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Biomedical subjects

G Cauwenbergh

Publications and source records attributed to G Cauwenbergh.

At least 19 recordsLinked to original sources

Dynamics of skin barrier repair following topical applications of miconazole nitrate.

The skin barrier function (SBF) is an important aspect of skin biology, particularly in the elicitation of inflammation. The SBF recovery rate after tape stripping and surfactant challenge can be assessed by measuring the transepidermal water loss (TEWL). Previous clinical studies have shown some inflammatory effect after topical applications of miconazole. The aim of this study was to compare the effect of pastes (petrolatum and 15% zinc oxide) containing or not miconazole nitrate on controlled impaired SBF. Fifteen volunteers were enrolled. In each subject, successive cyanoacrylate skin surface strippings were harvested from 5 sites of the volar forearm until TEWL raised above 15 g/cm(2)/h on all test sites. In addition, one daily soak session with a 0.2% dishwashing liquid further damaged the SBF. Each of the test formulations was applied twice daily for 5 days at two dosages, namely 1 and 2 mg/cm(2), on randomized test sites. Another site remained untreated. TEWL was measured daily for 5 days. A fastened SBF repair was observed on all treated sites, particularly where the largest amount of the products had been applied. A faster SBF recovery rate was obtained at the site receiving the miconazole nitrate paste. We conclude that the occlusive effect of a paste helped mitigate SBF defect. The adjunction of miconazole nitrate improved the efficacy.

Administration, Topical↗

Healing effect of ketanserin on chronic leg ulcers in patients with diabetes.

BACKGROUND: The treatment of chronic leg ulcers remains a stubborn problem in many patients. Topical 2% ketanserin ointment, a 5HT2-serotoninergic blocking agent, has been reported to improve healing of decubitus, venous, diabetic and ischaemic ulcers. METHOD: The present double-blind intra-individual comparative study was performed in 12 women with diabetes presenting with at least two similar leg ulcers. In each subject, the two lesions were randomly assigned to be treated for 8 weeks by 2% ketanserin ointment or its unmedicated vehicle. OBJECTIVE: assessments of the dynamics of wound healing were performed using computerized morphometry. Evaluations were performed at 2-week intervals for 8 weeks. RESULTS: A significant decrease in relative wound area was observed on the ketanserin-treated ulcers compared with the placebo group. CONCLUSION: Topical ketanserin is a valuable therapy for difficult-to-treat leg ulcers.

Administration, Cutaneous↗

Activity of the triazole antifungal r126638 as assessed by corneofungimetry.

BACKGROUND: R126638 is a novel triazole exhibiting potent in vitro and in vivo antifungal activity against fungal pathogens including dermatophytes and yeasts. OBJECTIVE: To determine the antifungal activity in time in the stratum corneum of healthy volunteers after oral intake of R126638 at a daily dose of 100 or 200 mg for 1 week. METHOD: Sixteen male volunteers were randomly allocated to oral treatment with either 100 or 200 mg of R126638 once daily for 1 week. Five cyanoacrylate skin surface strippings (CSSS) were obtained from the forearm of each subject before drug intake at day 1. CSSS were also collected during treatment at day 2 (24 h after the first drug intake, before the second drug intake), at day 4 (before the fourth drug intake) and at day 7 (10 h after the last drug intake). The post-treatment lingering effect was assessed at day 10 (3 days after treatment) and at day 14 (7 days after treatment). The corneofungimetry bioassay was performed on these CSSS to assess the antifungal profile of R126638. Cells of different fungal species (Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis, Candida albicans and Malassezia globosa) were deposited and cultured for 10 days on CSSS in a sterile and controlled environment. The extent of fungal growth on the stratum corneum was determined using computerized image analysis. RESULTS: R126638 clearly reduced the growth of all tested fungal species. The onset of effects of R126638 was evidenced at day 4 when it reached statistical significance for 3 of 5 species. At day 7, significance was reached for 4 of 5 species. During the posttreatment period, R126638 remained effective for 4 of 5 species at day 10, and this activity persisted until day 14 for 2 of 5 species. CONCLUSION: A broad spectrum antifungal activity was rapidly expressed in the stratum corneum after oral intake of R126638. The drug likely reached the upper layers of the stratum corneum by diffusion and persisted in this location for at least 7 days after treatment.

Administration, Oral↗

Fungal infections of the skin: infection process and antimycotic therapy.

Dermatomycoses are among the most widespread and common superficial and cutaneous fungal infections in humans. These typically nonfatal conditions are difficult to treat, especially infections of the nail. Dermatomycoses are caused by filamentous fungi such as Trichophyton, Microsporum or Epidermophyton species. These filamentous fungi have a high affinity for keratin, an important component of hair, skin and nails, which are the primary areas of infection by dermatophytes. The antifungal agents currently marketed for dermatomycoses are mainly inhibitors of ergosterol biosynthesis, except for griseofulvin, which interferes with the cytoplasmic and nuclear microtubular system. Three different types of inhibitors of the ergosterol biosynthetic pathway have been proven to be effective in clinic: the azoles (e.g. topical miconazole and topical/oral ketoconazole, itraconazole and fluconazole), the allylamines (e.g. terbinafine) and morpholines (amorolfine). Even today more effective antifungal azoles with less adverse effects and short-term therapy are deemed necessary to treat dermatophytosis. A promising novel triazole compound in this respect is R126638, which showed potent in vitro and in vivo activity.

Allylamine↗

Unraveling the patterns of subclinical pheomelanin-enriched facial hyperpigmentation: effect of depigmenting agents.

BACKGROUND: During photoaging, the density of melanin chromatophores is heterogeneous in the epidermis. AIMS: To define the patterns of pheomelanin-enriched melanotic hypermelanosis of the face in phototype II subjects and to assess the effect of depigmenting agents. Azelaic acid and glycolic acid were tested as well as a soy extract, reported to reduce pigmentation through interaction with the protease-activated receptor 2 (PAR-2) of keratinocytes. METHOD: Evaluations were made by image analysis of high magnification pictures obtained by a video camera equipped with an internal ultraviolet-emitting unit (Visioscan((R))). RESULTS: Three patterns of subclinical facial hypermelanosis were recognized including the spotty perifollicular type, the accretive globular type and the elongated type of the sunny side of wrinkles. Azelaic acid and the soy extract led to significant skin lightening after a 3-week treatment. By contrast, glycolic acid showed an inconsistent effect. CONCLUSION: Sensitive fluorescence video recording combined with image analysis represents an advance in the noninvasive assessment of the mottled subclinical skin pigmentation. The depigmenting effect observed with the soy extract indicates that the inhibition of PAR-2 may be a novel way to approach certain pigmentary disorders of the skin.

Facial Dermatoses↗

New insight into the topical management of excessive sebum flow at the skin surface.

The sebum flow dynamics at the skin surface results from a multistep process starting with sebocyte proliferation, intracellular lipid synthesis, cell lysis in the sebaceous duct, storage of sebum in the follicular reservoir, discharge through the follicular opening and spreading over the stratum corneum. A handful of topical products may decrease the sebum output, most of them acting at the level of the follicular reservoir function. Among them, elubiol exhibits a clinically relevant effect on oily skin.

Dioxolanes↗

Ketoconazole shampoo: effect of long-term use in androgenic alopecia.

BACKGROUND: The pathogenesis of androgenic alopecia is not fully understood. A microbial-driven inflammatory reaction abutting on the hair follicles might participate in the hair status anomaly. OBJECTIVE: The aim of our study was to determine if ketoconazole (KCZ) which is active against the scalp microflora and shows some intrinsic anti-inflammatory activity might improve alopecia. METHOD: The effect of 2% KCZ shampoo was compared to that of an unmedicated shampoo used in combination with or without 2% minoxidil therapy. RESULTS: Hair density and size and proportion of anagen follicles were improved almost similarly by both KCZ and minoxidil regimens. The sebum casual level appeared to be decreased by KCZ. CONCLUSION: Comparative data suggest that there may be a significant action of KCZ upon the course of androgenic alopecia and that Malassezia spp. may play a role in the inflammatory reaction. The clinical significance of the results awaits further controlled study in a larger group of subjects.

Adult↗

Trypsin-induced follicular papilla apoptosis results in delayed hair growth and pigmentation.

Programmed cell death is a controlled process that leads to the elimination of single cells via apoptosis. Programmed cell death is fundamental to development, morphogenesis, and homeostasis. Proteases play a major role in the death process. We have previously shown that a serine protease, secreted by a keratinocyte cell line, can induce apoptosis in numerous cell lines. Here we show that serine proteases can induce cell death in vivo as well. Using a synchronized hair growth mouse model, we show that topical trypsin treatment following depilation induces cell death at the follicular papilla. This results in delaying hair growth and pigmentation. We speculate that trypsin might affect a receptor-mediated signaling pathway that leads to follicular papilla cell death.

Animals↗

The effects of trypsin on apoptosis, utriculi size, and skin elasticity in the Rhino mouse.

Acne vulgaris is the result of multifactorial disorders of the pilosebaceous duct. The initial lesion is believed to be hyper-keratinization of the infundibulum. The Rhino mouse has been used as an experimental acne model system for screening anti-keratinizing and comedolytic agents. Using this system we show that trypsin could induce desquamation and utriculi-epidermal differentiation in the absence of irritation. Following five daily trypsin treatments, the biomechanical properties of the mouse skin improved, as demonstrated by cutometer measurements and increased elastin expression. Extensive programmed cell death and apoptosis are demonstrated in the utriculi epithelium of the untreated animals. This cell death is eliminated by the trypsin treatment. We speculate that co-administration of trypsin might increase the therapeutic value of topical acne treatments and improve skin elasticity while reducing irritating effects.

Acne Vulgaris↗

Age-related changes in facial skin contours and rheology.

OBJECTIVES: To evaluate the age effect on both the mechanical properties and wrinkling of facial skin. This topic has not previously been addressed in the literature. DESIGN: A total of 180 white women aged 18 to 67 years participated in the study. Each of the 5 decades of age was represented by 30 subjects, with the exception of menopausal women aged 48 to 57 years who were allocated to two groups of 30 according to the use or non-use of hormone replacement therapy (HRT). SETTING: A University medical center, Belgian SSTC Research Unit 5596. MEASUREMENTS: Mechanical properties of the skin were measured on the face using a computerized suction device. Skin contours were assessed using optical profilometry and computerized image analysis. RESULTS: Skin aging of the face is characterized by a progressive increase in extensibility associated with a decreased elasticity. The loss of tonicity is accompanied by a progressive deepening of facial creases. HRT appears to limit the age-related rheological changes without showing a preventive effect on wrinkling of facial skin. CONCLUSION: Aging of facial skin resembles, in some ways, the features previously reported on sun-protected areas of the forearms. HRT has a beneficial effect that may slow the overall process of aging without, however, limiting the number and depth of wrinkles.

Adolescent↗

Effect of ketoconazole-medicated shampoos on squamometry and Malassezia ovalis load in pityriasis capitis.

Pityriasis capitis is improved by the use of antifungal shampoos. A double-blind randomized, placebo-controlled study was conducted to compare the efficacy of ketoconazole 0.5 percent and 1 percent formulation shampoos. Evaluations were made in seventy-eight volunteers before and after a two-week duration of daily shampooing. Grading the Malassezia ovalis load in dandruff and values of squamometry were used as noninvasive methods to evaluate efficacy.

Adolescent↗

[Pharmacokinetics of itraconazole].

Itraconazole is a lipophilic triazole antifungal with a broad spectrum of activity. Most of the important fungal pathogens respond to itraconazole concentrations of 100 ng/ml. Therefore, itraconazole is suitable for treatment of a variety of systemic mycoses, as aspergillosis, cryptococcosis, candidosis as well as non-European endemic mycoses. The lipophilicity of the molecule is the reason for a pronounced tissue affinity meaning that the tissue levels of the drug usually are substantially higher than the corresponding plasma levels. This fact has to be kept in mind when plasma measurements are being used to decide a therapeutic approach for a systemic fungal infection. In contrast to the skin, internal organs will not show a long term retention of itraconazole in the tissues. This means that for systemic mycoses the therapy needs to be continued until clinical and mycological cure is obtained. Reduced itraconazole absorption may occur in a minority of patients because of underlying chemotherapy or dramatic changes in stomach pH. This is occasionally seen in patients with allogeneic bone marrow transplants and end-stage AIDS patients. Use of antacida and H2-antagonists somewhat reduces the absorption of itraconazole, however, often not in a clinically meaningful way. Itraconazole increases the levels of cyclosporin A. Itraconazole levels are decreased by rifampicin, phenytoin and phenobarbital. Caution is required in patients on concomitant anticoagulants.

AIDS-Related Opportunistic Infections↗

Posttreatment itraconazole levels in the nail. New implications for treatment in onychomycosis.

BACKGROUND: A problem in the treatment of onychomycosis is the lengthy duration of therapy. The pharmacokinetics of itraconazole suggest a potential for briefer treatment. OBJECTIVE: This study was designed to investigate itraconazole nail kinetics in 39 patients with onychomycosis in relation to their therapeutic outcome. METHODS: All patients received itraconazole for 3 months at a dose of 100 or 200 mg daily. Itraconazole levels of distal nail clippings were determined during a 6-month posttherapy period. RESULTS: Therapeutic itraconazole concentrations were found in the nail plates of fingernails and toenails for up to 6 months after treatment. Cure of the toenails was observed in 79% of the patients treated with the 200 mg dosage and in 26% of those treated with 100 mg at 6 months after therapy. CONCLUSION: The data suggest that the drug reaches the nail via incorporation into the matrix and by diffusion from the nail bed and is eliminated with regrowth of the nail after discontinuation of treatment.

Antifungal Agents↗

Itraconazole in the treatment of chromoblastomycosis due to Fonsecaea pedrosoi.

The efficacy and tolerability of itraconazole in chromoblastomycosis due to Fonsecaea pedrosoi were evaluated in a non-comparative open clinical trial in 19 Brazilian patients with histopathologically and mycologically proven active chromoblastomycosis. Patients were classified in terms of severity and received itraconazole at the dosage of 200 to 400 mg per day until previously described criteria of cure have been reached. Clinical, mycologic, histopathologic, and laboratory evaluations were performed before, during, and after therapy. The plasma levels of itraconazole and the in vitro susceptibility of the isolates were determined in 15 cases. Clinical and biologic cure were achieved by eight patients (42%) having mild to moderate disease, after a mean duration of therapy of 7.2 months (3.2-29.6 months). Sterile scarred lesions were observed in a post-therapy follow-up lasting on average 9.6 months that was carried out in this subgroup. Clinical cure alone occurred after a mean period of 25.1 months of treatment (16-30.5 months) in seven patients (36%) with moderate to severe disease. Finally, clinical improvement was obtained in four patients (21%) with severe lesions after a mean treatment time of 17.6 months (10.7-22.5 months). All patients responded favorably to itraconazole therapy. No significant side effects nor biochemical alteration during this trial were important enough to interrupt the treatment. Our results support those of previous trials, suggesting that itraconazole is an effective compound against chromoblastomycosis due to Fonsecaea pedrosoi.

Adult↗