Sting First Aid and Box Jelly General Informatio by Angel Yanagihara
Peer Reviewed Scientific Publications by Angel Yanagihara

Cnidarian envenomations are the leading cause of severe and lethal human sting injuries from mari... more Cnidarian envenomations are the leading cause of severe and lethal human sting injuries from marine life. The total amount of venom discharged into sting-site tissues, sometimes referred to as " venom load " , has been previously shown to correlate with tentacle contact length and sequelae severity. Since <1% of cnidae discharge upon initial tentacle contact, effective and safe removal of adherent tentacles is of paramount importance in the management of life-threatening cubozoan stings. We evaluated whether common rinse solutions or scraping increased venom load as measured in a direct functional assay of venom activity (hemolysis). Scraping significantly increased hemolysis by increasing cnidae discharge. For Alatina alata, increases did not occur if the tentacles were first doused with vinegar or if heat was applied. However, in Chironex fleckeri, vinegar dousing and heat treatment were less effective, and the best outcomes occurred with the use of venom-inhibiting technologies (Sting No More ® products). Seawater rinsing, considered a " no-harm " alternative, significantly increased venom load. The application of ice severely exacerbated A. alata stings, but had a less pronounced effect on C. fleckeri stings, while heat application markedly reduced hemolysis for both species. Our results do not support scraping or seawater rinsing to remove adherent tentacles.

Cubozoa-class cnidarian (box jellyfi sh) envenomations constitute a complex medical challenge and... more Cubozoa-class cnidarian (box jellyfi sh) envenomations constitute a complex medical challenge and public health threat. There are currently no validated standards of care for life-threatening stings. Increasing numbers and reported geographic ranges of serious cubozoan envenomations underscore the urgent need for mechanism-based emergency therapeutic options for lifeguards, fi rst responders and clinicians. For the most part, treatment and management approaches have been symptom-driven, utilizing therapeutics familiar to the practitioner and often based on extrapolation from other envenomation sequelae, rather than cubozoan-specifi c standardized protocols. Newly elucidated mechanisms of pathogenesis provide a context for directed clinical research to test novel therapeutic approaches that could greatly diminish human suffering and improve outcomes. The current state of our understanding about the pathophysiology of cnidarian envenomation and emerging therapeutic options for the medically relevant cubozoans will be presented.

/3-Adrenergic agonist-stimulated hyperpolarization,
whole-cell cAMP accumulation, and activity of... more /3-Adrenergic agonist-stimulated hyperpolarization,
whole-cell cAMP accumulation, and activity of isoproterenol-stimulated
membrane-bound adenylate cyclase
(EC 4.6.1.1) in Xenopus laevisovarian oocytes are entirely
dependent on the presence of nascent follicle cells. A
method was developed to remove rapidly and completely
all extra-oocyte cell types to yield defolliculated oocytes
that exhibited normal viability and resting membrane
potentials yet lacked /3-adrenergic receptor (/3AR)-
stimulated responses. Purified follicle membranes contained
/3AR.-stimulated adenylate cyclase activity, whereas
oocyte cell membranes did not. Purified oocyte membrane
preparations from X laevis oocytes previously
microinjected with C6-2B rat astrocytoma mRNA,
and subsequently defolliculated, exhibited novel /3AR
and forskolin-stimulated adenylate cyclase activity.
These experiments demonstrate that oocytes expressed
rat C6-2B mRNA coding for the /3-adrenergic receptor
and the components necessary for forskolin-stimulated
adenylate cyclase activity. - SMITH, A. A.; BROOKER,
T.; BROOKER, G. Expression of rat mRNA coding for
hormone-stimulated adenylate cyclase in Xenopzsroocytes.
FASEBJ 1: 380-387; 1987

Abstract: Despite the medical urgency presented by cubozoan envenomations, ineffective and
contra... more Abstract: Despite the medical urgency presented by cubozoan envenomations, ineffective and
contradictory first-aid management recommendations persist. A critical barrier to progress has been
the lack of readily available and reproducible envenomation assays that (1) recapitulate live-tentacle
stings; (2) allow quantitation and imaging of cnidae discharge; (3) allow primary quantitation of
venom toxicity; and (4) employ rigorous controls. We report the implementation of an integrated
array of three experimental approaches designed to meet the above-stated criteria. Mechanistically
overlapping, yet distinct, the three approaches comprised (1) direct application of test solutions on
live tentacles (termed tentacle solution assay, or TSA) with single image- and video-microscopy;
(2) spontaneous stinging assay using freshly excised tentacles overlaid on substrate of live human red
blood cells suspended in agarose (tentacle blood agarose assays, or TBAA); and (3) a “skin” covered
adaptation of TBAA (tentacle skin blood agarose assay, or TSBAA). We report the use and results
of these assays to evaluate the efficacy of topical first-aid approaches to inhibit tentacle firing and
venom activity. TSA results included the potent stimulation of massive cnidae discharge by alcohols
but only moderate induction by urine, freshwater, and “cola” (carbonated soft drink). Although
vinegar, the 40-year field standard of first aid for the removal of adherent tentacles, completely
inhibited cnidae firing in TSA and TSBAA ex vivo models, the most striking inhibition of both tentacle
firing and subsequent venom-induced hemolysis was observed using newly-developed proprietary
formulations (Sting No More™) containing copper gluconate, magnesium sulfate, and urea.

Chironex fleckeri (Australian box jellyfish) stings can cause acute cardiovascular collapse and d... more Chironex fleckeri (Australian box jellyfish) stings can cause acute cardiovascular collapse and death. We developed methods
to recover venom with high specific activity, and evaluated the effects of both total venom and constituent porins at doses
equivalent to lethal envenomation. Marked potassium release occurred within 5 min and hemolysis within 20 min in human
red blood cells (RBC) exposed to venom or purified venom porin. Electron microscopy revealed abundant ,12-nm
transmembrane pores in RBC exposed to purified venom porins. C57BL/6 mice injected with venom showed rapid decline in
ejection fraction with progression to electromechanical dissociation and electrocardiographic findings consistent with acute
hyperkalemia. Recognizing that porin assembly can be inhibited by zinc, we found that zinc gluconate inhibited potassium
efflux from RBC exposed to total venom or purified porin, and prolonged survival time in mice following venom injection.
These findings suggest that hyperkalemia is the critical event following Chironex fleckeri envenomation and that rapid
administration of zinc could be life saving in human sting victims.

Abstract: Just over a century ago, animal responses to injections of jellyfish extracts unveiled ... more Abstract: Just over a century ago, animal responses to injections of jellyfish extracts unveiled the phenomenon of
anaphylaxis. Yet, until very recently, understanding of jellyfish sting toxicity has remained limited. Upon contact,
jellyfish stinging cells discharge complex venoms, through thousands of barbed tubules, into the skin resulting in painful
and, potentially, lethal envenomations. This review examines the immunological and toxinological responses to stings by
prominent species of jellyfish including Physalia sp. (Portuguese Man-o-War, Blue-bottle), Cubozoan jellyfish including
Chironex fleckeri, several Carybdeids including Carybdea arborifera and Alatina moseri, Linuche unguiculta (Thimble
jellyfish), a jellyfish responsible for Irukandji syndrome (Carukia barnesi) and Pelagia noctiluca. Jellyfish venoms are
composed of potent proteinaceous porins (cellular membrane pore-forming toxins), neurotoxic peptides, bioactive lipids
and other small molecules whilst the tubules contain ancient collagens and chitins. We postulate that immunologically,
both tubular structural and functional biopolymers as well as venom components can initiate innate, adaptive, as well as
immediate and delayed hypersensitivity reactions that may be amenable to topical anti-inflammatory-immunomodifier
therapy. The current challenge for immunotoxinologists

TRANSACTIONS OF THE …, Jan 1, 2002
A retrospective review of medical records from 113 patients with cnidarian stings in western O'ah... more A retrospective review of medical records from 113 patients with cnidarian stings in western O'ahu, Hawai'i, was conducted for the 5-vear neriod 1994-98. The most common clinical feature was acute local pain, but cases of anaphylaxis or anaphylactoid syndrome and a persistent or delayed local cutaneous syndrome were also documented. Six cases resembled the Irukandji syndrome described from northern Australia, characterized by severe pain and signs of catecholamine excess, including muscle cramping, elevated blood pressure, diaphoresis, and tremor. Treatment with heat application, usually by means of a whole-body hot shower, appeared to provide better clinical improvement than parenteral analgesics or tranquillizers, particularly in patients with the Irukandji-like syndrome. The heat sensitivity of one or more of the Caybdea alata venom components might account for the effect of heat treatment. Prospective, randomized, controlled clinical trials should be performed to assess heat treatment for cnidarian envenomation.
The box jellyfish Alatina moseri forms monthly aggregations at Waikiki Beach 8-12 days after each... more The box jellyfish Alatina moseri forms monthly aggregations at Waikiki Beach 8-12 days after each full moon, posing a recurrent hazard to swimmers due to painful stings. We present an analysis of long-term (14 years:

Cell and tissue …, Jan 1, 2002
The ultrastructural characteristics of nematocysts from the cubozoan Carybdea alata Reynaud, 1830... more The ultrastructural characteristics of nematocysts from the cubozoan Carybdea alata Reynaud, 1830 (Hawaiian box jellyfish) were examined using light, scanning and transmission electron microscopy. We reclassified the predominant nematocyst in C. alata tentacles as a heterotrichous microbasic eurytele, based on spine, tubule and capsule measurements. These nematocysts exhibited a prominent and singular stylet, herein referred to as the lancet. Discharged nematocysts from fixed tentacle preparations displayed the following structures: a smooth shaft base, lamellae, a hemicircumferential fissure demarking the proximal end of a stratified lancet, and a gradually tapering tubule densely covered with large triangularly shaped spines. The lancet remained partially adjoined to the shaft base in a hingelike fashion in rapidly fixed, whole-tentacle preparations. In contrast, this structure was not observed in discharged nematocyst preparations which involved multiple transfer steps prior to fixation. Various approaches were designed to detect this structure in the absence of fixative. Detached lancets were located in proximity to discharged tubules in undisturbed coverslip preparations of fresh tentacles. In addition, examination of embedded nematocysts from fresh tentacles laid on polyacrylamide gels revealed still-attached lancets. To examine the function of this structure in prey capture, Artemia sp. laden tentacles were prepared for scanning electron microscopy. While carapace exteriors exhibited structures proximal to the lancet, i.e., the nematocyst capsule and shaft base, neither tubule nor lancet structures were visible. Taken together, the morphological data suggested a series of events involved in the discharge of a novel eurytele from C. alata.

PeerJ, 2015
Hydrozoans display the most morphological diversity within the phylum Cnidaria. While recent mole... more Hydrozoans display the most morphological diversity within the phylum Cnidaria. While recent molecular studies have provided some insights into their evolutionary history, sister group relationships remain mostly unresolved, particularly at mid-taxonomic levels. Specifically, within Hydroidolina, the most speciose hydrozoan subclass, the relationships and sometimes integrity of orders are highly unsettled. Here we obtained the near complete mitochondrial sequence of twenty-six hydroidolinan hydrozoan species from a range of sources (DNA and RNA-seq data, long-range PCR). Our analyses confirm previous inference of the evolution of mtDNA in Hydrozoa while introducing a novel genome organization. Using RNA-seq data, we propose a mechanism for the expression of mitochondrial mRNA in Hydroidolina that can be extrapolated to the other medusozoan taxa. Phylogenetic analyses using the full set of mitochondrial gene sequences provide some insights into the order-level relationships within Hy...

We are writing because we have serious concerns about the statistical analyses and data interpret... more We are writing because we have serious concerns about the statistical analyses and data interpretation reported by Welfare, Little, Pereira, and Seymour. The authors state in the Abstract, "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." The recovery of venom protein from a membrane after the application of vinegar subsequent to electrically stimulating tentacle cnidae to discharge, W4, was compared with protein recovered post stimulation in a saline wash, W3. Figure 2 shows W3 to be approximately 23 ± 20%. While the authors imply the statistical difference between "venom discharge after vinegar was applied compared to post electrical stimulation", or W4 vs W3, only the overall ANOVA significance comparing all four treatments was quoted (F = 77, P < 0.001) and no statistical significance was provided for this specific W4 vs W3 comparison. If we assume that stand...

Abstract: Cnidarians are the oldest extant lineage of venomous animals. Despite their
simple anat... more Abstract: Cnidarians are the oldest extant lineage of venomous animals. Despite their
simple anatomy, they are capable of subduing or repelling prey and predator species that are
far more complex and recently evolved. Utilizing specialized penetrating nematocysts,
cnidarians inject the nematocyst content or “venom” that initiates toxic and immunological
reactions in the envenomated organism. These venoms contain enzymes, potent pore
forming toxins, and neurotoxins. Enzymes include lipolytic and proteolytic proteins that
catabolize prey tissues. Cnidarian pore forming toxins self-assemble to form robust
membrane pores that can cause cell death via osmotic lysis. Neurotoxins exhibit rapid ion
channel specific activities. In addition, certain cnidarian venoms contain or induce the
release of host vasodilatory biogenic amines such as serotonin, histamine, bunodosine and
caissarone accelerating the pathogenic effects of other venom enzymes and porins. The
cnidarian attacking/defending mechanism is fast and efficient, and massive envenomation
of humans may result in death, in some cases within a few minutes to an hour after sting.
The complexity of venom components represents a unique therapeutic challenge and probably
reflects the ancient evolutionary history of the cnidarian venom system. Thus, they are
invaluable as a therapeutic target for sting treatment or as lead compounds for drug design.

Abstract: Cnidarian venom research has lagged behind other toxinological fields due to
technical ... more Abstract: Cnidarian venom research has lagged behind other toxinological fields due to
technical difficulties in recovery of the complex venom from the microscopic nematocysts.
Here we report a newly developed rapid, repeatable and cost effective technique of venom
preparation, using ethanol to induce nematocyst discharge and to recover venom contents
in one step. Our model species was the Australian box jellyfish (Chironex fleckeri), which
has a notable impact on public health. By utilizing scanning electron microscopy and
light microscopy, we examined nematocyst external morphology before and after ethanol
treatment and verified nematocyst discharge. Further, to investigate nematocyst content or
“venom” recovery, we utilized both top-down and bottom-up transcriptomics–proteomics
approaches and compared the proteome profile of this new ethanol recovery based method
to a previously reported high activity and recovery protocol, based upon density purified
intact cnidae and pressure induced disruption. In addition to recovering previously
characterized box jellyfish toxins, including CfTX-A/B and CfTX-1, we recovered putative
metalloproteases and novel expression of a small serine protease inhibitor. This study not
only reveals a much more complex toxin profile of Australian box jellyfish venom but also
suggests that ethanol extraction method could augment future cnidarian venom proteomics
research efforts.
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Sting First Aid and Box Jelly General Informatio by Angel Yanagihara
Peer Reviewed Scientific Publications by Angel Yanagihara
whole-cell cAMP accumulation, and activity of isoproterenol-stimulated
membrane-bound adenylate cyclase
(EC 4.6.1.1) in Xenopus laevisovarian oocytes are entirely
dependent on the presence of nascent follicle cells. A
method was developed to remove rapidly and completely
all extra-oocyte cell types to yield defolliculated oocytes
that exhibited normal viability and resting membrane
potentials yet lacked /3-adrenergic receptor (/3AR)-
stimulated responses. Purified follicle membranes contained
/3AR.-stimulated adenylate cyclase activity, whereas
oocyte cell membranes did not. Purified oocyte membrane
preparations from X laevis oocytes previously
microinjected with C6-2B rat astrocytoma mRNA,
and subsequently defolliculated, exhibited novel /3AR
and forskolin-stimulated adenylate cyclase activity.
These experiments demonstrate that oocytes expressed
rat C6-2B mRNA coding for the /3-adrenergic receptor
and the components necessary for forskolin-stimulated
adenylate cyclase activity. - SMITH, A. A.; BROOKER,
T.; BROOKER, G. Expression of rat mRNA coding for
hormone-stimulated adenylate cyclase in Xenopzsroocytes.
FASEBJ 1: 380-387; 1987
contradictory first-aid management recommendations persist. A critical barrier to progress has been
the lack of readily available and reproducible envenomation assays that (1) recapitulate live-tentacle
stings; (2) allow quantitation and imaging of cnidae discharge; (3) allow primary quantitation of
venom toxicity; and (4) employ rigorous controls. We report the implementation of an integrated
array of three experimental approaches designed to meet the above-stated criteria. Mechanistically
overlapping, yet distinct, the three approaches comprised (1) direct application of test solutions on
live tentacles (termed tentacle solution assay, or TSA) with single image- and video-microscopy;
(2) spontaneous stinging assay using freshly excised tentacles overlaid on substrate of live human red
blood cells suspended in agarose (tentacle blood agarose assays, or TBAA); and (3) a “skin” covered
adaptation of TBAA (tentacle skin blood agarose assay, or TSBAA). We report the use and results
of these assays to evaluate the efficacy of topical first-aid approaches to inhibit tentacle firing and
venom activity. TSA results included the potent stimulation of massive cnidae discharge by alcohols
but only moderate induction by urine, freshwater, and “cola” (carbonated soft drink). Although
vinegar, the 40-year field standard of first aid for the removal of adherent tentacles, completely
inhibited cnidae firing in TSA and TSBAA ex vivo models, the most striking inhibition of both tentacle
firing and subsequent venom-induced hemolysis was observed using newly-developed proprietary
formulations (Sting No More™) containing copper gluconate, magnesium sulfate, and urea.
to recover venom with high specific activity, and evaluated the effects of both total venom and constituent porins at doses
equivalent to lethal envenomation. Marked potassium release occurred within 5 min and hemolysis within 20 min in human
red blood cells (RBC) exposed to venom or purified venom porin. Electron microscopy revealed abundant ,12-nm
transmembrane pores in RBC exposed to purified venom porins. C57BL/6 mice injected with venom showed rapid decline in
ejection fraction with progression to electromechanical dissociation and electrocardiographic findings consistent with acute
hyperkalemia. Recognizing that porin assembly can be inhibited by zinc, we found that zinc gluconate inhibited potassium
efflux from RBC exposed to total venom or purified porin, and prolonged survival time in mice following venom injection.
These findings suggest that hyperkalemia is the critical event following Chironex fleckeri envenomation and that rapid
administration of zinc could be life saving in human sting victims.
anaphylaxis. Yet, until very recently, understanding of jellyfish sting toxicity has remained limited. Upon contact,
jellyfish stinging cells discharge complex venoms, through thousands of barbed tubules, into the skin resulting in painful
and, potentially, lethal envenomations. This review examines the immunological and toxinological responses to stings by
prominent species of jellyfish including Physalia sp. (Portuguese Man-o-War, Blue-bottle), Cubozoan jellyfish including
Chironex fleckeri, several Carybdeids including Carybdea arborifera and Alatina moseri, Linuche unguiculta (Thimble
jellyfish), a jellyfish responsible for Irukandji syndrome (Carukia barnesi) and Pelagia noctiluca. Jellyfish venoms are
composed of potent proteinaceous porins (cellular membrane pore-forming toxins), neurotoxic peptides, bioactive lipids
and other small molecules whilst the tubules contain ancient collagens and chitins. We postulate that immunologically,
both tubular structural and functional biopolymers as well as venom components can initiate innate, adaptive, as well as
immediate and delayed hypersensitivity reactions that may be amenable to topical anti-inflammatory-immunomodifier
therapy. The current challenge for immunotoxinologists
simple anatomy, they are capable of subduing or repelling prey and predator species that are
far more complex and recently evolved. Utilizing specialized penetrating nematocysts,
cnidarians inject the nematocyst content or “venom” that initiates toxic and immunological
reactions in the envenomated organism. These venoms contain enzymes, potent pore
forming toxins, and neurotoxins. Enzymes include lipolytic and proteolytic proteins that
catabolize prey tissues. Cnidarian pore forming toxins self-assemble to form robust
membrane pores that can cause cell death via osmotic lysis. Neurotoxins exhibit rapid ion
channel specific activities. In addition, certain cnidarian venoms contain or induce the
release of host vasodilatory biogenic amines such as serotonin, histamine, bunodosine and
caissarone accelerating the pathogenic effects of other venom enzymes and porins. The
cnidarian attacking/defending mechanism is fast and efficient, and massive envenomation
of humans may result in death, in some cases within a few minutes to an hour after sting.
The complexity of venom components represents a unique therapeutic challenge and probably
reflects the ancient evolutionary history of the cnidarian venom system. Thus, they are
invaluable as a therapeutic target for sting treatment or as lead compounds for drug design.
technical difficulties in recovery of the complex venom from the microscopic nematocysts.
Here we report a newly developed rapid, repeatable and cost effective technique of venom
preparation, using ethanol to induce nematocyst discharge and to recover venom contents
in one step. Our model species was the Australian box jellyfish (Chironex fleckeri), which
has a notable impact on public health. By utilizing scanning electron microscopy and
light microscopy, we examined nematocyst external morphology before and after ethanol
treatment and verified nematocyst discharge. Further, to investigate nematocyst content or
“venom” recovery, we utilized both top-down and bottom-up transcriptomics–proteomics
approaches and compared the proteome profile of this new ethanol recovery based method
to a previously reported high activity and recovery protocol, based upon density purified
intact cnidae and pressure induced disruption. In addition to recovering previously
characterized box jellyfish toxins, including CfTX-A/B and CfTX-1, we recovered putative
metalloproteases and novel expression of a small serine protease inhibitor. This study not
only reveals a much more complex toxin profile of Australian box jellyfish venom but also
suggests that ethanol extraction method could augment future cnidarian venom proteomics
research efforts.
whole-cell cAMP accumulation, and activity of isoproterenol-stimulated
membrane-bound adenylate cyclase
(EC 4.6.1.1) in Xenopus laevisovarian oocytes are entirely
dependent on the presence of nascent follicle cells. A
method was developed to remove rapidly and completely
all extra-oocyte cell types to yield defolliculated oocytes
that exhibited normal viability and resting membrane
potentials yet lacked /3-adrenergic receptor (/3AR)-
stimulated responses. Purified follicle membranes contained
/3AR.-stimulated adenylate cyclase activity, whereas
oocyte cell membranes did not. Purified oocyte membrane
preparations from X laevis oocytes previously
microinjected with C6-2B rat astrocytoma mRNA,
and subsequently defolliculated, exhibited novel /3AR
and forskolin-stimulated adenylate cyclase activity.
These experiments demonstrate that oocytes expressed
rat C6-2B mRNA coding for the /3-adrenergic receptor
and the components necessary for forskolin-stimulated
adenylate cyclase activity. - SMITH, A. A.; BROOKER,
T.; BROOKER, G. Expression of rat mRNA coding for
hormone-stimulated adenylate cyclase in Xenopzsroocytes.
FASEBJ 1: 380-387; 1987
contradictory first-aid management recommendations persist. A critical barrier to progress has been
the lack of readily available and reproducible envenomation assays that (1) recapitulate live-tentacle
stings; (2) allow quantitation and imaging of cnidae discharge; (3) allow primary quantitation of
venom toxicity; and (4) employ rigorous controls. We report the implementation of an integrated
array of three experimental approaches designed to meet the above-stated criteria. Mechanistically
overlapping, yet distinct, the three approaches comprised (1) direct application of test solutions on
live tentacles (termed tentacle solution assay, or TSA) with single image- and video-microscopy;
(2) spontaneous stinging assay using freshly excised tentacles overlaid on substrate of live human red
blood cells suspended in agarose (tentacle blood agarose assays, or TBAA); and (3) a “skin” covered
adaptation of TBAA (tentacle skin blood agarose assay, or TSBAA). We report the use and results
of these assays to evaluate the efficacy of topical first-aid approaches to inhibit tentacle firing and
venom activity. TSA results included the potent stimulation of massive cnidae discharge by alcohols
but only moderate induction by urine, freshwater, and “cola” (carbonated soft drink). Although
vinegar, the 40-year field standard of first aid for the removal of adherent tentacles, completely
inhibited cnidae firing in TSA and TSBAA ex vivo models, the most striking inhibition of both tentacle
firing and subsequent venom-induced hemolysis was observed using newly-developed proprietary
formulations (Sting No More™) containing copper gluconate, magnesium sulfate, and urea.
to recover venom with high specific activity, and evaluated the effects of both total venom and constituent porins at doses
equivalent to lethal envenomation. Marked potassium release occurred within 5 min and hemolysis within 20 min in human
red blood cells (RBC) exposed to venom or purified venom porin. Electron microscopy revealed abundant ,12-nm
transmembrane pores in RBC exposed to purified venom porins. C57BL/6 mice injected with venom showed rapid decline in
ejection fraction with progression to electromechanical dissociation and electrocardiographic findings consistent with acute
hyperkalemia. Recognizing that porin assembly can be inhibited by zinc, we found that zinc gluconate inhibited potassium
efflux from RBC exposed to total venom or purified porin, and prolonged survival time in mice following venom injection.
These findings suggest that hyperkalemia is the critical event following Chironex fleckeri envenomation and that rapid
administration of zinc could be life saving in human sting victims.
anaphylaxis. Yet, until very recently, understanding of jellyfish sting toxicity has remained limited. Upon contact,
jellyfish stinging cells discharge complex venoms, through thousands of barbed tubules, into the skin resulting in painful
and, potentially, lethal envenomations. This review examines the immunological and toxinological responses to stings by
prominent species of jellyfish including Physalia sp. (Portuguese Man-o-War, Blue-bottle), Cubozoan jellyfish including
Chironex fleckeri, several Carybdeids including Carybdea arborifera and Alatina moseri, Linuche unguiculta (Thimble
jellyfish), a jellyfish responsible for Irukandji syndrome (Carukia barnesi) and Pelagia noctiluca. Jellyfish venoms are
composed of potent proteinaceous porins (cellular membrane pore-forming toxins), neurotoxic peptides, bioactive lipids
and other small molecules whilst the tubules contain ancient collagens and chitins. We postulate that immunologically,
both tubular structural and functional biopolymers as well as venom components can initiate innate, adaptive, as well as
immediate and delayed hypersensitivity reactions that may be amenable to topical anti-inflammatory-immunomodifier
therapy. The current challenge for immunotoxinologists
simple anatomy, they are capable of subduing or repelling prey and predator species that are
far more complex and recently evolved. Utilizing specialized penetrating nematocysts,
cnidarians inject the nematocyst content or “venom” that initiates toxic and immunological
reactions in the envenomated organism. These venoms contain enzymes, potent pore
forming toxins, and neurotoxins. Enzymes include lipolytic and proteolytic proteins that
catabolize prey tissues. Cnidarian pore forming toxins self-assemble to form robust
membrane pores that can cause cell death via osmotic lysis. Neurotoxins exhibit rapid ion
channel specific activities. In addition, certain cnidarian venoms contain or induce the
release of host vasodilatory biogenic amines such as serotonin, histamine, bunodosine and
caissarone accelerating the pathogenic effects of other venom enzymes and porins. The
cnidarian attacking/defending mechanism is fast and efficient, and massive envenomation
of humans may result in death, in some cases within a few minutes to an hour after sting.
The complexity of venom components represents a unique therapeutic challenge and probably
reflects the ancient evolutionary history of the cnidarian venom system. Thus, they are
invaluable as a therapeutic target for sting treatment or as lead compounds for drug design.
technical difficulties in recovery of the complex venom from the microscopic nematocysts.
Here we report a newly developed rapid, repeatable and cost effective technique of venom
preparation, using ethanol to induce nematocyst discharge and to recover venom contents
in one step. Our model species was the Australian box jellyfish (Chironex fleckeri), which
has a notable impact on public health. By utilizing scanning electron microscopy and
light microscopy, we examined nematocyst external morphology before and after ethanol
treatment and verified nematocyst discharge. Further, to investigate nematocyst content or
“venom” recovery, we utilized both top-down and bottom-up transcriptomics–proteomics
approaches and compared the proteome profile of this new ethanol recovery based method
to a previously reported high activity and recovery protocol, based upon density purified
intact cnidae and pressure induced disruption. In addition to recovering previously
characterized box jellyfish toxins, including CfTX-A/B and CfTX-1, we recovered putative
metalloproteases and novel expression of a small serine protease inhibitor. This study not
only reveals a much more complex toxin profile of Australian box jellyfish venom but also
suggests that ethanol extraction method could augment future cnidarian venom proteomics
research efforts.
was originally described one hundred and eighty three years ago as Carybdea alata in La Centurie Zoologique—a monograph
published by René Primevère Lesson during the age of worldwide scientific exploration. While monitoring monthly
reproductive swarms of A. alata medusae in Bonaire, we documented the ecology and sexual reproduction of this cubozoan
species. Examination of forty six A. alata specimens and additional archived multimedia material in the collections
of the National Museum of Natural History, Washington, DC revealed that A. alata is found at depths ranging from surface
waters to 675 m. Additional studies have reported it at depths of up to 1607 m in the tropical and subtropical Atlantic
Ocean. Herein, we resolve the taxonomic confusion long associated with A. alata due to a lack of detail in the original
description and conflicting statements in the scientific literature. A new cubozoan character, the velarial lappet, is described
for this taxon. The complete description provided here serves to stabilize the taxonomy of the second oldest box
jellyfish species, and provide a thorough redescription of the species.
Biochemist, Assistant Research Professor, John A. Burns School of Medicine, University of Hawaii. Born in Anchorage, Alaska, where her father, a career officer in the Strategic Air Command was stationed, Dr. Angel (ne'e Smith) Yanagihara spent a good deal of time in, on, or near the water as a child, even wishing to become a fish. From a very young age, she was intrigued by marine life and began descriptive "studies" drawing, counting and observing various marine animals in Alaska, New Jersey, Cape Cod, Alabama and Virginia along the Potomac River. She graduated with honors in both biology and chemistry from the University of Virginia. Later, her graduate studies in biochemistry at Georgetown University were interrupted by the birth of three children. Upon moving to Hawaii in 1995, she completed her doctoral degree at the University of Hawaii in Manoa in 1997. An early-morning, mile swim and an unexpected but unforgettable encounter with a swarm of box jellyfish, which left her bed-ridden from painful stings, redirected her research trajectory and focus to unravel the mysteries of the venom and to develop an effective treatment.
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Aired: 02/22/2011 53:06 Rating: NR
Hunting down the most venomous animals to reveal their medical mysteries
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