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Enfermedades del Cabello/diagnóstico por imagen , Folículo Piloso/diagnóstico por imagen , Hidradenitis Supurativa/diagnóstico por imagen , Queratosis/diagnóstico por imagen , Prurito/diagnóstico por imagen , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , UltrasonografíaAsunto(s)
Caveolina 1/genética , Esclerodermia Localizada/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Variación Genética , Humanos , Masculino , Esclerodermia Localizada/diagnóstico por imagen , Esclerodermia Localizada/patología , Análisis de Secuencia de ADN , Ultrasonografía , Adulto JovenRESUMEN
OBJECTIVES: To assess hair morphology in androgenetic alopecia on sonography and electron microscopy. METHODS: A prospective study was performed in 33 patients with androgenetic alopecia and 10 unaffected control participants. In vivo sonography of the hair follicles of the scalp and in vitro sonography and electron microscopy of the hair shafts were performed according to a standardized protocol that included analysis of the right frontal and occipital regions. The upper frequency limit of the ultrasound probes ranged between 15 and 18 MHz. RESULTS: Scalp hair follicles and hair shafts were recognizable on sonography in all cases. Hair follicles in alopecia cases had significantly lower depths (P < .05). The hair shafts in alopecia also had a different distribution of their laminar pattern on in vitro sonography, with a greater presence of mixed (trilaminar and bilaminar) and solely bilaminar tracts in comparison with the controls (mostly trilaminar). On electron microscopy, the alopecia hair tracts showed irregularities and commonly a "melted candle" appearance of the cuticle. CONCLUSIONS: Sonography and electron microscopy uncover distinct abnormalities in the morphology of hair in androgenetic alopecia, which may potentially support the diagnosis and management of this common condition.
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Alopecia/diagnóstico por imagen , Cabello/diagnóstico por imagen , Adolescente , Adulto , Alopecia/patología , Cabello/patología , Folículo Piloso/diagnóstico por imagen , Folículo Piloso/patología , Humanos , Masculino , Estudios Prospectivos , Ultrasonografía , Adulto JovenRESUMEN
OBJECTIVES: The purpose of this study was to assess the sonographic morphology of the clinical and subclinical pathology of facial acne vulgaris. METHODS: We studied patients with facial acne vulgaris diagnosed by certified dermatologists, and using a standardized protocol for sonographic examinations, we sequentially described the sonographic pathomorphologic characteristics. Lesions of particular interest to the referring clinician were also analyzed separately. Additionally, acne involvement was staged clinically and sonographically (SOS-Acne) using morphologic definitions of the relevant lesions and predefined scoring systems for gradation of the severity of acne lesions. RESULTS: A total of 245 acne lesions in 20 consecutive patients were studied. Sonographic abnormalities consisted of pseudocysts, folliculitis, fistulas, and calcinosis. Most conditions were subclinical and mostly due to lesion extensions deep into the dermis and hypodermis (52% of pseudocysts and 68% of fistulas). The statistical concordance between acne severity scores assigned by two separate clinicians was strong (κ = 0.8020), but the corresponding sonographic scores generally showed more severe and clinically occult involvement. CONCLUSIONS: Facial acne vulgaris often involves deeper tissues, beyond the reach of the spatially restricted clinical examination; these subclinical conditions can be detected and defined with sonography. Additionally, acne vulgaris is amenable to sonographic scoring.
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Acné Vulgar/diagnóstico por imagen , Dermatosis Facial/diagnóstico por imagen , Piel/diagnóstico por imagen , Ultrasonografía Doppler en Color/métodos , Algoritmos , Femenino , Humanos , Masculino , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: The clinical diagnosis of fistulous tracts and recurrent fluid collections in hidradenitis suppurativa (HS) may be complex. Information on subclinical involvement and grading of severity may improve management. OBJECTIVE: To study HS lesions and evaluate the relevance of adding ultrasound (US) to the clinical examination. METHODS AND MATERIALS: We reviewed the sonograms of consecutive patients with HS from January 1, 2010 to May 31, 2012. The abnormalities observed in the US examinations were organized, classified, and integrated into a clinical-sonographic scoring system (SOS-HS), to stage the disease. RESULTS: Thirty-four patients with HS with a total of 142 lesional areas were evaluated. US findings included subclinical fluid collections in 76.4% of the patients, fistulous tracts in 29.4%, dermal pseudocysts in 70.6%, and widening of the hair follicles in 100%. Concordance with the clinical HS scoring performed by dermatologists showed a significant fair agreement (k = 0.30; p < .001); concordance of SOS-HS with clinical scores was acceptable but significantly lower (k = 0.27; p = .02) because clinical scores consistently underestimated disease stage and severity. CONCLUSION: US examination of HS lesions provides anatomic information that is clinically unavailable. HS is possible to stage sonographically.
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Hidradenitis Supurativa/diagnóstico por imagen , Adulto , Femenino , Hidradenitis Supurativa/patología , Humanos , Masculino , UltrasonografíaRESUMEN
OBJECTIVE: The purpose of this article is to review the sonographic outcomes of common cosmetic and plastic surgery procedures, taking advantage of recent developments in the field of ultrasound that opened its broad application to dermatologic practice. CONCLUSION: Because cosmetic procedures have increased dramatically in frequency, some procedures are being performed by unauthorized personnel and some agents are being used that are not approved by certifying institutions, leading to complications. Thus, documentation of these procedures is an important proposition.
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Técnicas Cosméticas , Dermatología/métodos , Cara/diagnóstico por imagen , Evaluación de Resultado en la Atención de Salud , Chile , Femenino , Humanos , Masculino , UltrasonografíaRESUMEN
BACKGROUND: Morphea (circumcripted cutaneous scleroderma) can be difficult to assess for lesion activity. Because variable-frequency ultrasound with color Doppler provides details of skin morphology and function, it may help in the categorization of morphea. OBJECTIVE: We sought to evaluate color Doppler ultrasound as a probing tool for assessing activity in morphea lesions. METHODS: Consecutive patients with cutaneous morphea referred by dermatologists were studied with color Doppler ultrasound, and the assessment of lesion activity was compared with histologic findings. Normal skin controls were obtained by performing ultrasound scans of healthy subjects or of unaffected areas of the patients themselves. Measurements included cutaneous layer thickness, relative echogenicity, and blood flow with peak systolic velocity. Ultrasound sensitivity and specificity were determined for each phase of morphea activity and the results correlated with histology. RESULTS: Fifty-one patients had a total of 104 morphea lesions. Of the lesions, 20% were active, 22% were atrophic, and 58% were inactive. Five of the patients had the Parry-Romberg syndrome with ipsilateral parotid gland inflammatory involvement, and one had an asymptomatic but sonographically active morphea lesion. Sensitivity and specificity for ultrasound diagnosis were 100% and 98.8%, respectively. The most accurate sonographic signs of lesion activity were increased subcutaneous tissue echogenicity and increased cutaneous blood flow (sensitivity and specificity 100% and 100% for each one). LIMITATIONS: Ultrasound cannot define lesions less than 0.1-mm deep. CONCLUSIONS: The morphologic and functional data obtained noninvasively and in real time with color Doppler ultrasound provide new insight into the pathogenesis of morphea. The technique represents a useful counterpart to histologic examination for the assessment of lesion activity.
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Esclerodermia Localizada/diagnóstico por imagen , Ultrasonografía Doppler en Color , Adolescente , Adulto , Anciano , Atrofia , Biopsia , Niño , Preescolar , Hemiatrofia Facial/complicaciones , Hemiatrofia Facial/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Glándulas Salivales/patología , Esclerodermia Localizada/etiología , Esclerodermia Localizada/patología , Sensibilidad y Especificidad , Piel/irrigación sanguínea , Adulto JovenRESUMEN
Diagnosis of pilomatrixomas may be difficult because they can mimic other clinical conditions. Color Doppler ultrasound had been proven useful in the study of localized lesions of the skin and can both define lesion morphology and determine blood flow changes in real time, and may thus help differentiate primary from secondary vascular skin lesions. We present 3 cases of pilomatrixomas that mimic vascular lesions of the skin on physical examination. Clinical, sonographic, intraoperative, and histologic images are provided to highlight the nature of these challenging cases.
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Pilomatrixoma/diagnóstico por imagen , Neoplasias Cutáneas/diagnóstico por imagen , Ultrasonografía Doppler en Color/estadística & datos numéricos , Neoplasias Vasculares/diagnóstico por imagen , Adolescente , Preescolar , Diagnóstico Diferencial , Femenino , Hemangioma/diagnóstico por imagen , Humanos , Lactante , Pilomatrixoma/patología , Pilomatrixoma/cirugía , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Neoplasias Vasculares/patología , Neoplasias Vasculares/cirugíaAsunto(s)
Enfermedades de la Uña/diagnóstico por imagen , Enfermedades de la Uña/patología , Adulto , Quemaduras/complicaciones , Femenino , Traumatismos de los Dedos/complicaciones , Dedos , Síndrome de Guillain-Barré/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Uña/etiología , Uñas/irrigación sanguínea , Uñas/diagnóstico por imagen , Dedos del Pie , Ultrasonografía , Adulto JovenRESUMEN
OBJECTIVE: The purpose of this study was to determine the scope of high-resolution sonography in the detection of benign tumors and pseudotumors of the nail unit. METHODS: We performed a retrospective study of the sonographic findings in 103 consecutive patients with benign tumors and pseudotumors of the nail that were medically derived and confirmed histologically. Statistical analysis (Student t test) was performed comparing clinical and sonographic diagnoses. RESULTS: Common benign tumors and pseudotumors of the nail can be detected on sonography, and they present different sonographic morphologic characteristics. According to origin, the lesions were considered ungual in 73% (n = 75) and periungual in 27% (n = 28) of the cases. Sonography showed their nature (solid or cystic), location, and extension as well as regional blood flow. In 35% of the cases, the use of sonography modified the clinical diagnosis, although the detailed anatomic information provided by sonography was useful in the planning of surgery in all cases. The addition of sonography was significant (P < .001) for the diagnosis of subungual exostosis and granulomas in comparison to clinical diagnosis. CONCLUSIONS: Sonography is a noninvasive imaging method that can reliably detect common benign tumors and pseudotumors of the nail and provide precise data about their characteristics. This imaging modality can support diagnosis and surgery and can allow a better definition and improvement of the cosmetic outcome of the treatment.
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Enfermedades de la Uña/diagnóstico por imagen , Uñas/diagnóstico por imagen , Neoplasias Cutáneas/diagnóstico por imagen , Ultrasonografía/métodos , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: High variable-frequency ultrasound is a recently available technique capable of clearly defining skin layers and deeper structures that also provides local perfusion patterns obtained in real time. OBJECTIVES: The aim of the study was to assess the performance of variable-frequency ultrasound in the evaluation of skin lesions. METHODS: We performed a retrospective study of 4338 skin ultrasound examinations in predominantly localized skin lesions, and in a group of 130 healthy controls. We determined ultrasound sensitivity, specificity, and statistical level of certainty, and compared ultrasound diagnoses with clinical diagnoses. RESULTS: Referring diagnosis was correct in 73% of the lesions, and addition of ultrasound increased correctness to 97% (P < .001 for the difference). Ultrasound overall sensitivity was 99%, specificity was 100%, and statistical diagnostic certainty was 99% LIMITATIONS: Ultrasound in its current version cannot detect lesions that are epidermal only or that measure less than 0.1 mm in depth. CONCLUSIONS: Ultrasound is a reliable adjuvant for the accurate and precise diagnosis of skin lesions.
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Enfermedades de la Piel/diagnóstico por imagen , Piel/diagnóstico por imagen , Adulto , Carcinoma Basocelular/diagnóstico por imagen , Preescolar , Diagnóstico Diferencial , Femenino , Cuerpos Extraños/diagnóstico por imagen , Hemangioma/diagnóstico por imagen , Histiocitoma Fibroso Benigno/diagnóstico por imagen , Humanos , Masculino , Melanoma/diagnóstico por imagen , Persona de Mediana Edad , Uñas/diagnóstico por imagen , Seno Pilonidal/diagnóstico por imagen , Estudios Retrospectivos , Sensibilidad y Especificidad , Piel/patología , Neoplasias Cutáneas/diagnóstico por imagen , Ultrasonografía Doppler en Color , Verrugas/diagnóstico por imagenRESUMEN
PURPOSE: To evaluate whether (a) Wnt5a expression in pancreatic cancer and malignant melanoma cells might be associated with constitutive levels of Toll-like receptor 3 (TLR3) and/or TLR3 signaling; (b) phenylmethimazole (C10), a novel TLR signaling inhibitor, could decrease constitutive Wnt5a and TLR3 levels together with cell growth and migration; and (c) the efficacy of C10 as a potential inhibitor of pancreatic cancer and malignant melanoma cell growth in vivo. EXPERIMENTAL DESIGN: We used a variety of molecular biology techniques including but not limited to PCR, Western blotting, and ELISA to evaluate the presence of constitutively activated TLR3/Wnt5a expression and signaling. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based technology and scratch assays were used to evaluate inhibition of cell growth and migration, respectively. TLR3 regulation of cell growth was confirmed using small interfering RNA technology. Nude and severe combined immunodeficient mice were implanted with human pancreatic cancer and/or melanoma cells and the effects of C10 on tumor growth were evaluated. RESULTS: We show that constitutive TLR3 expression is associated with constitutive Wnt5a in human pancreatic cancer and malignant melanoma cell lines, that C10 can decrease constitutive TLR3/Wnt5a expression and signaling, suggesting that they are interrelated signal systems, and that C10 inhibits growth and migration in both of these cancer cell lines. We also report that C10 is effective at inhibiting human pancreatic cancer and malignant melanoma tumor growth in vivo in nude or severe combined immunodeficient mice and associate this with inhibition of signal transducers and activators of transcription 3 activation. CONCLUSIONS: C10 may have potential therapeutic applicability in pancreatic cancer and malignant melanoma.
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Antitiroideos/farmacología , Melanoma/metabolismo , Metimazol/análogos & derivados , Neoplasias Pancreáticas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Neoplasias Cutáneas/metabolismo , Tionas/farmacología , Receptor Toll-Like 3/metabolismo , Proteínas Wnt/metabolismo , Animales , Línea Celular Tumoral , Quimiocina CXCL10/antagonistas & inhibidores , Quimiocina CXCL10/metabolismo , Técnicas de Silenciamiento del Gen , Humanos , Interferón beta/antagonistas & inhibidores , Interferón beta/metabolismo , Interleucina-6/antagonistas & inhibidores , Interleucina-6/metabolismo , Melanoma/tratamiento farmacológico , Melanoma/patología , Metimazol/farmacología , Ratones , Ratones Desnudos , Ratones SCID , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , ARN Interferente Pequeño/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Receptor Toll-Like 3/antagonistas & inhibidores , Receptor Toll-Like 3/genética , Proteínas Wnt/antagonistas & inhibidores , Proteína Wnt-5aRESUMEN
In the present study we provide direct evidence for the involvement of rat microsomal cytochrome P450s in melatonin O-demethylation and hydroxylation at two different positions: 2 and 6, as well as generation of N(1)-acetyl-N(2)-formyl-5-methoxy-kynuramine (AFMK) and two unknown products. Moreover, we found that mitochondrial cytochrome P450s also converts melatonin into AFMK, N-acetylserotonin, 2-hydroxymelatonin, 6-hydroxymelatonin and the same two unknown products. Eadie-Hofstee plots for 6-hydroxylation and O-demethylation reactions were curvilinear for all tested fractions, suggestive of involvement of at least two components, one with a high affinity and low capacity, and another with a low affinity and high capacity. Mitochondrial cytochrome P450s exhibited higher affinity (suggesting lower K(m) value) and higher V(max) for melatonin 6-hydroxylation and O-demethylation for both high-affinity and low-affinity components as compared with microsomal enzymes. The intrinsic clearance for melatonin hydroxylation by high- and low-affinity components displayed the highest values in all tested fractions, indicating that both mitochondrial and microsomal cytochrome P450s metabolize melatonin principally by 6-hydroxylation, with O-demethylation representing a minor metabolic pathway.
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Sistema Enzimático del Citocromo P-450/metabolismo , Melatonina/metabolismo , Microsomas Hepáticos/metabolismo , Mitocondrias Hepáticas/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Inhibidores Enzimáticos del Citocromo P-450 , Cinética , Kinuramina/análogos & derivados , Kinuramina/metabolismo , Hígado , Masculino , Melatonina/análogos & derivados , Ratas , Ratas Wistar , Serotonina/análogos & derivados , Serotonina/metabolismo , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Melatonin, a ubiquitous methoxyindole, is produced by and metabolized in the skin. Melatonin affects skin functions and structures through actions mediated by cell-surface and putative-nuclear receptors expressed in skin cells. Melatonin has both receptor-dependent and receptor-independent effects that protect against oxidative stress and can attenuate ultraviolet radiation-induced damage. The widespread expression and pleiotropic activity of the cutaneous melatoninergic system provides for a high level of cell-specific selectivity. Moreover, intra-, auto- and para-crine mechanisms equip this system with exquisite functional selectivity. The properties of endogenous melatonin suggest that this molecule is an important effector of stress responses in the skin. In this way, melatonin actions may counteract or buffer both environmental and endogenous stressors to maintain skin integrity.
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Melatonina/biosíntesis , Piel/metabolismo , Animales , Humanos , Melatonina/química , Melatonina/fisiología , Modelos Biológicos , Estructura Molecular , Receptores de Melatonina/metabolismo , Receptores de Melatonina/fisiologíaRESUMEN
Described as the body's largest organ, the skin is strategically located at the interface with the external environment where it has evolved to detect, integrate and respond to a diverse range of stressors. A flurry of recent findings has established the skin as an important peripheral (neuro)endocrine organ that is tightly networked to central stress axes. This capability is contributing to the maintenance of body homeostasis, and in this way could be harnessed for therapeutic strategies.
RESUMEN
Human skin expresses elements of the hypothalamo-pituitary-adrenal (HPA) axis including pro-opiomelanocortin (POMC), corticotropin releasing hormone (CRH), the CRH receptor-1 (CRH-R1), key enzymes of corticosteroid synthesis and synthesizes glucocorticoids. Expression of these elements is organized in functional, cell type-specific regulatory loops, which imitate the signaling hierarchy of the HPA axis. In melanocytes and fibroblasts CRH-induced CRH-R1 stimulation upregulates POMC expression and production of ACTH through activation of cAMP dependent pathway(s). Melanocytes respond with enhanced production of cortisol and corticosterone, which is dependent on POMC activity. Fibroblasts respond to CRH and ACTH with enhanced production of corticosterone, but not cortisol, which is produced constitutively. Organ-cultured human scalp hair follicles also show a fully functional HPA axis equivalent, including cortisol synthesis and secretion and negative feedback regulation by cortisol on CRH expression. Thus, differential, CRH-driven responses of defined cutaneous cell populations reproduce key features of the central HPA axis at the tissue/single cell levels.
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Sistema Hipotálamo-Hipofisario/fisiología , Sistema Hipófiso-Suprarrenal/fisiología , Fenómenos Fisiológicos de la Piel , Animales , Fibroblastos/fisiología , Humanos , Melanocitos/fisiología , Esteroides/biosíntesisRESUMEN
We report the expression of endogenous CRF1 in COS-7 cells (African green monkey origin). Cloning of the coding region of CRF1 gene identified three alternatively spliced isoforms with nucleotide and predicted amino acid sequences corresponding to the membrane bound alpha and c and soluble e isoforms. DNA sequencing of the main isoform CRF1alpha showed homologies of 99%, 97% and 91% with the rhesus monkey, human and rodent genes, respectively; the deduced protein sequence differed in only one amino acid with rhesus monkey and human. Western blot analysis with antibodies against human CRF1 demonstrated immunoreactive proteins with MW of 37, 52, 70 and 80-85 in crude membrane or cytoplasm preparation; two additional species of 40 and 60 kDa were detected only in the cytoplasmic fraction. On immunocytochemistry CRF1 was localized to both the cell surface and intracellularly. The receptor was functional, e.g., addition of CRF to COS-7 cells inhibited cell proliferation and stimulated release of arachidonic acid; nevertheless, it was poorly coupled to cAMP production (its stimulation was minimal in native cells). In conclusion, COS cells that are routinely used for the study of transfected CRF receptors do express endogenous CRF1 mRNA with splicing behavior similar to that reported in human and rodent cells, and translated into functional CRF1 receptors.
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Empalme Alternativo , Clonación Molecular , Receptores de Hormona Liberadora de Corticotropina/genética , Secuencia de Aminoácidos , Animales , Células COS , Chlorocebus aethiops , AMP Cíclico/biosíntesis , Datos de Secuencia Molecular , Filogenia , Biosíntesis de Proteínas , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , ARN Mensajero , Receptores de Hormona Liberadora de Corticotropina/química , Alineación de SecuenciaRESUMEN
We report an alternative, hydroxylating pathway for the metabolism of vitamin D2 in a cytochrome P450 side chain cleavage (P450scc; CYP11A1) reconstituted system. NMR analyses identified solely 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 derivatives. 20-Hydroxyvitamin D2 was produced at a rate of 0.34 mol x min(-1) x mol(-1) P450scc, and 17,20-dihydroxyvitamin D2 was produced at a rate of 0.13 mol x min(-1) x mol(-1). In adrenal mitochondria, vitamin D2 was metabolized to six monohydroxy products. Nevertheless, aminoglutethimide (a P450scc inhibitor) inhibited this adrenal metabolite formation. Initial testing of metabolites for biological activity showed that, similar to vitamin D2, 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 inhibited DNA synthesis in human epidermal HaCaT keratinocytes, although to a greater degree. 17,20-Dihydroxyvitamin D2 stimulated transcriptional activity of the involucrin promoter, again to a significantly greater extent than vitamin D2, while the effect of 20-hydroxyvitamin D2 was statistically insignificant. Thus, P450scc can metabolize vitamin D2 to generate novel products, with intrinsic biological activity (at least in keratinocytes).