%0 Journal Article
%T Application of Purified Botulinum Type A Neurotoxin to Treat Experimental Trigeminal Neuropathy in Rats and Patients with Urinary Incontinence and Prostatic Hyperplasia
%A Yoshizo Matsuka
%A Teruhiko Yokoyama
%A Yumiko Yamamoto
%A Tomonori Suzuki
%A Ni Nengah Dwi Fatmawati
%A Atsushi Nishikawa
%A Tohru Ohyama
%A Toshihiro Watanabe
%A Takuo Kuboki
%A Atsushi Nagai
%A Keiji Oguma
%J Journal of Toxicology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/648384
%X Type A neurotoxin (NTX) of Clostridium botulinum was purified by a simple procedure using a lactose gel column. The toxicity of this purified toxin preparation was retained for at least 1 year at £¿30¡ãC by supplementation with either 0.1% albumin or 0.05% albumin plus 1% trehalose. When purified NTX was used to treat 49 patients with urinary incontinence caused by either refractory idiopathic or neurogenic detrusor overactivity, 36 patients showed significant improvement in symptoms. These beneficial effects were also observed in cases of prostatic hyperplasia. The results obtained with NTX were similar to that of Botox. The effects of NTX on trigeminal neuralgia induced by infraorbital nerve constriction (IoNC) in rats were also studied. Trigeminal ganglion neurons from ipsilateral to IoNC exhibited significantly faster onset of FM4-64 release than sham-operated contralateral neurons. Intradermal injection of NTX in the area of IoNC alleviated IoNC-induced pain behavior and reduced the exaggerated FM4-64 release in trigeminal ganglion neurons. 1. Introduction In this manuscript, three main topics are described: (1) the structure of type A progenitor toxin and purification of type A neurotoxin by a lactose gel column based on progenitor toxin characteristics; (2) treatment of patients with urinary incontinence and prostate hyperplasia with this purified neurotoxin; (3) application of the purified neurotoxin for treating trigeminal neuralgia in a rat model. Introduction including the purpose of these three topics is described at the beginning of each paragraph. 2. Structure of Type A Progenitor Toxin and Purification of Type A Neurotoxin Clostridium botulinum strains produce immunologically distinct neurotoxins (NTX; types A to G) with molecular masses (Mr) of approximately 150£¿kDa. In an activated form, the NTXs have a cleavage site at the one third position of their N terminus conjugated with an S¨CS bond, which can be cleaved by cellular proteases or exogenously added trypsin. In culture fluid and in acidic foods, the NTXs associate with nontoxic components and form large complexes designated progenitor toxins (PTXs). PTXs are found in three forms with Mr of 900£¿kDa (19S, LL), 500£¿kDa (16S, L), and 300£¿kDa (12S, M); later, it became clear that the actual Mr of the L and LL toxins is much larger than 500 and 900£¿kDa, respectively (see below). The M toxin is composed of an NTX and a nontoxic component having no hemagglutinin (HA) activity (designated nontoxic non-HA; NTNH), whereas the L and LL toxins are composed of an NTX(s), an NTNH(s), and HAs. The
%U http://www.hindawi.com/journals/jt/2012/648384/