• The korean journal of orthodontics
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• v.47 no.4
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• pp.222-228
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• 2017

Objective: To evaluate soft- and hard-tissue changes in the mandibular angle area after the administration of botulinum toxin type A (BoNT-A) injection to patients with masseteric hypertrophy by using three-dimensional cone-beam computed tomography (3D-CBCT). Methods: Twenty volunteers were randomly divided into two groups of 10 patients. Patients in group I received a single BoNT-A injection in both masseter muscles, while those in group II received two BoNT-A injections in each masseter muscle, with the second injection being administered 4 months after the first one. In both groups, 3D-CBCT was performed before the first injection and 6 months after the first injection. Results: Masseter muscle thicknesses and cross-sectional areas were significantly reduced in both groups, but the reductions were significantly more substantial in group II than in group I. The intergonial width of the mandibular angle area did not change significantly in either group. However, the bone volume of the mandibular gonial angle area was more significantly reduced in group II than in group I. Conclusions: The repeated administration of BoNT-A injections may induce bone volume changes in the mandibular angle area.

• Journal of Dental Rehabilitation and Applied Science
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• v.30 no.4
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• pp.299-306
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• 2014

Botulinum toxin (BoNT) has been used for a wide spectrum of therapeutic and cosmetic indications, and the range of indications is continually increased. Though BoNT is a powerful poison, the fact that not only the effect but also the adverse effect of it fader about 6 months after injection makes clinicians to neglect its dangerous property in clinical application. But Many reports about the adverse effects including death of BoNT injection have been reported, the FDA edited in additional warnings about hospitalizations and deaths. In this study, we intended to look through the metabolic process in human body, possible adverse effect, matters to be attended in application, and cases reports about deaths of BoNT by reviewing the previous studies.

• Journal of Dental Rehabilitation and Applied Science
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• v.28 no.2
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• pp.171-178
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• 2012

Botulinum toxin type A (BoNT-A) has been applied successfully to treat chronic migraine, dystonia, spasticity and temporomandubular disorders(TMDs) as well as frontal wrinkle and glabella wrinkle. Recently it has been reported that BoNT-A, reversibly blocks presynaptic acetylcholine release, also inhibits the release of substance P, CGRP(calcitonin gene related peptide) and glutamate related to peripheral sensitization and neurogenic inflammation in sensory nerve, In this study we reviewed animal nerve injury model such as rat and rabbit and identify the analgesic effect and mechanism of nerve injury pain after dental treatment.

• International Journal of Oral Biology
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• v.40 no.2
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• pp.71-77
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• 2015

The activation of glial cells in the spinal cord has been contribute to the initiation and maintenance of pain facilitation induced by peripheral inflammation and nerve injury. The present study investigated effects of botulinum toxin type A (BoNT-A), injected subcutaneously or intracisternally, on the expression of microglia and astrocytes in rats. Complete Freund's Adjuvant (CFA)-induced inflammation was employed as an orofacial chronic inflammatory pain model. A subcutaneous injection of $40{\mu}L$ CFA into the vibrissa pad was performed under 3% isoflurane anesthesia in SD rats. Immunohistochemical analysis for changes in Iba1 (a microglia marker) and GFAP (an astrocyte marker), were performed 5 days after CFA injection. Subcutaneous injection of CFA produced increases in Iba1 and GFAP expression, in the ipsilateral superficial lamia I and II in the medullary dorsal horn of rats. Subcutaneous treatment with BoNT-A attenuated the up-regulation of Iba1 and GFAP expressions induced by CFA injection. Moreover, intracisternal injection of BoNT-A also attenuated the up-regulated Iba1 and GFAP expressions. These results suggest that the anti-nociceptive action of BoNT-A is mediated by modulation activation of glial cells, including microglia and astrocyte.

• Journal of Dental Rehabilitation and Applied Science
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• v.27 no.2
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• pp.247-251
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• 2011

Botulinum toxin type A (BoNT-A) is used for treating bilateral masseter hypertrophy since 1994. Recently there have been more clinical studies in this area, with some authors reporting that BoNT-A can reduce the size of the masseter muscle, as documented by photography, ultrasonography, computed tomography, and 3D(three dimensional) laser scan. However, earlier studies were only for bilateral masseter hypertrophy cases, not for unilateral masseter hypertrophy cases. The aim of this study was to use 3D laser scanning to evaluate changes in the external facial contour induced by unilateral BoNT-A injection. BoNT-A was injected into hypertrophic masseter muscle unilaterally in 10 patients with asymmetric masseter hypertrophy. The clinical effects of unilaterally injected BoNT-A were evaluated before the injection and 4, 8, and 12weeks after the injection using 3D laser scan. And the mean values of both sides (injection and non-injection sides) were compared with. At injection side, mean values of the volume and the bulkiest height at each time point diminished significantly between pre-injection and 4, 8, and 12weeks post-injection. At non-injection side, in contrast, mean values of the volume and the bulkiest height diminished also but less than that of injected side, and there was no statistical significance. In this limited study, we concluded that the unilaterally BoNT-A injection side showed greater mean values of the reduction of muscle volume than non-injection side at 4, 8, and 12 weeks after the injection.

• Journal of Dental Rehabilitation and Applied Science
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• v.33 no.1
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• pp.1-6
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• 2017

Botulinum toxin (BoNT) injections have been used not only in the field of cosmetic surgery such as forehead and eye wrinkle treatment but also in the treatment of chronic migraine, dystonia, spasticity, temporomandibular disorders (TMD). BoNT injections are the only approved therapies to date for prophylactic treatment of chronic migraine patients. Unlike the previously known paralysis of motor neurons, the mechanism of action for migraine is to block the release of non-cholinergic neurotransmitters such as substance P, CGRP, and glutamate, which are associated with peripheral sensitization and neurogenic inflammation in the sensory nerve, it is hypothesized that the signal is blocked. This review focuses on the analgesic effects of BoNT and suggests the direction for the development of injection methods for chronic migraine patients.

• Journal of Microbiology and Biotechnology
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• v.29 no.7
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• pp.1165-1176
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• 2019

Botulinum neurotoxins (BoNTs), produced by Clostridium botulinum, are the most toxic substances known. However, the number of currently approved medical countermeasures for these toxins is very limited. Therefore, studies on therapeutic antitoxins are essential to prepare for toxin-related emergencies. Currently, more than 10,000 Halla horses, a crossbreed between the native Jeju and Thoroughbred horses, are being raised in Jeju Island of Korea. They can be used for equine antitoxin experiments and production of hyperimmune serum against BoNT/A1. Instead of the inactivated BoNT/A1 toxoid, Halla horse was immunized with the receptor-binding domain present in the C-terminus of heavy chain of BoNT/A1 (BoNT/A1-HCR) expressed in Escherichia coli. The anti-BoNT/A1-HCR antibody titer increased rapidly by week 4, and this level was maintained for several weeks after boosting immunization. Notably, $20{\mu}l$ of the week-24 BoNT/A1-HCR(-immunized) equine serum showed an in vitro neutralizing activity of over 8 international units (IU) of a reference equine antitoxin. Furthermore, $20{\mu}l$ of equine serum and $100{\mu}g$ of purified equine $F(ab^{\prime})_2$ showed 100% neutralization of 10,000 $LD_{50}$ in vivo. The results of this study shall contribute towards optimizing antitoxin production for BoNT/A1, which is essential for emergency preparedness and response.

• BMB Reports
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• v.39 no.5
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• pp.642-647
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• 2006

Botulinum neurotoxin A (BoNT/A) has been used therapeutically to treat muscular hypercontractions and sudomotor hyperactivity and it has been reported that BoNT/A might have analgesic properties in headache. PEP-1 peptide is a known carrier peptide that delivers fulll-ength native proteins in vitro and in vivo. In this study, a BoNT/A gene were fused with PEP-1 peptide in a bacterial expression vector to produce a genetic in-frame PEP-1-BoNT/A fusion protein. The expressed and purified PEP-1-BoNT/A fusion proteins were efficiently transduced into cells in a time- and dose-dependent manner when added exogenously in a culture medium. In addition, immuno-histochemical analysis revealed that PEP-1-BoNT/A fusion protein efficiently penetrated into the epidermis as well as the dermis of the subcutaneous layer, when sprayed on mice skin. These results suggest that PEP-1-BoNT/A fusion protein provide an efficient strategy for therapeutic delivery in various human diseases related to this protein.

• Journal of Oral Medicine and Pain
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• v.48 no.1
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• pp.16-24
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• 2023

Purpose: To determine the effects of botulinum toxin (BoNT) injection into the human masseter muscle on the morphology of the mandibular condyle bone using cone-beam computed tomography (CBCT). Methods: Twenty volunteers were randomly assigned to one of two groups. Group I received a single BoNT injection; Group II received two injections, with the second being administered 4 months after the first. CBCT scans of both temporomandibular joints (TMJs) were performed before and 6 months after the first injection. Bony changes in the cortical layers of the condyle heads were evaluated and the long and short axes of both mandibular condyles were measured. The thickness at the thinnest part of glenoid fossa was also quantitatively measured. Results: There was no significant difference between pre- and post-injection CBCT images. Furthermore, no changes in the cortical layers of the condyle heads were observed among the subjects who exhibited mild degenerative TMJ changes. The quantitative measurements (long axis, short axis, and the thickness of thinnest part of glenoid fossa roof) did not differ significantly between pre- and post-injection except for the long axis in Group I. Conclusions: Within the limitations of this study, it appears that BoNT injections into human masseter muscles do not alter the morphology of the mandibular condyle bone in healthy adults.

• Journal of Microbiology and Biotechnology
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• v.13 no.2
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• pp.287-291
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• 2003

Botulinum neurotoxin type A (BONT/A) is an extremely potent toxin, which is produced by Clostridium botulinum. The light chain of this protein (BONT/A LC), which is known as a zinc endopeptidase, cleaves SNAP-25 involved in the exocytosis process. In this work, the expression of recombinant BoNT/A LC in E. coli is described. The BONT/A LC gene of C. botulinum contains a high frequency of the arginine AGA and isoleucine ATA codons that are rarely used in genes of E. coli, hampering the translation of recombinant protein. The argD and ilex tRNA genes were cloned into pACYC184 vector, resulting in pAAD131X plasmid. The translational stress of the toxin gene related to codon bias was reversed by fupplernentation of the AGA arginyl tRNA of T4 phage and AUA isoleucyl tRNA of E. coli. This system may be applicable for the expression of a variety of AT-rich heterologous genes in E. coli.