Local Tolerability and Performance Evaluation in Domestic Pigs of a Fractional Radiofrequency Device for Dermatologic Treatment.

Information on the safety of energy-based dermatological surgical devices in domestic pigs, and fractional radiofrequency (RF) devices in particular, is very limited. The aim of this study was to evaluate in a GLP-compliant study in domestic pigs the local reaction and performance of a novel fractional RF device. Five female domestic pigs were subjected to fractional RF pulses, using different energy and pulse durations and depth of penetration of the pulses. The animals were evaluated clinically and histologically at different time points (days 0, 1, 3, 7, and 14) postenergy exposure. There were no microscopic or macroscopic local adverse effects in any tested power settings, and there was time-related progressive healing, reaching complete macroscopic and microscopic healing by 7 days postapplication. As expected, there was power-related progressive increase in the incidence of ablation (destruction of skin tissue by vaporization) and coagulative necrosis of the dermis from low to high power setting. This comprehensive study, using multiple power settings (both ablative and coagulative) and several time points, will be of benefit for future studies evaluating new fractional RF devices.

Pneumatic Delivery of Hyaluronan for Skin Remodeling: A Comparative Review

Jet Volumetric Remodeling (JVR) utilizes the principle of superficial soft tissue delivery of fluids, such as hyaluronic acid (HA) and other therapeutic materials. Dermal delivery of HA activates fibroblasts increasing collagen and elastin synthesis with a long-lasting dermal remodeling and thickening effect. JVR-injected HA causes immediate and diffuse skin hydration resulting in an aesthetically pleasing aspect. JVR technology is able to target different layers during the same treatment with only minor side effects. The article reviews JVR delivery of hyaluronan in comparison to current skin remodeling treatment modalities. J Drugs Dermatol. 2020;19(2)170-175. doi:10.36849/JDD.2020.3641

Fractional ablative and nonablative radiofrequency for skin resurfacing and rejuvenation of Thai patients.

BACKGROUND: Fractional radiofrequency (RF) technology is often the preferable skin resurfacing treatment, especially among Asian patients. Second generation fractional RF technology has exclusive capability to produce separate biological responses (ablation, coagulation, or a combination of both) with 3 distinguished penetration depth programs. AIMS: The aim of this study was to evaluate the efficacy and safety of a fractional RF handpiece such as this, on the Thai population. METHODS: Fifty-five Thai patients were treated with a fractional RF handpiece. The clinical assessment included a pain score, satisfaction survey, physician assessment, a combined patient and physician's assessment of skin condition, and clinical photographic assessments. The wound healing response was evaluated according to 5-time points: immediately after applying a pulse, post 24 hours, post 7 days, post 1 month and post 8 weeks. RESULTS: The obtained patient satisfaction score was "very satisfied" among 74% of the patients, post 3 sessions. Positive correlation was found between patient satisfaction and the physician's assessment. The skin condition assessment showed an increase from an average of 4.2 to 7.9. All treated symptoms improved after each treatment and the clinical outcome lasted at least up to 3-5 months. No significant adverse events were recorded. The in vivo prospective study showed a dose-related response in the deepness of the coagulation injury. In addition, there was evidence for a progressive healing process beginning shortly after exposure and completed within a week. CONCLUSIONS: This study clinically and histologically supports the efficacy of fractional RF handpiece in question with a high safety profile.

Intense Pulsed Light Pulse Configuration Manipulation Can Resolve the Classic Conflict Between Safety and Efficacy.

The widely used intense pulse light (IPL) technology was first commercially launched to the medical market in 1994 and similar to lasers, is based on the basic principle of selective photothermolysis. The main conflict during treatments with light-based technologies is between safety and efficacy of the treatment. The aim of this study was to evaluate new IPL technology, which integrates three different pulse configurations, with specific attention on the safety and efficacy of the treatment. 101 volunteers (with Fitzpatrick skin types I-VI) were treated as follows: 9 patients underwent 8 bi-weekly acne clearance treatments, 51 patients underwent 6-12 hair removal treatments, 11 patients were treated for general skin rejuvenation, 15 patients were treated for pigmentation lesions, and 15 patients were treated for vascular lesions. No serious adverse events were recorded. All patients that were treated for hair removal achieved significant hair clearance. The patients with facial rosacea responded the fastest to the treatment. Eight of nine patients that were treated for acne clearance achieved significant reduction in acne appearance. The results represented in this study support the approach that when taking into consideration both efficacy of the treatment and safety of the patients, the system should be "flexible" enough to allow exact treatment settings profile for each patient, according to their skin type and the symptom's biophysical characteristics. <

New vision in fractional radiofrequency technology with switching, vacuum and cooling.

INTRODUCTION: Since the introduction of fractional technology, various systems were launched to the market. The first generation of fractional RF systems created epidermal ablation with coagulative/necrosis of the dermis with sufficient clinical outcomes, but with some limitations. The aim of this study was to evaluate the efficacy and safety of SVC technology, based on the principle of separate biological responses. MATERIAL AND METHODS: Fifty-two patients were treated for 3-6 sessions using fractional RF handpiece and eight patients received combination treatments with non-invasive RF handpiece. RESULTS: All volunteers showed notable to significant improvement in the photoageing symptoms, without any significant complications or adverse events. DISCUSSION: Due to its wide spectrum of parameters, the SVC technology can promote different biological responses. Owing to the "Switching" technology, the control of energy depth penetration enables delivery of the necessary thermal dose to the targeted skin layer. In addition, this novel technology includes the "Vacuum" and "Cooling" mechanisms, each contributing to the safety of the treatment. The Smart Heat function reduces the necessary energy levels and thereby reduces the pain level and risks for side effects.

Many of the functional differences between acetohydroxyacid synthase (AHAS) isozyme I and other AHASs are a result of the rapid formation and breakdown of the covalent acetolactate-thiamin diphosphate adduct in AHAS I.

Acetohydroxy acid synthase (AHAS; EC 2.2.1.6) is a thiamin diphosphate (ThDP)-dependent decarboxylase-ligase that catalyzes the first common step in the biosynthesis of branched-chain amino acids. In the first stage of the reaction, pyruvate is decarboxylated and the reactive intermediate hydroxyethyl-ThDP carbanion/enamine is formed. In the second stage, the intermediate is ligated to another 2-ketoacid to form either acetolactate or acetohydroxybutyrate. AHAS isozyme I from Escherichia coli is unique among the AHAS isozymes in that it is not specific for 2-ketobutyrate (2-KB) over pyruvate as an acceptor substrate. It also appears to have a different mechanism for inhibition by valine than does AHAS III from E. coli. An investigation of this enzyme by directed mutagenesis and knowledge of detailed kinetics using the rapid mixing-quench NMR method or stopped-flow spectroscopy, as well as the use of alternative substrates, suggests that two residues determine most of the unique properties of AHAS I. Gln480 and Met476 in AHAS I replace the Trp and Leu residues conserved in other AHASs and lead to accelerated ligation and product release steps. This difference in kinetics accounts for the unique specificity, reversibility and allosteric response of AHAS I. The rate of decarboxylation of the initially formed 2-lactyl-ThDP intermediate is, in some AHAS I mutants, different for the alternative acceptors pyruvate and 2-KB, putting into question whether AHAS operates via a pure ping-pong mechanism. This finding might be compatible with a concerted mechanism (i.e. the formation of a ternary donor-acceptor:enzyme complex followed by covalent, ThDP-promoted catalysis with concerted decarboxylation-carboligation). It might alternatively be explained by an allosteric interaction between the multiple catalytic sites in AHAS.

Exploring channeling optimized radiofrequency energy: a review of radiofrequency history and applications in esthetic fields.

INTRODUCTION: Because of its high efficiency and safety, radiofrequency (RF) energy is widely used in the dermatological field for heating biological tissue in various esthetic applications, including skin tightening, skin lifting, body contouring, and cellulite reduction. This paper reviews the literature on the use of nonablative RF energy in the esthetic field and its scientific background. The purpose of this article is to describe in detail the extensive use of medical devices based on RF technology, the development of these medical devices over the years, and recent developments and trends in RF technology. METHODS: The authors conducted a systematic search of publications that address safety and efficacy issues, technical system specifications, and clinical techniques. Finally, the authors focused on their own clinical experiences with the use of patented Channeling Optimized RF Energy technique and mechanical massage. An in-vivo study was conducted in domestic pigs, with a thermal video camera. Twenty-seven female patients participated in a cellulite and body shaping study. The treatments were conducted according to a three-phase protocol. An additional 16 females participated in a skin tightening case study. All of the patients underwent three treatment sessions at 3-week intervals, each according to a protocol specific to the area being treated. RESULTS: The review of the literature on RF-based systems revealed that these systems are safe, with low risks for potential side effects, and effective for cellulite, body contouring, and skin tightening procedures. The in-vivo measurements confirmed the theory that the penetration depth of RF is an inverse function of its frequency, and using a vacuum mechanism makes an additional contribution to the RF energy penetration. The heating effect of RF was also found to increase blood circulation and to induce collagen remodeling. The results from the cellulite and body shaping treatments showed an overall average improvement of 55% in the appearance of cellulite, with an average circumferential reduction of 3.31 cm in the buttocks, 2.94 cm in the thighs, and 2.14 cm in the abdomen. The results from the skin tightening procedure showed moderate improvement of skin appearance in 50% and significant improvement in 31%. At the follow-up visits the results were found to be sustained without any significant side effects. CONCLUSION: Of all tissue heating techniques, RF-based technologies appear to be the most established and clinically proven. The design and specifications of the described vacuumassisted bipolar RF device fall within the range of the specifications currently prescribed for esthetic, nonablative RF systems.

Interactions between large and small subunits of different acetohydroxyacid synthase isozymes of Escherichia coli.

The large, catalytic subunits (LSUs; ilvB, ilvG and ilvI, respectively) of enterobacterial acetohydroxyacid synthases isozymes (AHAS I, II and III) have molecular weights approximately 60 kDa and are paralogous with a family of other thiamin diphosphate dependent enzymes. The small, regulatory subunits (SSUs) of AHAS I and AHAS III (ilvN and ilvH) are required for valine inhibition, but ilvN and ilvH can only confer valine sensitivity on their own LSUs. AHAS II is valine resistant. The LSUs have only approximately 15, <<1 and approximately 3%, respectively, of the activity of their respective holoenzymes, but the holoenzymes can be reconstituted with complete recovery of activity. We have examined the activation of each of the LSUs by SSUs from different isozymes and ask to what extent such activation is specific; that is, is effective nonspecific interaction possible between LSUs and SSUs of different isozymes? To our surprise, the AHAS II SSU ilvM is able to activate the LSUs of all three of the isozymes, and the truncated AHAS III SSUs ilvH-Delta80, ilvH-Delta86 and ilvH-Delta89 are able to activate the LSUs of both AHAS I and AHAS III. However, none of the heterologously activated enzymes have any feedback sensitivity. Our results imply the existence of a common region in all three LSUs to which regulatory subunits may bind, as well as a similarity between the surfaces of ilvM and the other SSUs. This surface must be included within the N-terminal betaalphabetabetaalphabeta-domain of the SSUs, probably on the helical face of this domain. We suggest hypotheses for the mechanism of valine inhibition, and reject one involving induced dissociation of subunits.

Structure of the regulatory subunit of acetohydroxyacid synthase isozyme III from Escherichia coli.

The enzyme acetohydroxyacid synthase (AHAS) catalyses the first common step in the biosynthesis of the three branched-chain amino acids. Enzymes in the AHAS family generally consist of regulatory and catalytic subunits. Here, we describe the first crystal structure of an AHAS regulatory subunit, the ilvH polypeptide, determined at a resolution of 1.75 A. IlvH is the regulatory subunit of one of three AHAS isozymes expressed in Escherichia coli, AHAS III. The protein is a dimer, with two beta alpha beta beta alpha beta ferredoxin domains in each monomer. The two N-terminal domains assemble to form an ACT domain structure remarkably close to the one predicted by us on the basis of the regulatory domain of 3-phosphoglycerate dehydrogenase (3PGDH). The two C-terminal domains combine so that their beta-sheets are roughly positioned back-to-back and perpendicular to the extended beta-sheet of the N-terminal ACT domain. On the basis of the properties of mutants and a comparison with 3PGDH, the effector (valine) binding sites can be located tentatively in two symmetrically related positions in the interface between a pair of N-terminal domains. The properties of mutants of the ilvH polypeptide outside the putative effector-binding site provide further insight into the functioning of the holoenzyme. The results of this study open avenues for further studies aimed at understanding the mechanism of regulation of AHAS by small-molecule effectors.

Acetohydroxyacid synthase isozyme I from Escherichia coli has unique catalytic and regulatory properties.

AHAS I is an isozyme of acetohydroxyacid synthase which is apparently unique to enterobacteria. It has been known for over 20 years that it has many properties which are quite different from those of the other two enterobacterial AHASs isozymes, as well as from those of "typical" AHASs which are single enzymes in a given organism. These include a unique mechanism for regulation of expression and the absence of a preference for forming acetohydroxybutyrate. We have cloned the two subunits, ilvB and ilvN, of this Escherichia coli isoenzyme and examined the enzymatic properties of the purified holoenzyme and the enzyme reconstituted from purified subunits. Unlike other AHASs, AHAS I demonstrates cooperative feedback inhibition by valine, and the kinetics fit closely to an exclusive binding model. The formation of acetolactate by AHAS I is readily reversible and acetolactate can act as substrate for alternative AHAS I-catalyzed reactions.