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1.
Br J Dermatol ; 184(1): 96-110, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32271938

RESUMEN

BACKGROUND: Human hair is highly responsive to stress, and human scalp hair follicles (HFs) contain a peripheral neuroendocrine equivalent of the systemic hypothalamic-pituitary-adrenal (HPA) stress axis. Androgenetic alopecia (AGA) is supposed to be aggravated by stress. We used corticotropin-releasing hormone (CRH), which triggers the HPA axis, to induce a stress response in human ex vivo male AGA HFs. Caffeine is known to reverse testosterone-mediated hair growth inhibition in the same hair organ culture model. OBJECTIVES: To investigate whether caffeine would antagonize CRH-mediated stress in these HFs. METHODS: HFs from balding vertex area scalp biopsies of men affected by AGA were incubated with CRH (10-7 mol L-1 ) with or without caffeine (0·001% or 0·005%). RESULTS: Compared to controls, CRH significantly enhanced the expression of catagen-inducing transforming growth factor-ß2 (TGF-ß2) (P < 0·001), CRH receptors 1 and 2 (CRH-R1/2) (P < 0·01), adrenocorticotropic hormone (ACTH) (P < 0·001) and melanocortin receptor 2 (MC-R2) (P < 0·001), and additional stress-associated parameters, substance P and p75 neurotrophin receptor (p75NTR ). CRH inhibited matrix keratinocyte proliferation and expression of anagen-promoting insulin-like growth factor-1 (IGF-1) and the pro-proliferative nerve growth factor receptor NGF-tyrosine kinase receptor A (TrkA). Caffeine significantly counteracted all described stress effects and additionally enhanced inositol trisphosphate receptor (IP3 -R), for the first time detected in human HFs. CONCLUSIONS: These findings provide the first evidence in ex vivo human AGA HFs that the stress mediator CRH induces not only a complex intrafollicular HPA response, but also a non-HPA-related stress response. Moreover, we show that these effects can be effectively antagonized by caffeine. Thus, these data strongly support the hypothesis that stress can impair human hair physiology and induce hair loss, and that caffeine may effectively counteract stress-induced hair damage and possibly prevent stress-induced hair loss.


Asunto(s)
Hormona Liberadora de Corticotropina , Receptor de Melanocortina Tipo 2 , Hormona Adrenocorticotrópica/metabolismo , Andrógenos , Cafeína/farmacología , Hormona Liberadora de Corticotropina/metabolismo , Folículo Piloso/metabolismo , Humanos , Sistema Hipotálamo-Hipofisario/metabolismo , Masculino , Sistema Hipófiso-Suprarrenal/metabolismo , Proteínas Tirosina Quinasas Receptoras , Receptores de Factor de Crecimiento Nervioso , Cuero Cabelludo/metabolismo , Sustancia P
2.
Br J Dermatol ; 179(2): 471-477, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29577247

RESUMEN

BACKGROUND: Increased skin-surface pH is an important host-related factor for deteriorated barrier function in aged skin. OBJECTIVES: We investigated whether restoration of skin pH through topical application of a water-in-oil emulsion with pH 4 improved the barrier homeostasis in aged skin, and compared the effects with an identical galenic formulation with pH 5·8. METHODS: The effects of the test formulations on barrier recovery were investigated by repeated measurements of transepidermal water loss (TEWL) and skin pH 3 h, 6 h and 24 h after acetone-induced impairment of barrier function in aged skin. The long-term effects of the pH 4 and pH 5·8 emulsions were analysed by investigation of the barrier integrity and cohesion, the skin-surface pH and the skin roughness and scaliness before and after a 4-week, controlled application of the formulations. RESULTS: The application of the pH 4 emulsion accelerated barrier recovery in aged skin: 3 h and 6 h after acetone-induced barrier disruption the differences in the TEWL recovery between the pH 4 treated and acetone control fields were significant. Furthermore, long-term application of the pH 4 formulation resulted in significantly decreased skin pH, enhanced barrier integrity and reduced skin-surface roughness and scaliness. At the same time points, the pH 5·8 formulation exerted only minor effects on the barrier function parameters. CONCLUSIONS: Exogenous acidification through topical application of a water-in-oil emulsion with pH 4 leads to improvement of the skin barrier function and maintenance of the barrier homeostasis in aged skin.


Asunto(s)
Fármacos Dermatológicos/administración & dosificación , Envejecimiento de la Piel/efectos de los fármacos , Piel/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Fármacos Dermatológicos/química , Emulsiones , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Aceites/química , Estudios Prospectivos , Piel/química , Factores de Tiempo , Resultado del Tratamiento , Agua/química , Pérdida Insensible de Agua/efectos de los fármacos
3.
Br J Dermatol ; 171(5): 1031-43, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24836650

RESUMEN

BACKGROUND: Caffeine reportedly counteracts the suppression of hair shaft production by testosterone in organ-cultured male human hair follicles (HFs). OBJECTIVES: We aimed to investigate the impact of caffeine (i) on additional key hair growth parameters, (ii) on major hair growth regulatory factors and (iii) on male vs. female HFs in the presence of testosterone. METHODS: Microdissected male and female human scalp HFs were treated in serum-free organ culture for 120 h with testosterone alone (0·5 µg mL(-1)) or in combination with caffeine (0·005-0·0005%). The following effects on hair shaft elongation were evaluated by quantitative (immuno)histomorphometry: HF cycling (anagen-catagen transition); hair matrix keratinocyte proliferation; expression of a key catagen inducer, transforming growth factor (TGF)-ß2; and expression of the anagen-prolonging insulin-like growth factor (IGF)-1. Caffeine effects were further investigated in human outer root sheath keratinocytes (ORSKs). RESULTS: Caffeine enhanced hair shaft elongation, prolonged anagen duration and stimulated hair matrix keratinocyte proliferation. Female HFs showed higher sensitivity to caffeine than male HFs. Caffeine counteracted testosterone-enhanced TGF-ß2 protein expression in male HFs. In female HFs, testosterone failed to induce TGF-ß2 expression, while caffeine reduced it. In male and female HFs, caffeine enhanced IGF-1 protein expression. In ORSKs, caffeine stimulated cell proliferation, inhibited apoptosis/necrosis, and upregulated IGF-1 gene expression and protein secretion, while TGF-ß2 protein secretion was downregulated. CONCLUSIONS: This study reveals new growth-promoting effects of caffeine on human hair follicles in subjects of both sexes at different levels (molecular, cellular and organ).


Asunto(s)
Cafeína/farmacología , Cabello/crecimiento & desarrollo , Factor I del Crecimiento Similar a la Insulina/efectos de los fármacos , Inhibidores de Fosfodiesterasa/farmacología , Factor de Crecimiento Transformador beta2/efectos de los fármacos , Andrógenos/farmacología , Antígenos/metabolismo , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Femenino , Cabello/efectos de los fármacos , Folículo Piloso/efectos de los fármacos , Humanos , Técnicas In Vitro , Factor I del Crecimiento Similar a la Insulina/metabolismo , Proteínas de Filamentos Intermediarios/metabolismo , Queratinocitos/efectos de los fármacos , Masculino , Testosterona/farmacología , Factor de Crecimiento Transformador beta2/metabolismo
4.
J Eur Acad Dermatol Venereol ; 28 Suppl 3: 9-15, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24702445

RESUMEN

BACKGROUND: Whereas emollients are integral to the long-term management of atopic dermatitis (AD), the evidence for their efficacy in disease flares is limited. OBJECTIVE: We aimed to investigate the stand-alone efficacy of an emollient formulation with regard to improvement of the clinical symptoms, skin barrier function and reduction of pathogenic bacterial colonization in acute stage of AD. MATERIALS AND METHODS: Twenty AD volunteers aged 12-65 years with symmetric, mild to moderately severe inflammatory lesions on the forearms/arms were recruited for the study. At inclusion, the forearms/arms of each volunteer were randomized to receive for 1 week either an o/w formulation containing licochalcone A (Glycyrrhiza Inflata root extract), decanediol, menthoxypropanediol and ω-6-fatty acids (emollient arm) or 1% hydrocortisone (HC arm); after 1 week, the application of the emollient and HC were discontinued and the volunteers applied a w/o emollient containing licochalcone A and ω-6-fatty acids on both arms for further 3 weeks. The outcomes included reduction of the clinical and itch severity, decrease in S.aureus colonization, improvement of the barrier function, skin hydration and skin tolerability assessed after 1 week (D7) and after 4 weeks (D28) respectively. RESULTS: In both arms, there was a significant decrease in the severity score, itch intensity, erythema and TEWL on D7 and D28 compared to baseline. In addition, emollient use resulted in pronounced decrease in S.aureus colonization and significant increase of skin hydration on D7. The comparison of the outcomes, based on percentage change from baseline, showed no significant differences between the emollient and HC arm at any time point. CONCLUSIONS: The results of the study indicate that the 1-week stand-alone application of an emollient, tailored to target inflammation, pruritus, compromised barrier function and pathogenic bacterial colonization may offer benefit for the improvement of mild to moderately severe localized flares of AD.


Asunto(s)
Dermatitis Atópica/tratamiento farmacológico , Emolientes/uso terapéutico , Adolescente , Adulto , Anciano , Niño , Dermatitis Atópica/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto Joven
5.
J Eur Acad Dermatol Venereol ; 27 Suppl 2: 6-11, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23731195

RESUMEN

BACKGROUND: Inflammation, increased sebum production and P. acnes colonization are key factors in acne pathogenesis. Cosmetic formulations based on a combination of active compounds with in vitro proven anti-inflammatory, sebum regulating and P. acnes reducing properties may therefore contribute to improve the clinical signs and associated burden of disease. OBJECTIVE: To provide in vivo proof-of-concept, we performed a 9-week, double-blind, randomized, vehicle-controlled study to assess the stand-alone efficacy of a skin care formulation containing licochalcone A, l-carnitine and 1,2-decanediol in volunteers with mild to moderately severe acne (10-25 inflammatory lesions) involving the face. MATERIALS AND METHODS: After enrolment followed by a 1-week standardization of the cleansing procedure, 60 volunteers aged 14-40 years (40 women and 20 men, mean age 22.4 years) were randomized into two groups of 30 volunteers each, to apply either the active formulation or the vehicle twice daily on the face for 8 weeks. Reduction in the lesion count, P. acnes and sebum levels, stratum corneum hydration, Dermatology Life Quality Index (DLQI) and skin tolerability, assessed after 4 and 8 weeks were defined as outcomes. RESULTS: Compared to baseline, the active formulation group showed at the end of the study a reduction in the mean total lesions count and papular lesions, significant reduction in the pustules (P < 0.05) and sebum levels (P < 0.01), marked reduction in P. acnes and improvement of DLQI. No significant changes in the respective parameters were found in the vehicle group. At the end of the study, greater reduction in the total lesion count, papules and pustules, P. acnes colonization, sebum production and more pronounced improvement of life quality in the active formulation group compared to the vehicle were found. CONCLUSIONS: Our results provide evidence for improved outcomes in result of the application of the active formulation compared to the vehicle from both physician's and patient's perspective.


Asunto(s)
Acné Vulgar/tratamiento farmacológico , Carnitina/uso terapéutico , Chalconas/uso terapéutico , Alcoholes Grasos/uso terapéutico , Glicoles/uso terapéutico , Adolescente , Adulto , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Masculino , Vehículos Farmacéuticos , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Adulto Joven
6.
Br J Dermatol ; 167(4): 787-93, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22578221

RESUMEN

BACKGROUND: The barrier perturbation pattern and molecular markers of inflammation upon tandem repeated irritation in chronologically aged skin have not been previously studied. OBJECTIVES: We aimed to investigate the barrier impairment kinetic and in vivo cytokine profile following sequential irritation with sodium lauryl sulfate (SLS) and undiluted toluene (Tol) in aged compared with young skin. METHODS: Four fields on the volar forearm of healthy aged and young volunteers (median age, respectively, 63.9 and 32.6 years) were sequentially exposed to 0.5% SLS and undiluted toluene in a controlled tandem repeated irritation test; an adjacent nontreated field served as control. The permeability barrier function was monitored by repeated measurements of transepidermal water loss (TEWL), capacitance and erythema every 24 h up to 96 h. The stratum corneum cytokines were harvested by sequential tape stripping and quantified by multiplex bead array and enzyme-linked immunosorbent assay. RESULTS: Compared with young skin, aged skin was characterized by delayed and/or less pronounced alterations in the visual irritation score, TEWL, chromametry a*-value and capacitance, assessed by the respective Δ-values for each parameter and monitoring time point. In both groups, exposure to SLS/SLS, SLS/Tol and Tol/SLS resulted in decreased interleukin (IL)-1α levels, whereas the application of Tol/Tol induced an increase in IL-1α. Furthermore, decreased IL-1 receptor antagonist (IL-1RA) levels and a lower IL-1RA/IL-1α ratio were found following repeated exposure to the irritants. CONCLUSIONS: Our results provide evidence for selective alterations in the cytokine profile and distinct barrier impairment kinetic following tandem repeated irritation with SLS and Tol in aged compared with young skin in vivo.


Asunto(s)
Citocinas/metabolismo , Dermatitis Irritante/etiología , Epidermis/efectos de los fármacos , Envejecimiento de la Piel/efectos de los fármacos , Piel/efectos de los fármacos , Dodecil Sulfato de Sodio/toxicidad , Tensoactivos/toxicidad , Adulto , Anciano , Agua Corporal/metabolismo , Dermatitis Irritante/metabolismo , Ensayo de Inmunoadsorción Enzimática , Epidermis/metabolismo , Eritema/inducido químicamente , Femenino , Humanos , Interleucina-1alfa/metabolismo , Masculino , Persona de Mediana Edad , Receptores Tipo I de Interleucina-1/antagonistas & inhibidores , Receptores Tipo I de Interleucina-1/metabolismo , Solventes/toxicidad , Tolueno/toxicidad , Adulto Joven
7.
Z Gerontol Geriatr ; 45(1): 45-9, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22278006

RESUMEN

PURPOSE: The aim was to present current knowledge about pain assessment in people with dementia and to discuss special challenges and possible solutions. METHODS: A literature search in MEDLINE® was performed. RESULTS: Due to the changing demographics of an aging population, an increasing number of people with dementia is expected. Many of these people will simultaneously suffer pain. Under-detection and under-treatment of pain in persons suffering from dementia is often described. As dementia progresses, the ability of the sufferer to verbally communicate his/her pain is often compromised, complicating the task of recognizing and treating pain. To improve pain recognition in dementia, many pain assessment tools have been developed. However, psychometric properties have to date been insufficiently examined. IMPLICATIONS: Self-report ratings should be performed as long as justifiable. Behavioural pain assessment tools should be used in advanced dementia despite their current imperfections: in particular, the PAINAD for daily use and the PACSLAC at longer intervals. All available additional information about pain should be considered.


Asunto(s)
Demencia/diagnóstico , Demencia/epidemiología , Autoevaluación Diagnóstica , Evaluación Geriátrica/métodos , Dimensión del Dolor/métodos , Dolor/diagnóstico , Dolor/epidemiología , Anciano , Anciano de 80 o más Años , Comorbilidad , Femenino , Evaluación Geriátrica/estadística & datos numéricos , Humanos , Masculino , Dimensión del Dolor/estadística & datos numéricos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
8.
Hautarzt ; 60(12): 962-72, 2009 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-19957072

RESUMEN

Melatonin, the pineal gland hormone and a strong antioxidant, has long been known, particularly in animal-experiment based research and the wool-producing industry, to be a potent regulatory neuroendocrine substance in relation to hair growth, hair color and hair cycle, depending on light periods, seasonal rhythms, environmental factors and reproductive rhythms. Nevertheless, the biological mechanisms of this extremely versatile hormone, especially with regard to human hair follicles, are not fully understood. In recent years, however, essential knowledge has been gained on the melatoninergic system of the skin, melatonin levels in keratinocytes and hair follicles, extrapineal intrafollicular melatonin synthesis and noradrenalin-induced increase in synthesis, as well as hair cycle-dependent expression of the membrane-bound melatonin receptor MT2 and the nuclear receptor RORalpha. Functional data on the growth of human hair both in vitro and in vivo show that melatonin might play an essential role in hair physiology.


Asunto(s)
Cabello/fisiología , Melatonina/fisiología , Andrógenos/fisiología , Animales , Línea Celular , Receptor alfa de Estrógeno/fisiología , Estrógenos/fisiología , Femenino , Color del Cabello , Folículo Piloso/fisiología , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Miembro 1 del Grupo F de la Subfamilia 1 de Receptores Nucleares/fisiología , Receptor de Melatonina MT1/fisiología , Receptor de Melatonina MT2/fisiología
9.
J Pineal Res ; 44(4): 397-407, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18086147

RESUMEN

Melatonin is a recognized antioxidant with high potential as a protective agent in many conditions related to oxidative stress such as neurodegenerative diseases, ischemia/reperfusion syndromes, sepsis and aging. These processes may be favorably affected by melatonin through its radical scavenging properties and/or antiapoptotic activity. Also, there is increasing evidence that these effects of melatonin could be relevant in keratinocytes, the main cell population of the skin where it would contribute to protection against damage induced by ultraviolet radiation (UVR). We therefore investigated the kinetics of UVR-induced apoptosis in cultured keratinocytes characterizing the morphological and mitochondrial changes, the caspases-dependent apoptotic pathways and involvement of poly(ADP-ribose) polymerase (PARP) activation as well as the protective effects of melatonin. When irradiated with UVB radiation (50 mJ/cm(2)), melatonin treated, cultured keratinocytes were more confluent, showed less cell blebbing, more uniform shape and less nuclear condensation as compared to irradiated, nonmelatonin-treated controls. Preincubation with melatonin also led to normalization of the decreased UVR-induced mitochondrial membrane potential. These melatonin effects were followed by suppression of the activation of mitochondrial pathway-related initiator caspase 9 (casp-9), but not of death receptor-dependent casp-8 between 24 and 48 hr after UVR exposure. Melatonin down-regulated effector caspases (casp-3/casp-7) at 24-48 hr post-UV irradiation and reduced PARP activation at 24 hr. Thus, melatonin is particularly active in UV-irradiated keratinocytes maintaining the mitochondrial membrane potential, inhibiting the consecutive activation of the intrinsic apoptotic pathway and reducing PARP activation. In conclusion, these data provide detailed evidence for specific antiapoptotic mechanisms of melatonin in UVR-induced damage of human keratinocytes.


Asunto(s)
Antioxidantes/farmacología , Caspasa 3/biosíntesis , Caspasa 7/biosíntesis , Caspasa 9/biosíntesis , Queratinocitos/enzimología , Melatonina/farmacología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de la radiación , Poli(ADP-Ribosa) Polimerasas/biosíntesis , Rayos Ultravioleta/efectos adversos , Animales , Línea Celular , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/efectos de la radiación , Activación Enzimática/efectos de los fármacos , Activación Enzimática/efectos de la radiación , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/efectos de la radiación , Humanos , Queratinocitos/patología , Poli(ADP-Ribosa) Polimerasa-1 , Piel/enzimología , Piel/patología , Factores de Tiempo
10.
Int J Oncol ; 29(3): 665-72, 2006 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16865283

RESUMEN

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.


Asunto(s)
Depuradores de Radicales Libres/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Melanoma/genética , Melatonina/farmacología , NAD(P)H Deshidrogenasa (Quinona)/genética , Quinona Reductasas/genética , Receptores Citoplasmáticos y Nucleares/genética , Transactivadores/genética , Núcleo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Medio de Cultivo Libre de Suero , Citosol/metabolismo , Humanos , Melanoma/metabolismo , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Miembro 1 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Quinona Reductasas/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores de Ácido Retinoico/genética , Receptores de Ácido Retinoico/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transactivadores/metabolismo , Células Tumorales Cultivadas , Ensayo de Tumor de Célula Madre
12.
Ther Umsch ; 59(5): 238-42, 2002 May.
Artículo en Alemán | MEDLINE | ID: mdl-12090121

RESUMEN

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.


Asunto(s)
Alopecia/etiología , Adulto , Niño , Diagnóstico Diferencial , Femenino , Humanos , Medicina Interna , Masculino , Remisión Espontánea , Factores de Riesgo
15.
Int J Dermatol ; 46(1): 27-35, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17214716

RESUMEN

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.


Asunto(s)
Alopecia/patología , Andrógenos/farmacología , Cafeína/farmacología , Folículo Piloso/efectos de los fármacos , Inhibidores de Fosfodiesterasa/farmacología , Testosterona/farmacología , Adulto , Alopecia/metabolismo , Biopsia , Folículo Piloso/crecimiento & desarrollo , Humanos , Inmunohistoquímica , Técnicas In Vitro , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Cuero Cabelludo/patología
16.
Br J Dermatol ; 154(6): 1112-7, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16704642

RESUMEN

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.


Asunto(s)
Biomarcadores/sangre , Dermatitis Atópica/sangre , Adolescente , Adulto , Quimiocina CCL22 , Quimiocinas CC/sangre , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/patología , Fármacos Dermatológicos/uso terapéutico , Selectina E/sangre , Proteína Catiónica del Eosinófilo/sangre , Femenino , Humanos , Interleucina-16/sangre , Masculino , Índice de Severidad de la Enfermedad
17.
J Pineal Res ; 40(1): 18-26, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16313494

RESUMEN

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.


Asunto(s)
Apoptosis/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Queratinocitos/efectos de la radiación , Melatonina/farmacología , Células Cultivadas , Relación Dosis-Respuesta en la Radiación , Humanos , Etiquetado Corte-Fin in Situ , Queratinocitos/metabolismo , Timidina/metabolismo , Rayos Ultravioleta
18.
Skin Pharmacol Physiol ; 18(4): 195-200, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15908760

RESUMEN

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.


Asunto(s)
Calendula , Dermatitis Irritante/tratamiento farmacológico , Rosmarinus , Dodecil Sulfato de Sodio/toxicidad , Administración Cutánea , Adolescente , Adulto , Antiinflamatorios/uso terapéutico , Dermatitis Irritante/etiología , Femenino , Humanos , Hidrocortisona/uso terapéutico , Masculino , Extractos Vegetales/uso terapéutico , Método Simple Ciego
19.
Br J Dermatol ; 153(4): 767-73, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16181458

RESUMEN

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.


Asunto(s)
Dermatitis Atópica/diagnóstico , Índice de Severidad de la Enfermedad , Enfermedad Aguda , Adolescente , Adulto , Biomarcadores/sangre , Dermatitis Atópica/patología , Dermatitis Atópica/fisiopatología , Diagnóstico por Computador/métodos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Interleucina-16/sangre , Masculino , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Pérdida Insensible de Agua
20.
Skin Pharmacol Appl Skin Physiol ; 16(6): 379-85, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-14528062

RESUMEN

The hormone melatonin is characterized by numerous pharmacological effects. The influence of melatonin on the growth of the human hair follicle was shown in previous investigations. In the present study, the effects of melatonin were investigated by means of proliferation tests of HaCaT keratinocytes using the [3H]thymidine incorporation, a fluorescence assay with Hoechst dye 33342 and the ATP bioluminescence assay. The aim of the study was to find melatonin concentrations suitable for treatments of the skin and whether there is a cytotoxic effect on HaCaT cells. The different proliferative activity of melatonin depending on its concentration and the time of incubation could be shown in all investigations.


Asunto(s)
Folículo Piloso/efectos de los fármacos , Folículo Piloso/crecimiento & desarrollo , Queratinocitos/efectos de los fármacos , Melatonina/farmacología , Adenosina Trifosfato/metabolismo , Bencimidazoles , División Celular/efectos de los fármacos , Línea Celular , Colorantes , Fluorometría , Humanos , Mediciones Luminiscentes , Melatonina/administración & dosificación , Timidina/metabolismo
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