Six cross-linked HA soft tissue fillers (Restylane and Perlane from Medicis, Scottsdale, AZ; Restylane SubQ from Q-Med, Uppsala, Sweden; and Juvéderm Ultra, Juvéderm Ultra Plus, and Juvéderm Voluma from Allergan, Pringy, France) and a soft tissue filler consisting of CaHA microspheres in a carrier gel containing carboxymethyl cellulose (Radiesse, BioForm Medical, Inc., San Mateo, CA). METHODS The viscosity and elasticity of each filler gel were quantified according to deformation oscillation measurements conducted using a Thermo Haake RS600 Rheometer (Newington, NH) using a plate and plate geometry with a 1.2-mm gap. All measurements were performed using a 35-mm titanium sensor at 30°C. Oscillation measurements were taken at 5 pascal tau (τ) over a frequency range of 0.1 to 10 Hz (interpolated at 0.7 Hz). Researchers chose the 0.7-Hz frequency because it elicited the most reproducible results and was considered physiologically relevant for stresses that are common to the skin. RESULTS The rheological measurements in this study support the concept that soft tissue fillers that are currently used can be divided into three groups. CONCLUSION Rheological evaluation enables the clinician to objectively classify soft tissue fillers, to select specific filler products based on scientific principles, and to reliably predict how these products will perform--lifting, supporting, and sculpting--after they are appropriately injected.

Rheologic evaluation reliably predicts tissue integration patterns and appropriate clinical applications of the studied fillers. Paradigms of layered filler placement can be designed to optimally address individual patient need.

Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and is caused by autoantibodies against desmoglein 3 (Dsg3) on epidermal keratinocytes. Because the production of autoantibodies is presumably T cell dependent, Dsg3-specific T cell reactivity was investigated in 14 PV patients and 12 healthy donors. Peripheral blood mononuclear cells from seven PV patients with active disease showed a primary in vitro response to a recombinant protein containing the extracellular portion (EC1-5) of Dsg3, whereas two of seven PV patients in remission or under immunosuppressive treatment exhibited only secondary (2 degrees) or tertiary (3 degrees) T cell responses to Dsg3. T cell responses to Dsg3 were also observed in four of 12 healthy individuals upon 2 degrees or 3 degrees stimulation with Dsg3. Both PV patients and healthy responders were either positive for DRbeta1*0402 -- which is highly prevalent in PV -- or positive for DR11 alleles homologous to DRbeta1*0402. Two CD4+ Dsg3-specific T cell lines and 12 T cell clones from two PV patients and two CD4+ T cell lines and eight T cell clones from two normals were also stimulated by a Dsg3 protein devoid of the EC2-3 (deltaN1), suggesting that epitopes were located in the EC1, EC4, and/or EC5. Using Dsg3 peptides, one immunodominant peptide (residues 161-177) was also identified in the EC2. These observations demonstrate that T cell responses to Dsg3 can be detected in PV patients and in healthy donors carrying major histocompatibility class II alleles identical or similar to those highly prevalent in PV.

Background:Although the safety profile of hyaluronic acid fillers is favorable, adverse reactions can occur. Clinicians and patients can benefit from ongoing guidance on adverse reactions to hyaluronic acid fillers and their management.Methods:A multinational, multidisciplinary group of experts in cosmetic medicine convened the Global Aesthetics Consensus Group to review the properties and clinical uses of Hylacross and Vycross hyaluronic acid products and develop updated consensus recommendations for early and late complications associated with hyaluronic acid fillers.Results:The consensus panel provided specific recommendations focusing on early and late complications of hyaluronic acid fillers and their management. The impact of patient-, product-, and technique-related factors on such reactions was described. Most of these were noted to be mild and transient. Serious adverse events are rare. Early adverse reactions to hyaluronic acid fillers include vascular infarction and compromise; inflammatory reactions; injection-related events; and inappropriate placement of filler material. Among late reactions are nodules, granulomas, and skin discoloration. Most adverse events can be avoided with proper planning and technique. Detailed understanding of facial anatomy, proper patient and product selection, and appropriate technique can further reduce the risks. Should adverse reactions occur, the clinician must be prepared and have tools available for effective treatment.Conclusions:Adverse reactions with hyaluronic acid fillers are uncommon. Clinicians should take steps to further reduce the risk and be prepared to treat any complications that arise.

The genome sequencing of H37Rv strain of Mycobacterium tuberculosis was completed in 1998 followed by the whole genome sequencing of a clinical isolate, CDC1551 in 2002. Since then, the genomic sequences of a number of other strains have become available making it one of the better studied pathogenic bacterial species at the genomic level. However, annotation of its genome remains challenging because of high GC content and dissimilarity to other model prokaryotes. To this end, we carried out an in-depth proteogenomic analysis of the M. tuberculosis H37Rv strain using Fourier transform mass spectrometry with high resolution at both MS and tandem MS levels. In all, we identified 3176 proteins from Mycobacterium tuberculosis representing ϳ80% of its total predicted gene count. In addition to protein database search, we carried out a genome database search, which led to identification of ϳ250 novel peptides. Based on these novel genome search-specific peptides, we discovered 41 novel protein coding genes in the H37Rv genome. Using peptide evidence and alternative gene prediction tools, we also corrected 79 gene models. Finally, mass spectrometric data from N terminus-derived peptides confirmed 727 existing annotations for translational start sites while correcting those for 33 proteins. We report creation of a high confidence set of protein coding regions in Mycobacterium tuberculosis genome obtained by high resolution tandem mass-spectrometry at both precursor and fragment detection steps for the first time. This proteogenomic approach should be generally applicable to other organisms whose genomes have already been sequenced for obtaining a more accurate catalogue of protein-coding genes.

). Keywords► growth factors ► cosmeceuticals ► platelet-rich plasma ► skin aging ► skin rejuvenation ► cytokines ► platelet-rich fibrin matrix ► transforming growth factor-β ► platelet-derived growth factor ► vascular endothelial growth factor AbstractGrowth factors and cytokines (referred to collectively hereafter as GFs) control cell growth, proliferation, and differentiation via a network of inter and intracellular signaling pathways. There are striking parallels between the pathways involved in skin wound healing and those implicated in photoaging of the skin. In recent years, topical and injectable GFs have emerged as an intriguing therapeutic modality that can be harnessed for aesthetic and medical purposes. This article provides a review of available evidence for the role in skin regeneration of topical GFs, and of injectable GFs contained in autologous platelet-rich plasma (PRP). It presents data from recent studies of GFs, offers a discussion of their potential to serve as antiaging actives, and includes safety considerations. As studies of injectable GFs typically assume preexisting familiarity with PRP protocols and the theory behind them, explanatory notes are provided. An assessment is provided of the evidence gaps that exist currently between experimental observations regarding GFs and their proven clinical benefits. Data of evidence levels II and III support the use for skin rejuvenation of topical GFs derived from sources including secretions or lysate of human dermal fibroblasts, and secretions of the snail Cryptomphalus aspersa. GFs with associated stem cell proteins, secreted by human dermal fibroblasts under hypoxic stress, can accelerate skin healing after laser resurfacing. In vitro and animal studies, small case series of PRP-treated patients and one prospective clinical study of its variant, platelet-rich fibrin matrix (PRFM), suggest the value of injectable GFs for skin rejuvenation. However, data of higher power are required to expand this proof of concept into an evidence-based paradigm. The clinical applications of topical and injectable GFs are promising, and remain to be fully defined.With continued study, data of higher evidence level can be accrued and formulations can be developed that offer optimal clinical efficacy, safety, tolerability, and stability. Better understanding of the mechanism of action of GFs can potentially advance our general understanding of dermal signaling pathways, and hence of hyaluronic acid and other alloplastic fillers; and allow the development of protocols for synergistic combination of GFs with other skin rejuvenation modalities. 157This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.In recent years, topical and injectable growth factors and cytokines have emerged as intriguing therapeutic modalities, with burgeoning interest in their potential to serve as actives for skin rejuvenation. Growth factors and cytokines (hereafter referred to collectively as GFs) may be applied topically in cosmeceutical fo...

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