Dual Role of Stratum Corneum Carotenes/Lycopene Against the Development of Chemotherapy-induced PPE in Patients With Cancer.

Palmar-plantar erythrodysaesthesia (PPE) is a common side effect of chemotherapy treatment in patients with cancer. The exact pathophysiologic mechanisms of the development of PPE remain unclear. Here, we report two important physiological functions of carotenoids without hydroxyl groups (α-carotene, ß-carotene, γ-carotene, ξ-carotene, lycopene, phytoene, phytofluene and their isomers) in the stratum corneum (SC) of glabrous skin: The powerful antioxidant protection of the integrity of the SC components against the destructive action of free radicals and maintaining the skin barrier function by the creation of an orthorhombic organization of intercellular lipids within lamellae using carotenoids as a skeleton. The dual protective role of carotenoids without hydroxyl groups is important for both healthy skin and, in the authors' opinion, for the skin of chemotherapy-treated patients against the development of PPE, as the chemotherapy-induced reduction of the carotenoid concentration in the stratum corneum considerably weakens the skin resistance to cytotoxic and other adverse reactions.

Tattoo Pigments Are Localized Intracellularly in the Epidermis and Dermis of Fresh and Old Tattoos: In vivo Study Using Two-Photon Excited Fluorescence Lifetime Imaging.

BACKGROUND: The knowledge about the location and kinetics of tattoo pigments in human skin after application and during the recovery is restricted due to the limitation of in vivo methods for visualizing pigments. Here, the localization and distribution of tattoo ink pigments in freshly and old tattooed human skin during the regeneration of the epidermis and dermis were investigated in vivo. METHODS: Two-photon excited fluorescence lifetime imaging (TPE-FLIM) was used to identify tattoo ink pigments in human skin in vivo down to the reticular dermis. One subject with a freshly applied tattoo and 10 subjects with tattoos applied over 3 years ago were investigated in the epidermal and dermal layers in vivo. One histological slide of tattooed skin was used to localize skin-resident tattoo pigment using light microscopy. RESULTS: The carbon black particles deposited around the incision have still been visible 84 days after tattoo application, showing delayed recovery of the epidermis. The TPE-FLIM parameters of carbon black tattoo ink pigments were found to be different to all skin components except for melanin. Distinction from melanin in the skin was based on higher fluorescence intensity and agglomerate size. Using TPE-FLIM in vivo tattoo pigment was found in 75% of tattoos applied up to 9 years ago in the epidermis within keratinocytes, dendritic cells, and basal cells and in the dermis within the macrophages, mast cells, and fibroblasts. Loading of highly fluorescent carbon black particles enables in vivo imaging of dendritic cells in the epidermis and fibroblasts in the dermis, which cannot be visualized in native conditions. The collagen I structures showed a higher directionality similar to scar tissue resulting in a greater firmness and decreased elasticity of the tattooed skin. CONCLUSIONS: Here, we show the kinetics and location of carbon black tattoo ink pigment immediately after application for the first time in vivo in human skin. Carbon black particles are located exclusively intracellularly in the skin of fresh and old tattoos. They are found within macrophages, mast cells, and fibroblasts in the dermis and within keratinocytes, dendritic cells, and basal cells in the continuously renewed epidermis even in 9-year-old tattoos in skin showing no inflammation.

Carotenoids in Human SkinIn Vivo: Antioxidant and Photo-Protectant Role against External and Internal Stressors.

The antioxidant system of the human body plays a crucial role in maintaining redox homeostasis and has an important protective function. Carotenoids have pronounced antioxidant properties in the neutralization of free radicals. In human skin, carotenoids have a high concentration in the stratum corneum (SC)-the horny outermost layer of the epidermis, where they accumulate within lipid lamellae. Resonance Raman spectroscopy and diffuse reflectance spectroscopy are optical methods that are used to non-invasively determine the carotenoid concentration in the human SC in vivo. It was shown by electron paramagnetic resonance spectroscopy that carotenoids support the entire antioxidant status of the human SC in vivo by neutralizing free radicals and thus, counteracting the development of oxidative stress. This review is devoted to assembling the kinetics of the carotenoids in the human SC in vivo using non-invasive optical and spectroscopic methods. Factors contributing to the changes of the carotenoid concentration in the human SC and their influence on the antioxidant status of the SC in vivo are summarized. The effect of chemotherapy on the carotenoid concentration of the SC in cancer patients is presented. A potential antioxidant-based pathomechanism of chemotherapy-induced hand-foot syndrome and a method to reduce its frequency and severity are discussed.

In vivo Skin Penetration, Radical Protection, and Structural Changes after Topical Application of a Herbal Oil Cream Compared to Topical Calcipotriol in Mild to Moderate Psoriasis.

BACKGROUND: The chronicity of psoriasis often requires continuous topical treatment. MATERIALS AND METHODS: Here, the radical protection of a cream containing various herbal oils was evaluated in vivo by electron paramagnetic resonance (EPR) spectroscopy and its skin penetration by Raman microscopy in intact and barrier-disturbed skin. Changes in skin barrier properties were evaluated after 4 weeks of daily topical application using in vivo laser scanning microscopy (LSM) and transepidermal water loss in 26 healthy volunteers. A randomized, controlled, double-blind, three-arm parallel clinical study evaluated the efficacy of the herbal oil cream compared to a 0.05% calcipotriol-containing cream and to a vehicle cream, in 135 patients with mild to moderate plaque psoriasis with the change in Psoriasis Area and Severity Index (PASI) from baseline to week 12 as the primary endpoint. RESULTS: EPR spectroscopy disclosed a significantly higher radical formation in untreated than skin treated with the herbal oil cream (p ≤ 0.05). LSM measurements indicated a protective skin barrier effect in treated compared to untreated skin. In the clinical trial, the topical application of herbal oils showed a significant reduction of the PASI score compared to topical calcipotriol at week 12 (p = 0.016). The mean reduction in PASI was 49% for the herbal oil cream, 38% for calcipotriol, and 55% for the vehicle cream. The percentage of patients, who reached PASI 50 and 75 at any time point, was 55.9% and 29.4% for the herbal oil cream, 47.4% and 15.8% for calcipotriol, and 23 (60.5%) and 13 (34.2%) for the vehicle, respectively (p > 0.05). The vehicle, originally designed as a placebo, contained a main ingredient of the herbal oil cream and therefore showed corresponding results. CONCLUSION: The herbal oil cream demonstrated effectiveness in the treatment of mild to moderate plaque psoriasis.

Kinetics of the carotenoid concentration degradation of smoothies and their influence on the antioxidant status of the human skin in vivo during 8 weeks of daily consumption.

The antioxidant status of the skin shows constant alterations depending on nutrition and other lifestyle factors. Carotenoids can serve as marker substances for the antioxidant status of the epidermis in vivo. The carotenoid concentration of 2 homemade green smoothies and a commercial green smoothie, all containing fruits and vegetables, was assessed by resonance Raman spectroscopy. Furthermore, a pilot study was conducted to investigate changes of the cutaneous carotenoid concentration of 20 healthy volunteers under the daily intake of either a homemade smoothie or the commercial smoothie in vivo using reflectance spectroscopy. We hypothesized that higher carotenoid concentrations in the homemade smoothies compared to those of the commercial one would lead to a faster increase of the cutaneous carotenoid concentration in healthy volunteers. The measurements of the homemade smoothies showed notably higher initial carotenoid concentrations (7.6 ±0.8)*10-4arbitrary units (a.u.) (smoothie A) and (10.4 ± 0.6)*10-4 a.u. (smoothie B) compared to the commercial smoothie (5.8 ± 0.2)*10-4 a.u. Nevertheless, the commercial smoothie showed a higher stability of carotenoids over 24 hours. 8 weeks after daily consumption of the homemade smoothies, volunteers showed an insignificant increase of cutaneous carotenoids from (4.5 ± 0.1)*10-4 a.u. at baseline to (4.8 ± 0.3)*10-4 a.u. (means ± standard error of the mean). The volunteers consuming the commercial smoothie showed an insignificant increase of cutaneous carotenoids from (4.3 ± 0.2)*10-4 a.u. to (4.7 ± 0.2)*10-4 a.u. after 8 weeks. The observed increase of cutaneous carotenoid concentrations could be classified as a strong tendency. Fresh homemade smoothies can exhibit a higher carotenoid concentration compared to commercial smoothies but need to be consumed immediately after preparation.

Determination of the pH Gradient in Hair Follicles of Human Volunteers Using pH-Sensitive Melamine Formaldehyde-Pyranine Nile Blue Microparticles.

Nanoparticles can be applied to the hair follicles, which can serve as reservoirs for triggered drug release. A valid measurement method for the determination of the pH within the hair follicle in vivo has not been shown yet. Here, melamine formaldehyde particles up to 9 µm in size were applied on 40 freshly plucked scalp hairs of eight individuals to determine the pH along the hair shaft down to the root area of the hair. For fluorescent pH indicators, pyranine and Nile blue were incorporated into the particles. Measurements were conducted using confocal laser scanning microscopy. A pH decay gradient could be found from the hair sheath towards the external hair shaft (p = 0.012) with pH values at the hair sheath of 6.63 ± 0.09, at the hair sheath end at 6.33 ± 0.11, and at the external hair shaft at 6.17 ± 0.09 (mean ± SE). The pH difference between the hair sheath end and the external hair shaft was found to be significant (p = 0.036). The results might be comparable with the pH within the hair follicle in vivo indicating a pH increase towards the hair root.

In vivo detection of changes in cutaneous carotenoids after chemotherapy using shifted excitation resonance Raman difference and fluorescence spectroscopy.

BACKGROUND: Various cutaneous toxicities under chemotherapy indicate a local effect of chemotherapy by secretion after systemic application. Here, changes in the fluorescence and Raman spectral properties of the stratum corneum subsequent to intravenous chemotherapy were assessed. METHODS: Twenty healthy subjects and 20 cancer patients undergoing chemotherapy were included. Measurement time points in cancer patients were before the first cycle of chemotherapy (Tbase ) and immediately after intravenous application of the chemotherapy (T1 ). Healthy subjects were measured once without any further intervention. Measurements were conducted using an individually manufactured system consisting of a handheld probe and a wavelength-tunable diode laser-based 488 nm SHG light source. Hereby, changes in both skin fluorescence and shifted excitation resonance Raman difference spectroscopy (SERRDS) carotenoid signals were assessed. RESULTS: Healthy subjects showed significantly (P < .001) higher mean concentrations of carotenoids compared to cancer subjects at Tbase . An increase in fluorescence intensity was detected in almost all patients after chemotherapy, especially after doxorubicin infusion. Furthermore, a decrease in the carotenoid concentration in the skin after chemotherapy was found. CONCLUSION: The SERRDS based noninvasive detection can be used as an indirect quantitative assessment of fluorescent chemotherapeutics. The lower carotenoid SERRDS intensities at Tbase might be due to cancerous diseases and co-medication.

Reflectance confocal microscopy for noninvasive examination of nonmelanocytic tumors and virus-associated skin lesions in organ transplant recipients.

BACKGROUND: Drug-induced immunosuppression is necessary to prevent rejection of the foreign organ in transplanted patients, but neoplastic and virus-associated skin diseases are frequent complications. Reflectance confocal microscopy (RCM) recently emerged as a promising tool for the early diagnosis of skin lesions. MATERIALS AND METHODS: A total of 61 skin lesions, among them 20 basal cell carcinomas, six Bowen's diseases, 23 actinic keratoses, and 12 verrucae, were analyzed. All lesions were clinically evaluated followed by RCM evaluation by two independent dermatologists and histological examination. RESULTS: For the diagnosis of basal cell carcinoma, a sensitivity of 100% by both investigators (INV I + II) and a specificity of 100% by INV I and 80% by INV II were achieved. The sensitivity average rate for RCM features reached by both investigators ranged between 60% and 100%, and the specificity between 55% and 90%. For the diagnosis of actinic keratosis, a concordant sensitivity of 94.4% and a specificity of 80% (INV I) and 60% (INV II) were detected. The sensitivity average rate of specific RCM criteria ranged between 72.3% and 97.2%, whereas specificity ranged between 20% and 90%. Regarding verrucae, RCM confirmed the histological diagnosis with a sensitivity of 85.7% (INV I) and 100% (INV II), while specificity was 100% and 80%, respectively. CONCLUSION: Reflectance confocal microscopy resulted to be a reliable tool for the noninvasive diagnosis of neoplastic and virus-associated skin changes in organ transplant recipients. Nevertheless, given the frequency and diagnostic complexity of the hyperkeratotic lesions occurring post-transplantation, larger cohorts of patients are required to confirm and consolidate these findings.

Influence of polyester spacer fabric, cotton, chloroprene rubber, and silicone on microclimatic and morphologic physiologic skin parameters in vivo.

BACKGROUND: Skin diseases can develop upon disadvantageous microclimate in relation to skin contact with textiles of supporting devices. Increased temperature, moisture, mechanical fracture, pressure, and inflammatory processes often occur mutually and enhance each other in their adverse effects. Therefore, the early prevention of skin irritations by improvement of microclimatic properties of skin in contact with supporting devices is important. MATERIALS AND METHODS: In this study, the microclimate under occlusion with polyester, cotton, chloroprene rubber, and silicone textiles, used for supporting devices, was analyzed by determining several characteristic physiologic skin parameters in vivo, including temperature, moisture, and transepidermal water loss (TEWL). This is achieved by comparing a miniaturized in vivo detection device with several established optical and sensory methods in vivo. RESULTS: A highly significant TEWL decrease was found after polyester, chloroprene rubber, and silicone application. The application of all materials showed highly significant decrease in skin surface temperature, with chloroprene rubber showing the lowest. Similarly, all materials showed highly significant increase in relative moisture, where the highest increase was found for chloroprene rubber and silicone and the lowest increase for cotton. The cutaneous carotenoid concentration of chloroprene rubber, silicone, and polyester decreased. A manipulation of the surface structure of the stratum corneum was recognized for all materials except for cotton by laser scanning microscopy. CONCLUSION: The skin parameters temperature, relative moisture, antioxidant status, and TEWL can effectively characterize the microclimatic environment during occlusion with medical supporting materials. These parameters could potentially be used to develop standardized testing procedures for material evaluation.

Influence of Sorafenib, Sunitinib and Capecitabine on the Antioxidant Status of the Skin.

BACKGROUND/AIM: The aim of the present study was to examine the effect of orally administered sorafenib (Nexavar®), sunitinib (Sutent®) and capecitabine (Xeloda®), which cause palmoplantar erythrodysesthesia (PPE), on the antioxidant status of the skin and the formation of free radicals. PATIENTS AND METHODS: A total of 42 patients were enrolled, of which 36 (85%) completed the study. Overall, 19 received capecitabine (2,000-4,000 mg per day), 10 sunitinib (25-50 mg per day) and 7 sorafenib (400-800 mg per day). Cutaneous carotenoids as markers of the antioxidant status of the skin were measured 1 day before the first oral administration (Tbase) and at day 18 of treatment (T1). RESULTS: The mean antioxidant concentrations increased significantly in patients treated with sunitinib from 3.99±1.01 to 4.68±1.32, p=0.047 and sorafenib from 4.83±0.74 to 5.3±0.78, p=0.007. Treatment with capecitabine did not significantly increase the mean antioxidant concentration. CONCLUSION: Formation of free radicals may not be the underlying patho-mechanism of tyrosine kinase inhibitors (TKI)- and capecitabine-associated PPE.

Lactobacillus plantarum Strain Ln4 Attenuates Diet-Induced Obesity, Insulin Resistance, and Changes in Hepatic mRNA Levels Associated with Glucose and Lipid Metabolism.

The prevalence of obesity and associated metabolic disorders, including diabetes and cardiovascular disease, is rapidly becoming a severe global health problem. Recent reports have suggested that the alteration of the gut ecosystem through the consumption of probiotics and fermented foods, such as yogurt and Kimchi, can significantly impact obesity and Type 2 diabetes (T2D)-related biomarkers. In this study, we screened over 400 strains of lactic acid bacteria (LAB) that were isolated from fermented foods to identify potent anti-obesogenic and diabetic probiotics in vitro. Of the strains tested, Lactobacillus plantarum Ln4 (Ln4), which was obtained from napa cabbage kimchi, significantly reduced lipid accumulation and stimulated glucose uptake in 3T3-L1 adipocytes. Oral administration of Ln4 reduced weight gain and epididymal fat mass in mice fed on a high-fat diet (HFD). Total plasma triglyceride level was significantly lower in mice that were treated Ln4 as compared with mice fed HFD. The protein levels of adipokines such as C-reactive protein (CRP), insulin-like growth factor binding proteins-3 (IGFBP-3), and monocyte chemoattractant protein-1 (MCP-1) decreased in white adipose tissues of Ln4-treated mice. Furthermore, these mice exhibited a significant reduction of insulin resistance index (HOMA-IR) and the improvement of glucose tolerance (OGTT) and insulin response (ITT) following Ln4 administration. This was associated with changes in several hepatic gene expressions (increased mRNA levels of IRS2, Akt2, AMPK, LPL, and reduced CD36) that regulate glucose and lipid metabolism. Taken together, these results indicate that in vitro and in vivo Ln4 treatment attenuates diet-induced obesity and T2D biomarkers, highlighting the potential of Ln4 as a therapeutic probiotic agent for metabolic disorders.

Effects of glucocorticoids on stratum corneum lipids and function in human skin-A detailed lipidomic analysis.

BACKGROUND: Topical glucocorticoids (GCs) are known to induce atrophy of human skin including thinning of epidermal and dermal compartments by influencing keratinocyte proliferation and synthesis of extracellular matrix proteins. GCs are also known to reduce skin barrier integrity but little is known about the changes in lipid composition in human skin following topical administration of GCs. OBJECTIVE: This study investigated the effects of GCs on stratum corneum (SC) function and lipid profile of human skin in vivo. METHOD: Over a period of 4 weeks, 16 healthy volunteers were treated on the forearms once daily with topical clobetasol proprionate (CP), betamethasone diproprionate (BDP) or vehicle. One day after last application (Day 29) SC lipids were collected by tape stripping and analysed by a high sensitivity liquid chromatography-mass spectrometry method. Gene expression was analysed in skin biopsies. The full skin, epidermal and SC thickness were assessed by ultrasound, optical coherence tomography and confocal microscopy, respectively, and barrier integrity was assessed by measuring transepidermal water loss (TEWL). RESULTS: Compared to vehicle controls, GCs induced significant alterations in SC lipid profiles. CP caused a reduction in 98 lipids of 226 analysed while BDP treatment only resulted in a significant change of 29 lipids. Most pronounced changes occurred among long chain, ester-linked, ceramide classes while other ceramide classes were much less affected. Almost the complete profile of triacylglycerols (TGs) was significantly decreased by CP while more modest changes were observed in free fatty acids. Topical GCs reduced the thickness of skin layers and increased TEWL. GC treatment also induced changes in expression of genes coding for extracellular markers and enzymes involved in lipid synthesis. CONCLUSIONS: This study shows a reduction in specific SC lipid classes following topical GC treatment of human skin and contributes to the characterisation of the barrier disruption in human skin induced by topical steroids.

Impact of Body Site, Age, and Gender on the Collagen/Elastin Index by Noninvasive in vivo Vertical Two-Photon Microscopy.

BACKGROUND/AIMS: Extrinsic and intrinsic skin aging is subject to constant remodeling and degradation processes, primarily in components of the extracellular matrix. While collagen fibers thin out during the aging process, the amorphous elastin fibers accumulate. These are essential formative components of the dermis. So far, these processes have been detected in vertical histological sections of invasive biopsies and recently in noninvasive horizontal scans. METHODS: In this pilot study, a modified noninvasive 2-photon microscope was applied to measure the collagen/elastin index of skin in vivo. The obtained images permit an immediate vertical survey and allow a conclusion on the dermal composition at once. The collagen/elastin index was quantified by the second harmonic to autofluorescence aging index of dermis (SAAID) depending on volunteers' age (18-66 years), gender, and body area. RESULTS: The highest SAAID was measured at the volar forearm as compared to the abdominal SAAID, which was significantly lower (p < 0.05). The gluteal region showed the significantly lowest SAAID (p < 0.05). The SAAID in female skin was higher compared to male skin and decreased with increasing age. CONCLUSION: These effects are to be considered in subsequent studies to be able to specifically detect and evaluate influences.

In vivo characterization of structural changes after topical application of glucocorticoids in healthy human skin.

Topical glucocorticoids (GC) are known to induce changes in human skin with the potential to develop skin atrophy. Here, atrophogenic effects and subsequent structural changes in the skin after topical application of GC were investigated in vivo. Sixteen healthy volunteers were topically treated daily on the forearms with clobetasol propionate, betamethasone dipropionate, and the petrolatum vehicle for 4 weeks. All treated skin areas and a nontreated control area were examined by ultrasound, optical coherence tomography, confocal laser scanning microscopy, multiphoton tomography (MPT), and resonance Raman spectroscopy at baseline 1 day after last application and 1 week after last application. Investigated parameters included stratum corneum thickness, epidermal, and full skin thickness, keratinocyte size and density, keratinocyte nucleus-to-cytoplasm ratio, skin surface classification, relative collagen and elastin signal intensity, second-harmonic generation-to-autofluorescence aging index of dermis (SAAID), and the antioxidant status of the skin. A reduction in epidermal and dermal skin thickness was observed in GC treated as well as in vehicle-treated and untreated skin areas on the volar forearm. MPT analysis showed an increased epidermal cell density and reduced cell size and nucleus-to-cytoplasm ratio and a significant increase of SAAID after GC treatment indicating a restructuring or compression of collagen fibers clinically being observed as atrophic changes.

Body regions have an impact on the collagen/elastin index of the skin measured by non-invasive in vivo vertical two-photon microscopy.

It is known that the collagen and elastin fibre structures are changing with age. There is little knowledge about the influence of body area as these investigations have been limited for ethical reasons, so far. Thus, modified non-invasive two-photon microscopy was used providing vertical optical sections of second harmonic generation and autofluorescence to calculate the collagen-to-elastin ratio and its alterations depending on the investigated body site in vivo. The results of this study indicate that the impact of different body areas could be higher than the influence of age and should be considered in future studies.

Do nanoparticles have a future in dermal drug delivery?

More and more investigations confirm that nanoparticles are incapable of overcoming the intact skin barrier in vivo. Do nanoparticles still have a future in dermal drug delivery? Unlike many other topically applied substances, nanoparticles have not been reported to utilize the intercellular penetration pathway and preferentially make use of the follicular penetration pathway. Deep penetration into the follicular ducts has been described for a variety of particles and appears to be strongly influenced by particle size. For targeted drug delivery, smart nanoparticles are required which are able to release their loaded drugs subsequent to internal or external trigger stimuli, and thereby enable the translocation of the active agents into the viable epidermis. In the recent manuscript, three nanoparticles systems are summarized and compared which release their model drugs upon different trigger mechanisms. The BSA hydrogel nanoparticles release their model drug TRITC-dextran by passive diffusion due to a concentration gradient via a porous surface. The protease-triggered controlled release BSA nanoparticles release their model drug if they are applied simultaneously with protease nanoparticles, resulting in an enzymatic degradation of the particles and a release of the model drug FITC. Finally, the IR-triggered controlled release AuNP-doped BSA nanoparticles release their model drug FITC after photoactivation with wIRA. For all three nanoparticle systems, the release of their model drugs could be observed. For the first nanoparticle system, only low follicular penetration depths were found which might by due do an agglomeration effect. For the last two nanoparticle systems, deep follicular penetration and even an uptake by the sebaceous glands were verified. In conclusion, it could be demonstrated that nanoparticles do have a future in dermal drug delivery if smart nanoparticle systems are utilized which are able to release their drug at specific times and locations within the hair follicle.

Influence of Chemotherapy on the Antioxidant Status of Human Skin.

BACKGROUND: Palmoplantar erythrodysesthesia is a frequent dermal side-effect during chemotherapy. Previous investigations showed radical formation subsequent to doxorubicin infusion and preventative and therapeutic effects of an antioxidant-containing ointment. PATIENTS AND METHODS: Using a non-invasive vivomeasuring system (Biozoom®; Biozoom Services GmbH, Kassel, Germany) changes in the antioxidant status (as measured by relative carotenoid concentration) of the skin prior to and after intravenous administration of paclitaxel, docetaxel and 5-fluorouracil were investigated in 42 patients with cancer. RESULTS: A significant decrease of antioxidant concentration subsequent to intravenous administration was found for all investigated chemotherapeutic agents. The mean concentration of carotenoids decreased from 3.59±1.26 arbitrary units (a.u.) to 3.41±1.28 a.u. (p<0.001) after paclitaxel administration, from 6.33±2.43 to 5.63±2.29 a.u. after docetaxel (p=0.027) and from 4.26±1.81 to 3.98±1.53 a.u. (p=0.042) after 5-fluorouracil infusion. CONCLUSION: Oxidative stress might play a significant role in the pathomechanism of palmoplantar erythrodysesthesia associated with paclitaxel, docetaxel and 5-fluorouracil. Therefore, an antioxidant-containing ointment might serve as preventative and therapeutic option.

Detection of capecitabine (Xeloda®) on the skin surface after oral administration.

Palmoplantar erythrodysesthesia (PPE), or hand-foot syndrome, is a cutaneous toxicity under various chemotherapeutics contributing to the most frequent side effects in patients treated with capecitabine (Xeloda®). The pathomechanism of PPE has been unclear. Here, the topical detection of capecitabine in the skin after oral application was shown in 10 patients receiving 2500 mg/m 2 /day 2500 mg/m2/day capecitabine. Sweat samples were taken prior to and one week after oral administration of capecitabine. Using high-resolution continuum source absorption spectrometry, the changes in concentrations of fluorine, which is an ingredient of capecitabine, were quantified and statistically analyzed. Here, we show an increase in fluorine concentrations from 40±10 ppb 40±10 ppb (2±0.5 pM 2±0.5 pM ) before capecitabine administration to 27.7±11.8 ppm 27.7±11.8 ppm (14.6±6.5 nM 14.6±6.5 nM ) after application, p<0.001 p<0.001 . The results show the secretion of capecitabine on the skin surface after oral administration, indicating a local toxic effect as a possible pathomechanism of PPE.

Influence of mechanical stress on palmoplantar erythrodysesthesia--a case report.

BACKGROUND: Cutaneous adverse events can have an important negative influence on quality of life and compliance in affected patients. Palmoplantar erythrodysesthesia (PPE; hand-foot syndrome) is a cutaneous toxicity associated with chemotherapeutic treatment, which necessitates treatment interruption or dose reduction in severe cases. This case report of pegylated liposomal doxorubicin-induced PPE shows the influence of mechanical stress on the development of skin lesions in various locations and the importance of patient education and compliance. CASE REPORT: We present the case of a 43-year-old female patient diagnosed with ovarian cancer and having undergone surgical and chemotherapeutic treatment. The development of extensive grade 3 PPE affecting numerous areas of the body particularly exposed to mechanical pressure necessitated dermatological treatment. The combination of local application of an antioxidant-containing ointment and the patient's compliance made it possible to continue chemotherapy without interruption or dose reduction. CONCLUSION: The development of PPE often limits the use of chemotherapeutic agents, and this case report can provide a possible therapeutic and preventive strategy for affected patients.

Spectroscopic biofeedback on cutaneous carotenoids as part of a prevention program could be effective to raise health awareness in adolescents.

The cutaneous carotenoid concentration correlates with the overall antioxidant status of a person and can be seen as biomarker for nutrition and lifestyle. 50 high school students were spectroscopically measured for their cutaneous carotenoid concentrations initially in a static phase, followed by an intervention phase with biofeedback of their measured values, living a healthy lifestyle and on healthy food this time. The volunteers showed higher carotenoid concentrations than found in previous studies. A significant correlation of healthy lifestyle habits and a high antioxidant status could be determined. Subjects improved their nutritional habits and significantly increased their carotenoid concentration during intervention. Follow-up five months later showed a consolidation of the increase. The investigations show that a healthy diet and a well-balanced lifestyle correlate with a high cutaneous antioxidant concentration and that spectroscopic biofeedback measurement of cutaneous carotenoids as part of an integrated prevention program is a feasible and effective means to raise the health awareness in adolescents.