mass dermatolgic, pulmonary, and systemic reactions following caterpillar encounters throughout the world.

Studies of arthropod defensive chemistry continue to bring to light novel structures and unanticipated biosynthetic capabilities. Insect alkaloids, such as the heptacyclic acetogenin chilocorine and the azamacrolides, exemplify both of these aspects of arthropod chemistry. Spider venoms are proving to be rich sources of neuroactive components of potential medical interest. The venom of a fishing spider, Dolomedes okefinokensis, has yielded a polyamine which reversibly blocks L- and R-type voltage-sensitive calcium channels. Most recently, we have characterized, from the funnel-web spider Hololena curta, a sulfated nucleoside glycoside which serves as a reversible blocker of glutamate-sensitive calcium channels. The ability to synthesize or acquire an extremely diverse array of compounds for defense, offense, and communication appears to have contributed significantly to the dominant position that insects and other arthropods have attained.

We have purified the arrow poison extracted from Diamphidia nigro-ornata pupae by the !Kung Bushmen of Southern Africa, and named it diamphotoxin. The toxin is a single chain polypeptide of Mr = 60,000 with an isoelectric point of pH 9.5. It blocks neuromuscular function and is cardiotoxic and hemolytic, and the minimum lethal dose for mice is 25 pg (less than 0.5 fmol). The toxin binds tightly to cells, permitting the resolution of two distinct phases. Erythrocytes exposed to toxin in the absence of divalent cations show no apparent lesion (phase I). After washing and addition of 1 mM Ca2+, there occurs a rapid efflux of K+ followed by the loss of hemoglobin (phase II). The pH optimum for phase I is pH 6.7 and for phase II pH 8.6. The action of the toxin is noncatalytic, requiring a solution concentration of approximately 65 toxin molecules/cell for hemolysis of sheep erythrocytes under standard conditions. Ca2+ ions induce a conformational change in the free, purified toxin molecule. We propose that this change also occurs in membrane-bound toxin. Hemolysis would result from the formation of channels permitting the diffusion of small cations.

The venom of female spiders (Aphonopelma seemanni) induces necrosis of skeletal muscle in mice. This effect was demonstrated by histology and by the increase in the plasma levels of the enzyme creatine kinase (CK).

The local effects induced as a consequence of applications of four external secretions from the spider Sphaerobothria hoffmanni were recorded. Macroscopic lesions were not found; the only local effect microscopically observed was a weak necrosis in the skeletal muscle in mice.

The mammalian toxicity of the potently algogenic venom of the ant Pogonomyrmex badius is greater than that reported for any other insect venom. This enzyme-rich venom contains high concentrations of phospholipase A2 and B, hyaluronidase, acid phosphatase, lipase, and esterases. This hemolytic secretion from the poison gland products unusual symptoms in mammals and appears to have been evolved as a deterrent for vertebrate predators.

A search for potent toxins that inhibit neuronal calcium channels in Drosophila melanogaster has resulted in the identification of a presynaptic neurotoxin from the venom of the hunting spider Hololena curta. Using Drosophila neuromuscular junction as an assay, presynaptic inhibitory activity was purified using gel filtration and reverse-phase HPLC. Data from gel electrophoresis indicate that the toxin is composed of two different subunits of Mr 7000 and 9000. At nanomolar concentrations the toxin produced a complete and long-lasting inhibition of synaptic transmission at the Drosophila larval neuromuscular junction without affecting the amplitudes of the spontaneously occurring miniature junction potentials. The block of transmission produced by the toxin was observed even during the direct depolarization of the motor nerve terminal. These physiological results indicate that the terminal is the site of action for the toxin. Indirect evidence using abnormally excitable Drosophila mutants suggests that the toxin is inhibiting transmitter release by altering the electrical properties of the nerve terminal rather than by interfering with nonelectrical events that may occur subsequent to calcium influx. All of the actions of the Hololena toxin can be explained by a specific and direct effect on presynaptic calcium channels in Drosophila motor neurons.

A physiological and morphological study has been made of the effects of the venom of the spider Phoneutria nigriventer on peripheral nerve and skeletal muscle of the mouse. Venom was injected either into the sciatic nerve, via a glass micropipette, or into the calf muscles. Repetitive firing of nerve fibres commenced within seconds of injection and caused fasciculation of muscles and irregular trains of end-plate potentials. These physiological disturbances were associated with swelling of the nodal and paranodal axoplasm and the development of vacuoles in the periaxonal space. The segments of internode between the vacuoles became attenuated, with an increase in the density of axoplasmic organelles and a reduction in axonal calibre. The repetitive firing ceased after 1-3 h with development of conduction block. Both the physiological and the morphological abnormalities gradually resolved and by 24 h nerve conduction and morphology had largely returned to normal. It seems likely that these short-lived abnormalities are a consequence of the influx of sodium ions at the nodes of Ranvier, caused by the action of the venom on sodium channels.