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Introducción: La hipertensión arterial (HTA) representa el principal factor de riesgo individual, con mayor carga a nivel mundial de enfermedades cardiovasculares (ECV). En nuestro país, algunos trabajos epidemiológicos han mostrado marcadas diferencias en las prevalencias de estos factores de riesgo de acuerdo con la población evaluada. Sin embargo, no hay estudios epidemiológicos de evaluación de factores de riesgo cardiovascular exclusivos referentes a barrios vulnerables con muy bajos recursos económicos, socioculturales y poca accesibilidad a los sistemas de salud. Materiales y métodos: Estudio observacional de corte transversal multicéntrico en habitantes de comunas vulnerables de muy bajos recursos, como asentamientos populares y barrios carenciados con muestreo aleatorizado simple de casas. Se realizaron tomas de presión arterial (PA), medidas antropométricas, así como cuestionarios epidemiológicos, económicos y socioculturales. Se describen los hallazgos: prevalencia, conocimiento y control de la PA en las distintas regiones. Se efectuó una regresión logística para determinar las variables independientes a los resultados principales. Resultados: Se analizaron 989 participantes. La prevalencia de HTA global fue de 48,2%. Un total de 82% tenía un índice de masa corporal (IMC) >25 kg/m2. De estos pacientes, 45,3% tenían menos de seis años de educación. Este último aspecto se asoció a mayor prevalencia de HTA de forma independiente. De los hipertensos, 44% desconocían su padecimiento y solo en 17,2% estaba controlado, asociándose esto a tener obra social (OS) y mayor nivel educativo. Únicamente 24% estaban bajo tratamiento combinado. Conclusión: La prevalencia de HTA en barrios vulnerables es elevada, superando a la de otros estratos sociales con niveles de conocimiento, tratamiento y control de la HTA bajos, similar a otras poblaciones. Se detectó un uso insuficiente de la terapia combinada.
Introduction: Hypertension (HTN) represents the primary individual risk factor, contributing significantly to the global burden of cardiovascular diseases (CVD). In our country, epidemiological research has highlighted substantial variations in the prevalence of these risk factors across different populations. However, there is a lack of epidemiological studies assessing exclusive cardiovascular risk factors within vulnerable neighborhoods characterized by extremely limited economic resources, sociocultural challenges, and inadequate healthcare access. Methods: A multicenter cross-sectional observational study was conducted among individuals residing in economically deprived and marginalized communities, including informal settlements and underprivileged neighborhoods. Simple random sampling of households was employed. Blood pressure measurements, anthropometric assessments, and epidemiological, economic, and sociocultural questionnaires were administered. Results encompass prevalence rates, awareness levels, and blood pressure control across diverse regions. Logistic regression was utilized to identify independent variables influencing primary outcomes. Results: A total of 989 participants were analyzed. The overall prevalence of hypertension was 48.2%. About 82% had a body mass index (BMI) >25. Approximately 45.3% had less than 6 years of formal education. Independent association was established between education levels below 6 years and higher hypertension prevalence Among hypertensive individuals, 44% were unaware of their condition, with only 17.2% achieving control, correlated with having health insurance and a higher educational background. Merely 24% were receiving combined therapy. Conclusion: The prevalence of hypertension within vulnerable neighborhoods is alarmingly high, surpassing rates in other social strata. Knowledge, treatment, and control levels of hypertension are suboptimal, comparable to other populations... (AU)
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Humanos , Ciencias de la Salud , Epidemiología , Hipertensión , Determinantes Sociales de la Salud , Prevalencia , Conocimiento , ArgentinaRESUMEN
INTRODUCTION: Hypertension (HTN) represents the primary individual risk factor, contributing significantly to the global burden of cardiovascular diseases (CVD). In our country, epidemiological research has highlighted substantial variations in the prevalence of these risk factors across different populations. However, there is a lack of epidemiological studies assessing exclusive cardiovascular risk factors within vulnerable neighborhoods characterized by extremely limited economic resources, sociocultural challenges, and inadequate healthcare access. METHODS: A multicenter cross-sectional observational study was conducted among individuals residing in economically deprived and marginalized communities, including informal settlements and underprivileged neighborhoods. Simple random sampling of households was employed. Blood pressure measurements, anthropometric assessments, and epidemiological, economic, and sociocultural questionnaires were administered. Results encompass prevalence rates, awareness levels, and blood pressure control across diverse regions. Logistic regression was utilized to identify independent variables influencing primary outcomes. RESULTS: A total of 989 participants were analyzed. The overall prevalence of hypertension was 48.2%. About 82% had a body mass index (BMI) >25. Approximately 45.3% had less than 6 years of formal education. Independent association was established between education levels below 6 years and higher hypertension prevalence. Among hypertensive individuals, 44% were unaware of their condition, with only 17.2% achieving control, correlated with having health insurance and a higher educational background. Merely 24% were receiving combined therapy. CONCLUSION: The prevalence of hypertension within vulnerable neighborhoods is alarmingly high, surpassing rates in other social strata. Knowledge, treatment, and control levels of hypertension are suboptimal, comparable to other populations. Inadequate use of combination therapy was observed. This study underscores the urgent need for targeted interventions addressing cardiovascular risk factors in poor areas to mitigate the burden of CVD.
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Enfermedades Cardiovasculares , Hipertensión , Humanos , Estudios Transversales , Prevalencia , Argentina/epidemiología , Presión Sanguínea/fisiología , Factores de Riesgo , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & controlRESUMEN
Lymph nodes (LNs) aid the interaction between lymphocytes and antigen-presenting cells, resulting in adequate and prolonged adaptive immune responses. LN stromal cells (LNSCs) are crucially involved in steering adaptive immune responses at different levels. Most knowledge on LNSCs has been obtained from mouse studies, and few studies indicate similarities with their human counterparts. Recent advances in single-cell technologies have revealed significant LNSC heterogeneity among different subsets with potential selective functions in immunity. This review provides an overview of current knowledge of LNSCs based on human and murine studies describing the role of these cells in health and disease.
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Ganglios Linfáticos , Células del Estroma , Animales , Células Presentadoras de Antígenos , RatonesRESUMEN
Tumor initiation, progression, and metastasis are tissue context-dependent processes. Cellular and non-cellular factors provide the selective microenvironment that determines the fate of the evolving tumor through mechanisms that include metabolic reprogramming. Genetic and epigenetic changes contribute to this reprogramming process, which is orchestrated through ongoing communication between the mitochondrial and nuclear genomes. Metabolic flexibility, in particular the ability to rapidly adjust the balance between glycolytic and mitochondrial energy production, is a hallmark of aggressive, invasive, and metastatic cancers. Tumor cells sustain damage to both nuclear and mitochondrial DNA during tumorigenesis and as a consequence of anticancer treatments. Nuclear and mitochondrial DNA mutations and polymorphisms are increasingly recognized as factors that influence metabolic reprogramming, tumorigenesis, and tumor progression. Severe mitochondrial DNA damage compromises mitochondrial respiration. When mitochondrial respiration drops below a cell-specific threshold, metabolic reprogramming and plasticity fail to compensate and tumor formation is compromised. In these scenarios, tumorigenesis can be restored by acquisition of respiring mitochondria from surrounding stromal cells. Thus, intercellular mitochondrial transfer has the potential to confer treatment resistance and to promote tumor progression and metastasis. Understanding the constraints of metabolic, and in particular bioenergetic reprogramming, and the role of intercellular mitochondrial transfer in tumorigenesis provides new insights into addressing tumor progression and treatment resistance in highly aggressive cancers.
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Mitocondrias/metabolismo , Neoplasias/metabolismo , Neoplasias/patología , Animales , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Humanos , Mitocondrias/genética , Metástasis de la Neoplasia , Neoplasias/genética , Fosforilación OxidativaRESUMEN
We tested the effects of microiontophoretic application of serotonin (5-HT) on the firing rate of neurons located in the gracile nucleus (GN) of rats. Application of 5-HT1A and 5-HT2 agonists and antagonists respectively mimicked/ modulated and blocked the effects produced by the amine, respectively. Among the tested neurons, 88.2% modified their background firing activity in the presence of 5-HT. Responsive neurons decreased their mean firing activity (MFA) in 56.7% of cases and increased it in the remaining 43.3%. To ascertain the specificity of the effects induced by 5-HT, we utilized 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and alpha-methyl-5-hydroxytryptamine (α-MET-5-HT), agonists for 5-HT1A and 5-HT2 receptors, respectively. The microiontophoresis of 8-OH-DPAT modified the background firing rate of all GN neurons (100% of tested neurons) mimicking the decrease of MFA evoked by 5-HT. The application of a-MET-5-HT modified the MFA in 76.9% of tested neurons, decreasing it in 61.5% of cases and increasing in the remaining 23.1%. The decrease of MFA induced by 8-OH-DPAT was antagonized by application of the 5-HT1A receptor antagonist N-[2-[-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY100635), while application of 5-HT2 receptor antagonist ketanserine tartrate (KET) antagonized only the increase of MFA induced by a-MET-5-HT. These results indicate that 5-HT is able to modulate the background firing activity of GN neurons by 5-HT1A and 5-HT2 receptors.
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Potenciales de Acción/efectos de los fármacos , Bulbo Raquídeo/citología , Neuronas/efectos de los fármacos , Serotonina/farmacología , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Animales , Iontoforesis , Ketanserina/farmacología , Masculino , Piperazinas/farmacología , Piridinas/farmacología , Ratas , Ratas Wistar , Receptor de Serotonina 5-HT1A , Receptores de Serotonina 5-HT2 , Serotonina/análogos & derivados , Agonistas del Receptor de Serotonina 5-HT1/farmacología , Antagonistas del Receptor de Serotonina 5-HT1/farmacología , Agonistas del Receptor de Serotonina 5-HT2/farmacología , Antagonistas del Receptor de Serotonina 5-HT2/farmacologíaRESUMEN
Limb somatosensory signals modify the discharge of vestibular neurons and elicit postural reflexes, which stabilize the body position. The aim of this study was to investigate the contribution of the γ-amino-butyric-acid (GABA) to the responsiveness of vestibular neurons to somatosensory inputs. The activity of 128 vestibular units was recorded in anesthetized rats in resting conditions and during sinusoidal foreleg rotation around the elbow or shoulder joints (0.026-0.625Hz, 45° peak amplitude). None of the recorded units was influenced by elbow rotation, while 40% of them responded to shoulder rotation. The selective GABAA antagonist receptor, bicuculline methiodine (BIC), was applied by microiontophoresis on single vestibular neurons and the changes in their activity at rest and during somatosensory stimulation was studied. In about half of cells the resting activity increased after the BIC application: 75% of these neurons showed also an increased response to somatosensory inputs whereas 17% exhibited a decrease. Changes in responsiveness in both directions were detected also in the units whose resting activity was not influenced by BIC. These data suggest that the responses of vestibular neurons to somatosensory inputs are modulated by GABA through a tonic release, which modifies the membrane response to the synaptic current. It is also possible that a phasic release of GABA occurs during foreleg rotation, shaping the stimulus-elicited current passing through the membrane. If this is the case, the changes in the relative position of body segments would modify the GABA release inducing changes in the vestibular reflexes and in learning processes that modify their spatio-temporal development.
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Bicuculina/farmacología , Neuronas/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Vestíbulo del Laberinto/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Antagonistas de Receptores de GABA-A/farmacología , Masculino , Neuronas/fisiología , Ratas Sprague-Dawley , Receptores de GABA-A/metabolismo , Reflejo Vestibuloocular/efectos de los fármacos , Rotación , Transmisión Sináptica/fisiología , Vestíbulo del Laberinto/fisiologíaRESUMEN
The etiology of testicular cancer is largely unexplained. Research has mainly focused on prenatal exposures, especially to sex hormones, while less attention has been paid to exposures that may act also postnatally. As baldness has been previously associated with testicular cancer risk we focused on baldness and body hairiness, which are both associated with androgen activity. We used data of the Postnatal Exposures and Male Health (EPSAM) study, a case-control study on testicular cancer conducted in the Province of Turin, Italy, involving cases diagnosed between 1997 and 2008. Information was collected using mailed questionnaires. Analyses included 255 cases and 459 controls. We calculated ORs and 95% CIs to estimate testicular cancer risk among those who developed baldness and among those with body hairiness. We found an inverse association between testicular cancer and baldness (OR: 0.67, 95% CI: 0.46-0.98) and body hairiness (OR: 0.78, 95% CI: 0.53-1.16), although the latter had wider CIs. The inverse association between baldness and testicular cancer is consistent with the results from previous studies. These results suggest that androgens activity may influence testicular cancer risk.
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Alopecia/complicaciones , Andrógenos/fisiología , Cabello , Neoplasias de Células Germinales y Embrionarias/etiología , Neoplasias Testiculares/etiología , Adolescente , Adulto , Estudios de Casos y Controles , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Comprehensive molecular profiling led to the recognition of multiple prostate cancer (PCa) molecular subtypes and driving alterations, but translating these findings to clinical practice is challenging. PATIENTS AND METHODS: We developed a formalin-fixed paraffin-embedded (FFPE) tissue compatible integrative assay for PCa molecular subtyping and interrogation of relevant genetic/transcriptomic alterations (MiPC). We applied MiPC, which combines capture-based next generation sequencing and quantitative reverse transcription PCR (qRT-PCR), to 53 FFPE PCa specimens representing cases not well represented in frozen tissue cohorts, including 8 paired primary tumor and lymph node metastases. Results were validated using multiplexed PCR based NGS and Sanger sequencing. RESULTS: We identified known and novel potential driving, somatic mutations and copy number alterations, including a novel BRAF T599_V600insHT mutation and CYP11B2 amplification in a patient treated with ketoconazole (a potent CYP11B2 inhibitor). qRT-PCR integration enabled comprehensive molecular subtyping and provided complementary information, such as androgen receptor (AR) target gene module assessment in advanced cases and SPINK1 over-expression. MiPC identified highly concordant profiles for all 8 tumor/lymph node metastasis pairs, consistent with limited heterogeneity amongst driving events. MiPC and exome sequencing were performed on separately isolated conventional acinar PCa and prostatic small cell carcinoma (SCC) components from the same FFPE resection specimen to enable direct comparison of histologically distinct components. While both components showed TMPRSS2:ERG fusions, the SCC component exclusively harbored complete TP53 inactivation (frameshift variant and copy loss) and two CREBBP mutations. CONCLUSIONS: Our results demonstrate the feasibility of integrative profiling of routine PCa specimens, which may have utility for understanding disease biology and enabling personalized medicine applications.
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Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica/métodos , Neoplasias de la Próstata/genética , Biopsia , Variaciones en el Número de Copia de ADN , Análisis Mutacional de ADN , Estudios de Factibilidad , Fijadores , Formaldehído , Regulación Neoplásica de la Expresión Génica , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Metástasis Linfática , Masculino , Mutación , Adhesión en Parafina , Fenotipo , Polimorfismo de Nucleótido Simple , Medicina de Precisión , Valor Predictivo de las Pruebas , Pronóstico , Neoplasias de la Próstata/clasificación , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Fijación del TejidoRESUMEN
BACKGROUND: The role of global DNA methylation in prostate cancer (PCa) remains largely unknown. Our aim was to summarize evidence on the role of global DNA hypomethylation in PCa development and progression. METHODS: We searched PubMed through December 2013 for all studies containing information on global methylation levels in PCa tissue and at least one non-tumor comparison tissue and/or studies reporting association between global methylation levels in PCa tissue and survival, disease recurrence or at least one clinicopathological prognostic factor. We summarized results using non-parametric comparisons and P-value summary methods. RESULTS: We included 15 studies in the review: 6 studies with both diagnostic and prognostic information, 5 studies with only diagnostic information and 4 studies with only prognostic information. Quantitative meta-analysis was not possible because of the large heterogeneity in molecular techniques, types of tissues analyzed, aims and study designs. Summary statistical tests showed association of DNA hypomethylation with PCa diagnosis (P<0.006) and prognosis (P<0.001). Restriction to studies assessing 5-methylcytosine or long interspersed nucleotide element-1 revealed results in the same direction. Analyses restricted to specific clinicopathological features showed association with the presence of metastasis and tumor stage in all tests with P<0.03, and no association with Gleason score (all tests P>0.1 except for the weighted Z-test, P=0.05). CONCLUSION: DNA hypomethylation was associated with PCa development and progression. However, due to the heterogeneity and small sample sizes of the included studies, along with the possibility of publication bias, this association requires additional assessment.
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Metilación de ADN/genética , Recurrencia Local de Neoplasia/genética , Pronóstico , Neoplasias de la Próstata/genética , Progresión de la Enfermedad , Humanos , Elementos de Nucleótido Esparcido Largo/genética , Masculino , Clasificación del Tumor , Recurrencia Local de Neoplasia/patología , Neoplasias de la Próstata/patología , PubMedRESUMEN
AIM: The degree of inflammation within the atherosclerotic plaque can be detected non-invasively by positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG). The incidence of aortic plaques with 18F-FDG increased uptake in octogenarians with aortic stenosis is unknown. Aim of this study was to evaluate the frequency of inflamed aortic atherosclerotic plaques in octogenarians with or without severe aortic stenosis and their correlations with calcifications. METHODS: The study group comprised 27 patients older than 80 years who underwent a 18FDG PET/CT. Nine patients with severe symptomatic aortic stenosis, eligible to TAVI procedure (TAVI Group), and 18 patients age and sex matched, without clinical evidence of aortic stenosis (No TAVI Group), were selected and analysed. RESULTS: In the whole population 4/27 patients (9.3%) had a significant focal aortic vessel wall 18F-FDG increased uptake: 1 patient (11.1%) in TAVI group and 3 in non-TAVI Group (16.7%). Overall 81 aortic segments were analysed. 18F-FDG uptake rates were similar in the two groups (1/27, 3.7% in TAVI Group and 3/54, 5.5% in No TAVI Group, P=0.7). At CT scan calcifications were significantly more frequent in the TAVI Group compared to non-TAVI Group (23/27, 85.2% and 28/54, 51.8% P=0.005). None of the sites of arterial calcification had an increased focal 18F-FDG uptake. CONCLUSION: Irrespectively to the presence of aortic stenosis, a significant FDG plaque uptake in octogenarians is rare while calcifications are extremely frequent.
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Estenosis de la Válvula Aórtica/patología , Placa Aterosclerótica/patología , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/diagnóstico , Calcinosis/diagnóstico , Calcinosis/epidemiología , Calcinosis/patología , Estudios de Casos y Controles , Femenino , Fluorodesoxiglucosa F18/administración & dosificación , Humanos , Incidencia , Inflamación/diagnóstico , Inflamación/patología , Masculino , Imagen Multimodal/métodos , Placa Aterosclerótica/diagnóstico , Placa Aterosclerótica/epidemiología , Radiofármacos/administración & dosificación , Índice de Severidad de la EnfermedadRESUMEN
AIM: Aim of the study was to report on the feasibility and early safety and efficacy of Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) for coronary artery bifurcations (CABs) treatment at a single high-volume center. METHODS: All patients treated with Absorb implantation at our institution from March 2013 to March 2014 were enrolled in the prospective, single-center, ongoing, all-comers registry, which has the main purpose of evaluating the safety and efficacy of Absorb implantation in unselected patients treated in daily practice. In-hospital and at follow-up clinical outcomes of 46 patients undergoing treatment with Absorb in 46 CAB lesions were reported in the present study. RESULTS: Treated CAB lesions involved the left main in 13.0% of cases, the left anterior descending artery in 65.0%, the left circumflex in 19.6%, and the right coronary artery in 2.2%. Bifurcations were classified as true (47.8%) and non-true (52.2%) according to the Medina classification. The provisional and the two-BVS techniques were used in 78.3% and 21.7%, respectively. Two-BVS techniques included: mini-crush 13.0%; reverse culotte 2.2%; T-stenting 2.2%; and V-stenting 4.3%. No in-hospital adverse events occurred. At 6 months no adverse events occurred. Only one case of target lesion revascularization was observed at day 227. No stent thrombosis occurred during follow-up. CONCLUSION: Our preliminary experience suggested that CABs treatment with Absorb is feasible and associated with promising immediate and short-term clinical outcomes. However, larger studies with long-term follow-up are needed to adequately address the safety and efficacy of BVS use in CABs.
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Enfermedad de la Arteria Coronaria/terapia , Stents Liberadores de Fármacos , Sirolimus/análogos & derivados , Andamios del Tejido , Implantes Absorbibles , Anciano , Enfermedad de la Arteria Coronaria/patología , Everolimus , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sirolimus/administración & dosificación , Factores de Tiempo , Resultado del TratamientoRESUMEN
Excitatory responses evoked by N-methyl-d-aspartate (NMDA) in the vestibular nuclei (VN) of the rat were studied in vivo during microiontophoretic application of noradrenaline (NA) and/or its agonists and antagonists. Ejection of NA-modified excitatory responses mediated by NMDA receptors (NMDAR) in all neurons tested; the effect was enhancement in 59% of cases and depression in the remaining 41%. Enhancements prevailed in all VN with the exception of the lateral vestibular nucleus, where both effects were recorded in an equal number of cases. The enhancing action of NA on NMDAR-mediated responses was mimicked by the noradrenergic beta-receptor agonist isoproterenol, the beta1 specific agonist denopamine and the alpha2 agonist clonidine. These effects were blocked respectively by the generic beta-receptor antagonist timolol, the beta1 antagonist atenolol and the alpha2 antagonist yohimbine. In contrast, application of the alpha1 receptor agonist cirazoline and the specific alpha1 antagonist prazosin respectively mimicked and partially antagonized the depression of NMDAR-mediated excitations induced by NA. Double-labeling immunohistochemical techniques demonstrated broad colocalization of NMDAR (specifically NR1 and NR2 subunits) with noradrenergic receptors (alpha1, alpha2 and beta1) in many VN neurons; only minor differences were found between nuclei. These results indicate that NA can produce generalized modulation of NMDAR-mediated excitatory neurotransmission in VN, which may in turn modify synaptic plasticity within the nuclei.
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Neuronas/fisiología , Norepinefrina/farmacología , Receptores de N-Metil-D-Aspartato/metabolismo , Núcleos Vestibulares/metabolismo , Animales , Fenómenos Electrofisiológicos , Inmunohistoquímica , Masculino , N-Metilaspartato/farmacología , Neuronas/efectos de los fármacos , Norepinefrina/agonistas , Norepinefrina/antagonistas & inhibidores , Ratas , Ratas Wistar , Receptores Adrenérgicos/análisis , Receptores Adrenérgicos/metabolismo , Receptores de N-Metil-D-Aspartato/análisis , Núcleos Vestibulares/efectos de los fármacosRESUMEN
Vestibulospinal reflexes elicited by head displacement in space depend on the direction of body displacement, because the neuronal responses to labyrinthine stimulation are tuned by neck displacement: a directional tuning takes place in the medial cerebellum and in spinal motoneurons, while a gain and a basal activity tuning can be observed in the reticular formation, a target structure of the medial cerebellum. In the present study, we investigated whether also the response of vestibular nuclear neurons (another target of the medial cerebellum) to labyrinthine stimulation is tuned by neck displacement and which parameters of the response are modulated by it. In urethane-anaesthetized Wistar rats, single-unit activity was recorded from the vestibular nuclei at rest and during wobble of the whole animal at 0.156 Hz. This stimulus tilted the animal's head by a constant amplitude (5°), in a direction rotating at a constant velocity over the horizontal plane, either in clockwise or counter clockwise direction. The gain and the direction of neuronal responses to wobble were evaluated through Fourier analysis, in the control position (with coincident head and body axes) and following a body-to-head rotation of 5-30° over the horizontal plane, in both directions. Most of the vestibular neurons modified their response gain and/or their basal activity following body-to-head rotation, as it occurs in the reticular formation. Only few neurons modified their response direction, as occurs in the cerebellum and in spinal motoneurons. The different behaviour of cerebellar neurons and of their vestibular and reticular target cells, suggests that the role played by the cerebellum in the neck tuning of vestibulospinal reflexes has to be reconsidered.
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Cabeza/fisiología , Neuronas/fisiología , Rotación , Torso/fisiología , Núcleos Vestibulares/citología , Núcleos Vestibulares/fisiología , Vestíbulo del Laberinto/fisiología , Potenciales de Acción/fisiología , Animales , RatasRESUMEN
Vestibulospinal reflexes can be elicited in humans by low amplitudes direct (galvanic) currents lasting tens of milliseconds and applied across the two mastoids bones, which can be delivered by particular stimulators. The stimulus induces a perception of body sway and a postural response appropriate to counteract the perceived sway. Both the direction of the perceived and induced body sway are modulated by the orientation of the head with respect to the body. This phenomenon is due to the fact that integration of vestibular and neck signals allows to correctly infer the direction of body sway from the labyrinthine input, which is instead related to direction of head motion. The modulation of stimulus-elicited body sway by neck rotation could be utilised for testing the effectiveness of neck proprioceptive signals in modifying the reference frame for labyrinthine signals from the head to the body. In the present experiments we showed that labyrinthine stimulation can be performed also by using train of pulses of 1 msec duration, which can be delivered by virtually all stimulators allowed for human use. Moreover, we developed a simple technique for visualising the time course of the changes in the direction of the postural response, based on the evaluation of the velocity vector of subject's centre of pressure. This method could be exploited in order to the test the efficacy of neck proprioceptive information in modifying the reference frame for processing vestibular signals in both physiological and pathological condition.
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Movimiento/fisiología , Postura/fisiología , Reflejo/fisiología , Médula Espinal/fisiología , Vestíbulo del Laberinto/fisiología , Biofisica , Estimulación Eléctrica , Electromiografía , Potenciales Evocados Motores/fisiología , Humanos , Apófisis Mastoides/inervación , Apófisis Mastoides/fisiología , Piel/inervación , Voluntarios , Adulto JovenRESUMEN
Vestibulospinal reflexes elicited by head displacement become appropriate for body stabilization owing to the integration of neck input by the cerebellar anterior vermis. Due to this integration, the preferred direction of spinal motoneurons' responses to animal tilt rotates by the same angle and by the same direction as the head over the body, which makes it dependent on the direction of body displacement rather than on head displacement. It is known that the cerebellar control of spinal motoneurons involves the reticular formation. Since the preferred directions of corticocerebellar units' responses to animal tilt are tuned by neck rotation, as occuring in spinal motoneurons, we investigated whether a similar tuning can be observed also in the intermediate station of reticular formation. In anaesthetized rats, the activity of neurons in the medullary reticular formation was recorded during wobble of the whole animal at 0.156 Hz, a stimulus that tilted the animal's head by a constant amplitude (5°), in a direction rotating clockwise or counter clockwise over the horizontal plane. The response gain and the direction of tilt eliciting the maximal activity were evaluated with the head and body axes aligned and during a maintained body-to-head displacement of 5-20° over the horizontal plane, in either direction. We found that the neck displacement modified the response gain and/or the average activity of most of the responsive neurons. Rotation of the response direction was observed only in a minor percentage of the recorded neurons. The modifications of reticular neurons' responses were different from those observed in the P-cells of the cerebellar anterior vermis, which rarely showed gain and activity changes and often exhibited a rotation of their response directions. In conclusion, reticular neurons take part in the neck tuning of vestibulospinal reflexes by transforming a head-driven sensory input into a body-centred postural response. The present findings prompt re-evaluation of the role played by the reticular neurons and the cerebellum in vestibulospinal reflexes.
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Oído Interno/fisiología , Neuronas/fisiología , Equilibrio Postural/fisiología , Postura/fisiología , Formación Reticular/fisiología , Animales , Cerebelo/fisiología , Cabeza , Ratas , Ratas Wistar , Reflejo/fisiología , Rotación , TorsoAsunto(s)
Síndrome Coronario Agudo/terapia , Sustitución de Medicamentos/métodos , Stents Liberadores de Fármacos , Neoplasias Pulmonares , Pulmón , Inhibidores de Agregación Plaquetaria/administración & dosificación , Tirosina/análogos & derivados , Anciano , Biopsia con Aguja , Clopidogrel , Reestenosis Coronaria/terapia , Esquema de Medicación , Stents Liberadores de Fármacos/efectos adversos , Humanos , Pulmón/patología , Pulmón/cirugía , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Retratamiento/métodos , Ticlopidina/administración & dosificación , Ticlopidina/análogos & derivados , Tirofibán , Tirosina/administración & dosificaciónRESUMEN
The authors describe the case of a child with craniofrontonasal syndrome (CFNS) (MIM 304110), the diagnostic process performed, the identification of the main clinical features in the proband (hypertelorism, facial asimmetry, bifid nasal tip, corpus callosum hypoplasia, broad thumb, curly and wiry hair), and the comparison with known data in literature. They also describe the detection, through gene sequencing of EFNB1, of responsible mutation and its correlation with the phenotypic variants. They explain the etiophatogenetic basis of the "unusual" inheritance pattern of CFNS: X-linked disease that occurs with greater severity in heterozygous females than hemizygous males. Finally, attention is placed on the need for careful genetic counseling for patients with CFNS, with special care in familial anamnesis taking. In the studied case, the presence of abnormalities of thumbs in the proband's mother and in two of her cousins, orientates principally toward a mutation of maternal origin or to a suspected somatic and germline mosaicism by creating a recurrence risk greater than general population. Because patients with CFNS reported in the literature are few, the AA consider that the observed case may help to improve understanding of the mechanisms of gene expression responsible for the syndrome, of its peculiar phenotypic manifestations and of its frequency in the population with known and easy to assign phenotypes, and possible mosaicisms that are difficult to detect.
Asunto(s)
Anomalías Craneofaciales/genética , Anomalías Craneofaciales/diagnóstico , Femenino , Humanos , Recién Nacido , Linaje , FenotipoRESUMEN
Changing the foot position modifies the mechanical action exerted by the ankle extensor and flexor muscles over the body. We verified, in two groups of healthy subjects standing with the heels touching or apart, whether a 90° external rotation of the right leg and foot also changes the pattern of vestibulospinal reflexes elicited by electrical stimulation of the labyrinth. With the head oriented forward, leg rotation did not modify the labyrinthine-driven displacements of the center of pressure (CoP). When the head was rotated in the horizontal plane, either to the right or to the left, the CoP displacement increased along the y axis in all subjects. Changes in the x component in most instances appropriate to preserve unmodified the direction of body sway elicited by the stimulus were observed. Right leg rotation increased the basal EMG activity of ankle extensors and flexors on the left side, while the right side activity was unaffected. The EMG responses to labyrinthine stimulation were modified only on the left side, in a way appropriate to correct the effects of the altered torque pattern exerted on the body by right leg muscles. It appears, therefore, that somatosensory signals related to leg rotation and/or copy of the corresponding voluntary motor commands modify the pattern of vestibulospinal reflexes and maintain the postural response appropriate to counteract a body sway in the direction inferred by labyrinthine signals.
Asunto(s)
Oído Interno/fisiología , Cinestesia/fisiología , Pierna/inervación , Orientación/fisiología , Equilibrio Postural/fisiología , Postura/fisiología , Reflejo/fisiología , Percepción Espacial/fisiología , Médula Espinal/fisiología , Adulto , Anciano , Electromiografía , Femenino , Movimientos de la Cabeza/fisiología , Humanos , Masculino , Persona de Mediana Edad , Contracción Muscular/fisiología , Músculo Esquelético/inervación , Rotación , Torque , Soporte de Peso/fisiologíaRESUMEN
The neuronal repellent SLIT2 is repressed in a number of cancer types primarily through promoter hypermethylation. SLIT2, however, has not been studied in prostate cancer. Through genome-wide location analysis we identified SLIT2 as a target of polycomb group (PcG) protein EZH2. The EZH2-containing polycomb repressive complexes bound to the SLIT2 promoter inhibiting its expression. SLIT2 was downregulated in a majority of metastatic prostate tumors, showing a negative correlation with EZH2. This repressed expression could be restored by methylation inhibitors or EZH2-suppressing compounds. In addition, a low level of SLIT2 expression was associated with aggressive prostate, breast and lung cancers. Functional assays showed that SLIT2 inhibited prostate cancer cell proliferation and invasion. Thus, this study showed for the first time the epigenetic silencing of SLIT2 in prostate tumors, and supported SLIT2 as a potential biomarker for aggressive solid tumors. Importantly, PcG-mediated repression may serve as a precursor for the silencing of SLIT2 by DNA methylation in cancer.