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Using a partial transcriptome of the snakelocks anemone ( Anemonia sulcata ) we identify toxin gene candidates that were incorrectly assembled into several Trinity components. Our approach recovers hidden diversity found within some toxin gene families that would otherwise go undetected when using Trinity, a widely used program for venom-focused transcriptome reconstructions. Unidentified hidden transcripts may significantly impact conclusions made regarding venom composition (or other multi-copy conserved genes) when using Trinity or other de novo assembly programs. [ABSTRACT FROM AUTHOR]

The Chinese scorpion, Mesobuthus martensii (Karsch, 1879), is a medically important arthropod, with its venom representing a rich resource for bioactive molecules. Very little is known about the natural enemies of scorpion, albeit some populations are on the verge of extinction due to human over-exploitation. In this study, we found, for the first time, that a medically and forensically important flesh fly, Sarcophaga dux (Thompson, 1869), can parasitize M. martensii in China. We identified the flesh flies by both morphology and DNA-based methods employing the mitochondrial cytochrome C oxidase I gene. Our phylogenetic analyses indicated that S. dux was not monophyletic with respect to Sarcophaga aegyptica (Salem, 1935) and Sarcophaga harpax (Pandelle, 1896), and was comprised of two distinct mitochondrial lineages. The flesh flies infesting the Chinese scorpion formed one of the paraphyletic lineages of S. dux. These lineages together with S. aegyptica and S. harpax represented a species complex with genetic distances ranging from 1.0 to 1.5%. Our findings suggested that S. dux was capable of larviposition nocturnally. [ABSTRACT FROM AUTHOR]

Venomous animals have evolved with sophisticated bio-chemical strategies to arrest prey and defend themselves from natural predators. In recent years, peptide toxins from venomous animals have drawn considerable attention from researchers due to their surprising chemical, biochemical, and pharmacological diversity. Similar to other venomous animals, centipedes are one of the crucial venomous arthropods that have been used in traditional medicine for hundreds of years in China. Despite signifying pharmacological importance, very little is known about the active components of centipede venoms. More than 500 peptide sequences have been reported in centipede venomous glands by transcriptome analysis, but only a small number of peptide toxins from centipede has been functionally described. Like other venomous animals such as snakes, scorpions, and spiders, the venom of centipedes could be an excellent source of peptides for developing drugs for treatments as well as bio-insecticides for agrochemical applications. Although centipede venoms are yet to be adequately studied, the venom of centipedes as well as their components described to date, should be compiled to help further research. Therefore, based on previous reports, this review focusses on findings and possible therapeutic applications of centipede venoms as well as their components. [ABSTRACT FROM AUTHOR]

Some venom components are known to present potential biological activities that are useful as tools in therapeutics. In this study anti-tumoral activity of Androctonus australis hector ( Aah ) venom and its purified fraction on early step of hepato-carcinogenesis initiated by Fumonisin (FB1), was tested. Initiated hepatic tumor was assessed in mice by decreased doses of Fumonisin B1 associated to phenobarbital. Scorpion venom was used to investigate its activity on initiated tumor by FB1. Evaluation of oxidative unbalance, enzymatic activities and DNA quantification in the liver were correlated with tissue analysis. Obtained results showed that the initiated pathogenesis by FB1 at seven months was characterized by tissue alterations and biomarker variations. These alterations were characterized by atypical lesions such as muffled nucleus, karyo- and cyto-megaly; up normal and large number of nuclei into hepatocytes. These alterations were confirmed by DNA alteration. An unbalance of oxidative status was also observed, characterized by an increased levels of respectively oxidant (NO and MDA) and antioxidant (GSH and catalase activity) mediators. Aah venom and its non-toxic fraction used at low doses seemed to be able to restore partially the hepatic altered tissue induced by FB1. Decreased levels of oxidative and anti-oxidative mediators were also observed. DNA in hepatocytes returned also to the physiological values. Structure of hepatic tissue showed restoration of some alterations such as karyo- and cyto-megaly; decrease of polyploidy hepatocytes induced by FB1. Aah venom and its non-toxic fraction seem to contain some bioactive components with anti-tumoral activity. Purification of this activity from non-toxic fraction F1 could be of interest to identify the components with anti-tumoral activities. [ABSTRACT FROM AUTHOR]

The present study evaluated the acute bio-physiological effects of Lethal dose 50 (LD 50) of crude venom of Black Pakistani Cobra, Naja naja karachiensis, collected from Southern Punjab, Pakistan. Adult mice (n=20) were injected intramuscularly with normal saline (n/s) or LD50 of crude venom (1.2mg/kg). Blood was collected by cardiac puncture after anesthesia at intervals 0 (n/s), and 1, 1.5, 2 (LD50 venom) hours. Complete blood count, glucose, serum Alanine aminotransferase (ALT), albumin, total proteins and urea were measured to assess the physiology. One way ANOVA was used to analyze the data (P<0.05). A significant increase in erythrocyte count, its indices and thrombocytosis was observed during the study. Leukocyotsis was observed after a transient leucopenia at 1 hour post envenomation. No significant difference was observed for lymphocytes and monocytes. Serum concentrations of urea, total proteins, albumin and ALT were also increased significantly with all time intervals. Hypoglycemia was observed initially followed by hyperglycemia at 1.5 and 2 hours. The changes indicate that venom has severe hemotoxic potential and disrupts physiological processes by affecting vital organs like kidneys and liver in mice. [ABSTRACT FROM AUTHOR]

Background: Russell’s viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy. This study aimed to investigate the kinetics and dynamics of venom and clotting function in Russell’s viper envenoming. Methodology/Principal Findings: In a prospective cohort of 146 patients with Russell’s viper envenoming, we measured venom concentrations, international normalised ratio [INR], prothrombin time (PT), activated partial thromboplastin time (aPTT), coagulation factors I, II, V, VII, VIII, IX and X, and von Willebrand factor antigen. The median age was 39y (16–82y) and 111 were male. The median peak INR was 6.8 (interquartile range[IQR]:3.7 to >13), associated with low fibrinogen [median,<0.01g/L;IQR:<0.01–0.9g/L), low factor V levels [median,<5%;IQR:<5–4%], low factor VIII levels [median,40%;IQR:12–79%] and low factor X levels [median,48%;IQR:29–67%]. There were smaller reductions in factors II, IX and VII over time. All factors recovered over 48h post-antivenom. The median INR remained >3 at 6h post-antivenom but had reduced to <2, by 24h. The aPTT had also returned to close to normal (<50sec) at 24h. Factor VII, VIII and IX levels were unusually high pre-antivenom, median peak concentrations of 393%, 307% and 468% respectively. Pre-antivenom venom concentrations and the INR (r = 0.20, p = 0.02) and aPTT (r = 0.19, p = 0.03) were correlated (non-parametric Spearman analysis). Conclusions: Russell’s viper coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and X which recover over 48h. Severity of clotting abnormalities was associated with venom concentrations. [ABSTRACT FROM AUTHOR]

Hymenopteravenoms are known to cause life-threatening IgE-mediated anaphylactic reactions in allergic individuals. Venom immunotherapy is a recommended treatment of insect allergy with still the mechanism not being completely understood. We decided to assess the serum CCL5/RANTES level in patients who experienced severe anaphylactic reaction toHymenopteravenom and to find out changes in the course of immunotherapy. Twenty patients (9 men, 11 women, mean age: 31.91 ± 7.63 years) with history of anaphylactic reaction after insect sting were included into the study. Diagnosis was made according to sIgE and skin tests. All of them were enrolled into rush venom immunotherapy with bee or wasp venom extracts (Pharmalgen, ALK-Abello, Horsholm, Denmark). Serum levels of CCL5/RANTES were measured using a commercially available ELISA kit (R&D Systems, Minneapolis, MN). CCL5/RANTES serum concentration are higher in insect venom allergic patients than in healthy controls (887.5 ± 322.77 versus 387.27 ± 85.11 pg/ml). Serum concentration of CCL5/RANTES in insect venom allergic patient was significantly reduced in the course of allergen immunotherapy already after 6 days of vaccination (887.5 ± 322.77 versus 567.32 ± 92.16 pg/ml). CCL5/RANTES serum doesn’t correlate with specific IgE. Chemokine CCL5/RANTES participates in allergic inflammation induced byHymenopteravenom allergens. Specific immunotherapy reduces chemokine CCL5/RANTES serum level already after initial days of venom immunotherapy. [ABSTRACT FROM PUBLISHER]

Neurodegenerative diseases are relentlessly progressive, severely impacting affected patients, families and society as a whole. Increased life expectancy has made these diseases more common worldwide. Unfortunately, available drugs have insufficient therapeutic effects on many subtypes of these intractable diseases, and adverse effects hamper continued treatment. Wasp and bee venoms and their components are potential means of managing or reducing these effects and provide new alternatives for the control of neurodegenerative diseases. These venoms and their components are well-known and irrefutable sources of neuroprotectors or neuromodulators. In this respect, the present study reviews our current understanding of the mechanisms of action and future prospects regarding the use of new drugs derived from wasp and bee venom in the treatment of major neurodegenerative disorders, including Alzheimer's Disease, Parkinson's Disease, Epilepsy, Multiple Sclerosis and Amyotrophic Lateral Sclerosis. [ABSTRACT FROM AUTHOR]

Within the Apidae, the largest family of bees with over 5600 described species, the honeybee is the sole species with a well studied venom proteome. So far, only little research has focused on bumblebee venom. Recently, the genome sequence of the European large earth bumblebee ( Bombus terrestris ) became available and this allowed the first in-depth proteomic analysis of its venom composition. We identified 57 compounds, with 52 of them never described in bumblebee venom. Remarkably, 72% of the detected compounds were found to have a honeybee venom homolog, which reflects the similar defensive function of both venoms and the high degree of homology between both genomes. However, both venoms contain a selection of species-specific toxins, revealing distinct damaging effects that may have evolved in response to species-specific attackers. Further, this study extends the list of potential venom allergens. The availability of both the honeybee and bumblebee venom proteome may help to develop a strategy that solves the current issue of false double sensitivity in allergy diagnosis, which is caused by cross-reactivity between both venoms. A correct diagnosis is important as it is recommended to perform an immunotherapy with venom of the culprit species. [ABSTRACT FROM AUTHOR]

Intracranial haemorrhage (ICH) is a rare life-threatening consequence of venom induced consumption coagulopathy in snake-bite. It is unclear why certain patients haemorrhage. We aimed to investigate ICH in snake envenoming. Cases of venom-induced consumption coagulopathy from July 2005–June 2014 were identified from the Australian Snakebite Project, a prospective multicentre cohort of snake-bites. Cases with venom-induced consumption coagulopathy were extracted with data on the snake-bite, clinical effects, laboratory investigations, treatment and outcomes. 552 cases had venom-induced consumption coagulopathy; median age, 40 y (2–87 y), 417 (76%) males, 253 (46%) from brown snakes and 17 died (3%). There were 6/552 (1%) cases of ICH; median age, 71 y (59–80 y), three males and five from brown snakes. All received antivenom and five died. All six had a history of hypertension. Time to onset of clinical effects consistent with ICH was 8–12 h in four cases, and within 3 h in two. Difficult to manage hypertension and vomiting were common. One patient had a normal cerebral CT on presentation and after the onset of focal neurological effects a repeat CT showed an ICH. ICH is rare in snake-bite with only 1% of patients with coagulopathy developing one. Older age and hypertension were associated with ICH. [ABSTRACT FROM AUTHOR]

Brown snake ( Pseudonaja spp.)-induced early cardiovascular collapse is a life-threatening medical emergency in Australia. We have previously shown that this effect can be mimicked in animals and is mediated via the release of endogenous mediators. In the present study, we aimed to purify and characterize the component in Pseudonaja textilis venom which induces cardiovascular collapse following envenoming. The component (fraction 3) was isolated using a combination of techniques including hydroxyapatite and reverse phase chromatography. Fraction 3 (10 or 20 μg/kg, i.v.) produced a rapid decrease in mean arterial pressure (MAP) followed by cardiovascular collapse. Fraction 3-induced early collapse was abolished by prior administration of smaller priming doses of fraction 3 (i.e. 2 and 5 μg/kg, i.v.) or heparin (300 units/kg, i.v.). P. textilis whole venom (1 and 3 μg/ml), but not fraction 3 (1 or 3 μg/ml), induced endothelium-dependent relaxation in isolated rat mesenteric arteries. SDS-PAGE gel indicated the presence of 9–10 protein bands of fraction 3. Using proteomic based analysis some protein bands of fraction 3 were identified as subunits of venom prothrombin activator, pseutarin C of P. textilis venom. Our results conclude that prothrombin activator-like toxin is likely to be a contributor to the rapid collapse induced by P. textilis venom. [ABSTRACT FROM AUTHOR]

Scorpions have been shown to control their venom usage in defensive encounters, depending on the perceived threat. Potentially, the venom amount that is injected could be controlled by reducing the flow speed, the flow duration, or both. We here investigated these variables by allowing scorpions to sting into an oil-filled chamber, and recording the accreting venom droplets with high-speed video. The size of the spherical droplets on the video can then be used to calculate their volume. We recorded defensive stings of 20 specimens representing 5 species. Significant differences in the flow rate and total expelled volume were found between species. These differences are likely due to differences in overall size between the species. Large variation in both venom flow speed and duration are described between stinging events of single individuals. Both venom flow rate and flow duration correlate highly with the total expelled volume, indicating that scorpions may control both variables in order to achieve a desired end volume of venom during a sting. [ABSTRACT FROM AUTHOR]

Parasitoid wasps inject insect hosts with a cocktail of venoms to manipulate the physiology, development, and immunity of the hosts and to promote development of the parasitoid offspring. The jewel wasp Nasonia vitripennis is a model parasitoid with at least 79 venom proteins. We conducted a high-throughput analysis of Nasonia venom effects on temporal changes of 249 metabolites in pupae of the flesh fly host ( Sarcophaga bullata), over a 5-day time course. Our results show that venom does not simply arrest the metabolism of the fly host. Rather, it targets specific metabolic processes while keeping hosts alive for at least 5 days post venom injection by the wasp. We found that venom: (a) activates the sorbitol biosynthetic pathway while maintaining stable glucose levels, (b) causes a shift in intermediary metabolism by switching to anaerobic metabolism and blocking the tricarboxylic acid cycle, (c) arrests chitin biosynthesis that likely reflects developmental arrest of adult fly structures, (d) elevates the majority of free amino acids, and (e) may be increasing phospholipid degradation. Despite sharing some metabolic effects with cold treatment, diapause, and hypoxia, the venom response is distinct from these conditions. Because Nasonia venom dramatically increases sorbitol levels without changing glucose levels, it could be a useful model for studying the regulation of the sorbitol pathway, which is relevant to diabetes research. Our findings generally support the view that parasitoid venoms are a rich source of bioactive molecules with potential biomedical applications. [ABSTRACT FROM AUTHOR]

This study reports on a cytotoxic toxin derived from the venom of the crown-of-thorns starfish Acanthaster planci (CAV). The protein toxin was isolated through both ion-exchange and gel-filtration chromatography, and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrum analyzes. The CAV was identified as plancitoxin I protein. The mechanistic role of the CAV toxin was explored in human malignant melanoma A375.S2 cell death. The results indicated that after incubation with CAV toxin, cells significantly decreased in A375.S2 cell viability and increased in the lactate dehydrogenase (LDH) level in a dose-dependent manner. The assays indicated that CAV toxin promoted reactive oxygen species (ROS) production, induced nitric oxide (NO) formation, lost mitochondrial membrane potential (ΔΨm) and induced inter-nucleosomal DNA fragmentation in A375.S2 cells. The molecular cytotoxicity of the CAV toxin was tested through evaluation of the apoptosis/necrosis ratio by double staining with annexin V-FITC and a propidium iodide (PI) assay. The results suggested that CAV toxin induced a cytotoxic effect in A375.S2 cells via the apoptotic procedure, and may be associated with the regulation of the p38 pathways. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A myographic study was performed to compare the neuromuscular effects of venoms and crotoxin-like proteins from Crotalus durissus ruruima and Crotalus durissus cumanensis in mice phrenic-diaphragm preparation. It was concluded that both venoms present neurotoxic activity as a consequence of their crotoxin content. Furthermore, crotoxin from C.d. cumanensis is more potent than that from C.d. ruruima venom. At the concentration range in which both venoms express neurotoxic activity, only C.d. cumanensis venom also manifest a direct myotoxic effect that probably involves the synergic participation of other components than crotoxin. [ABSTRACT FROM AUTHOR]

Naja haje envenomation is one of the leading causes of death due to snakebite. Antiserum therapy sometimes fails to provide enough protection against venom toxicity. In this study, we investigated the protective effects of melatonin against N. haje venom in rats. The animals were injected with venom (0.25 mg/kg) and/or melatonin (10 mg/kg) and compared with vehicle-treated rats. There was oxidative/nitrosative damage and apoptosis in the liver, heart, and kidneys of venom-injected rats. Melatonin counteracted the increased lipoperoxidation and nitric oxide, prevented decreased glutathione peroxidase and reductase activity, reduced the glutathione disulfide/glutathione (GSSG/GSH) ratio, and maintained the GSH pool. Furthermore, melatonin administration was associated with a reduction of apoptosis, which was increased in venom-injected rats. Overall, these results suggest that melatonin mitigates oxidative/nitrosative stress in venom-induced cardio-hepato-renal injury in rats. Our results suggest that melatonin treatment may ameliorate some of the effects of N. haje envenomation. [ABSTRACT FROM AUTHOR]

Background: An alarming number of fatal accidents involving snakes are annually reported in Africa and most of the victims suffer from permanent local tissue damage and chronic disabilities. Envenomation by snakes belonging to the genus Bitis, Viperidae family, are common in Sub-Saharan Africa. The accidents are severe and the victims often have a poor prognosis due to the lack of effective specific therapies. In this study we have biochemically characterized venoms from three different species of Bitis, i.e., Bitis arietans, Bitis gabonica rhinoceros and Bitis nasicornis, involved in the majority of the human accidents in Africa, and analyzed the in vitro neutralizing ability of two experimental antivenoms. Methodology/Principal Findings: The data indicate that all venoms presented phospholipase, hyaluronidase and fibrinogenolytic activities and cleaved efficiently the FRET substrate Abz-RPPGFSPFRQ-EDDnp and angiotensin I, generating angiotensin 1–7. Gelatinolytic activity was only observed in the venoms of B. arietans and B. nasicornis. The treatment of the venoms with protease inhibitors indicated that Bitis venoms possess metallo and serinoproteases enzymes, which may be involved in the different biological activities here evaluated. Experimental antivenoms produced against B. arietans venom or Bitis g. rhinoceros plus B. nasicornis venoms cross-reacted with the venoms from the three species and blocked, in different degrees, all the enzymatic activities in which they were tested. Conclusion: These results suggest that the venoms of the three Bitis species, involved in accidents with humans in the Sub-Saharan Africa, contain a mixture of various enzymes that may act in the generation and development of some of the clinical manifestations of the envenomations. We also demonstrated that horse antivenoms produced against B. arietans or B. g. rhinoceros plus B. nasicornis venoms can blocked some of the toxic activities of these venoms. [ABSTRACT FROM AUTHOR]

Envenomation by Scolopendra heros, the Texas redheaded centipede, can present variably. Although transient pain and erythema are often treated conservatively, complications may include cellulitis, necrosis, myocardial infarction, and rhabdomyolysis. We present a case of an elderly man who came to the emergency department with lymphangitis and dermatitis secondary to a centipede sting that awoke him from sleep. It is important to recognize the potential of centipede envenomation to have severe local and systemic manifestations. [ABSTRACT FROM AUTHOR]

The case history and clinical signs of a fatal self-envenomation event by a brown tree snake, Boiga irregularis , in South-east Queensland, Australia, are presented. Clinical signs began 20 minutes post-envenomation with muscle twitching, ataxia, and heat seeking behavior which progressed to partial paralysis by 6 hours, generalised paralysis and respiratory arrest at 10 hours and cardiac arrest by 12 hours post-envenomation. Clinical signs are suggestive of potent neurotoxicity for B. irregularis to its own venom. [ABSTRACT FROM AUTHOR]

Cnidarians rely on their nematocysts and the venom injected through these unique weaponry systems to catch prey and protect themselves from predators. The development and physiology of the nematocysts of Hydra magnipapillata , a classic model organism, have been intensively studied, yet the composition and biochemical activity of their venom components are mostly unknown. Here, we show that hydra actinoporin-like toxins (HALTs), which have previously been associated with Hydra nematocysts, belong to a multigene family comprising six genes, which have diverged from a single common ancestor. All six genes are expressed in a population of Hydra magnipapillata . When expressed recombinantly, HALT-1 (Δ-HYTX-Hma1a), an actinoporin-like protein found in the stenoteles (the main penetrating nematocysts used in prey capture), reveals hemolytic activity, albeit about two-thirds lower than that of the anemone actinoporin equinatoxin II (EqTII, Δ-AITX-Aeq1a). HALT-1 also differs from EqTII in the size of its pores, and likely does not utilize sphingomyelin as a membrane receptor. We describe features of the HALT-1 sequence which may contribute to this difference in activity, and speculate on the role of this unusual family of pore-forming toxins in the ecology of Hydra. [ABSTRACT FROM AUTHOR]

Aim: To determine the indications for, duration of, complications, duration of hospitalisation and outcomes in patients treated with positive-pressure ventilation (PPV) in Australia. Materials and Methods: Medical records of 302 patients (262 dogs and 40 cats) treated with PPV were reviewed for the indication for ventilation, duration of PPV, complications, duration of hospitalisation and outcome. Patients were assigned into one of four groups based on the indication for ventilation. Results: The present study showed higher survival rates for patients treated with PPV than previously reported. Patients ventilated for hypoventilation and unsustainable respiratory effort had the highest survival rates. Snake envenomation and tick paralysis were the most common underlying diseases in patients treated with PPV and had good survival rates. Conclusion: The indication for ventilation is associated with outcome. PPV should be instigated early when unsustainable respiratory effort is evident to give patients the best chance of survival. [ABSTRACT FROM AUTHOR]

A retrospective study was conducted in cats and dogs with Mainland tiger snake (Notechis scutatus) and Eastern brown snake (Pseudonaja textillis) envenomation in Melbourne, Australia, to compare clinical signs and treatment and to determine if a coagulopathy is seen as frequently as in human envenomation cases. Neurotoxicity was common in both tiger and brown snake envenomation. Myotoxicity was seen in 83% of dogs and 96% of cats with tiger snake envenomation. Prolonged coagulation tests were common in animals with tiger snake envenomation, but not in those with brown snake envenomation. Clinical bleeding was less common than laboratory evidence of a coagulopathy. Dogs were treated with a median of 2 vials and cats with a median of 1 vial of tiger/brown polyvalent antivenom. The overall proportion of cases presenting for snake envenomation that were euthanased for financial reasons was 12% for dogs and 13% for cats. Of the remaining cases, 95% of dogs and 97% of cats survived. Due to the similarity of clinical signs in tiger and brown snake envenomation, it is not recommended that diagnosis and choice of antivenom be based on clinical signs alone. [ABSTRACT FROM AUTHOR]

Background. Crotaline snakebites are routinely assessed with serial external examinations. We sought to correlate external findings with changes observed on ultrasound imaging. Methods. This was a prospective, observational study of consecutive rattlesnake envenomation in patients treated at a single hospital in central California. Information recorded for each case included clinical data, gross external examination, and ultrasound images of tissue edema, localized fluid collections, and video footage of muscle fasciculations. Results. Thirteen patients were enrolled. Ultrasound imaging of the bitten extremity was consistent with external examination of the bitten limb. The most common sonographic finding was subcutaneous tissue edema. Edema and necrosis in 3 patients with rapidly progressive leg swelling spared the deeper muscle layers and fascial planes. In 2 patients with bites on the fingers, edema and tendon involvement were readily visualized using a water-bath technique (placement of the hand in a pool of water, allowing more detailed examination of the tissue planes). Conclusion. Ultrasound imaging may allow for a more complete understanding of the local effects of snakebite. We were also able to document normal deeper muscle integrity in cases with diffuse leg edema. More studies are needed to fully elaborate the strengths and limitations of bedside ultrasound as a diagnostic adjunct in envenomation assessment. [ABSTRACT FROM AUTHOR]

During the summer period 2011-2012, seven widow spider bites in Greece were reported to the Hellenic Center for Disease Control and Prevention. Widow spiders (in the genus Latrodectus) are found all over the world, including Europe, Asia, Africa, Australia, and the US. Alpha-latrotoxin (main mammalian toxin) causes the toxic effects observed in humans. Victims should receive timely medical care to avoid suffering. Latrodectus bites are very rarely fatal. All the patients reported having an insect bite 30 minutes to 2 hours before they arrived at the Emergency Department of the local hospital. Severe muscle cramps, weakness, tremor, abdominal pain, and increased levels of creatinine phosphokinase were present in all patients. The Emergency Operation Center of the Hellenic Center for Disease Control and Prevention was informed immediately in all cases. Antivenin was administered to four patients upon the request of their physicians. All patients recovered fully. It is essential that health care workers recognize early the symptoms and signs of Latrodectus bites to provide the necessary care. The management of mild to moderate Latrodectus envenomations is primarily supportive. Hospitalization and possibly antivenin should be reserved for patients exhibiting serious systemic symptoms or inadequate pain control. The most important thing for all of these patients is early pain relief. [ABSTRACT FROM AUTHOR]

Abstract: Snakes demonstrate a great deal of variation in the amount of venom injected in both predatory and defensive strikes. There is some evidence that snakes can adaptively meter venom dosage. An underlying assumption in the evolution of venom metering is that the production of venom is energetically costly. To date there has been very little research that has quantified the metabolic costs associated with venom production. We used open-flow respirometry to test for significant differences between Prairie Rattlesnakes (Crotalus v. viridis) that had venom extracted and control snakes that did not. Although previous studies demonstrated high metabolic costs for venom production, we found that snakes that had venom extracted did not have significantly higher metabolic rates than control snakes. The pattern of metabolic deviation from baseline measurements was similar for both treatments, and on average snakes that had venom extracted only exhibited a 1.1% increase over baseline compared to a 2.5% increase in control snakes. Our data suggest that venom is not energetically costly to produce and that perhaps other costs associated with venom can better explain the variability in venom expenditure. [Copyright &y& Elsevier]

Introduction and objective. Mast cells (MC) are effector cells during severe systemic reactions (SR) to Hymenoptera stings. Venom specific immunotherapy (VIT) is the treatment of choice for prevention of SR to stings. Tryptase and prostaglandin D2 metabolites (PGD2) are the markers of MC activation. The study design was to 1. compare baseline values of serum tryptase concentration (BST) and PGD2 metabolites in children with/without venom sensitization, 2. to evaluate an influence of rush VIT on MC markers in treated children. Materials and methods. Sensitized group: 25 children with SR to Hymenoptera sting. Control group: 19 healthy children. Active treatment: 5-day-rush-VIT. BST was evaluated by ImmunoCAP, PGD2 metabolites in blood and urine by GC-NICI-MS. Results. The baseline blood levels of MC markers were significantly higher, while urinary concentration of 9α,11β-PGF2 was significantly lower in the whole group of venom-sensitized children compared to controls. Severity of SR showed negative correlation with urinary PGD2 metabolites, while positive with plasma 9α,11β-PGF2 and BST concentration The highest sensitivity was obtained for plasma 9α,11β-PGF2 whereas the highest specificity for urinary PGD-M. Conclusions. In children with IgE-mediated SR to Hymenoptera stings, elevation of baseline values of PGD2 metabolites in blood is accompanied by decreased excretion of its urinary metabolites. Assessment of stable PGD2 metabolites might serve as an independent MC marker to identify allergic children. There is an association between urinary PGD2 metabolites and severity of the SR to Hymenoptera stings. [ABSTRACT FROM AUTHOR]

Abstract: Spiders of the Loxosceles genus represent a risk to human health due to the systemic and necrotic effects of their bites. The main symptoms of these bites vary from dermonecrosis, observed in the majority of cases, to occasional systemic hemolysis and coagulopathy. Although the systemic effects are well characterized, the mechanisms of cell death triggered by the venom of these spiders are poorly characterized. In this study, we investigated the cell death mechanisms induced by the whole venom of the spider Loxosceles similis in human skin fibroblasts. Our results show that the venom initiates an apoptotic process and a caspase cascade involving the initiator caspase-9 and the effector caspases-3, -6, and -7. [Copyright &y& Elsevier]

Viper bites cause high morbidity and mortality worldwide and regarded as a neglected tropical disease affecting a large healthy population. Classical antivenom therapy has appreciably reduced the snakebite mortality rate; it apparently fails to tackle viper venom-induced local manifestations that persist even after the administration of antivenom. Recently, viper venom-induced oxidative stress and vital organ damage is deemed as yet another reason for concern; these are considered as postmedicated complications of viper bite. Thus, treating viper bite has become a challenge demanding new treatment strategies, auxiliary to antivenin therapy. In the last decade, several studies have reported the use of plant products and clinically approved drugs to neutralize venom-induced pharmacology. However, very few attempts were undertaken to study oxidative stress and vital organ damage. Based on this background, the present study evaluated the protective efficacy of melatonin in Echis carinatus ( EC) venom-induced tissue necrosis, oxidative stress, and organ toxicity. The results demonstrated that melatonin efficiently alleviated EC venom-induced hemorrhage and myonecrosis. It also mitigated the altered levels of inflammatory mediators and oxidative stress markers of blood components in liver and kidney homogenates, and documented renal and hepatoprotective action of melatonin. The histopathology of skin, muscle, liver, and kidney tissues further substantiated the overall protection offered by melatonin against viper bite toxicities. Besides the inability of antivenoms to block local effects and the fact that melatonin is already a widely used drug promulgating a multitude of therapeutic functionalities, its use in viper bite management is of high interest and should be seriously considered. [ABSTRACT FROM AUTHOR]

Background: We recently showed a desensitization of FcεRI-mediated basophil response after short-term VIT. Our aim was to evaluate the allergen specificity of this desensitization. Methods: In 11 Hymenoptera-venom double positive subjects, basophil threshold sensitivity (CD-sens) to anti-FcεRI, honeybee, and Vespula venom was assessed at the beginning and just before the first maintenance dose (MD) of single ultra-rush VIT. In some patients we also monitored CD-sens to rApi m 1 and/or rVes v 5 or other co-sensitizations (i.e., grass pollen). In additional 7 patients, basophils were stripped and sensitized with house dust mite (HDM) IgEs at the same time points. Results: We demonstrated a marked reduction of CD-sens to anti-FcεRI and VIT-specific venom before the first MD in all 18 subjects included. Furthermore, in 10 out of 11 double positive subjects, a significant and comparable decrease before the first MD was also evident for non-VIT venom; this nonspecific decrease was further supported by the opposite recombinant species-specific major allergen. In one subject with additional grass pollen allergy, a decrease of CD-sens to grass allergen was also demonstrated. Similarly, in 7 cases of patients with passively HDM-sensitized basophils, a significant reduction of CD-sens was also evident to de novo sensitized HDM allergen. Conclusions: Short-term VIT induced basophil desensitization to VIT-specific as well as to VIT-nonspecific venom. As opposed to long-term VIT, which induces venom-specific changes, the effect of short-term VIT seems to be venom-nonspecific. [ABSTRACT FROM AUTHOR]

Summary: Background: The venoms of predators have been an excellent source of diverse highly specific peptides targeting ion channels. Here we describe the first known peptide antagonist of the nociceptor ion channel transient receptor potential ankyrin 1 (TRPA1). Results: We constructed a recombinant cDNA library encoding ∼100 diverse GPI-anchored peptide toxins (t-toxins) derived from spider venoms and screened this library by coexpression in Xenopus oocytes with TRPA1. This screen resulted in identification of protoxin-I (ProTx-I), a 35-residue peptide from the venom of the Peruvian green-velvet tarantula, Thrixopelma pruriens, as the first known high-affinity peptide TRPA1 antagonist. ProTx-I was previously identified as an antagonist of voltage-gated sodium (NaV) channels. We constructed a t-toxin library of ProTx-I alanine-scanning mutants and screened this library against NaV1.2 and TRPA1. This revealed distinct partially overlapping surfaces of ProTx-I by which it binds to these two ion channels. Importantly, this mutagenesis yielded two novel ProTx-I variants that are only active against either TRPA1or NaV1.2. By testing its activity against chimeric channels, we identified the extracellular loops of the TRPA1 S1–S4 gating domain as the ProTx-I binding site. Conclusions: These studies establish our approach, which we term “toxineering,” as a generally applicable method for isolation of novel ion channel modifiers and design of ion channel modifiers with altered specificity. They also suggest that ProTx-I will be a valuable pharmacological reagent for addressing biophysical mechanisms of TRPA1 gating and the physiology of TRPA1 function in nociceptors, as well as for potential clinical application in the context of pain and inflammation. [Copyright &y& Elsevier]

Objective: To determine the effect acetic acid (vinegar) has on discharged nematocysts in a simulated sting from Chironex fleckeri. Method: This research was performed in 2 parts: 1 C. fleckeri tentacles placed on amniotic membrane were electrically stimulated, and venom washings collected before and after application of vinegar. Lyophilised venom washings were run through a fast-performance protein liquid chromatography column to confirm the venom profile, with a quantitative measure of venom from each washing calculated using UNICORN™ software. 2 The toxicity of the washings was determined by application to human cardiomyocytes, with percentage of cell detachment providing a measure of cell mortality, and hence toxicity. Results: Part 1: There was a 69 +/- 32% (F = 77, P < 0.001) increase in venom discharge after vinegar was applied compared to post electrical stimulation. Part 2: Venom collected after the administration of vinegar demonstrated the same toxicity as venom from electrically stimulated C. fleckeri tentacles and milked venom, causing cell mortality of 59 +/- 13% at 10 µg ml-1 compared to 57 +/- 10% and 65 +/- 7% respectively. Conclusion: This in-vitro research suggests that vinegar promotes further discharge of venom from already discharged nematocysts. This raises concern that vinegar has the potential to do harm when used as first aid in C. fleckeri envenomation. [ABSTRACT FROM AUTHOR]

Proteases from Russell's viper venom (RVV) induce a variety of toxic effects in victim. Therefore, four new RVV protease isoenzymes of molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, were characterized in this study. The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. These proteases were found to be different from previously reported factor V activators isolated from snake venoms. These proteases showed significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities but no fibrinolytic, TAME-esterase or amidolytic activity against the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa. Their Km and Vmax values towards fibrinogen were determined in the range of 6.6 to 10.5 µM and 111.0 to 125.5 units/mg protein, respectively. On the basis of fibrinogen degradation pattern, they may be classified as A/B serine proteases isolated from snake venom. These proteases contain ∼42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. In vitro these protease isoenzymes induce blood coagulation through factor V activation, whereas in vivo they provoke dose-dependent defibrinogenation and anticoagulant activity in the mouse model. At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis. [ABSTRACT FROM AUTHOR]

Background: Venom-induced acute kidney injury (AKI) is a frequent complication of Bothrops snakebite with relevant morbidity and mortality. The aim of this study was to assess the effects of Schizolobium parahyba (SP) extract, a natural medicine with presumed anti-Bothrops venom effects, in an experimental model of Bothrops jararaca venom (BV)-induced AKI. Methodology: Groups of 8 to 10 rats received infusions of 0.9% saline (control, C), SP 2 mg/kg, BV 0.25 mg/kg and BV immediately followed by SP (treatment, T) in the doses already described. After the respective infusions, animals were assessed for their glomerular filtration rate (GFR, inulin clearance), renal blood flow (RBF, Doppler), blood pressure (BP, intra-arterial transducer), renal vascular resistance (RVR), urinary osmolality (UO, freezing point), urinary neutrophil gelatinase-associated lipocalin (NGAL, enzyme-linked immunosorbent assay [ELISA]), lactate dehydrogenase (LDH, kinetic method), hematocrit (Hct, microhematocrit), fibrinogen (Fi, Klauss modified) and blinded renal histology (acute tubular necrosis score). Principal Findings: BV caused significant decreases in GFR, RBF, UO, HcT and Fi; significant increases in RVR, NGAL and LDH; and acute tubular necrosis. SP did not prevent these changes; instead, it caused a significant decrease in GFR when used alone. Conclusion: SP administered simultaneously with BV, in an approximate 10∶1 concentration, did not prevent BV-induced AKI, hemolysis and fibrinogen consumption. SP used alone caused a decrease in GFR. [ABSTRACT FROM AUTHOR]

The members of Scorpaenidae family, including stonefish (genus Synanceja) are among the most dangerous and venomous fishes in the word that inhibit in the tropical shallow waters. The toxinology of the venom of stonefish (genus Synanceja) showed that it is a mixture of proteins, containing several enzymes like hyaluronidase. The crude venom can produce cytolytic, hemolytic, neurotoxic and hypotensive effects in vivo. Immediate increasing intensive pain, local ischemia followed by cyanosis, edema and swelling are the local clinical presentations. Systemic manifestations are not uncommon. Hot water immersion of the injured limb, a local anesthetic agent without adrenaline, infiltrated into and around the wound, debridement of the necrotic tissue and the prescription of prophylactic antibiotic are the main therapeutic measures. The administration of antivenom may be considered. [ABSTRACT FROM AUTHOR]

We describe a case of severe scorpion envenomation in an adult patient, with the presence of very rapid sustained ventricular tachycardia followed by cardiogenic shock, which was reversed by scorpion antivenom administration. Scorpion venom causes cardiac changes that can lead to an environment favoring arrhythmogenesis. [ABSTRACT FROM AUTHOR]

Abstract: The number and types of venom components that affect ion-channel function are reviewed. These are the most important venom components responsible for human intoxication, deserving medical attention, often requiring the use of specific anti-venoms. Special emphasis is given to peptides that recognize Na+-, K+- and Ca++-channels of excitable cells. Knowledge generated by direct isolation of peptides from venom and components deduced from cloned genes, whose amino acid sequences are deposited into databanks are nowadays in the order of 1.5 thousands, out of an estimate biodiversity closed to 300,000. Here the diversity of components is briefly reviewed with mention to specific references. Structural characteristic are discussed with examples taken from published work. The principal mechanisms of action of the three different types of peptides are also reviewed. Na+-channel specific venom components usually are modifier of the open and closing kinetic mechanisms of the ion-channels, whereas peptides affecting K+-channels are normally pore blocking agents. The Ryanodine Ca++-channel specific peptides are known for causing sub-conducting stages of the channels conductance and some were shown to be able to internalize penetrating inside the muscle cells. [Copyright &y& Elsevier]

Snakebite is classified by the WHO as a neglected tropical disease. Envenoming is a significant public health problem in tropical and subtropical regions. Neurotoxicity is a key feature of some envenomings, and there are many unanswered questions regarding this manifestation. Acute neuromuscular weakness with respiratory involvement is the most clinically important neurotoxic effect. Data is limited on the many other acute neurotoxic manifestations, and especially delayed neurotoxicity. Symptom evolution and recovery, patterns of weakness, respiratory involvement, and response to antivenom and acetyl cholinesterase inhibitors are variable, and seem to depend on the snake species, type of neurotoxicity, and geographical variations. Recent data have challenged the traditional concepts of neurotoxicity in snake envenoming, and highlight the rich diversity of snake neurotoxins. A uniform system of classification of the pattern of neuromuscular weakness and models for predicting type of toxicity and development of respiratory weakness are still lacking, and would greatly aid clinical decision making and future research. This review attempts to update the reader on the current state of knowledge regarding this important issue. [ABSTRACT FROM AUTHOR]

Abstract: Venoms contain active substances with highly specific physiological effects and are increasingly being used as sources of novel diagnostic, research and treatment tools for human disease. Experimental characterisation of individual toxin activities is a severe rate-limiting step in the discovery process, and in-silico tools which allow function to be predicted from sequence information are essential. Toxins are typically members of large multifunctional families of structurally similar proteins that can have different biological activities, and minor sequence divergence can have significant consequences. Thus, existing predictive tools tend to have low accuracy. We investigated a classification model based on physico-chemical attributes that can easily be calculated from amino-acid sequences, using over 250 (mostly novel) viperid phospholipase A2 toxins. We also clustered proteins by sequence profiles, and carried out in-vitro tests for four major activities on a selection of isolated novel toxins, or crude venoms known to contain them. The majority of detected activities were consistent with predictions, in contrast to poor performance of a number of tested existing predictive methods. Our results provide a framework for comparison of active sites among different functional sub-groups of toxins that will allow a more targeted approach for identification of potential drug leads in the future. [Copyright &y& Elsevier]

Although exposure to animal venom and poison, such as snakebites, bee stings, and contact, with toads, is a common problem, reported deaths are rare. The present report discusses 18 fatal cases in China. Causes of death were grouped into 6 categories, including 1 case of tetrodotoxin poisoning, 1 case of gallbladder poisoning, 3 cases of snake venom toxicity, 4 cases of melittin toxicity, 4 cases of cantharidin poisoning and 5 cases of venenum bufonis poisoning. The epidemiology of each venom-induced death, the mechanism of exposure to venom, and the target organs and tissues affected by these toxic animals were here systematically reviewed. Such details are important to even suspected cases of venom damage. The associated problems related to forensic medicine, such as manner of death and possible attribution to the toxic effects of various animals, are also discussed herein. [ABSTRACT FROM AUTHOR]

Highlights: [•] The PA gene was cloned from the venom gland of Gloydius brevicaudus using RT-PCR. [•] The MW of rGBV-PA expressed in E. coli was 27.9kDa. [•] rGBV-PA can reduce the plasma ELT in rabbits and prevent thrombosis in rats. [ABSTRACT FROM AUTHOR]

Bothrops snakes are the major cause of ophidian envenomings in Latin America. Their venom contains myotoxins that cause prominent muscle damage, which may lead to permanent disability. These toxins include myotoxins Mt- I and Mt- II, which share the phospholipase A2 ( PLA2) fold, but Mt- II lacks enzymatic activity because the essential active site Asp49 is replaced by Lys. Both myotoxins cause sarcolemma alterations, with Ca2+ entry and loss of ATP and K+ from muscle cells, but the molecular lesions at the basis of their cellular action are not known, particularly the role of phospholipid hydrolysis. Here we tested their PLA2 activity in vivo, and evaluated the hypothesis that Ca2+-activated endogenous PLA2s may be involved in the action of Mt- II. The time course of phospholipid hydrolysis by Mt- I and Mt- II in myotubes in culture and in tibialis anterior mouse muscles was determined. Mt- I rapidly hydrolyzed phosphatidylcholine and phosphatidylethanolamine but not phosphatidylserine, but no phospho-lipids were hydrolyzed in the presence of Mt- II. Whole Bothrops asper venom induced a higher extent of phospholipid hydrolysis than Mt- I alone. These results demonstrate in vivo PLA2 activity of Mt- I for the first time, and indicate that it acts only on the external monolayer of the sarcolemma. They also exclude activation of endogenous PLA2s in the action of Mt- II, implying that plasma membrane disruption by this toxin does not depend on phospholipid hydrolysis. Therefore, both Bothrops myotoxins induce Ca2+ entry and release of ATP and cause myonecrosis, but through different biochemical mechanisms. [ABSTRACT FROM AUTHOR]

Abstract: This manuscript describes the general biochemical properties and immunological characteristics of Peruvian spider Loxosceles laeta venom (PLlv), which is responsible for the largest number of accidents involving venomous animals in Peru. In this work, we observed that the venom of this spider is more lethal to mice when compared with L. laeta venom from Brazil (BLlv). The LD50 of PLlv was 1.213 mg/kg when the venom was intradermally injected. The venom displayed sphingomyelinase activity and produced dermonecrotic, hemorrhagic and edema effects in rabbits. 2-D SDS-PAGE separation of the soluble venoms resulted in a protein profile ranging from 20 to 205 kDa. Anti-PLlv and anti-BLlv sera produced in rabbits and assayed by ELISA showed that rabbit antibodies cross-reacted with PLlv and BLlv and also with other Brazilian Loxosceles venoms. Western blotting analysis showed that bands corresponding to 25–35 kDa are the proteins best recognized in every Loxosceles spp venoms analyzed. The immunized rabbits displayed protective effect after challenge with PLlv and BLlv. In vitro assays with horse anti-loxoscelic antivenoms produced in Brazil and Peru demonstrated that these commercial antivenoms were efficient to inhibit the sphingomyelinase activity of PLlv and BLlv. [Copyright &y& Elsevier]

Abstract: Voltage-gated Na+ channels (Nav) are the targets of a variety of scorpion toxins. Here, we investigated the effects of Amm VIII, a toxin isolated from the venom of the scorpion Androctonus mauretanicus mauretanicus, on pain-related behaviours in mice. The effects of Amm VIII were compared with the classic scorpion α-toxin AaH II from Androctonus australis. Contrary to AaH II, intraplantar injection of Amm VIII at relatively high concentrations caused little nocifensive behaviours. However, Amm VIII induced rapid mechanical and thermal pain hypersensitivities. We evaluated the toxins’ effects on Nav currents in nociceptive dorsal root ganglion (DRG) neurons and immortalized DRG neuron-derived F11 cells. Amm VIII and AaH II enhanced tetrodotoxin-sensitive (TTX-S) Nav currents in DRG and F11 cells. Both toxins impaired fast inactivation and negatively shifted activation. AaH II was more potent than Amm VIII at modulating TTX-S Nav currents with EC50 of 5nM and 1μM, respectively. AaH II and Amm VIII also impaired fast inactivation of Nav1.7, with EC50 of 6.8nM and 1.76μM, respectively. Neither Nav1.8 nor Nav1.9 was affected by the toxins. AaH II and Amm VIII reduced first spike latency and lowered action potential threshold. Amm VIII was less efficient than AaH II in increasing the gain of the firing frequency-stimulation relationship. In conclusion, our data show that Amm VIII, although less potent than AaH II, acts as a gating-modifier peptide reminiscent of classic α-toxins, and suggest that its hyperalgesic effects can be ascribed to gain-of-function of TTX-S Na+ channels in nociceptors. [Copyright &y& Elsevier]

Context. Limited information exists on the coagulopathy caused by hump-nosed pit viper ( Hypnale hypnale) envenoming. Objectives. This study aimed to characterise the coagulopathy in hump-nosed pit viper bites by measuring laboratory clotting times and factor studies. Materials and methods. Cases of hump-nosed pit viper envenoming were included from a prospective cohort study of Sri Lankan snake-bite patients. Patient age, sex, snake identification, time of bite and clinical effects were recorded. Patients did not receive anti-venom because no specific anti-venom to hump-nosed vipers exists. All patients received supportive care and serial 20-min whole blood clotting tests (WBCT20). The prothrombin time (PT), international normalised ratio (INR), activated partial thromboplastin time (aPTT), coagulation factors I, II, V, VII, VIII, IX and X, von Willebrand factor (vWF) antigen and D-Dimer concentrations were measured. The median of highest or lowest test result for each patient was reported with interquartile range (IQR). Results. There were 80 hump-nosed pit viper bites, median age was 37 years (IQR: 26-51 years) and 48 were male. The WBCT20 was positive in one patient. The median highest INR was 1.9 (1.5-2.2; Range: 1.3 to > 12) and median highest aPTT was 54 s (46-72 s; Range: 35-170 s). There was low fibrinogen [median: 1.3 g/L;1, -1.8 g/L; Range: < 0.2-2.9], low factor VIII levels [median: 23%; 16-37%] and low factor V levels [median: 43%; 23-74%]. D-Dimer concentrations [median: 3.4 mg/L; 2-7.4 mg/L] were slightly elevated. Factors II, VII and X and vWF antigen concentrations were normal. Discussion and Conclusions. Hump-nosed pit viper bites result in a mild coagulopathy which is usually not detected by a WBCT20. It is characterised by mild elevation of INR, low fibrinogen and Factors V and VIII which may be consistent with the venom containing a thrombin-like enzyme. [ABSTRACT FROM AUTHOR]

Brown recluse spider (Loxosceles reclusa) envenomations with subsequent necrotic skin lesions occur infrequently, and systemic loxoscelism is rarer still. We report a case of 2 successive developing necrotic lesions, each on adjacent medial aspects of the legs, secondary to presumed Loxosceles envenomation. A 31-year-old man with no significant past medical history presented to the emergency department with 2, large, necrotic lesions, 1 on each medial thigh. They had progressed over the course of 1 month from small blisters to large necrotic lesions with eschar. He underwent surgical debridement without skin grafting with no further complications. Bites from recluse spiders that progress to necrosis usually present as single lesions. The differential diagnoses for a necrotic skin lesion is large. The presence of more than 1 lesion argues against Loxosceles envenomation; however, in the absence of underlying infection, systemic diseases, immunodeficiency, or malignancy, the diagnosis must be considered if the case presents in an endemic area. Brown recluse spiders rarely bite multiple times, thus confounding the diagnosis of an already nonspecific clinical finding. [ABSTRACT FROM AUTHOR]

Background: Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors. Objective: Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters with the frequency of VIT failure during the maintenance phase. Methods: In this observational prospective multicenter study, we followed 357 patients with established honey bee or vespid venom allergy after the maintenance dose of VIT had been reached. In all patients, VIT effectiveness was either verified by sting challenge (n = 154) or patient self-reporting of the outcome of a field sting (n = 203). Data were collected on BTC, age, gender, preventive use of anti-allergic drugs (oral antihistamines and/or corticosteroids) right after a field sting, venom dose, antihypertensive medication, type of venom, side effects during VIT, severity of index sting reaction preceding VIT, and duration of VIT. Relative rates were calculated with generalized additive models. Results: 22 patients (6.2%) developed generalized symptoms during sting challenge or after a field sting. A strong association between the frequency of VIT failure and BTC could be excluded. Due to wide confidence bands, however, weaker effects (odds ratios <3) of BTC were still possible, and were also suggested by a selective analysis of patients who had a sting challenge. The most important factor associated with VIT failure was a honey bee venom allergy. Preventive use of anti-allergic drugs may be associated with a higher protection rate. Interpretation: It is unlikely that an elevated BTC has a strong negative effect on the rate of treatment failures. The magnitude of the latter, however, may depend on the method of effectiveness assessment. Failure rate is higher in patients suffering from bee venom allergy. [ABSTRACT FROM AUTHOR]

Ultrastructural answer of bone marrow erythroid series and of red blood cells (RBCs) in Wistar rats to bee venom (BV) was analyzed by transmission and scanning electron microscopy, and corroborated with hematological data. A 5-day and a 30-day treatment with daily doses of 700 μg BV/kg and an acute-lethal treatment with a single dose of 62 mg BV/kg were performed. The 5-day treatment resulted in a reduced cellularity of the bone marrow, with necrosed proerythroblasts, polymorphous erythroblasts, and reticulocytes with cytoplasmic extensions, and a lower number of larger RBCs, with poikilocytosis (acanthocytosis) and anisocytosis, and reduced concentrations of hemoglobin. After the 30-day treatment, the bone marrow architecture was restored, but polymorphous erythroblasts and reticulocytes with thin extensions could still be observed, while the RBCs in higher number were smaller, many with abnormal shapes, especially acanthocytes. The acute treatment produced a partial depopulation of the bone marrow and ultrastructural changes of erythroblasts including abnormal mitochondrial cristae. The RBCs in lower number were bigger and crenated, with reduced concentrations of hemoglobin. Overall, BV was able to promote stress erythropoiesis in a time- and dose-related manner, mitochondrial cristae modification being a critical factor involved in the toxicity of the BV high doses. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we evaluated the effect of the Crotalus durissus terrificus (Cdt) venom on the chronic paw edema induced by the injection of bacillus Calmette-Guérin (BCG) into the footpad of mice. The BCG injection evoked chronic edema, which was significantly diminished in animals treated subcutaneously (s.c.) with Cdt venom 1 h before or after the BCG injection. This inhibition persisted throughout the evaluation period (15 days). In mice injected with Cdt venom 6 or 11 days after injection of BCG, we observed a significant reduction in edema only in the period after the venom injection. While studying possible mechanisms involved in this inhibition, we observed that pre-treatment with dexamethasone, zileuton or Boc2 (a selective antagonist of formyl peptide receptors), but not with indomethacin, canceled out the inhibitory effect of Cdt venom on the edema induced by BCG. These results strongly suggest that this rattlesnake venom can stimulate the generation of mediators from the lipoxygenase pathway, which can down-regulate this chronic inflammatory edema. Using fractionated venom, the results indicated that crotoxin was the only component of Cdt venom responsible for this inhibitory effect. These results indicated that crotoxin, the main toxin of the C. durissus terrificus venom, has a significant inhibitory effect on BCG-induced chronic edema, possibly by generating anti-inflammatory mediators from the lipoxygenase pathway. [Copyright &y& Elsevier]

Abstract: Animal venoms are complex chemical mixtures that typically contain hundreds of proteins and non-proteinaceous compounds, resulting in a potent weapon for prey immobilization and predator deterrence. However, because venoms are protein-rich, they come with a high metabolic price tag. The metabolic cost of venom is sufficiently high to result in secondary loss of venom whenever its use becomes non-essential to survival of the animal. The high metabolic cost of venom leads to the prediction that venomous animals may have evolved strategies for minimizing venom expenditure. Indeed, various behaviors have been identified that appear consistent with frugality of venom use. This has led to formulation of the “venom optimization hypothesis” (Wigger et al. (2002) Toxicon 40, 749–752), also known as “venom metering”, which postulates that venom is metabolically expensive and therefore used frugally through behavioral control. Here, we review the available data concerning economy of venom use by animals with either ancient or more recently evolved venom systems. We conclude that the convergent nature of the evidence in multiple taxa strongly suggests the existence of evolutionary pressures favoring frugal use of venom. However, there remains an unresolved dichotomy between this economy of venom use and the lavish biochemical complexity of venom, which includes a high degree of functional redundancy. We discuss the evidence for biochemical optimization of venom as a means of resolving this conundrum. [Copyright &y& Elsevier]