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Biomedical subjects

L Dubertret

Publications and source records attributed to L Dubertret.

At least 307 records · Page 17Linked to original sources

Binding of 5-methoxypsoralen to human serum low density lipoproteins.

5-methoxypsoralen (5-MOP) binds to human serum low density lipoproteins (LDL) according to a two-step process. Scatchard analysis of the first step yields K = 1.4 X 10(5) M-1 and 4 binding sites. It involves the LDL apoprotein. The second step corresponds to a solubilization, in the lipidic core, of congruent to 45 molecules of 5MOP per LDL molecule. It is accompanied by a large blue shift of the 5MOP fluorescence. The ability of LDL to bind 5MOP and to carry it into various cells may explain some biological effects sometimes encountered during PUVA therapy.

5-Methoxypsoralen↗

The contractility of fibroblasts in a collagen lattice is reduced by corticosteroids.

Normal human and rat skin fibroblasts, incorporated into a three-dimensional collagen lattice, were assayed for their ability to contract collagen fibrils. This capacity is inhibited in a dose-dependent fashion by both dexamethasone and hydrocortisone. The inhibition is reversed when the corticosteroids are removed from the culture medium, but while the effect of hydrocortisone is almost entirely reversible, that of dexamethasone is not.

Adrenal Cortex Hormones↗

Psoriasis: a defect in the regulation of epidermal proteases, as shown by serial biopsies after cantharidin application.

The possible role of epidermal serine proteases in the genesis of psoriatic lesions was investigated by sequential biopsies of the epidermal damage induced by topical cantharidin. In the skin of normal subjects, epidermal damage was followed by the transient appearance of proteolytic activity in the upper epidermis accompanied by temporary hyperacanthosis and perivascular inflammatory cells in the superficial dermis. In the uninvolved skin of five patients with psoriasis this proteolysis persisted longer, for more than 7 days. Thereafter, in three of the patients, the proteolysis abated, and this was followed by disappearance of the hyperacanthosis and the dermal infiltrate; in the other two psoriatics the proteolysis and hyperacanthosis increased, and a typical Koebner phenomenon ensued. Migration of neutrophils into the epidermis occurred as a later event. Thus the abnormal persistence of proteolytic activity in the upper epidermis after cantharidin application distinguishes the normal from the psoriatic skin injury response and might initiate the psoriatic lesion.

Cantharidin↗

Photophysical, photochemical and photobiological studies of 4'-methylangelicins, potential agents for photochemotherapy.

In order to study the relationship between certain photophysical and photochemical properties of furocoumarins and their photobiological activities, the quantum yields of the formation of excited triplet states, the capacity to generate singlet oxygen in vitro and the effect of oxygen on photoinduced cell killing and on the induction of cytoplasmic "petite" mutations in Saccharomyces cerevisiae were determined for a series of 4'-methylangelicins and 3-carbethoxypsoralen (3-CPs). The capacity to generate singlet oxygen, in good agreement with the photophysical data, correlates well with the oxygen effect observed on the lethality of Saccharomyces cerevisiae shown by the various compounds and followed the ranking order 3-CPs greater than 4',4-dimethylangelicin greater than 4'-methylangelicin greater than 4',5-dimethylangelicin. On the other hand the oxygen effect on the induction of cytoplasmic "petite" mutations on yeast appears much less pronounced than that shown on survival. Concerning other photobiological properties previously studied no correlation was observed between the capacity to generate singlet oxygen in vitro and the skin photosensitizing activity of the compounds. Moreover, the generation of singlet oxygen by furocoumarins does not appear as the main cause for the photoinduction of skin tumors in mice.

Chemical Phenomena↗

[Contact dermatitis from hexamidine].

Twenty patients with contact dermatitis to hexamidine, a commonly used antiseptic solution are reported. They have been collected during a 7 months period, thus suggesting that this contact allergy is not infrequent. Hydroalcoholic solution applied on epidermless skin is most frequently responsible for the contact dermatitis. Clinical features are very peculiar with papular semi-spheric and papulo-vesicular lesions being more frequently seen than classical vesicular eczema lesions. Due to this peculiar aspect, contact dermatitis to hexamidine is frequently misdiagnosed. The delay between onset and diagnosis has been sometimes longer than one year. It is four months as a mean. Pathologic aspect of these lesions is unusual too: dermal vasculitis either lymphocytic or with pycnotic polymorphonuclear is the most frequent aspect (14 out of 23 histological sections). Epidermal spongiosis is infrequent (5 cases). Contact dermatitis has usually a long standing evolution despite removal of the allergen and topical cortico-steroid treatment. Patch-test to hexamidine are frequently followed by a worsening of cutaneous lesions. One case of anaphylaxis following patch-testing has been reported. Clinical and pathological features of this contact dermatitis, suggests that humoral immune mechanisms play a key-role in its pathogenesis.

Anti-Infective Agents, Local↗

[Cutaneous responses to an injectable collagen implant (zyderm). Clinical, histological and ultrastructural correlations after intradermal tests].

A test implant of Zyderm collagen was carried out on 250 patients using the volar forearm site. The behaviour of the implant in the host tissue was followed-up in 6 cases by both direct and electron microscopy. There were 14 positive reactions. Biopsy was carried out in 3 cases, all of which exhibited severe reactions; foreign body granulomata were found in 2 of these, perivascular lymphocytic infiltration in the third. All 3 had a follow-up for 3 months and the biopsy sites healed normally. Trial implants are always advisable with collagen material. In order to avoid the possibility of such delayed hypersensitivity reactions, the test implant should be investigated at 72 hours and kept under observation for 4 weeks prior to carrying out the full corrective procedure. In two cases, reactive adverse reactions at the collagen implant treatment site were observed in spite of negative reaction at the test site. Nevertheless evidence suggests that Zyderm injectable collagen is a suitable material, leading to good cosmetic results; it carries minimal risk and is well tolerated even after a long period of time.

Adult↗

[Hyperimmunoglobulinemia E syndrome with recurrent infections (Buckley's syndrome) associated with membranoproliferative glomerulonephritis. A case in an adult].

A 35-year old male patient who, since the age of 17, had membranoproliferative glomerulonephritis presented with recurrent atopic eczema and sinusitis. Outbursts of eczema, sinusitis and proteinuria occurred simultaneously. Signs of immune deficiency, with permanently extreme IgE levels (greater then 10.000 I.U/ml), defective neutrophil chemotaxis and monocyte phagocytotic function (Buckley's syndrome) were present. The role of these abnormalities in the pathogenesis of glomerulonephritis (chronic antigen production associated with focal infection and resulting in the formation of immune complexes, defective elimination of these circulating immune complexes) is discussed.

Adolescent↗

Physicochemical properties and stability of anthralin in model systems and human skin.

The physico-chemical properties and the stability of anthralin, a potent antipsoriatic agent, has been investigated in model systems by optical absorption and fluorescence spectroscopy and by gas chromatography coupled to mass spectrometry. Systematic studies were carried out on anthralin and its oxidation products (1,8-dihydroxyanthraquinone and 1,8-1',8'-tetrahydroxydianthron). Anthralin and 1,8-dihydroxyanthraquinone are shown to readily bind to human serum albumin and not to DNA. Anthralin bound to albumin readily oxidizes, yielding the 1,8-dihydroxyanthraquinone which is fairly stable. These results are correlated with those obtained with intact whole human epidermis and suction blister fluid showing that, in the former case, anthralin binds to protein as suggested by absorption and fluorescence spectroscopies. Gas chromatography-mass spectrometry analysis makes it easy to detect anthralin and 1,8-dihydroxyanthraquinone in suction blister fluid doped with anthralin but not in suction blister obtained after topical application on normal human skin.

Anthracenes↗

Endogenous peroxidases in normal human dermis: a marker of fibroblast differentiation.

Incubation of unfixed and unfrozen slices of normal human skin allows visualization of a peroxidase activity associated with the perinuclear envelope and with the endoplasmic reticulum of resident dermal macrophages, dermal mastocytes, and also of some dermal fibroblasts. No peroxidase activity can be detected in fibroblasts cultivated in monolayer, while 80% of fibroblasts in an "in vitro" collagen lattice, called a dermal equivalent, express a peroxidase activity in the perinuclear envelope and the endoplasmic reticulum. Hence expression of this peroxidase activity in normal human skin fibroblasts serves as a marker of fibroblast differentiation and seems to depend on an interaction to fibroblast with the elements of a three-dimensional matrix.

Adult↗

The reconstitution of living skin.

A living-skin equivalent useful as a skin replacement and as a model system for basic studies has been fabricated and tested extensively. It consists of two components: (1) a dermal equivalent made up of fibroblasts in a collagen matrix that is contracted and modified by the resident cells, and (2) an epidermis that develops from keratinocytes "plated" on the dermal equivalent. A multilayered keratinizing epidermis with desmosomes, tonofilaments, and hemidesmosomes forms. Basement lamella formation occurs within 2 weeks in vitro when rat cells are used. With human cells, crypt or pseudofollicular morphogenesis is observed in vitro within 3 weeks after plating cells on the dermal equivalent. Autografts and isografts of rat-skin equivalents made with cultured cells from biopsies are rapidly vascularized, block wound contraction, and persist essentially for the lifespan of the host. Seven to 9 days after grafting, donor cells become activated biosynthetically and mitotically. By 1 year, the dermal population decreases to a normal level and the matrix has been extensively remodeled. The grafts remain free of hair and sebaceous glands. Grafts to rats have been in place for over 2 years. Now, allografts of dermal equivalents have been made across a major histocompatibility barrier and are not rejected. The persistence of cellular elements of the grafts is monitored by use of a genetic marker. Challenge of the allograft with a second skin-equivalent graft after 1 month does not result in rejection of the original graft or of the second skin-equivalent graft. We propose that allografts of tissue equivalents are tolerated because cells with class II antigens are selected against during in vitro cultivation and are excluded from the graft. Thus the fabrication of skin-equivalent tissues or of other equivalent tissues with parenchymal cells that do not bear class II antigens may render transplants of such tissues immunologically acceptable despite the presence of allogeneic cells. The capacity to graft across major histocompatibility barriers using living tissue equivalents may have important clinical significance.

Animals↗

Photobiological activity of suction blister fluid from patients treated with 8-methoxypsoralen.

Suction blister fluid was collected from normal human volunteers before (SBF) and 2 h after (SBF 8-MOP) oral 8-methoxypsoralen (0.6 mg/kg) ingestion without irradiation. In SBF 8-MOP the concentration of 8-MOP was 150 ng/ml, and fluorescent metabolites were also present. The toxicity of SBF 8-MOP was then determined with and without UV-A irradiation in the diploid strain D7 of the yeast Saccharomyces cerevisiae which is suitable for the detection of lethal, mutagenic and recombinogenic events. It was compared with that of SBF, SBF with 8-MOP added in vitro (150 ng/ml) and 8-MOP (150 ng/ml) in water. SBF showed no effect with UV-A doses up to 360 kJ m-2; SBF 8-MOP showed a slight decrease in survival and a dose-dependent increase in nuclear mutations, mitotic gene conversion and crossing over; SBF with 8-MOP added in vitro showed increased photobiological activity compared with SBF 8-MOP. This photobiological activity was increased by a factor of six when using 8-MOP in water. These results indicate a different bioavailability of 8-MOP in water and in interstitial fluid containing proteins. The metabolites of 8-MOP in human skin did not increase the photobiological activity of the drug. We conclude that the 8-MOP present in human skin during PUVA therapy is mutagenic and recombinogenic for eukaryotic cells.

Biological Availability↗