Scientific review of the aesthetic uses of botulinum toxin type A.

Botulinum toxin type A (BoNT-A), onabotulinumtoxinA (Botox) was approved by the United States Food and Drug Administration for temporary improvement of glabellar lines in patients 65 years and younger in 2002, and has also been used widely for aesthetic purposes such as hyperhidrosis, body shape contouring, and other noninvasive facial procedures. BoNT-A inhibits presynaptic exocytosis of acetylcholine (ACh)-containing vesicles into the neuromuscular junction at cholinergic nerve endings of the peripheral nervous system, thereby paralyzing skeletal muscles. ACh is the most broadly used neurotransmitter in the somatic nervous system, preganglionic and postganglionic fibers of parasympathetic nerves, and preganglionic fibers or postganglionic sudomotor nerves of sympathetic nerves. The scientific basis for using BoNT-A in various cosmetic procedures is that its function goes beyond the dual role of muscle paralysis and neuromodulation by inhibiting the secretion of ACh. Although the major target organs for aesthetic procedures are facial expression muscles, skeletal body muscles, salivary glands, and sweat glands, which are innervated by the somatic or autonomic nerves of the peripheral cholinergic nerve system, few studies have attempted to directly explain the anatomy of the areas targeted for injection by addressing the neural physiology and rationale for specific aesthetic applications of BoNT-A therapy. In this article, we classify the various cosmetic uses of BoNT-A according to the relevant component of the peripheral nervous system, and describe scientific theories regarding the anatomy and physiology of the cholinergic nervous system. We also review critical physiological factors and conditions influencing the efficacy of BoNT-A for the rational aesthetic use of BoNT-A. We hope that this comprehensive review helps promote management policies to support long-term, safe, successful practice. Furthermore, based on this, we look forward to developing and expanding new advanced indications for the aesthetic use of BoNT-A in the future.

Comparison of botulinum neurotoxin type A formulations in Asia.

RESULTS: All protein-based therapeutics, such as botulinum neurotoxin type A (BoNT/A), are potentially immunogenic and can lead to anaphylaxis, autoimmunity, or diminished or complete absence of therapeutic efficacy, especially if administered repeatedly. Therefore, the protein quantity in BoNT/A products is an important consideration when selecting products for treatment. However, essential formulation data are not always publicly accessible. MATERIALS AND METHODS: The neurotoxin protein content of products newly introduced in Asia, such as (listed alphabetically) Botulax®, Meditoxin®, Nabota®, and Relatox®, was measured by sandwich enzyme-linked immunosorbent assay with antisera directed against BoNT/A compared to Xeomin®. RESULTS: Compared to Xeomin with no inactive neurotoxin, although Botulax and Nabota contained 844 and 754 pg of neurotoxin protein, respectively, the percentage of inactive neurotoxin was calculated to be 103 and 81, respectively, while the potency per pg of neurotoxin was 0.118 and 0.133 U, respectively. Meditoxin and Relatox had 575 and 578 pg of neurotoxins, respectively, marginally higher than that of Xeomin, while the percentage of inactive neurotoxins was 38 and 33, respectively, and the potency per pg of neurotoxin was 0.174 and 0.173 U, respectively. However, Xeomin, which has 416 pg/vial of purified neurotoxin and 0.240 U of efficacy per pg of neurotoxin, has the lowest neurotoxin protein content and consequently the highest specific potency compared to the four Asian BoNT/A preparations in this study. CONCLUSION: Although Botulax and Nabota had more neurotoxin than Xeomin in an equivalent volume, they contained greater amounts of inactive neurotoxin. In addition, although Meditoxin and Relatox had slightly more neurotoxin than Xeomin, both contained greater amounts of inactive neurotoxin.

Effect of the refrigerator storage time on the potency of botox for human extensor digitorum brevis muscle paralysis.

BACKGROUND AND PURPOSE: It is recommended that Botox be used within 5 hours of reconstitution, which results in substantial quantities being discarded. This is not only uneconomic, but also inconvenient for treating patients. The aim of this study was to determine the potencies of Botox used within 2 hours of reconstitution with unpreserved saline, the same Botox refrigerated (at +4℃) 72 hours after reconstitution, and during the next 4 consecutive weeks (weeks 1, 2, 3, and 4). This comparison was used to determine the length of refrigeration time during which reconstituted Botox will maintain the same efficacy as freshly reconstituted toxin. METHODS: Individual paralysis rates in the extensor digitorum brevis (EDB) compound muscle action potential (CMAP) amplitude and area were measured 1 week after injecting fresh reconstituted 2.5 MU of Botox on one side of the foot, and when the same quantity of Botox that had been refrigerated for a designated time (i.e., 72 h, or 1, 2, 3, or 4 weeks) into the other side of the foot. The EDB CMAP amplitude and area at 12 and 16 weeks postinjection were also measured to compare the efficacy durations in all five comparative groups. RESULTS: Ninety-four volunteers were divided into five groups according to the refrigerator storage time of the second Botox injection. The paralysis of the EDBs was significant for each injection of Botox, both fresh and refrigerated, with no statistically significant differences between them, regardless of the refrigeration time. There was a tendency toward increased CMAP amplitude and area at 12 or 16 weeks postinjection (p<0.0001). The duration of effective muscle paralysis did not differ significantly throughout the 16-week follow-up period between all five groups. CONCLUSIONS: The potency of reconstituted Botox is not degraded by subsequent refrigeration for 4 weeks. However, there are definite concerns regarding its sterility, and hence its safety, since multiple withdrawals from the same vial over long periods can introduce bacterial contamination.

The change of maximum bite force after botulinum toxin type a injection for treating masseteric hypertrophy.

BACKGROUND: A botulinum toxin type A injection into the masseter muscle has been used as a noninvasive treatment for masseteric hypertrophy. However, muscle atrophy inevitably causes a change of bite force. The aim of this study was to evaluate the change in the maximum bite force after a botulinum toxin type injection for the treatment of masseteric hypertrophy. METHODS: Seven patients who had presented for treatment of masseteric hypertrophy participated in this study. Twenty-five units of botulinum toxin type was injected into each masseter muscle, 50 units in total, at two to five points at the prominent portions of the mandibular angle. The bite-force measurement apparatus included a digital multimeter and a bite-force transducer. The maximum bite force between the maxillary and mandibular first molars was measured before injection and at 2, 4, 8, and 12 weeks after injection. RESULTS: The difference in maximum bite force between the preinjection and 2-, 4-, and 8-week postinjection time points was statistically significant. However, there was no such difference between the preinjection and 12-week postinjection values (p < 0.05). CONCLUSIONS: The maximum bite force was significantly reduced after injection of botulinum toxin type A for the treatment of masseteric hypertrophy. However, it gradually recovered by 12 weeks.

Dual inhibitory effects of furonaphthoquinone compound on enzyme activity and lipopolysaccharide-induced expression of cyclooxygenase-2 in macrophages.

2-Methyl-2-(2-methylpropenyl)-2,3-dihydronaphtho[2,3-b]furan-4,9-dione (NFD-37) is a synthetic furonaphthoquinone compound. In the present study, the NFD-37 compound was found to inhibit prostaglandin (PG) E(2) production in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7. NFD-37 compound exhibited a preferred inhibition on enzyme activity of cyclooxygenase (COX)-2 over COX-1. Further, NFD-37 compound attenuated LPS-induced synthesis of both mRNA and protein of COX-2, and suppressed LPS-induced COX-2 promoter activity in the macrophages, indicating that the furonaphthoquinone compound could down-regulate LPS-induced COX-2 expression at the transcription level. Even though COX-2 promoter behaves as a sophisticated biosensor for host defense, nuclear factor (NF)-kappaB activation has been evidenced to play a major mechanism for LPS-induced COX-2 expression in macrophages. NFD-37 compound exhibited a dose-dependent inhibitory effect on LPS-induced phosphorylation of inhibitory kappaBalpha (IkappaBalpha) protein, and subsequently inhibited IkappaBalpha degradation, DNA binding activity of NF-kappaB complex as well as NF-kappaB transcriptional activity in macrophages RAW 264.7. In another experiment, NFD-37 compound inhibited both COX-2 promoter activity and GST-IkappaBalpha phosphorylation elicited by an expression vector encoding IkappaB kinase beta. Taken together, NFD-37 compound inhibited enzyme activity of COX-2 but also suppressed COX-2 expression depending on NF-kappaB activation, and thus could provide an invaluable tool to investigate pharmacological potential in the excess PG-related disorders.

Sophorae radix extract inhibits high glucose-induced vascular cell adhesion molecule-1 up-regulation on endothelial cell line.

BACKGROUND: Sophorae radix (SR) has been used for various diseases including atherosclerosis and arrhythmias. Atherosclerosis induced by hyperglycemia is an important factor in the promotion of diabetic complications. An early event in atherosclerosis is the adhesion of monocytes to endothelium via adhesion molecules. Among them, vascular cell adhesion molecule-1 (VCAM-1) expression mediates the binding of monocytes and lymphocytes to vascular endothelial cells. METHODS: The study was performed on vascular endothelial cells (ECV304 cells) that were pretreated with various concentrations of SR extract for 3 h before exposure with high glucose (55.5 mmol/l) for 48 h. The protein expression of VCAM-1 was measured by enzyme-linked immunosorbent assay (ELISA) and its mRNA expression was by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: SR extract significantly inhibited high glucose-induced expression of VCAM-1 in a dose-dependent manner and reduced the level of VCAM-1 mRNA through interfering with translocation of nuclear factor-kappaB (NF-kappaB). Decreased VCAM-1 expression by SR extract was associated reduction of adherence between high glucose-stimulated ECV304 cells and human monocyte-like HL-60 cells. CONCLUSIONS: These data suggest that SR extract inhibits high glucose-mediated monocytes-endothelial cells adhesions and expression of VCAM-1 via inhibition of NF-kappaB translocation.

Botulinum toxin type A treatment for contouring of the lower face.

BACKGROUND: Since type A botulinum toxin was first reported for the treatment of masseter muscle hypertrophy in 1994, there have been few reports about cosmetic indications for contouring procedures of the lower face with injection of botulinum toxin type A, and this procedure remains unpredictable. OBJECTIVES: This study attempted a quantitative prospective analysis of reduction of masseter muscle hypertrophy after Botox injection, using ultrasound and computerized tomography (CT) scans to analyze the possible use of botulinum toxin type A as a contouring procedure for the lower face. METHODS: Forty-five patients consented to the study and received a contouring procedure of the lower face from November 2001 to April 2002. Twenty five to 30 U of Botox per side was injected at five to six points into the prominent portions of the mandibular angle. Serial measurements were made of the thickness of the masseter muscle by ultrasound and CT before the injections and at 1 and 3 months thereafter. A quantitative analysis for the masseter thickness changes was performed on just one patient who underwent all ultrasound and CT scans. Statistical analysis of the masseter thickness change was by two-way and multiple comparison analysis. To evaluate clinical long-term effects, the patient's satisfaction with the procedure and any side effects after injections were monitored during 4 to 10 months of follow-up. RESULTS: Among the total of 45 patients, 15 underwent the three ultrasound measurements, and 14 had the three CT measurements. With regard to quantitative analysis of the thickness change to the masseter on both sides of the face according to time points, this was gradually reduced by both the ultrasound and CT measurements during the first 3 months. By ultrasound, the maximum reduction in masseter thickness was seen 1 month after the injections, with a slight increase being observed at 3 months after injection. A continued reduction of masseteric muscle thickness was seen on the CT up to 3 months after injection. In terms of patient satisfaction for up to 10 months of follow-up, the results were as follows: very satisfied, 1; satisfied, 36; slight improvement, 3; no change or dissatisfied, 5. Main local side effects included masticatory difficulties, muscle aching at injection sites, and speech disturbance. However, these side effects were transitory, usually lasting from 1 to 4 weeks after the injections. CONCLUSIONS: Preliminary results from this study suggest that an injection of Botox resulted in relatively satisfactory clinical effects, although there was only a short-term follow-up. It is suggested that the use of botulinum toxin type A for contouring of the lower face can be established as a simple, predictable, alternative facial contouring procedure without a prolonged recovery time.