Untreated Skin Research Articles

Immediate and extended effects of abrasion on stratum corneum natural moisturizing factor.

Natural moisturizing factor (NMF), principally comprised of hygroscopic amino acids and derivatives that absorb moisture from the surrounding environment, serves as the primary humectant of the stratum corneum (SC). Acute barrier disruption has been shown to differentially affect the concentration of NMF in the SC. This study measured the recovery kinetics of NMF after mechanical damage of the SC, which is not well understood. The study population included 20 healthy female volunteers (18-72-year old) with no history of dermatological disorders. Transepidermal water loss (TEWL), erythema, and SC water and NMF were measured at all sites before abrasion, 30 min following abrasion, and 1-3, 6, 8, and 10 days following abrasion. Measurements obtained from the abraded site were compared with those obtained from an untreated site. As expected, both TEWL and erythema increased significantly with abrasion. Erythema and TEWL values remained higher at the abraded site for 2 and 6 days, respectively, after abrasion. No changes in NMF component levels in the SC were observed at 30 min after abrasion. One day following abrasion, reduced levels of glycine, histidine pH4, trans-urocanic acid (tUca) pH4, and tUca pH8 were observed. In addition, a significantly lower level of serine was observed at the abraded site 2 and 6 days following abrasion. Within 8 days after abrasion, these components returned to levels comparable to those observed in untreated skin. Throughout the study, no differences were observed in the level of water in the SC. These results demonstrate that acute barrier disruption induced by mechanical abrasion has relatively little impact on biochemical events responsible for NMF generation. Though reductions in certain NMF components were observed, abrasion had no measureable effect on SC water content over the duration of the study. This implies that the reduced NMF components may not contribute substantially to water retention in the SC. The reduced components belong to a group of NMF molecules thought to be principally derived through degradation of S-100 proteins in the epidermis. NMF components measured in this study that are derived from sweat and/or urea cycling were not impacted. These data imply that while abrasion elicits clinical signs of barrier disruption within the SC, effects on its biochemical constituents and ability to retain water are relatively minor.

Assessment of different diagnostic methods for scabies with follow-up of cellular immune response

Objectives The aim of the study was to compare between clinical examination, skin scraping, and histopathological examinat ion in the diagnosis of scabies and assess the role of immune cells (CD4+ and CD8+) and transforming growth factor b (TGF-b) to differentiate between scabietic and nonscabietic patients. Background Scabies is a contagious skin infection characterized clinically by nocturnal pruritus and visible burrows. Scabies can occur in epidemic or endemic form. Scabies is still a major public health problem in many resource-poor regions, with prevalence rates reaching up to 10% in the general population and 50% in children. The diagnosis of scabies is challenging, leading to the observation that scabies is at once the easiest and most difficult diagnosis in medicine. Patients and methods Physical examination, skin scraping, and histopathological analysis were carried out for diagnosing scabies. Biopsies were taken from untreated skin lesions of patients 35 with scabies, six with psoriasis, eight with lichen planus and eight normal individuals. T-cell subsets (CD4+ and CD8+) and anti-inflammatory cytokine (TGF-b) were evaluated by immunohistochemical analysis. Results Skin scraping and histopathological examination were highly specific (100%) when compared with physical examination, but the sensitivity of histopathology (88%) was superior to scraping (23%) and clinical diagnosis (85.6%). The highest number of CD4+ T cells was found in scabies and lichen planus but not in psoriasis. In contrast, the highest number of CD8+ T cells was found in psoriasis but not in scabies or lichen planus. There was statistically significant difference between scabietic and nonscabietic patients with regard to CD4+, CD8+, and CD4+/CD8+ ratio. Mild expression of TGF-b was observed in patients with scabies compared with moderate to strong expression in lichen planus and psoriasis. Conclusion Histopathology is an accurate diagnostic method but recommended in suspicious cases only as it is an invasive technique. A high number of CD4+ cells and low expression of TGF-b are characteristic of scabietic lesions.

Evidence that reduced nitric oxide signal contributes to cutaneous microvascular dysfunction in peripheral arterial disease.

Peripheral arterial disease (PAD) is associated with cutaneous microvascular dysfunction and an increased risk of arterial ulceration in the affected lower-limb(s). The purpose of this study was to investigate the role of nitric oxide (NO) in cutaneous microvascular dysfunction in patients with PAD. Using laser-Doppler flowmetry, we measured skin blood flow (SkBF) in 5 patients with unilateral symptomatic PAD and 10 age-matched healthy controls at baseline and during 40 min of local skin heating to 42°C at 1) untreated lower-leg sites, and 2) lower-leg sites treated with 20 mM N(G)-nitro-L-arginine methyl ester (L-NAME) to inhibit NO synthase activity. SkBF was expressed as laser-Doppler flux (LDF) and normalized to maximal LDF (%LDF(max)) achieved through localized heating to 44°C and concomitant infusion of 56 mM sodium nitroprusside. Pharmacological agents and control treatments (lactated Ringer's) were administered using intradermal microdialysis. The plateau LDF response to local skin warming at the untreated skin sites was significantly (P<0.05) lower in the diseased limb of the PAD patients (70.3±13.6 %max) compared to the non-diseased contralateral limb (85.0±10.2 %max) and the response observed for the control participants (89.0±5.2 %max). The NO contribution to the plateau SkBF response tended to be lower in the diseased limb of the PAD patients (45.1±16.4% versus 56.1±10.7% [P=0.12] and 55.4±11.5% [P=0.13], respectively). The results suggest that PAD impairs downstream cutaneous microvascular vasodilatory function and that the microvascular dysfunction is probably explained, at least in part, by a reduced NO signal.

Improvement of arbutin trans-epidermal delivery using radiofrequency microporation

Purpose: To assess the ability of radiofrequency (RF) microporation to promote trans-epidermal delivery of arbutin.Methods: To investigate the enhancing effect of RF microchannels on skin permeation of arbutin, in vitro skin permeability studies were performed with RF microporation-treated Hartley albino guinea pig skin using Franz diffusion cell system. Furthermore, improved depigmentation effects in brown guinea pig in vivo after treatment with RF microporation was evaluated to create hydrophilic microchannels for arbutin trans-epidermal delivery.Results: RF microporator caused disruption of the stratum corneum (SC) and created 50 μm diameter microchannels at a depth of 100 μm in the skin. RF microporation increased skin permeability of arbutin 2.25-fold compared to untreated skin exposed to RF in vitro. Arbutin administration led to considerable skin depigmentation following RF microporation of UV-induced hyperpigmented skin in a 28-day in vivo experiment (ΔL-value on day 28: UV, 0.17 ± 0.50; UV + RF, 0.07 ± 0.48; UV + arbutin, 1.32 ± 0.51 and UV + RF + arbutin, 1.82 ± 0.53).Conclusion: RF microporation seems to be a suitable physical trans-epidermal delivery technology for topical application of highly hydrophilic depigmentation agents through the hydrophobic skin barrier.Keywords: Radiofrequency microporation, Trans-epidermal delivery, Depigmentation, Arbutin

Mesembryanthemum crystallinum L. als dermatologisch wirksame Heilpflanze - erste Ergebnisse aus 3 Pilotstudien

Hintergrund: Neben vielen bekannten Heilpflanzen der rationalen Phytotherapie gibt es eine Vielzahl von Pflanzen, deren Wirkung nur unzureichend erforscht oder deren Wirkpotential in Vergessenheit geraten ist. Zu diesen Pflanzen gehört die Kristall-Mittagsblume (Mesembryanthemum crystallinum L.). In der vorliegenden Arbeit werden 3 Pilotstudien vorgestellt, die die dermatologische Wirkung des Mittagsblumenextrakts (Mesem-Creme) näher untersuchen. Material und Methoden: In 2 Anwendungsbeobachtungen wurde zunächst das Wirkprofil der Mesem-Creme näher untersucht. Neben einer retrospektiven Anwenderbefragung wurde außerdem bei 6 Rollstuhlfahrern eine prospektive Befragung zur Veränderung des Hautstatus im Prä-post-Design durchgeführt. In einer dritten placebokontrollierten Pilotstudie wurde die Hautfeuchtigkeitsveränderung mittels Corneometermessung an 6 Probanden mit trockener Haut analysiert. Ergebnisse: Im Vergleich zur unbehandelten Haut konnte in der Corneometer-Studie eine signifikante Steigerung der Hautfeuchtigkeit mit der Mesem-Creme erzielt werden (25,8 ± 5,8 vorher zu 46,6 ± 9,2 nachher vs. 26,3 ± 6,0 vorher zu 33,8 ± 6,0 nachher) sowie ein statistischer Trend (p = 0,11; t-Test) im Vergleich zur Basiscreme ohne Mesem-Zusatz (25,1 ± 4,7 vorher zu 41,9 ± 7,3 nachher). Dieser Effekt der Steigerung der Hautfeuchtigkeit wurde auch in den Anwendungsbeobachtungen verifiziert. Die Hauttrockenheit hatte sich bei 17 von 29 Probanden «sehr verbessert» oder «verbessert». Auch die Anwendungsbeobachtung bei einer Kohorte von 6 Rollstuhlfahrern ergab signifikante Verbesserungen des Hautzustands in Bezug auf die Weichheit und Trockenheit der Haut im Vorher-nachher-Vergleich. Schlussfolgerung: In dieser Arbeit wurde die Mesem-Creme durch 2 Anwendungsbeobachtungen im Hinblick auf Wirkung, Produkteigenschaften und Verträglichkeit und durch den etablierten Corneometertest auch in Hinblick auf objektivierbare Hautfeuchtigkeitsveränderungen evaluiert. Aufgrund der geringen Fallzahlen gibt es trotz der ermutigenden Ergebnisse Limitationen in der Ergebnisinterpretation. Zudem sollte das Design künftiger Studien klarer sein und den hautfeuchtigkeitsverbessernden Effekt der Mesem-Creme besser fokussieren.

Gene expression in the skin of dogs sensitized to the house dust mite Dermatophagoides farinae.

Atopic dermatitis is a multifactorial allergic skin disease in humans and dogs. Genetic predisposition, immunologic hyperreactivity, a defective skin barrier, and environmental factors play a role in its pathogenesis. The aim of this study was to analyze gene expression in the skin of dogs sensitized to house dust mite antigens. Skin biopsy samples were collected from six sensitized and six nonsensitized Beagle dogs before and 6 hr and 24 hr after challenge using skin patches with allergen or saline as a negative control. Transcriptome analysis was performed by the use of DNA microarrays and expression of selected genes was validated by quantitative real-time RT-PCR. Expression data were compared between groups (unpaired design). After 24 hr, 597 differentially expressed genes were detected, 361 with higher and 226 with lower mRNA concentrations in allergen-treated skin of sensitized dogs compared with their saline-treated skin and compared with the control specimens. Functional annotation clustering and pathway- and co-citation analysis showed that the genes with increased expression were involved in inflammation, wound healing, and immune response. In contrast, genes with decreased expression in sensitized dogs were associated with differentiation and barrier function of the skin. Because the sensitized dogs did not show differences in the untreated skin compared with controls, inflammation after allergen patch test probably led to a decrease in the expression of genes important for barrier formation. Our results further confirm the similar pathophysiology of human and canine atopic dermatitis and revealed genes previously not known to be involved in canine atopic dermatitis.

Comparing safety of abrasion and tape-stripping as skin preparation in allergen-specific epicutaneous immunotherapy

Comparing safety of abrasion and tape-stripping as skin preparation in allergen-specific epicutaneous immunotherapy

Alternative Cellular Energy (ACE) Pathway Activation as the Mode of Action of Neutral Red Dye Phototherapy of Human Viruses

Ultraviolet (UV) light illumination of herpes simplex virus (HSV) skin lesions pretreated with freshly prepared neutral red dye leads to near immediate symptomatic relief and expedites the subsequent healing of the lesions. This therapy is similarly effective in the recovery from both shingles caused by herpes zoster virus (HZV) and warts caused by human papillomavirus (HPV). The present paper describes a series of findings consistent with the hypothesis thathealing occurs via activation of the alternative cellular energy (ACE) pathway. Of particular note is the appearance of UV skin and hair fluorescence beyond the treated lesions and the healing that can simultaneously occur in both directly treated and more distant untreated skin lesions. Neutral red induced fluorescence of intact skin occurring in the sites of previous HSV outbreaks may offera surrogate marker for HSV shedding and/or impending recurrence and providesthe opportunity for preventative phototherapy. Systemic non-immunological activation of the ACE pathway also holdspromise in the therapy of other virus infections for which the immune response is inadequate.

Effects of water-filtered infrared-A and of heat on cell death, inflammation, antioxidative potential and of free radical formation in viable skin – First results

The effects of water-filtered infrared-A (wIRA) and of convective heat on viability, inflammation, inducible free radicals and antioxidative power were investigated in natural and viable skin using the ex vivo Bovine Udder System (BUS) model. Therefore, skin samples from differently treated parts of the udder of a healthy cow were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, by prostaglandin E2 (PGE2) measurement and by electron spin resonance (ESR) spectroscopy. Neither cell viability, the inflammation status, the radical status or the antioxidative defence systems of the skin were significantly affected by wIRA applied within 30min by using an irradiance of 1900Wm−2 which is of relevance for clinical use, but which exceeded the maximum solar IR-A irradiance at the Earth’s surface more than 5 times and which resulted in a skin surface temperature of about 45°C without cooling and of about 37°C with convective cooling by air ventilation. No significant effects on viability and on inflammation were detected when convective heat was applied alone under equivalent conditions in terms of the resulting skin surface temperatures and exposure time. As compared with untreated skin, free radical formation was almost doubled, whereas the antioxidative power was reduced to about 50% after convective heating to about 45°C.

Optical clearing agent perfusion enhancement via combination of microneedle poration, heating and pneumatic pressure.

Optical clearing agents (OCAs) have shown promise for increasing the penetration depth of biomedical lasers by temporarily decreasing optical scattering within the skin. However, their translation to the clinic has been constrained by lack of practical means for effectively perfusing OCA within target tissues in vivo. The objective of this study was to address this limitation through combination of a variety of techniques to enhance OCA perfusion, including heating of OCA, microneedling and/or application of pneumatic pressure over the skin surface being treated (vacuum and/or positive pressure). While some of these techniques have been explored by others independently, the current study represents the first to explore their use together. Propylene glycol (PG) OCA, either at room-temperature or heated to 45°C, was topically applied to hydrated, body temperature ex vivo porcine skin, in conjunction with various combinations of microneedling pre-treatment (0.2 mm length microneedles, performed prior to OCA application), vacuum pre-treatment (17-50 kPa, performed prior to OCA application), and positive pressure post-treatment (35-172 kPa, performed after OCA application). The effectiveness of OCA perfusion was characterized via measurements of transmittance, reduced scattering coefficient, and penetration depth at a number of medically-relevant laser wavelengths across the visible spectrum. Topical application of room-temperature (RT) PG led to an increase in transmittance across the visible spectrum of up to 21% relative to untreated skin. However, only modest increases were observed with addition of various combinations of microneedling pre-treatment, vacuum pre-treatment, and positive pressure post-treatment. Conversely, when heated PG was used in conjunction with these techniques, we observed significant increases in transmittance. Using an optimal PG perfusion enhancement protocol consisting of 45°C heated PG + microneedle pre-treatment + 35 kPa vacuum pre-treatment + 103 kPa positive pressure post-treatment, we observed up to 68% increase in transmittance relative to untreated skin, and up to 46% increase relative to topical RT PG application alone. Using the optimal PG perfusion enhancement protocol, we also observed up to 30% decrease in reduced scattering coefficient relative to untreated skin, and up to 20% decrease relative to topical RT PG alone. Finally, using the optimal protocol, we observed up to 25% increase in penetration depth relative to untreated skin, and up to 23% increase relative to topical RT PG alone. The combination of heated PG, microneedling pre-treatment, vacuum pre-treatment, and positive pressure-post treatment were observed to significantly enhance the perfusion of topically applied PG. Although further studies are required to evaluate the efficacy of combined perfusion enhancement techniques in vivo, the current results suggest promise for facilitating the translation of OCAs to the clinic.

Evidence that cutaneous microvascular dysfunction in peripheral arterial disease is due to reduced nitric oxide (678.9)

We investigated the role of nitric oxide (NO) in cutaneous microvascular dysfunction in patients with symptomatic unilateral peripheral arterial disease (PAD) and in limbs of disease‐free, age‐matched controls in response to local skin warming. In 5 patients with unilateral PAD and 10 age‐matched controls, skin blood flow (SkBF) was measured using laser‐Doppler flowmetry. Local skin temperature was controlled with heater probe holders. Microdialysis was used to administer L‐NAME to inhibition NO synthase activity. Ringer’s was perfused at control sites. Data are presented as cutaneous vascular conductance (SkBF / blood pressure). Vasodilation (plateau phase) at the untreated skin sites was significantly lower in the diseased limb of the PAD patients (70.20 ± 12.41 %max) compared to the healthy contralateral limb (85.14 ± 9.26 %max, P = 0.021) and the response achieved in the control participants (86.58 ± 6.99 %max, P = 0.003). There were no differences between the NO‐inhibited skin sites of the PAD patients and healthy participants (38.32 %max vs. 38.72 %max, P = 0.395) or between the diseased and healthy leg of the PAD patients (37.19 %max, P = 0.393). The primary findings of this study are that cutaneous vasodilation is markedly reduced in response to local skin warming and this decreased response appears to be due to NO.

Fat and epidermal cell suspension grafting: a new advanced one-step skin regeneration surgical technique

BackgroundDystrophic skin scarring commonly occurs following skin cancer resections. In particular, the cosmetic outcome of skin graft reconstructions, following epidermoidal carcinoma removal, is generally poor due to wide marginal tumour excision, loss of subcutaneous tissues, and subsequent pigmented atrophic scarring of the graft coverage. Skin grafting sequelae need a three dimensional correction to restore either the epidermal layer or the dermal/subdermal volume and vascularization.MethodsThe surgeons combined CO2 laser ablation, subdermal lipofilling according to the Coleman’s technique and epidermal cell suspension autografting to correct wide depressed and dyschromic facial scar. The Authors applied this new technique on three nasal skin cancer resected patients: two of them actually need a longer follow-up, the third patient, a 48 yr old caucasian male, presented a skin grafting scar due to sclerodermiform basal cell carcinoma removal. This case is reported discussing pre-intra and post-operative records up to a complete twelve months follow-up.ResultsRecords at six and twelve months follow-up after surgery demonstrate a fully integrated skin graft and a good restoration of the treated area, presenting the same texture and pigmentation of the adjacent untreated skin. Optimal, stable three-dimensional skin cosmetic restoration was obtained in a single stage surgical procedure.ConclusionAutologous non-cultured epidermal cell suspension transplantation on an epidermal laser ablated skin area, in combination with lipofilling subdermal reconstruction, appears to be an effective, simple and time-saving method to correct skin graft sequelae, in skin cancer patients. This new technique allows to restore a three-dimensional morphological structure of the treated area and to recover a natural appearance of the skin at the same time. The Authors believe that this technique can be safely used to treat any kind of dystrophic scarring.

In Vivo Cosmetic Product Efficacy Testing by Analyzing Epidermal Proteins Extracted from Tape Strips

The objective of this in vivo pilot study was to investigate whether differential biomarker analysis from skin tape strips could be used, not only to evaluate the difference between treated and untreated skin, but also to evaluate the effect of different product treatments. Ten volunteers were included in the study, applying two different basic formulations on their forearms. After four weeks of product application, and also after one week of treatment remission, tape strips were collected from the different treatment sites, as well as from untreated skin. The biomarkers investigated were selected to cover different aspects of epidermal differentiation and in connection with moisturization and barrier function. Levels of Involucrin were increased in both treatments, compared to untreated skin, whereas the levels of Keratin-6 were decreased for both treatments. In addition, a pattern for increased levels of Hornerin and Claudin-1 was also detected. There were no significant differences between the two treatments, only for treatment compared to untreated, but there were tendencies for different effect on some of the biomarkers investigated, differences that may reach significance with increased sample size. The major differences between the two treatments in this study were seen after one week of product remission, although due to too small sample size these differences were not significant.

In vivo enhancement of imaging depth for optical coherence tomography by eudermic agents on ridged and meshed human skin

Non-invasive skin analysis by optical coherence tomography (OCT) is limited because of the absorption and scattering properties of the tissue. There are several possibilities for enhancing OCT images. The purpose of this study was to demonstrate that image quality can be improved using the hyperosmolar agents glucose and glycerol while investigating human ridged and meshed skin areas, without causing damage to the tissue. The experiments were carried out on the palm and the forearm of ten volunteers. After application of the substances in the test area, the penetration depth and image contrast were measured at intervals of 5 min for a total duration of 60 min. Both agents clearly improved the OCT imaging depth in comparison to untreated human skin. The results demonstrated that glucose had a faster diffusion rate than glycerol. Consequently, it can be concluded that the treatment with glucose or glycerol for optical clearing of the skin tissue results in an improved image quality if applied 15–25 min prior to clinical testing.

Development and validation of an alternative disturbed skin model by mechanical abrasion to study drug penetration

Pharmaceuticals and cosmetics for dermal application are usually tested on healthy skin, although the primary permeation barrier, the stratum corneum, is often impaired by skin diseases or small skin lesions, especially on the hands. These skin conditions can considerably influence the permeation of chemicals and drugs. Furthermore, risk assessment for example of nanoparticles should be performed under various skin conditions to reflect the true circumstances. Therefore, an alternative and reproducible method for a high throughput of skin samples with impaired skin barrier was developed and verified by skin permeation studies (25h) of caffeine, sorbic acid and testosterone compared to healthy (untreated) and tape-stripped skin. Skin barrier disruption was controlled by TEWL measurement.Skin permeation of the three substances was increased in tape-stripped and abraded skin compared to untreated skin due to the reduced barrier integrity. Enhancement of drug uptake was highest for the most hydrophilic substance, caffeine, followed by sorbic acid and lipophilic testosterone. No significant difference in drug uptake studies was observed between the new abrasion method with an aluminum-coated sponge and the tape-stripping method. The obtained results demonstrate that this abrasion method is an alternative way to achieve a disturbed skin barrier for drug and chemical uptake studies.

Microneedle-assisted delivery of verapamil hydrochloride and amlodipine besylate

The aim of this project was to study the effect of stainless steel solid microneedles and microneedle rollers on percutaneous penetration of verapamil hydrochloride and amlodipine besylate.Verapamil, 2-(3,4-dimethooxyphenyl)-5-[2-(3,4 dimethoxyphenyl)ethyl-methyl-amino]-2-propan-2-yl-pentanenitrile is a calcium channel blocker agent that regulates high blood pressure by decreasing myocardial contractilty, heart rate and impulse conduction. Amlodipine, (R, S)-2-[(2-aminoethoxy) methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1, 4-dihydropyridine, is a calcium channel blocker that is used for the management of hypertension and ischemic heart disease. Passive penetration of verapamil and amlodipine across the skin is low. In vitro studies were performed with microneedle-treated porcine ear skin using vertical static Franz diffusion cells (PermeGear, Hellertown, PA, USA). The receiver chamber contained 5ml of PBS (pH7.4) and was constantly maintained at 37°C temperature with a water circulation jacket. The diffusion area of the skin was 1.77cm2. The donor compartment was loaded with 1ml of the solution containing 2.5mg/ml of amlodipine besylate. The donor chamber was covered with parafilm to avoid evaporation. Passive diffusion across untreated porcine skin served as control. Aliquots were taken every 2h for 12h and analyzed by liquid chromatography–mass spectrometry. Transcutaneous flux of verapamil increased significantly from 8.75μg/cm2/h to 49.96μg/cm2/h across microneedle-roller treated porcine skin. Percutaneous flux of amlodipine besylate following the use of stainless steel microneedles was 22.39μg/cm2/h. Passive flux for the drug was 1.57μg/cm2/h. This enhancement of amlodipine flux was statistically significant. Transdermal flux of amlodipine with microneedle roller was 1.05μg/cm2/h in comparison with passive diffusion flux of 0.19μg/cm2/h. The difference in flux values was also statistically significant. Stainless steel solid microneedles and microneedle rollers increased percutaneous penetration of verapamil hydrochloride and amlodipine besylate. It may be feasible to develop transdermal microneedle patches for these drugs.

The Unwounded Skin Remodeling in Animal Models of Diabetes Types 1 and 2

Diabetes mellitus types 1 and 2 are chronic diseases that cause serious health complications, including dermatologic problems. The diabetic skin is characterized by disturbances in collagen metabolism. A tissue remodeling depends on the degradation of extracellular matrix through the matrix metalloproteinases, which are regulated by e.g. the tissue inhibitors of metalloproteinases. The balance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) is essential to maintain homeostasis in the skin. The aim of this study was to determine the concentration of metalloproteinase 2, tissue inhibitor of metalloproteinase 3 and the concentration of collagen type 1 in unwounded skin of diabetes type 1 and 2 and healthy controls. The treatment of diabetes resulted in a significant decrease of MMP2, increase of TIMP3 and COL1 concentrations in the skin as compared to the untreated diabetic skin. The concentrations of MMP2 in the skin of treated rats did not show significant differences from the healthy control group. TIMP3 concentrations in the skin of treated rats are not returned to the level observed in the control group. Disturbances of the extracellular matrix of the skin are similar in diabetes type 1 and 2. Application of insulin in diabetes therapy more preferably affects the extracellular matrix homeostasis of the skin.

Radical Protection by Differently Composed Creams in the UV/VIS and IR Spectral Ranges

Modern sunscreens are well suited to provide sufficient protection in the UV range because the filter substances absorb or scatter UV radiation. Although up to 50% of radicals are formed in the visible and infrared spectral range during solar radiation protection strategies are not provided in this range. Previous investigations of commercially available products have shown that in addition to physical filters, antioxidants (AO) are necessary to provide protective effects in the infrared range by neutralizing already formed radicals. In this study, the efficacy of filter substances and AO to reduce radical formation in both spectral ranges was investigated after UV/VIS or IR irradiation. Optical properties and radical protection were determined for the investigated creams. It was found that organic UV filters lower radical formation in the UV/VIS range to 35% compared to untreated skin, independent of the presence of AO. Further reduction to 14% was reached by addition of 2% physical filters, whereas physical filters alone were ineffective in the UV/VIS range due to the low concentration. In contrast, this filter type reduced radical formation in the IR range significantly to 65%; similar effects were aroused after application of AO. Sunscreens which contain organic UV filters, physical filters and AO ensure protection in the complete solar spectrum.

Noninvasive delivery of siRNA and plasmid DNA into skin by fractional ablation: Erbium:YAG laser versus CO2 laser

The present study was conducted to evaluate the impacts of fractional erbium (Er):YAG and CO2 lasers on skin permeation of small interfering (si)RNA and plasmid (p)DNA vectors. In vitro skin delivery was determined with a Franz diffusion cell. In vivo absorption was investigated by observing fluorescence and confocal microscopic imaging. Fractional laser-mediated ablation of the skin resulted in significant enhancement of dextran and siRNA penetration. Respective fluxes of dextran (10kDa) and siRNA, which had similar molecular size, with Er:YAG laser irradiation at 5J/cm2 were 56- and 11-fold superior to that of intact skin. The respective permeation extents of dextran and siRNA by the CO2 laser at 4mJ/400 spots were 42- and 12-fold greater than that of untreated skin. Fluorescence and confocal images showed increased fluorescence intensities and penetration depths of siRNA and pDNA delivery. According to an examination of the follicular permeant amount and fluorescence microscopy, hair follicles were important deposition areas for fractional laser-assisted delivery, with the Er:YAG modality revealing higher follicular siRNA selectivity than the CO2 modality. This is the first report of siRNA and pDNA penetrating the skin with a sufficient amount and depth with the assistance of fractional lasers.

Improvement of Periulcer Skin Condition in Venous Leg Ulcer Patients

The aim of this study was to investigate the influence of a biosynthetic cellulose wound dressing (BWD) to stimulate wound healing in patients with a venous leg ulcer on periulcer skin condition when compared with standard care using a foam dressing. Each patient with a venous ulcer received compression therapy with a short stretch bandage system and either a BWD + foam (study group [SG]) or foam (control group [CG]). Periulcer skin condition was compared with the untreated lower leg skin and the forearm skin, using noninvasive parameters, comparing day 0 versus day 28 results. Ulcers were further evaluated for healing rate. The study period was 28 days, and the follow-up period was 12 weeks. Fifty patients were recruited to the study, of which N = 46 (SG, n = 26; CG, n = 20) completed the 28-day study period and were included in the analysis. The BWD showed a more improved periulcer skin condition versus the CG. Transepidermal water loss was significantly less in the SG (P = .003), as well as the results shown with the chromatometer (P =. 05). Ulcer healing rate was also statistically significant in favor of the SG (P = .0001). Treatment for the BWD + foam group was shown to be safe and significantly improved periwound skin condition, leading to more expeditious wound healing than treatment with foam alone.