RESUMEN
Child maltreatment, including all forms of mal¬treatment, remains a major public health problem in high-income countries. Healthcare professionals only contribute to a small proportion of reports. In French-speaking Belgium, almost 100 % of school-aged children are regularly submitted to periodical school health visits. The school health doctor is well placed to recognize neglected or abused children. Based on international good practice recommendations, this paper proposes means for the detection and management of child abuse in the context of school medicine.
La maltraitance infantile représente, dans les pays à haut niveau de revenus, un «problème de santé publique majeur¼, 5 à 10 % des enfants étant concernés, toutes formes de maltraitances confondues. Les professionnels de santé contribuent à une petite proportion seulement des signale¬ments. En Fédération Wallonie-Bruxelles, les bilans de santé scolaire périodiques couvrant près de 100 % des enfants sco¬larisés, le médecin scolaire est bien placé pour le repérage d'enfants exposés à une négligence de soins et/ou à de mauvais traitements. Se basant sur des recommandations de bonne pratique publiées, cet article propose des pistes d'action per¬mettant de contribuer à un meilleur repérage et à une prise en charge adaptée de la maltraitance infantile dans le cadre de la médecine scolaire.
Asunto(s)
Maltrato a los Niños , Rol del Médico , Guías de Práctica Clínica como Asunto , Servicios de Salud Escolar , Niño , Maltrato a los Niños/diagnóstico , Maltrato a los Niños/prevención & control , Maltrato a los Niños/terapia , Protección a la Infancia/tendencias , Preescolar , Humanos , Servicios de Salud Escolar/normas , Recursos HumanosRESUMEN
Duchenne muscular dystrophy is characterized by progressive muscle weakness and early death resulting from dystrophin deficiency. Spontaneous canine muscular disorders are interesting settings to evaluate the relevance of innovative therapies in human using pre-clinical trials.
RESUMEN
In an attempt to improve the survival of implanted dopamine cells, we have readdressed the optimal embryonic donor age for dopamine grafts. In a rat model of Parkinson's disease, animals with unilateral 6-hydroxydopamine lesions of the median forebrain bundle received dopamine-rich ventral mesencephalic grafts derived from embryos of crown to rump length 4, 6, 9, or 10.5 mm (estimated embryonic age (E) 11, E12, E13 and E14 days post-coitus, respectively). Grafts derived from 4 mm embryos survived poorly, with less than 1% of the implanted dopamine cells surviving. Grafts derived from 9 mm and 10.5 mm embryos were similar to those seen in previous experiments with survival rates of 8% and 7% respectively. The best survival was seen in the group that received 6 mm grafts, which were significantly larger than all other graft groups. Mean dopamine cell survival in the 6 mm group (E12) was 36%, an extremely high survival rate for primary, untreated ventral mesencephalic grafts applied as a single placement, and more than fivefold larger than the survival rate observed in the 10.5 mm (E14) group. As E12 ventral mesencephalic tissues contain few, if any, differentiated dopamine cells we conclude that the large numbers of dopamine cells seen in the 6 mm grafts must have differentiated post-implantation. We consider the in vivo conditions which allow this differentiation to occur, and the implications for the future of clinical trials based on dopamine cell replacement therapy.
Asunto(s)
Trasplante de Tejido Encefálico/métodos , Dopamina/metabolismo , Neuronas/fisiología , Enfermedad de Parkinson/cirugía , Factores de Edad , Anfetamina/farmacología , Animales , Conducta Animal , Recuento de Células , Diferenciación Celular/fisiología , Supervivencia Celular , Modelos Animales de Enfermedad , Inhibidores de Captación de Dopamina/farmacología , Embrión de Mamíferos , Femenino , Mesencéfalo/citología , Embarazo , Ratas , Ratas Sprague-Dawley , Conducta Estereotipada/efectos de los fármacos , Conducta Estereotipada/fisiología , Trasplantes , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
The poor survival of dopamine grafts in Parkinson's disease is one of the main obstacles to the widespread application of this therapy. One hypothesis is that implanted neurons, once removed from the embryonic environment, lack the differentiation factors needed to develop the dopaminergic phenotype. In an effort to improve the numbers of dopamine neurons surviving in the grafts, we have investigated the potential of adenoviral vectors to deliver the differentiation factor sonic hedgehog or the glial cell line-derived neurotrophic factor GDNF to dopamine-rich grafts in a rat model of Parkinson's disease. Adenoviral vectors containing sonic hedgehog, GDNF, or the marker gene LacZ were injected into the dopamine depleted striatum of hemiparkinsonian rats. Two weeks later, ventral mesencephalic cell suspensions were prepared from embryos of donor ages E12, E13, E14 or E15 and implanted into the vector-transduced striatum. Pre-treatment with the sonic hedgehog vector produced a three-fold increase in the numbers of tyrosine hydroxylase-positive (presumed dopaminergic) cells in grafts derived from E12 donors, but had no effect on E13-E15 grafts. By contrast, pre-treatment with the GDNF vector increased yields of dopamine cells in grafts derived from E14 and E15 donors but had no effect on grafts from younger donors. The results indicate that provision of both trophic and differentiation factors can enhance the yields of dopamine neurons in ventral mesencephalic grafts, but that the two factors differ in the age and stage of embryonic development at which they have maximal effects.
Asunto(s)
Trasplante de Tejido Fetal/métodos , Terapia Genética/métodos , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Mesencéfalo/trasplante , Enfermedad de Parkinson/terapia , Transactivadores/genética , Adenoviridae/genética , Anfetamina/farmacología , Animales , Recuento de Células , Modelos Animales de Enfermedad , Dopamina/fisiología , Femenino , Edad Gestacional , Proteínas Hedgehog , Actividad Motora/efectos de los fármacos , Oxidopamina , Enfermedad de Parkinson/patología , Embarazo , Ratas , Ratas Sprague-Dawley , Simpaticolíticos , Simpatomiméticos/farmacologíaRESUMEN
We have investigated the in vivo dynamics of an adenovirus-based, LacZ expressing vector, RAd36, at different doses, when injected unilaterally into the corpus striatum of normal rats. We have further investigated the characteristics of this vector in the presence of a 6-OHDA lesion of the nigrostriatal pathway. The dopamine-depleting lesion had an effect on both the number and the distribution of cells transduced by the adenoviral vector. The lesioned side of the brain contained significantly greater numbers of beta-galactosidase positive cells than the unlesioned side at 3 days, 1 week and 4 weeks post-injection and the distribution of transduced cells was altered by the presence of a dopamine lesion. We conclude that the increased levels of transgene expression seen in the lesioned hemisphere are due to a change in the diffusion characteristics of the injected vector in the lesioned hemisphere. These results indicate that, when investigating the use of virus-based vectors, ultimately for use in gene therapies in the CNS, the in vivo dynamics of the vector need to be assessed not only in the normal brain, but also in the pathological brain state such as animal models of target diseases.
Asunto(s)
Adenoviridae/genética , Regulación Viral de la Expresión Génica/genética , Terapia Genética/métodos , Vectores Genéticos/genética , Trastornos Parkinsonianos/terapia , Transgenes/genética , Animales , Cuerpo Estriado/metabolismo , Cuerpo Estriado/fisiopatología , Cuerpo Estriado/cirugía , Modelos Animales de Enfermedad , Dopamina/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Genes Reporteros/genética , Vectores Genéticos/uso terapéutico , Operón Lac/genética , Vías Nerviosas/metabolismo , Vías Nerviosas/fisiopatología , Oxidopamina , Trastornos Parkinsonianos/genética , Trastornos Parkinsonianos/metabolismo , Ratas , Ratas Sprague-Dawley , Sustancia Negra/metabolismo , Sustancia Negra/fisiopatología , Simpaticolíticos , Transfección/métodosRESUMEN
The molecular mechanisms underlying the heterogeneous effects of retinoic acid (RA) treatment on malignant glioma cells remain poorly understood. In this study, we present the first evidence of a functional role of the signal transduction factors (STATs) in RA-induced proliferation, in a human glioblastoma GL-15 cell line. We first observed that STAT-3 was constitutively activated and present in the GL-15 cell nuclei. We then showed that at low doses (0.01-1 microM) RA increased both the proliferation rate of GL-15 cells and the phosphotyrosine (PY) activation of STAT-3. This RA effect involved transcriptional processes and the transactivation of RA target genes, including RA receptors isoforms RARalpha2, -beta2, and -gamma2. At higher concentrations, however, RA (5-10 microM) inhibits GL-15 proliferation, induces apoptosis, and fails to activate STAT-3. An inhibitory effect on GL-15 proliferation was also observed with the synthetic retinoids CD-437 and CD-2325, two structurally related RARgamma agonists, which also fail to activate STAT-3. In addition, the phorbol ester PMA, an inducer of GL-15 differentiation, and staurosporine, a broad inhibitor of protein kinases, abrogate the stimulatory effects of RA at low concentrations. Together these observations suggest that, in GL-15 cells, activation of STAT-3 and cell proliferation share common mechanisms and that STAT transcription factors may be involved in a switch between proliferation, differentiation, and apoptosis. The proliferating effect observed at low doses of RA may be related to the failures in RA efficiency observed in clinical assays in relapsing malignant gliomas. Combining specific inhibitors of tyrosine kinases with RA might optimize the clinical outcome.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , División Celular/efectos de los fármacos , Proteínas de Unión al ADN/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioma/tratamiento farmacológico , Transactivadores/efectos de los fármacos , Tretinoina/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/fisiopatología , Carcinógenos/farmacología , División Celular/fisiología , Núcleo Celular/efectos de los fármacos , Núcleo Celular/genética , Proteínas de Unión al ADN/fisiología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Regulación Neoplásica de la Expresión Génica/fisiología , Glioma/metabolismo , Glioma/fisiopatología , Humanos , Transporte de Proteínas/efectos de los fármacos , Transporte de Proteínas/genética , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Receptores de Ácido Retinoico/genética , Factor de Transcripción STAT3 , Estaurosporina/farmacología , Acetato de Tetradecanoilforbol/farmacología , Transactivadores/fisiología , Células Tumorales CultivadasRESUMEN
Ciliary neurotrophic factor (CNTF) acts on immature astrocytes that express its trimeric receptor. In contrast, mature astrocytes do not significantly express the specific CNTFalpha receptor subunit, yet they respond to CNTF administration in vivo. Here we show that this controversy may be solved by a shift in astroglial sensitivity to CNTF over time, related to a change in the type of receptor bound by the cytokine on mature astrocytes. A convergent set of results supports the hypothesis that the CNTF effect is due to the illegitimate binding on the leukemia inhibitory factor receptor (LIFR): (i) it requires high concentration of recombinant rat CNTF; (ii) it involves the Jak/Stat and Ras-MAPK pathways; (iii) it is preserved in CNTFRalpha-/- cells; (iv) it is potentiated by soluble CNTFRalpha added to the medium; and (v) it is significantly decreased by a partial antagonist of LIFR. On these bases, we propose a mechanistic model in which, in the adult brain, a CNTF/LIFR interglial system may be modulated by neurons that synthesize CNTFRalpha.
Asunto(s)
Astrocitos/enzimología , Factor Neurotrófico Ciliar/metabolismo , Factor Neurotrófico Ciliar/farmacología , Receptores de Citocinas/metabolismo , Animales , Astrocitos/química , Diferenciación Celular/fisiología , Dimerización , Relación Dosis-Respuesta a Droga , Proteína Ácida Fibrilar de la Glía/análisis , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia , Sistema de Señalización de MAP Quinasas/fisiología , Ratones , Ratones Noqueados , Neuronas/metabolismo , Receptor de Factor Neurotrófico Ciliar/genética , Receptor de Factor Neurotrófico Ciliar/metabolismo , Receptores de Citocinas/química , Receptores OSM-LIF , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
In 108 women over 80 (mean age 88,4 years, extremes 80 and 99 years) hospitalized in a geriatric service for various reasons, radiograms were made of both knees in the frontal aspect on standard film to detect calcinosis of the meniscus and chondrocalcinosis of the joint. In 25 women (23.1%) the radiographs revealed calcinosis of the meniscus with or without chondrocalcinosis. In these 25 cases a lateral X-ray was also made of the two knees, frontal X-rays were made of the pelvis, thumbs and shoulders. In 22 cases (88%) these revealed calcification of the fibrocartilages or articular cartilages in joints other than the knee. Seven of the 25 women had at least one attack of articular inflammation (especially of the knee) resembling a pseudo-gout crisis. The frequency of chronic arthropathies resembling arthroses was high in the 25 patients with chondrocalcinosis: 8 (32%) had an internal or external femoro-tibial arthrosis, as against 11 of the 83 patients (13%) of the same age without chondrocalcinosis, a significant difference. Eleven of the 25 women had signs of femororotular arthrosis on the lateral X-rays of the knees, 5 had coxarthrosis (with in 3 cases a radiological image of fibrocartilaginous or coxofemoral cartilaginous calcification). One women had chronic radiocarpal arthropathy evocative or chondrocalcinosis. Ten had a scaphotrapezoidal arthrosis, 5 arthrosis of the shoulder, 3 with radiological aspect of glenohumeral chondrocalcinosis.