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Biomedical subjects

P Agache

Publications and source records attributed to P Agache.

At least 19 recordsLinked to original sources

A new technique to study the mechanical properties of collagen lattices.

A new technique to study the mechanical properties of collagen lattices or dermal equivalents is described. With the help of the load-extension curve obtained with a uniaxial traction apparatus, a stiffness modulus varying from 0.06 to 1 MPa is calculated from the studied parameters (duration of culture, collagen and fibroblast concentration). The technique is presented as a new tool for testing the effect of pharmacological agents on the mechanical properties of the skin.

Biomechanical Phenomena

Effect of occlusion on in vitro percutaneous absorption of two compounds with different physicochemical properties.

It is a general rule that percutaneous absorption is increased when the site of application is occluded. In this study we compared the in vitro permeation profiles of two molecules with different physicochemical properties under occluded versus unoccluded conditions. Human abdominal skin samples were mounted on Dianorm Teflon macro 1 cells and Franz diffusion cells which represented occluded or unoccluded conditions, respectively. Our data show that occlusion increased the permeation of citropten (lipophilic compound) 1.6 times whereas that of caffeine (amphiphilic compound) remained unchanged. This lack of penetration enhancement under occluded conditions has also been observed by other authors, especially concerning hydrophilic and slightly lipophilic molecules. Our results support the view that occlusion does not necessarily increase the percutaneous absorption of a chemical.

Caffeine

Transepidermal water loss related to volar forearm sites in humans.

The aim of this study was to demonstrate differences in human skin transepidermal water loss (TEWL) in vivo related to site on volar forearm. Fourteen healthy volunteers entered the study and seven sites were tested. After randomization of both forearm and measure order, TEWL measurements were performed using the Servo Med Evaporimeter. TEWL values next to the wrist were found statistically greater than on the other sites. Hence wrist region should preferably be excluded from TEWL measurements on forearm.

Adult

A new micronized 5-methoxypsoralen preparation. Higher bioavailability and lower UVA dose requirement.

A new tablet of micronized 5-methoxypsoralen (5-MOP) and a commonly used tablet in therapy (Psoraderm 5) were compared in 12 healthy subjects. Each subject ingested 1.2 mg/kg body weight of each formulation on different days. Bioavailability and phototoxicity of 5-MOP were compared. The results showed that serum and suction blister concentrations were significantly higher and occurred earlier after the oral intake of the micronized preparation. A series of graduated UVA doses were administered, one dose each time the concentration serum peaked, in order to determine the minimum phototoxic dose for each formulation. The micronized preparation induced greater photosensitivity than the unmicronized one. The micronized 5-MOP tablet may thus allow lower doses of UVA to achieve therapeutic results in photochemotherapy and a shortened waiting period following ingestion of drug.

5-Methoxypsoralen

[Calcifying panniculitis].

We report a case of calcifying panniculitis which occurred in a 67-year old woman suffering from chronic renal failure and primarily involved anticoagulant injection sites. Calcifying panniculitis is a rare condition belonging to the spectrum of calciphylaxis first described by Selye in 1962. This disease seems to imply necessarily a specific morbid background including renal failure together with calcium-phosphate metabolism impairment. Following the action of a so-called "challenger" (in the present case calcium heparinate [Calciparine], a subcutaneously administered anticoagulant drug), the lesions start as painful subcutaneous nodules soon turning into plaques of necrosis. The area involved mainly includes the abdomen and thighs, due to the preferential distribution of fat and the classical use of such regions for subcutaneous injections. In our patients, histological examination disclosed an initial involvement of subcutaneous fat vessels mimicking mediacalcosis, soon followed by calcium-phosphate deposits within interadipocyte spaces. An electron microscopy study confirmed the presence of calcium crystals within the cytoplasms of some connective tissue cells and the extracellular matrix. From a review of the literature, it seems reasonable to normalize the calcium-phosphate product by reducing hyperparathyroidism as a first therapeutic step. Then, wide surgical excision of the necrotic areas should be performed to rule out any possibility of self worsening of the lesions and provide the best chance of healing without superinfection. The use of diphosphonates on pathophysiological grounds is discussed.

Aged

[Cutaneous pigmentation induced by minocycline: ultrastructural analysis and X-ray microanalysis].

The authors report a case of cutaneous pigmentation induced by minocycline. The patient (aged 59) presented with a bluish-grey pigmentation on her face, legs and nails. She had been receiving minocycline for 8 years for asthma. The cumulative dose was 400 g. Skin biopsy specimens from the pigmented areas were examined by light and electron microscopy. Light microscopy displayed hyperpigmentation with Fontana's stain in the dermis, macrophages and basal layer of the epidermis. Electron microscopy showed an increase in melanosomes within the basal keratinocytes, and dense granules in macrophages of the dermis. An X-ray microanalysis of the electron-dense granules showed the presence of larger quantities of iron and smaller quantities of sulphur and calcium. The different types of pigmentation are reviewed. Several pigments are thought to be responsible for the pigmentation but the underlying mechanism remains unclear.

Female

Simple equilibrium dialysis-high-performance liquid chromatographic method for the in vitro assessment of 5-methoxypsoralen bound to human albumin.

Increasingly used in therapeutics, 5-methoxypsoralen (5-MOP), a linear furocoumarin, associated with UVA irradiation (PUVA), is now an established treatment for skin diseases such as vitiligo, mycosis funcoides and particularly psoriasis. Successful PUVA therapy depends on a sufficiently high peak 5-MOP plasma concentration coinciding with the UVA irradiation. However, as with most drugs, only the free plasma fraction is able to enter the target cells and has a pharmacological effect. In this work, the binding of 5-MOP to human albumin was studied in vitro, using a dialysis chamber. Bound and free 5-MOP fractions were quantified by a modification of Stolk's high-performance liquid chromatographic method. Dialysis was performed at 37 degrees C and pH 7.4 for 2 h, against a 4% albumin solution in phosphate buffer. The 5-MOP concentrations used were from 5 x 10(-5) to 5 x 10(-2) g/l in 1 x 10(-1) g/l steps. The 5-MOP bound strongly to human albumin in an unsaturable way. The mean 5-MOP binding to albumin was 95.3%. These results are in accordance with those published by Artuc et al. and not with those of Veronese et al., who found a lower saturable fixation (91%). These two research groups used tritiated 5-MOP. The technique used in this work is simple and inexpensive. It can be employed easily in vivo, e.g., for the assessment of 5-MOP free fractions in different therapeutic conditions.

5-Methoxypsoralen

High-performance liquid chromatographic determination of citropten and bergapten in suction blister fluid after solar product application in humans.

Citropten (5,7-dimethoxycoumarin) and bergapten (5-methoxypsoralen) are present in bergamot oil which is used as a tanning cosmetic product. The aim of this study was to quantify, using high-performance liquid chromatography, the amount of citropten and bergapten in the skin after suntan products application (an emulsion and an oil formulation). A suction blister technique performed of the anterior aspect of the forearm permitted the collection of these two accumulated molecules. Fluorometric and ultraviolet detections were used for citropten and bergapten determinations, respectively.

5-Methoxypsoralen

Peak blistering point: influence on fluid levels of 5-MOP in human skin in vivo after systemic administration.

The concentration of 5-methoxypsoralen (5-MOP) in suction blister fluid (SBF) after oral intake was determined in relation to the peak blistering point. Interstitial fluid was obtained from nine healthy male volunteers by applying mild suction (300-350 mmHg) to the skin of the volar aspect of the forearm. Blisters were raised at three different times: 18 h prior to drug administration (group I); 2 h prior to drug administration (group II); and during drug ingestion (group III). SBF levels of 5-MOP were determined in each group of blisters 2 h after oral administration of 1.2 mg/kg micronized 5-MOP. The results showed a statistically significant difference in the concentrations of 5-MOP between each group of blisters. The highest concentration of 5-MOP in the SBF was found in group III and the lowest in group II blisters. These findings suggest that the point of peak blistering in relation to drug administration needs to be known in each pharmacological study using suction blisters.

5-Methoxypsoralen

The tetracyclines in dermatology.

Tetracycline is one of the most widely used antibiotics. It may share some properties with conventional immunosuppressive drugs and act as an anti-inflammatory agent in the treatment of inflammatory disease. This article reviews cutaneous diseases that have been treated with tetracyclines and their antiinflammatory and immunosuppressive properties.

Humans

Intestinal permeability in patients with psoriasis.

A possible relationship between intestinal structure and function in the pathogenesis of psoriasis has recently brought about considerable interest. The purpose of this study was to evaluate the intestinal permeability in psoriatic patients by comparing it with healthy controls. 15 psoriatic patients and 15 healthy volunteers entered the study. Intestinal permeability was evaluated using the 51Cr-labeled EDTA absorption test. The 24-h urine excretion of 51Cr-EDTA from psoriatic patients was 2.46 +/- 0.81%. These results differed significantly from controls (1.95 +/- 0.36%; P less than 0.05). The difference in intestinal permeability between psoriatic patients and controls could be due to alterations in the small intestinal epithelium of psoriatics.

Adolescent