Search PubMed⌕ Search

Biomedical subjects

T W Fischer

Publications and source records attributed to T W Fischer.

At least 19 recordsLinked to original sources

Effect of caffeine and testosterone on the proliferation of human hair follicles in vitro.

BACKGROUND: Androgenetic alopecia (AGA) is a common problem in men of all ages, affecting approximately 50% at 50 years of age. The underlying cause is an androgen-dependent miniaturization of genetically predetermined hair follicles. Here, the hair organ culture model was used to investigate the effects of testosterone and caffeine; the latter being a promising candidate for hair growth stimulation. METHODS: Hair follicles from 14 biopsies, taken from the vertex areas from male AGA patients, were cultivated for 120-192 h in vitro with normal William's E medium (control) or William's E medium containing different concentrations of testosterone and/or caffeine. Hair shaft elongation was measured daily and at the end of cultivation, cryosections of follicles were stained with Ki-67 to evaluate the degree and localization of keratinocyte proliferation. RESULTS: Significant growth suppression was found in hair follicles treated with 5 microg/ml testosterone. This was counteracted by caffeine in concentrations of 0.001% and 0.005%. Moreover, caffeine alone led to a significant stimulation of hair follicle growth. These results were confirmed immunohistochemically by Ki-67 staining. CONCLUSIONS: Androgen-dependent growth inhibition of ex vivo hair follicles from patients suffering from AGA was present in the human hair organ culture model, a constellation which may serve for future studies to screen new substances against androgen-dependent hair loss. Caffeine was identified as a stimulator of human hair growth in vitro; a fact which may have important clinical impact in the management of AGA.

Adult↗

Significance of interleukin-16, macrophage-derived chemokine, eosinophil cationic protein and soluble E-selectin in reflecting disease activity of atopic dermatitis--from laboratory parameters to clinical scores.

BACKGROUND: The search for the ideal clinical score reflecting atopic dermatitis (AD) severity has developed in parallel with unveiling key events in disease pathogenesis and finding laboratory parameters for monitoring disease activity. A major difficulty in assessing the relevance of reported serum markers of AD severity is the use of nonvalidated referent tools, which compromises comparison of results across studies. OBJECTIVES: The aim of our study was to compare the significance of serum levels of interleukin (IL)-16, macrophage-derived chemokine (MDC), soluble E-selectin (sE-selectin) and eosinophil cationic protein (ECP) in reflecting AD severity and identify the most relevant parameter for monitoring the course of disease. Serum levels were tested against the same referent severity score in the same time frame and group of patients. METHODS: The Severity Scoring of Atopic Dermatitis (SCORAD) index was used for assessment of disease severity in 21 adult patients in acute stage of AD and after complete resolution of clinical findings. Serum levels of IL-16, MDC, ECP and sE-selectin were measured at the same time points in 18 patients and compared with healthy nonatopic controls. The correlation between SCORAD and each laboratory parameter was tested for significance and compared. RESULTS: Serum levels of IL-16, MDC, ECP and sE-selectin were significantly higher in patients in acute stage of AD compared with controls and decreased significantly after treatment, in parallel with clinical improvement. All monitored parameters reflected disease severity assessed by the clinical score. We found the highest significance level of correlation with SCORAD for IL-16 (r = 0.68, P =0.0019), followed by ECP (r = 0.65, P = 0.0032) and MDC (r = 0.55, P =0.0326). There was significant correlation between serum levels of IL-16 and MDC (r = 0.53, P = 0.0443) and ECP and sE-selectin (r = 0.48, P = 0.0427). CONCLUSIONS: The study established a significant correlation between serum levels of IL-16 and SCORAD in adult AD patients. We report a significant correlation between IL-16 and MDC, both T-helper 2 activation markers. Our data suggested that IL-16 reflects most convincingly disease severity and may be used as a marker in clinical studies preferentially in combination with a clinical activity score.

Adolescent↗

Melatonin increases survival of HaCaT keratinocytes by suppressing UV-induced apoptosis.

Melatonin is a potent antioxidant and direct radical scavenger. As keratinocytes represent the major population in the skin and UV light causes damage to these cells, the possible protective effects of melatonin against UV-induced cell damage in HaCaT keratinocytes were investigated in vitro. Cells were preincubated with melatonin at graded concentrations from 10(-9) to 10(-3) m for 30 min prior to UV irradiation at doses of 25 and 50 mJ/cm2. Biological markers of cellular viability such as DNA synthesis and colony-forming efficiency as well as molecular markers of apoptosis were measured. DNA synthesis was determined by [3H]-thymidine incorporation into insoluble cellular fraction, clonogenicity through plating efficiency experiments and apoptosis by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. DNA synthesis experiments showed a strong protective effect by preincubation with melatonin at concentrations of 10(-4) m (P < 0.01) and 10(-3) m (P < 0.001). Additional postirradiation treatment with melatonin showed no increase in the pre-UV incubation protective effect. These results indicate that preincubation is a requirement for melatonin to exert its protective effects. The mechanism of melatonin's protective effect (10(-6) to 10(-3) m) includes inhibition of apoptosis as measured by TUNEL assay. Moreover, the biological significance of these effects is supported by clonogenic studies showing a significantly higher number of colonies in cultures treated with melatonin compared to controls. Thus, pretreatment with melatonin led to strong protection against UVB-induced damage in keratinocytes.

Apoptosis↗

Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines.

Melatonin has been shown to have oncostatic effects on malignant melanoma in vitro and in vivo. We studied the growth suppressive effects of melatonin over a wide range of concentrations in four melanoma cell lines (SBCE2, WM-98, WM-164 and SKMEL-188) representative for different growth stages and phenotype. Melanoma cells were incubated with melatonin 10(-12)-10(-3) M, and proliferation and clonogenicity was assessed at 12 h and 14 days, respectively. We also determined the expression of cytosolic quinone oxidoreductases NQO1, NQO2 (known as MT3 receptor) and nuclear receptor RORalpha by RT-PCR. Melatonin at pharmacological concentrations (10(-3)-10(-7) M) suppressed proliferation in all melanoma cell lines. In SKMEL-188 cells cultured in serum-free media, melatonin at low concentrations (10(-12)-10(-10) M) also slightly attenuated the proliferation. The effects of pharmacological doses of melatonin were confirmed in the clonogenic assay. Expression of NQO1 was detected in all cell lines, whereas NQO2 and nuclear receptor RORalpha including its isoform RORalpha4 were present only in SBCE2, WM-164 and WM-98. Thus, melatonin differentially suppressed proliferation in melanoma cell lines of different behaviour. The intensity of the oncostatic response to melatonin could be related to the cell-line specific pattern of melatonin cellular receptors and cytosolic binding protein expression.

Cell Nucleus↗

Protective effects of different marigold (Calendula officinalis L.) and rosemary cream preparations against sodium-lauryl-sulfate-induced irritant contact dermatitis.

In the present study, we evaluated the protective action of cream preparations containing seven different types of marigold and rosemary extracts in vivo in healthy volunteers with experimentally induced irritant contact dermatitis (ICD). Marigold and rosemary extracts in base cream DAC (Deutscher Arzneimittel-Codex = German Pharmaceutical Codex) were tested in a 4-day repetitive irritation test using sodium lauryl sulfate. The effect was evaluated visually and quantified by noninvasive bioengineering methods, namely chromametry and tewametry. When the test products were applied parallel to the induction period of ICD, a statistically significant protective effect of all cream preparations was observed by all methods. This effect, although not statistically significant, was superior to control by undyed marigold und faradiol ester-enriched extracts in chromametry and by dyed and undyed rosemary extracts in tewametry. The sequential treatment (postirritation) once a day for 5 days was without any effect. Thus, a protective effect of some marigold and rosemary extracts against ICD could be shown in the elicitation phase.

Administration, Cutaneous↗

The objective severity assessment of atopic dermatitis (OSAAD) score: validity, reliability and sensitivity in adult patients with atopic dermatitis.

BACKGROUND: The Objective Severity Assessment of Atopic Dermatitis (OSAAD) score is a recently developed scale for evaluation of severity of atopic dermatitis, constructed from the assessment of epidermal barrier function, and properties using noninvasive bioengineering methods and computer-assisted estimates of disease extent. The method has been validated for use in infants and children with atopic dermatitis and compared with a referent scoring system. OBJECTIVES: The aim of the present study was to test the validity, reliability and sensitivity of the OSAAD score as an objective tool for the assessment of the severity of atopic dermatitis in adult patients. METHODS: Thirty-two adult patients with atopic dermatitis were included in the study. To assess the validity of the OSAAD score we tested it against the Severity Scoring of Atopic Dermatitis (SCORAD) index of the European Task Force on Atopic Dermatitis as a referent clinical severity scale, and the serum levels of interleukin (IL)-16 as a laboratory variable for monitoring the activity of atopic dermatitis. Responsiveness to change was assessed in a longitudinal study comparing OSAAD, SCORAD and serum levels of IL-16 before and after treatment. To test the reliability of the OSAAD score we studied the interobserver variability of the score recorded by three independent board-certified dermatologists in 16 patients and compared it with SCORAD. RESULTS: We report a significant correlation between the OSAAD and the SCORAD index as an acknowledged referent severity scale. The OSAAD score correlated significantly with the serum levels of IL-16 in the acute stage of atopic dermatitis. In a longitudinal study, the OSAAD score decreased significantly, parallel with improvement of the skin findings and a significant decrease in the SCORAD score and IL-16 serum levels. We report improved interobserver variability for the OSAAD score compared with SCORAD. CONCLUSIONS: This is the first study validating the OSAAD score as a sensitive and reliable tool for the assessment of the severity of atopic dermatitis in adult patients.

Acute Disease↗

Melatonin increases anagen hair rate in women with androgenetic alopecia or diffuse alopecia: results of a pilot randomized controlled trial.

BACKGROUND: In addition to the well-known hormonal influences of testosterone and dihydrotestosterone on the hair cycle, melatonin has been reported to have a beneficial effect on hair growth in animals. The effect of melatonin on hair growth in humans has not been investigated so far. OBJECTIVES: To examine whether topically applied melatonin influences anagen and telogen hair rate in women with androgenetic or diffuse hair loss. METHODS: A double-blind, randomized, placebo-controlled study was conducted in 40 women suffering from diffuse alopecia or androgenetic alopecia. A 0.1% melatonin or a placebo solution was applied on the scalp once daily for 6 months and trichograms were performed to assess anagen and telogen hair rate. To monitor effects of treatment on physiological melatonin levels, blood samples were taken over the whole study period. RESULTS: Melatonin led to a significantly increased anagen hair rate in occipital hair in women with androgenetic hair loss compared with placebo (n=12; P=0.012). For frontal hair, melatonin gave a significant increase in the group with diffuse alopecia (n=28; P=0.046). The occipital hair samples of patients with diffuse alopecia and the frontal hair counts of those with androgenetic alopecia also showed an increase of anagen hair, but differences were not significant. Plasma melatonin levels increased under treatment with melatonin, but did not exceed the physiological night peak. CONCLUSIONS: To the authors' knowledge, this pilot study is the first to show that topically applied melatonin might influence hair growth in humans in vivo. The mode of action is not known, but the effect might result from an induction of anagen phase.

Administration, Topical↗

The quality of human skin xenografts on SCID mice: a noninvasive bioengineering approach.

BACKGROUND: Animal models are important tools for studies in skin physiology and pathophysiology. Due to substantial differences in skin characteristics such as thickness and number of adnexa, the results of animal studies cannot always be directly transferred to the human situation. Therefore, transplantation of human skin on to SCID (severe combined immunodeficiency) mice might offer a promising tool to perform studies in viable human skin without the direct need for human volunteers. OBJECTIVES: To characterize the physiological and anatomical changes of a human skin transplant on a SCID animal host. METHODS: In this study human skin was transplanted on to 32 SCID mice and followed for 6 months. Barrier function was assessed by transepidermal water loss (TEWL; tewametry) and moisture content of the stratum corneum was studied by measurement of electrical capacitance (corneometry). RESULTS: The results showed considerable deviations of TEWL values and skin hydration between the grafts and human skin in vivo. The human skin showed epidermal hyperkeratosis and moderate sclerosis of the corium 4 and 6 months after transplantation on to SCID mice. CONCLUSIONS: Our results indicate that human skin does not completely preserve its physiological and morphological properties after transplantation on to SCID mice. Therefore, results from experiments using this model system need to be discussed cautiously.

Animals↗

[Hair loss in internal medical illnesses].

Hair loss related to internal diseases is generally temporary and often fully reversible. An iron- or protein-deficiency induced hair loss may be cured by simple substitution. In acute internal diseases, fever and after operations the patient may expect complete recovery of the hair loss without therapy. Symptomatic alopecia due to chronic diseases has a different prognosis and is dependent on the severity and character of the underlaying disease. If the systemic disease can be cured the hair loss may be decreased. Treatment and diagnosis of the systemic disease is recommended to be performed in cooperation with experts of internal medicine, oncologists and specialists of endocrinology.

Adult↗

[Hairdex: a tool for evaluation of disease-specific quality of life in patients with hair diseases].

Because of a strong reduction of life quality in patients with hair loss, a special questionnaire was developed following the general Skindex questionnaire for dermatoses. The Hairdex was evaluated in 75 female hair patients. The aim of the study was to prove the questionnaire's statistical values, reliability, validity, general acceptance and accuracy. The clinical manifestation of hair loss was categorized as "not visible", slightly visible" and "obviously visible". The hair loss lead to great differences in the life quality of both the patients with obvious hair loss and in patients with non-visible hair loss, especially in the categories "emotions", "self-confidence" and "stigmatization". The convergent and discriminant validity of the questionnaire was satisfactory. The acceptance of the questionnaire was very good with 90%. The hairdex-questionnaire represents a reliable and patient-oriented instrument for evaluation of life quality in hair diseases. The reliability of the questionnaire concerning longitudinal therapeutic effects will need to be investigated in further studies.

Adult↗

Melatonin reduces UV-induced reactive oxygen species in a dose-dependent manner in IL-3-stimulated leukocytes.

Reactive oxygen species (ROS) are presumed to be involved in inflammatory UV reactions of the skin. This in vitro study was performed to investigate the suppressive effect of melatonin in interleukin-3 (IL-3) stimulated leukocytes. Neutrophilic granulocytes were isolated from EDTA-treated whole blood and placed in a phosphate-buffered saline (PBS) containing IL-3. Cell suspensions were either treated with PBS (control) or with increasing doses of melatonin (0.1, 0.5, 1, 2, 3, 5, 7.5, 10 mmol). One PBS solution was left unirradiated and the other nine solutions (PBS and melatonin) were irradiated with 750 mJ/cm2 UVB light (280-360 nm, max: 310 nm). Radical formation was measured by the chemiluminescence technique. UV-irradiated leukocytes showed a 5-fold higher radical formation than unirradiated leukocytes. Melatonin, in increasing doses in powers of ten, led to a maximum suppression of free radicals at 10 nmol (P= 0.01) and 1 mmol melatonin (P= 0.001), showing a biphasic, non-linear, dose response relationship. Melatonin, given in amounts of 0.1-10 mmol, led to a direct dose-dependent suppression of ROS. Radical formation was suppressed significantly in a range from 0.5 to 10 mmol (P= 0.001). Melatonin is known to function as a radical scavenger and antioxidant; some of these melatonin effects may be receptor independent, while others may be receptor dependent.

Dose-Response Relationship, Drug↗

Strategies of coping and quality of life in women with alopecia.

BACKGROUND: Measurements of the quality of life (QoL) have recently become an integral part of dermatological studies. Our hypothesis is that QoL in patients with certain diseases can be affected by strategies of coping behaviour, as well as by personality traits. OBJECTIVES: The aim of this study was to explore the particular correlation between QoL and strategies of coping in female patients with alopecia. PATIENTS: Fifty female patients, diagnosed with either diffuse or androgenetic alopecia, were evaluated by the use of Hairdex, an instrument developed to measure QoL in patients with hair loss. Most patients also underwent additional psychological assessments. RESULTS: Findings indicated that patients with highly visible hair loss reported a more negative impact on four Hairdex dimensions (functioning, emotions, self-confidence and stigmatization) than patients whose hair loss was only slightly visible. However, a subgroup of patients, with non-visible symptoms of hair loss, showed striking signs of psychological disturbance. These disturbed patients displayed either dysmorphophobic or affective disorder tendencies. CONCLUSIONS: Future studies using QoL as an instrument in research on patients with alopecia should consider that in cases of female alopecia these measurements may be affected by psychological disturbances.

Adaptation, Psychological↗