• 대한치과교정학회지
• /
• 제47권4호
• /
• pp.222-228
• /
• 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.

• 구강회복응용과학지
• /
• 제30권4호
• /
• pp.299-306
• /
• 2014

보툴리눔 독소는 여러 영역에서 치료적 목적으로 사용되어 왔으며, 그 사용량과 적용범위가 점차 커지는 추세이다. 보툴리눔 독소가 강력한 독성 물질임에도 불구하고, 그 효과가 6개월이면 사라지는 가역적 치료방법이라는 인식이 강해서, 부작용이나 사용시 주의사항을 중요하게 생각하지 않는 경향이 있었다. 하지만 미국에서 부작용으로 사망하는 사례가 발생하여, 사용시 사망에 대한 주의사항이 추가되었다. 이에 본 종설은 보툴리눔 독소가 인체 내에서 대사되는 과정과, 발생 가능한 부작용, 사용시 유의사항, 사망 부작용 사례 등에 대해 지금까지 보고된 문헌들을 토대로 자세히 검토하고자 한다.

• 구강회복응용과학지
• /
• 제28권2호
• /
• pp.171-178
• /
• 2012

보툴리눔 독소 주사는 이마, 눈가 주름치료 등 미용성형분야 뿐만 아니라 구강 악안면 분야에서는 만성 편두통(chronic migraine), 근육긴장이상(dystonia), 경직(spasticity), 측두하악장애(temporomandibular disorders, TMD)의 치료 등에 사용되어 왔다. 최근 보툴리눔 독소 주사가 운동신경에서 마비효과 뿐만 아니라 감각신경에서 말초감작과 신경원성염증과 관련되는 substance P, CGRP, glutamate 등 비콜린성 신경전달물질의 유리를 차단하여 통증신호를 차단하는 역할을 한다는 가설이 제기되고 있다. 따라서 본 연구는 쥐, 토끼 등 동물 신경 손상 모델에 대한 실험과 치과 치료 후 발생한 신경 손상 환자에서 보툴리눔 독소의 진통 효과 및 작용 기전을 살펴보고자 한다.

• International Journal of Oral Biology
• /
• 제40권2호
• /
• pp.71-77
• /
• 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.

• 구강회복응용과학지
• /
• 제27권2호
• /
• pp.247-251
• /
• 2011

교근비대 환자들은 그들의 각진 턱을 심미적으로 개선시키기 위해 교근 두께를 줄이기를 희망한다. 과거엔 수술적인 방법이 널리 알려져 왔지만 최근 양측으로 주사하는 보톡스 시술이 수술에 비해 덜 침습적이기에 그 대안으로 관심이 대두되고 있다. 이 연구의 목적은 기존의 양측성 교근비대에서 양측에 동량을 주사하는 방법과 달리 편측성 교근비대 환자에서 보툴리눔 독소를 편측으로만 주입 후 삼차원 레이저스캐너를 이용하여 안모의 부피변화를 측정하고자 하였다. 삼차원 레이저스캐너를 이용하여 술전에 편측성 교근비대 환자 10명의 하안모 부피를 측정한 후, 편측으로 보툴리눔 A형 독소 주사 25U이 주사되었다. 주사 4주, 8주, 12주 후 같은 방법으로 하안모의 부피를 측정한 뒤 술전의 삼차원 사진과 중첩하여 변화된 부피를 측정하였다. 주사한 쪽의 부피는 술전에 비해 보툴리눔 독소 주사 4주, 8주, 12주 후 현저히 줄어들었으며 통계학적으로 유의미한 결과를 보였다. 반면 주사안한 쪽의 부피는 특기할 변화가 없었다. 따라서 편측성 교근비대 환자에서 편측 보툴리눔 독소 주사 후 주사한 쪽의 부피가 현저히 감소하여 근육성 비대칭 환자에서 편측 보툴리눔 독소 주사가 심미적 개선에 도움을 줄 수 있을 것으로 사료된다.

• 구강회복응용과학지
• /
• 제33권1호
• /
• pp.1-6
• /
• 2017

보툴리눔 독소 주사는 이마, 눈가 주름치료 등 미용성형분야 뿐만 아니라 만성 편두통(chronic migraine), 근육긴장이상(dystonia), 경직(spasticity), 측두하악장애의 치료 등에 사용되어 왔다. 특히 보툴리눔 독소 주사는 만성편두통환자의 예방적 치료요법으로 현재까지 유일하게 승인된 요법이다. 기존에 잘 알려진 운동신경에서의 마비효과와는 달리, 편두통에 대한 작용기전은 감각신경에서 말초감작과 신경원성염증과 관련되는 substance P, CGRP, glutamate 등 비콜린성 신경전달물질의 유리를 차단하여 통증신호를 차단하는 역할을 한다는 가설이 제기되고 있다. 본 논문에서는 보툴리눔독소가 갖는 진통효과에 대한 고찰과 함께 이를 통하여 추후 만성편두통환자에 대한 주사법 개발에 대한 방향성을 제시하고자 한다.

• Journal of Microbiology and Biotechnology
• /
• 제29권7호
• /
• pp.1165-1176
• /
• 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
• /
• 제39권5호
• /
• pp.642-647
• /
• 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
• /
• 제48권1호
• /
• pp.16-24
• /
• 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
• /
• 제13권2호
• /
• pp.287-291
• /
• 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.