Ready-to-use abobotulinumtoxinA solution versus powder botulinumtoxinA for treatment of glabellar lines: Investigators' and subjects' experience in a Phase IV study.

BACKGROUND: Botulinum neurotoxin type A (BoNT-A) is well-established for treatment of glabellar lines (GLs), and mostly formulated as powders requiring reconstitution for injection. The approved liquid formulation, ready-to-use (RTU) abobotulinumtoxinA was developed to ease injection procedures and prevent reconstitution errors. This multicenter, open-label, Phase IV study evaluated GL treatment experience using RTU abobotulinumtoxinA versus powder BoNT-A (onabotulinumtoxinA). METHODS: Females with experience of BoNT-A facial treatment were randomized 2:1 to GL treatment with 50 U RTU abobotulinumtoxinA (N = 99) or 20 U powder BoNT-A (N = 51) and followed-up for 6 months or 1 month, respectively. Assessments included: time to prepare each product for injection (primary endpoint); investigators' experience with product preparation/reconstitution; investigators' and subjects' treatment experience; safety; and for the RTU product: aesthetic improvement of GLs; subject satisfaction. RESULTS: Compared with powder BoNT-A, RTU abobotulinumtoxinA required statistically significantly less preparation time (mean 0:33 vs. 1:34 min: s; p < 0.0001). Investigators preferred RTU abobotulinumtoxinA over powder BoNT-A (81% of treatment sessions) and found it allowed more time to communicate with subjects (97%). All investigators (100%) also found it easy-to-use, easy-to-learn, and that it fulfilled their expectations. Subjects found the RTU abobotulinumtoxinA treatment comfortable (91%), and through 6 months posttreatment, most reported satisfaction with their appearance (≥88%), looking natural (≥95%) and refreshed (≥80%). At Month 1, 99% of RTU-treated subjects had investigator-assessed improved aesthetic appearance in GLs, maintained in 76% at Month 6. No serious adverse events occurred. CONCLUSION: RTU abobotulinumtoxinA for GL treatment is well-tolerated, efficacious, shows high levels of subject satisfaction throughout 6 months, saves time, and is preferred by clinicians over powder BoNT-A. GOV REGISTRY: NCT05277337.

The Endogenous Dual Retinoid Receptor Agonist Alitretinoin Exhibits Immunoregulatory Functions on Antigen-Presenting Cells.

Retinoids are a frequently used class of drugs in the treatment of inflammatory as well as malignant skin diseases. Retinoids have differential affinity for the retinoic acid receptor (RAR) and/or the retinoid X receptor (RXR). The endogenous dual RAR and RXR agonist alitretinoin (9-cis retinoic acid) demonstrated remarkable efficacy in the treatment of chronic hand eczema (CHE) patients; however, detailed information on the mechanisms of action remains elusive. Here, we used CHE as a model disease to unravel immunomodulatory pathways following retinoid receptor signaling. Transcriptome analyses of skin specimens from alitretinoin-responder CHE patients identified 231 significantly regulated genes. Bioinformatic analyses indicated keratinocytes as well as antigen presenting cells as cellular targets of alitretinoin. In keratinocytes, alitretinoin interfered with inflammation-associated barrier gene dysregulation as well as antimicrobial peptide induction while markedly inducing hyaluronan synthases without affecting hyaluronidase expression. In monocyte-derived dendritic cells, alitretinoin induced distinct morphological and phenotypic characteristics with low co-stimulatory molecule expression (CD80 and CD86), the increased secretion of IL-10 and the upregulation of the ecto-5'-nucleotidase CD73 mimicking immunomodulatory or tolerogenic dendritic cells. Indeed, alitretinoin-treated dendritic cells demonstrated a significantly reduced capacity to activate T cells in mixed leukocyte reactions. In a direct comparison, alitretinoin-mediated effects were significantly stronger than those observed for the RAR agonist acitretin. Moreover, longitudinal monitoring of alitretinoin-responder CHE patients could confirm in vitro findings. Taken together, we demonstrate that the dual RAR and RXR agonist alitretinoin targets epidermal dysregulation and demonstrates strong immunomodulatory effects on antigen presenting cell functions.

Recognizing cisplatin as a potential radiation recall trigger: case report and focused systematic review.

We present a case of mild radiation recall dermatitis triggered by cisplatin chemotherapy given simultaneously to re-irradiation. The dermatitis area correlated to skin exposure of the previous radiation therapy, characterizing the reaction clearly as a recall. Cisplatin has not yet been recognized as a potential trigger for recall reactions. Although it was part of several reported multidrug trigger combinations, all review works referred to cisplatin as not suspicious, suggesting the combination partner as the effector. We performed a focused systematic literature review aiming to re-evaluate the real role of cisplatin as a (co-)triggering factor. In total, 30 reported cases were found, 90% triggered by multidrug combinations. The latter tended to cause more severe symptoms. Besides findings supporting the 20 Gy-threshold theory, no correlation between radiation dose and severity or prevalence was found. Recognition of cisplatin as a trigger of the recall phenomenon and its supportive management may prevent unnecessary cessation of systemic chemotherapy. Systematic reporting of recall events as a secondary endpoint of prospective clinical trials applying radiation therapy could support understanding the recall phenomenon.

Time- and Dose-Dependent Effects of Hyaluronidase on the Degradation of Different Hyaluronan-Based Fillers In Vitro.

BACKGROUND: Hyaluronidase (HYAL) is regarded as the standard for the management of complications associated with hyaluronan (HA)-based fillers. Therefore, the understanding of interactions of HA fillers and HYAL is essential. METHODS: Nine different commercially available HA fillers (Belotero, Juvéderm, and Restylane) with varying degrees of cross-linking were used for the analysis. Fluorescently dyed HA fillers were individually incubated with varying doses of HYAL [bovine HYAL (Hylase "Dessau"; Riemser Pharma, Germany); 5, 10, and 20 U/mL] or sodium chloride and monitored by time-lapse microscopy. HA filler degradation was assessed as a decrease in fluorescence intensity of HA filler plus HYAL compared to HA filler plus control, quantified by computerized image analysis. RESULTS: HA fillers show significant differences in their reaction to HYAL. Levels of degradation of HA fillers are positively correlated with increasing concentrations of HYAL. At the highest concentration of HYAL (20 U/mL), all fillers except one (Belotero Volume) reached a significant level of degradation at 5 to 9 hours. CONCLUSIONS: In this study, the authors show that most HA fillers can be dissolved by HYAL in a dose- and time-dependent manner. Of note, the fillers' technology and degree of cross-linking seem to exert stronger effects on the degradability by HYAL as compared to the concentration of HA. CLINICAL RELEVANCE STATEMENT: The authors' in vitro analyses support clinical recommendations stating that in the case of a vascular filler incident, HYAL should be applied early and at significant doses ("Time is skin!"). CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Immunothrombotic Mechanisms Induced by Ingenol Mebutate Lead to Rapid Necrosis and Clearance of Anogenital Warts.

Ingenol mebutate (IM) is highly effective in the treatment of human papillomavirus (HPV)-induced anogenital warts (AGW) leading to fast ablation within hours. However, the exact mode of action is still largely unknown. We performed dermoscopy, in vivo confocal microscopy (CLM), histology, immunohistochemistry, and immunofluorescence to gain insights in mechanisms of IM treatment in AGW. In addition, we used in vitro assays (ELISA, HPV-transfection models) to further investigate in vivo findings. IM treatment leads to a strong recruitment of neutrophils with thrombosis of small skin vessels within 8 h, in a sense of immunothrombosis. In vivo and in vitro analyses showed that IM supports a prothrombotic environment by endothelial cell activation and von Willebrand factor (VWF) secretion, in addition to induction of neutrophil extracellular traps (NETosis). IM superinduces CXCL8/IL-8 expression in HPV-E6/E7 transfected HaCaT cells when compared to non-infected keratinocytes. Rapid ablation of warts after IM treatment can be well explained by the observed immunothrombosis. This new mechanism has so far only been observed in HPV-induced lesions and is completely different from the mechanisms we see in the treatment of transformed keratinocytes in actinic keratosis. Our initial findings indicate an HPV-specific effect, which could be also of interest for the treatment of other HPV-induced lesions. Larger studies are now needed to further investigate the potential of IM in different HPV tumors.

Prognostic markers for the clinical course in the blood of patients with SARS-CoV-2 infection.

BACKGROUND: The presentation of peptides and the subsequent immune response depend on the MHC characteristics and influence the specificity of the immune response. Several studies have found an association between HLA variants and differential COVID-19 outcomes and have shown that HLA genotypes are associated with differential immune responses against SARS-CoV-2, particularly in severely ill patients. Information, whether HLA haplotypes are associated with the severity or length of the disease in moderately diseased individuals is absent. METHODS: Next-generation sequencing-based HLA typing was performed in 303 female and 231 male non-hospitalized North Rhine Westphalian patients infected with SARS-CoV2 during the first and second wave. For HLA-Class I, we obtained results from 528 patients, and for HLA-Class II from 531. In those patients, who became ill between March 2020 and January 2021, the 22 most common HLA-Class I (HLA-A, -B, -C) or HLA-Class II (HLA -DRB1/3/4, -DQA1, -DQB1) haplotypes were determined. The identified HLA haplotypes as well as the presence of a CCR5Δ32 mutation and number of O and A blood group alleles were associated to disease severity and duration of the disease. RESULTS: The influence of the HLA haplotypes on disease severity and duration was more pronounced than the influence of age, sex, or ABO blood group. These associations were sex dependent. The presence of mutated CCR5 resulted in a longer recovery period in males. CONCLUSION: The existence of certain HLA haplotypes is associated with more severe disease.

S2k guideline: Laser therapy of the skin.

This guideline aims to improve the efficiency and safety of lasers and optical radiation sources with similar effects (especially IPL). Laser therapy of skin lesions with an increased amount of melanocytes should be performed with caution. Laser treatment of pigmented melanocytic nevi is not recommended. The guideline contains recommendations regarding the treatment of lentigines and café-au-lait spots, non-pigmented dermal nevi, Becker nevus, nevus of Ota/Hori/Ito and melasma. Further recommendations focus on the treatment of skin lesions without an increased amount of melanocytes (ephelides, postinflammatory hyperpigmentation including berloque dermatitis, seborrheic keratoses, traumatic/decorative tattoos and metallic deposits), hypopigmentation (vitiligo), benign non-pigmented neoplasms (fibrous papule of the nose, nevus sebaceus, epidermal nevus, neurofibroma, sebaceous gland hyperplasia, syringoma, xanthelasma palpebrarum), inflammatory dermatoses (acne papulopustulosa/conglobata, acne inversa, granuloma faciale, lichen sclerosus, lupus erythematosus, psoriasis vulgaris, rosacea, rhinophyma), wrinkles/dermatochalasis/striae, hypertrichosis, scars (atrophic, hypertrophic; keloids, burn/scald scars), laser-assisted skin healing, onychomycosis, precancerous lesions and malignant tumors (actinic keratoses/field cancerization, cheilitis actinica, basal cell carcinoma), vascular skin lesions (angiokeratoma, angioma, hemangioma, malformation, spider veins, granuloma telangiectaticum (pyogenic granuloma), rubeosis (erythrosis interfollicularis colli, ulerythema ophryogenes), nevus flammeus, telangiectasias and Osler's disease (hereditary hemorrhagic telangiectasia) and viral skin lesions (condylomata acuminata, mollusca contagiosa, verrucae planae juveniles/vulgares/ verrucae palmares et plantares).

Effect of age on quality of life after gastric bypass: data from the Scandinavian Obesity Surgery Registry.

BACKGROUND: Whether patients aged 60 years or older should be recommended bariatric surgery is still controversial. OBJECTIVE: To assess the effect of age on health-related quality of life (QoL) over time after gastric bypass. SETTING: Data from the Swedish national registry for bariatric surgery. METHODS: Data of 57,215 patients undergoing gastric bypass were retrieved from the Scandinavian Obesity Surgery Register with a follow-up rate at 1,2, and 5 years at 89%, 69%, and 59%, respectively. Patients were divided into 5-years age intervals. Odds ratios for the relative mean changes in QoL were compared by logistic regression. RESULTS: Preoperatively, patients aged 60 years or older scored better on mental aspects (Mental Component Summary score, MCS) of RAND-36 (Short Form Health Survey (higher values better)) as well as OP (Obesity related Problem scale (lower values better)) better than the entire cohort of patients (MCS: mean [95% CI], 46.2 [45.5-46.9] versus 43.5 [43.4-43.7], respectively; OP: mean [95% CI], 55.3 [54.0-56.6] versus 64.1 [63.9-64.4], respectively), whereas the Physical Component Summary (PCS) scores of patients aged 60 years or older were lower (mean [95% CI], 32.3 [31.7-32.8] for the ≥60-yr cohort versus 36.4 [36.2-36.5] for the entire cohort; P < .001 for all). In all age groups, MCS was improved at 1 and 2 years but decreased to baseline at 5 years. The postoperative improvements in PCS and OP were sustained in all age groups. Although the relative increases for PCS and OP in patients aged ≥60 years were somewhat lower compared with the entire cohort at 5 years, the values were well above baseline levels (mean [95% CI], 41.0 [40.0-42.0] versus 32.3 [31.7-32.8] and 22.2 [20.3-24.0] versus 55.3 [54.0-56.6], respectively; P < .001). CONCLUSION: Mental QoL is transiently improved after bariatric surgery without marked differences between age groups. However, patients aged ≥60 years report pronounced and sustained improvements in physical and obesity-specific QoL 5 years postoperatively. These observations support previous studies that older patients should not be denied bariatric surgery from a risk-benefit perspective, solely based on age.

Acute cardiac side effects after COVID-19 mRNA vaccination: a case series.

BACKGROUND: Vaccination against SARS-CoV-2 has been the main tool to contain the pandemic. The rush development of the 3 vaccines and their expedited approval have led to inoculation of millions of patients around the world, leading to a containment of the disease. Despite continuous viral mutations and the identification of weaker variants, the severity of the infections has been mild, with many patients being either asymptomatic or recovering at home. Currently the focus has shifted from the host of organ damage related to the infection to potential side effects of the vaccine. Myocarditis has been reported as one of the potential side effects from the mRNA vaccine, affecting young healthy individuals. Up to September 30, 2021, 1.243 cases of myocarditis after vaccination with BNT162b2 Comirnaty© were registered in young adults by the Paul-Ehrlich-Institute in Germany alone. The exact pathophysiology and the risk factors for myocarditis following vaccination remain unclear. We present a case series of eight patients with cardiac symptom shortly after SARS-CoV-2 mRNA vaccination (BNT162b6, Biontech, Comirnaty© or mRNA-1237 Moderna, Spikevax©). PATIENTS AND METHODS: Eight patients between 13 and 56 years of age, vaccinated with either BNT162b2 or mRNA-1273 mRNA vaccine between January and August 2021 developed cardiac side effects shortly after either their first or second dose of the vaccine. Clinical data were retrieved from the clinical information system and analyzed. To support diagnosis of myocarditis or pericarditis, cardiac magnetic resonance imaging (MRI) was performed shortly after the onset of symptoms, with further investigations in severe cases. Symptoms were defined as dyspnea, chest pain and cardiac arrhythmia as determined by electrocardiography. RESULTS: Eight patients (5 males and 3 females) developed cardiac symptoms compatible with myocarditis, according to the CDC criteria, shortly after SARS-CoV-2 mRNA vaccination. Three patients (2 males, 1 female) required hospitalization due to severe chest pain and elevated troponin levels. All patients recovered fully within 7 days from the symptom onset. CONCLUSIONS: Our data suggest that cardiac adverse events such as myocarditis or pericarditis shortly after SARS-CoV-2 mRNA vaccination are rare but possible and occur particularly in male patients.

Impact of Age on Obesity-related Comorbidity After Gastric Bypass: A Cohort Study From the Scandinavian Obesity Surgery Registry (SOReg).

OBJECTIVE: To evaluate the resolution of obesity-related comorbidities after gastric bypass in relation to age. SUMMARY BACKGROUND DATA: Previous studies have shown that age >60 years is associated with a significant, but small, increased risk of complications after gastric bypass. The effect in terms of improvement of obesity-related comorbidities in this group of patients is not studied. METHODS: Data on 57,215 patients operated with primary gastric bypass between May 2007 and December 2018 was extracted from the Scandinavian Obesity Surgery Registry. Odds ratio and 95% confidence interval for resolution of comorbidities in 5-years age groups at 1, 2, and 5 years postoperatively was calculated by logistic regression with the entire cohort of patients as reference. Resolution was defined as no longer in need for pharmacological (or continuous positive airway pressure) treatment. RESULTS: Follow-up rates in all eligible patients were 89%, 69%, and 59% at 1, 2, and 5 years, respectively, and 64% in patients >60 years at 5 years. At baseline, the prevalence of most comorbidities was higher in patients above 60 years. In this group of patients, the preoperative prevalence of diabetes, hypertension, dyslipidemia and obstructive sleep apnea syndrome was reduced at 5years by 45%, 10%, 24%, and 62%, respectively. Compared to all patients, the odds ratio (95% confidence interval) for resolution of these comorbidities in patients above 60 years at five years were 0.70 (0.57-0.86) 0.45 (0.37-0.53), 0.80 (0.63-1.01), and 0.54 (0.40-0.72). CONCLUSIONS: Although to somewhat lower rates compared to younger patients, marked and sustained improvements in obesity-related comorbidities are seen after gastric bypass in patients >60 years. This, together with the finding that bariatric surgery is safe in this group of patients, suggests that age should not be considered an exclusion criterion by itself.

Static and Dynamic Anatomy of the Face, in Particular Eyebrows, Eyelids and Lips.

A characteristic feature of the anatomy of the human face is its arrangement in layers. The main layers include, from outside to inside: (i) the skin; (ii) the subcutaneous fat; (iii) the superficial musculoaponeurotic system; (iv) the deep fat, and (iv) the periosteum overlying the bony structures of the skull. Herein, the facial bones provide the basis for the ligaments and other facial structures that are attached to them. In contrast, the muscles control the mimics and movements, hence the dynamic anatomy of the face. The skin represents the outermost structure of the body and protects the organism from external physical, chemical, and biological stresses. The strive for facial attractiveness and beauty is a strong motivation for cosmetic and aesthetic procedures, including (permanent) makeup, minimal-invasive up to invasive surgical interventions, which have dramatically increased in numbers over the past decades. A youthful appearance is regarded as one of the essential characteristics of an attractive face. The characteristic features of the aging face are a downward migration of the facial soft tissues, a loss in volume of the fat compartments, the formation of mimic wrinkles, a decrease in dermal hydration, and others. Modern anti-aging treatments aim to reverse these alterations with the least possible side effects. However, effective and safe cosmetic, aesthetic, and medical treatments presume a profound knowledge of facial anatomy.

Informed consent and informed intervention: SARS-CoV-2 vaccinations not just call for disclosure of newly emerging safety data but also for hypothesis generation and testing.

BACKGROUND: COVID-19 infection is a major threat to patients and health care providers around the world. One solution is the vaccination against SARS-CoV-2. METHODS: We performed a comprehensive query of the latest publications on the prevention of viral infections including the recent vaccination program and its side effects. RESULTS: The situation is evolving rapidly and there is no reasonable alternative to population-scale vaccination programs as currently enrolled. CONCLUSION: Therefore, regulatory authorities should consider supplementing their conventional mandate of post-approval pharmacovigilance, which is based on the collection, assessment, and regulatory response to emerging safety findings.

Delayed skin reaction after mRNA-1273 vaccine against SARS-CoV-2: a rare clinical reaction.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is associated with a wide clinical spectrum of skin manifestations, including urticarial, vesicular, vasculitic and chilblain-like lesions. Recently, delayed skin reactions have been reported in 1% individuals following mRNA vaccination against SARS-CoV-2. The exact pathophysiology and the risk factors still remain unclear. PATIENTS AND METHODS: 6821 employees and patients were vaccinated at our institutions between February and June 2021. Every patient received two doses of the mRNA-1273 vaccine in our hospitals, and reported back in case of any side effects which were collected in our hospital managed database. RESULTS: Eleven of 6821 vaccinated patients (0.16%) developed delayed skin reactions after either the first or second dose of the mRNA-1273 vaccine against SARS-CoV-2. Eight of 11 patients (73%) developed a rash after the first dose, while in 3/11 (27%), the rash occurred after the second dose. More females (9/11) were affected. Four of 11 patients required antihistamines, with two needing additional topical steroids. All the cutaneous manifestations resolved within 14 days. None of the skin reactions after the first dose of the vaccine prevented the administration of the second dose. There were no long-term cutaneous sequelae in any of the affected individuals. CONCLUSION: Our data suggests that skin reactions after the use of mRNA-1273 vaccine against SARS-CoV-2 are possible, but rare. Further studies need to be done to understand the pathophysiology of these lesions.

Repetitive Daylight Photodynamic Therapy versus Cryosurgery for Prevention of Actinic Keratoses in Photodamaged Facial Skin: A Prospective, Randomized Controlled Multicentre Two-armed Study.

Actinic keratoses are a chronic condition in ultraviolet-damaged skin, with a risk of progressing to invasive skin cancer. The aim of this study was to investigate the preventive potential of field-directed repetitive daylight photodynamic therapy for actinic keratoses. A randomized trial was performed, including 58 patients with ≥5 actinic keratoses on photodamaged facial skin, who received either 5 full-face sessions of daylight photodynamic therapy within a period of 2 years or lesion-directed cryosurgery. Primary outcome was the mean cumulative number of new actinic keratoses developed between visits 2 and 6 (visit 6 being a follow-up). This outcome was lower after daylight photo-dynamic therapy (7.7) compared with cryosurgery (10.2), but the difference did not reach significance (-2.5, 95% confidence interval -6.2 to 1.2; p=0.18). Several signs of photoageing (fine lines, pigmentation, roughness, erythema, sebaceous gland hyperplasia) were significantly reduced after daylight photodynamic therapy, but not after cryosurgery. Significantly less pain and fewer side-effects were reported during daylight photodynamic therapy than during cryosurgery. This study found that repetitive daylight photodynamic therapy had photo-rejuvenating effects. However, the prevention of actinic keratoses by this therapy could not be proven in a statistically reliable manner.

Vanucizumab mode of action: Serial biomarkers in plasma, tumor, and skin-wound-healing biopsies.

Vanucizumab is a novel bispecific antibody inhibiting vascular endothelial growth factor (VEGF-A) and angiopoietin-2 (Ang-2) that demonstrated safety and anti-tumor activity in part I of a phase I study of 42 patients with advanced solid tumors. Part II evaluated the pharmacodynamic effects of vanucizumab 30 or 15 mg/kg every 2 weeks in 32 patients. Serial plasma samples, paired tumor, and skin-wound-healing biopsies were taken over 29 days to evaluate angiogenic markers. Vanucizumab was associated with marked post-infusion reductions in circulating unbound VEGF-A and Ang-2. By day 29, tumor samples revealed mean reductions in density of microvessels (-32.2%), proliferating vessels (-47.9%) and Ang-2 positive vessels (-62.5%). Skin biopsies showed a mean reduction in density of microvessels (-49.0%) and proliferating vessels (-25.7%). Gene expression profiling of tumor samples implied recruitment and potential activation of lymphocytes. Biopsies were safely conducted. Vanucizumab demonstrated a consistent biological effect on vascular-related biomarkers, confirming proof of concept. Skin-wound-healing biopsies were a valuable surrogate for studying angiogenesis-related mechanisms.

Dose- and time-dependent effects of hyaluronidase on structural cells and the extracellular matrix of the skin.

INTRODUCTION: Hyaluronic acid (hyaluronan; HA) is an essential component of the extracellular matrix (ECM) of the skin. The HA-degrading enzyme hyaluronidase (HYAL) is critically involved in the HA-metabolism. Yet, only little information is available regarding the skin's HA-HYAL interactions on the molecular and cellular levels. OBJECTIVE: To analyze the dose- and time-dependent molecular and cellular effects of HYAL on structural cells and the HA-metabolism in the skin. MATERIALS AND METHODS: Chip-based, genome-wide expression analyses (Affymetrix® GeneChip PrimeView™ Human Gene Expression Array), quantitative real-time PCR analyses, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (DAB), and in vitro wound healing assays were performed to assess dose-dependent and time-kinetic effects of HA and HYAL (bovine hyaluronidase, Hylase "Dessau") on normal human dermal fibroblasts (NHDF), primary human keratinocytes in vitro and human skin samples ex vivo. RESULTS: Genome-wide expression analyses revealed an upregulation of HA synthases (HAS) up to 1.8-fold change in HA- and HYAL-treated NHDF. HA and HYAL significantly accelerated wound closure in an in vitro model for cutaneous wound healing. HYAL induced HAS1 and HAS2 mRNA gene expression in NHDF. Interestingly, low concentrations of HYAL (0.015 U/ml) resulted in a significantly higher induction of HAS compared to moderate (0.15 and 1.5 U/ml) and high concentrations (15 U/ml) of HYAL. This observation corresponded to increased concentrations of HA measured by ELISA in conditioned supernatants of HYAL-treated NHDF with the highest concentrations observed for 0.015 U/ml of HYAL. Finally, immunohistochemical analysis of human skin samples incubated with HYAL for up to 48 h ex vivo demonstrated that low concentrations of HYAL (0.015 U/ml) led to a pronounced accumulation of HA, whereas high concentrations of HYAL (15 U/ml) reduced dermal HA-levels. CONCLUSION: HYAL is a bioactive enzyme that exerts multiple effects on the HA-metabolism as well as on the structural cells of the skin. Our results indicate that HYAL promotes wound healing and exerts a dose-dependent induction of HA-synthesis in structural cells of the skin. Herein, interestingly the most significant induction of HAS and HA were observed for the lowest concentration of HYAL.

Effective removal of solar lentigines by combination of pre- And post-fluorescent light energy treatment with picosecond laser treatment.

We present a novel treatment for removal of SL that is efficient and enables removal or lesions not immediately visible. Kleresca® FLE technology combined with picosecond laser treatment removes SL lesions and improves skin quality and appearance.