The effect of botulinum toxin A on fat graft survival.

BACKGROUND: Autologous fat grafting is a common procedure used in plastic surgery to correct soft tissue deficiency or depression deformity. However, absorption of grafted fat in the recipient area is unpredictable, and various methods for improving fat survival have been developed clinically. This study analyzed the changes and viability of injected fat in relation to the effects of botulinum neurotoxin type A (BoNTA). METHODS: Fat tissue was harvested from the pre-urinary bladder cavity of four Sprague-Dawley rats and processed using the Coleman technique. The experiment was performed on the backs of eight BALB/c-nu mice. The injection of free fat grafts was performed on the bilateral side of the back of each mouse. The one side (experimental) was treated with 0.5 ml of a free fat injection combined with 0.5 IU of BoNTA in 0.1 ml of saline. The other side (control) was treated with 0.5 ml of free fat injection combined with 0.1 ml of saline. The mice were killed after 9 weeks, and the injected fat grafts were explanted, after which the weight and volume were measured. Histologic study was performed with hematoxylin and eosin staining. Statistical analysis of the weight and volume from both sides, the histologic parameters, and cellular integrity was performed. CONCLUSION: A difference in the weight, volume, and histologic parameters of the injected fat grafts was observed. The BoNTA-treated side exhibited a significantly higher survival rate than the control side. The histologic examination of the fat grafts also demonstrated that the grade scale of cellular integrity was higher for the BoNTA-treated sides. Botulinum toxin A significantly reduces the level of fat graft resorption. Therefore, an injected fat graft can be used in conjunction with botulinum toxin A and offers better volumetric improvement. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.

Pathophysiologic characteristics of balloon cells in cortical dysplasia.

OBJECTS: Balloon cells are histopathological hallmarks of cortical malformations, i.e., focal cortical dysplasia (FCD) of the Taylor type or the cortical tubers of tuberous sclerosis, and they are believed to be the epileptogenic substrate and cause therapeutic drug resistant epilepsy in man. This study was carried out to investigate the developmental histogenesis and epileptogenesis of balloon cells in FCD. MATERIALS AND METHODS: We used an immunohistochemical approach to examine the expressions of primitive neuroepithelial cell antigens (CD34, nestin, and vimentin), ionotrophic glutamate receptor subunits (NR1, NR2A/B, GluR1, GluR2, GluR3, GluR4, and GluR5/6/7), and P-glycoprotein in balloon cells from FCD and normal cerebral cortex epileptogenic lesions. CONCLUSION: Balloon cells presented in clusters or as scattered cells throughout FCD lesions involving the gray and white matter. We found the balloon cells to be classifiable into three subtypes based on glial fibrillary acidic protein (GFAP) and neurofilament protein (NF-L) immunohistochemistry, i.e., as neuronal, astrocytic, and uncommitted. Immunopositivity for nestin, CD34, and vimentin in balloon cells of FCD suggests that they may be derived from the abnormal development and differentiation of neural stem cells. Moreover, it appears that epileptogenesis in cortical dysplasia is partly caused by the upregulations of some glutamate receptor subunit proteins (NR1, NR2A/B, GluR1, and GluR3) in balloon cells and dysplastic neurons. We speculate that the presence of the drug resistance protein P-glycoprotein in balloon cells might explain medically refractory epilepsy in FCD.

The structure-activity relationship of the series of non-peptide small antagonists for p56lck SH2 domain.

The antagonists for the SH2 domain are regarded as novel therapeutic candidates for cancer, autoimmune disease, and chronic inflammatory disease. Previously, we identified rosmarinic acid (alpha-o-caffeoyl-3,4-dihydroxyphenyl-lactic acid; RosA) from Prunella vulgaris as an antagonist for the p56lck SH2 domain by screening natural products. RosA not containing phosphotyrosine surrogate had a considerable inhibitory activity for T-cell antigen receptor (TCR)-induced interleukin (IL)-2 expression, and subsequent T-cell proliferation in vitro cell assay. To investigate the structure-activity relationship of RosA and to identify a novel p56lck SH2 antagonist with more potent in vitro T-cell inhibitory activity, we synthesized several analogs of RosA by using rational design. All synthesized compounds were tested in vitro binding activity for the SH2 domain and in vitro T-cell inhibitory activity. All four hydroxyl groups of RosA were essential for binding with the p56lck SH2 domain and T-cell inhibitory activity. Unexpectedly, conformationally less constrained analogs 4 and 9 showed a more potent binding affinity for the SH2 domain than that of RosA, and chirality of the analog did not play an important role in protein binding. We successfully identified several RosA analogs with a more potent T-cell inhibitory activity than that of RosA. Overall results revealed important structural requirements of the p56lck SH2 antagonists for in vitro T-cell inhibitory activity and in vitro protein binding activity.

Development of novel lipid-peptide hybrid compounds with antibacterial activity from natural cationic antibacterial peptides.

Seven depsipeptides were synthesized by appending seven amino acids (Lys, Leu, Val, Phe, Ser, Gln, and Pro) at the N-terminus of the active fragment [TE-(33-43)], respectively corresponding to the C-terminal beta sheet domain of tenecin 1, an antibacterial protein and their activities were measured against Staphylococcus aureus. Considering the relationship between the activity and the characteristic of amino acid at the N-terminal of the peptide, novel derivatives were designed and synthesized from TE-(33-43) by introduction of fatty acids at the N-terminal. In this process, we synthesized novel lipid-peptide hybrid compounds with a potent antibacterial activity and more improved bioavailabilities. We characterized the important structural parameters of the lipid-peptide hybrid compounds for the antibacterial activities.

Design and synthesis of small chemical inhibitors containing different scaffolds for lck SH2 domain.

On the basis of the structure of (R)-rosmarinic acid, a series of small chemical compounds with a different scaffold was synthesized as inhibitors for lck SH2 domain. From ELISA results, most of all chemical compounds showed a similar or a little lower binding activity for lck SH2 domain compared to the lead compound, (R)-rosmarinic acid. It was characterized that the backbone rigidity between two catechol substructures was required for the full activity and acid substructure of the lead compound was important for the activity. We successfully identified novel lead compounds that did not contain phosphotyrosine moiety and might have an improved bioavailability as inhibitor for lck SH2 domain.