Biomedical subjects
Publications and source records attributed to J L Leveque.
We have improved the optical interferometric imaging technique that was recently used to measure local organic material concentrations in quasicylindrical cells. This allowed similar measurements for cells of arbitrary shape. The setup was used to measure the thickness of skin corneocytes.
BACKGROUND: Few studies have attempted to quantitatively assess in vivo changes in the microvasculature with age. OBJECTIVE: The objective was to assess in vivo structural and functional changes in the cutaneous microvasculature with aging and to analyze the contribution of the microvasculature to skin color. METHODS: Video capillaroscopy, in conjunction with fluorescein angiography, and laser-Doppler flowmetry were used to compare elderly and young normal volunteers. Skin color differences were assessed with a handheld color reflectance meter. A photoexposed site, the forehead, and the relatively photoprotected ventral forearm were studied to differentiate photoaging from chronologic aging. RESULTS: Dermal papillary loops were significantly reduced in old skin compared with young skin (forehead by 40%; forearm by 37%). Horizontal vessels showed increased volume fraction in elderly forehead and forearm skin. Laser-Doppler studies demonstrated no significant differences between young and old skin; indeed, hyperemic responsiveness appeared more rapid in the elderly. Color measurements showed elderly skin, particularly in men, to be significantly darker and redder. CONCLUSION: A marked loss in dermal nutritional vessel density and surface area for exchange is a feature of both chronologic aging and photoaging.
The cumulative and comparative effects of chronological and actinic changes to the skin were studied in an elderly population. Two adjacent sites with different degrees of exposure to the sun were examined to distinguish the contribution of each factor, by means of noninvasive measurements. The following parameters were measured on the skin of the low neck (an exposed site), as well as on the adjacent clothes-protected skin of 30 elderly women: electrical conductance, color, microrelief, biomechanical properties and the thickness of both the full skin and the subepidermal nonechogenic band (SENEB), using ultrasound measurements. Persistent exposure to the sun accentuated most of the age-induced modifications. The following changes were significantly more marked in exposed skin: SENEB thickening, full-skin thinning, loss of extensibility and elasticity, and color heterogeneity. The cumulative effects of sun exposure and chronological aging lead to atrophy in elderly people. These results suggest that, if there is an autoprotective skin reaction, such as thickening in young adults, it is eliminated in old people.
Real-time confocal microscopy has brought substantial improvements to the imaging of the human skin in vivo. On early images, the stratum corneum could be distinguished from the living epidermis and the circulatory network of the superficial dermis. We have adapted the Tandem Scanning Microscope to obtain images of the living skin, showing thinner structures such as the stratum lucidum and the dermo-epidermal junction, both of which are essential markers for micron-order measurements of the thickness of the stratum corneum and living epidermis. The measurements were corrected for the differences in the refractive index of the various cutaneous layers, and the undulation of the dermo-epidermal junction. Furthermore, nucleus size and number could be assessed from horizontal optical sections. To illustrate the sensitivity of the thickness measurements, changes in the thickness of the epidermis were recorded during and after stripping of the horny layers. This non-invasive methodology is a very promising tool for morphometric studies of the living human skin at the cellular level.
The age-related modifications of magnetic resonance imaging parameters in the skin have been studied in vivo. Modification of these parameters should provide important information about alterations in water structure and content in aged skin. Relaxation times, T1 and T2, and relative proton density, which corresponds to the mobile water proton fraction of tissues, have been measured on people under age 40 and over 70 on a sun-protected area. Results have confirmed in vivo skin layer differentiation through relaxation times performed in a previous study. Moreover, relative proton density quantification has shown that epidermal mobile water is at least twice as abundant as dermal mobile water. No significant age-related T1 and T2 modification could be established, basically because of a large dispersion of values. The main result concerns the upper part of dermis (about 200 microns in thickness) which contains significantly more mobile water protons in chronologic aged skin than in young adult skin. This increase has been related both to an increase of total water content in dermis with age and to an apparent decrease of collagen and proteoglycan content. Associated with alterations of their structure, this decrease reduces macromolecular-water interaction sites. This finding has to be compared with ultrasound evaluation of aged skin, which is characterized by modifications of the echogenicity, related to collagen bundles size and density, in the outer part of dermis, too. Both of the imaging techniques tend to consider the outer part of dermis as one of the privileged sites of skin aging.
The physical properties of the skin were measured by using noninvasive methods on 72 people displaying various levels of solar elastosis on the neck. The physical parameters measured were the skin extensibility, the elastic recovery, the skin colour, the skin thickness and the electrical conductance. The correlation between the above parameters, the clinical grades of elastosis and the chronological age of each subject were studied using two different statistical approaches. They both showed that elastotic skin is less elastic, dryer, darker, more erythematous and less yellowish than the nonexposed skin. The similarities and differences between the properties of elastotic skin and purely chronologically aged skin are discussed.
The role of race in modulating skin responses has been investigated. Several parameters (skin thickness, transepidermal water loss, water content of the stratum corneum and skin biomechanics) have been measured using noninvasive tools in whites, Hispanics and blacks to assess whether the melanin content could induce changes in skin biophysical properties. Marked differences between races appear in stratum corneum water content and in skin extensibility, recovery and elastic modulus. Measurements done in different sun-exposed sites highlight the effects of solar irradiation on the skin and the role of melanin in preventing skin damage. The study shows that racial differences in skin physiology exist and are mainly related to the protective role of melanin present in races with darker skin. Moreover, differences in skin hydration are not fully explained according to the site and presence of hair.
High-resolution magnetic resonance (MR) images of the skin were acquired with a whole-body MR system at 1.5 T by adding a specific imaging module: A saddle-shaped surface gradient coil was connected in place of one of the gradient coils of the system, and a surface radio-frequency coil with a 1.5-cm radius was placed at the center of the gradient coil. The images, acquired in 3 minutes 25 seconds, represent a field of view of 18 x 50 mm2, which corresponds to a pixel size of 70 x 390 micro2; the section thickness was 1.2 mm. With this spatial resolution, the different layers of the skin are clearly delineated: Epidermis appears as a high-signal-intensity layer, while dermis appears hypointense due to its very short T2. Pilosebaceous units appear as inclusions of epidermis inside dermis. The high quality of the images obtained enables in vivo MR characterization of skin.
Changes in the composition of human stratum corneum lipids (SCL) were studied at various times after an induced inflammatory reaction. Three kinds of injury were inflicted: 3 MED of ultraviolet radiation, 3 MED of solar radiation or 30 strippings of the horny layer with plastic tape. The SCL were evaluated qualitatively and quantitatively at short intervals. Marked changes in the SCL were detected between the 9th and the 11th day. With all 3 insults, the SCL increased quantitatively and showed a more polar pattern, i.e. a decrease in neutral fractions and an increase in the polar ones. These changes were synchronous with the marked shedding which occurs between the 9th and the 11th day. These findings have implications for the role of lipids in stratum corneum cohesiveness.
Images of the hamster flank organ were obtained in vivo by high resolution ultrasound (B-scan). The planimetric measurements of the ultrasonic image that determined the size of the flank organ, with a reproducibility of about 10%, highly correlated with the measurements of histological sections. This new method provides a simple and non-invasive method for determining the size of the hamster flank organ after various treatments which does not involve the killing of the animal under investigation.
A new non-invasive technique for assessing the efficacy of topical non-steroidal anti-inflammatory drugs (NSAID) in man is proposed. The NSAID are initially applied to the skin under occlusion before inflammation is induced by a methyl nicotinate solution. The inflammatory response is quantified in terms of cutaneous blood flow by a laser Doppler velocimeter (LDV). The efficacy of NSAID preparations is calculated by comparing the responses of the LDV to the methyl nicotinate challenge on the pretreated and the non-treated skin sites. This protocol has been used to investigate the effect of three different NSAID preparations (indomethacin, niflumic acid, palmitoyl collagenic acid) and the influence of the vehicle on the efficacy of indomethacin. The three preparations tested gave positive results but with different amplitudes in response. The efficacy of indomethacin varied with the vehicle used.
The effects of UV irradiation on the human stratum corneum (SC) were studied under both artificial and natural conditions. Artificial UV exposure was performed with a solar simulator. Single doses of radiation from 1 to 3 MED were delivered on the backs of volunteers and the measurements were recorded for a period of one month. Corneocytes were harvested from the skin surface by using a "turbine-machine". Their count and projected area were measured by image analysis. The evolution of corneocyte counts showed 3 steps: 1) a background level of desquamation until the 8th day; 2) a sharp increase from day 9 to day 11; and 3) a plateau until the 20th day. No evolution of the corneocyte size occurred at 1 MED, but a decrease was recorded at day 20 for 2 MED and earlier for 3 MED. Natural sun exposure was investigated in 2 different experiments: on a population living in a sunny coastline and on professional racing cyclists. In these natural conditions, the response of the SC to UV led to an increase in corneocyte count associated with a decreased size. Even though natural environment involves both weather and sun influences, results showed similar SC responses. In case of acute irradiation, the skin recovers its initial state one month later, but in the natural environment, it maintains altered features as long as the UV irradiation occurs.
The effects of solar exposure on the microtopography of the human skin can be followed, in vivo, by comparing 2 nearby areas, protected and non-protected, of the arm. This has been possible in the case of professional cyclists, whose short-sleeved outerwear provides a clear demarcation of the 2 zones. The microrelief was measured from negative replicas by an automatic image analysis method. The skin pattern showed clear changes between the 2 zones. Results are discussed in an attempt to outline similarities and differences between the effects of the actual aging process and solar radiation.
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In order to quantify the intensity of skin blanching and thus predict the bioavailability of topical corticoids, a physical device allowing the measurement of light reflected from skin without any contact between the probe and the skin was used (Leveque et al., 1984). Three series of experiments were carried out: firstly, to assess the vasoconstrictor potency of four corticoids; secondly, to show the influence of the vehicle on the bioavailability of the same drug under various galenic forms, such as fatty ointments or water in oil (W/O) and oil in water (O/W) creams; thirdly, to determine the reservoir effects, if any, of some of these formulations. The results confirm previous findings about the potency of hydrocortisone acetate, triamcinolone 17-acetonide, betamethasone 17-valerate, diflucortolone valerate and clobetasol 17-propionate.
In vivo measurements taken by valid methods, help to interpret the phenomena associated with the aging process. The authors developed some routine techniques to measure physical properties of the skin both deep in the dermis-epidermis and at the surface (stratum corneum). Measurements on the forearm of 150 people yielded the following results regarding the dermis-epidermis level: (1) skin thickness begins to decrease at 45 years of age for men and women, when women's skin becomes thinner than men's skin; (2) torsion extensibility, normalized for a given skin thickness, sharply decreases after 35 years of age; (3) skin optical properties are modified, ie the photoplethysmographic signal, measured on the forehead, greatly increase after 60 years of age; (4) at the cutaneous surface level, the main modifications are increased shedding of stratum corneum after 60 years of age in parallel with a modification of the stratum corneum cohesivity, altered skin microrelief during the aging process, and slightly decreased transepidermal water loss while the corneocyte projected size increases. These findings allow consideration of the aging process at the skin level as a phased process. The alterations of the physical properties and their kinetics suggest a various process according to the different cutaneous sections.
A modified photometric technique has shown considerable differences between the refatting kinetics of the scalp and forehead. The refatting on the forehead occurs rapidly, probably due to the large follicular reservoir. The follicular reservoir of the scalp, which bears a large terminal hair, is much smaller and so the refatting time is longer. Thus, sebum excretion and sebum production rates probably correlate better on the scalp than on the forehead, and we suggest that the scalp may be a better site than the forehead for investigating sebaceous gland physiology.