Venomous Injuries Research Articles

Selective reaction of conjugated polymers with basic proteins for broad-spectrum antivirulence therapy

Antivirulence therapy has proven to be an attractive method for the treatment of bacterial infections and venomous injuries; however, the approaches for neutralizing multiple types of virulence through one platform are limited. To address this challenge, we have developed a reactive conjugated polymer, PPV–NHS, which functions as a broad-spectrum antidote for directly inactivating basic toxins. The antivirulence is achieved via multivalent electrostatic recognition and subsequent amidation reactions between PPV–NHS and toxins. The resultant bioconjugates significantly reduced neurotoxicity and cytotoxicity. In the mouse model, PPV–NHS effectively inhibited the toxicity of cardiotoxin (CTX) and improved the survival rate of toxin-challenged mice. This work represents the rational design of functionalized conjugated polymers for antivirulence therapy with both high efficiency and broad applicability.

Injury trends from envenoming in Australia, 2000–2013

Accidental injury is a major public health problem in developed countries with 20 years elapsed since a national overview of venomous bites undertaken in Australia. Provide the first contemporary epidemiological insight into venomous injuries based on demographics and geography nationally in Australia in the period 2000-2013. An analysis of national hospitalisation and mortality data was undertaken to examine the incidence of injury and death due to envenoming in Australia. Rates were calculated using the intercensal population for all Australian age groups. Over the study period, deaths occurred due to an anaphylactic event (0.16 per 100 000), snake envenoming (0.13 per 100 000) or box jellyfish envenoming (0.01 per 100 000). Only 44% of cases involving anaphylaxis reached medical care prior to death, compared to 74% of those envenomed by snakes. Over half of all deaths (52%) occurred at home, and 64% of these occurred within a major city or inner regional area, with 48% of work-related anaphylaxis deaths. Hospital admission rates of 199 per 100 000 persons over the 11 years were caused by contact with wasps or bees (31%), spiders (30%) and snakes (15%), with a predominant age range of 30-44 years. The greatest burden of injury due to envenoming was caused by arthropods and snakes. Causes of death were led by anaphylaxis subsequent to an arthropod bite or sting, followed by death from snake envenoming. Over half the incidents resulting in death occurred at home, in areas where healthcare is accessible. Operational data routinely collected are informative, with variations of injury incidence between the States and Territories, indicating a need for a more localised approach to the management of this injury.

Functional Nanoparticles Activate a Decellularized Liver Scaffold for Blood Detoxification

Extracorporeal devices have great promise for cleansing the body of virulence factors that are caused by venomous injuries, bacterial infections, and biological weaponry. The clinically used extracorporeal devices, such as artificial liver-support systems that are mainly based on dialysis or electrostatic interaction, are limited to remove a target toxin. Here, a liver-mimetic device is shown that consists of decellularized liver scaffold (DLS) populated with polydiacetylene (PDA) nanoparticles. DLS has the gross shape and 3D architecture of a liver, and the PDA nanoparticles selectively capture and neutralize the pore-forming toxins (PFTs). This device can efficiently and target-orientedly remove PFTs in human blood ex vivo without changing blood components or activating complement factors, showing potential application in antidotal therapy. This work provides a proof-of-principle for blood detoxification by a nanoparticle-activated DLS, and can lead to the development of future medical devices for antidotal therapy.

A biomimetic nanosponge that absorbs pore-forming toxins

Detoxification treatments such as toxin-targeted anti-virulence therapy1, 2 offer ways to cleanse the body of virulence factors that are caused by bacterial infections, venomous injuries, and biological weaponry. Because existing detoxification platforms such as antisera3, monoclonal antibodies4, small-molecule inhibitors5, 6, and molecularly imprinted polymers7 act by targeting the molecular structures of the toxins, customized treatments are required for different diseases. Here we show a biomimetic toxin nanosponge that functions as a toxin decoy in vivo. The nanosponge, which consists of a polymeric nanoparticle core surrounded by red blood cell membranes, absorbs membrane-damaging toxins and diverts them away from their cellular targets. In a mouse model, the nanosponges markedly reduce the toxicity of staphylococcal alpha-hemolysin (α-toxin) and thus improve the survival rate of toxin-challenged mice. This biologically inspired toxin nanosponge presents a detoxification treatment that can potentially treat a variety of injuries and diseases caused by pore-forming toxins.

Circus Venomous: An interactive tool for toxinology education

BackgroundClinical education about envenomations and their treatment may convey clinical and zoological details inadequately or flatly. In recent years, the widespread availability of models and videos of venomous species have created unique opportunities for toxinology education. We share our experiences using a new toolkit for educating a diverse array of clinicians, students, and wilderness medicine enthusiasts. MethodsWe examined the cost, number of participants, and satisfaction data since the initiation of a portable workshop featuring high-fidelity exhibits of venomous species. Termed the “Circus Venomous,” this educational toolkit consists of several boxes of props, such as plastic models, photos, and preserved specimens of injurious species. The workshop consists of three phases: 1.) participants view all exhibits and answer clinical questions regarding venomous injuries; 2.) short video clips from television, internet, and cinema are viewed together, and myths about envenomation injuries are debunked; 3.) debriefing session and wrap-up. ResultsWe have utilized the Circus Venomous to teach medical students, residents, practicing community clinicians, nurses, PAs, national and regional parkmedics, and wilderness enthusiasts. The major cost (about $800) was spent on the purchase of highly durable, lifelike models and well preserved real reptile and arachnid specimens. When formal feedback was solicited, the participants expressed high levels of satisfaction, scoring an average of 4.3, 4.4, and 4.3 out of 5 points in the respective areas of content, presentation, and practical value of the activity. Since we have used this exhibit with approximately 250 participants over 2 years, we estimate the materials cost per participant is approximately $3. ConclusionsThe Circus Venomous is a novel, interactive, flexible, and cost-effective teaching tool about envenomation emergencies. We hope that this concept will encourage other clinical educators toward further innovation. Future directions for our group include greater inclusion of marine species into the Circus Venomous, and formal longitudinal testing to measure knowledge retention based on this approach.

Pulsed ultrasound therapy accelerates the recovery of skeletal muscle damage induced by Bothrops jararacussu venom

We studied the effect of pulsed ultrasound therapy (UST) and antibothropic polyvalent antivenom (PAV) on the regeneration of mouse extensor digitorum longus muscle following damage by Bothrops jararacussu venom. Animals (Swiss male and female mice weighing 25.0 ± 5.0 g; 5 animals per group) received a perimuscular injection of venom (1 mg/kg) and treatment with UST was started 1 h later (1 min/day, 3 MHz, 0.3 W/cm2, pulsed mode). Three and 28 days after injection, muscles were dissected and processed for light microscopy. The venom caused complete degeneration of muscle fibers. UST alone and combined with PAV (1.0 mL/kg) partially protected these fibers, whereas muscles receiving no treatment showed disorganized fascicules and fibers with reduced diameter. Treatment with UST and PAV decreased the effects of the venom on creatine kinase content and motor activity (approximately 75 and 48%, respectively). Sonication of the venom solution immediately before application decreased the in vivo and ex vivo myotoxic activities (approximately 60 and 50%, respectively). The present data show that UST counteracts some effects of B. jararacussu venom, causing structural and functional improvement of the regenerated muscle after venom injury.

Origin of Interstitial Fibroblasts in an Accelerated Model of Angiotensin II-Induced Renal Fibrosis

To determine whether previous renal injury accelerates the progression of glomerulosclerosis and interstitial fibrosis, we examined the effect of treating rats with angiotensin II after Habu venom injury. After initiating disease, we examined the origin of interstitial myofibroblasts by locating alpha-smooth muscle actin (alpha-SMA)-positive and Na+,K+-ATPase-positive cells relative to interstitial space, tubular epithelial cells, the tubular basement membrane (TBM), and vascular structures. Tubular epithelial-mesenchymal transition was also assessed by examining TBM integrity and by using Texas Red (TR)-dextran in intravital tracking experiments. The staining of alpha-SMA-positive myofibroblasts dramatically increased in peritubular interstitial spaces 48 hours after Habu venom plus angiotensin II, particularly in and around perivascular and periglomerular regions, while tubular epithelial cells were alpha-SMA-negative. Na+,K+-ATPase-positive and TR-dextran-labeled cells were restricted to the tubular epithelium and excluded from the interstitium. By 7 and 14 days, expanded interstitial space contained only alpha-SMA-positive myofibroblasts without TR-dextran endocytic particles. Epithelium of atrophic tubules containing TR-dextran remained confined by surrounding interstitium and myofibroblasts. These studies indicate that early expansion of alpha-SMA-positive cells in the interstitium and loss of tubular area occur via encroachment of interstitial myofibroblasts from perivascular into atrophic tubular spaces rather than via epithelial-mesenchymal transition and migration of tubular cells through the TBM into the interstitium.

Efficacy, safety, and use of snake antivenoms in the United States

The mainstay of hospital treatment for venomous snakebite is antivenom. There is currently only one antivenom available in the United States for the treatment of pit viper envenomation, Antivenin (Crotalidae) Polyvalent (ACP). The general indication for the administration of antivenom is presence of progressive venom injury. Progressive injury is defined as worsening local injury (eg, swelling, ecchymosis), a clinically important coagulation abnormality, or systemic effects (eg, hypotension, altered mental status). Unfortunately, there are no prospective data available regarding the efficacy of ACP. The efficacy of a new antivenom (CroFab; FabAV) composed of purified Fab specific to indigenous snake species has been demonstrated in prospective trials. FabAV appears as effective as IgG antivenoms. However, Fab molecules have a shorter half-life than IgG molecules and may allow recurrence of venom effects, if additional doses are not administered. It has also been found that other antivenoms, including ACP, also allow recurrence of venom effects. The Fab preparation has produced fewer acute or delayed (serum sickness) allergic reactions; however, further experience is needed to confirm this observation. Evaluation of this new antivenom has led to advances in our understanding of antivenoms in terms of solubility and durability. Fab fragments enter solution quickly, thereby shortening the time to antivenom administration and are remarkably stable under extreme conditions of heat and handling. [Dart RC, McNally J. Efficacy, safety, and use of snake antivenoms in the United States. Ann Emerg Med. February 2001;37:181-188.]

Antivenin therapy in the emergency department

Venomous animal injuries constitute a significant medical problem worldwide. It is estimated that 40,000 people die annually from venomous snakebite alone. The total morbidity and mortality due to venomous reptiles, arthropods, and marine animals is unknown. The majority of venomous injuries are found in developing countries where the combination of rural populations, high density venomous animal species, and inadequate medical facilities generate a serious public health problem. While venomous animal injuries are less of a problem in the United States, when they do occur they may become a difficult problem to manage and often a major life threat.‘-” Emergency medicine physicians are likely to be involved wth the diagnosis and management of a venomous injury because of their position at the vanguard of the medical system. As in many other emergent conditions, the initial therapy is extremely important and will influence the final outcome of the envenomation. The definitive treatment of envenomation injuries, especially those due to snakebite, is antivenin

Mast Cells and Local Resistance to Russell's Viper Venom

Summary It was observed that the subcutaneous injection of Russell's Viper venom initiated an explosive release of heparin-containing granules from local tissue mast cells and that the shed granules were subsequently ingested by fibroblasts and various other cell types involved in the connective tissue response to venom injury. Investigations of the significance of these cellular events indicated that heparin can form acid-base complexes with noxious factors of the venom in vitro and inhibit both local and systemic injury by this venom in mice. Inasmuch as this antivenom effect of heparin is only one aspect of a more general antitoxic activity of this mucopolysaccharide, it is suggested that the degranulation of mast cells may serve an important function in local resistance to injury by various cationic substances.