Hand Rejuvenation With A Hyaluronic Acid-Based Dermal Filler: A 12-Month Clinical Follow-Up Case Series.

BACKGROUND: Requests for hand rejuvenation, in particular with nonsurgical aesthetic procedures, are increasing. Several injectable dermal fillers are currently used to restore soft tissue volume; however, the anatomic complexity of the hand and extreme mobility of its underlying tissues involve the use of specific implants and adapted injection technique. We report a case series demonstrating the efficacy, durability, and safety of a hyaluronic acid-based dermal filler (HA-filler) for hand rejuvenation. METHODS: Five female subjects aged 56 to 67 with moderate to severe hand aging were treated by one physician (PM) at his private office. The HA-filler was injected in the hypodermis using a retrograde injection technique. A massage performed at the site of injection ensured optimal cosmetic results. Four subjects had a touch-up 3 months later. The aesthetic effect was evaluated on each hand, by 5 evaluators and the subjects, up to 12 months following the last injection. Adverse events, including pain, were collected. RESULTS: Merz Aesthetic Hand Aging Scale (MAS) and the Global Aesthetic Improvement Scale (GAIS) scores indicated stable and significant improvement in hand aging up to 12 months following the last injection. Despite a slight decrease over time, there was a durable enhancement of skin glow, quality, and hydration on the GAIS. The retrograde injection of the HA-filler, which was usually described as painless, was well tolerated by all subjects. CONCLUSIONS: Hand rejuvenation using a HA-filler and a retrograde injection technique was associated with subjects’ satisfaction and was proved safe for the 5 subjects of this case-series. J Drugs Dermatol. 20(4):451-459. doi:10.36849/JDD.5154.

Comparison of Two Swiss-Designed Hyaluronic Acid Gels: Six-Month Clinical Follow-Up.

The aim of this paper is to compare 2 hyaluronic acid gel fillers from the same Swiss manufacturer and with the same indications: filling of line wrinkles and folds. The products differ by their cross-linking process. With very simple easy-to-reproduce tests, cohesivity and resistance to traction forces were examined. Also, both gels were injected under ultrasound control in the mid reticular dermis of three subjects. The papules were controlled under ultrasound and biopsies at D0 and D15. Results showed significant differences between the 2 gels in all the tests. The new gel, manufactured with a lower-crosslinking density, seems to benefit from better integration in the tissue of the mid reticular dermis and to have a more cohesive nature than its comparator from a previous crosslinking technology. Under clinical observation, the range of new products present excellent tissue integration properties.

J Drugs Dermatol. 2017;16(2):154-161.

Visual, Ultrasonographic, and Microscopic Study on Hyaluronic Acid-Based Gel.

BACKGROUND: Hyaluronic acid (HA) fillers are commonly used for enhancement of lips, and for softening fine lines and correcting skin depressions. OBJECTIVE: This study sought to investigate whether the Vycross™ technology used for Volbella™ gel resulted in a cohesive gel, as documented in our previous studies with three other HA fillers (Restylane® NASHA™ [Q-MED, Uppsala, Sweden], Esthélis® Basic CPM™ [Anteis SA, Geneva, Switzerland], and Juvéderm® Ultra 3 using Hylacross technology [Allergan, Irvine, CA, USA]).
METHOD: The "resistance traction test" and "cohesiveness test" were conducted according to standard methods. Juvéderm® Volbella™ gel was injected into the buttock area, both in the superficial reticular and mid-reticular dermis. Tissue samples were analyzed at days 0, 15, and 90 by histology and immunohistochemistry, and visualized using electron microscopy. For Volbella™ gel, the same ultrasound devices as previously used were employed.
RESULTS: Prior to staining, Volbella™ gel presented resistance to spreading, suggesting a certain degree of cohesiveness. When smeared between two slides and following toluidine blue staining, the gel was visible through the microscope in the form of multiple tiny discrete particles, possibly resulting from gel desintegration. At 1/3 dilution with saline serum, Volbella™ gel disintegrated into several lumps, whereas at 1/1 dilution, Volbella gel appeared more cohesive. Yet when adding one drop 70% ethanol, the gel resembled a poorly defined magma, with numerous small lumps. On ultrasound, Volbella™ gel was found to leak in the hypodermis. On histological analysis, Volbella™ gel was visible as pools of variables sizes, particularly in the superficial and mid-reticular dermis, but also hypodermis.
CONCLUSION: Juvéderm Volbella™ gel appears to be a gel characterized by low-medium cohesiveness. The study findings, combined with our previous work, show that HA fillers using Vycross™ technology are not ideally suited for superficial use, unlike HA fillers using CPM technology™.

J Drugs Dermatol. 2016;15(9):1092-1098.

Quantifying Depth of Injection of Hyaluronic Acid in the Dermis: Data from Clinical, Laboratory, and Ultrasound Settings.

Although manufacturers' instructions for use of dermal fillers ordinarily direct injection in the superficial, mid or deep dermis, or, in some cases, the hypodermis (subcutis), the precise depth of injection may not always be for injectors. In this article, investigators report findings gathered from histopathology, ultrasound, "live" one on one training injections, as well as application of a mathematical formula for depth calculation of the various layers within the dermis. Areas of particular interest are the superficial reticular dermis and the mid dermis. Following the depth measurements detailed by Della Volpe et al in 2012, investigators compare and contrast their own depth findings of the various layers, arriving at the conclusion that the depth of the dermis is not as deep as had been previously assumed. The investigators also develop an argument for the appropriate angles of injection for placement of dermal filler into the various layers, demonstrating that the heretofore widely used angles of 30˚ and 45˚ are far more acute than required.

Superficial dermal injection of hyaluronic acid soft tissue fillers: comparative ultrasound study.

BACKGROUND: Superficial dermal injection of hyaluronic acids (HAs) has not been well studied. OBJECTIVES: To study HAs injected into the superficial dermis using ultrasound examination and measurements, to evaluate induration and pain, and to examine histology. MATERIALS AND METHODS: Three commercial HAs were injected into the superficial dermis (0.2 mL). The HAs used were a biphasic gel, a monophasic monodensified gel, and a monophasic polydensified gel. Ultrasound measurements and images were obtained, pain assessed, and biopsies performed at 7 days. RESULTS: Participants experienced pain from the HAs that did not contain lidocaine. After 8 days, the biphasic HA papules appeared erythematous, with two-thirds reporting the biphasic HA papules as tender. Ultrasound demonstrated superficial placement of HA gels in the upper dermis. The gels each exhibited unique characteristic patterns on ultrasound. Skin biopsies of the superficial dermal placement confirmed earlier patterns. Superficial placement of the biphasic product is associated with tenderness and an eosinophilic inflammatory infiltrate. CONCLUSION: Superficial placement of HAs is possible, as demonstrated by ultrasonography. Gels that do not have lidocaine within them are more painful. Injection of biphasic HA gels superficially in the dermis is associated with clinical erythema and tenderness and histology showing an eosinophilic infiltrate.

Hyaluronic acid gel based on CPM® technology with and without lidocaine: Is there a difference?

BACKGROUND: In 2011, a cohesive polydensified matrix (CPM® ) hyaluronic acid (HA) gel filler was approved by the USA Food and Drug Administration. In 2014, lidocaine was added to the gel during its manufacturing process. OBJECTIVES: To compare the behavior and rheological properties of a CPM® HA gel with and without lidocaine. METHODS: In our office, we performed simple tests to document the cohesiveness and resistance to traction force of both gels. In two different laboratories, the rheological properties of both gels were measured. We used comparative data of the gel without lidocaine collected from over 6 years. We also observed the gels' behavior when injected into the superficial and mid-reticular dermis, comparing their distribution using both ultrasonography and histology. RESULTS: Over more than 10 years, we observed no difference between both gels, even if clinically we felt a difference in the gels' viscosity upon injection. Their behaviors during injection were similar. Using more sophisticated tests measuring the gels' rheological properties with different techniques, namely sheer sweeps, a difference was, however, noted between the two gels. CONCLUSIONS: Adding lidocaine to CPM® HA gel renders it more viscous. Whether this means a difference in the clinical results, however, would require a comparative clinical study over an extended time period.

Two Crosslinking Technologies for Superficial Reticular Dermis Injection: A Comparative Ultrasound and Histologic Study.

Background: Few hyaluronic acid fillers have been developed for superficial injection. Objective: To compare the diffusion and integration properties of cohesive polydensified matrix and Vycross® technology hyaluronic acid fillers with lidocaine following injection into the superficial reticular dermis. Methods and materials: Two subjects received two injections each of cohesive polydensified matrix and Vycross® hyaluronic acid (0.2mL/site) in the superficial reticular dermis of the buttock under ultrasound control. Biopsies were obtained at Days 0, 15, and/or 90. Ultrasound and histologic analyses were performed, plus a series of simple rheological tests. Results: Day 0 ultrasound images showed cohesive polydensified matrix hyaluronic acid homogeneous with the surrounding dermis. Vycross® hyaluronic acid showed more heterogeneity and some leakage into the hypodermis. Day 15 and Day 90 images were similar to Day 0. Histologic examination of biopsy tissue showed cohesive polydensified matrix hyaluronic acid homogeneously distributed among collagen fibrils with no visible particles. Vycross® hyaluronic acid appeared as variable-sized pools with a particulate appearance. Neither gel was associated with an inflammatory reaction. Laboratory tests showed cohesive polydensified matrix hyaluronic acid to have greater cohesivity and resistance to traction forces than Vycross®. Conclusion: cohesive polydensified matrix gel with lidocaine is homogeneously distributed following injection in the superficial reticular dermis and may be particularly suited for aesthetic indications requiring superficial injection.

Ultrasound and Histologic Examination after Subcutaneous Injection of Two Volumizing Hyaluronic Acid Fillers: A Preliminary Study.

BACKGROUND: This study examined the influence of hyaluronic acid (HA) crosslinking technology on the ultrasound and histologic behavior of HA fillers designed for subcutaneous injection. METHODS: One subject received subcutaneous injections of 0.25 ml Cohesive Polydensified Matrix (CPM) and Vycross volumizing HA in tissue scheduled for abdominoplasty by bolus and retrograde fanning techniques. Ultrasound analyses were performed on days 0 and 8 and histologic analyses on days 0 and 21 after injection. A series of simple rheologic tests was also performed. RESULTS: Day 0 ultrasound images after bolus injection showed CPM and Vycross as hypoechogenic papules in the hypodermis. CPM appeared little changed after gentle massage, whereas Vycross appeared more hyperechogenic and diminished in size. Ultrasound images at day 8 were similar. On day 0, both gels appeared less hypoechogenic after retrograde fanning than after bolus injection. Vycross was interspersed with hyperechogenic areas (fibrous septa from the fat network structure) and unlike CPM became almost completely invisible after gentle massage. On day 8, CPM appeared as a hypoechogenic pool and Vycross as a long, thin rod. Day 0 histologic findings confirmed ultrasound results. Day 21 CPM histologic findings showed a discrete inflammatory reaction along the injection row after retrograde fanning. Vycross had a more pronounced inflammatory reaction, particularly after retrograde fanning, with macrophages and giant cells surrounding the implant. Rheologic tests showed CPM to have greater cohesivity and resistance to traction forces than Vycross. CONCLUSIONS: CPM HA volumizer appears to maintain greater tissue integrity than Vycross after subcutaneous injection with less inflammatory activity.

A blanching technique for intradermal injection of the hyaluronic acid Belotero.

With the proliferation of dermal fillers in the aesthetic workplace have come instructions from various manufacturers regarding dermal placement. Determination of injection needle location in the dermis has in large part been based on physician expertise, product and needle familiarity, and patient-specific skin characteristics. An understanding of the precise depth of dermal structures may help practitioners improve injection specificity. Unlike other dermal fillers that suggest intradermal and deep dermal injection planes, a new hyaluronic acid with a cohesive polydensified matrix may be more appropriate for the superficial dermis because of its structure and its high degree of integration into the dermis. To that end, the authors designed a small study to quantify the depth of the superficial dermis by means of ultrasound and histology. Using ultrasound resources, the authors determined the depths of the epidermis, the dermis, and the reticular dermis in the buttocks of six patients; the authors then extrapolated the depth of the superficial reticular dermis. Histologic studies of two of the patients showed full integration of the product in the reticular dermis. Following determination of injection depths and filler integration, the authors describe a technique ("blanching") for injection of the cohesive polydensified matrix hyaluronic acid into the superficial dermis. At this time, blanching is appropriate only for injection of the cohesive polydensified matrix hyaluronic acid known as Belotero Balance in the United States, although it may have applications for other hyaluronic acid products outside of the United States.

Biological models and genes of tumor reversion: cellular reprogramming through tpt1/TCTP and SIAH-1.

Tumor reversion is the process by which some cancer cells lose their malignant phenotype. This study was aimed at defining some of the molecular and phenotypic properties of this process. Biological models of tumor reversion were isolated from human leukemia and breast cancer cell lines by using the H-1 parvovirus as a selective agent. Differential gene expression analysis was performed between the parental malignant cells and their revertants or alternatively between these parental cells and their SIAH-1 transfectant counterparts. These SIAH-1 transfectants have a suppressed malignant phenotype and were used as a control for a viral-free system. Two hundred sixty-three genes were found to be either activated or inhibited during the reversion process, as confirmed by Northern blot analysis or quantitative PCR. Of these, 32% were differentially expressed in all systems, irrespective of whether parvovirus-selected, SIAH-1 overexpressing, or p53 mutant or wild-type cell lines were used, suggesting the existence of a universal mechanism underlying tumor reversion. Translationally Controlled Tumor Protein (tpt1/TCTP) has the strongest differential expression, down-regulated in the reversion of U937- and SIAH-1-overexpressing cells. Inhibition of TCTP expression by anti-sense cDNA or small interfering RNA molecules results in suppression of the malignant phenotype and in cellular reorganization, similar to the effect of SIAH-1. Hence, tumor reversion can be defined at the molecular level, not just as the reversal of malignant transformation, but as a biological process in its own right involving a cellular reprogramming mechanism, overriding genetic changes in cancer, by triggering an alternative pathway leading to suppression of tumorigenicity.

Translationally controlled tumor protein is a target of tumor reversion.

By analyzing the gene expression profile between tumor cells and revertant counterparts that have a suppressed malignant phenotype, we previously reported a significant down-regulation of translationally controlled tumor protein (TCTP) in the revertants. In the present study, we derived, by using the H1 parvovirus as a selective agent, revertants from three major solid cancers: colon, lung, and melanoma cell lines. These cells have a strongly suppressed malignant phenotype both in vitro and in vivo. The level of TCTP is decreased in most of the revertants. To verify whether inhibition of TCTP expression induces changes in the malignant phenotype, in the classical, well established model of "flat reversion," v-src-transformed NIH3T3 cells were transfected with antisense TCTP. By inhibiting the expression of TCTP, the number of revertant cells was raised to 30%, instead of the reported rate for spontaneous flat revertants of 10(-6). Because TCTP encodes for a histamine-releasing factor, we tested the hypothesis that inhibitors of the histaminic pathway could be effective against tumor cells. We show that some antihistaminic compounds (hydroxyzine and promethazine) and other pharmacological compounds with a related structure (including thioridazine and sertraline) kill tumor cells and significantly decrease the level of TCTP. All together, these data suggest that, with tumor reversion used as a working model, TCTP was identified as a target and drugs were selected that decrease its expression and kill tumor cells.