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BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a major problem in aviation medicine because it is responsible for sleepiness and high cardiovascular risk, which could jeopardize flight safety. Residual sleepiness after the treatment is not a rare phenomenon and its management is not homogenous in aviation medicine. Thus, we decided to perform a study to describe this management and propose guidelines with the help of the literature.METHODS: This is a retrospective study including all aircrew members with a history of OSAS who visited our aeromedical center between 2011 and 2018. Residual sleepiness assessment was particularly studied.RESULTS: Our population was composed of 138 aircrew members (mean age 50.1 ± 9.6 yr, 76.8% civilians, 80.4% pilots); 65.4% of them had a severe OSAS with a mean Epworth Sleepiness Scale (ESS) at 8.5 ± 4.7 and a mean apnea hypopnea index of 36.2 ± 19.2/h. Of our population, 59.4% performed maintenance of wakefulness tests (MWT) and 10.1% had a residual excessive sleepiness. After the evaluation, 83.1% of our population was fit to fly.DISCUSSION: An evaluation of treatment efficiency is required in aircrew members with OSAS. Furthermore, it is important to have an objective proof of the absence of sleepiness. In this case, ESS is not sufficient and further evaluation is necessary. Many tests exist, but MWT are generally performed and the definition of a normal result in aeronautics is important. This evaluation should not be reserved to solo pilots only.Monin J, Rebiere E, Guiu G, Bisconte S, Perrier E, Manen O. Residual sleepiness risk in aircrew members with obstructive sleep apnea syndrome. Aerosp Med Hum Perform. 2023; 94(2):74–78.

Background Atopic dermatitis (AD) is a composite disease characterized by derangement of the skin permeability barrier (SPB), altered immune defence, and dysbiosis. Little is known on the role played by the sebaceous gland (SG) activity in the SPB integrity and in the AD pathomechanisms. Objectives To investigate profiles of sebaceous and epidermal free fatty acids (FFAs), squalene, cholesterol, triglycerides (TGs), and wax esters (WEs) in sebum and stratum corneum (SC) from seborrheic and non-seborrheic areas, in healthy subjects and patients with AD. To simultaneously acquire aminoacidome in SC. Methods In healthy controls and patients with AD, sebum and SC were sampled consecutively from facial areas (forehead, and cheeks). SC was sampled also from non sebaceous areas (arm) in healthy controls and from the non lesional and lesional areas on the arm in AD. Sampling was preceded by assessments of skin biophysics, i.e. TEWL and corneometry. Results Disruption of the SBP was associated with decreased levels of lipids of both sebaceous and epidermal type. Extent of lipid derangement in the SG and the SC was correlated with the AD severity. Relative composition of natural moisturizing factors was altered in the SC of patients with AD. Conclusions The SG activity is compromised in adult AD. Aminoacidome is deranged in the facial areas in AD. Lipid signatures in association with aminoacidome, and skin physical properties may serve the definition of phenotype clusters that associate with AD severity.

/objectives: Sleep disorders are a critical issue for flight safety. Previous studies have shown a high prevalence of sleep disorders and excessive sleepiness in the general population and some aircrews. The objectives of this study are to measure the prevalence of excessive daytime sleepiness and sleep disorders in aircrews, and to determine the risk factors of falling asleep during a flight.this is a monocentric study based on questionnaires, including all professional civilian and military aircrews examined in an aeromedical center between January and May 2021. The questionnaire, created for this study, included information about socio-demographic characteristics, aeronautical experience, lifestyle, sleep habits, an Epworth sleepiness scale, and screening tests for chronic insomnia, sleep apnea syndrome and restless legs syndrome.749 aircrew members were included (86.2% male, 58.9% civilian, 74.1% pilot, mean age 43.4 ± 9.6 years), 45.9% of the population had at least one sleep disorder (chronic insomnia 39.5%, sleep apnea syndrome 10.5%, restless legs syndrome 4.1%), 15.5% had an excessive daytime sleepiness, and 24.6% reported in-flight sleep while on duty. Chronic insomnia, screen use before bedtime, use of sleeping pills, inadequate recovery time after a flight, female gender and civilian status were found as risk factors of in-flight sleep in the multivariate analysis.this study emphasizes the need to improve the screening and prevention of sleep disorders in this particular population.

Background: Skincare products are used daily to maintain a healthy skin (cleansing, moisturizing, protecting…), but their impact on this first layer, which corresponds to the skin microbiome, is still poorly understood. Preserving natural resources and mechanisms of the skin ecosystem is essential; an original approach based on these premises, called ecobiology, has recently emerged in skincare. Ecobiology considers the skin as an ever-evolving ecosystem which hosts human and microbial cells that interact together with their environment. In this context, we evaluated the impact on the skin microbiome of three types of leave-on face skincare products: a hydrophilic sterile solution, a micellar solution, and an oil-in-water emulsion. Materials and Methods: The individual microbial profiles of 20 Caucasian females were investigated. Samples were obtained twenty-four hours and four days following a daily application of the skincare products versus control area where no product was applied. To analyze the bacterial diversity and abundance of skin microbiome, a 16SrRNA gene sequencing was performed using the Illumina MiSeq platform. Results: Our results confirm the overall diversity of skin microbiome as previously observed and notably reveal the prevalence of Cutibacterium spp. and Staphylococcus spp. on sebaceous site (the back). Bacterial diversity and abundance were not affected by the products either twenty-four hours or four days after application, as indicated by comparison with the control. Moreover, no dissimilarity was observed between the three products versus their control, neither between each product. Conclusions: These preliminary results demonstrated for the first time that three different types of leave-on face skincare products such as a hydrophilic sterile solution, a micellar solution, and an emulsion have no impact on skin microbiome and can be considered as “microbiome friendly”.

Background Aircrew members of airlines are exposed to travel risks. The objectives of our study are to assess the experience of aircrews about these risks and their knowledge about prevention means. Methods We conducted an observational qualitative study in commercial aircrews at the aeromedical center of Percy Military Hospital between November 2018 and June 2019. Results 200 aircrews answered the questionnaire, 54% of which were pilots, 91% work on long and/or medium-haul flights, 82.5% of airmen are concerned by their immunization status. Vaccination rate varied according to the vaccine. Two third of airmen usually go to malaria-endemic countries, 12% of respondents use antimalarial treatment in such infected countries, while 93.5% protect themselves against mosquito bites mainly with insect repellent. In case of a fever after a stay in a malaria-endemic country, only 51.5% of respondents immediately think about acute malaria. Aircrews are very motivated by their job but 58% of them feel tired probably linked to quality of sleep and effects of jet-lag, with a statistically significant difference between pilots and cabin crews (43% vs 75% [p Conclusion Aircrew members know a lot about travel issues. Malaria remains a major concern for aircrews, but it is necessary to maintain information about this topic throughout their career and to provide them with repellents, what many airlines actually do. Fatigue management is also important for airmen, so as they use different technics to accelerate recovery. Some airlines try to help them with a guide for aircrew fatigue management. This particular population involved in flight safety has few risky behaviors; nevertheless, alcohol misuse and drug use are screened during medical examinations and by airlines.

Summary Introduction In France, a systematic EEG is performed during initial examination in military aircrew applicants, which may provide an estimation of the prevalence of benign epileptiform variants in healthy adults. Methods We analyzed standard EEG (21 scalp electrodes, 20 minutes, 400 Hz sampling rate) of military aircrew applicants examined in the French Main Aeromedical Center in 2016. EEGs were analyzed using both bipolar and referential montages. The collected data were EEG abnormalities and benign epileptiform variants. The kappa inter-observer index for the detection of benign epileptiform variants was calculated. Results Our population was composed of 495 subjects (86.7% males, mean age 22.5 ± 4.8 years), wishing to become a pilot in 69.7% of cases. None of the applicants reported any neurological disease and none was taking regular medication. EEG was considered as normal for 96.4% of them. Encountered EEG abnormalities were mainly asymmetric and sharp slow wave bursts. Drowsiness was recorded during 13.9% of these EEG. Benign epileptiform variants were present in 7.7% of our population: anterior theta activities (4%), posterior slow waves (2.8%), alpha variants (0.6%) and wicket spikes (0.2%). Hyperventilation induced EEG slowing in 14.1% of cases. During intermittent photic stimulation, physiological photic driving was observed in 15.2% of subjects. Discussion Many previous studies have been dedicated to the prevalence of benign epileptiform variants but results are often heterogeneous and based on patients in whom there was an indication for EEG. Our results thus bring data on benign epileptiform variants prevalence in a young adult population characterized by the absence of neurologic disorders. Our study demonstrates that anterior theta activities, posterior slow waves, alpha variants and wicket spikes are the most frequent benign EEG variants in such a young adult population.

Background Immunosuppressive treatments are increasingly prescribed in a variety of diseases. This issue concerns airmen. Methods To assess the problem, we conducted an observational retrospective study in the aircrew population examined in 2014 at the Aeromedical Center of Percy Military Hospital. Results Airmen treated with immunosuppressive drugs accounted for 0.5% of the total population (N = 13,326). Rheumatic and digestive diseases were the main etiologies, respectively 43% and 35% of cases. One-third of airmen took such medications during at least 3 yr and three-quarters of airmen were declared fit to fly, with some limitations. Discussion Due to their working conditions, airmen are exposed to a real infectious risk, which is, however, difficult to evaluate. The risk is obviously increased by immunosuppressive drugs and may affect flight safety. Aeromedical evaluation should consider this problem. Vaccination plays a central role in the prevention of infectious risk. Based on French recommendations, we propose a vaccination schedule for these particular patients.Guiu G, Monin J, Hamm-Hornez A-P, Manen O, Perrier E. Epidemiology of airmen treated with immunosuppressive drugs and vaccination concerns. Aerosp Med Hum Perform. 2018; 89(4):377-382.

Background Recommendations for the interpretation of electrocardiogram have been published in 2009. The aim of this study was to define the prevalence of intraventricular conduction disturbances (ICoDs) in a large population, using these recommendations. Methods From 01/31/1996 to 09/22/2010, an electrocardiogram was performed at each visit for all aircrew members examined for fitness assessment in an aeromedical center. The prevalence of left bundle branch block (LBBB), right bundle branch block (RBBB), incomplete LBBB, incomplete RBBB, nonspecific intraventricular disturbance (NIVCD), left anterior fascicular block (LAFB), and left posterior fascicular block (LPFB) was measured and compared by age and gender. Results The global prevalence of ICoD was 3.09% in our population of 69,186 patients. The most frequent types of ventricular blocks were IRBBB (1.25%) and LAFB (1.10%), whereas RBBB (0.46%), LBBB (0.08%), ILBBB (0.03%), NIVCD (0.05%), and LPFB (0.13%) were rare findings. ICoDs are more frequent for males and older age groups (P < 0.001). Discussion Our results are comparable to studies concerning low cardiovascular risks populations. The association between ICoD and cardiovascular diseases needs to be studied in this population.

International audience; This paper presents an in-depth analysis on the effect of the coexistence in the 2.4 GHz band between IEEE 802.15.4 and IEEE 802.11 on the medium access control. We focus on the slotted CSMA/CA medium access algorithm that is used by IEEE 802.15.4 and analyse the delay that frames undergo when suffering from interference from a WiFi activity. We measure the overhead caused by the additional delay spent in the MAC sublayer frame queue before accessing the medium due to the presence of WiFi interference. We experimented different scenarios with overlapping channels and non-overlapping channels. We show that the two wireless protocols can coexist if we take into considerations the relative positions of the nodes to avoid very high interference and if we avoid monopolizing the channel with a very high rate WiFi traffic even under overlapping channels.

Skin acts as a barrier between the environment and internal organs and performs functions that are critical for the preservation of body homeostasis. In mammals, a complex network of circadian clocks and oscillators adapts physiology and behavior to environmental changes by generating circadian rhythms. These rhythms are induced in the central pacemaker and peripheral tissues by similar transcriptional-translational feedback loops involving clock genes. In this work, we investigated the presence of functional oscillators in the human skin by studying kinetics of clock gene expression in epidermal and dermal cells originating from the same donor and compared their characteristics. Primary cultures of fibroblasts, keratinocytes, and melanocytes were established from an abdominal biopsy and expression of clock genes following dexamethasone synchronization was assessed by qPCR. An original mathematical method was developed to analyze simultaneously up to nine clock genes. By fitting the oscillations to a common period, the phase relationships of the genes could be determined accurately. We thereby show the presence of functional circadian machinery in each cell type. These clockworks display specific periods and phase relationships between clock genes, suggesting regulatory mechanisms that are particular to each cell type. Taken together, our data demonstrate that skin has a complex circadian organization. Oscillators are present not only in fibroblasts but also in epidermal keratinocytes and melanocytes and are likely to act in coordination to drive rhythmic functions within the skin.

Background Vasovagal episodes are common events but may have consequences for flight safety, particularly in high-performance aircrafts, where the autonomic nervous system is impacted during +G(z) accelerations. However, the risk is difficult to assess in the case of ground presyncopes. Case report A 27-yr-old fighter pilot experienced a feeling of faintness at a daily briefing. He had previously shown no medical history except for a single episode. The initial physical examination was normal. During vagal maneuvers, the pilot developed a cardiac pause and a tilt-table test was positive. Other investigations were normal.The pilot lost consciousness twice in centrifuge testing while previous tests had shown a good cardiovascular tolerance. He was declared unfit to fly fast jets but fit as a multicrew transport pilot with a waiver. Discussion The epidemiology of vasovagal reactions is difficult to estimate in aircrew. A late occurrence in the career can be explained by either a newly acquired hypervagotonia, or an old predisposition with specific triggering factors in which psychosocial aspects are important. In such circumstances three steps are necessary to assess fitness: 1) to check for other etiologies; 2) to look for vasovagal predisposition; and 3) to check psychiatric condition. The studies about the predictive value of the tilt-test must be taken into account. Conclusion In the case of vasovagal presyncope in a fighter pilot, the aeromedical decision should consider the medical history of the pilot, the results of investigations, and the experience and motivation of the individual under review. Centrifuge testing may be useful in difficult situations.

The process of facial skin aging differs between different ethnic populations. Standardized tools to objectively evaluate facial skin aging in clinical and epidemiological studies in different ethnic populations are needed. We designed and validated a photonumeric scale for assessment of facial aging in the Indian population. A total of 149 subjects were selected from an electronic photographic database of 300 women from the Mumbai region. An expert consensus panel selected nine subjects representing a spectrum of skin damage from none to severe, on the basis of wrinkling and tissue slackening. The nine-point scale, composed of one face-on and one oblique photo of the same subject per grade, was validated by nine independent judges in 99 subjects with a repetition two weeks later. Inter-observer reliability and intra-observer reproducibility were calculated using Kappa coefficients. Validation of the scale showed a high level of inter-observer reliability between the consensus and independent panels, and intra-observer reproducibility between the two evaluations performed by the independent judges. In conclusion, this nine-point facial aging scale is a reliable tool for clinical evaluations of skin damage in Indian women, suitable for use in clinical and epidemiological studies.

Introduction Coronary artery disease (CAD) is a major preoccupation for flight surgeons because of the risk of in-flight incapacity it may lead to. That's why the prevention and the screening of CAD among aircrew members (AM) is systematic. The constant progress of cardiological tests, especially imaging, can help the flight surgeon to diagnose a CAD in AM before the onset of symptoms. Methods The aims of this study are to describe the population of AM with a diagnosis of CAD, to analyze the tests performed that lead to the diagnosis and those performed for the AM rehabilitation. All the medical files of AM suffering from CAD were extracted from the 86,691 files of AM who were examined in our aeromedical center from 01/01/2010 to 12/31/2015. Results Our population was composed of 120 AM with a CAD (mean age: 53.2 ± 8.9 yo, 98.3% males, 79.2% civilians, 76.7% pilots). CAD were discovered on acute cardiovascular events (myocardial infraction/sudden death) for 55% of the population, and on moderated symptoms for 22.5% of the population. For the 22.5% others, the diagnosis was performed thanks to the systematical electrocardiogram or thanks to the prescription of paraclinic tests (exercise test, coronary tomography, cardiac MRI, myocardial scintigraphy) made as a result of an elevated cardio-vascular risk. The coronarography revealed a bitroncular stenosis for 29.1% of patients and a tritroncular stenosis for 24.8% of them. After a complete cardiological evaluation, 70% of AM were declared fit with waivers. Discussion Coronary tomography and stress tests are helping tools, which permit in our study to diagnose CAD before the onset of symptoms or acute events for a part of the population. Nowadays, the diagnosis of CAD is not synonymous of unfitness, even in pilots. A complete cardiological assessment remains mandatory in order to evaluate the sequels, the risk of complications and relapse. A multi-pilot limitation seems necessary for most of cases.

INTRODUCTION AND OBJECTIVES: Many dispensing errors occur in the hospital, and these can endanger patients. The purpose of this study was to assess the rate of dispensing errors by a unit dose drug dispensing system, to categorize the most frequent types of errors, and to evaluate their potential clinical significance. METHODS: A prospective study using a direct observation method to detect medication-dispensing errors was used. From March 2007 to April 2007, "errors detected by pharmacists" and "errors detected by nurses" were recorded under six categories: unauthorized drug, incorrect form of drug, improper dose, omission, incorrect time, and deteriorated drug errors. The potential clinical significance of the "errors detected by nurses" was evaluated. RESULTS: Among the 734 filled medication cassettes, 179 errors were detected corresponding to a total of 7249 correctly fulfilled and omitted unit doses. An overall error rate of 2.5% was found. Errors detected by pharmacists and nurses represented 155 (86.6%) and 24 (13.4%) of the 179 errors, respectively. The most frequent types of errors were improper dose (n = 57, 31.8%) and omission (n = 54, 30.2%). Nearly 45% of the 24 errors detected by nurses had the potential to cause a significant (n = 7, 29.2%) or serious (n = 4, 16.6%) adverse drug event. CONCLUSIONS: Even if none of the errors reached the patients in this study, a 2.5% error rate indicates the need for improving the unit dose drug-dispensing system. Furthermore, it is almost certain that this study failed to detect some medication errors, further arguing for strategies to prevent their recurrence.

The skin harbors two dendritic cell (DC) subsets, Langerhans cells (LC) and interstitial/dermal DC (IDDC), which traffic to lymph nodes after inflammation and ultraviolet stress. To demonstrate that monocytes may act as DC precursors for skin DC in postinflammatory recolonization, we generated LC and IDDC from monocytes by using cytokines related to the T helper cell type 2 environment [granulocyte macrophage-colony stimulating factor/transforming growth factor-β/interleukin-13/tumor necrosis factor α (GM-CSF/TGF-β/IL-13/TNF-α)]. In this study, skin DC [LC as Langerin/CD207+ cells and IDDC as DC-specific intercellular adhesion molecule-grabbing nonintegrin (SIGN)/CD209+ cells] displayed desynchronized programs along their differentiation, activation/maturation processes in response to stimuli characteristics of a proinflammatory context. First, we demonstrate that monocytes are able to diverge simultaneously along two distinct pathways toward Langerin+-LC-type DC and DC-SIGN+-IDDC. Second, as TGF-β is known to antagonize the TNF-α-induced maturation process of DC, we showed that IDDC did not mature and acquired a low CC chemokine receptor 7 (CCR7) receptor expression even when stimulated with prolonged incubation with TNF-α. It is striking that the LC subset is able to express a high level of CCR7 expression and the maturation marker DC-lysosome-associated membrane protein (DC-LAMP). Third, mixed LC and IDDC subsets secrete IL-10 and IL-12 when stimulated by CD40 ligand and lipopolysaccharide (LPS) but not after prolonged incubation with TNF-α. In contrast, LPS was a better activator of IL-10 secretion than the CD40 ligand for GM-CSF/IL-4-generated DC and for GM-CSF/TGF-β/IL-13-generated LC and IDDC populations. To summarize, the phenotypic/migratory maturation status of LC may be more easily enhanced by stimuli mimicking a proinflammatory situation, and IDDC are more resistant. Moreover, our culture system provided a means of studying cross-talk between two skin DC outside of their respective skin compartment.

Melanin play a major role in human skin protection and their biosynthesis is vital. Due to their color, they contribute to the skin pigmentation. Tyrosinase is a key enzyme involved in the first stage of melanin synthesis, catalyzing the transformation of tyrosine to l-dopaquinone. The aim of the present study was to study molecules able to inhibit melanin synthesis through inhibition of tyrosinase and their potential use in treating pigmentation-related disorders. We targeted amides obtained from coupling p-hydroxycinnamic acid derivatives with phenylalkylamines. The biological activity was evaluated on human melanocytes by an assay which measures tyrosine-catalyzed L-Dopa oxidation. The most active amides were: trans-N-caffeoyltyramine, N-dihydrocaffeoyltyramine, and trans-N-dihydro-p-hydroxycinnamoyltyramine which induce complete inhibition at 0.1mM. At the latter concentration, kojic acid, which was used as the reference inhibitor, was inactive.

Tyrosinase is a copper-dependent enzyme which converts l- tyrosine to dopaquinone and is involved in different biological processes such as melanogenesis and skin hyperpigmentation. The purpose of this study was to investigate naturally occurring aurones (Z-benzylidenebenzofuran-3(2H)-one) and analogues as human tyrosinase inhibitors. Several aurones bearing hydroxyl groups on A-ring and different substituents on B-ring were synthesized and evaluated as inhibitors of human melanocyte-tyrosinase by an assay which measures tyrosinase-catalyzed l-Dopa oxidation. We found that unsubstituted aurones were weak inhibitors; however, derivatives with two or three hydroxyl groups preferably at 4,6 and 4' positions are able to induce significant tyrosinase inhibition. The most potent aurone was found to be the naturally occurring 4,6,4'-trihydroxyaurone which induces 75% inhibition at 0.1 mM concentration and is highly effective when compared to kojic acid, one of the best tyrosinase inhibitors known so far (the latter is completely inactive at such concentrations). Active aurones are devoid of toxic effects as shown by in vivo studies.

We aimed to quantify ambiguous coronary stenosis using the minimal lumen area with 16-slice computed tomography compared with intravascular ultrasound. The sensitivity, specificity, and accuracy for significant lesion classification was 68%, 86%, and 78%, respectively. The correlation between intravascular ultrasound and CT minimal lumen area was r = 0.73 (p

Raman spectroscopy was used to demonstrate the effects of UV light and oxygen on vitamin A1 (all-trans retinol) in an oily solvent. The retinol concentrations tested were those used in cosmetics. UVA light transformed this retinoid into several derivatives in a few hours. UVA light was more destructive than UVB. A UVA filter protected the active principle and confirmed the damage was due to UVA light. Aeration also accelerated retinol photodegradation, while an antioxidant limited the number of photoproducts detected. Thus retinol photodamage is amplified by oxygen. Raman measurements allow ‘in situ’ observation and identification of these complex processes. The changes in retinol, retinal and anhydrovitamin A concentrations were quantified directly. Retinol was converted to an electrocyclized retinoid (1606 cm−1) and a deconjugated oxidized species (1629.5 cm−1). Little anhydrovitamin A was formed and enough accumulated for the formation of carotene-like species (1527 cm−1). Copyright © 2004 John Wiley & Sons, Ltd.

The inducible epidermal beta-defensins and the chemokine macrophage inflammatory protein-3alpha (MIP-3alpha/CCL20) are important mediators involved in innate and adaptive immunity and in the recruitment of immune cells. The aim of our study was to determine whether calcium could trigger the induction of beta-defensins (hBD-2 and hBD-3) mRNA and the release of MIP-3alpha by normal human keratinocyte monolayers. Epidermal cells derived from foreskin were cultured in defined medium supplemented with different calcium levels (0.09, 0.8 and 1.7 mM) and were stimulated or not with the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha 1-500 ng/ml) or interferon-gamma (INF-gamma 1-100 ng/ml). A high calcium concentration (1.7 mM) alone applied in culture medium for 4 days was sufficient to induce hBD-2 and hBD-3 mRNA expression. Whatever interindividual variability in the expression of hBD-2 and hBD-3 mRNA and MIP-3alpha secretion, the addition of TNF-alpha for a short duration (26h), initiated a dose-dependent and coordinated up-regulation of hBD-2 and hBD-3 mRNA and MIP-3alpha release in keratinocyte cultures. Unlike hBD-2 and hBD-3 mRNA was preferentially stimulated by IFN-gamma rather than TNF-alpha. In our experimental conditions, L-isoleucine, described to stimulate beta-defensin in bovine epithelial cells, did not exert any effect either on hBD-2 and hBD-3 transcripts or MIP-3alpha protein. Taken together, these results confirm the major role of the maturation/differentiation process of normal human keratinocytes in the induction of inducible beta-defensins and MIP-3alpha chemokine, which contribute in vivo to the immunosurveillance of the skin barrier function.

The development of new materials for tissue engineering of skin substitutes requires an increasing knowledge of their interactions with human skin cells. Since carbohydrate recognition is involved in numerous biologic processes, including skin regeneration, the aim of this study was to identify sugar receptors expressed at the surface of human dermic and epidermic cells. Binding of fluorescent sugar-polyhydroxyethylacrylamide derivatives was analyzed by flow cytofluorimetry on cultured human skin fibroblasts, keratinocytes, and melanocytes. We observed that these three cell types express a membrane receptor specific for GlcNAc6S. Since the polysaccharide heparin contains this sugar moiety, we further investigated the interactions of heparin with skin cells. We analyzed the in vitro cell binding and ex vivo diffusion with the Franz cell of heparin and of two other polysaccharides of similar molecular weight, dextran and chondroitin sulfate. We found evidence of the preferential binding of heparin on keratinocytes and its high transcutaneous penetration of skin. Altogether, our results describe the affinity of heparin for human skin cells and suggest it may be an excellent candidate for use in the skin delivery of drugs or cosmetics and also as an active component in engineered skin.

Vitamin A is known to support cell growth promotion, maintenance, and differentiation of epithelial tissues. Retinol is currently used in cosmetic formulations and products to deliver these and other benefits to the skin. However, retinol is known to be unstable and, therefore, remains of great concern to the cosmetic industry. The decomposition pathways of the retinoids in general have been previously postulated and investigated mostly by high-performance liquid chromatography (HPLC) with UV/Vis spectroscopy. In our studies, we examined specific conditions at which retinol degrades and subsequently identified and quantified the products of retinol decomposition by Raman spectroscopy. We reveal which experimental settings and computational tools allow monitoring of in situ evolution of an all-trans retinol solution when submitted to UV light in the presence of oxygen.

Background: GM-CSF, IL-4 and TGF-β1 can drive the differentiation of CD14+ monocytes towards the immature Langerhans (LC) dendritic cell (DC) pathway. Their in vivo epidermal LC counterparts are mainly identified by the langerin molecules which are cross-linked into Birbeck granules (BG) upon mannose residue activation. Objective: The IL-13 and IL-14 cytokines sharing similar anti-inflammatory/immune functions, we investigated whether IL-13 (plus GM-CSF/TGF-β1) can substitute for IL-4 to preferentially skew the CD14+ monocyte differentiation towards LC. Methods: CD14+ monocytes cultured in the presence of GM-CSF/TGF-β1/IL-13 (IL-13-DC) for 6 days were then compared to GM-CSF/TGF-β1/IL-4-generated LC (IL-4-DC) by studying their phenotype, ultrastructural and functional features. Results: IL-13, in synergy with GM-CSF/TGF-β1, induced CD14+ monocytes to differentiate into LC after a short TNF-α stimulation more efficiently than IL-4. IL-13-DC are more immature than IL- 4-DC, as shown by both their preserved expression of monocyte markers (CD14, CD68) and their strong capacity of FITC-dextran uptake. Conclusion: IL-13 in combination with GM-CSF/TGF-β1/TNF-α favors CD14+ monocyte differentiation into LC which display numerous BG.

Background To assess the prevalence, the appearance, and the distribution, as well as the fluctuation over time of early repolarization patterns after four years in a female population derived from the French aviation sector. Methods This was a retrospective longitudinal study from 1998 to 2010 of a population of female employees who received a full clinical examination and an electrocardiogram (ECG) upon their recruitment and after a period of four years. Results A total of 306 women were included (average of 25.87 ± 3.3 years of age). The prevalence of early repolarization was 9.2%. The most common appearance was J-point slurring for 64.3% (i.e. 20/28 subjects) that occurred in the inferior leads for 28.6% (i.e. 8/28 subjects). After four years, the prevalence was 7.5%, with a regression of this aspect in five of the subjects. There were no changes in the ECG in terms of the distribution and the appearance among the 23 subjects for whom the aspect persisted. Over the course of this four year period all of the subjects remained asymptomatic. Conclusions Early repolarization in this largely physically inactive female population was common, and it fluctuated over time. At present, no particular restrictions can be placed on asymptomatic flight crew who exhibit this feature in the absence of a prior medical history for heart disease.

BACKGROUND: During an aircraft ejection, the pilot is exposed to accelerations to the point of human tolerance, which may cause spinal injuries. Many nations have reported a spinal trauma rate of about 20-30%, with plain radiography as the first-line exam. Insofar as ejection seats and diagnostic imaging have improved, the objectives of this study are to describe the spine injuries among recently ejected French aircrew, to analyze the spinal imaging used, and, if necessary, to propose a better standardized radiological procedure. METHODS: A retrospective cohort study included all aircrews of the French forces who ejected from 2000 to 2008, with an authorized access to the technical reports of the investigations. RESULTS: There were 36 ejections collected, 75% with an MK-10 seat and an arrival on dry land. All pilots were alive, but 42% of them sustained 24 spinal fractures, most of the time with a simple compression of the thoracic segment, but also 4 ligamentous or discal lesions. Computed tomography or RMI was used in 64% of cases and four fractures were missed or underestimated on X-ray. One complex fracture required surgical treatment. A return to flying duties was frequently possible within a period of 6 mo. CONCLUSIONS: New generation ejection seats remain highly traumatic for the spine. It is recommended that all ejected aircrews be assessed with computed tomography to improve the sensitivity of the screening for fractures. The risk of asymptomatic lesions makes necessary the systematic use of a stretcher for initial evacuation when possible. Language: en

The European Community directive, imposing that effects claimed for cosmetic actives must be validated using non-animal procedures, has stimulated the use of in vitro models for pharmacotoxicological trials. In this paper, an efficacy study of a new biopeptide, a hydrolysate obtained by fermentation of milk proteins, was performed using an in vitro skin equivalent (SE). This SE is obtained by seeding normal human keratinocytes onto a dermal equivalent comprising a collagen-glycosaminoglycan(GAG)-chitosan porous matrix populated by normal human fibroblasts, which neosynthesize their own extracellular matrix (ECM). A gel containing 2% milk biopeptide was applied topically (10 microliters) every 2 days during 15 days. Subsequent investigations of the biopeptide effects were based on morphological criteria after histological analysis and on synthesis of ECM components. Collagen and GAG synthesis were measured by tritiated proline, glucosamine and Na2(35)SO4 incorporation. Qualitatively, the histological features of the biopeptide-treated SEs showed a thicker epidermis than the untreated control SEs, where only a few layers of stratum corneum were observed. The dermal porous matrix seems to be more filled by neosynthesized ECM than the control. Quantitatively, milk biopeptide treatment induced a significant activation of hyaluronic acid (+46%) and sulfated GAG (+53%) synthesis, whereas only non-significant increases of total protein and collagen synthesis were observed (Student's test, p < 0.001).The European Community directive, imposing that effects claimed for cosmetic actives must be validated using non-animal procedures, has stimulated the use of in vitro models for pharmacotoxicological trials. In this paper, an efficacy study of a new biopeptide, a hydrolysate obtained by fermentation of milk proteins, was performed using an in vitro skin equivalent (SE). This SE is obtained by seeding normal human keratinocytes onto a dermal equivalent comprising a collagen-glycosaminoglycan(GAG)-chitosan porous matrix populated by normal human fibroblasts, which neosynthesize their own extracellular matrix (ECM). A gel containing 2% milk biopeptide was applied topically (10 microliters) every 2 days during 15 days. Subsequent investigations of the biopeptide effects were based on morphological criteria after histological analysis and on synthesis of ECM components. Collagen and GAG synthesis were measured by tritiated proline, glucosamine and Na2(35)SO4 incorporation. Qualitatively, the histological features of the biopeptide-treated SEs showed a thicker epidermis than the untreated control SEs, where only a few layers of stratum corneum were observed. The dermal porous matrix seems to be more filled by neosynthesized ECM than the control. Quantitatively, milk biopeptide treatment induced a significant activation of hyaluronic acid (+46%) and sulfated GAG (+53%) synthesis, whereas only non-significant increases of total protein and collagen synthesis were observed (Student's test, p < 0.001).

Human cysteine cathepsin S (catS) participates in distinct physiological and pathophysiological cellular processes and is considered as a valuable therapeutic target in autoimmune diseases, cancer, atherosclerosis, and asthma. We evaluated the capacity of negatively charged glycosaminoglycans (heparin, heparan sulfate, chondroitin 4/6-sulfates, dermatan sulfate, and hyaluronic acid) to modulate the activity of catS. Chondroitin 4-sulfate (C4-S) impaired the collagenolytic activity (type IV collagen) and inhibited the peptidase activity (Z-Phe-Arg-AMC) of catS at pH 5.5, obeying a mixed-type mechanism (estimated Ki = 16.5 ± 6 μM). Addition of NaCl restored catS activity, supporting the idea that electrostatic interactions are primarly involved. Furthermore, C4-S delayed in a dose-dependent manner the maturation of procatS at pH 4.0 by interfering with the intermolecular processing pathway. Binding of C4-S to catS was demonstrated by gel-filtration chromatography, and its affinity was measured by surface plasmon resonance (equilibrium dissociation constant Kd = 210 ± 40 nM). Moreover, C4-S induced subtle conformational changes in mature catS as observed by intrinsic fluorescence spectroscopy analysis. Molecular docking predicted three specific binding sites on catS for C4-S that are different from those found in the crystal structure of the cathepsin K-C4-S complex. Overall, these results describe a novel glycosaminoglycan-mediated mechanism of catS inhibition and suggest that C4-S may modulate the collagenase activity of catS in vivo.

Cutaneous aging translates drastic structural and functional alterations in the extracellular matrix (ECM). Multiple mechanisms are involved, including changes in protease levels. We investigated the age-related protein expression and activity of cysteine cathepsins and the expression of two endogenous protein inhibitors in young and aged Caucasian women skin epidermis. Immunofluorescence studies indicate that the expression of cathepsins K, S and V, as well as cystatins A and M/E within keratinocytes is reduced in photoprotected skin of aged women. Furthermore, the overall endopeptidase activity of cysteine cathepsins in epidermis lysates decreased with age. Albeit dermal elastic fiber and laminin expression is reduced in aged skin, staining of nidogen-1, a key protein in BM assembly that is sensitive to proteolysis by cysteine, metallo- and serine proteases, has a similar pattern in both young and aged skin. Since cathepsins contribute to the hydrolysis and turnover of ECM/basement membrane components, the abnormal protein degradation and deposition during aging process may be related in part to a decline of lysosomal/endosomal cathepsin K, S and V activity.

In female, the prevalence of ER is lower but reported variously and has been poorly studied in aeronautical medicine. Our study described and evaluated the prevalence and long-term (4 years) evolution of ECG ER pattern in the female population of the French aeronautical staff. This is a retrospective single-center study, conducted over a period of 12 years (1998-2010) at the Centre of Medical Expertise in Navigant Personnel of Hospital of Percy, Clamart, France. The study was conducted from clinical data and through the systematic recording of ECG on a digital database (TRACE MASTER VIEW – PHILIPS ©). The study population included asymptomatic subjects aged >18 years and with no cardiovascular disease. An initial ECG (P1) was recorded in all patients at incorporation and a second 4 years later (P2). ECG were interpreted by 2 cardiologists. The presence of ER is rated “ER+” and its absence “ER-”. On each ECG were recorded: the heart rate (HR), the Sokolow-Lyon index and the corrected QT (QTc) interval. The study population included 306 women. The majority was stewardess (in 95.1% of cases; mean age 25.9±3.3 years). Only 170 subjects (56%) practiced sports up to one hour per week. At P1: PR + prevalence was 9.2%. The most common pattern was “slurring” in 64.3% of cases, in the inferior leads (28.3%). The ST segment is horizontal or descending in 53.6% of patients. At P2, the prevalence of RP+ was 7.5% (a loss of RP+ in 5 patients). At P1, the Sokolw-Lyon index was higher in RP+ patients (p The author hereby declares no conflict of interest

Application of hormesis in aging research and interventions is becoming increasingly attractive and successful. The reason for this is the realization that mild stress-induced activation of one or more stress response (SR) pathways, and its consequent stimulation of repair mechanisms, is effective in reducing the age-related accumulation of molecular damage. For example, repeated heat stress-induced synthesis of heat shock proteins has been shown to have a variety of anti-aging effects on growth and other cellular and biochemical characteristics of normal human skin fibroblasts, keratinocytes and endothelial cells undergoing aging in vitro. Therefore, searching for potential hormetins - conditions and compounds eliciting SR-mediated hormesis - is drawing attention of not only the researchers but also the industry involved in developing healthcare products, including nutriceuticals, functional foods and cosmeceuticals. Here we present the example of a skin care cosmetic as one of the first successful product developments incorporating the ideas of hormesis. This was based on the studies to analyse the molecular effects of active ingredients extracted from the roots of the Chinese herb Sanchi (Panax notoginseng) on gene expression at the level of mRNAs and proteins in human skin cells. The results showed that the ginsenosides extracted from Sanchi induced the transcription of stress genes and increased the synthesis of stress proteins, especially the heat shock protein HSP1A1 or Hsp70, in normal human keratinocytes and dermal fibroblasts. Furthermore, this extract also has significant positive effects against facial wrinkles and other symptoms of facial skin aging as tested clinically, which may be due to its hormetic mode of action by stress-induced synthesis of chaperones involved in protein repair and removal of abnormal proteins. Acceptance of such a hormesis-based product by the wider public could be instrumental in the social recognition of the concept of hormesis as the beneficial effects of mild stress of choice, and will encourage the development of novel health care products with physical, nutritional and mental hormetins.

International audience; Neurotrophins (NTs) belong to a family of growth factors that play a critical role in the control of skin homeostasis. NTs act through the low-affinity receptor p75NTR and the high-affinity receptors TrkA, TrkB, and TrkC. Here we show that dermal fibroblasts (DF) and myofibroblasts (DM) synthesize and secrete all NTs and express NT receptors. NTs induce differentiation of DF into DM, as shown by the expression of α-SMA protein. The Trk inhibitor K252a, TrkA/Fc, TrkB/Fc, or TrkC/Fc chimera prevents DF and DM proliferation. In addition, p75NTR siRNA inhibits DF proliferation, indicating that both NT receptors mediate DF proliferation induced by endogenous NTs. Autocrine NTs also induce DF migration through p75NTR and Trk, as either silencing of p75NTR or Trk/Fc chimeras prevent this effect, in absence of exogenous NTs. Finally, NGF or BDNF statistically increase the tensile strength in a dose dependent manner, as measured in a collagen gel through the GlaSbox device. Taken together, these results indicate that NTs exert a critical role on fibroblast and could be involved in tissue re-modeling and wound healing.

Optimal search on Bayesian network structure is known as an NP-hard problem and the applicability of existing optimal algorithms is limited in small Bayesian networks with 30 nodes or so. To learn larger Bayesian networks from observational data, some heuristic algorithms were used, but only a local optimal structure is found and its accuracy is not high in many cases. In this paper, we review optimal search algorithms in a constraint search space; The skeleton of the learned Bayesian network is a sub-graph of the given undirected graph called super-structure. The introduced optimal search algorithm can learn Bayesian networks with several hundreds of nodes when the degree of super-structure is around four. Numerical experiments indicate that constraint optimal search outperforms state-of-the-art heuristic algorithms in terms of accuracy, even if the super-structure is also learned by data.

Transfer of the melanocyte-specific and lysosome-related organelle, the melanosome, from melanocytes to keratinocytes is crucial for the protection of the skin against harmful ultraviolet radiation (UVR)--our main physiological cutaneous stressor. However, this commonplace event remains a most enigmatic process despite several early hypotheses. Recently, we and others have proposed a role for filopodia in melanin transfer, although conclusive experimental proof remained elusive. Using known filopodial markers (MyoX/Cdc42) and the filopodial disrupter, low-dose cytochalasin-B, we demonstrate here a requirement for filopodia in melanosome transfer from melanocytes to keratinocytes and also, unexpectedly, between keratinocytes. Melanin distribution throughout the skin represents the key phenotypic event in skin pigmentation. Melanocyte filopodia were also necessary for UVR-stimulated melanosome transfer, as this was also inhibited by MyoX knockdown and low-dose cytochalasin-B. Knockdown of keratinocyte MyoX protein, in its capacity as a phagocytosis effector, resulted in the inhibition of melanin uptake by keratinocytes. This indicates a central role for phagocytosis by keratinocytes of melanocyte filopodia. In summary, we propose a new model for the regulation of pigmentation in human skin cells under both constitutive and facultative (post-UVR) conditions, which we call the "filopodial-phagocytosis model." This model also provides a unique and highly accessible way to study lysosome-related organelle movement between mammalian cells.

Venous thromboembolism (VTE) remains a great challenge because of its frequency and of its potential severity. However, VTE treatment can also lead to iatrogenic complications. We report a case of thigh haematoma by a 83-year-old woman under fondaparinux for a solear thrombosis. Then we discuss the indications of Unfractionated Heparin (UFH), Low-Molecular-Weight Heparins (LMWH) and Fondaparinux, which are the three classes of rapidly acting anticoagulant treatments nowadays available. As their efficacy is comparable, the choice between these classes relies on the risk of adverse effects, which depends on some patient’s characteristics. LMWH and fondaparinux are contra-indicated by the patients with a renal clearance under 30 ml/min. Only UFH are authorised during the whole pregnancy even though LMWH are more and more used. Fondaparinux has proven its safety by patients over 100 kg. UFH requires a daily biological management whereas it is optional for LMWH and fondaparinux, as long as their contra-indications are taken into account. No Heparin-induced-thrombocytopenia Syndrome (HIT-Sd) has been proven yet under fondaparinux so that platelets management seems not necessary, contrary to UFH and LMWH which require a twice-weekly platelets count. The accuracy of the therapeutic indication should result in the best benefit/risk assessment.

Several aquaporins (AQPs) are expressed in mammalian skin. Some are directly involved in water transport, such as AQP5, which is involved in sweat secretion. In contrast, the physiological role of skin aquaglyceroporins, which permeate both water and glycerol, appears more and more complex. AQP3 is the most abundant skin aquaglyceroporin. Both water and glycerol transport by AQP3 appear to play an important role in hydration of mammalian skin epidermis. In addition, recent data suggest that glycerol transport by AQP3 is involved in the metabolism of lipids in skin as well as in the regulation of proliferation and differentiation of keratinocytes. Finally, AQP3 is also believed to be important in wound healing, as a water channel by facilitating cell migration, and as a glycerol transporter by enhancing keratinocyte proliferation and differentiation.

Several aquaporins (AQPs) are expressed in mammalian skin. Some are directly involved in water transport, such as AQP5, which is involved in sweat secretion. In contrast, the physiological role of skin aquaglyceroporins, which permeate both water and glycerol, appears more and more complex. AQP3 is the most abundant skin aquaglyceroporin. Both water and glycerol transport by AQP3 appear to play an important role in hydration of mammalian skin epidermis. In addition, recent data suggest that glycerol transport by AQP3 is involved in the metabolism of lipids in skin as well as in the regulation of proliferation and differentiation of keratinocytes. Finally, AQP3 is also believed to be important in wound healing, as a water channel by facilitating cell migration, and as a glycerol transporter by enhancing keratinocyte proliferation and differentiation.

The aim of this study was to prospectively evaluate the diagnostic accuracy for neurocardiogenic syncopes (NCS) of two Head-Up Tilt table test (HUT) strategies in 991 patients with syncopes/presyncopes of unknown aetiology after negative clinical and non invasive investigations. HUT is a widely accepted tool in the evaluation of patients with evidence of VVS but questions remain about the sensitivity and the use of provocative agents.Clomipramine (CP), a serotonin re-uptake inhibitor, was recently proposed as a new drug challenge test for the diagnosis of neurocardiogenic syncope (NCS). Group A : the first 341 pts (207 male ; mean age = 49,9 ± 23 years) were passively tilted at 60° for 30 minutes (min), then for 15 min with 2 μg/min isoproterenol infusion rate. Group B : the following 650 pts (383 male ; mean age = 48,3 ± 21 years) were tilted at 60° for 20 min with 5 mg CP infused during the first 5 min of tilt. A positive HUT was defined as reproducting the patient’s syncope or presyncope, associated with an abrupt fall in blood pressure (systolic blood pressure

Exposure of human skin to solar ultraviolet (UV) light induces local and systemic immune suppression. It is known that alterations of immune functions of Langerhans cells (LCs) and dermal dendritic cells (DDCs) mediate this phenomenon. The purpose of this study was to mimic in vitro the early UV-induced skin disruption to better understand the involvement of the skin micro-environment in triggering this immunosuppressive state. We therefore developed skin equivalents (SEs) integrating LCs and DDCs derived from monocytes (mo-LCs and mo-DDCs, respectively). First, we showed that Langerin(+) mo-LC and dendritic cell (DC)-specific ICAM-3 grabbing nonintegrin (SIGN)(+) mo-DDCs were immunolocalized in situ in epidermal and dermal compartments of SEs, respectively. The SE micro-environment without immune cells displayed full cytokine profile that may ensure and maintain differentiation, localization, and immaturity of LCs and DDCs in situ, as shown by secretion of granulocyte-macrophage colony-stimulating factor, transforming growth factor beta (beta)-1, interleukin (IL)-4, IL-13, and IL-15 involved in cell differentiation; presence of complete chemokine network as macrophage inflammatory protein 3 alpha (alpha); low secretion of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha), IL-1 beta, IL-6, and IL-8; and surprising secretion of immunosuppresive cytokine IL-10. Second, we demonstrated that skin micro-environment homeostasis was greatly disrupted under solar UV irradiation of SEs. In fact, we showed a pro-inflammatory state characterized by high secretion of TNF-alpha, IL-1 beta, IL-6, and IL-8 and low secretion of IL-10. This breakdown of immune homeostasis was visualized at the same time as in situ migration of mo-LCs and mo-DDCs into the dermal equivalent of SEs. Moreover, this tissue migration of mo-LCs and mo-DDCs into SEs was in accordance with the chemokine (C-C motif) receptor 7 expression and the DC-lysosome-associated membrane glycoprotein acquisition only on mo-LCs. Our results highlighted major participation of the skin micro-environment in the triggering and modulating of UV-induced skin immune responses. In addition, it could be concluded that these SEs are reliable tools for modeling biological events inaccessible in humans.Exposure of human skin to solar ultraviolet (UV) light induces local and systemic immune suppression. It is known that alterations of immune functions of Langerhans cells (LCs) and dermal dendritic cells (DDCs) mediate this phenomenon. The purpose of this study was to mimic in vitro the early UV-induced skin disruption to better understand the involvement of the skin micro-environment in triggering this immunosuppressive state. We therefore developed skin equivalents (SEs) integrating LCs and DDCs derived from monocytes (mo-LCs and mo-DDCs, respectively). First, we showed that Langerin(+) mo-LC and dendritic cell (DC)-specific ICAM-3 grabbing nonintegrin (SIGN)(+) mo-DDCs were immunolocalized in situ in epidermal and dermal compartments of SEs, respectively. The SE micro-environment without immune cells displayed full cytokine profile that may ensure and maintain differentiation, localization, and immaturity of LCs and DDCs in situ, as shown by secretion of granulocyte-macrophage colony-stimulating factor, transforming growth factor beta (beta)-1, interleukin (IL)-4, IL-13, and IL-15 involved in cell differentiation; presence of complete chemokine network as macrophage inflammatory protein 3 alpha (alpha); low secretion of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha), IL-1 beta, IL-6, and IL-8; and surprising secretion of immunosuppresive cytokine IL-10. Second, we demonstrated that skin micro-environment homeostasis was greatly disrupted under solar UV irradiation of SEs. In fact, we showed a pro-inflammatory state characterized by high secretion of TNF-alpha, IL-1 beta, IL-6, and IL-8 and low secretion of IL-10. This breakdown of immune homeostasis was visualized at the same time as in situ migration of mo-LCs and mo-DDCs into the dermal equivalent of SEs. Moreover, this tissue migration of mo-LCs and mo-DDCs into SEs was in accordance with the chemokine (C-C motif) receptor 7 expression and the DC-lysosome-associated membrane glycoprotein acquisition only on mo-LCs. Our results highlighted major participation of the skin micro-environment in the triggering and modulating of UV-induced skin immune responses. In addition, it could be concluded that these SEs are reliable tools for modeling biological events inaccessible in humans.

[corrected] The signs of aging may originate from natural processes or from exposure to the sun, wind, or other environmental factors. To evaluate the anti-aging effects of potential agents researchers must first identify and be able to quantify epidermal markers that change with aging. This paper summarizes the results of studies conducted to evaluate the transcriptional effects of an Aframomum angustifolium seed extract and Malva Sylvestris extract, and the antiaging efficacy of a skin care product containing the Aframomum angustifolium seed extract.The transcriptional effect of an Aframomum angustifolium seed extract on normal human keratinocytes (NHKs) and normal human fibroblasts (NHF) was evaluated in vitro with the use of a low-density DNA array technology. The Malva Sylvestris extract was studied with a commercial DNA macroarray and by a real-time quantitative reverse transcriptase-polymerase chain reaction. The in vitro anti-aging activities of the Malva sylvestris extract were compared with those of all-trans retinoic acid (RA), a well-established topical therapy for photodamage and wrinkles. The genes studied were known to be modified by RA. The anti-aging efficacy of a facial skin care product containing Aframomum angustifolium seed extract was evaluated in a single-center study using image processing analysis and in a 2-center study by evaluation of the photographs by the investigator, independent evaluators, and subjects.In general, the Aframomum angustifolium seed extract strongly modified the gene expression profiles of NHKs and weakly modified the gene expression profiles of NHFs. After incubation with Aframomum angustifolium seed extract, the expressions of 3 antioxidant genes (metallothionein 1, metallothionein 2, and thioredoxin) were increased in NHKs, while expressions of 1 antioxidant gene (glutathione peroxidase) was increased in NHFs. Concerning the Malva sylvestris extract, a cDNA macro-array technology experiment with the reconstructed human epidermis model showed that some genes modulated by treatment with the Malva sylvestris extract are also regulated by RA treatment indicating a similar activity at the mRNA level. In the single-center study, a facial skin care product containing the Aframomum angustifolium seed extract significantly improved the homogeneity of the skin. The areas of the detected objects (skin imperfections) decreased significantly on each studied area of the face and the variance decreased significantly over the entire face. In the 2-center study, 28% percent of the subjects reported a greater than 50% overall global improvement in their skin by the end of the study compared to 11% of the subjects after 4 weeks of treatment. Seventy-six percent of subjects said they would purchase the cream.The authors developed a low-density DNA chip method that permitted the study of the transcriptional effect of Malva Sylvestris extract and of Aframomum angustrifolium seed extract. The gene expression profiles obtained demonstrate the anti-aging properties of these compounds. An in vivo single-center study, performed and analyzed with an assay based on image processing analysis, demonstrated the antiwrinkle activity of a formulation containing the Aframomum angustifolium seed extract. The data obtained in the 2-center study suggests that the cosmeceutical containing Aframomum angustifolium seed extract produces a global rejuvenation effect in terms of redness, pigmentation, and fine lines similar to that noted utilizing an intense pulse light source.

Skin without significant dyschromia is an aesthetic goal of people worldwide. Current options for lightening skin could have significant drawbacks. The antisense strategy may be a viable alternative. The reactions in melanogenesis are catalyzed mainly by tyrosinase, tyrosinase-related protein 1 (TRP-1), and TRP-2. Activation of tyrosinase is associated with phosphorylation by protein kinase C-betaI (PKC-betaI) and formation of a complex between phosphorylated tyrosinase and TRP-1. The aim of this study was to use 2 antisense oligonucleotides to modulate the synthesis of the tyrosinase/TRP-1 complex, PKC-beta, or both by interacting with the targeted mRNA, thus whitening skin by interfering with melanogenesis at the translational level.In the in vitro study, the effect of the antisense oligonucleotides was evaluated by measuring the rate at which dihydroxyphenylalanine (DOPA) oxidase transforms L-DOPA to DOPAchrome in the pathway for melanin biosynthesis. A reduction in the reaction rate compared to the controls corresponded to a decrease in the enzyme activity and, consequently, to a reduction of the formation of melanin pigments. To evaluate the in vivo lightening effect of the antisense oligonucleotides, 30 Asian women volunteers with pigmented spots on both hands applied the test product twice daily for 8 weeks. The test product was applied to 2 marked-off areas of the hand: a pigmented spot (to evaluate the effect of the test product on the color of the spot) and a nonpigmented spot area (to evaluate the effect of the test product on normal skin pigmentation). The lightening effect was evaluated by comparing chromametric and mexametric parameters before treatment, after 4 weeks, and after 8 weeks.In vitro DOPA-oxidase activity was inhibited by 13% in melanocytes treated with the antisense sequence for PKC-BI alone, by 16% with the antisense sequence for TRP-1 alone, and by 36% with the association of 2 sequences. The inhibiting effect with both sequences required the specific sequences with nonreversed polarities. In vivo clinical results showed statistically significant whitening in both pigmented spots and nonpigmented spots when the test product was applied twice daily for 8 weeks by up to 30 Asian women.The association of TRP-1 and PKC-betaI antisense molecules significantly increased the inhibition of tyrosinase activity on human melanocytes. Antisense oligonucleotides are a new generation of active cosmetic ingredients that offer unprecedented specificity, biological stability, and safety in lightening skin. This is the first report of positive results in a cosmetic based on the use of these new active agents.

Ultraviolet (UV) light produces reactive oxygen species (ROS) in skin, which accelerate aging by damaging DNA, proteins, lipids, and other cellular constituents. The aims of this study were to 1) evaluate the antioxidant properties of a Vitis vinifera shoot extract on cultured normal human keratinocytes, 2) compare the in vivo antioxidant of this extract in combination with a biotechnological extract (Ronacare Hydroine), and 3) evaluate the efficacy on photoaging skin of a serum based on a combination (Vitis vinifera shoot extract in hydroglycolic solution, or Sarmentine, and Ronacare Hydroine) after a 4-week application, and to quantify the additional improvement given by applying a cream with the serum.An in vitro study was conducted to evaluate the antioxidant properties of Vitis vinifera shoot extract added to cultured normal human keratinocytes. A fluorescent probe was used to quantify cytoplasmic endogenous species formed in response to oxidative stress induced by H2O2. The antioxidant activity of Vitis vinifera shoot extract was compared to that of a solvent control and 2 positive controls, vitamin E and vitamin C. In the first in vivo study, 2 test products were included in a comparative, randomized, single-blind trial in which 27 subjects acted as their own (untreated) controls. Products were applied 4 times to randomized areas of the inner surface of the forearm for one day. The following day, treated and untreated (control) areas of stratum corneum were sampled for fluorimetric analysis. A decrease in fluorescence compared with untreated control reflected a decrease in the level of ROS, in which case the product had a scavenging effect. The 2 products contained a combination of Sarmentine and Ronacare Hydroine, whose antioxidant properties were under investigation. Other products were known antioxidants. In the second in vivo study, 60 female subjects applied either serum or serum plus cream twice daily for 28 days for clinical evaluation. Overall improvement was rated on a quartile scale (0%-25%, 26%-50%, 51%-75%, 76%-100%) and changes in firmness, radiant glow, evenness, smoothness, wrinkles, fine lines, hydration, texture, and softness were rated on a negative to positive scale (-5=worse to +5=greatly improved).Vitis vinifera shoot extract appears to have significantly stronger in vitro antioxidant capacity than vitamin C or vitamin E. In the same vehicle (placebo emulsion), ascorbic acid (0.5%), Sarmentine (1%), and the Sarmentine (1%) plus Ronacare Hydroine (1%) combination had a significant in vivo antioxidant effect versus a nontreated area. The combination Sarmentine (1%) plus Ronacare Hydroine (1%) showed a higher efficacy than Sarmentine alone. The dermatologic evaluation showed that a 4-week twice-daily application of a serum containing the combination improved the main clinical signs of photoaged skin. The addition of the cream with the serum appears to enhance the serum-induced improvement of most of the skin characteristics.