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The redback spider (Latrodectus hasseltii) is nonindigenous to Japan but has now spread throughout the country. Bites to humans are rare but can be fatal. We prepared freeze-dried redback spider antivenom for therapeutic use against bites in Japan by immunization of horse plasma. This study included two nonclinical tests of the antivenom: a local irritation study involving a single intramuscular administration to rabbits (with injections of physiological saline and an existing freeze-dried diphtheria antitoxin as control and comparison substances, respectively) and a 2-week repeated intermittent intravenous-dose toxicity study in rats. The irritation study showed the antivenom's irritancy to be comparable with that of the saline and the existing antitoxin preparations under the test conditions. In a repeated-dose toxicity study, no toxicity change was found in male or female rats, and the no-observed-adverseeffect level (NOAEL) was judged to be a dose volume of 20 mL/kg (1082 units/kg antivenom activity) in both male and female rats. In addition, there was no toxicological difference between proteinaceous diphtheria antitoxin and redback spider antivenom prepared to have the same protein content and the same additive composition. Based on these findings, we will further advance our research towards clinical application of the redback spider antivenom. This research was supported by the Research Program on Emerging and Re-emerging Infectious Disease of the Japan Agency for Medical Research and Development. [ABSTRACT FROM AUTHOR]

Introduction: The botulinum neurotoxin type A complex is the drug of choice for neurological disorders in the world. Botulinum toxin has the ability to inhibit muscle activity by blocking the release of acetylcholine at neuromuscular junctions. In this study, we evaluated type A2 150kDa neurotoxin (A2NTX) and type A1 progenitor toxin (A1LL) by the twitch tension assay with isolated mouse phrenic nerve–hemidiaphragm. Methods: The twitch tension of isolated phrenic nerve–hemidiaphragm preparations induced by electrical stimulations of the phrenic nerve at pH 7.4 was recorded before and after the preparations were exposed to A2NTX (Kaketsuken) and A1LL, respectively. In addition, assuming the possible muscle pH conditions of patients on muscle contraction, these twitch tension responses were compared under an acidic condition of pH 6.8 using lactic acid. Results and discussion: In the electrical stimulation of the phrenic nerve, each botulinum toxin preparation caused attenuation of the twitch tension of the diaphragm ex vivo. In comparing the linear range of the dose–response relationship between NTX and A1LL, it was revealed that the neuromuscular blocking activity of A2NTX was approximately 2 times more potent at pH 7.4, and was 4 times more potent at pH 6.8. These results suggested that NTX shows marked potency as a pharmacological agent compared with the A1 type progenitor toxin. [Copyright &y& Elsevier]