Severe neurotoxic envenoming by the Malayan krait Bungarus candidus (Linnaeus): response to antivenom and anticholinesterase.

Warrell, D A; Looareesuwan, Sornchai; White, N J; Theakston, R.D.G.; Warrell, M. J.; Kosakarn, Waipot; Reid, H. A.

doi:10.1136/bmj.286.6366.678

Cited by 104 publications

(62 citation statements)

References 6 publications

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“…In Vivo Toxicity of Haditoxin-In preliminary experiments to observe the biological effects of haditoxin, all mice injected with the toxin (5, 10, and 25 mg/kg) showed typical symptoms of peripheral neurotoxicity, such as paralysis of hind limbs and labored breathing, and finally died, presumably due to respiratory paralysis (47,48). The time of death was recorded for each animal, with the average calculated to be 94, 32.5, and 20 min, respectively, for the 5, 10, and 25 mg/kg doses.…”

Section: Resultsmentioning

confidence: 99%

Structural and Functional Characterization of a Novel Homodimeric Three-finger Neurotoxin from the Venom of Ophiophagus hannah (King Cobra)

Roy

Zhou

Chong

et al. 2010

Journal of Biological Chemistry

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Snake venoms are a mixture of pharmacologically active proteins and polypeptides that have led to the development of molecular probes and therapeutic agents. Here, we describe the structural and functional characterization of a novel neurotoxin, haditoxin, from the venom of Ophiophagus hannah (King cobra). Haditoxin exhibited novel pharmacology with antagonism toward muscle (␣␤␥␦) and neuronal (␣ 7 , ␣ 3 ␤ 2 , and ␣ 4 ␤ 2 ) nicotinic acetylcholine receptors (nAChRs) with highest affinity for ␣ 7 -nAChRs. The high resolution (1.5 Å ) crystal structure revealed haditoxin to be a homodimer, like -neurotoxins, which target neuronal ␣ 3 ␤ 2 -and ␣ 4 ␤ 2 -nAChRs. Interestingly however, the monomeric subunits of haditoxin were composed of a three-finger protein fold typical of curaremimetic shortchain ␣-neurotoxins. Biochemical studies confirmed that it existed as a non-covalent dimer species in solution. Its structural similarity to short-chain ␣-neurotoxins and -neurotoxins notwithstanding, haditoxin exhibited unique blockade of ␣ 7 -nAChRs (IC 50 180 nM), which is recognized by neither shortchain ␣-neurotoxins nor -neurotoxins. This is the first report of a dimeric short-chain ␣-neurotoxin interacting with neuronal ␣ 7 -nAChRs as well as the first homodimeric three-finger toxin to interact with muscle nAChRs.Snake venoms are a rich source of pharmacologically active proteins and polypeptides targeting a variety of receptors with high affinity and specificity (1). Because of their high specificity, some of these molecules have contributed significantly (a) to the isolation and characterization of different receptors and their subtypes in the field of molecular pharmacology and (b) as lead compounds in the development of therapeutic agents (2, 3). For example, the discovery of ␣-bungarotoxin, a postsynaptic neurotoxin from the venom of Bungarus multicinctus, led to the identification of the nicotinic acetylcholine receptor (nAChR), 3 the first isolated receptor protein (4) as well as the first one to be characterized electrophysiologically (5) and biochemically (6, 7). Subsequently, it was also used to characterize several other nAChRs (8 -10).Snake venom proteins can be broadly classified as enzymatic and non-enzymatic proteins. Three-finger toxins (3FTxs) are the largest group of non-enzymatic snake venom proteins (1, 11). They are most commonly found in the venoms of elapid and hydrophiid snakes. Recently, our laboratory has also demonstrated the presence of 3FTxs from colubrid venoms (12, 13), and 3FTx transcripts have been found in the venom gland transcriptome of viperid snakes (14, 15). The proteins in this family of toxins share a common structural scaffold of three ␤-sheeted loops emerging from a central core (11,16). Despite the overall similarity in structure, these proteins have diverse functional properties. Members of this family include neurotoxins targeting the cholinergic system (7, 11, 16), cytotoxins/cardiotoxins interacting with the cell membranes (17), calciseptine and related toxins that block th...

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Section: Resultsmentioning

confidence: 99%

Structural and Functional Characterization of a Novel Homodimeric Three-finger Neurotoxin from the Venom of Ophiophagus hannah (King Cobra)

Roy

Zhou

Chong

et al. 2010

Journal of Biological Chemistry

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“…Although antivenoms against B. multicinctus are available in China and Taiwan, clinical reports regarding their efficacy have only rarely been published [3,8,9]. In some series of cases, antivenom treatment has been tried after snakebites by other Bungarus species, but with rather conflicting clinical results [10,11]. In Vietnam, no specific antivenom against B. multicinctus has been available until recently, when it was developed and produced for clinical use.…”

Section: Introductionmentioning

confidence: 99%

A Controlled Clinical Trial of A Novel Antivenom in Patients Envenomed by Bungarus multicinctus

et al. 2010

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In northern Vietnam, a majority of severely envenomed patients are bitten by Bungarus multicinctus. Hitherto, these victims have received supportive care only. The aims of this study were to assess the possible efficacy and side effects of a new antivenom. This trial (ClinicalTrials.gov Identifier: NCT00811239) was performed during [2004][2005][2006] at an ICU in Hanoi. For ethical reasons, the study was not randomized. All patients who fulfilled the inclusion criteria during 2004-2005 were prospectively enrolled, carefully recorded, and treated with optimal supportive therapy (control group). The patients who entered the study 2006 were treated with antivenom in addition to supportive care (antivenom group). The inclusion criteria were: envenomation by B. multicinctus, presence of systemic envenomation, and (during 2006) provision of written informed consent. Predefined endpoints were number of patients requiring mechanical ventilation, duration of mechanical ventilation, length of ICU stay, duration of muscle paralysis, and number of patients with ventilatorassociated pneumonia. Eighty-one patients were included, 54 during 2004-2005 and 27 during 2006. Baseline characteristics were similar in the groups. The antivenomgroup patients had a shorter duration of muscle paralysis of the limbs (p<0.001), of the diaphragm (p<0.001), and of ptosis (p<0.001). The duration of mechanical ventilation and length of ICU stay were shorter in the antivenom group (p<0.001). The rate of ventilator-associated pneumonia was lower in the antivenom group (p<0.02). However, the relative number of patients requiring mechanical ventilation was not reduced in the antivenom group. The rate of adverse reactions to the antivenom was 7.4%. A favorable efficacy and acceptable safety of this antivenom were demonstrated.

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“…[9] Typically, neuromuscular symptoms develop early, but after Krait bite, there may be delay of more than 10 hours. [2] Extraocular muscles are most sensitive to neuromuscular blockage and in some patients, the only feature of envenomation is ptosis and ophthalmoplagia. (2) The only effective treatment of poisonous snake bite is ASV administration.…”

Section: Slmentioning

confidence: 99%

“…Several studies have reported successfully treating neurotoxic envenoming without the use of ASV. (2) Anticholinesterases have a variable but potentially harmful effect in patients with neurotoxic envenoming especially when postsynaptic neurotoxin is involved. (1,2,12) So many trials have addressed the minimum effective dose of ASV in viper bite.…”

Section: Introductionmentioning

confidence: 99%

“…(2) Anticholinesterases have a variable but potentially harmful effect in patients with neurotoxic envenoming especially when postsynaptic neurotoxin is involved. (1,2,12) So many trials have addressed the minimum effective dose of ASV in viper bite. (3) As per our best knowledge, there are no trials addressing the question of optimal dose of ASV in neurotoxic (elapid) bite.…”

Section: Introductionmentioning

confidence: 99%

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Outcome of Patient With Neuroparalytic Snake Bite Treated With Low Dose (50 Ml) v/S High Dose (100 Ml) Asv

Singh¹,

Mahur²,

Raiger³

et al. 2014

jemds

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It was always been a matter of great-controversy regarding the dosage protocol of antisnake venom (ASV) in the management of snake envenomation. The only definitive treatment of poisonous snake bite is ASV administration. MATERIAL AND METHODS: This study was carried out for a period of two years. All patients of neuroparaplytic snake bite who presented to the emergency department were included in this prospectively study. RESULTS: Fifty eight patients of neurotoxic snake bite became eligible for the study over a period of 2 yrs. By using chi-square test, the outcomes in low and high bolus dose group were statistically non-significant (P>0.05). Statistical analysis showed no significant difference in both groups. From this study it can be firmly concluded that low dose ASV is as effective as high dose in treatment of neurotoxic snake bite.

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Severe neurotoxic envenoming by the Malayan krait Bungarus candidus (Linnaeus): response to antivenom and anticholinesterase.

Cited by 104 publications

References 6 publications

Structural and Functional Characterization of a Novel Homodimeric Three-finger Neurotoxin from the Venom of Ophiophagus hannah (King Cobra)

Structural and Functional Characterization of a Novel Homodimeric Three-finger Neurotoxin from the Venom of Ophiophagus hannah (King Cobra)

A Controlled Clinical Trial of A Novel Antivenom in Patients Envenomed by Bungarus multicinctus

Outcome of Patient With Neuroparalytic Snake Bite Treated With Low Dose (50 Ml) v/S High Dose (100 Ml) Asv

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