wound

Synthetic peptide inspired by Komodo dragon blood speeds wound healing

dr. dolittle — Wed, 19 Apr 2017 00:52:01 +0000

Synthetic peptide inspired by Komodo dragon blood speeds wound healing

Image of a Komodo dragon By Charlesjsharp - Own work, from Sharp Photography, sharpphotography, CC BY-SA 4.0, via Wikimedia Commons

Researchers at George Mason University have created a synthetic version of a peptide found in the blood of Komodo dragons (Varanus komodoensis). They dubbed the synthetic peptide DRGN-1. Living up to its name, DRGN-1 proved to be pretty tough against microbes (Pseudomonas aeruginosa and Staphylococcus aureus) as well as biofilms. Bacteria stick together to create biofilms that attach to surfaces and help to protect themselves during an infection. Even infected wounds healed faster when they were treated with DRGN-1 and the layers of skin were rehabilitated. Given the positive outcomes of this study, the hope is to create a topical treatment for wound healing.

Source:

EMC Chung, SN Dean, CN Propst, BM Bishop, ML van Hoek. Komodo dragon-inspired synthetic peptide DRGN-1 promotes wound-healing of a mixed-biofilm infected wound. npj Biofilms and Microbiomes 3, Article number: 9 (2017). doi:10.1038/s41522-017-0017-2

dr. dolittle Tue, 04/18/2017 - 20:52

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Life Science

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Wound healing with fish?

dr. dolittle — Sun, 22 Feb 2015 02:04:30 +0000

Wound healing with fish?

Pictoral abstract showing the use of nanofibers from fish collagen in wound healing. Image from Zhou et al., 2015.

Researchers in China have discovered that collagen isolated from the skin of tilapia effectively reduce wound healing time in mice. The usefulness of collagen, a major structural protein found in connective tussues, in wound healing has been known. Using fish proteins instead of typical mammalian sources reduces the risk for potential pathogens.

Dr. Jiao Sun (Shanghai Jiaotong University School of Medicine) and colleagues isolated collagen from the skin of tilapia and spun the collagen into nanofibers.The nanofibers were shown to have high tensile strength (great for keeping the skin together while moving around) and were hydrophilic and stable thermally. Most importantly, the fish collagen did not cause an immune response in rodents and actually reduced healing time of wounds on rats in comparison to untreated wounds or wounds treated with alginate dressings.

In a quote from Chemistry World, Dr. Giuseppe Tronci (University of Leeds) who was not involved in the study stated "Given the outstanding in vivo data, it would be interesting to see how the skin regeneration potential of this material compared with that of a commercially available collagen-based wound dressing, such as Promogran from Systagenix or Biostep from Smith & Nephew. I would also be curious to see what kind of gelling properties these materials show in physiological conditions and to what extent the collagenous structure (triple helices, fibrils) is retained in the resulting mesh, since both aspects are crucial in terms of wound exudate management and skin wound healing."

dr. dolittle Sat, 02/21/2015 - 21:04

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This is a really interesting idea. If it proves to be very effective there could be a great market for it and endless supply as it is very easy to farm Tilapia. The question is would it be financially viable to process all the skin on a large scale and would the meat still be available for sale to the food industry as well?

Technology has advance to such an extent as is, it is hard to believe the rate of new discoveries. Though this is still an ongoing experiment, if this happens to be a viable alternative it could vastly improve the current shelf products available for would healing. Biostep, a product of Smith and Nephew, is also a collagen dressing, it maintains an optimal moist wound environment while focusing on the patients comfort. Provided this proves to be a success, incorporating Tilapia proteins in these products would add the benefit of reduced wound healing time. Introducing an additional use for Tilapia wont necessarily affect the supply in food as Tilapia is simple to farm. However, if demand increases drastically due to this discovery the Tilapia species may be threatened as the previous comment suggests.

u15102808.

I have done some further research and the tests done so far have definitely shown a dominant pattern of success. Reduced wound healing time would be an important development in Health Care because Allied Health Care processes such as Physiotherapy and Occupational Therapy can only commence once wounds are healed. Therefore, if the wounds heal faster, therapy can begin sooner and the patient can get back to their normal life in a shorter time. I do think this is a clever alternative; however I also agree that this will one day put strain on the tilapia populations. This problem can be overcome if we manage our sources right from the beginning and are not foolishly reassured by the fact that the fish can “be farmed easily”.

This is a revolutionary approach to cosmetic recovery. specific measures should be put in place to monitor the fish stocks

Fish farms should sign contracts with the medical company's to ensure the sustainability of the treatment and fish stocks.

As scientists their should be more studies done to mutate the collagen till the point is reached where healing time is so drastically shortened that there are better healing towards larger wounds. This would be a vital asset in military exploits.
u15169988

According to a study by the Nagasaki University Graduate School of Biomedical Sciences, the tilapia collagen is safe for clinical application. It was tested for bacteria, virusses, cell toxicity and other potentially harmful factors, but all results were negative. Clearly it has excellent potential and obstacles concerning the future of tilapia populations can surely be overcome.

I think that this would impact Tilapia numbers, anything that requires fish to be removed from their natural habitat would.

This research seems to yield very promising results and is a highly innovative technique is wound healing. Decreasing the wound healing time could mean patients spending less time in hospital and thus more space being made available faster, in order for new patients to come in and be treated.

The only downfall is that the Tilapia fish numbers could take a seriously plunge if this technique in wound healing had to take off. It could soon be demanded all over the world, thus putting huge strain on the Tilapia population. I think that more research needs to be done into how they could replicate the collagen fibers in order to reduce the strain on the Tilapia populations.

There are a lot of proffesions that are being neclected as due to the workers being incapable of performing those proffesions because of injuries. If the healing time of all wounds could be reduced the injured parties can go back to work quicker, and therefore the industrie's growth can be increased making it and the economy grow. The quantity of the injured parties being healed will also increased as due to the fact that healing time is less.

Is fish farming a viable option? At least temporarily?

Another very inventive approach to helping the human body heal. A decrease in wound healing time has multiple benefits in the field of medicine. This decrease in healing time will allow patients to return to their daily routine sooner. Promising for military field, burn patients and patients who underwent surgery.

It is, however, important that we take into consideration the Tilapia population. Would it be possible for scientists to develop a way to duplicate the fibres in order to preserve the species?

u15092977

this is so amazing but I think this should not be taken as only method of healing rats. As it could also reduce the number of tilipias. Remember the tilipias are already being used as food. Using them again as 'medicine' will only double the rate of harvesting them. Results also show that the harvesting of tilipias is increasing yearly.

Would it be profitable to farm with Tilapia? Would it have a negative impact on Tilapia population in their natural habitat?

How long would it take until people can start using it?

Technology is amazing.

Would it be profitable to farm with Tilapia? Would it have a negative impact on Tilapia population in their natural habitat?
u15006663

How profitable would fish farming be? And how would the discovery affect the Tilapia fish population in it's natural habitat?

How profitable would fish farming be? And how would the discovery affect the Tilapia fish population in it’s natural habitat?
u15006663

I've always know Tilapia as being a fish served with some chips and tartar sauce so reading this blog has been extremely interesting. I read into the topic a bit more and I see that the study of finding methods that accelerate healing have been going on for a while. I'm just curious as to how much skin of the Tilapia fish is needed or rather used to generate enough collagen to treat wounds?

This is fascinating and potentially a medical break through. However, how much is healing time reduced? Are there any side effects? What impact could this have in the fish population.
it certainly sounds like a medical solution but is this a viable form of treatment for humans?

I know Tilapia as being a fish served with chips and tartar sauce so reading this blog has been extremely interesting. I read into the topic a bit more and i see that the study of finding methods that accelerate healing have been going on for a while. I'm just curious as to how much skin of the Tilapia fish is needed or rather used to generate enough collagen to treat wounds?

With a potential break through such as this many questions are raised. According to the article the time for wounds to heal was shortened, but by how much and if one assumes the healing time is shortened by a significant amount is this a viable medical solution. will there be an impact on the fish or can we fish farm this breed and if we do will this have an effect on how efficiently they reduce wound heeling time?
u15078851

I think that its very interesting and has great potential. If they can combine the information they found with nanotechnology they can make an synthetic material with the exact same properties. This way there is no need to farm with tilapia and puts no strain on their population.
u14224781

I did my matric life sciences research task on Tilapia (specifically the Milawian strains, although there are over 100 strains being actively used in the aquaponic and fishing industries worldwide) which allowed me to do a lot of research and experiments with the fish (within ethical boundaries). Tilapia can be grown to adulthood in a relatively shorter time compared to other fish types and can survive in very extreme envirnments. These qualities allow the Tilapia to be a good choice for medical research because if they prove to be an asset (which this article proves they are) then they can be farmed efficiently, allowing more research to be done until a final product is achieved, and even after that (which is ethically allowable if the fish are not harmed in the harvesting of the collagen nanofibers).

Makes one think – the next time when I go fishing, the “Tilapia” I catch can be used for medicinal purpose – great research. Fish farming a definite must !
(u15016928)

This is a very interesting discovery indeed. Rapid wound healing is desirable for sure. However should the Tilapia be dead when extracting the collagen? Or can it be extracted when its still alive? Besides should the fish grow to adult size for the extraction to be done?

The skin of a Tilapia fish reduces wound healing in time of mice, but will it be as effective in humans?
15320074

it is very interesting.
I would appreciate it if more posts can be done on this subject due to the lack of studies in proteins that heals wounds.
(u150393160

what an amazing discovery to the world of medicine.

15320074

wow! who knew that fish can heal wounds
15320074

This is remarkable, with this information many things can be achieved in the near future and could have a positive affect on the environment.

This is some super interesting information.

wow! the healing power of nature
15320074

I think that to start farming with Tilapia fish would be remarkable if only if it will be effected as suggested by Melissa Pistorius. This research can have an enormous effect on the medicine practice and wound healing, there may possibly be other useful uses of the Tilapia. The Tilipia fish used for wound healing is very interesting and makes one question the sufficient opportunities that the universe gives us.

This is a very interesting blog. Who knew fish has the potential to do so much. This medical research could be the answer to reducing death rate in areas such as war zones. Healing of wounds at a faster rate will save a lot of lives in crisis areas.
u15139264

Wound healing is very desirable indeed. However the fish should be dead in order to extract the collagen?

this is very interesting.

Massive applications in regenerative medicine. Burn victims were the first to pop into my mind. Being able to heal burned skin to a great extent would almost diminish the need for skin grafting. The time, energy and, most importantly, trauma, would be avoided or minimized. Injuries to other parts of the body, both internal and external, could also benefit from this. Sports-related injuries that would have otherwise ended a player's career could also be targeted.

Co-Existence is astonishing ! there are even zebra fish who have recently been identified as having almost shared 70% of the human genome! We are discovering the functions of many unknown genes in the human genome along with compounds that might help cure heart disease. One of the many reasons why we need to conserve and preserve all species

Wow amazing stuff ! i agree preservation is key ! cant discover such things from fossils

There is so much research that this can be applied to ! very exciting

The regenerative medicine application are endless. When you consider burn victims, healing their own skin would be much more beneficial than getting a skin grafting surgery. Healing would be very swift. Functionality could also improve. Sports medicine could also benefit greatly from this. If modified, this treatment could heal injuries of the knee and tendons; Injuries that are likely to create injuries that at the best cause the athlete to miss several months of the season and at worst end their career. These are but a few examples to the many possibilities of the potential breakthrough.

This is a very helpful breakthrough of coarse but immediately the problem of overfishing arises. If this is truely a way of speeding the healing process, I think the first thing to do is to establish farms for these fish to avoid our only lead on speeding healing to die out before the world gets to use this amazing technology.
04667124

African rodent species resist scarring

dr. dolittle — Fri, 28 Sep 2012 13:40:04 +0000

African rodent species resist scarring

You might be familiar with tissue regeneration in amphibians and reptiles where limbs can be fully regenerated following an injury. Until now, tissue regeneration following a wound was thought to be limited in mammals (ex: deer shed and regrow their antlers annually; some mice can regrow the tips of their fingers).

Researchers discovered that African spiny mice are able to regrow skin, complete with hair follicles, after an injury. We are not talking about simple wound healing, but actual skin regeneration without scarring. Researchers suspect this unique ability may have evolved to help them avoid predators since they are capable of shedding large patches of skin to escape. Researchers found their skin to be less elastic than laboratory mice (M. musculus), increasing its susceptibility to tearing. Sometimes the tears are so deep, the muscles below become exposed.

A transdermal injury at day 3. Figure from: Nature doi: 10.1038/nature11499

Transdermal injury at day 30. Figure from Nature doi: 10.1038/nature11499

The researchers found that epithelial cell migration to the site of injury was much faster in the African mice. The collagen fibers also organized into loose bundles, preventing scarring. In contrast, collagen fibers in laboratory mice form dense, organized bundles that promote scars. Moreover, the African mice actually regrow hair follicles, whereas laboratory mice do not. Not only can the animals regrow torn skin, but they are also able to heal holes pierced into their ears complete with cartilage, hair follicles, skin, sebaceous glands and fat without scarring, although the regrown tissue lacked muscle. This ear regeneration is regulated by specialized cells called blastema that are similar to those found in lizards capable of regrowing tails.

Researchers hope this research will help to better understand tissue regeneration, as opposed to scarring, capabilities in mammals.

This research reminds me of the futuristic technology in Star Trek episodes, where they use light to heal wounds with minimal scarring.

Source:
Seifert AW, Kiama SG, Seifert MG, Goheen JR, Palmer TM, Maden M. Skin shedding and tissue regeneration in African spiny mice (Acomys). Nature. 489:561-566, 2012.

dr. dolittle Fri, 09/28/2012 - 09:40

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Venomous Komodo dragons kill prey with wound-and-poison tactics

edyong — Mon, 18 May 2009 15:00:33 +0000

Venomous Komodo dragons kill prey with wound-and-poison tactics

For the longest time, people believed that the world's largest lizard, the Komodo dragon, killed its prey with a dirty mouth. Strands of rotting flesh trapped in its teeth harbour thriving colonies of bacteria and when the dragon bites an animal, these microbes flood into the wound and eventually cause blood poisoning.

But that theory was contested in 2005 when Bryan Fry from the University of Melbourne discovered that a close relative, the lace monitor, has venom glands in its mouth. The discovery made Fry suspect that Komodo dragons also poison their prey and he has just confirmed that in a whirlwind of a paper, which details the dragon's "sophisticated combined-arsenal killing apparatus".

By putting a virtual dragon skull through a digital crash-test, Fry showed that its bite is relatively weak for a predator of its size - instead it's adapted to resist strong pulling forces. This is a hunter built to inflict massive wounds through a "grip and rip" style that involves biting lightly but tearing ferociously.

The wounds provide a large open area for the dragon to inject its venom and Fry unquestionably showed that the dragons poison their prey. By placing the head of a terminally ill dragon in an MRI scanner, he managed to isolate the venom glands, which turn out to be more structurally complex than those of any other snake or lizard. He even managed to analyse a sample of venom, which is loaded with toxins that prevent blood from clotting and induce shock.

And as the icing on the cake, Fry concluded that Varanus prisca, a extinct close relative of the Komodo dragon probably also had venom glands. Also known as Megalania, V.prisca was three times the size of the Komodo dragon, making it (to our knowledge) the largest venomous animal to have ever lived.

Fry used a CT scanner to create a three-dimensional model of a Komodo dragon's skull and he assessed its properties with a technique called finite element analysis. Engineers use the method to crash-test cars; Fry used it to compare the dragon's skull to that of another giant reptile - the saltwater crocodile. Of the two, the dragon had a much weaker bite, exerting just 39N of force with its jaws compared to the 252N chomp of the croc. If a dragon bit with that much strength, its skull would fracture.

The dragon's skull wasn't much better at coping with twisting or shaking movements either - this is not an animal that can bite and hold onto a prey animal for long. However, Fry found that its skull is highly resistant to pulling forces, and that's the key to its method of attack. Biologists watching these animals have noted that when they bite, they often yank their heads back with powerful neck muscles. Their skulls take the brunt and their sharp, serrated teeth open considerable wounds in their prey.

Other studies using finite element analysis have found that other famous predators, like sabre-toothed cats and great white sharks, do similar things. For their size, they have relatively weak bites but they made up for it with strong neck muscles and very sharp teeth. In all cases, prey start losing blood, but those bitten by the Komodo dragon suffer from another weapon - venom.

Fry used a medical MRI scanner to analyse the preserved head of a dead Komodo dragon and found that it has two long venom glands, running down the length of its jaw. They are the most structurally complex venom glands of any reptile. Each consists of six compartments, with ducts leading from each one to openings between the teeth. Other venomous lizards, like the Gila monster, channel venom down grooves that run the length of their teeth but the Komodo dragon doesn't have these - it just drips venom straight into the wounds that it inflicts.

The venom itself consists of over 600 toxins, a chemical arsenal that rivals those of many snakes. Many of these poisons are familiar and they greatly exacerbate the blood loss caused by the dragon's bite. They cause internal haemorrhaging from leaky blood vessels, prevent blood from clotting and cause muscle contractions and paralysis. Fry calculated that a typical adult dragon would need only 4mg of venom proteins to send a 40kg deer into toxic shock from collapsing blood pressure. A full venom gland packs at least eight times this amount.

If the dragon has venom, you can be sure that it uses it. Venom is so costly to produce that the moment it becomes obsolete, natural selection rapidly does away with it. That's happened in other reptiles - members of venomous families that have developed other ways of feeding (like constriction, or egg-eating) quickly lost their venom system. The glands atrophied, the fangs became smaller and the genes that produce toxic proteins built up debilitating mutations. The Komodo dragon, on the other hand, has strong glands that are loaded with poison.

These results don't discredit the salivary bacteria idea, but Fry has little time for it. For a start, he says that since the dragon was first 'discovered' by Western scientists in 1912, no one has actually documented a case of a dragon victim falling foul of blood poisoning. While dangerous bacteria have been isolated from the mouths of Komodo dragons, no single species has been consistently identified in all individuals. This variability makes it very unlikely that dragons could rely on the presence of toxic bacteria as a reliably strategy to hinge their evolutionary success upon.

One study suggested that the bacterium, Pasteurella multocida, accounted for much of the saliva's killing power, but the researchers didn't find this lethal bug in all the dragons they looked at. P.multocida is rare in reptiles but common in mammals, especially those that are sick or old - exactly the demographic that dragons prefer to kill. As such, Fry believes that the bacteria isolated from the mouths of dragons actually came from the animals they fed on. To him, Komodo dragon victims die not from bacterial sepsis, but from heavy, bleeding wounds that are exacerbated by the toxic effects of the giant lizard's venom.

The dragon's extinct and even bigger relative, V.prisca or Megalania, may have done the same. This giant lizard also had a strong skull but relatively slender jawbones. It was very closely related to the Komodo dragon and the lace monitor, both of which are venomous. And Fry has previously shown that the capacity to produce venom evolved once in the common ancestor of snakes and lizard groups like the iguanas and monitors. There's every reason to think that V.prisca used venom too, which would make it the largest venomous animal to have ever lived.

For more venomous animals, and some truly amazing stories, be sure to check out Bryan Fry's blog Sex, Drugs and Rockin' Venom: Confessions of an Extreme Scientist.

Reference: Fry, B., Wroe, S., Teeuwisse, W., van Osch, M., Moreno, K., Ingle, J., McHenry, C., Ferrara, T., Clausen, P., Scheib, H., Winter, K., Greisman, L., Roelants, K., van der Weerd, L., Clemente, C., Giannakis, E., Hodgson, W., Luz, S., Martelli, P., Krishnasamy, K., Kochva, E., Kwok, H., Scanlon, D., Karas, J., Citron, D., Goldstein, E., Mcnaughtan, J., & Norman, J. (2009). A central role for venom in predation by Varanus komodoensis (Komodo Dragon) and the extinct giant Varanus (Megalania) priscus Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0810883106; Dragon photos by Chris Kegelman; skull image from paper.

More on komodo dragons and other lizards:

edyong Mon, 05/18/2009 - 11:00

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Seems strange that something so large needs venom, but there you go. Terrific stuff.

Stupidly, I never really thought hard about that whole septic bite thing - I mean, wouldn't that take AGES to kill the prey?

Frank, it might not take ages to kill the prey if the bacteria that infected the wound were toxic enough. The theory I'd heard is that the deer get sick (and blind!) over the course of a few days, and then when it dies the dragons sniff out the carcass nearby and gather and feed. So it is a "bite and wait" strategy. I have no idea if this is true or how this new venom evidence affects the time for the deer to drop or drop dead.

Is there any documentated cases the whole way from bite to devour with these dragons? That would give some good answers. I have also seen a program in which a local man shows a leg bite he got from a dragon, and how these bites take a long time to heal and even then they don't heal well.

@frank
it might take a day or two, but it would be low energy cost.

Fascinatingly enough, no one has ever seen a dragon track a deer for a few day, wait for it to die of infection and then eat it. Every documentary purporting to show this has staged the scenes. In attempt to recreate... something that doesn't actually exist!

What we have seen, however, are sustained frenzied attacks persisting for several minutes until the large prey item is dead from blood loss. The venom supplements the mechanical damage by keeping the bleeding going through anticoagulation and also helping induce shock.

Cheers
B

In the 1990s, I got to visit the island of Komodo with a CA Academy of Sciences group (mostly ichthyologists & their diver friends, looking for various fish species-- no herpetologists on the trip.

The dragons are so amazing. I believed the "dirty mouth" hypothesis at the time.

The venomous mouth theory is so much more parsimonious.

It is an amazing thing to see an old, unproven, but widely held belief be replaced overnight.

> toxic shock from collapsing blood pressure

@Ed

You're describing cardiogenic shock here, not necessarily toxic shock. Failure of circulation secondary to hemorrhage is cardiogenic.

The article however is nice. I always (wrongly) believed the "toxic" saliva theory.

Bryan - Thanks for commenting. Awesome work.

Frank - I think the point is that their arsenal allows them to kill things that are even larger.

J - I concur. All of this reminds me of a story I covered two years ago, where moray eels were found to have a second set of ballistic jaws in their throat, rather like Giger's Alien. And they're animals found in most large aquariums. It just goes to show that even "familiar" species are often nothing but.

Wow, those things are freaking scary dude!

RT
www.privacy-center.de.tc

Fascinating! I'll have to have a look at this paper and see if there are any unusual peptides in the venom.

toxic shock from collapsing blood pressure

@Ed

You're describing cardiogenic shock here, not necessarily toxic shock. Failure of circulation secondary to hemorrhage is cardiogenic.

A quick read of the article leads me to disagree here. Admittedly, I'm a med student, not a physiologist.
Table 1 from the article lists the following in toxins
PLA2(T-III) - thats a platelet inhibitor, which is anticoagulation and would lead to hemorrhage
Kallikrein - increases vascular permeability
Natriuretic - I believe this one is both antiplatelet, AND vasodilator (someone correct me if I'm wrong here).

So, Kallikrein and natriuretic would be vasodilation related shock that decrease blood pressure, rather than hemorrhage leading to decreased blood pressure, so I think that counts as toxic shock.

Reading this makes me wonder what we can really tell about other reptiles - like dinosaurs for example - that we only have palentological data for. Is it possible that those large reptiles also may have had venom? Would we be able to tell by looking at bones if venom glands had existed to help paralyze particularly large prey?

Heather, sadly, venom sacs don't have osteological correlates. The only way you could really tell is if a theropod tooth (I assume it would be a theropod) had a groove or hollow channel in it, which would indicate the presence of venom. So far, that hasn't been found.

Ed, wonderful article. Makes me all the more reluctant to visit the Komodo islands. :-)

The only way you could really tell is if a theropod tooth (I assume it would be a theropod) had a groove or hollow channel in it, which would indicate the presence of venom

And as this story shows, the grooved tooth isn't necessary for venom.

Re-read bits of the post. You're right! That's terrifying. So in a way, it's a simplified version of the gila monster system: the venom is almost mixing in with the saliva, which sops into the wound instantly.

So, damn. I guess there's no way to tell for sure whether theropods had venom systems or not. It would certainly make life easier for the smaller carnivores, like compsognathids and microraptorines. But as we've seen with giant varanids, it's clear that enormosity does not preclude the evolution of venom glands.

I suppose we'd have to use phylogenetic bracketing. No living crocs have venom, and as far as I know, no bird has a venom delivery system (in its mouth). So until we find some osteological evidence for venom in a dinosaur, the only thing we can say right now is "probably not."

So regarding the phylogeny, one of Fry's earlier papers suggested a clade called Toxicofera, which includes all snakes, and some lizards including monitors, iguanas, agamids, chameleons and the two species we've known were venomous for the longest time. I think the idea is that reptile venom evolved once in the origin of this group and has been subsequently lost in some.

Right. Secondarily lost in many groups, and is BEING lost in some right now. Also, chameleons? Whoa!

Ah, varanids, how I love thee.

I did take an accidental bite from an exanthematicus once and didn't notice any ill effects beyond the actual, physical trauma and the amount of bleeding seemed normal.

That was also the last time I fed a varanid by hand (hey, I was young....ish).

Why 600 toxins? That seems overkill. I'm struggling to see how a creature with 599 toxins in its bite might need to evolve the 600th...

Wouldn't 10 or 20 be enough?

There are no toxins listed in this article.

@zutroi67
To be precise, all shock is defined by falling perfusion and, frequently, falling blood pressure...be that septic, hypovolemic, cardiogenic or obstructive shock. Blood pressure falls in septic shock just as it would in cardiogenic shock. And, shock due to blood loss is hypovolemic, not cardiogenic. Cardiogenic would be some defect of the function of the heart itself (like myocarditis).