RESUMEN
Acne in adult females is triggered mainly by hormones. Doxycycline is a reference treatment in acne. Spironolactone targets the androgen receptor of sebaceous glands and is prescribed off-label for female adult acne. This multicentre, controlled, randomized, double-blind prospective and parallel study assessed the efficacy of spironolactone compared with doxycycline in adult female acne. A total of 133 women with moderate acne were randomized to receive treatment with: (i) doxycycline and benzoyl peroxide for 3 months followed by a 3-month treatment with its placebo and benzoyl peroxide, or (ii) spironolactone and benzoyl peroxide for 6 months. Successfully treated patients continued with benzoyl peroxide or spironolactone alone for a further 6 months. Primary endpoints were treatment success at month 4 and month 6 with the AFAST score. At all visits, the ECLA score, lesion counts, local and systemic safety and quality of life were assessed. Spironolactone performed better at month 4 and showed a statistically significant better treatment success after 6 months than doxycycline (p = 0.007). Spironolactone was 1.37-times and 2.87-times more successful compared with doxycycline at respective time-points. AFAST and ECLA scores, as well as lesion counts always improved more with spironolactone. Patients' quality of life was better with spironolactone at month 4 and month 6. Spironolactone was very well tolerated. This is the first study to show that, in female adults with moderate acne, treatment with spironolactone is significantly more successful than doxycycline and very well tolerated.
Asunto(s)
Acné Vulgar , Doxiciclina , Adulto , Humanos , Femenino , Doxiciclina/efectos adversos , Espironolactona/efectos adversos , Calidad de Vida , Estudios Prospectivos , Acné Vulgar/diagnóstico , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/inducido químicamente , Peróxido de Benzoílo/uso terapéutico , Resultado del Tratamiento , Método Doble CiegoRESUMEN
Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and leonine facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor ß and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.
Asunto(s)
Paraproteinemias/complicaciones , Paraproteinemias/terapia , Células Plasmáticas/patología , Escleromixedema/complicaciones , Escleromixedema/terapia , Adulto , Anciano , Antineoplásicos/uso terapéutico , Bortezomib/uso terapéutico , Dexametasona/uso terapéutico , Femenino , Glucocorticoides/uso terapéutico , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Lenalidomida/uso terapéutico , Masculino , Persona de Mediana Edad , Paraproteinemias/genética , Paraproteinemias/patología , Células Plasmáticas/efectos de los fármacos , Células Plasmáticas/metabolismo , Plasmaféresis , Estudios Retrospectivos , Escleromixedema/genética , Escleromixedema/patología , Piel/metabolismo , Piel/patología , TranscriptomaRESUMEN
Zygotes from Fucus species have been used extensively to study cell polarization and rhizoid outgrowth, and in this model system cell wall deposition aligns with the establishment of polarity. Monoclonal antibodies are essential tools for the in situ analysis of cell wall glycans, and here we report the characteristics of six monoclonal antibodies to alginates (BAM6-BAM11). The use of these, in conjunction with monoclonal antibodies to brown algal sulfated fucans, has enabled the study of the developmental dynamics of the Fucus zygote cell walls. Young zygotes are spherical and all alginate epitopes are deposited uniformly following cellulose deposition. At germination, sulfated fucans are secreted in the growing rhizoid wall. The redistribution of cell wall epitopes was investigated during treatments that cause reorientation of the growth axis (change in light direction) or disrupt rhizoid development (arabinogalactan-protein-reactive Yariv reagent). Alginate modeling was drastically impaired in the latter, and both treatments cause a redistribution of highly sulfated fucan epitopes. The dynamics of cell wall glycans in this system have been visualized in situ for the first time, leading to an enhanced understanding of the early developmental mechanisms of Fucus species. These sets of monoclonal antibodies significantly extend the available molecular tools for brown algal cell wall studies.
Asunto(s)
Pared Celular/metabolismo , Fucus/metabolismo , Semillas/metabolismo , Anticuerpos Monoclonales/inmunología , Ensayo de Inmunoadsorción Enzimática , Epítopos/inmunología , Fucus/crecimiento & desarrollo , Germinación/fisiología , Semillas/crecimiento & desarrolloRESUMEN
PURPOSE: Whereas vismodegib is effective in the treatment of locally advanced/metastatic basal cell carcinoma, dysgeusia and weight loss are common side effects of such treatment. The main objective of this study was to monitor the nutritional status of vismodegib-treated patients. Secondary objective was to assess the incidence of dysgeusia and the benefit of early nutritional management. METHODS: This prospective study included all patients who started vismodegib between October 2011 and May 2013 at Nantes University Hospital. Prior to July 2012, patients treated with vismodegib had not received any specific nutritional management (Historical cohort). Body weight and presence of dysgeusia were recorded monthly. Patients treated after July 2012 (Nutrition cohort) were evaluated by a physician of the Nutrition Support Unit and received dietary counseling at vismodegib initiation. A standardized nutritional management protocol was initiated in case of significant weight loss. RESULTS: Forty-five patients (21 and 24 in the Nutrition and Historical cohort, respectively) were enrolled. In the Nutrition cohort, five patients (24 %) were undernourished at vismodegib initiation, and the 6-month cumulative incidence of dysgeusia was 71 %. Eight patients (38 %) and 13 patients (54 %) had a weight loss greater than 5 % in the Nutrition and Historical cohort, respectively (p = 0.3727). CONCLUSION: The results of this pilot study suggest the benefit of early nutritional screening. The potential benefit of nutritional support in this setting warrants further investigation.
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Anilidas/efectos adversos , Antineoplásicos/efectos adversos , Carcinoma Basocelular/tratamiento farmacológico , Disgeusia/inducido químicamente , Piridinas/efectos adversos , Neoplasias Cutáneas/tratamiento farmacológico , Pérdida de Peso/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Anilidas/administración & dosificación , Antineoplásicos/administración & dosificación , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Piridinas/administración & dosificaciónAsunto(s)
Acné Vulgar/microbiología , Antibacterianos/farmacología , Propionibacterium acnes/aislamiento & purificación , Acné Vulgar/tratamiento farmacológico , Adolescente , Adulto , Factores de Edad , Antibacterianos/uso terapéutico , Técnicas de Tipificación Bacteriana , Niño , Farmacorresistencia Bacteriana , Femenino , Humanos , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Propionibacterium acnes/clasificación , Propionibacterium acnes/fisiología , Estudios Prospectivos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Adulto JovenAsunto(s)
Azetidinas/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/etiología , Melanoma/tratamiento farmacológico , Piperidinas/efectos adversos , Neoplasias Cutáneas/tratamiento farmacológico , Vemurafenib/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Azetidinas/uso terapéutico , Síndrome de Hipersensibilidad a Medicamentos/fisiopatología , Quimioterapia Combinada , Femenino , Humanos , Masculino , Melanoma/diagnóstico , Persona de Mediana Edad , Piperidinas/uso terapéutico , Pronóstico , Medición de Riesgo , Muestreo , Índice de Severidad de la Enfermedad , Neoplasias Cutáneas/diagnóstico , Vemurafenib/uso terapéuticoRESUMEN
Congenital erythropoietic porphyria (CEP), or Gunther disease, is a rare genetic disease responsible for severe dermatologic, hepatic and/or haematological damages related to the deficient activity of the uroporphyrinogen III synthase. Allogeneic stem cell transplantation (Allo-SCT) represents the only curative treatment and few allotransplanted cases have been reported in children but not in adults. Here we report for the first time the successful cure of a 46-year old man with CEP with a 5-year follow-up after Allo-SCT.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Imidazoles/efectos adversos , Melanoma/tratamiento farmacológico , Oximas/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Piodermia Gangrenosa/inducido químicamente , Piridonas/efectos adversos , Pirimidinonas/efectos adversos , Neoplasias Cutáneas/tratamiento farmacológico , Infecciones Estafilocócicas/inducido químicamente , Anciano , Antibacterianos/uso terapéutico , Humanos , Masculino , Melanoma/genética , Melanoma/secundario , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Piodermia Gangrenosa/diagnóstico , Piodermia Gangrenosa/tratamiento farmacológico , Piodermia Gangrenosa/microbiología , Factores de Riesgo , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Resultado del TratamientoAsunto(s)
Benzotiazoles/efectos adversos , Agonistas de Dopamina/efectos adversos , Indanos/efectos adversos , Indoles/efectos adversos , Conducta Autodestructiva/inducido químicamente , Conducta Autodestructiva/complicaciones , Tricotilomanía/inducido químicamente , Tricotilomanía/complicaciones , Quimioterapia Combinada/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Inhibidores de la Monoaminooxidasa/efectos adversos , PramipexolRESUMEN
BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease of the follicles in the apocrine glands and is associated with a deficiency in the innate immunity of the skin. It is characterized by the occurrence of nodules, abscesses, fistulas, scars. OBJECTIVE: Although a relationship has already been demonstrated between HS and innate immunity, IGF-1 status in patients with HS is still unknown. The objective of this pilot study was to determine IGF-1 status in patients with HS as well as its potential relationship with the clinical profile of the disease. METHODS: This monocentric and cross-sectional study involved 39 patients hospitalized at the Dermatology Department of CHU Nantes between November 2014 and January 2018. Clinical data and IGF1 status were collected during the follow-up consultation. RESULTS: Forty-nine percent of the patients had very low levels of IGF-1. At the clinical level, these patients were young and with a short duration of disease. The major difference was that IGF1-deficient patients had a higher BMI than others. The others factors differing between the two patient groups did not reach statistical significance. CONCLUSION: This exploratory pilot study indicates that HS with a low level of IGF-1 could represent a specific phenotype of patients with HS. These preliminary results have to be confirmed with a larger cohort, as they could have practical consequences in the therapeutic care of these patients.
Asunto(s)
Hidradenitis Supurativa , Humanos , Hidradenitis Supurativa/tratamiento farmacológico , Proyectos Piloto , Factor I del Crecimiento Similar a la Insulina/uso terapéutico , Insulina/uso terapéutico , Estudios TransversalesRESUMEN
Shoot branching is a key process for plant growth and fitness. Newly produced axes result from axillary bud outgrowth, which is at least partly mediated through the regulation of BRANCHED1 gene expression (BRC1/TB1/FC1). BRC1 encodes a pivotal bud-outgrowth-inhibiting transcription factor belonging to the TCP family. As the regulation of BRC1 expression is a hub for many shoot-branching-related mechanisms, it is influenced by endogenous (phytohormones and nutrients) and exogenous (light) inputs, which involve so-far only partly identified molecular networks. This review highlights the central role of BRC1 in shoot branching and its responsiveness to different stimuli, and emphasizes the different knowledge gaps that should be addressed in the near future.
RESUMEN
BACKGROUND: Acne is an inflammatory disease of the pilosebaceous follicle, affecting 41-54% of adult women, with a particular form that involves the mandible. METHODS: We characterized infundibulum morphology in two groups of adult women using reflectance confocal microscopy. First, we investigated acne visually "healthy zones" on the forehead in 15 adult women with diffuse acne and compared with acne-free controls. We then compared healthy forehead and affected mandibular zone in 15 acne patients with mandibular involvement. Exposed results had a P < 0.05. RESULTS: Seven hundred and ninety-one follicles were observed on apparently healthy skin of 15 adult women with acne, with a larger diameter, thicker (68%), and hyper keratinized (65%) follicle border, and more keratin plugs (44%) than in controls. In the second group of 15 adult women with mandibular acne, we compared 569 follicles in the mandibular zone and 475 on forehead. In the mandibular area, follicles were significantly larger, thicker (76%), more hyper keratinized (72%), with more keratin plugs (47%) and increased inflammation (23%) compared with the forehead area. In the mandibular area, 0.2% of follicles showed isolated inflammation without hyper keratinization, and 15.3% had both thickened borders with an onion-like appearance and keratin plugs associated with inflammation. CONCLUSIONS: Hyper keratinization was higher in healthy skin of adult women with acne compared with controls, confirming that microcomedo is crucial in the development of acne lesions. We also demonstrate that the repartition of comedones and microcomedones is inhomogeneous with a great number in the mandibular area where acne lesions are located.
Asunto(s)
Acné Vulgar/diagnóstico por imagen , Dermatosis Facial/diagnóstico por imagen , Folículo Piloso/diagnóstico por imagen , Adulto , Estudios de Casos y Controles , Mejilla , Mentón , Femenino , Frente , Humanos , Microscopía Confocal , Persona de Mediana EdadRESUMEN
Nitrogen is required for optimal plant growth, especially in young organs such as secondary axes (axes II) after axillary bud outgrowth. Several studies have shown an increase of nitrogen concentration in xylem sap concomitantly with bud outgrowth, but the relation between nitrogen, sugars and plant hormones in axis II still remains unclear. We investigated in Rosa hybrida the involvement of nitrogen nutrition in axis II elongation in relation with sugars and cytokinins using 15N-labeled nitrate and sugars, amino acids and cytokinin quantifications. Besides, we measured the effect of the exogenous supply of these compounds on axis II elongation using in vitro excised bud culture. We demonstrated that nitrogen in the axis II comes mainly from new root uptake after decapitation. Asparagine, which concentration increases in sap exudates and tissues during axis II elongation, was the sole amino acid able to sustain an efficient elongation in vitro when supplied in combination with sucrose.
Asunto(s)
Asparagina/metabolismo , Nitrógeno/metabolismo , Rosa/metabolismo , Sacarosa/metabolismo , Transporte Biológico , Citocininas/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Raíces de Plantas/metabolismo , Rosa/crecimiento & desarrolloRESUMEN
Few satisfactory treatment options are available for widespread areas affected by multiple actinic keratoses (AKs). Our primary objective was to assess the response rate to weekly 5-fluorouracil (5-FU) chemowraps on widespread AK lesions, and secondarily to assess tolerability, the percentage of patients with recurrence and time to recurrence, the response rate for patients with associated Bowen's disease (BD), and the percentage of squamous cell carcinomas (SCCs) identified after treatment. We conducted an open study which included all the patients who had been treated with weekly 5-FU chemowraps in our department over the course of five years for areas of widespread AKs. The response rate for AKs was 60%, with 20% complete responses among 25 patients after an average of 9.6 sessions (1 to 64). The treatment had to be discontinued because of toxicity in four patients; one case of contact dermatitis, one case of erosive pustular dermatosis, and two cases of Grade 2 irritations. Invasive SCCs were identified in five patients after treatment cessation. The median recurrence-free survival was five months. A 64% response rate was achieved for associated BD. The weekly application of 5-FU under occlusion seems to be an interesting, well-tolerated therapeutic option for the treatment of widespread AKs.
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Fármacos Dermatológicos/administración & dosificación , Fluorouracilo/administración & dosificación , Queratosis Actínica/tratamiento farmacológico , Administración Cutánea , Anciano , Anciano de 80 o más Años , Esquema de Medicación , Femenino , Humanos , Queratosis Actínica/patología , Masculino , Persona de Mediana Edad , Uso Fuera de lo Indicado , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The prevalence of acne in the adult population is increasing, particularly in women. Spironolactone regulates sebaceous gland activity by blocking androgen receptor. To evaluate retrospectively the efficacy of spironolactone in women with acne. Data from 70 women of at least 20 years, treated for their acne between 2010 and 2015 with low-dose spironolactone (≤150 mg/day), were analysed. Remission was defined by the number of retentional lesions inferior or equal to five and inflammatory lesions inferior or equal to two on the face. Variables influencing the response were studied using the Cox model. The mean age was 31.3 years; 39 (56%) women had prior courses of isotretinoin and 53 (76%) had an oral contraception prior to treatment. Remission data from a median treatment period of six months (95% CI: 4-9) were obtained from 47 (71%) women. Markers for a positive response to spironolactone were a high number of inflammatory lesions at inclusion (OR: 1.08; 95% CI: 1.03-1.13; p = 0.001) and relapse with previous isotretinoin (OR: 2.46; 95% CI: 1.09-5.54; p = 0.03). The marker for a negative response was an association with oral contraceptives containing first or second-generation progestin (OR: 2.77; 95% CI: 1.35-5.71; p = 0.005). This retrospective data analysis confirms that the use of low doses of spironolactone is a valuable alternative in women with acne in whom oral isotretinoin has failed. Moreover, the analysis shows that first and second-generation oral contraceptives decrease the efficacy of spironolactone, confirming the interest of using two third or fourth-generation oral contraceptives.