Gérald Pierard

Interaction Between Collagen Type I and Type III in Conditioning Bundles Organization

Type I and type III collagen extracted from skin was purified by differential salt precipitation and chromatography. By heating to 37 degrees, type I formed after a lag phase a floppy and opalescent gel of high optical density and type III formed more rapidly a translucent and rigid gel of low optical density. Addition of type III to type I resulted in formation of gels of reduced optical density and lag phase related to the proportion of type III added. Phase contrast and scanning electronmicroscopy demonstrated the formation of thick bundles of type I, thin fibers of type III and bundles of intermediate size related to the proportion of type III. The relationship between collagen type and bundle architecture might prove most significant in conditioning the mechanical properties of the connective tissues in normal and pathological conditions.

Effect of Hormone Replacement Therapy for Menopause on the Mechanical Properties of Skin

OBJECTIVE: To evaluate the effect of hormone replacement therapy (HRT) for menopause on the mechanical properties of the skin in healthy women.

Antifungal Pulse Therapy for Onychomycosis: A Pharmacokinetic and Pharmacodynamic Investigation of Monthly Cycles of 1-Week Pulse Therapy With Itraconazole

BACKGROUND AND DESIGN In the treatment of onychomycosis, oral therapies have generally been given as a continuous-dosing regimen. For example, the suggested dose of itraconazole for the treatment of onychomycosis has thus far been 200 mg/d for 3 months. Based on the advances in our understanding of the pharmacokinetics of itraconazole, we investigated the efficacy and nail kinetics of intermittent pulse-dosing therapy with oral itraconazole in patients who were suffering from onychomycosis. Fifty patients with confirmed onychomycosis of the toenails, predominantly Trichophyton rubrum, were recruited and randomly assigned to three (n = 25) or four (n = 25) pulses of 1-week itraconazole therapy (200 mg twice daily for each month). Clinical and mycological evaluation of the infected toenails, and determination of the drug levels in the distal nail ends of the fingernails and toenails, were performed at the end of each month up to month 6 and then every 2 months up to 1 year. RESULTS In the three-pulse treatment group, the mean concentration of itraconazole in the distal ends of the toenails ranged from 67 (month 1) to 471 (month 6) ng/g, and in the distal ends of the fingernails, it ranged from 103 (month 1) to 424 (month 6) ng/g. At month 11, the drug was still present in the distal ends of the toenails at an average concentration of 186 ng/g. The highest individual concentrations of 1064 and 1166 ng/g were reached at month 6 for toenails and fingernails, respectively. At end-point follow-up, toenails in 84% of the patients were clinically cured with a negative potassium hydroxide preparation and culture in 72% and 80% of the patients, respectively. In the four-pulse treatment group, the mean concentration of itraconazole in the distal ends of the toenails ranged from 32 (month 1) to 623 (month 8) ng/g, and in the distal ends of the fingernails, it ranged from 42 (month 1) to 380 (month 6) ng/g. The highest individual concentrations of 1549 and 946 ng/g were reached at month 7 for toenails and at month 9 for fingernails, respectively. At month 12, the drug was still present in the distal ends of the toenails at an average concentration of 196 ng/g. At end-point follow-up, toenails in 76% of the patients were clinically cured with a negative potassium hydroxide preparation and culture in 72% and 80% of the patients, respectively. There were no significant intergroup differences between the three- and four-pulse treatment groups for the primary efficacy parameters. The drug was well tolerated with no significant side effects in either patient group. CONCLUSIONS Following pulse therapy with itraconazole (400 mg/d given for 1 week each month for 3 to 4 months), the drug has been detected in the distal ends of nails after the first pulse, and it has reached therapeutic concentrations with further therapy. After stopping the last pulse, the drug remains in the nail plate at levels above 300 ng/g for several months. Clinical cure rates between 76% and 84% and negative mycological examination findings between 72% and 80%, respectively, were observed in toenail onychomycosis. The data suggest that pulse therapy with itraconazole is an effective and safe treatment option for onychomycosis.

Cellulite : From standing fat herniation to hypodermal stretch marks

There are glaring discrepancies in the microanatomical descriptions of cellulite in the literature. We revisited this common skin condition in women with a microscopic examination of 39 autopsy specimens. A control group consisted of 4 women and 11 men showing no evidence of cellulite. The lumpy aspect of the dermohypodermal interface appeared to represent a gender-linked characteristic of the thighs and buttocks without being a specific sign of cellulite. Incipient cellulite identified by the mattress phenomenon was related to the presence of focally enlarged fibrosclerotic strands partitioning the subcutis. Such strands possibly serve as a physiologic buttress against fat herniation limiting the outpouching of fat lobules on pinching the skin. These structures might represent a reactive process to sustained hypodermal pressure caused by fat accumulation. Full-blown cellulite likely represents subjugation of the hypertrophic response when connective tissue is overcome by progressive fat accumulation. Histologic aspects reminiscent of stretch marks are identified within the hypodermal strands, resulting in clinical skin dimpling.

EEMCO guidance to the in vivo assessment of tensile functional properties of the skin. Part 1: relevance to the structures and ageing of the skin and subcutaneous tissues.

From an engineering point of view, the skin and subcutaneous tissue represent an integrated load-transmitting structure. It is subjected to intrinsic and environmental influences. An attempt to use a four-layered model is offered to explain how the integument withstands and transmits loads through deforming appropriately. The stratum corneum, the association between the living epidermis and papillary dermis, the reticular dermis and the hypodermis have each their own intimate structures whose tensile functions are ideally balanced to respond adequately to the casual mechanical demands. A series of physiological variables, ageing and skin diseases alter the tensile functions of the organ. In the overall analysis, truly comprehensive multidisciplinary approaches in this field have brought advances in the understanding of functional skin biology. The assessment of tensile functions of skin also provides incentives for progress in skin care.

Interleukin-6 and the skin

Interleukin-6 is a pleiotropic cytokine with numerous biological activities. It is produced by normal constituents of the skin, including epidermal cells, fibroblasts and dermal endothelial cells. It is also synthesized by inflammatory cells infiltrating the skin in various pathological conditions. We reviewed the presumed activities of interleukin-6 in normal skin and in some diseases with cutaneous involvement. The action of some drugs used in dermatology was also considered with regard to the modulation of the cytokine release. It is concluded that several important cellular lineages of the skin release interleukin-6. The cytokine appears to play a crucial role in the pathogenesis of both local and systemic inflammation, tumor development and autoimmune diseases.

Acanthosis nigricans associated with insulin resistance : pathophysiology and management.

AbstractThe association of acanthosis nigricans, skin tags, diabetes mellitus due to insulin resistance, and obesity in adolescents and young adults represents a well defined syndrome. Hyperandrogenism may also be present. The endocrine origin of this condition is beyond doubt. Insulin and insulin-like growth factor-1, and their receptors on keratinocytes are obviously involved in the complex regulations leading to the peculiar epidermal hyperplasia. This condition is unrelated to other types of acanthosis nigricans, including the congenital and the paraneoplastic types.Control of obesity contributes largely to reverse the whole process, essentially by reducing both insulin resistance and compensatory hyperinsulinemia. Several drugs including metformin, octreotide, retinoids and topical colecalciferol (vitamin D3) analogs are also beneficial in clearing acanthosis nigricans.

EEMCO Guidance for the in vivo Assessment of Skin Greasiness

Sebaceous gland activity has four distinct components which are sebum production (a secretion rate function), storage (a volume function), surface output (a delivery rate function) and stratum corneum permeation (an influx rate function). The oily appearance of skin results from an excess of sebum excretion and spreading over the body surface and its interaction with the skin surface. A multi-pronged approach is often useful to assess skin greasiness with precision. The clinical evaluation of skin greasiness and its shiny appearance should be further complemented by quantifying the large pores, follicular plugs and comedones. The sebum amount present at the skin surface can be measured non-invasively using one of several methods based on solvent extraction, cigarette paper pads, photometric assessment, bentonite clay and lipid-sensitive tapes. Quantitative parameters include the sebum casual level, the sebum excretion rate, the sebum replacement time, the instant sebum delivery, the follicular excretion rate, the density in sebum-enriched reservoirs and the sustainable rate of sebum excretion. A series of environmental and biological features influence the data. Hence rigorous methodological designs are mandatory to support claims. As a rule, accuracy of the methods is adversely affected by skin temperature, degree of hydration and surface roughness. An additional confounding factor is the inherent difficulty of collecting the surface lipids without a contribution from the follicular reservoir. A better understanding of factors that alter the sebum amount at the skin surface may well assist in the development of sebosuppressive agents to help the reduction of the skin greasiness and improve acne.

Inter-observer variation in the histopathological diagnosis of clinically suspicious pigmented skin lesions

When a biopsy is taken of a suspicious pigmented skin lesion, histological examination is expected to establish the definitive diagnosis. This study evaluated the inter‐observer variation of 20 pathologists in the histological diagnosis of a randomly selected set of suspicious pigmented skin lesions (PSLs), by comparing their diagnoses to a reference diagnosis. Overall sensitivity for melanoma was 87%, ranging from 55% to 100% between the observers. Sensitivity was significantly lower for thin (Breslow thickness <1 mm) than for thick melanomas (83% versus 97%, p=0.005). Overall melanoma specificity was 94%, ranging from 83% to 100% between observers. Dysplastic naevus was the most important source of false‐positive diagnoses, mainly in situ melanomas. Positive and negative predictive values in the given test set were 75% and 97%, respectively. In the case of melanoma, there was quite some variation in measured Breslow thickness. This would have led to a different therapeutic approach in 12% of the readings. Some of the variation seemed to be due to a different interpretation of the presence of a co‐existent naevus. In 9% (3/35) of the readings, participants did not agree on the presence of ulceration. These results reflect a tendency to overdiagnose mainly thin melanomas in general histopathological practice. They also demonstrate variation in the assessment of major prognostic factors of melanoma. Copyright

Onychomycosis and Other Superficial Fungal Infections of the Foot in the Elderly: A Pan-European Survey

Background: The escalating ageing population in the western world has led to an increased incidence of superficial fungal infections. The most common infections include onychomycosis, tinea pedis and tinea cruris. With the increasing life expectancy, the prevalence of onychomycosis and other superficial fungal infections is likely to increase further without adequate prevention and treatment. Objective: To study the prevalence of foot mycoses in Europe. Method: The Achilles project represents a survey of 90,085 subjects from 16 European countries. Results: Approximately half of the total screened population had evidence of fungal foot infection, with tinea pedis and onychomycosis affecting one quarter of these individuals. Advancing age showed an unfavourable effect on the prevalence of these infections. Conclusion: As the number of aged people in developed countries continues to increase, skin diseases will constitute a greater pharmaco-economic concern of worldwide healthcare. Better recognition by clinicians and patients of mycotic foot disease will help prevent direct morbidity and further complications.