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Biomedical subjects

Jan Faergemann

Publications and source records attributed to Jan Faergemann.

At least 19 recordsLinked to original sources

Action of topical thyroid hormone analogue, triiodothyroacetic acid in reversing glucocorticoid-induced skin atrophy in humans.

The present study concerns the effect of topical treatment with a cream formulation of triiodothyroacetic acid (TRIAC) in comparison with a placebo preparation in producing a reversal of skin atrophy induced by long-term employment of topical glucocorticoid therapy in humans. A total of 39 patients with clinically verified skin atrophy due to long-term use of topical potent glucocorticoids were randomized. The changes in skin thickness, elastic fibers, and hyaluronic acid were evaluated by means of sonography and histology. After 8 weeks' treatment, the skin thickness measured by sonography increased by 16% in the epidermis, 8% in the dermis, and epidermis + dermis in the placebo group. In the TRIAC 0.1% group, the corresponding values were 24% ( p=0.063) in the epidermis, 28% ( p=0.042) in the dermis, and 25% ( p=0.039) in the epidermis + dermis. After 8 weeks, in the placebo group, the skin thickness measured by biopsy increased by 5% in the epidermis, epidermis + dermis, and 6% in the dermis. In the TRIAC 0.1% group, the corresponding values were 31% ( p=0.041) in the epidermis, 46% ( p=0.041) in the dermis and 44% ( p=0.043) in the epidermis + dermis. After 8 weeks, the elastic fibers of moderately irregular and thickened fibers increased by 56% in the placebo group and 100% ( p=0.043) in the TRIAC 0.1 group. This study indicates that topical treatment with TRIAC appears to reverse glucocorticoid-induced skin atrophy under the narrow conditions tested.

Administration, Topical↗

Action of topical thyroid hormone analogues on glucocorticoid-induced skin atrophy in mice.

Previously we demonstrated the stimulation of collagen synthesis in triiodothyroacetic acid (TRIAC)-topically treated human and mice. In the present study, we have evaluated the dose response effect of thyroid hormone (TH) analogues and tretinoin on glucocorticoid-induced skin atrophy in a haired mouse model. For this investigation, we treated haired mice twice daily for 7 days with various topically administered doses of TRIAC, triiodothyronine-sodium salt (T(3)-Na), diiodothyroacetic acid (DIAC), 3,5-diiodothyropropionic acid (DITPA), and tretinoin with 0.2 mM betamethasone17-valerate (BM), or with the vehicle as a control group. We also investigated a combination of commercial betamethasone dipropionate (BD) 0.05% cream and various doses of TRIAC on mouse skin. TRIAC was able to reverse the skin atrophy by 25% in a daily dose of 1 nmol/cm(2) in the presence of 0.2 mM BM (p < 0.05). Neither other TH analogues nor TRIAC in lower and higher concentrations had a significant inhibitory effect on dermal atrophy (p > 0.05). A combination of 0.2 mM BM and 10 nmol/cm(2) TRIAC was able to prevent dermal atrophy by 18%. The addition of TRIAC to 0.05% BD cream in a final concentration of 0.1% was able partially to reverse the dermal atrophy by 15% (p < 0.05). TRIAC alone in a concentration of 1,000 nmol/cm(2) stimulated dermal proliferation by 34% (p < 0.05). Other TH analogues alone had no stimulatory effect on dermal proliferation. Tretinoin 0.8 mM was able to inhibit dermal atrophy by 20% (p < 0.05) and had an effect on dermal thickness of 85% (p < 0.05). However, severe side effects with edema, erythema, and scaling were commonly observed in all tretinoin-treated mouse skin, which could partly explain the increase in dermal thickness. In contrast, no skin side effects were observed after treatment with TRIAC. This study indicates that TRIAC may have a therapeutic effect on BM-induced dermal atrophy in mouse skin and a direct stimulatory effect on dermal proliferation when given alone.

Acetates↗

Atopic dermatitis in adults: does it disappear with age?

There is limited knowledge of the prognosis in adult atopic dermatitis. We previously published a long-term follow-up questionnaire study of adults with atopic dermatitis. This study is a clinical examination of 79 adults (mean age 57 years) recruited 3 years after that study. Most patients (68%) still reported that they had atopic dermatitis and 53% had ongoing eczema at examination, mainly located on the head and neck. Severity was mainly mild to moderate, but 12% had severe atopic dermatitis. IgE antibodies to Malassezia (m70) were more common in patients with ongoing atopic dermatitis, while positive Malassezia culture was seen mainly in patients with no ongoing atopic dermatitis. M. obtusa and M. globosa were the most commonly cultured Malassezia species. In conclusion, considering increased prevalence of atopic dermatitis in children in recent decades and the fact that atopic dermatitis in most adults continues for many years, we should expect to see more adults with atopic dermatitis in the future.

Aged↗

In vitro activity of R126638 and ketoconazole against Malassezia species.

The in vitro activity of a new triazole R126638 against Malassezia yeasts was compared with that of ketoconazole. With the agar dilution technique, minimal inhibitory concentrations were lower for R126638 compared with ketoconazole against Malassezia globosa, M. obtusa, M. slooffiae, M. restricta and two strains of M. sympodialis. On human stratum corneum in vitro, both R126638 and ketoconazole were very effective in reducing the production of hyphae from 15% to 1% with R126638 and to 2% with ketoconazole. Scanning electron microscopy did not reveal obvious surface differences between untreated cultures and cultures exposed to ketoconazole or R126638 in the concentration range 0.01-1 microg/ml. However, transmission electron microscopy showed partial to complete necrosis of the cytoplasmic organelles of Malassezia yeasts. The combined scanning electron microscopy and transmission electron microscopy findings confirm earlier observations of the "mummifying" effect of azoles against Malassezia spp. In conclusion, R126638 is an interesting new triazole with high activity against the Malassezia yeasts, which are involved in pityriasis versicolor and seborrhoeic dermatitis.

Antifungal Agents↗

Pentane-1,5-diol as a percutaneous absorption enhancer.

Propylene glycol (propane-1,2-diol) is the only diol widely used in dermatology. Pentane-1,5-diol is mainly used as a plasticizer in cellulose products and adhesives, in dental composites and in brake fluid compositions and as a preservative for grain. However, pentane-1,5-diol is also an effective solvent, water-binding substance, antimicrobial agent and preservative and may therefore replace several ingredients in a skin composition. The release of tri-iodothyroacetic acid (TRIAC) and percutaneous absorption of hydrocortisone and mometasone furoate with either pentane-1,5-diol or propane-1,2-diol and 2-methyl-pentane-2,4-diol (hexylene glycol), respectively, as enhancers was compared. The release of TRIAC was 21% higher when pentane-1,5-diol was used as an enhancer instead of propane-1,2-diol. The percutaneous absorption of hydrocortisone through the skin was increased 12 times with propane-1,2-diol compared to 4.4 times with pentane-1,5-diol. However, the percutaneous absorption of hydrocortisone into the skin was 50% higher with pentane-1,5-diol compared to propane-1,2-diol. There was no significant difference, between the original mometasone furoate cream, with 2-methyl-pentane-2,4-diol, and the new cream with pentane-1,5-diol in the amount of mometasone furoate that was absorbed into the skin and through the skin. However, the cosmetic properties of the new mometasone furoate cream was superior to the original mometasone furoate cream, for examples, no bad odour, more even texture, goes better into the skin and has less greasiness. Pentane-1,5-diol can be used as a technology platform, which adds a series of desirable properties to dermatological preparations and enhances product usability. This will result in improved formulations for a series of major and commonly used dermatological drugs. When used in pharmaceutical topical preparations, pentane-1,5-diol will increase the percutaneous absorption of the active substance and it is an efficient antimicrobial agent that will act as an effective preservative in topical formulations. Pentane-1,5-diol is cosmetically attractive, has low risk for skin and eye irritation compared to other diols, low toxicity risk and no bad odour.

Administration, Cutaneous↗

The prevalence of Malassezia yeasts in patients with atopic dermatitis, seborrhoeic dermatitis and healthy controls.

Cultures for Malassezia yeasts were taken from both normal-looking skin and lesional skin in 124 patients with atopic dermatitis, 16 patients with seborrhoeic dermatitis and from normal skin of 31 healthy controls. Positive Malassezia growth was found in fewer patients with atopic dermatitis (56%) than in patients with seborrhoeic dermatitis (88%) or in healthy controls (84%, p<0.01). In the patients with atopic dermatitis, fewer positive cultures were found in lesional (28%) than in non-lesional skin (44%, p<0.05), while positive cultures were found in 75% of both lesional and non-lesional skin of patients with seborrhoeic dermatitis (not significant). M. sympodialis dominated in patients with atopic dermatitis (46%) and in healthy controls (69%). In patients with seborrhoeic dermatitis both M. sympodialis and M. obtusa were cultured in 43%. A Malassezia species extract mixture would increase the possibility of detecting IgE sensitization to Malassezia in patients with atopic dermatitis.

Adolescent↗

The vulvar skin microenvironment: impact of tight-fitting underwear on microclimate, pH and microflora.

The aim of the present study was to investigate if tight-fitting underwear (string panties) equipped with string panty liners affected the vulvar skin microenvironment differently to regular panties with standard panty liners. Thirty-two healthy women participated in a crossover study where temperature, humidity, surface pH and aerobic microflora were measured on vulvar skin. Vulvar skin temperature was 35.2 +/- 0.19 (mean +/- SEM) and 35.3 +/- 0.17 degrees C, respectively, for the two underwear systems. Mean humidity and mean skin surface pH at vulvar skin did not differ between the two systems. Barely noticeable differences were found for the aerobic microflora both at labium majus and at perineum. The mean total number of microorganisms in the two different panty liners was the same, 6.0 +/- 0.15 and 6.0 +/- 0.16, respectively (log CFU per panty liner). The differences in panty and panty liner design studied seem to have negligible impact on the vulvar skin microclimate, skin surface pH and aerobic microflora. No support was found for the assumption that a string panty system would result in higher contamination of vulvar skin by anorectal microflora.

Adult↗

The in vitro activity of pentane-1,5-diol against aerobic bacteria. A new antimicrobial agent for topical usage?

Multi-resistance to antibiotic therapy and to biocides is becoming increasingly common, which has led to mounting concern worldwide regarding the future use of traditional antimicrobials. Diols or glycols also have antimicrobial effects. Pentane-1,5-diol has low oral toxicity, is essentially non-irritating to the skin and has high antimicrobial activities against bacteria, fungi and viruses. The effect of pentane-1,5-diol against both sensitive and multi-resistant Gram-positive and Gram-negative bacteria was tested in vitro against 85 bacterial strains showing minimal inhibitory concentrations in the range of 2.5 to 15.0% (vol/vol) against both antibiotic-susceptible and multi-resistant aerobic bacteria. The exact mechanism of action is unknown but probably pentane-1,5-diol sucks water out of the bacterial cells which then collapse, a mechanism to which it is probably very difficult to develop resistance. The high activity against multi-resistant bacteria makes pentane-1,5-diol an interesting new compound for topical antimicrobial therapy in humans.

Administration, Cutaneous↗

The vulvar skin microenvironment: influence of different panty liners on temperature, pH and microflora.

The aim of this study was to confirm findings that vapour-impermeable panty liners might impair skin climate, and to assess their impact on the skin microflora. Temperature, surface pH and aerobic microflora were measured on vulvar skin of 102 women. The mean skin temperature was 1.1 degrees C higher when using a vapour-impermeable panty liner compared with not using one. Use of panty liners with vapour-permeable back sheets and acidic cores resulted in skin temperature, pH and microflora levels that were very close to those observed in persons not using liners. The temperature, pH and total number of microorganisms were significantly lower for users of vapour-permeable panty liners than for users of vapour-impermeable ones (p <0.05, p<0.001 and p<0.001, respectively). The microorganism densities were usually higher when using the vapour-impermeable panty liner, but mean differences were minor. The use of panty liners seems not to imply a microbial risk for normal, healthy women.

Adult↗

A thyroid hormone analogue, triiodothyroacetic acid, corrects corticosteroid-downregulated collagen synthesis.

The aim of this study was to compare the change in collagen synthesis between topical treatments with two doses of triiodothyroacetic acid (TRIAC), a thyroid hormone analogue, and placebo, after pretreatment with topical betamethasone 17-valerate (BM). Eighteen healthy volunteers were pretreated with BM on abdominal skin for 3 days, and were then treated for 14 days with a cream containing TRIAC (0.03% or 0.1%) or a placebo cream. Collagen production was assessed by quantifying the amino terminal propeptides of human type I and type III procollagen (PINP and PIIINP) in fluids from suction-induced blisters on the treated skin. Three days of treatment with BM led to an average reduction of PINP of 70% and of PIIINP of 50%. Seven days after treatment, the median increase in PINP was 230% (p = 0.03) in the Triac 0.03% group, 148% (p = 0.2) in the TRIAC 0.1% and 5% in the placebo group. The median increase in PINP in the skin area from the start of treatment to the end of treatment was 521% (p = 0.06) in the TRIAC 0.03% group, 339% (p = 0.2) in the TRIAC 0.1% group, and 55% in the placebo group (the p values are related to baseline). Seven days after treatment, the median increase in PIIINP was 24% (p = 0.6) in the Triac 0.03% group, 23% (p = 0.6) in the TRIAC 0.1% group, and -12% in the placebo group. The median increase in PIIINP in the skin area from the start of treatment to the end of treatment was 137% (p = 0.7) in the TRIAC 0.03% group, 230% (p = 0.9) in the TRIAC 0.1% group and 58% in the placebo group (the p values are related to baseline). Histologic examinations of sections from punch biopsies taken at the end of the treatment showed more thickened collagen fibers and increased density of PINP-producing dermal fibroblasts in the TRIAC groups compared to the placebo group. The result suggests a potential role for TRIAC-containing cream concomitant with anti-inflammatory topical treatment with potent glucocorticoids to prevent their suppressive activity on dermal collagen production.

Adrenal Cortex Hormones↗

Pityriasis versicolor.

Pityriasis versicolor is a mild or chronic condition characterized by scaly hypopigmented or hyperpigmented lesions usually affecting the trunk. The lesions vary depending on tropical or temperate climates. The disease seems to occur mainly at adolescence when the sebaceous glands are more active. Malassezia yeasts have been implicated in the pathogenesis of this disease. The mycelial form of the fungus has been suggested to be the cause of lesions. Antifungal preparations have been used to treat the initial presentation effectively, although in a proportion of patients the disease tends to reoccur. They are available in a wide range of formulations and have been shown to be safe.

Administration, Cutaneous↗

The vulva skin microclimate: influence of panty liners on temperature, humidity and pH.

Many women use panty liners between menstrual periods. The aim of this study was to investigate whether the use of such products might influence the vulva skin. Twelve healthy women were studied on four occasions with three different product constructions and on one occasion without products. Temperature, surface wetness and surface pH were measured on vulva skin. Mean skin temperature when the women were wearing a conventional panty liner (with a non-breathable back sheet) was 35.9 degrees C, compared to 34.4 degrees C when wearing no panty liner at all (p < 0.01) and 34.5 degrees C when using a panty liner with a breathable (i.e. vapour permeable) back sheet (p < 0.01). Skin humidity was significantly higher when the conventional panty liner was used compared to no panty liner or to the breathable panty liner (both cases p < 0.01). The mean pH value at the exterior aspect of the labium majus was 5.8 with the conventional panty liner, 5.2 with no panty liner and 5.3 with the breathable panty liner (p < 0.001 and p < 0.01, respectively). The results indicate that the conventional panty liner changes the vulva skin microclimate, but that the breathable panty liner to a substantial degree keeps the microclimate at an undisturbed level. The actual effect of these differences on microbiological flora will be addressed in a subsequent study.

Adult↗

Scalp psoriasis: synergy between the Malassezia yeasts and skin irritation due to calcipotriol.

To investigate if there is a synergy between the presence of the Malassezia yeasts and the adverse reaction during treatment of scalp psoriasis with calcipotriol scalp solution, patients were treated with itraconazole to reduce the number of Malassezia yeasts. This study was a double-blind, placebo-controlled parallel group study between oral itraconazole or placebo for 8 weeks in patients with scalp psoriasis. After 2 weeks, calcipotriol scalp solution was applied twice daily for 6 weeks. Altogether 137 patients, 67 in the itraconazole group and 70 in the placebo group, comprised the intention-to-treat population. There were 13 (19.4%) patients with local skin irritation in the itraconazole group compared to 33 (47.1%) in the placebo group (p < 0.001). The skin irritation was significantly lower in patients with a low number of cultured Malassezia yeasts (p = 0.017). Thus, when Malasessia was eliminated or the numbers reduced, the irritation produced by calcipotriol was significantly diminished.

Administration, Oral↗

Medical history.

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Antitussive Agents↗

Efficacy of itraconazole in the prophylactic treatment of pityriasis (tinea) versicolor.

BACKGROUND: Pityriasis (tinea) versicolor has a high tendency to recur after being treated successfully. Prophylactic treatment to reduce recurrence is needed. OBJECTIVE: To determine whether recurrence of pityriasis versicolor could be prevented by prophylactic itraconazole treatment. DESIGN: Open treatment followed by a randomized, double-blind, placebo-controlled phase. SETTING: Multinational outpatient centers. PATIENTS: A total of 239 consecutive patients were included; 238 started open treatment. A total of 209 patients started prophylactic treatment: 106 in the itraconazole group and 103 in the placebo group. INTERVENTIONS: Open treatment: itraconazole, 200 mg once daily for 7 days. Prophylactic treatment: itraconazole, 200 mg, or placebo twice daily 1 day per month for 6 consecutive months. MAIN OUTCOME MEASURES: Mycological cure rates at the end of open treatment and at the end of prophylactic treatment. RESULTS: Mycological cure at the end of open treatment was 92% (205/223). At the prophylactic treatment end point (6 months), mycological cure was 88% (90/102) in the itraconazole group and 57% (56/99) in the placebo group (P<.001). In open treatment, 11 patients were not able to be evaluated for efficacy. In prophylactic treatment, 4 patients in the itraconazole group and 4 in the placebo group were not able to be evaluated. Adverse events were reported during open treatment by 26 patients (11%) and during prophylactic treatment by 17 (16%) in the itraconazole group and 14 (14%) in the placebo group. No patients experienced any serious adverse events. CONCLUSIONS: Prophylactic itraconazole treatment is efficacious for pityriasis versicolor after 6 months, as is itraconazole in the treatment of pityriasis versicolor.

Adolescent↗

Estrogen receptor alpha, but not estrogen receptor beta, is involved in the regulation of the hair follicle cycling as well as the thickness of epidermis in male mice.

Estrogen is of importance for the regulation of hair growth and epidermal thickness. The effects of estrogen have predominantly been studied in females; however, recent studies demonstrate that estrogen also is critical for males. The aim of this study was to investigate the relative functional importance of estrogen receptor alpha and estrogen receptor beta in the regulation of the hair follicle cycling and epidermal thickness in male mice. Seven month old transgenic male mice, lacking estrogen receptor alpha (ERKO), estrogen receptor beta (BERKO), or both receptors (DERKO), were orchidectomized and treated for 3 week with 17beta-estradiol or vehicle. Orchidectomy induced a synchronized anagen phase of the hair follicles, which was inhibited by 17beta-estradiol treatment in wild-type and BERKO mice, but not in ERKO and DERKO mice. Furthermore, 17beta-estradiol treatment increased the thickness of epidermis in wild-type and BERKO mice, but not in ERKO and DERKO. This study demonstrates that estrogen is of importance for the regulation of hair follicle cycling and epidermal thickness in male mice. The effect on hair follicle cycling is caused by an estrogen receptor alpha mediated inhibition of telogen-anagen transition and the effect of estrogen to increase epidermal thickness is associated with an estrogen receptor alpha mediated increase in the proliferative rate of the keratinocytes in the basal cell layer of the epidermis.

Animals↗

Dose-response effects of tri-iodothyroacetic acid (Triac) and other thyroid hormone analogues on glucocorticoid-induced skin atrophy in the haired mouse.

Thyroid hormones have an influence on the connective tissue biology of the skin and, theoretically, topically applied thyroid hormones or hormone analogues could have a stimulatory effect on collagen synthesis. In this investigation the effect of topical tri-iodothyroacetic acid (Triac) and other thyroid hormone analogues were tested for their effect in preventing betamethasone-induced skin atrophy in the normal haired mouse. Triac, tri-iodoproprionic acid (Triprop) and the synthetically developed thyroid hormone analogue KB-026 and 2 different Triac cream formulations were applied along with betamethasone on shaved mouse skin. Triac in daily doses of 1 nmol/cm2 and higher was able to block the betamethasone-induced skin atrophy in mice skin. In high doses, Triprop and KB-026 also had a blocking effect. Triac alone had a stimulatory effect on dermal thickness. This study indicates that thyroid hormone analogues may be used to prevent corticosteroid-induced skin atrophy.

Administration, Topical↗