Chain dynamics of human dermis by Thermostimulated currents: A tool for new markers of aging.

BACKGROUND/PURPOSE: The purpose of this clinical study was to identify dielectric markers to complete a previous thermal and vibrational study on the molecular and organizational changes in human dermis during intrinsic and extrinsic aging. METHODS: Sun-exposed and non-exposed skin biopsies were collected from 28 women devised in two groups (20-30 and ≥60 years old). The dielectric relaxation modes associated with localized and delocalized dynamics in the fresh and dehydrated state were determined by the Thermostimulated currents technique (TSC). RESULTS: Intrinsic and extrinsic aging induced significant evolution of some of the dielectric parameters of localized and delocalized dynamics of human skin. With photo-aging, freezable water forms a segregated phase in dermis and its dynamics is close to free water, what evidences the major role of extrinsic aging on water organization in human skin. Moreover, TSC indicators highlight the restriction of localized mobility with intrinsic aging due to glycation, and the cumulative effect of chronological aging and photo-exposition on the molecular mobility of the main structural proteins of the dermis at the mesoscopic scale. CONCLUSION: TSC is a well-suited technique to scan the molecular mobility of human skin. It can be uses as a relevant complement of vibrational and thermal characterization to follow human skin modifications with intrinsic and extrinsic aging.

Dermatology today and tomorrow: from symptom control to targeted therapy.

For many decades and until recently, medical approach to dermatologic diseases has been based on the physician's ability to recognize and treat symptoms. Nowadays, advances in the understanding of the biology of diseases and in technologies for intervening against them have allowed physicians to diagnose and treat underlying disease processes rather than simply addressing the symptoms. This means that rather than addressing 'the disease in humans', physicians can now address the particular pathologic (biologic, molecular) disturbance as it presents in the individual patient, i.e., physicians now can practice something much closer to 'personalized medicine', leading to greater benefits for the patients and the health of society in general. The deeper understanding of ultraviolet radiation, the importance of photoprotection and increased knowledge about signalling pathways of melanoma and carcinoma have led to more complete care for the dermatologic patient. The current popularity for excessive exposure to the sun, without adequate application of the appropriate photoprotection remedies, is the origin of melanoma, but also for the weakening of the structure and functions of the skin. Indeed, fragility of the skin can affect humans around the world. In the senior population, this skin fragility is accompanied by pruritus, whereas atopic dermatitis is an inflammatory disease with highest prevalence in children and adolescents. Acne, the number one reason for dermatologic consultations worldwide, increases its prevalence in adolescents and in females. Senescent alopecia affects humans after menopause and andropause. The articles in this publication present an overview of the current advanced understanding of the diagnosis and therapeutic approaches in 6 fields of dermatology - dermatopaediatry and gerontodermatology, oncodermatology, hair loss, atopic dermatitis, photoprotection and acne - and thereby serve as a useful compendium of updated information and references for all healthcare professionals who see patients with presentations of the symptoms of these diseases.

Green microparticles based on a chitosan/lactobionic acid/linoleic acid association. Characterisation and evaluation as a new carrier system for cosmetics.

The association chitosan/linoleic acid/lactobionic acid in aqueous solution spontaneously led to the formation of stable microparticles with a liquid hydrophobic core consisting of linoleic acid surrounded by a shell of chitosan/lactobionic acid. The originality of the microparticles arises from the fact that they are formed by the association of three ingredients of cosmetic interest, including a skin penetration enhancer (linoleic acid). Dynamic light scattering (DLS) measurements showed microparticles with a mean diameter of 1-2 µm. The presence of a hydrophobic liquid core was observed by transmission electron microscopy (TEM). The ability of these microparticles to encapsulate phenylethyl resorcinol, a hydrophobic skin lightener, was evaluated and its encapsulation was confirmed thanks to T2 measurements and nuclear Overhauser effects (nOe) signs.

Follow-up of solar lentigo depigmentation with a retinaldehyde-based cream by clinical evaluation and calibrated colour imaging.

BACKGROUND AND OBJECTIVE: To assess an objective method evaluating the effects of a retinaldehyde-based cream (RA-cream) on solar lentigines; 29 women randomly applied RA-cream on lentigines of one hand and a control cream on the other, once daily for 3 months. METHODS: A specific method enabling a reliable visualisation of the lesions was proposed, using high-magnification colour-calibrated camera imaging. Assessment was performed using clinical evaluation by Physician Global Assessment score and image analysis. Luminance determination on the numeric images was performed either on the basis of 5 independent expert's consensus borders or probability map analysis via an algorithm automatically detecting the pigmented area. RESULTS: Both image analysis methods showed a similar lightening of ΔL* = 2 after a 3-month treatment by RA-cream, in agreement with single-blind clinical evaluation. CONCLUSION: High-magnification colour-calibrated camera imaging combined with probability map analysis is a fast and precise method to follow lentigo depigmentation.

Nfkb1 is a haploinsufficient DNA damage-specific tumor suppressor.

NF-κB proteins play a central and subunit-specific role in the response to DNA damage. Previous work identified p50/NF-κB1 as being necessary for cytotoxicity in response to DNA alkylation damage. Given the importance of damage-induced cell death for the maintenance of genomic stability, we examined whether Nfkb1 acts as a tumor suppressor in the setting of alkylation damage. Hprt mutation analysis demonstrates that Nfkb1(-/-) cells accumulate more alkylator-induced, but not ionizing radiation (IR)-induced, mutations than similarly treated wild-type cells. Subsequent in vivo tumor induction studies reveal that following alkylator treatment, but not IR, Nfkb1(-/-) mice develop more lymphomas than similarly treated Nfkb1(+/+) animals. Heterozygous mice develop lymphomas at an intermediate rate and retain functional p50 in their tumors, indicating that Nfkb1 acts in a haploinsufficient manner. Analysis of human cancers, including therapy-related myeloid neoplasms, demonstrates that NFKB1 mRNA expression is downregulated compared with control samples in multiple hematological malignancies. These data indicate that Nfkb1 is a haploinsufficient, pathway-specific tumor suppressor that prevents the development of hematologic malignancy in the setting of alkylation damage.

Fragility of epidermis and its consequence in dermatology.

The skin is the largest organ of the body, providing a protective barrier against bacteria, chemicals and physical insults while maintaining homeostasis in the internal environment. Such a barrier function the skin ensures protection against excessive water loss. The skin's immune defence consists of several facets, including immediate, non-specific mechanisms (innate immunity) and delayed, stimulus-specific responses (adaptive immunity), which contribute to fending off a wide range of potentially invasive microorganisms. This article is an overview of all known data about 'fragile skin'. Fragile skin is defined as skin with lower resistance to aggressions. Fragile skin can be classified into four categories up to its origin: physiological fragile skin (age, location), pathological fragile skin (acute and chronic), circumstantial fragile skin (due to environmental extrinsic factors or intrinsic factors such as stress) and iatrogenic fragile skin. This article includes the epidemiologic data, pathologic description of fragile skin with pathophysiological bases (mechanical and immunological role of skin barrier) and clinical description of fragile skin in atopic dermatitis, in acne, in rosacea, in psoriasis, in contact dermatitis and other dermatologic pathologies. This article includes also clinical cases and differential diagnosis of fragile skin (reactive skin) in face in adult population. In conclusion, fragile skin is very frequent worldwide and its prevalence varies between 25% and 52% in Caucasian, African and Asian population.

Prevalence and risk factors for xerosis in the elderly: a cross-sectional epidemiological study in primary care.

BACKGROUND: Limited information is available concerning the prevalence and risk factors of xerosis in the elderly. OBJECTIVE: To establish the prevalence of xerosis and associated factors in elderly patients. METHODS: A national, multicenter, observational, cross-sectional study in patients aged 65 or older was performed. The data collected by general practitioners were demographics and medical history, including history of atopic disease. Xerosis was evaluated using the Overall Dry Skin score. RESULTS: 756 patients were included. The prevalence of xerosis was 55.6%. Xerosis was significantly associated with older age (OR: 1.48, 95% CI: 1.16-1.89), female sex (OR: 1.80, 95 CI%: 1.29-2.53), treatments that can potentially cause xerosis (OR: 2.21, 95 CI%: 1.54-3.17), itching during sweating (OR: 7.11, 95% CI: 3.90-12.95), a history of dry skin (OR: 2.89, 95% CI: 1.65-5.08) and a history of atopic dermatitis (OR: 3.60, 95% CI: 1.99-6.52). CONCLUSION: Xerosis is highly prevalent in the elderly. A history of atopy, especially atopic dermatitis, is associated with an increased risk of xerosis in the elderly.

Evaluation of sensitive scalp severity and symptomatology by using a new score.

BACKGROUND: Among localizations of sensitive skin, scalp is one of the less known. OBJECTIVES: We performed a study for a better understanding of sensitive scalp and proposed a new score: the 3S score. METHODS: An opinion poll was conducted on 2117 persons, which were representative of the French population. The total score was obtained by multiplying score severity of abnormal sensations by the number of these sensations. RESULTS: About one-third of the population declared to suffer from a sensitive scalp. It was increasingly frequent with age. The 3S questionnaire allowed discrimination among subjects with slightly sensitive, sensitive and very sensitive scalps. Itching and prickling were the most frequent symptoms. Sensitive scalp was sometimes associated with some scalp diseases. Dandruff cannot be considered as a symptom of sensitive scalp. CONCLUSIONS: This study is only the third reported study about sensitive scalp. The 3S questionnaire is a convenient and effective tool for investigating the severity and symptomatology of the sensitive scalp.

Modulation of Interleukin-8 and staphylococcal flora by Avène hydrotherapy in patients suffering from chronic inflammatory dermatoses.

BACKGROUND: A number of studies argue in favour of an important role of microbial colonization, in particular of Staphylococcus aureus, in triggering atopic dermatitis (AD) flare-up and psoriasis, in particular through the superantigenic properties of toxins generated by S. aureus. OBJECTIVES: The aim of this study was to assess the efficacy of a 3-week Avène hydrotherapy on the skin surface of patients suffering from psoriasis or atopic dermatitis. METHODS: Skin samples were taken from healthy subjects or atopic (n = 18) or psoriatic patients (n = 39) undergoing hydrotherapy at Avène at the beginning (D0) and the end of treatment (D18). The severity of the dermatosis was evaluated according to SCORing Atopic Dermatitis (SCORAD) or Psoriasis Area Severity Index (PASI) scores at D0 and D18. Marker of inflammation interleukin 8 (IL-8), S. aureus colonization (protein A) and enterotoxins were assessed in skin samples using RT-PCR. RESULTS: At D0, significant differences were observed between healthy subjects and atopic or psoriatic patients in all the parameters evaluated (IL-8, protein A). At the end of the hydrotherapy, a significant decrease in SCORAD was associated with a significant reduction of IL-8, S. aureus colonization and enterotoxin D in patients with atopic dermatitis. Similarly, a significant decrease in PASI was associated with a significant reduction of IL-8, S. aureus colonization and enterotoxin N in patients with psoriasis. CONCLUSIONS: This study demonstrates the positive effects of Avène hydrotherapy on the skin of patients suffering from chronic dermatosis, with decreased inflammation and reduced colonization by S. aureus.

VHL inactivation is an important pathway for the development of malignant sporadic pancreatic endocrine tumors.

A small subset of familial pancreatic endocrine tumors (PET) arises in patients with von Hippel-Lindau syndrome and these tumors may have an adverse outcome compared to other familial PET. Sporadic PET rarely harbors somatic VHL mutations, but the chromosomal location of the VHL gene is frequently deleted in sporadic PET. A subset of sporadic PET shows active hypoxia signals on mRNA and protein level. To identify the frequency of functionally relevant VHL inactivation in sporadic PET and to examine a possible prognostic significance we correlated epigenetic and genetic VHL alterations with hypoxia signals. VHL mutations were absent in all 37 PETs examined. In 2 out of 35 informative PET (6%) methylation of the VHL promoter region was detected and VHL deletion by fluorescence in situ hybridization was found in 14 out of 79 PET (18%). Hypoxia inducible factor 1alpha (HIF1-alpha), carbonic anhydrase 9 (CA-9), and glucose transporter 1 (GLUT-1) protein was expressed in 19, 27, and 30% of the 152 PETs examined. Protein expression of the HIF1-alpha downstream target CA-9 correlated significantly with the expression of CA-9 RNA (P<0.001), VHL RNA (P<0.05), and VHL deletion (P<0.001) as well as with HIF1-alpha (P<0.005) and GLUT-1 immunohistochemistry (P<0.001). These PET with VHL alterations and signs of hypoxia signalling were characterized by a significantly shortened disease-free survival. We conclude that VHL gene impairment by promoter methylation and VHL deletion in nearly 25% of PET leads to the activation of the HIF-pathway. Our data suggest that VHL inactivation and consecutive hypoxia signals may be a mechanism for the development of sporadic PET with an adverse outcome.

Human immunodeficiency virus atropy induces modification of subcutaneous adipose tissue architecture: in vivo visualization by high-resolution magnetic resonance imaging.

BACKGROUND: Human immunodeficiency virus (HIV) infection generally induces lipodystrophy. For targeted treatment a better understanding of its development is necessary. The utility of high-resolution magnetic resonance imaging (MRI) is explored. OBJECTIVES: The present study presents a way to visualize the adipose tissue architecture in vivo and to inspect modifications associated with the atrophy. METHODS: High-resolution MRI scans with surface coils were performed on the calf and at the lumbar region of three groups of patients: HIV patients with lipoatrophy, HIV patients without lipoatrophy and healthy volunteers. All patients underwent a clinical examination. In addition, dual energy X-ray absorptiometry (DEXA) measurements were taken. On the MRI scans adipose tissue thickness and adipose nodule size were measured. Results High-resolution MRI enabled identification of a clear disorganization of adipose tissue in patients with lipoatrophy. In addition, these patients presented a very small adipose tissue thickness on the calf and a very small nodule size. RESULTS: led to the hypothesis that adipose tissue disorganization appears before changes in DEXA measurements or clinically visible modifications. CONCLUSIONS: High-resolution MRI enabled visualization in vivo of precise changes in tissue organization due to HIV lipoatrophy. This imaging technique should be very informative for better monitoring of the atrophy.

A multitechnique evaluation of topical corticosteroid treatment.

BACKGROUND/PURPOSE: Corticosteroids are widely prescribed for systemic or local treatment of inflammatory autoimmune disorders. Long-term therapy is associated with side effects and causes cutaneous atrophy of the epidermis and the dermis. The present study aims to evaluate with several noninvasive techniques, the skin modifications observed during corticosteroids treatment. The potential of skin mechanical measurement and ultrasound radio frequency (RF) signal analysis are proposed as new measures more closely related to the functional impairments. METHODS: Thirteen young healthy women volunteers had two applications per day on one arm of topical Clobetasol propionate 0.05% for 28 days, and they were followed for 28 days more. Skin modifications were studied by high-frequency ultrasound imaging, ultrasound RF signal analysis, optical coherence tomography and by the suction test. RESULTS: For all the techniques, a statistically significant change is observed with treatment. Large variations, around 30%, are observed for all techniques, but less for ultrasound imaging (10%). Dermis and epidermis thickness presented stable measurements on the nontreated zone. At the end of the study, measures returned to normal. The dynamic is mainly observed within the first 14 days of treatment and within the first 14 days after its cessation. CONCLUSION: Similar dynamics of skin modification during corticosteroid treatment was observed with very different techniques. Moreover, the potential of RF ultrasound analysis and mechanical skin measurement for characterizing skin structural and functional impairments has been evaluated.

Validation of a non-contact technique for local skin temperature measurements.

UNLABELLED: Here we propose to quantify local temperature variations using thermal imaging to assess the effect of dermatological lasers. OBJECTIVES: To quantify the temperature raise induced by laser application and to differentiate the effects of a potassium titanyl phosphate (KTP) laser and an intense pulsed light (IPL). METHODS: A randomized comparative study was performed on 10 adult volunteers with symmetrical rosacea treated by KTP laser or IPL. Skin temperature measurements were performed on inclusion, immediately after laser treatment and 3 min after thermal water application, using a high-resolution (0.08 degrees C) infrared thermal video camera. RESULTS: KTP laser treatment induced a significant rise in local skin temperature whereas no significant change was revealed by the IPL treatment. The infrared camera is a reliable and reproducible technique that allows a follow-up of skin temperature without skin contact. CONCLUSION: Thermography using an infrared camera could potentially be applied in clinical pharmacology for inflammatory reactions or scarring processes.

Molecular characterization of inflammation and Staphylococcus aureus colonization of involved skin of atopic dermatitis patients. A non-invasive approach.

Atopic dermatitis (AD) is a multifactorial chronic inflammatory disease mainly stemming from a genetic predisposition that leads to hypersensitivity to environmental factors and a common involvement of Staphylococcus aureus (SA) colonization. The aim of this work was to propose a new non-invasive approach to enumerate the genes coding for the toxins of SA in atopic skin samples. In parallel, the study aimed to evaluate the change in AD through 3 markers of the inflammatory response: IL-8, IL-1RA/IL-1alpha and IL-18. These methods were tested on 31 patients with AD, and finally on a group of 19 subjects for whom clinical improvement had been reported after various treatments. The study revealed the presence of a large number of genes encoding toxins in atopic samples, indicating a high rate of SA colonization, and also an increase in the level of all cytokine markers in atopic skin compared to the skin of healthy subjects. Finally, we found a positive correlation between increases in the SCORAD (Scoring Atopic Dermatitis Index) value after treatment and the corresponding evolution of the SA density. These methods provide a means to clinically evaluate the course of AD, and may help in the development of potential treatments.

Sensitive skin is not limited to the face.

BACKGROUND: Sensitive skin (or reactive or hyper-reactive skin) is defined as skin that reacts by erythema and/or subjective symptoms (pricking, burning, pain, pruritus etc.) to stimuli that are not pathogens in themselves (e.g. wind, heat, cold, water, cosmetics, stress). This phenomenon is very frequent, occurring in about 50% of the European population. OBJECTIVES: Sensitive skin is always reported on the face. The aim of our study was to determine if it can occur in other localizations. METHODS: We have performed this study in two centres. One was a department of dermatology in a university hospital while the other one was a centre for cosmetological studies. A questionnaire was given to women aged > 15 years. The questions were: Do you have sensitive skin? If yes, in which localization? What are the symptoms and triggering factors? RESULTS: Four hundred subjects were included in the study (200 in each centre). The two populations were similar in terms of age, sex, and most of the results. The mean age was 40 years. Eighty-five per cent of the 400 subjects declared that they had sensitive skin on the face, and 70% had sensitive skin in another area: hands (58%), scalp (36%), feet (34%), neck (27%), torso (23%) or back (21%). Triggering factors included cold (66%), heat (28%), stress (61%), sun exposure (51%), wind (42%), water from a shower (29%) or a swimming pool (40%), soaps (42%), cosmetics (28%) and pollution (18%). Friction from clothes was reported in 28% of cases. Sensitive skin was observed as redness in most cases along with various subjective symptoms. CONCLUSIONS: The proportion of subjects presenting with sensitive skin is probably overestimated. However, the main result of this study is that sensitive skin is not restricted to the face but rather it is also present at other localizations, mainly the hands, and often the scalp and feet.

DNA copy number status is a powerful predictor of poor survival in endocrine pancreatic tumor patients.

The clinical behavior of endocrine pancreatic tumors (EPTs) is difficult to predict in the absence of metastases or invasion to adjacent organs. Several markers have been indicated as potential predictors of metastatic disease, such as tumor size > or =2 cm, Ki67 proliferative index > or =2%, cytokeratin (CK) 19 status, and recently in insulinomas, chromosomal instability (CIN). The goal of this study was to evaluate the value of these markers, and in particular of the CIN, to predict tumor recurrence or progression and tumor-specific death, using a series of 47 insulinomas and 24 non-insulinoma EPTs. From these EPT cases, a genomic profile has been generated and follow-up data have been obtained. The proliferative index has been determined in 68 tumors and a CK19 expression pattern in 50 tumors. Results are statistically analyzed using Kaplan-Meier plots and the log-rank statistic. General CIN, as well as specific chromosomal alterations such as 3p and 6q loss and 12q gain, turned out to be the most powerful indicators for poor tumor-free survival (P< or =0.0004) and tumor-specific death (P< or =0.0113) in insulinomas. The CIN, chromosome 7q gain, and a proliferative index > or =2% were reliable in predicting a poor tumor-free survival in non-insulinoma EPTs (P< or =0.0181, whereas CK19 expression was the most optimal predictor of tumor-specific death in these tumors. In conclusion, DNA copy number status is the most sensitive and efficient marker of adverse clinical outcome in insulinomas and of potential interest in non-insulinoma EPTs. As a consequence, this marker should be considered as a prognosticator to improve clinical diagnosis, most practically as a simple multi-target test.