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1.
Sports Biomech ; : 1-16, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38190252

RESUMEN

This study aimed to evaluate the validity and reliability of a wearable device and a phone application for measuring spatiotemporal parameters and their relationship with running economy (RE) by comparing them with photocell data in runners of different abilities. Twenty-three male runners were divided into well-trained and recreational groups and performed a 4-min running bout at 17 and 13 km·h-1 respectively. During the bout, were measured the spatiotemporal parameters with three devices (Stryd, Runmatic, and Optojump) and RE with a gas analyser. Pearson correlation showed perfect relationships for stride frequency (SF) and stride length (SL) between the devices, and moderate for flight time (FT) and contact time (CT). There were no correlations between the spatiotemporal parameters and RE measurements. Coefficient of variation was ~ 5% in all devices for CT, SF, and SL, and higher for FT (15-24%). CT was underestimated (15-16% with Runmatic and Stryd, respectively) and FT was overestimated (36-40%) compared to Optojump. Bland-Altman plots revealed that Runmatic could be a more accurate system than Stryd. In conclusion, both devices were valid tools for measuring spatiotemporal parameters during running at RE speed. Runmatic was more valid and reliable in comparison with Stryd. In addition, at lower running speeds the devices showed less reliability.

2.
Ann Ig ; 35(6): 617-630, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37796469

RESUMEN

Background: During the COVID-19 pandemic, the paediatric population plays a minor role in the spread of the SARS-CoV-2 virus. However, in order to keep schools open and reduce SARS-CoV spreading, it is necessary to identify and isolate early SARS-CoV-2 positive paediatric patients even if they are asymptomatic. The aim of this study was to describe a setting for SARS-CoV 2 testing based on the spontaneous presentation of paediatric patients attending school without a medical prescription and explore its appropriateness. Study design: Cross-sectional study. Methods: The study performed between September 2020 and March 2021 among a sample of 13,283 paediatric patients who underwent a swab in four different hospital settings (school hot spot, emergency department, day hospital setting and hospital wards). For each patients we collected: date of swab execution, type of swab, execution setting of the swab, result of the swab, information about community spread of the virus in the 14 days prior to the swab execution, sex and age. Results: In our sample, females accounted for 45.8%. The median age was 6.8 years (IQR 3.0-11.2) and the most frequent age category was between 6 and 11 years (27.9%). At multivariable models with a swab tested positive as outcome. The swabs executed in all the hospital settings had a lower likelihood of resulting positive compared with the school hot spot setting. Compared with adolescents aged between 14 and 19 years old, new-borns below 3 months (adjOR 1.83, 95% C.I. 1.14-3) and patients aged between 11 and 14 years old (adjOR 1.32, 95% C.I. 1.07-1.63) reported a higher probability of a swab tested positive. Instead, children aged between 3 months and 3 years (adjOR 0.77, 95% C.I. 0.61-0.96) and children aged between 3 years and 6 years (adjOR 0.66, 95% C.I. 0.53-0.83) were less likely to result positive. The higher was the mean of pooled Rt in the 14 days preceding the swab, the higher was the likelihood of resulting positive (adjOR 1.75, 95% C.I. 1.53-1.99). Conclusion: In conclusion, we found a high incidence of paediatric patients positive to the test for the detection of SARS-CoV-2 at the school hot spot compared with other settings during the period of observation. The free access modality to the nasopharyngeal swab was effective in identifying patients with COVID-19. Public health authorities should implement these testing modality in order to help reduce the spread of SARS-CoV-2 in school settings.


Asunto(s)
COVID-19 , SARS-CoV-2 , Femenino , Adolescente , Humanos , Niño , Preescolar , Lactante , COVID-19/diagnóstico , COVID-19/epidemiología , Pandemias , Estudios Transversales , Prueba de COVID-19
3.
Life Sci Space Res (Amst) ; 18: 1-11, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30100142

RESUMEN

As manned spaceflights beyond low Earth orbit are in the agenda of Space Agencies, the concerns related to space radiation exposure of the crew are still without conclusive solutions. The risk of long-term detrimental health effects needs to be kept below acceptable limits, and emergency countermeasures must be planned to avoid the short-term consequences of exposure to high particle fluxes during hardly predictable solar events. Space habitat shielding cannot be the ultimate solution: the increasing complexity of future missions will require astronauts to protect themselves in low-shielded areas, e.g. during emergency operations. Personal radiation shielding is promising, particularly if using available resources for multi-functional shielding devices. In this work we report on all steps from the conception, design, manufacturing, to the final test on board the International Space Station (ISS) of the first prototype of a water-filled garment for emergency radiation shielding against solar particle events. The garment has a good shielding potential and comfort level. On-board water is used for filling and then recycled without waste. The successful outcome of this experiment represents an important breakthrough in space radiation shielding, opening to the development of similarly conceived devices and their use in interplanetary missions as the one to Mars.


Asunto(s)
Astronautas , Radiación Cósmica/efectos adversos , Protección Radiológica/instrumentación , Trajes Espaciales/normas , Vestuario , Humanos , Modelos Teóricos , Fantasmas de Imagen , Dosis de Radiación , Traumatismos por Radiación/etiología , Traumatismos por Radiación/prevención & control , Vuelo Espacial
4.
EBioMedicine ; 25: 112-121, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29100778

RESUMEN

More efficacious treatment regimens are needed for tuberculosis, however, drug development is impeded by a lack of reliable biomarkers of disease severity and of treatment effect. We conducted a directed screen of host biomarkers in participants enrolled in a tuberculosis clinical trial to address this need. Serum samples from 319 protocol-correct, culture-confirmed pulmonary tuberculosis patients treated under direct observation as part of an international, phase 2 trial were screened for 70 markers of infection, inflammation, and metabolism. Biomarker assays were specifically developed for this study and quantified using a novel, multiplexed electrochemiluminescence assay. We evaluated the association of biomarkers with baseline characteristics, as well as with detailed microbiologic data, using Bonferroni-adjusted, linear regression models. Across numerous analyses, seven proteins, SAA1, PCT, IL-1ß, IL-6, CRP, PTX-3 and MMP-8, showed recurring strong associations with markers of baseline disease severity, smear grade and cavitation; were strongly modulated by tuberculosis treatment; and had responses that were greater for patients who culture-converted at 8weeks. With treatment, all proteins decreased, except for osteocalcin, MCP-1 and MCP-4, which significantly increased. Several previously reported putative tuberculosis-associated biomarkers (HOMX1, neopterin, and cathelicidin) were not significantly associated with treatment response. In conclusion, across a geographically diverse and large population of tuberculosis patients enrolled in a clinical trial, several previously reported putative biomarkers were not significantly associated with treatment response, however, seven proteins had recurring strong associations with baseline radiographic and microbiologic measures of disease severity, as well as with early treatment response, deserving additional study.


Asunto(s)
Biomarcadores/sangre , Índice de Severidad de la Enfermedad , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/tratamiento farmacológico , Adulto , Anciano , Antituberculosos , Combinación de Medicamentos , Etambutol/administración & dosificación , Femenino , Humanos , Isoniazida/administración & dosificación , Masculino , Persona de Mediana Edad , Pirazinamida/administración & dosificación , Rifampin/administración & dosificación , Resultado del Tratamiento , Tuberculosis Pulmonar/patología
5.
Pathologica ; 108(3): 148-150, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28195268

RESUMEN

Vulvar tumors are not very common and account for about 4% of all cancers affecting the female genital organs. Frequently, malignant neoplasia of this site have squamous phenotype and the rare cases of metastasization are reported in the locoregional lymph nodes and in the surrounding organs. We report a case of metastasization of a vulvar squamous cell carcinoma in an unusual place such as the parietal pleura, in a relapsing patient that was submitted to a surgical vulvectomy the previous year.


Asunto(s)
Carcinoma de Células Escamosas/secundario , Derrame Pleural Maligno/patología , Neoplasias Pleurales/secundario , Neoplasias de la Vulva/patología , Anciano , Biomarcadores de Tumor/análisis , Biopsia , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/complicaciones , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/etiología , Neoplasias Pleurales/química , Neoplasias Pleurales/complicaciones , Valor Predictivo de las Pruebas , Tomografía Computarizada por Rayos X
6.
Curr Mol Med ; 14(2): 246-54, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24467204

RESUMEN

The caspases are a family of ubiquitously expressed cysteine proteases best known for their roles in programmed cell death. However, caspases play a number of other roles in vertebrates. In the case of caspase-8, loss of expression is an embryonic lethal phenotype, and caspase-8 plays roles in suppressing cellular necrosis, promoting differentiation and immune signaling, regulating autophagy, and promoting cellular migration. Apoptosis and migration require localization of caspase-8 in the periphery of the cells, where caspase-8 acts as part of distinct biosensory complexes that either promote migration in appropriate cellular microenvironments, or cell death in inappropriate settings. In the cellular periphery, caspase-8 interacts with components of the focal adhesion complex in a tyrosine-kinase dependent manner, promoting both cell migration in vitro and metastasis in vivo. Mechanistically, caspase-8 interacts with components of both focal adhesions and early endosomes, enhancing focal adhesion turnover and promoting rapid integrin recycling to the cell surface. Clinically, this suggests that the expression of caspase-8 may not always be a positive prognostic sign, and that the role of caspase-8 in cancer progression is likely context-dependent.


Asunto(s)
Caspasa 8/metabolismo , Movimiento Celular/fisiología , Animales , Apoptosis/genética , Apoptosis/fisiología , Caspasa 8/genética , Movimiento Celular/genética , Humanos
7.
Radiol Med ; 116(2): 302-9, 2011 Mar.
Artículo en Inglés, Italiano | MEDLINE | ID: mdl-21076886

RESUMEN

PURPOSE: This study retrospectively analysed the results of biopsies obtained during percutaneous vertebroplasty (PVP) in patients with presumed osteoporotic vertebral compression fractures, with a view to highlighting the importance of coaxial biopsy in determining the aetiology of vertebral fractures and planning subsequent treatment. MATERIALS AND METHODS: Between November 2003 and March 2009, 98 patients (78 women; 20 men) with a clinical and imaging suspicion of osteoporotic vertebral compression fractures underwent coaxial biopsy in conjunction with PVP of the thoracic and lumbar vertebrae. Mean age at the time of the procedure was 72.6 years. A pathologist interpreted all the biopsy samples. RESULTS: In 83 patients, the biopsy results were consistent with the presumed osteoporotic aetiology. In two patients, a malignancy was identified. Biopsy samples from 13 patients were considered insufficient or unsuitable by the pathologist for evaluation. CONCLUSIONS: Despite the number of biopsy samples considered insufficient or unsuitable, coaxial biopsy during PVP is useful in verifying the presumed aetiology of vertebral compression fractures, which is often unclear on the basis of clinical and imaging examinations. It is therefore both convenient and advisable to perform a vertebral coaxial biopsy in all patients undergoing a PVP.


Asunto(s)
Biopsia con Aguja/métodos , Fracturas por Compresión/patología , Fracturas por Compresión/cirugía , Fracturas Osteoporóticas/patología , Fracturas Osteoporóticas/cirugía , Fracturas de la Columna Vertebral/patología , Fracturas de la Columna Vertebral/cirugía , Vertebroplastia/métodos , Anciano , Anciano de 80 o más Años , Biopsia con Aguja/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía Intervencional , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Vertebroplastia/instrumentación
8.
Oncogene ; 28(40): 3551-62, 2009 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-19668227

RESUMEN

Microtubule-perturbing drugs have become front-line chemotherapeutics, inducing cell-cycle crisis as a major mechanism of action. However, these agents show pleiotropic effects on cells and can induce apoptosis through other means. Paclitaxel, a microtubule-stabilizing agent, induces a caspase-dependent apoptosis, although the precise mechanism(s) remain unclear. Here, we used genetic approaches to evaluate the role of caspase 8 in paclitaxel-mediated apoptosis. We observed that caspase 8-expressing cells are more sensitive to paclitaxel than caspase 8-deficient cells. Mechanistically, caspase 8 was found associated with microtubules, and this interaction increased after paclitaxel treatment. The prodomains death effector domains (DEDs) of caspase 8 were sufficient for interaction with microtubules, but the caspase 8 holoprotein was required for apoptosis. DED-only forms of caspase 8 were found in both primary and tumor cell lines, associating with perinuclear microtubules and the centrosome. Microtubule association, and paclitaxel sensitivity, depends on a critical lysine (K156) within a microtubule-binding motif (KLD) in DED-b of caspase 8. The results show an unexpected pathway of apoptosis mediated by caspase 8.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Caspasa 8/fisiología , Microtúbulos/fisiología , Neuroblastoma/tratamiento farmacológico , Paclitaxel/farmacología , Caspasa 8/química , Línea Celular Tumoral , Centrosoma/fisiología , Humanos , Neuroblastoma/patología , Estructura Terciaria de Proteína
9.
Radiol Med ; 114(4): 595-607, 2009 Jun.
Artículo en Inglés, Italiano | MEDLINE | ID: mdl-19444592

RESUMEN

PURPOSE: The purpose of this study was to compare exposure of patient and operator to ionising radiation during percutaneous vertebroplasty performed under combined computed tomography (CT) and fluoroscopic guidance or fluoroscopic guidance alone. MATERIALS AND METHODS: With the collaboration of our physics department, we measured exposure on ten patients undergoing vertebroplasty with combined CT and fluoroscopic guidance and on ten undergoing vertebroplasty with fluoroscopic guidance alone. RESULTS: Mean operator dose was approximately 0.8 microSv during vertebroplasty done with combined CT and fluoroscopic guidance and 5.8 microSv in procedures with fluoroscopic guidance alone. Mean patient dose was approximately 6 mSv for combined guidance and 8 mSv for fluoroscopic guidance, a difference that was not found to be statistically significant. CONCLUSIONS: Although combined CT and fluoroscopic guidance is normally preferred for difficult areas such as the cervical and upper thoracic vertebrae, to ensure operator radiation protection, the technique should also be considered for areas normally treated under fluoroscopic guidance alone. However, a larger patient series is needed to correctly evaluate the real contribution of low-dose CT to patient exposure.


Asunto(s)
Fluoroscopía/efectos adversos , Exposición Profesional/análisis , Monitoreo de Radiación/métodos , Radiografía Intervencional/métodos , Vertebroplastia/métodos , Algoritmos , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Fluoroscopía/métodos , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Exposición Profesional/prevención & control , Dosis de Radiación , Radiación Ionizante , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/cirugía
10.
Radiol Med ; 113(1): 101-13, 2008 Feb.
Artículo en Inglés, Italiano | MEDLINE | ID: mdl-18338131

RESUMEN

PURPOSE: This article reports on our experience treating vertebral fractures with percutaneous vertebroplasty. A clinical and imaging follow-up designed to identify the early (especially pulmonary embolism of bone cement) and late complications of the technique is proposed. MATERIAL AND METHODS: On the basis of the current guidelines, 101 patients were selected: 64 osteoporotic and 37 neoplastic. A total of 173 vertebrae were treated. Procedures were performed with both computed tomography and fluoroscopic guidance. Residual pain was evaluated with a visual analogue scale score immediately after vertebroplasty and 1, 15, 30, 90, 180 and 270 days later. Spine and chest radiographs were obtained 24 h after vertebroplasty; spine radiography was repeated 30 days later. RESULTS: Therapeutic success was obtained in 88% of osteoporotic patients and in 84% of neoplastic patients. Pulmonary cement emboli were identified in four patients, all of whom were asymptomatic. CONCLUSIONS: Percutaneous vertebroplasty is a safe and effective technique for the treatment of osteoporotic and neoplastic vertebral fractures. Clinical and imaging followup allows effective patient monitoring and early detection of possible complications.


Asunto(s)
Fracturas de la Columna Vertebral/cirugía , Vertebroplastia/métodos , Adulto , Anciano , Anciano de 80 o más Años , Cementos para Huesos/efectos adversos , Femenino , Fluoroscopía/métodos , Estudios de Seguimiento , Fracturas Espontáneas/cirugía , Humanos , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Osteoporosis/cirugía , Dimensión del Dolor , Dolor Postoperatorio/etiología , Complicaciones Posoperatorias/diagnóstico , Embolia Pulmonar/diagnóstico por imagen , Radiografía Intervencional/métodos , Enfermedades de la Columna Vertebral/cirugía , Neoplasias de la Columna Vertebral/cirugía , Vértebras Torácicas/cirugía , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento
11.
Radiol Med ; 109(1-2): 118-24, 2005.
Artículo en Inglés, Italiano | MEDLINE | ID: mdl-15729192

RESUMEN

PURPOSE: The aim of this study is to assess the effectiveness and safety of the use of Vasoseal ES collagen plug in heavily anticoagulated patients with high risk of complications at the vascular access site who had undergone vascular radiological intervention. MATERIALS AND METHODS: Between January 2002 and March 2003 180 consecutive transfemoral arterial accesses in 169 patients subjected to vascular radiological procedures were performed (bilateral access was performed in 11 patients): 140 percutaneous transluminal angioplasties and 40 transarterial chemoembolisations. All the patients who underwent angioplasty were given 3,000 IU of sodic heparin intravenously during the procedure and later a prolonged antiaggregant therapy was undertaken (ticlopidine 500 mg/day and aspirin 150 mg/day). The sheaths were removed at the end of the surgical manoeuvre and two cartridges of collagen were positioned on the external surface of the artery. The mean values of platelets and partial thromboplastin time were 42,000/ml and 170 s, respectively, in cirrhotic patients against 250,000/ml and 200 s in patients with peripheral arteriopathy. The next day a colour Doppler examination was performed at the puncture site. RESULTS: The technique proved successful in 89.4% of cases (161/180). In 19/180 vascular accesses placement of the haemostatic cartridges was not possible owing to the inability to compress the common femoral artery proximal to the release site (4/19), owing to a pre-existing haematoma (5/19) and owing to the limited presence of subcutaneous tissue (10/19). The mean time required for the placement of Vasoseal ES was 4 min. The mean time-to-haemostasis was 6 min. The mean time-to-mobilisation was 4 hr. Only in two patients was there an onset of a pseudoaneurysm of the right common femoral artery; the lesions were treated with ultrasonography -guided compression. In addition, 16 small local haematomas were recorded. In 4 cases early re-puncture of the femoral artery was performed (24-48 hr following the use of the device) without consequences. CONCLUSIONS: Vasoseal ES is a safe collagen closure device characterised by a high success rate. In anticoagulated patients the device can reduce the time-to-mobilisation and the incidence of complications.


Asunto(s)
Cateterismo Periférico , Arteria Femoral , Técnicas Hemostáticas/instrumentación , Adulto , Anciano , Anciano de 80 o más Años , Cateterismo Periférico/efectos adversos , Colágeno/administración & dosificación , Femenino , Técnicas Hemostáticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad
12.
Invest Ophthalmol Vis Sci ; 42(13): 3349-56, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11726644

RESUMEN

PURPOSE: To evaluate the optical aberrations induced by LASIK refractive surgery for myopia on the anterior surface of the cornea and the entire optical system of the eye. METHODS: Total and corneal aberrations were measured in a group of 14 eyes (preoperative myopia ranging from -2.5 to -13 D) before and after LASIK surgery. Total aberrations were measured using a laser ray-tracing technique. Corneal aberrations were obtained from corneal elevation maps measured using a corneal system and custom software. Corneal and total wave aberrations were described as Zernike polynomial expansions. Root-mean-square (RMS) wavefront error was used as a global optical quality metric. RESULTS: Total and corneal aberrations (third-order and higher) showed a statistically significant increase after LASIK myopia surgery, by a factor of 1.92 (total) and 3.72 (corneal), on average. This increase was more pronounced in patients with the highest preoperative myopia. There is a good correlation (r = 0.97, P < 0.0001) between the aberrations induced in the entire optical system and those induced in the anterior corneal surface. However, the anterior corneal spherical aberration increased more than the total spherical aberration, suggesting also a change in the spherical aberration of the posterior corneal surface. Pupil centration and internal optical aberrations, which are not accounted for in corneal topography, play an important role in evaluating individual surgical outcomes. CONCLUSIONS: Because LASIK surgery induces changes in the anterior corneal surface, most changes in the total aberration pattern can be attributed to changes in the anterior corneal aberrations. However, because of individual interactions of the aberrations in the ocular components, a combination of corneal and total aberration measurements is critical to understanding individual outcomes, and by extension, to designing custom ablation algorithms. This comparison also reveals changes in the internal aberrations, consistent with the posterior corneal changes reported using scanning slit corneal topography.


Asunto(s)
Topografía de la Córnea , Ojo/fisiopatología , Queratomileusis por Láser In Situ , Miopía/cirugía , Adulto , Córnea/patología , Córnea/fisiopatología , Femenino , Humanos , Masculino , Periodo Posoperatorio , Resultado del Tratamiento
13.
Biochem Biophys Res Commun ; 288(2): 301-8, 2001 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-11606043

RESUMEN

We investigated the role of the HIV-1 protein Tat in AIDS-associated dementia, by studying its toxicity on rat cortical and hippocampal neurons in vitro. We evaluated the involvement of astroglial cells and of caspase transduction pathway in determining Tat toxicity. Here we report that synthetic Tat(1-86) induced apoptotic death on cultured rat neurons in a time-dependent manner that was not influenced by glial coculture, and that was abolished by blocking caspase transduction pathway. A microfluorimetric analysis on the Tat excitatory properties on neurons, and its effect on intracellular calcium concentrations, revealed that Tat(1-86) induced increase in cytoplasmic free calcium concentrations in rat hippocampal and cortical neurons. This effect required extracellular calcium and was differently reduced by voltage dependent calcium channel blockers and both NMDA and non-NMDA glutamate receptors antagonists. Furthermore, we observed that Tat(1-86)-treated neurons showed increased sensitivity to the glutamate excitotoxicity. Thus, the Tat-induced neuronal injury seems to occur through a direct interaction of the protein with neurons, requires activation of caspases, and is likely to derive from Tat(1-86)-induced calcium loads and disruption of glutamatergic transmission.


Asunto(s)
Apoptosis , Calcio/metabolismo , Productos del Gen tat/farmacología , Homeostasis/efectos de los fármacos , Neuronas/efectos de los fármacos , Animales , Células Cultivadas , Neuronas/citología , Neuronas/metabolismo , Ratas , Ratas Sprague-Dawley
14.
Front Neuroendocrinol ; 22(3): 147-84, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11456467

RESUMEN

Chemokines are a family of proteins associated with the trafficking of leukocytes in physiological immune surveillance and inflammatory cell recruitment in host defence. They are classified into four classes based on the positions of key cystiene residues: C, CC, CXC, and CX3C. Chemokines act through both specific and shared receptors that all belong to the superfamily of G-protein-coupled receptors. Besides their well-established role in the immune system, several recent reports have demonstrated that these proteins also play a role in the central nervous system (CNS). In the CNS, chemokines are constitutively expressed by microglial cells, astrocytes, and neurons, and their expression can be increased after induction with inflammatory mediators. Constitutive expression of chemokines and chemokine receptors has been observed in both developing and adult brains, and the role played by these proteins in the normal brain is the object of intense study by many research groups. Chemokines are involved in brain development and in the maintenance of normal brain homeostasis; these proteins play a role in the migration, differentiation, and proliferation of glial and neuronal cells. The chemokine stromal cell-derived factor 1 and its receptor, CXCR4, are essential for life during development, and this ligand-receptor pair has been shown to have a fundamental role in neuron migration during cerebellar formation. Chemokine and chemokine receptor expression can be increased by inflammatory mediators, and this has in turn been associated with several acute and chronic inflammatory conditions. In the CNS, chemokines play an essential role in neuroinflammation as mediators of leukocyte infiltration. Their overexpression has been implicated in different neurological disorders, such as multiple sclerosis, trauma, stroke, Alzheimer's disease, tumor progression, and acquired immunodeficiency syndrome-associated dementia. An emerging area of interest for chemokine action is represented by the communication between the neuroendocrine and the immune system. Chemokines have hormone-like actions, specifically regulating the key host physiopathological responses of fever and appetite. It is now evident that chemokines and their receptors represent a plurifunctional family of proteins whose actions on the CNS are not restricted to neuroinflammation. These molecules constitute crucial regulators of cellular communication in physiological and developmental processes.


Asunto(s)
Sistema Nervioso Central/fisiología , Quimiocinas/fisiología , Receptores de Quimiocina/fisiología , Animales , Enfermedades del Sistema Nervioso Central/genética , Enfermedades del Sistema Nervioso Central/metabolismo , Enfermedades del Sistema Nervioso Central/fisiopatología , Humanos , Sistemas Neurosecretores/fisiología
15.
J Neurochem ; 77(5): 1226-36, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11389173

RESUMEN

Stromal cell-derived factor-1 (SDF-1), the ligand of the CXCR4 receptor, is a chemokine involved in chemotaxis and brain development that also acts as co-receptor for HIV-1 infection. We previously demonstrated that CXCR4 and SDF-1alpha are expressed in cultured type-I cortical rat astrocytes, cortical neurones and cerebellar granule cells. Here, we investigated the possible functions of CXCR4 expressed in rat type-I cortical astrocytes and demonstrated that SDF-1alpha stimulated the proliferation of these cells in vitro. The proliferative activity induced by SDF-1alpha in astrocytes was reduced by PD98059, indicating the involvement of extracellular signal-regulated kinases (ERK1/2) in the astrocyte proliferation induced by CXCR4 stimulation. This observation was further confirmed showing that SDF-1alpha treatment selectively activated ERK1/2, but not p38 or stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). Moreover, both astrocyte proliferation and ERK1/2 phosphorylation, induced by SDF-1alpha, were inhibited by pertussis toxin (PTX) and wortmannin treatment indicating the involvement of a PTX sensitive G-protein and of phosphatidyl inositol-3 kinase in the signalling of SDF-1alpha. In addition, Pyk2 activation represent an upstream components for the CXCR4 signalling to ERK1/2 in astrocytes. To our knowledge, this is the first report demonstrating a proliferative effect for SDF-1alpha in primary cultures of rat type-I astrocytes, and showing that the activation of ERK1/2 is responsible for this effect. These data suggest that CXCR4/SDF-1 should play an important role in physiological and pathological glial proliferation, such as brain development, reactive gliosis and brain tumour formation.


Asunto(s)
Astrocitos/efectos de los fármacos , Quimiocinas CXC/farmacología , Receptores CXCR4/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Animales , Western Blotting , Calcio/metabolismo , División Celular/efectos de los fármacos , Células Cultivadas , Corteza Cerebral/citología , Corteza Cerebral/efectos de los fármacos , Quimiocina CXCL12 , ADN/biosíntesis , Indicadores y Reactivos , Proteína Quinasa 3 Activada por Mitógenos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Fosforilación , Ratas , Receptores CXCR4/metabolismo , Timidina/metabolismo
16.
Invest Ophthalmol Vis Sci ; 42(6): 1396-403, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-11328757

RESUMEN

PURPOSE: To determine objectively the changes in the ocular aberrations (3rd order and above) induced by myopic LASIK refractive surgery and its impact on image quality. METHODS: The ocular aberrations of 22 normal myopic eyes (preoperative refraction ranged from -13 to -2 D) were measured before (2.9 +/- 4.3 weeks) and after (7.7 +/- 3.2 weeks) LASIK refractive surgery using a laser ray tracing technique. A set of laser pencils is sequentially delivered onto the eye through different pupil locations. For each ray, the corresponding retinal image is collected on a CCD camera. The displacement of the image centroid with respect to a reference provides direct information of the ocular aberrations. Root-mean-square (RMS) wavefront error was taken as image quality metric. RESULTS: RMS wavefront error increased significantly in all eyes but two after surgery. On average, LASIK induced a significant (P = 0.0003) 1.9-fold increase in the RMS error for a 6.5-mm pupil. The main contribution was due to the increase (fourfold, P < 0.0001) of spherical aberration. The increase in the RMS for a 3-mm pupil (1.7-fold) was also significant (P = 0.02). The modulation transfer (computed for 6.5-mm pupil) decreased on average by a factor of 2 for middle-high spatial frequencies. CONCLUSIONS: (1) Laser ray tracing is a well-suited, robust, and reliable technique for the evaluation of the change of ocular aberrations with refractive surgery. (2) Refractive surgery induces important amounts of 3rd and higher order aberrations. The largest increase occurs for spherical aberration. Decentration of the ablation pattern seems to generate 3rd order aberrations. (3) This result is important for the design of customized ablation algorithms, which should cancel existing preoperative aberrations while avoiding the generation of new aberrations.


Asunto(s)
Córnea/cirugía , Queratomileusis por Láser In Situ , Miopía/cirugía , Fenómenos Fisiológicos Oculares , Visión Ocular/fisiología , Adulto , Femenino , Humanos , Rayos Láser , Masculino , Psicofísica , Pupila/fisiología , Retina/fisiología
17.
Brain Res Brain Res Protoc ; 5(3): 273-81, 2000 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10906493

RESUMEN

Ciliary neurotrophic factor (CNTF) promotes the survival of several populations of neurons, including sensory and motor neurons. It is mainly produced by Schwann cells and astrocytes and exerts its biological function via a specific membrane receptor. We recently determined the nuclear localization of CNTF in producing cells, after transfection and in the heterologous system of Xenopus oocytes. In the present paper, we describe in detail the techniques for the detection of CNTF in the nucleus of rat astrocytes, transfected cells, isolated nuclei and injected Xenopus oocytes.


Asunto(s)
Astrocitos/química , Núcleo Celular/química , Factor Neurotrófico Ciliar/análisis , Técnica del Anticuerpo Fluorescente Indirecta , Transfección/métodos , Animales , Anticuerpos Monoclonales , Células COS , Factor Neurotrófico Ciliar/inmunología , Femenino , Glioma , Microinyecciones , Microscopía Confocal/métodos , Oocitos/fisiología , Pruebas de Precipitina/métodos , ARN Mensajero , Ratas , Ratas Sprague-Dawley , Células Tumorales Cultivadas , Xenopus laevis
18.
J Neurochem ; 73(6): 2348-57, 1999 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10582593

RESUMEN

Chemokines are a family of proteins that chemoattract and activate cells by interacting with specific receptors on the surface of their targets. The chemokine stromal cell-derived factor 1, (SDF1), binds to the seven-transmembrane G protein-coupled CXCR4 receptor and acts to modulate cell migration, differentiation, and proliferation. CXCR4 and SDF1 are reported to be expressed in various tissues including brain. Here we show that SDF1 and CXCR4 are expressed in cultured cortical type I rat astrocytes, cortical neurons, and cerebellar granule cells. In cortical astrocytes, prolonged treatment with lipopolysaccharide induced an increase of SDF1 expression and a down-regulation of CXCR4, whereas treatment with phorbol esters did not affect SDF1 expression and down-modulated CXCR4 receptor expression. We also demonstrated the ability of human SDF1alpha (hSDF1alpha) to increase the intracellular calcium level in cultured astrocytes and cortical neurons, whereas in the same conditions, cerebellar granule cells did not modify their intracellular calcium concentration. Furthermore, in cortical astrocytes, the simultaneous treatment of hSDF1alpha with the HIV-1 capside glycoprotein gp120 inhibits the cyclic AMP formation induced by forskolin treatment.


Asunto(s)
Complejo SIDA Demencia/metabolismo , Astrocitos/metabolismo , Señalización del Calcio/efectos de los fármacos , Quimiocinas CXC/biosíntesis , VIH-1/fisiología , Proteínas del Tejido Nervioso/biosíntesis , Neuroglía/metabolismo , Neuronas/metabolismo , Receptores CXCR4/biosíntesis , Animales , Northern Blotting , Western Blotting , Células COS , Células Cultivadas , Cerebelo/citología , Corteza Cerebral/citología , Quimiocina CXCL12 , Quimiocinas CXC/genética , Chlorocebus aethiops , Colforsina/farmacología , AMP Cíclico/biosíntesis , Técnica del Anticuerpo Fluorescente Indirecta , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/antagonistas & inhibidores , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/fisiología , Regulación de la Expresión Génica , Proteína gp120 de Envoltorio del VIH/farmacología , Humanos , Ligandos , Lipopolisacáridos/farmacología , Proteínas del Tejido Nervioso/genética , Especificidad de Órganos , Ratas , Ratas Sprague-Dawley , Receptores CXCR4/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sistemas de Mensajero Secundario/efectos de los fármacos , Factores de Virulencia de Bordetella/farmacología
20.
Ann N Y Acad Sci ; 876: 201-9, 1999 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-10415611

RESUMEN

Human immunodeficiency virus (HIV-1) infects the brain and causes a progressive encephalopathy in 20 to 30% of infected children and adults called AIDS dementia complex. Evidence from in vitro and in vivo studies suggests a role for the viral envelope glycoprotein gp120, as a mediator of neurotoxicity. However, the site of interaction of gp120 with neurons and astrocytes to mediate neuronal death is still unknown. Recently the chemokine receptors, CCR5 and CXCR4, have been identified as co-receptors together with CD4 for HIV-1 entry into the target cells, suggesting a possible role for these receptors in the pathogenesis of the HIV-1 infection in the brain. Here we report the expression of CCR5 and CXCR4 in many different rat brain areas. We also found both receptors in cultured type I astrocytes demonstrating that glial cells may represent an important target for chemokines in vivo. Indeed, the functional capacity of CXCR4 receptor in astrocytes was demonstrated showing that SDF 1 alpha induced an increase of intracellular calcium concentration.


Asunto(s)
Encéfalo/metabolismo , Receptores de Quimiocina/metabolismo , Animales , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Calcio/metabolismo , Células Cultivadas , Quimiocina CXCL12 , Quimiocinas CXC/farmacología , Técnica del Anticuerpo Fluorescente , Ratas , Ratas Sprague-Dawley , Receptores CCR5/metabolismo , Receptores CXCR4/metabolismo
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