Binding by calmodulin is coupled to transient unfolding of the third FF domain of Prp40A.

Human pre-mRNA processing protein 40 homolog A (hPrp40A) is a splicing factor that interacts with the Huntington's disease protein huntingtin (Htt). Evidence has accumulated that both Htt and hPrp40A are modulated by the intracellular Ca2+ sensor calmodulin (CaM). Here we report characterization of the interaction of human CM with the third FF domain (FF3 ) of hPrp40A using calorimetric, fluorescence and structural approaches. Homology modeling, differential scanning calorimetry and small angle X-ray scattering (SAXS) data show FF3 forms a folded globular domain. CaM was found to bind FF3 in a Ca2+ -dependent manner with a 1:1 stoichiometry and a dissociation constant (Kd ) of 25 ± 3 µM at 25°C. NMR studies showed that both domains of CaM are engaged in binding and SAXS analysis of the FF3 -CaM complex revealed CaM occupies an extended configuration. Analysis of the FF3 sequence showed that the anchors for CaM binding must be buried in its hydrophobic core, suggesting that binding to CaM requires unfolding of FF3 . Trp anchors were proposed based on sequence analysis and confirmed by intrinsic Trp fluorescence of FF3 upon binding of CaM and substantial reductions in affinity for Trp-Ala FF3 mutants. The consensus model of the complex showed that binding to CaM binding occurs to an extended, non-globular state of the FF3 , consistent with coupling to transient unfolding of the domain. The implications of these results are discussed in the context of the complex interplay of Ca2+ signaling and Ca2+ sensor proteins in modulating Prp40A-Htt function.

Calidad de vida en personas con lesión medular de más de 10 años de evolución. La implicación de las complicaciones secundarias / Quality of life in patients with spinal cord injury for at least 10years: Importance of secondary health complications

Objetivo: Determinar la calidad de vida que presentan los lesionados medulares con más de 10 años de evolución. Valorar la prevalencia de complicaciones secundarias y su relación con la calidad de vida y el tiempo desde la lesión. Pacientes y método Diseño: Estudio epidemiológico transversal. Sujetos del estudio Pacientes: con lesión medular traumática, de más 10 años desde la lesión, y que cumplían los criterios de inclusión.Método: calidad de vida se valoró mediante el International spinal cord injury quality of life basic data set. Como variables se incluyeron: factores individuales, déficit neurológico, nivel de lesión y complicaciones secundarias. Resultados: Ciento treinta y un sujetos fueron incluidos en el estudio con edad media de 49 años y un tiempo desde la lesión de 21 años (11-53 años). La media de complicaciones secundarias fue de 2, siendo la más frecuente las urológicas, en 76 sujetos (58%). No existieron diferencias significativas entre el número de complicaciones y el tiempo transcurrido desde la lesión medular. La calidad de vida fue significativamente menor en aquellos que presentaban un mayor número de complicaciones (p = 0,003). Las complicaciones urológicas (p=0,04, IC del 95%, –1,02-2), el dolor musculoesquelético (p=0,01, IC del 95% IC, 1-6), las complicaciones respiratorias (p=0,05, IC del, –3-0,1) y el dolor neuropático que interfería con actividades básicas de la vida (p=0,01, IC del 95%, 1-5) se relacionaban significativamente con una menor calidad de vida. Conclusiones : Las complicaciones secundarias son frecuentes tras la lesión medular, aunque su número no aumenta con el tiempo desde la lesión. La calidad de vida sí está condicionada por la existencia de distintas complicaciones, como la existencia de dolor musculoesquelético.(AU)

Objective: To determine the quality of life of spinal cord injuries with more than 10 years of evolution. Assess the prevalence of secondary complications, and their relationship with quality of life and time since the injury. Patients and method Design: Cross-sectional epidemiological study. Study subjects: Patients with traumatic spinal cord injury, more than 10 years after the injury, and who met the inclusion criteria. Method: Quality of life was assessed using the International spinal cord injury quality of life basic data set. Variables included: individual factors, neurological deficit, level of injury and secondary complications. Results: 131 subjects were included in the study with a mean age of 49 years, and a time since the injury of 21 years (11–53 years). The mean number of secondary complications was 2, the most frequent being urological, in 76 subjects (58%). There were no significant differences between the number of complications and the time elapsed since the spinal cord injury. The quality of life was significantly lower in those with a higher number of complications (P=.003). Urological complications (P=.04, 95% CI: −1.02 to 2), musculoskeletal pain (P=.01, 95% CI: 1–6), respiratory complications (P=.05, 95% CI: −3 to 0.1) and neuropathic pain that interfered with basic life activities (P=.01, 95% CI: 1–5) were significantly related to a lower quality of life. Conclusions: Secondary complications are common after spinal cord injury, although their number does not increase over time after injury. Quality of life is conditioned by the existence of different complications such as the existence of musculoskeletal pain.(AU)

[Quality of life in patients with spinal cord injury for at least 10years: Importance of secondary health complications]. / Calidad de vida en personas con lesión medular de más de 10 años de evolución. La implicación de las complicaciones secundarias.

OBJECTIVE: To determine the quality of life of spinal cord injuries with more than 10 years of evolution. Assess the prevalence of secondary complications, and their relationship with quality of life and time since the injury. PATIENTS AND METHOD DESIGN: Cross-sectional epidemiological study. STUDY SUBJECTS: Patients with traumatic spinal cord injury, more than 10 years after the injury, and who met the inclusion criteria. METHOD: Quality of life was assessed using the International spinal cord injury quality of life basic data set. Variables included: individual factors, neurological deficit, level of injury and secondary complications. RESULTS: 131 subjects were included in the study with a mean age of 49 years, and a time since the injury of 21 years (11-53 years). The mean number of secondary complications was 2, the most frequent being urological, in 76 subjects (58%). There were no significant differences between the number of complications and the time elapsed since the spinal cord injury. The quality of life was significantly lower in those with a higher number of complications (P=.003). Urological complications (P=.04, 95% CI: -1.02 to 2), musculoskeletal pain (P=.01, 95% CI: 1-6), respiratory complications (P=.05, 95% CI: -3 to 0.1) and neuropathic pain that interfered with basic life activities (P=.01, 95% CI: 1-5) were significantly related to a lower quality of life. CONCLUSIONS: Secondary complications are common after spinal cord injury, although their number does not increase over time after injury. Quality of life is conditioned by the existence of different complications such as the existence of musculoskeletal pain.

Encefalitis y abscesificación cerebral como complicación de una sinusitis frontal aguda en un niño

Resumen Las sinusitis son procesos infecciosos-inflamatorios de las cavidades neumáticas paranasales. Entre las complicaciones de las sinusitis agudas se encuentra la afectación intracraneal, con meningoencefalitis e incluso abscesos extra o subdurales. En este trabajo se describe un caso de meningoencefalitis y empiemas subdurales derivados de una sinusitis frontal aguda en un niño de 12 años, que acudió a urgencias presentando alteración del nivel de conciencia y hemiparesia derecha. Se realizan estudios de tomografía computada y resonancia magnética cerebral, evidenciándose ocupación de seno frontal izquierdo, acompañada de extensa afectación hipercaptante en cubiertas en hemisferio cerebral izquierdo, con formación de empiemas subdurales a nivel frontal izquierdo, parafalciano y en reborde tentorial. Ingresa para tratamiento antibiótico intravenoso y dado el nivel de afectación y la escasa respuesta a tratamiento médico, se decide realizar cirugía endoscópica DRAF IIa con drenaje del absceso frontal, etmoidectomía y meatotomía media izquierda, con sonda de drenaje a fosa nasal. Las complicaciones a nivel de sistema nervioso central son graves y han de tenerse siempre presentes, requiriendo en ocasiones drenaje quirúrgico con abordaje por vía endonasal o abierta.

Abstract Sinusitis are infectious-inflammatory processes of the pneumatic paranasal cavities. Among the complications of acute sinusitis, we can find intracranial involvement, with meningoencephalitis and even extra or subdural abscesses. In this article we describe a case of meningoencephalitis and subdural empyemas associated with acute frontal sinusitis in a 12-year-old child who presented to the emergency room referring altered level of consciousness and right hemiparesis. Computed tomography scan and brain magnetic resonance imaging studies were performed, evidencing left frontal sinus occupation, accompanied by extensive hypercaptant defects in the left cerebral hemisphere, with formation of subdural empyemas at the left frontal level, parafalcian and in the tentorial area. He was hospitalized for intravenous antibiotic treatment, and given the lack of response to medical treatment, a DRAF IIa sinus surgery and drainage of the frontal abscess, ethmoidectomy and left middle meatotomy with drainage tube to the nasal cavity were performed. Complications at the central nervous system are serious and must always be kept in mind, sometimes requiring surgical drainage with an endonasal or open approach.

The impact of hip fracture on health-related quality of life and activities of daily living: the SPARE-HIP prospective cohort study.

PURPOSE: The medical morbidity and mortality associated with neck of femur fractures is well-documented, whereas there is limited data for patient-reported outcomes. The aim of this study was to characterize the impact of neck of femur fractures on activities of daily living and patient-reported health-related quality of life. METHODS: Design and participants: Multicentric prospective cohort study. Consecutive sample patients with fragility hip fracture over 50 years old admitted in 48 hospitals in Spain. OUTCOMES: daily living activity function (Barthel Index) and health-related quality of life (EQ-5D) pre-fracture, admission to hospital and at 1- and 4-month follow-up post-fracture. STATISTICS: Barthel and EQ-5D over time are described as mean (SD) and median (interquartile range). RESULTS: A total of 997 patients were recruited at baseline with 4-month outcomes available for, and 856 patients (89.5%). Barthel Index fell from 78.77 (23.75) at baseline to 43.62 (19.86) on admission to hospital with the fracture. Scores partially recovered to 54.89 (25.40) and 64.09 (21.35) at 1- and 4-month post-fracture, respectively. EQ-5D fell from a median of 0.75 (0.47-0.91) to - 0.01 (- 0.03 to 0.51) on admission. Partial recovery was observed again to (0.51 (- 0.06 to 0.67)) and (0.60 (0.10 to 0.80)) at 1- and 4-month post-fracture, respectively. CONCLUSIONS: Hip fracture results in a large decline in the ability to perform activities of daily living and patient-reported health-related quality of life with only partial recovery amongst survivors 4-month post-fracture.

Dermoscopy of cutaneous smooth muscle neoplasms: a morphological study of 136 cases.

BACKGROUND: A variety of cutaneous smooth muscle neoplasms may arise in the skin and are frequently unrecognized by clinicians. There is sparse data relating to the dermoscopy of piloleiomyomas (PL), and nothing has been published about the dermoscopy of angioleiomyomas (AL) and leiomyosarcomas (LS). OBJECTIVES: To evaluate the morphological findings of a large series of cutaneous PL, AL and LS under dermoscopic observation, comparing these findings among them. METHODS: Digital dermoscopic images of 136 histopathologically confirmed cases of cutaneous smooth muscle neoplasms (114 PL, 13 AL and 9 LS) collected from 10 Hospitals in Spain, Austria and Italy were evaluated for the presence of dermoscopic structures and patterns. RESULTS: The pattern composed of a symmetric, total delicate pigment network with the variable presence of multiple hypopigmented areas in a painful lesion is the most common dermoscopic pattern associated with PL. This pattern was found in 69.3% of PL and in no cases of AL and LS. The most common and characteristic pattern associated with AL was the one composed of symmetric pink-reddish tumour with vessels, white structures and the absence of ulceration, which was found in 46.2% of AL, but also in 3.5% of PL, and in 22.2% of LS. Finally, the most common pattern associated with LS was the one composed of an asymmetric, multilobulated tumour with linear-irregular or polymorphic-atypical vessels and white structures, which was found in 44.4% of cases, but also in 0.9% of PL and in 15.4% of AL. CONCLUSION: Dermoscopy is helpful in improving the diagnostic accuracy of PL. The dermoscopic patterns associated with AL and LS were more variable and less specific.

Registro de linfomas cutáneos primarios de la AEDV: primer año de funcionamiento / The First Year of the AEVD Primary Cutaneous Lymphoma Registry

ANTECEDENTES Y OBJETIVO: Los linfomas primarios cutáneos son enfermedades poco frecuentes. Este artículo describe el Registro de linfomas cutáneos primarios de la AEDV y sus primeros resultados. PACIENTES Y MÉTODOS: Registro de enfermedad de pacientes con linfomas cutáneos primarios. Los centros participantes recogieron datos prospectivamente de todos los pacientes, incluyendo datos del diagnóstico, de los tratamientos, de las pruebas realizadas y del estado actual del paciente. Se realizó un análisis descriptivo. RESULTADOS: En diciembre del 2017 el registro tenía datos de 639 pacientes pertenecientes a 16 hospitales universitarios. Un 60% eran hombres y los diagnósticos, por orden de frecuencia, fueron: micosis fungoide/síndrome de Sézary (MF/SS) (348 casos; 55%), linfoma cutáneo primario de células B (LCCB) (184; 29%), trastorno linfoproliferativo de células T CD30+ (LTCD30+) (70; 11%) y otro tipo de linfoma T (OLT) (37; 5%). El número de casos incidentes recogidos durante el primer año fue de 105 (16,5%). En los pacientes con MF/SS, el diagnóstico más frecuente fue MF clásica (77,3%). La mitad de estos casos se diagnosticaron en estadio IA. La mayoría de los pacientes estaban en remisión parcial (32,5%) o enfermedad estable (33,1%). Los tratamientos más usados fueron los corticoides tópicos (90,8%) seguidos de fototerapia. En los pacientes con LCCB el diagnóstico más frecuente fue el linfoma de la zona marginal (50%). Casi todos los pacientes tuvieron afectación exclusivamente cutánea y casi la mitad fue T1a. La mayoría (76,1%) estaba en remisión completa. Los tratamientos más utilizados fueron la cirugía (55,4%) y la radioterapia (41,9%). En los pacientes con LTCD30+, el diagnóstico más frecuente fue la papulosis linfomatoide (68,6%). La mayoría fueron clasificados T3b (31,4%). La mitad de los casos estaban en remisión completa. Los tratamientos más frecuentes fueron los esteroides tópicos (68,6%), seguidos de la quimioterapia sistémica (32,9%). CONCLUSIÓN: Las características del paciente con linfoma cutáneo primario en España no difieren de otras series descritas en la literatura. El registro facilitará al grupo de linfomas de la AEDV realizar investigación clínica

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas are uncommon. This article describes the Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV) and reports on the results from the first year. PATIENTS AND METHODS: Disease registry for patients with primary cutaneous lymphoma. The participating hospitals prospectively recorded data on diagnosis, treatment, tests, and disease stage for all patients with primary cutaneous lymphoma. A descriptive analysis was performed. RESULTS: In December 2017, the registry contained data on 639 patients (60% male) from 16 university hospitals. The most common diagnoses, in order of frequency, were mycosis fungoides/Sézary syndrome (MF/SS) (348 cases, 55%), primary cutaneous B-cell lymphoma (CBCL) (184 cases, 29%), primary cutaneous CD30+ T-cell lymphoproliferative disorder (CD30+ CLPD) (70 cases, 11%), and other types of T-cell lymphoma (37 cases, 5%). In total, 105 (16.5%) of the cases recorded were incident cases. The most common diagnosis in the MF/SS group was classic MF (77.3%). Half of the patients with MF had stage IA disease when diagnosed, and the majority were either in partial remission (32.5%) or had stable disease (33.1%). The most widely used treatments were topical coricosteroids (90.8%) and phototherapy. The most common form of primary CBCL was marginal zone lymphoma (50%). Almost all of the patients had cutaneous involvement only and nearly half had stage T1a disease. Most (76.1%) were in complete remission. The main treatments were surgery (55.4%) and radiotherapy (41.9%). The most common diagnosis in patients with CD30+ CLPD was lymphomatoid papulosis (68.8%). Most of the patients (31.4%) had stage T3b disease and half were in complete remission. The most common treatments were topical corticosteroids (68.8%) and systemic chemotherapy (32.9%). CONCLUSION: The characteristics of patients with primary cutaneous lymphoma in Spain do not differ from those described in other series in the literature. The registry will facilitate clinical research by the AEDV's lymphoma group

The First Year of the AEVD Primary Cutaneous Lymphoma Registry. / Registro de linfomas cutáneos primarios de la AEDV: primer año de funcionamiento.

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas are uncommon. This article describes the Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV) and reports on the results from the first year. PATIENTS AND METHODS: Disease registry for patients with primary cutaneous lymphoma. The participating hospitals prospectively recorded data on diagnosis, treatment, tests, and disease stage for all patients with primary cutaneous lymphoma. A descriptive analysis was performed. RESULTS: In December 2017, the registry contained data on 639 patients (60% male) from 16 university hospitals. The most common diagnoses, in order of frequency, were mycosis fungoides/Sézary syndrome (MF/SS) (348 cases, 55%), primary cutaneous B-cell lymphoma (CBCL) (184 cases, 29%), primary cutaneous CD30+ T-cell lymphoproliferative disorder (CD30+ CLPD) (70 cases, 11%), and other types of T-cell lymphoma (37 cases, 5%). In total, 105 (16.5%) of the cases recorded were incident cases. The most common diagnosis in the MF/SS group was classic MF (77.3%). Half of the patients with MF had stage IA disease when diagnosed, and the majority were either in partial remission (32.5%) or had stable disease (33.1%). The most widely used treatments were topical corticosteroids (90.8%) and phototherapy. The most common form of primary CBCL was marginal zone lymphoma (50%). Almost all of the patients had cutaneous involvement only and nearly half had stage T1a disease. Most (76.1%) were in complete remission. The main treatments were surgery (55.4%) and radiotherapy (41.9%). The most common diagnosis in patients with CD30+ CLPD was lymphomatoid papulosis (68.8%). Most of the patients (31.4%) had stage T3b disease and half were in complete remission. The most common treatments were topical corticosteroids (68.8%) and systemic chemotherapy (32.9%). CONCLUSION: The characteristics of patients with primary cutaneous lymphoma in Spain do not differ from those described in other series in the literature. The registry will facilitate clinical research by the AEDV's lymphoma group.

ALDH1A3 is epigenetically regulated during melanocyte transformation and is a target for melanoma treatment.

Despite the promising targeted and immune-based interventions in melanoma treatment, long-lasting responses are limited. Melanoma cells present an aberrant redox state that leads to the production of toxic aldehydes that must be converted into less reactive molecules. Targeting the detoxification machinery constitutes a novel therapeutic avenue for melanoma. Here, using 56 cell lines representing nine different tumor types, we demonstrate that melanoma cells exhibit a strong correlation between reactive oxygen species amounts and aldehyde dehydrogenase 1 (ALDH1) activity. We found that ALDH1A3 is upregulated by epigenetic mechanisms in melanoma cells compared with normal melanocytes. Furthermore, it is highly expressed in a large percentage of human nevi and melanomas during melanocyte transformation, which is consistent with the data from the TCGA, CCLE and protein atlas databases. Melanoma treatment with the novel irreversible isoform-specific ALDH1 inhibitor [4-dimethylamino-4-methyl-pent-2-ynthioic acid-S methylester] di-methyl-ampal-thio-ester (DIMATE) or depletion of ALDH1A1 and/or ALDH1A3, promoted the accumulation of apoptogenic aldehydes leading to apoptosis and tumor growth inhibition in immunocompetent, immunosuppressed and patient-derived xenograft mouse models. Interestingly, DIMATE also targeted the slow cycling label-retaining tumor cell population containing the tumorigenic and chemoresistant cells. Our findings suggest that aldehyde detoxification is relevant metabolic mechanism in melanoma cells, which can be used as a novel approach for melanoma treatment.

Microarray study reveals a transforming growth factor-ß-dependent mechanism of fibrosis in discoid lupus erythematosus.

BACKGROUND: Discoid lupus erythematosus (DLE) is characterized by scarring lesions that develop and perpetuate fibrotic lesions. These are not observed in subacute cutaneous lupus erythematosus (SCLE). The pathophysiological basis of this is currently unknown. OBJECTIVES: To identify contradistinctive signalling pathways and cellular signatures between the two type of lupus, with a focus on the molecular mechanisms leading to fibrosis. METHODS: We conducted a gene expression microarray analysis in lesional and nonlesional skin biopsy specimens of patients with DLE (n = 10) and SCLE (n = 10). Confirmatory reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed on selected transcripts in a new cohort of paraffin-embedded skin biopsies (n = 20). Changes over time of a group of selected inflammatory and fibrotic genes were also evaluated in a second biopsy taken 12 weeks later. In vitro functional studies were performed in primary isolated fibroblasts. RESULTS: Compared with nonlesional skin, DLE samples expressed a distinctive T-cell gene signature. DLE samples displayed a significant CD4 T-cell enrichment with an imbalance towards T helper 1 cytokine predominance and a relative increased forkhead box (FOX)P3 response. RT-qPCR and immunochemical analysis over time showed a progressive increment of fibrotic markers and persistent FOXP3 recruitment. Ex vivo upregulation of SERPINE1, MMP9, TGFBR1, phosphorylated SMAD3 and TGFB1 suggested a transforming growth factor (TGF)-ß-dependent mechanism of fibrosis in DLE, also confirmed by the results observed following in vitro stimulation with TGF-ß. CONCLUSIONS: These results highlight major pathogenic pathways in DLE and provide novel molecular targets for the development of new therapies. The data suggest the existence of a TGF-ß-dependent pathway inducing fibrosis in DLE.

Linfadenopatías gigantes de curso benigno: enfermedad de Rosai-Dorfman / Benign massive lymphadenopathy: Rosai-Dorfman disease

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Interleukin-6 deletion in mice driven by aP2-Cre-ERT2 prevents against high-fat diet-induced gain weight and adiposity in female mice.

AIM: Interleukin-6 (IL-6) is a major cytokine controlling body weight and metabolism, but because many types of cells can synthesize and respond to IL-6 considerable uncertainty still exists about the mechanisms underlying IL-6 effects. Therefore, the aim of this study was to analyse the effects of tissue-specific deletion of IL-6 using a fatty acid binding protein (aP2) promoter-Cre inducible system (aP2-Cre-ERT2). METHODS: Tissue-specific IL-6 KO mice (aP2-IL-6 KO mice) were produced upon tamoxifen administration and were fed a high-fat diet (HFD, 58.4% kcal from fat) or a control diet (18%) for 14 weeks. RESULTS: aP2-IL-6 KO female mice on a HFD gained less weight and adiposity than littermate wild-type mice, but these effects were not observed in males. Hypothalamic factors such as NPY and AgRP showed a pattern of expression consistent with this sex-specific phenotype. PGC-1α expression was increased in several tissues in aP2-IL-6 KO female mice, which is compatible with increased energy expenditure. Serum leptin, insulin, glucose, cholesterol and triglycerides levels were increased by HFD, and in females IL-6 deficiency reversed this effect in the case of insulin and cholesterol. HFD induced impaired responses to insulin and glucose tolerance tests, but no significant differences between genotypes were observed. CONCLUSION: The present results demonstrate that deletion of IL-6 driven by aP2-Cre regulates body weight, body fat and metabolism in a sex-specific fashion.

Enfermedad del injerto contra el huésped crónica liquenoide con patrón blaschkoide / Lichenoid Chronic Graft-vs-Host Disease Following Blaschko Lines

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Interleukin-6 regulates the expression of hypothalamic neuropeptides involved in body weight in a gender-dependent way.

Interleukin (IL)-6 has been involved in the control of body weight and body fat. Nevertheless, the mechanisms underlying these effects are not completely understood because central and peripheral actions of IL-6 are plausible. To gain further insight into the central effects of IL-6, we used transgenic mice expressing the IL-6 gene under the control of the glial fibrillary acidic protein (GFAP) promoter (GFAP-IL-6 mice), therefore with central nervous system-restricted over-expression of IL-6, and we studied the expression of the main neuropeptides responsible for energy homeostasis in specific hypothalamic nuclei. Neuropeptide Y (NPY), agouti-related peptide (AgRP), melanin-concentrating hormone (MCH), prepro-orexin (preproOX) (orexigenic and anabolic neuropeptides), pro-opiomelanocortin (POMC) and corticotrophin-releasing hormone (CRH) (anorexigenic and catabolic peptides) mRNA levels were determined using in situ hybridisation in young (2-4 month-old) and old (10-12 month-old) female and male mice under different feeding conditions: normal diet (control) and high-fat diet (HFD), and 24 h-food deprivation. In GFAP-IL-6 females fed a control diet (GFAP-IL-6-control), we showed a significant decrease in NPY and AgRP mRNA levels at all ages, and a late increase in POMC expression (only significant in older animals). These differences were blunted in HFD mice. By contrast, GFAP-IL-6-control males showed a decrease in CRH mRNA content at early ages (2-4 months), and an increase in older mice (10-12 months). Interestingly, these differences were again blunted in HFD mice. Finally, central IL-6 was not able to counteract the effects of 24 h of fasting on body weight, plasma glucose levels and the mRNA content of the peptides evaluated in the present study. Our results demonstrate that IL-6 may regulate the expression of hypothalamic neuropeptides involved in the control of body weight and body fat acting at the central level in a gender- and age-dependent way.

Nódulo hipertricótico en la pierna de un niño de 3 años / Hypertrichotic nodule on the leg of a 3-year-old child

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