Surgeon's Guide to Facial Soft Tissue Filler Injections: Relevant Anatomy and Safety Considerations.

The purpose of this study is to provide a review of the relevant facial anatomy related to soft tissue filler injections. Facial fillers are used daily in our clinical practice. Although their use is safe and predictable, adverse events do occur. Some of these dire events include vascular complications leading to blindness, ischemia, and even stroke. Proper knowledge and understanding of the anatomic landmarks can minimize the risk of these vascular events. In addition, early recognition and treatment are necessary to prevent permanent complications.

Enzymatic recycling of ascorbic acid from dehydroascorbic acid by glutathione-like peptides in the extracellular loops of aminergic G-protein coupled receptors.

The intracellular recycling of ascorbic acid from dehydroascorbic acid by the glutathione-glutathione reductase system has been well-characterized. We propose that extracellular recycling of ascorbic acid is performed in a similar manner by cysteine-rich, glutathione-like regions of the first and second extracellular loops of some aminergic receptors including adrenergic, histaminergic, and dopaminergic receptors. Previous research in our laboratory demonstrated that ascorbic acid binds to these receptors at a site on their first or second extracellular loops, significantly enhancing ligand activity, and apparently recycling hundreds of times their own concentration of ascorbate in an enzymatic fashion. In this study, we have synthesized 25 peptides from the first and second extracellular loops of aminergic and insulin receptors and compared them directly to glutathione for their ability to prevent the oxidation of ascorbate and to regenerate ascorbate from dehydroascorbic acid. Peptide sequences that mimic glutathione in containing a cysteine and a glutamic acid-like amino acid also mimic glutathione activity in effects and in kinetics. Some (but not all) peptide sequences that contain one or more methionines instead of cysteine can significantly retard the oxidation of ascorbic acid but do not recycle it from dehydroascorbate into ascorbate. Peptides lacking both cysteines and methionines uniformly failed to alter significantly ascorbate or dehydroascorbate oxidation or reduction. We believe that this is the first proof that receptors may carry out both ligand binding and enzymatic activity extracellularly. Our results suggest the existence of a previously unknown extracellular system for recycling ascorbate. Copyright © 2016 John Wiley & Sons, Ltd.

Tartaric Acid Enhances Adrenergic Receptor Activity: Test of a General Theory of Extracellular Aminergic GPCR Enhancer Discovery.

Several different classes of compounds enhance the potency of aminergic receptor ligands three-fold or more and increase their duration of activity up to ten-fold. These enhancers include the vitamins ascorbic acid and folic acid, chelators such as ethylenediaminetetraacetic acid, corticosteroids, and opioids, opiates and opiate antagonists. We have previously demonstrated that all of these classes of enhancers share a common molecular motif consisting of a linear array of two hydroxyls and a carbonyl. We demonstrate here that because of this common molecular motif, all compounds known to enhance aminergic receptor ligands bind to highly conserved regions of the first or second extracellular loops of aminergic receptors at physiologically or pharmacologically relevant concentrations. These compounds also bind directly to aminergic ligands with significant specificity and affinity. These results suggest three very simple, complementary methods for screening for novel extracellular aminergic receptor enhancers: 1) in silico screening for the presence of the common aminergic receptor enhancer motif; 2) screening for binding to the aminergic ligand of choice; and 3) screening for binding to receptor peptides representing the enhancer binding site on the receptor. Using these three complementary methods, we predict a new class of enhancers (tartaric acids) and demonstrate the predicted enhancement in an in vitro smooth muscle assay.