The molecular basis of tRNA selectivity by human pseudouridine synthase 3.

Pseudouridine (Ψ), the isomer of uridine, is ubiquitously found in RNA, including tRNA, rRNA, and mRNA. Human pseudouridine synthase 3 (PUS3) catalyzes pseudouridylation of position 38/39 in tRNAs. However, the molecular mechanisms by which it recognizes its RNA targets and achieves site specificity remain elusive. Here, we determine single-particle cryo-EM structures of PUS3 in its apo form and bound to three tRNAs, showing how the symmetric PUS3 homodimer recognizes tRNAs and positions the target uridine next to its active site. Structure-guided and patient-derived mutations validate our structural findings in complementary biochemical assays. Furthermore, we deleted PUS1 and PUS3 in HEK293 cells and mapped transcriptome-wide Ψ sites by Pseudo-seq. Although PUS1-dependent sites were detectable in tRNA and mRNA, we found no evidence that human PUS3 modifies mRNAs. Our work provides the molecular basis for PUS3-mediated tRNA modification in humans and explains how its tRNA modification activity is linked to intellectual disabilities.

Aesthetic Improvement With Topical Body Skin Treatment as a Complement to Cryolipolysis.

BACKGROUND: A firming and toning cosmetic body lotion (FTB) was developed to target key pathways relevant to body skin health and rejuvenation that may complement the improvements observed after noninvasive body contouring (NIBC). A pilot study explored the efficacy and tolerability of FTB as an adjunct to cryolipolysis. METHODS: An open-label, single-site, single-arm, 12-week study enrolled subjects aged 20 to 65 who had pre-elected to receive 1 or more cryolipolysis treatments (CoolSculpting® or CoolSculpting® Elite; Zeltiq Aesthetics, Inc.) on the inner thigh, back/bra fat, or submental areas. Immediately post-procedure, the investigator applied FTB to the treated area. Subjects then applied FTB topically twice daily for 12 weeks on the treated area. Skin texture and firmness were graded visually by the investigator using a 10-point scale, and subjects graded effectiveness, product attributes, and satisfaction with a questionnaire.  Results: Seventeen subjects (16 women, 1 man) enrolled. After 12 weeks of FTB application, significant improvements in skin firmness were observed in all treated areas, while skin texture showed improvements on the inner thigh and back/bra fat (all P≤0.009). With continued use following cryolipolysis, more than 70% of subjects agreed that FTB improved skin firmness, smoothness, and overall appearance. Subjects indicated that FTB was an effective adjunct to cryolipolysis. Throughout the study, 86% to 92% of subjects reported “fair,” “good,” or “excellent” satisfaction with FTB.  Conclusion: This pilot study suggests that FTB may complement skin improvements seen post-NIBC.J Drugs Dermatol. 2024;23(4): doi:10.36849/JDD.7917.

Effects of a Topical Growth Factor Regimen Following Pre-elected Cosmetic Facial Injection Procedures.

BACKGROUND: There are limited studies evaluating topical cosmetic skincare products following cosmetic facial injections. OBJECTIVE: An open-label study assessed a novel medical-grade topical skincare regimen following cosmetic facial injections. METHODS: The study enrolled 20 women with moderate to severe facial photodamage who used non–physician-dispensed skincare products and pre-elected to receive facial neuromodulator and hyaluronic acid (HA) dermal filler injections. All subjects continued regular skincare through week 4 after facial injection, then switched to the novel regimen (growth factor product, TNS Advanced+; day/night antioxidant serum system, Lumivive; HA-based hydrator, HA5; and basic skincare components) through week 16. RESULTS: At week 4, significant (P≤0.05) improvements from baseline were seen for multiple investigator-graded skin quality parameters, including overall photodamage, tactile roughness, and skin tone evenness, as well as fine and coarse lines/wrinkles. After switching to the novel regimen, additional significant improvements in overall skin quality and forehead, cheek, and perioral fine lines/wrinkles were observed at week 8 (all P≤0.05 vs week 4), which continued through week 16. CONCLUSION: This study highlights the importance of topical skincare in conjunction with cosmetic facial injections to holistically optimize overall skin quality and appearance. J Drugs Dermatol. 2023;21(1): doi:10.36849/JDD.7160.

Restoration of Aging Body Skin: Evidence-Based Development of a Topical Formulation for Improving Body Skin Quality.

BACKGROUND: Age-related changes in body skin are emerging as important therapeutic targets. A novel topical firming and toning body lotion (FTB) has been developed to target multiple pathways involved in body skin rejuvenation. METHODS: FTB was evaluated in a randomized, double-blind, vehicle-controlled, 12-week study in women (N=54) with mild to moderate lack of firmness on the upper arms and mild to moderate cellulite on the thighs. Investigator clinical assessments, instrumentation evaluations, and patient questionnaires were performed. Histological assessment of ex vivo human skin treated with FTB and gene expression analysis in 3-dimensional human skin models following application of FTB or product comparators were conducted. RESULTS: At week 12, FTB treatment significantly improved (vs baseline) firmness, sagging, smoothness, texture, cellulite, and crepiness on investigator-, instrument-, and photographically assessed outcomes. Participants reported significant improvements in self-perceived efficacy and overall satisfaction with the appearance of their skin following FTB treatment vs vehicle control. Adverse events were mild or moderate in severity. FTB supported new collagen and elastic fiber formation in ex vivo skin. FTB increased skin rejuvenation–associated gene expression vs comparator products. CONCLUSIONS: FTB provided significant improvements in the upper arms and thighs compared with baseline and vehicle control across multiple investigator and instrumentation evaluations. Most participants reported greater efficacy and treatment satisfaction with FTB vs vehicle. FTB treatment stimulated dermal extracellular matrix renewal and induced expression of genes involved in skin rejuvenation pathways. This study provides clinical and preclinical evidence supporting the use of FTB to improve body skin quality. Citation: Makino ET, Jiang LI, Acevedo SF, et al. Restoration of aging body skin: evidence-based development of a topical formulation for improving body skin quality. J Drugs Dermatol. 2023;22(9):887-897. doi:10.36849/JDD.7292.

Development of an in vitro Functional Assay to Evaluate the Occlusive Properties of Moisturizers on Dry Skin.

INTRODUCTION: Dry skin is a hallmark of impaired skin barrier function. Moisturizers are a mainstay of treatment to help the skin retain moisture, and there is a high consumer demand for effective products. However, the development and optimization of new formulations are hampered due to lack of reliable efficacy measures using in vitro models. METHODS: In this study, a microscopy-based barrier functional assay was developed using an in vitro skin model of chemically induced barrier damage to evaluate the occlusive activity of moisturizers. RESULTS: The assay was validated by demonstrating the different effects on barrier function between humectant (glycerol) and occlusive (petrolatum). Significant changes in barrier function were observed upon tissue disruption, which was ameliorated by commercial moisturizing products. CONCLUSION: This newly developed experimental method may be helpful to develop new and improved occlusive moisturizers for the treatment of dry skin conditions.

Assessing changes in facial skin quality using noninvasive in vivo clinical skin imaging techniques after use of a topical retinoid product in subjects with moderate-to-severe photodamage.

BACKGROUND: Studies utilizing reflectance confocal microscopy (RCM) and dynamic optical coherence tomography (D-OCT) to assess cosmetic skin changes are limited. METHODS: A 12-week, open-label study was conducted using RCM and D-OCT to evaluate the effects of a topical cosmetic retinol (RET05) on subjects with facial photodamage. Study endpoints included investigator grading, standardized (VISIA-CR) and 3D photography (Antera 3D), independent RCM (VivaScope1500) and D-OCT (VivoSight) image analysis, validated FACE-Q scales, and subject questionnaires. RESULTS: Twenty-three subjects, 45- to 68-year old, with Fitzpatrick skin types II-IV completed the study. After 12 weeks of repeated application, RET05 demonstrated significant corresponding cosmetic improvements for overall photodamage, skin tone unevenness, tactile roughness, fine lines/wrinkles (forehead, periocular, and perioral), and coarse lines/wrinkles (forehead, periocular, and cheeks), and Allergan Skin Roughness Scale. FACE-Q assessments also demonstrated significant improvements from baseline at week 12. RCM analysis showed decreases in all epidermis, less compact stratum corneum (SC), more non-compact SC, decreases in coarse/huddled dermal fibers, and increases in fibrillar dermal fibers, as compared to baseline. D-OCT analysis showed significant decreases in epidermal thickness (ET), reduction of moderate/many collagen fragments and collagen bundles, and significant increases in the stroma attenuation coefficient and collagen density. Moreover, the dermal-epidermal junction was more pronounced, and vascular abundance at 300 and 500 µm depth increased. Independent evaluation of RCM and D-OCT images showed similar decreases in ET and improvements in dermal fibers. CONCLUSION: This study was the first to utilize RCM and D-OCT to evaluate the cosmetic effects of a topical retinoid and further substantiate improvements in skin quality.

Assessment of Circadian-based Antioxidants Plus a Comprehensive Brightener in Skin of Color Patients With Hyperpigmentation.

BACKGROUND: Hyperpigmentation disorders disproportionately affect individuals with skin of color. There is an unmet need for safe and effective topical treatments for this population. OBJECTIVE: The efficacy and tolerability of LYT2 in combination with LVS were assessed in skin of color patients with moderate to severe facial hyperpigmentation. METHODS: A single-arm study was performed in Asian, Hispanic, or African American patients (Fitzpatrick phototypes III–VI). Subjects applied LYT2 and LVS daily, in addition to a basic skincare regimen, for 12 weeks. Overall hyperpigmentation, skin-tone evenness, and radiance were evaluated by the investigator, and subjects completed questionnaires regarding self-perceived efficacy. RESULTS: After 12 weeks, the combination of LYT2 and LVS produced a 23% improvement in overall hyperpigmentation, a 33% increase in skin-tone evenness, and a 51% increase in radiance compared to baseline. At the study conclusion, all patients noted at least a slight improvement in skin condition, and 70% reported good or excellent satisfaction. One subject (8%) experienced a treatment-related adverse event. CONCLUSION: The combination of LYT2 and LVS was well-tolerated and improved the appearance of hyperpigmentation and overall quality in skin of color. J Drugs Dermatol. 2022;21(4):376-380. doi:10.36849/JDD.6687.

Defining Skin Quality: Clinical Relevance, Terminology, and Assessment.

BACKGROUND: Flawless skin is one of the most universally desired features, and demand for improvements in skin quality is growing rapidly. Skin quality has been shown to substantially impact emotional health, quality of life, self-perception, and interactions with others. Although skin quality improvements are a common end point in studies of cosmeceuticals, they are rarely assessed in clinical studies of other aesthetic treatments and products. Descriptive terminology for skin quality parameters also varies considerably within the aesthetic field, relying on a range of redundant and occasionally contradictory descriptors. In short, skin quality has not been clearly defined. OBJECTIVE: The goal of this review is to highlight the importance of skin quality to patients and physicians, explore known and unknown factors comprising skin quality, and provide clarity regarding terminology, descriptors, and evaluation tools for assessing skin quality. MATERIALS AND METHODS: A review of the literature on skin quality was performed without limitation on publication date. Relevant articles are presented. RESULTS AND CONCLUSION: We propose a framework of attributes contributing to skin quality rooted in 3 fundamental categories-visible, mechanical, and topographical-with the aim to provide information to help guide clinicians and inform future clinical studies.

Efficacy and Tolerability of a Novel Topical Treatment for Neck: A Randomized, Double-blind, Regimen-Controlled Study.

The neck plays a telling role as an age indicator. Due to its anatomy and function, neck skin ages differently than facial skin and special considerations need to be taken when providing treatment. A randomized, double-blind, regimen-controlled study was conducted to assess the efficacy and tolerability of a novel topical cosmetic cream (NCC) specifically tailored to address the signs of skin aging of the neck and décolletage. Twice daily application of NCC significantly improved skin sagging/laxity of the neck as well as the appearance of fine and coarse lines/wrinkles, crepiness, tactile roughness, overall skin texture, hyperpigmentation, skin tone evenness, and radiance. NCC also significantly improved the appearance of fine and coarse lines/wrinkles, tactile roughness, hyperpigmentation, skin tone evenness, and radiance of the décolletage. Investigator assessments were corroborated by objective cutometer measurements that demonstrated improved skin firmness and elasticity. In vitro analysis in human 3D skin models show that stimulation of neocollagenesis and neoelastogenesis as well as support of cellular proteostasis through proteasome and autophagy activation are potential mechanisms of action for the observed clinical outcomes. J Drugs Dermatol. 2021;20(2):184-191. doi:10.36849/JDD.5819 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Transtubular Endoscopic Posterolateral Decompression of the L5 Root under Navigation and O-arm: A Technical Note.

Among studies evaluating minimally invasive surgical (MIS) decompression of the L5 root, techniques involving transtubular endoscopic decompression under O-arm navigation are rare. We present the case of a 68-yearold woman with left leg pain, muscle weakness and gait disturbance of one month duration. The patient underwent transtubular endoscopic decompression under O-arm navigation. There is no radiation hazard to the operating room staff with this procedure. After surgery, the patient had significant pain relief and her left lower limb motor function had improved by follow-up at one year. C-arm-free endoscopic L5 root decompression is a safe and effective procedure.

Clinical Benefits of Circadian-based Antioxidant Protection and Repair.

Skin activities follow endogenous circadian rhythms resulting in differences between daytime and nighttime properties. To address the variations in skin needs, a novel circadian-based dual serum system (LVS) was developed. A 12-week, double-blind, randomized, regimen-controlled, multi-center study was conducted to assess the efficacy and tolerability of LVS on subjects presenting with moderate-severe photodamage. 61 Female subjects (36–65 years; Fitzpatrick skin types I–VI) completed the study. The active group received LVS (daytime serum and nighttime serum) and basic skin care regimen (moisturizer and SPF 35 sunscreen), while the control group received the basic skin care regimen only. In addition to clinical grading, subject self-assessment questionnaires, and standardized photography, punch biopsies were taken in a subset of subjects for immunohistochemistry. Additionally, swab samples were taken for skin surface oxidation analysis. Significant improvements over control were observed in the active group in Radiance (weeks 4, 8, and 12), Overall Photodamage, Tactile Toughness, and Global Fine Lines/Wrinkles (week 12). Biopsy results, skin swab analysis and standardized photographs support the clinical grading findings. At all follow-up visits, LVS was consistently highly rated over control by subjects, with a significant proportion of subjects agreeing at week 12 that LVS “improved the radiance of my skin,” and “improved the overall health and look of my skin”. Results from this study suggest that LVS may provide essential protective and reparative effects to skin exposed to the damaging effects of environmental factors, and also demonstrates the value of including skin circadian rhythm-based concepts in a topical skincare regimen. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5355.

Imaging Cardiovascular Emergencies: Real World Clinical Cases.

Cardiovascular emergencies represent life-threatening conditions requiring a high index of clinical suspicion. In an emergency scenario, a simple stepwise biomarker/imaging diagnostic algorithm may help prompt diagnosis and timely treatment along with related improved outcomes. This article describes several clinical cases of cardiovascular emergencies, such as coronary stent thrombosis-restenosis, takotsubo syndrome, acute myocarditis, massive pulmonary embolism, type A acute aortic dissection, cardiac tamponade, and endocarditis.

Addressing Male Facial Skin Concerns: Clinical Efficacy of a Topical Skincare Treatment Product for Men.

The growing male skincare market reflects the increased interest of men in addressing facial aging concerns and maintaining a healthy youthful appearance. Because of differences in skin structure and aging as well as in lifestyle and behavior, male facial skin presents unique challenges that may result in different priorities or treatment strategies compared to female skin. A clinical study was conducted to assess clinical efficacy and tolerability of a topical skincare treatment product that was developed to address several male facial skin concerns related to skin quality, skin aging, and shaving. The treatment product provided significant improvements in all clinical efficacy parameters including overall photodamage, tactile roughness, fine line/wrinkles, and coarse lines/wrinkles. Furthermore, significant improvements in erythema as well as dryness/scaling were observed. Subject self-assessment questionnaires showed that the treatment product was highly rated in both self-perceived efficacy as well as product attributes. Use of skincare treatment products that tackle specific male facial skin concerns could further optimize skin quality and support healthy and youthful looking skin in men.

J Drugs Dermatol. 2018;17(3):301-306.

Clinical Efficacy of a Novel Two-Part Skincare System on Pollution-Induced Skin Damage.

INTRODUCTION: Air pollution continues to be a global health concern and recent studies have shown that air pollutants can cause skin damage and skin aging through several pathways that induce oxidative stress, inflammation, apoptosis, and skin barrier dysfunction. Preventive measures need to be considered to retain optimal skin health, and topical skincare products may be able to alleviate the negative effects of air pollution on skin. A randomized, double-blind, placebo-controlled clinical usage study was conducted to assess the efficacy and tolerability of a novel two-part skincare system (LVS) that was developed to provide protection against environmental skin aggressors including air pollution. After 8 weeks of use in subjects exposed to extremely high levels of pollution, LVS provided significant improvements compared to placebo in all clinical efficacy parameters including crow's feet wrinkles, overall skin damage, skin tone evenness, tactile roughness, and visible redness. Subject self-assessment questionnaires showed that the treatment product was highly rated in self-perceived efficacy. Decreased SQOOH and MDA content in skin swab samples suggest that LVS helped to reduce oxidative stress in patients' skin. Histological analyses of biopsy samples using biomarkers related to skin structure, damage and function (collagen IV, MMP1, CPD, and CD1a) further support the clinical benefits of LVS. Altogether, the presented study is among the first to show that topical skincare products can help to reduce pollution-induced skin damage and improve skin quality, especially when specifically formulated with active ingredients that combat the harmful effects of air pollutants. J Drugs Dermatol. 2018;17(9):975-981.

Combination of In-Office Chemical Peels With a Topical Comprehensive Pigmentation Control Product in Skin of Color Subjects With Facial Hyperpigmentation.

Dyschromia is one of the primary complaints for patients with skin of color. Treatments need to achieve a balance between tolerability and efficacy to address existing hyperpigmentation without causing additional damage that could trigger post-inflammatory hyperpigmentation (PIH). An open-label, single-center study was conducted to assess the efficacy of a novel comprehensive pigmentation control serum (LYT2) combined with a series of three very superficial chemical peels (VP) in skin of color subjects. Seventeen female and male subjects aged 36 to 69 years with Fitzpatrick Skin Types III-VI and moderate to severe facial hyperpigmentation were enrolled in the 12-week clinical study. Subjects identified as Asian, Hispanic, African American, or Caucasian ethnicities. Subjects received a series of 3 VP treatments every 4 weeks. LYT2 was applied twice-daily in between VP treatments. Investigator assessments for overall hyperpigmentation, overall photodamage, and skin tone unevenness, as well as standardized digital photography and subject self-assessment questionnaires were conducted at all visits (baseline and weeks 4, 8, and 12). In vivo reflectance confocal microscopy (RCM) of a target lesion was conducted (in a subset of subjects) at baseline and week 12. Fourteen subjects completed the study. The treatment regimen provided statistically significant improvements in all efficacy parameters at weeks 8 and 12 (all P less than equal to 0.03, student's t-test). Standardized digital photography and RCM images support the improvements in overall hyperpigmentation observed by the investigator. At the end of treatment, the regimen was highly rated by subjects with 100% of subjects (strongly agree/agree) that the combination "decreased the appearance of uneven skin tone and discolorations" and "reduced the appearance of sun damage." In addition to this clinical study, independent case studies with this combination treatment regimen at a separate study site were also conducted with results that corroborate the formal clinical study findings. The comprehensive results from these studies suggest that the combination of a comprehensive pigmentation control serum with a series of 3 very superficial chemical peels may provide an effective treatment approach for hyperpigmentation in skin of color patients.

J Drugs Dermatol. 2017;16(4):301-306.

Clinical Assessment of Immediate and Long-Term Effects of a Two-Step Topical Hyaluronic Acid Lip Treatment.

Key features of lip aging include loss of volume, color, and definition as well as increases in lines/wrinkles and uneven skin texture. A single-center, open-label clinical study was conducted to assess the efficacy and tolerability of a novel, topical two-step lip treatment (HA5 LS) in female subjects presenting with mild to moderate lip dryness and mild to severe lip condition. Subjects were instructed to apply HA5 LS at least three times a day to ensure coverage 8 hours a day for four weeks. Clinical assessments for efficacy and tolerability were conducted at baseline, baseline post-application, week 2, and week 4. Standardized digital photography, subject self-assessment questionnaires, and instrumentation measurements for skin hydration (corneometer) and lip plumpness (digital caliper) were also conducted. Thirty-six female subjects aged 22-40 years enrolled in the study. HA5 LS provided instant and long term effects, achieving significant improvements in all clinical grading parameters including lip texture, color, definition/contour, scaling, cupping, lines/wrinkles, lip plumpness, and overall lip condition from baseline post-application to week 4 (all P less than equal to .001; Wilcoxon signed-rank test). Instrumentation measurements for hydration and digital caliper at weeks 2 and 4 were also significant (all P less than equal to .032; paired t-test). HA5 LS was also well-tolerated and highly-rated by subjects throughout the study duration. Results from this study suggest that HA5 LS addresses the key features of lip aging, providing both instant and long-term benefits.

J Drugs Dermatol. 2017;16(4):366-371.

Upregulation of Extracellular Matrix Genes Corroborates Clinical Efcacy of Human Fibroblast-Derived Growth Factors in Skin Rejuvenation.

Skin care products may use various active ingredients to support skin rejuvenation including growth factors and other molecules that help to regenerate extracellular matrix (ECM) and promote skin repair. The biological effect of skin care products with a strong anti-aging claim was assessed in gene expression analyses using an in vitro human skin model. Application of products containing human fibroblast-derived growth factors resulted in signifcant upregulation of genes encoding ECM components including collagens and elastin. Human fibroblasts cultured under hypoxic conditions show increased gene expression of stem cell markers, and their conditioned media could possibly further support skin rejuvenation. Furthermore, a double-blind, randomized, placebo-controlled study was con-ducted in subjects with moderate to severe facial photodamage to assess the cosmetic clinical efficacy of a product containing human fibroblast-derived growth factors. The test product group demonstrated significantly greater reductions in the appearance of fne lines/wrinkles, coarse line/wrinkles, and overall photodamage, compared to the placebo group. Altogether, the results suggest that human fibroblast-derived growth factors support skin rejuvenation by stimulating dermal fibroblasts to generate ECM.

Development and Clinical Assessment of a Comprehensive Product for Pigmentation Control in Multiple Ethnic Populations.

BACKGROUND: Pigmentary changes in people of different ethnic origins are controlled by slight variations in key biological pathways leading to different outcomes from the same treatment. It is important to develop and test products for desired outcomes in varying ethnic populations. OBJECTIVES: To develop a comprehensive product (LYT2) that affects all major biological pathways controlling pigmentation and test for clinical efficacy and safety in different ethnic populations. METHODS: A thorough analysis of biological pathways was used to identify ingredient combinations for LYT2 that provided optimal melanin reduction in a 3-D skin model. Expression of four key genes for melanogenesis, TYR, TYRP-1, DCT, and MITF was analyzed by qPCR. Clinical study was conducted to compare the efficacy and tolerability of LYT2 against 4% hydroquinone (HQ). RESULTS: Average melanin suppression by LYT2 in 7 independent experiments was 45%. All four key genes show significant down- regulation of expression. LYT2 provided statistically significant reductions in mean overall hyperpigmentation grades as early as week 2 compared to baseline, with continued significant improvements through week 12 in all ethnic groups tested. CONCLUSION: We have successfully combined management of 6 categories of pathways related to melanogenesis: melanocyte activation, melanosome development, melanin production, melanin distribution, keratinocyte turnover, and barrier function to create a comprehensive HQ-free product. The outcome clearly shows greater pigmentation control with LYT2 compared to other HQ-free products in skin tissue models and earlier control in clinical studies compared to 4% HQ. Clinical study shows pigmentation control benefits of LYT2 in people of Caucasian, Hispanic, and African ethnic origins. J Drugs Dermatol. 2016;15(12):1562-1570.

Rejuvenating Hydrator: Restoring Epidermal Hyaluronic Acid Homeostasis With Instant Benefits.

Skin aging is a combination of multifactorial mechanisms that are not fully understood. Intrinsic and extrinsic factors modulate skin aging, activating distinctive processes that share similar molecular pathways. One of the main characteristics of youthful skin is its large capacity to retain water, and this decreases significantly as we age. A key molecule involved in maintaining skin hydration is hyaluronic acid (HA). Concentration of HA in the skin is determined by the complex balance between its synthesis, deposition, association with cellular structures, and degradation. HA bio-equivalency and bio-compatibility have been fundamental in keeping this macromolecule as the favorite of the skincare industry for decades. Scientific evidence now shows that topically applied HA is unable to penetrate the skin and is rapidly degraded on the skin surface. SkinMedica's HA5 Rejuvenating Hydrator (SkinMedica Inc., an Allergan company, Irvine, CA) promotes restoration of endogenous epidermal HA homeostasis and provides instant smoothing and hydration of the skin. These dual benefits are accomplished through the combination of 2 breakthrough technologies: 1) a unique blend of actives powered by SkinMedica proprietary flower-derived stem cell extract that restores the endogenous production of HA; and 2) a proprietary mix of 5 HA forms that plump the skin, decreasing the appearance of fine lines/wrinkles. Pre-clinical studies demonstrated that HA5 induces expression of key epidermal differentiation and barrier markers as well as epidermal HA synthases. A decrease expression of hyaluronidases was also observed upon HA5 application. Initial clinical studies showed that within 15 minutes of application, HA5 instantly improves the appearance of fine lines/wrinkles and skin hydration. Subjects that continue using HA5 (for 8 weeks) demonstrated significant improvements in fine lines/wrinkles, tactile roughness, and skin hydration. In summary, the blend of these 2 key technologies present in HA5 promotes restoration of endogenous epidermal HA while delivering instant smoothing effects.

A randomized, double-blind, split-face study comparing the efficacy and tolerability of three retinol-based products vs. three tretinoin-based products in subjects with moderate to severe facial photodamage.

Retinol, has been shown to improve the appearance of photodamaged skin when applied topically, and is generally considered to be approximately ten times less potent than tretinoin. To assess this theory, three cosmetic formulations containing 0.25%, 0.5%, and 1.0% retinol were developed to correspond to the three commonly prescribed concentrations of tretinoin (0.025%, 0.05%, and 0.1%). A randomized, double-blind, split-face comparison study was conducted to compare the three concentrations retinol (Ret) including 0.25%, 0.5%, and 1.0%, against the respective three strengths of tretinoin (Tret) 0.025%, 0.05%, and 0.1% in subjects with moderate to severe facial photodamage. Subjects were randomized into three groups: Group 1 (Ret 0.25% vs. Tret 0.025%); Group 2 (Ret 0.5% vs. Tret 0.05%); and Group 3 (Ret 1.0% vs. Tret 0.1%). Within each group, subjects were randomized to apply Ret on one half of the face (left or right) and Tret on the other facial side, for a duration of twelve weeks. Clinical evaluations for efficacy and tolerability, as well as standardized digital photographs were conducted at baseline and at weeks 4, 8, and 12. Sixty-five subjects completed the twelve-week study (Group 1: n=24, Group 2: n=20, and Group 3: n=21). At week 12 in all treatment groups, both Ret and Tret produced statistically significant improvements from baseline in all efficacy parameters, including overall photodamage, fine lines/wrinkles, coarse lines/wrinkles, skin tone brightness, mottled pigmentation, and tactile roughness (all P<0.001). There were no significant differences in efficacy between Ret and Tret in these efficacy parameters. Results from this comparison study suggest that this sustained-release retinol complex containing multiple agents for optimal irritation control provides comparable improvements to tretinoin in the appearance of photodamage.