RELAX and FIRMNESS: The Combination of Muscle Relaxation with Botulinum Toxin and Collagen Biostimulation with Calcium Hydroxyapatite for the Treatment of the Cervical Region.

Introduction: There are several therapeutic modalities for neck rejuvenation, especially calcium hydroxylapatite. Botulinum toxin, by relaxing the mm. platysma, also provides improvement in facial contour. Combination treatments for this region are usually recommended as they offer better results. Objective: This study evaluated the efficacy and safety of the joint dilution of both products (Relax and Firmness - RF), applied in the same device, based on the treatment in the topography of the platysma muscle, ie, starting from the lower third of the face and extending to the neck. Methods: Prospective, blinded, controlled study with 10 participants randomly assigned to RF and 5 in the control group (treated with CaHA only). Results were recorded through the Vectra platform and subjectively evaluated through the GAIS scale by participants and blinded evaluators. Objective analysis was performed using corneometry. Times evaluated: pre-treatment, 30 and 90 days. Considered statistically significant when p<0.1. Results: 100% of the RF group reported "excellent improvement" at D30 and 30% at D90. In the control group, 100% reported "very improved" at D30 and 20% rated "excellent improvement" at D90. A higher and earlier satisfaction rate was observed in the RF group. No difference in corneometry was found between the groups at D30. At D90, the control group had a mean increase of 0.24 versus 5.17 in the RF group (p-value=0.089*). When we analyzed the percentage variation from baseline, the control group was stable, while the RF showed a mean increase of 8.89% (p-value=0.062*). Discussion: We demonstrated the safety and effectiveness of the association of both products, diluted and applied together through microcannulas. Minimization of punctures, patient comfort, and technique based on the anatomy of the platysma muscle underlie the technique. High rates of early satisfaction due to botulinum toxin (Relaxation) and late satisfaction due to CaHA (Firmness).

High Precision Use of Botulinum Toxin Type A (BONT-A) in Aesthetics Based on Muscle Atrophy, Is Muscular Architecture Reprogramming a Possibility? A Systematic Review of Literature on Muscle Atrophy after BoNT-A Injections.

Improvements in Botulinum toxin type-A (BoNT-A) aesthetic treatments have been jeopardized by the simplistic statement: "BoNT-A treats wrinkles". BoNT-A monotherapy relating to wrinkles is, at least, questionable. The BoNT-A mechanism of action is presynaptic cholinergic nerve terminals blockage, causing paralysis and subsequent muscle atrophy. Understanding the real BoNT-A mechanism of action clarifies misconceptions that impact the way scientific productions on the subject are designed, the way aesthetics treatments are proposed, and how limited the results are when the focus is only on wrinkle softening. We designed a systematic review on BoNT-A and muscle atrophy that could enlighten new approaches for aesthetics purposes. A systematic review, targeting articles investigating BoNT-A injection and its correlation to muscle atrophy in animals or humans, filtered 30 publications released before 15 May 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Histologic analysis and histochemistry showed muscle atrophy with fibrosis, necrosis, and an increase in the number of perimysial fat cells in animal and human models; this was also confirmed by imaging studies. A significant muscle balance reduction of 18% to 60% after single or seriated BoNT-A injections were observed in 9 out of 10 animal studies. Genetic alterations related to muscle atrophy were analyzed by five studies and showed how much impact a single BoNT-A injection can cause on a molecular basis. Seriated or single BoNT-A muscle injections can cause real muscle atrophy on a short or long-term basis, in animal models and in humans. Theoretically, muscular architecture reprogramming is a possible new approach in aesthetics.

Effect of a calcium-channel blocker (verapamil) on the morphology, cytoskeleton and collagenase activity of human skin fibroblasts.

The effects of verapamil modulating collagen biosynthesis have prompted us to study the role of this drug in cultured fibroblasts. In this article, we describe the effects of verapamil on fibroblast behaviour, with special emphasis to phenotypic modifications, reorganisation of actin filaments and secretion of MMP1. Human dermal fibroblasts treated with 50-µM verapamil changed their normal spindle-shaped morphology to stellate. Treated cells showed discrete reorganisation of actin filaments, as revealed by fluorescein isothiocyanate (FITC)-phalloidin staining and confocal microscopy. We hypothesised that these effects would be associated to lower levels of cytosolic Ca(2+). Indeed, short time loading with calcium green confirmed that verapamil-treated fibroblasts exhibited lower intracellular calcium levels compared to controls. We also observed that verapamil increases the secretion of MMP1 in cultured fibroblasts, as demonstrated by zymography, specific substrate assays and immunoblot. The morphological alterations induced by verapamil are neither cytotoxic nor associated with other dramatic cytoskeleton alterations. Thus we may conclude that this drug enhances collagenase secretion and does not disrupt the major tracks necessary to deliver these enzymes in the extracellular space. The present results suggested that verapamil could be used at physiological levels to enhance collagen I breakdown, and may be considered a potential candidate for intralesional therapy of wound healing and fibrocontractive diseases.

Estudo in vitro dos efeitos do bloqueador do canal decálcio (verapamil) sobre a biossíntese e contração damatriz extracelular / In vitro study of effects of calcium channel blocker (verapamil) on biosyntheses

Introdução: A adequada formação do tecido de granulação depende do equilíbrio entre abiossíntese e a degradação da matriz extracelular (MEC). A síntese excessiva de colágeno e adeficiente remodelação da MEC podem induzir o aparecimento de lesões dérmicas tipo quelóidese cicatrizes hipertróficas. Método: No presente estudo, utilizamos fibroblastos dérmicoshumanos povoados em gel de colágeno I, tratados ou não pelo bloqueador de canal de cálcio(verapamil). Uma vez no gel de colágeno, a morfologia tridimensional dos fibroblastos foianalisada por microscopia confocal e em cortes corados por hematoxilina & eosina. A atividadeda colagenase (MMP-I) foi determinada por “immunoblot” do meio condicionado. Resultados:Observamos neste estudo maior contração do gel de colágeno povoado por fibroblastoscontrole, quando comparado ao gel povoado por fibroblastos tratados com verapamil. A maiorcontração demonstrada pelos fibroblastos controle foi relacionada à reorientação das fibrascolágenas, à organização dos filamentos de actina e aos níveis de cálcio citosólico. Observamos,também, que o verapamil aumenta a secreção de colagenase. Conclusão: Concluímos que overapamil, ao alterar o metabolismo celular do cálcio, exerce influência sobre a contração daMEC e produção de proteases, com consequente efeito sobre o desenvolvimento de afecçõescicatriciais, como quelóides e cicatrizes hipertróficas.

Background: The appropriate formation of the granulation tissue depends on the balancebetween the biosyntheses and the degradation of the extracellular matrix (EM). The excessivesynthesis of collagen and the deficient degradation of the EM might cause dermal lesions suchas keloids and hypertrophic scars. Methods: In this study we used an experimental modelwhere collagen gels populated by dermal human fibroblast underwent progressive contraction.Fluorescence preparations were studied by confocal microscopy. Collagenase activity (MMPI)was determined in conditioned medium from fibroblasts using immunoblot. Results: Thisstudy showed a greater contraction of the gels populated with control fibroblasts per the timestudied in relation to the gels populated with fibroblasts treated with verapamil. Perhaps thishigher contracting ability is involved with actin organization and levels of cytosolic calcium.We also observed that verapamil increase the secretion of MMP-I. Conclusion: We concludethat cellular calcium metabolism appears to regulate EM production and contraction and thosehypertrophic disorders of wound healing (keloids and hypertrophic scars) may respond totherapy with calcium antagonist drugs (verapamil).