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J De Bersaques

Publications and source records attributed to J De Bersaques.

At least 19 recordsLinked to original sources

Pharmacokinetics and drug interactions of etretinate and acitretin.

Acitretin, the metabolite of etretinate, is eliminated far more rapidly from the human body than is etretinate. It had therefore been suggested that only a short period of contraception would be required after the cessation of long-term therapy with acitretin. However, recent studies have demonstrated the presence of etretinate in the plasma of patients who were treated with acitretin. In this article we provide results from a study in our center and discuss earlier data in light of the recently discovered metabolic pathways for acitretin. Reesterification of acitretin to etretinate, however, results in a loss of the metabolic advantages of acitretin. Because of this situation the recommended contraception period after acitretin therapy has been lengthened to 2 years.

Acitretin

The distribution of cis- and trans-acitretin in human epidermis.

The concentrations of trans-acitretin and its principal metabolite, cis-acitretin, were measured by h.p.l.c. after single and multiple dosing (50 mg orally for 13 days) in plasma, blister fluid and epidermal samples from four healthy male volunteers. Within-day epidermal concentrations of trans-acitretin exceeded those of the cis-form which were at the limit of assay sensitivity. No accumulation of trans-acitretin was observed in plasma or blister fluid but AUC values for the drug in blister roof cells tended to be higher after multiple dosing.

Acitretin

Use of topical lithium succinate in the treatment of seborrhoeic dermatitis.

Twenty-one patients with seborrhoeic dermatitis were included in an open trial of lithium succinate ointment (LSO) for a total duration of 8 weeks. The same clinician made assessments of the severity of redness, scaling, greasiness and overall clinical impression of the condition every 2 weeks. Because the results appeared to be satisfactory, we decided to perform a double-blind, placebo-controlled trial of LSO. Thirty patients with seborrhoeic dermatitis were included. The results also demonstrated the beneficial effect of LSO. A significantly higher number of patients treated with LSO showed remission or marked improvement compared with placebo. The main adverse events demonstrated consisted of minor transient skin irritation and/or stinging sensation. Studying the in vivo inhibitory effect of LSO on the growth of Pityrosporum revealed that Pityrosporum did not significantly have its growth inhibited by lithium. Topical lithium succinate appears to be a safe and an effective treatment for seborrhoeic dermatitis. The product presumably acts as an anti-inflammatory agent.

Adolescent

Keratinization of middle ear cholesteatomas. I. A histochemical study of epidermal transglutaminase.

A histochemical study was performed to determine the involvement of epidermal transglutaminase (ETgase) in the keratinization of middle ear cholesteatomatous lesions, and to compare it with its role in the middle ear mucosa and epidermis. In a first assay, we localized the (E)Tgase activity in situ. A second immunohistochemical assay revealed the distribution of the particulate form of ETgase, which is involved in cross-linked envelope formation. A remarkable difference between strongly keratinized epidermal tissues and the cholesteatoma matrix is the frequent observation in the latter of the remnants of (E)Tgase activity in cytosol, even in advanced stages of differentiation. As a consequence, the cell-membrane-associated ETgase activity, and thus the extent of cross-linking within the envelope, is at a lower level than expected. This aspect is reminiscent of the keratinization phenomenon manifested by thin epidermal tissues. In addition, our findings are the first to show that ETgase is a substantial marker of middle ear mucosa.

Cholesteatoma

An investigation of cytokeratin expression in skin epithelial cysts and some uncommon types of cystic tumours using chain-specific antibodies.

The differentiation state of skin epithelial cysts and some uncommon types of epithelial skin tumours was investigated by immunohistochemical staining, mainly using cytokeratin (CK) polypeptide-specific monoclonal antibodies. Samples of interfollicular epidermis, hair follicles and eccrine sweat glands were included as reference tissues. The CK reactivity in epidermoid cysts and milia is not restricted to CKs involved in epidermal-type differentiation, i.e. CK1, 5, 10 and 14, but in addition CK16, a hyperproliferative keratinocyte marker is suprabasally expressed. CK1 and 10 are other prominent suprabasal markers, while CK14 seems to be preferentially expressed in the basal cell layer. Of the non-epidermal CKs, only CK4 was focally or more extensively detected in about 50% of the cases. In terms of CK reactivity, keratinization of trichilemmal cysts corresponds to the keratinization of the anagen-phase hair follicle in the isthmus. The CK reactivity is again restricted to CK1, 5, 10, 14 and 16. However, the CK1 as well as CK10 reactivity is subject to serious limitations, since both CKs were only convincingly observed in foci of terminal differentiation. Eccrine hydrocystoma obligatorily expresses a complex CK set, including CK7, 8, 14, 18 and 19. This CK set perfectly corresponds to the CK composition observed in acini of eccrine sweat glands. In addition, a discontinuous CK4 and 16 reactivity was seen in about 50% of the sites, while CK1 and 10 displayed a strictly focal appearance. On the other hand, syringoma produces in its distinct structures, a CK pattern reminiscent of the one observed in eccrine sweat gland ducts and includes CK1, 5, 10, 14, 16 and 19.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal

A comparative immunohistochemical study of cytokeratin and vimentin expression in middle ear mucosa and cholesteatoma, and in epidermis.

Cytokeratin expression was studied in human middle ear cholesteatoma lesions, using a variety of immunohistological techniques and a wide range of polyclonal antisera and monoclonal antibodies against cytokeratin (CK) subgroups or individual CK polypeptides. The expression of the other cytoskeletal proteins, vimentin and desmin, was also investigated. Middle ear mucosa and epidermal tissues were used as reference tissues. Our investigations also included epithelial structures present in the cholesteatoma perimatrix and in dermal tissues. The results indicate that, compared with epidermal tissues, the expression profile of CKs in cholesteatoma matrix is representative of a hyperproliferative disease. Evaluating the presence of a marker of terminal keratinization - the 56.5 kD acidic CK n degrees 10 - we found supportive evidence of a pronounced retardation of its expression, which did not parallel histological differentiation. In epidermal tissues, the first prickle cell layers are CK10 positive whereas in many cholesteatomas this finding was observed near the stratum granulosum only. Probing the early stages of keratinization - the 58 kD basic CK n degrees 5 and the 50 kD acidic CK n degrees 14 - we regularly observed an extended staining area in the cholesteatoma matrix. In epidermal reference tissues, only the basal and nearest suprabasal layers were convincingly labeled. As a rule, non-epidermal CKs did not belong to the cholesteatoma CK set. However, exceptions to that rule were noticed as a focal or more extended expression of one or more non-epidermal CKs in about half of the cases. Together with the extended CK5 topography, this is further evidence that CK expression is seriously affected by the diseased state. CK expression in the perimatrix is limited to mucous glands, either normal, atrophic or hyperplastic. CKs n degrees 4, 5, 7, 14, 18 and 19, also displayed by middle ear mucosa, were consistently observed. Where ductal arrangements were present, CK10 was also detected, in analogy with the CK10 registration in ductal portions of mucous glands in the external ear canal skin. The absence of CK8 in mucous glands of the perimatrix, however, strongly differentiates these structures from the mucous gland acini and ducti in the external ear canal, where CK8 is systematically expressed. Vimentin staining was restricted to dendritic cells of the matrix (Langerhans cells) and to perimatrix fibroblasts, blood cells and vascular endothelium. Coexpression of CK and vimentin was not observed.

Animals

A retrospective study of the inpatient treatment of psoriasis with dithranol.

This study reports the results of the Ingram dithranol regimen for the treatment of psoriasis in 275 inpatients. The median duration of hospitalization until clearance was 25 days and the medians of the interval until a next treatment or hospitalization was needed were 11 and 8.5 months, respectively.

Anthralin

Nuclear differentiation and ultimate fate during epidermal keratinization. Two-wavelength and cytofluorometric DNA investigations completed by computerized scanning image analysis.

Quantitative DNA cytophotometric investigations were performed to clarify some aspects of the differentiation and fate of nuclei in bovine snout and human epidermis representing various sites and different degrees of keratinization. We elaborated optimal conditions for hydrolysis and Feulgen staining. Diverse cytophotometric techniques, including computerized scanning cytophotometry and image analysis were applied. This approach provided the first quantitative data concerning changes of nucleotype during soft keratinization. Cytophotometric DNA measurements provide evidence for a continuous decline of nuclear DNA content from immediately beyond the basal layer to the transition zone. The overall loss of DNA is an orderly process that intensifies gradually and culminates in the stratum granulosum. Gradual nuclear degeneration, however, is not a general phenomenon, and a significant number of nuclei retains a DNA content within the diploid limits throughout the entire stratum spinosum and part of the stratum granulosum. At any level of differentiation or decay, residual nucleoprotein complexes remain intact, as judged from their resistance to acid hydrolysis. Karyological features change completely during keratinization. Basal cell nuclei are rather compact, ellipsoid and heterochromatic. Beyond the basal layer, nuclei enlarge, round up and obviously evolve to an extremely euchromatic state, with preferential localization of the dispersed heterochromatic clumps at the more peripheral sites. In the upper stratum spinosum, nuclei undergo even more drastic changes: nuclear area and volume shrink, nuclei partially regain the ellipsoid shape and revert to heterochromasia. Nevertheless, euchromatin remains the major constituent of decaying nuclei. Terminal differentiation stages, except in human sole, are marked by heterochromatin clumping. In human sole, persistence or even progression of heterochromatin dispersion is observed. Heterochromatic dots are situated along the nuclear membrane in human terminal keratinocytes, but are almost randomly distributed in bovine stratum granulosum nuclei. Finally, nuclear contrast analysis partially reveals statistically significant changes throughout keratinization.

Animals

8-Methoxypsoralen plasma levels and phototoxic effect.

In 8 normal volunteers, the minimal phototoxic dose was determined at 15 min intervals up to 60 min and thereafter every 30 min up to 4 h; 8-methoxypsoralen (8-MOP) was administered as a solution and small additional doses were given during the course of the experiment, so that a more or less predictable and stable plasma concentration was obtained and maintained for about 2 h. Three of the subjects absorbed 8-MOP very rapidly, already reaching plasma concentrations above 200 ng/ml after 15 min; in the other 5, absorption was slower and comparable levels were achieved only after 30 to 90 min. In the fastest absorbers, there was a 15 to 30 min lag between reaching a high plasma level and a low MPD. In the other cases, such a delay was not seen. This suggests that the time to reach peak concentration in the skin is not influenced by changes in absorption rate: simulations based on the classical plasma concentration equations for a two-compartmental model also show this. Afterwards, the skin sensitivity decreased in most cases parallel to the plasma concentrations.

Female

Short-duration dithranol therapy for psoriasis.

40 outpatients with psoriasis vulgaris of limited extent were treated with daily brief applications of a 1, 2 or 3% dithranol ointment. The treatment was effective in cases of large plaques, small lesions and guttate psoriasis. There was a very poor therapeutic response in palmoplantar psoriasis and in residual lesions after Ingram's regimen.

Anthracenes

[Relation between plasma levels of 8-methoxypsoralen and the phototoxic effect].

Plasma concentrations of 8-MOP were studied in 6 subjects at three dose levels and the minimal phototoxic dose determined after 60, 120 and 180 min. Although there is an inverse correlation between these two values, none of the eight mathematical expressions examined gave a perfect fit in all cases.

Dose-Response Relationship, Drug