RESUMEN
Purpose: To examine factors decreasing participation in school-based vision programs from parent and teacher perspectives.Methods: We conducted 41 semi-structured focus groups (20 parent groups, 21 teacher/staff groups), at 10 Baltimore and 11 Chicago public elementary and middle schools offering school-based vision programs. School-based vision programs provided vision screening, eye exams, and eyeglasses if needed. Focus groups ranged in size from 2-9 participants (median = 5). Sessions were recorded, transcribed, and coded through an iterative process to develop themes using inductive analysis.Results: Ninety parents and 117 teachers/staff participated. Participants identified five major factors decreasing participation in school-based vision programs: (1) challenges with the consent form, including distribution, collection, and literacy and language barriers; (2) having existing eye care; (3) misunderstandings about the program, especially related to cost and insurance; (4) difficulty raising parental awareness of the program; and (5) certain attitudes towards vision, eye care, and school-based programs, including low prioritization of eye care, mistrust of the program, fear of sharing private information, not believing their child needs glasses, and reluctance accepting 'subsidized' services.Conclusion: Parents and teachers identified important structural barriers to participation (i.e., consent form challenges and low parental awareness) and specific reasons for non-participation (i.e., attitudes, misunderstanding of the program, existing eye care) in school-based vision programs. Effective strategies are needed to facilitate return of consent forms and promote awareness of school-based vision programs among parents. Programs should also target services towards those currently without access to eye care and increase awareness about paediatric vision needs.
Asunto(s)
Padres/psicología , Errores de Refracción/diagnóstico , Servicios de Salud Escolar/normas , Maestros/psicología , Selección Visual/métodos , Adolescente , Adulto , Anciano , Actitud Frente a la Salud , Concienciación , Niño , Preescolar , Anteojos , Grupos Focales/métodos , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , Persona de Mediana Edad , Investigación Cualitativa , Errores de Refracción/epidemiología , Servicios de Salud Escolar/estadística & datos numéricos , Maestros/estadística & datos numéricos , Instituciones Académicas/estadística & datos numéricos , Adulto JovenRESUMEN
Focal cerebral ischemia (stroke) and reperfusion injury leads to acute and chronic brain damage. The increase of the hypoxia-inducible transcription factor alpha (HIF-α), an important transcription factor for several genes, may attenuate ischemic brain injury. We recently identified a new WD-repeat protein designated Morg1 (MAPK organizer 1) that interacts with prolyl hydroxylase 3 (PHD3), an important enzyme involved in the regulation of HIF-1α and HIF-2α expression. While homozygous Morg1(-/-) mice are embryonically lethal, heterozygous Morg1(+/-) mice have a normal phenotype. Brain vasculature as well as systolic blood pressure in Morg1(+/-) mice were indistinguishable from wild-type (WT) animals. We show here that Morg1(+/-) mice were partially protected from cerebral ischemia/reperfusion injury in comparison to WT (Morg1(+/+)) animals using the middle cerebral artery occlusion model (MCAO). Morg1(+/-) mice compared with WT animals revealed a significantly reduced infarct volume as detected by Nissl and Map 2 staining despite a similar restriction of blood flow in both mice genotypes as measured by laser Doppler flowmetry. Immunohistochemistry revealed specific Morg1 expression in reactive astrocytes in the ipsilateral (ischemic) hemisphere in Morg1(+/-) and WT mice, especially in the penumbral regions. In the contralateral hemisphere, Morg1 was not detectable. Furthermore, Morg1 mRNA expression was significantly enhanced in the ischemic brain of WT, but not in ischemic brain tissue obtained from Morg1(+/-) animals. However, HIF-1α was expressed with the same intensity in Morg1(+/-) and WT mice with no difference between the ipsilateral and contralateral hemispheres. No positive staining for HIF-2α was found in ischemic (ipsilateral) and non-ischemic (contralateral) brain regions in Morg1(+/+) and Morg1(+/-) mice. Almost no PHD3 staining was found in the contralateral hemispheres of either WT or heterozygous Morg1(+/-) mice. Transcript expression for the HIF1α-dependent genes erythropoietin (Epo) and vascular endothelial growth factor 164 (VEGF 164) were significantly reduced in the ischemic brain from Morg1(+/-) mice. Positive staining for PHD3 in the ipsilateral hemisphere of WT mice was suggested to occur in astrocytes. A compensatory increase in Morg1 expression in astrocytes in the penumbra may negatively influence infarct volume. It appears that these effects are independent of the PHD3-HIF1α axis.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Heterocigoto , Infarto de la Arteria Cerebral Media/genética , Infarto de la Arteria Cerebral Media/fisiopatología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Encéfalo/metabolismo , Encéfalo/patología , Infarto Cerebral/etiología , Infarto Cerebral/genética , Circulación Cerebrovascular/genética , Modelos Animales de Enfermedad , Lateralidad Funcional/genética , Regulación de la Expresión Génica/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Procolágeno-Prolina Dioxigenasa/genética , Procolágeno-Prolina Dioxigenasa/metabolismo , Daño por Reperfusión/genética , Daño por Reperfusión/fisiopatología , Daño por Reperfusión/prevención & control , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Unraveling the causes of regeneration failure in the adult injured CNS has remained a challenge in neurobiology. The notion that CNS neurons lose their regenerative potential during development has been challenged by the identification of several promoters of axon growth. Novel methods are required that allow to study and quantify interactions of molecular determinants, and to envisage future treatment applications. Here we report a novel, highly reproducible method for monitoring axonal regeneration of mature retinal ganglion cells (RGCs) in vitro. In contrast to earlier explantation methods, primary cultures derived from adult rodent retina are kept viable without growth factor supplements. Further, since intraretinal RGC axons remain unmyelinated, regeneration can be followed independently of non-permissive white matter compounds. Applying tracing techniques prior to retinal explantation, cell survival can be correlated to outgrowth activity on the single cell level. Following intervention with pharmacological, growth factor, or gene transfer treatments, retinal explants, and partially RGC neurites, can be processed for protein and gene expression analysis. This novel procedure will prove useful to get insight into complex cell survival and regeneration promoting cascades, and will complement in vivo strategies such as transgenic and knock out mouse models.
Asunto(s)
Conos de Crecimiento/ultraestructura , Regeneración Nerviosa/genética , Técnicas de Cultivo de Órganos/métodos , Retina/crecimiento & desarrollo , Animales , Comunicación Celular/genética , Supervivencia Celular/genética , Modelos Animales de Enfermedad , Femenino , Técnicas de Transferencia de Gen , Vectores Genéticos/genética , Conos de Crecimiento/efectos de los fármacos , Conos de Crecimiento/fisiología , Sustancias de Crecimiento/farmacología , Ratones , Ratones Endogámicos BALB C , Fibras Nerviosas Amielínicas/efectos de los fármacos , Fibras Nerviosas Amielínicas/fisiología , Fibras Nerviosas Amielínicas/ultraestructura , Regeneración Nerviosa/efectos de los fármacos , Neuritas/efectos de los fármacos , Neuritas/fisiología , Neuritas/ultraestructura , Técnicas de Cultivo de Órganos/instrumentación , Proteínas Proto-Oncogénicas c-bcl-2/genética , Ratas , Ratas Sprague-Dawley , Retina/citología , Retina/efectos de los fármacos , Degeneración Retiniana/genética , Degeneración Retiniana/fisiopatología , Transducción Genética/métodos , Proteína bcl-XRESUMEN
One of the obstacles to efficient vector-mediated gene transfer to the CNS is limited transduction of target neurons. The VP22 tegument protein of HSV-1 can cross biological membranes and translocate the VP22 protein from primarily transfected cells to many surrounding cells in vitro. Here, we employed an adenoviral vector coding for a VP22-GFP fusion protein driven by a CMV promoter to test its capability of transducing CNS neurons in vivo. Intraocular administration of Ad.VP22-GFP in the rat doubled both the retinal area containing transduced, GFP-expressing cells and the absolute number of GFP-expressing retinal neurons compared to Ad.GFP transduction. Following injection of Ad.VP22-GFP into the mouse brain, the transduced striatal area was increased by a factor of 7 compared to intracerebral injection of Ad.GFP. In both retina and striatum, GFP-expressing cells were identified as mainly neurons. Thus, VP22 greatly augments adenovirus-mediated transgene delivery to CNS neuronsin vivo, making VP22 a promising tool for enhancing the efficacy of adenoviral gene transfer of protective factors to the CNS.
Asunto(s)
Adenoviridae/genética , Cuerpo Estriado/metabolismo , Vectores Genéticos , Retina/metabolismo , Proteínas Estructurales Virales/genética , Animales , Cuerpo Estriado/citología , Cuerpo Estriado/virología , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Proteínas Fluorescentes Verdes , Humanos , Inmunidad Celular , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Ratones , Neuronas/citología , Neuronas/metabolismo , Neuronas/virología , Fosfoproteínas/genética , Transporte de Proteínas , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes de Fusión/genética , Retina/citología , Retina/virología , Transducción GenéticaRESUMEN
1. Most segments of the gastrointestinal tract secrete HCO3-, but the molecular nature of the secretory mechanisms has not been identified. We had previously speculated that the regulator for intestinal electrogenic HCO3- secretion is the cystic fibrosis transmembrane regulator (CFTR) channel. To prove this hypothesis, we have now measured HCO3- secretion by pH-stat titration, and recorded the electrical parameters of in vitro duodenum, jejunum and ileum of mice deficient in the gene for the CFTR protein ('CF-mice') and their normal littermates. 2. Basal HCO3- secretory rates were reduced in all small intestinal segments of CF mice. Forskolin, PGE2, 8-bromo-cAMP and VIP (cAMP-dependent agonists), heat-stable enterotoxin of Escherichia coli (STa), guanylin and 8-bromo-cGMP (cGMP-dependent agonists) and carbachol (Ca2+ dependent) stimulated both the short-circuit current (Isc) and the HCO3- secretory rate (JHCO3-) in all intestinal segments in normal mice, whereas none of these agonists had any effect on JHCO3- in the intestine of CF mice. 3. To investigate whether Cl(-)-HCO3- exchangers, which have been implicated in mediating the response to some of these agonists in the intestine, were similarly active in the small intestine of normal and CF mice, we studied Cl- gradient-driven 36Cl- uptake into brush-border membrane (BBM) vesicles isolated from normal and CF mouse small intestine. Both the time course and the peak value for 4,4'-diisothiocyanostilbene-2',2-disulphonic acid (DIDS)-inhibited 36Cl- uptake was similar in normal and CF mice BBM vesicles. 4. In summary, the results demonstrate that the presence of the CFTR channel is necessary for agonist-induced stimulation of electrogenic HCO3- secretion in all segments of the small intestine, and all three intracellular signal transduction pathways stimulate HCO3- secretion exclusively via activation of the CFTR channel.
Asunto(s)
Bicarbonatos/metabolismo , Calcio/metabolismo , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/fisiología , Hormonas Gastrointestinales , Mucosa Intestinal/fisiología , Intestino Delgado/fisiología , 8-Bromo Monofosfato de Adenosina Cíclica/farmacología , Animales , Toxinas Bacterianas/farmacología , Carbacol/farmacología , Colforsina/farmacología , GMP Cíclico/análogos & derivados , GMP Cíclico/farmacología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/deficiencia , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Dinoprostona/farmacología , Duodeno/fisiología , Enterotoxinas/farmacología , Proteínas de Escherichia coli , Íleon/fisiología , Técnicas In Vitro , Mucosa Intestinal/efectos de los fármacos , Yeyuno/fisiología , Cinética , Ratones , Ratones Noqueados , Microvellosidades/fisiología , Péptidos Natriuréticos , Péptidos/farmacología , Péptido Intestinal Vasoactivo/farmacologíaRESUMEN
Se relata el caso de un paciente que presenta por primera vez crisis taquicardicas de muy alta frecuencia ventricular (mayores de 250 por minuto) a la edad de 69 anos. No tenia antecedentes cardiovasculares y no presentaba signos de cardiopatia organica. En base al examen electrovectocardiografico se presumio un sindrome de las fibras de Mahain (P-R: 0.15 seg, QRS: 0.12 seg, nitida onda delta) que fue confirmado por el estudio electrofisiologico (intervalo A-H normal, H-V disminuido,prolongacion del primero y del intervalo A-V sin cambios sustanciales del intervalo H-V) en diastoles cortas secundarias a extrasistoles auriculares espontaneos y marcapaseo auricular. Se indico propranolol (80 mg/dia, por boca) y controle periodicos (incluyendo ECG Holter de 24 h) durante um largo seguimiento (5 anos).Todo ello demostro la ausencia de taquiarritmias y el paciente permanecio asintomatico hasta la actualidad. El mayor interes de este caso con una rara forma de pre-excitacion radica en el comienzo tardio de arritmias que pusieron en peligro su vida y en el control prolongado de la eficacia del propranolol para prevenir las recidivas
Asunto(s)
Anciano , Humanos , Masculino , Propranolol , Taquicardia ParoxísticaRESUMEN
Se relata el caso de un paciente que presenta por primera vez crisis taquicardicas de muy alta frecuencia ventricular (mayores de 250 por minuto) a la edad de 69 anos. No tenia antecedentes cardiovasculares y no presentaba signos de cardiopatia organica. En base al examen electrovectocardiografico se presumio un sindrome de las fibras de Mahain (P-R: 0.15 seg, QRS: 0.12 seg, nitida onda delta) que fue confirmado por el estudio electrofisiologico (intervalo A-H normal, H-V disminuido,prolongacion del primero y del intervalo A-V sin cambios sustanciales del intervalo H-V) en diastoles cortas secundarias a extrasistoles auriculares espontaneos y marcapaseo auricular. Se indico propranolol (80 mg/dia, por boca) y controle periodicos (incluyendo ECG Holter de 24 h) durante um largo seguimiento (5 anos).Todo ello demostro la ausencia de taquiarritmias y el paciente permanecio asintomatico hasta la actualidad. El mayor interes de este caso con una rara forma de pre-excitacion radica en el comienzo tardio de arritmias que pusieron en peligro su vida y en el control prolongado de la eficacia del propranolol para prevenir las recidivas
Asunto(s)
Anciano , Humanos , Masculino , Propranolol , Taquicardia ParoxísticaRESUMEN
The electrophysiologic study of a patient with a history of fainting showed first- and second-degree Mobitz type I intraatrial and intra-His (IH) bundle blocks. Tachycardia and bradycardia-dependent IH block and bradycardia-dependent left bundle branch block were also present. Bradycardia-dependent block was probably caused by slight hypopolarization plus a slow rising slope of phase 4 depolarization and a shift of the threshold potential toward zero. Two months later a second electrophysiologic study was performed before, during and after administration of i.v. isoproterenol (IP). Shortening of atrium-His (AH1) and IH (H1H2) conduction time during faster heart rates caused by IP infusion may be related to its hyperpolarizing effect. Simultaneously, a shifting to the left of both bradycardia-dependent IH and left bundle branch block ranges was recorded during vagally induced cardiac slowing. These findings suggest that IP produces an increase in the slope of phase 4 depolarization of the His bundle and left bundle branch fibers and a simultaneous and concordant effect at both levels of the intraventricular conduction system.
Asunto(s)
Bradicardia/fisiopatología , Fascículo Atrioventricular/fisiopatología , Bloqueo de Rama/fisiopatología , Sistema de Conducción Cardíaco/fisiopatología , Isoproterenol/farmacología , Electrocardiografía , Electrofisiología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Tachycardia- and bradycardia-dependent, left anterior and left posterior hemiblocks as transient phenomena were registered in two patients spontaneously, and especially as a consequence of isoproterenol infusion. A chronic trifascicular type of A-V block was present in the first case, whereas in the second case a bradycardia-dependent left posterior hemiblock was registered during an acute myocardial infarction. In the first patient the isoproterenol effects were: (1) a shortening of the refractoriness and an increase of the conduction velocity in the injured fascicle, (2) an increase in the slope of phase-4 depolarization on the left posterior fascicle, and (3) a presumably shifting toward zero of threshold potential on the left anterior fascicle. Isoproterenol effects disappeared from 30 to 40 min after it was discontinued. In the second case the bradycardia-dependent left posterior hemiblock was registered during very fast heart rates (150 beats min). This finding supports the view that enhanced phase-4 depolarization is the main factor in the development of bradycardia-dependent intraventricular blocks in the course of acute myocardial ischemia.
Asunto(s)
Bradicardia/complicaciones , Bloqueo de Rama/etiología , Isoproterenol/efectos adversos , Taquicardia/complicaciones , Anciano , Bloqueo de Rama/fisiopatología , Electrocardiografía , Femenino , Humanos , Isoproterenol/administración & dosificación , Masculino , Infarto del Miocardio/complicaciones , Infarto del Miocardio/tratamiento farmacológicoRESUMEN
A patient with complete A-V block and atrial fibrillation was analyzed by multiple intra-atrial electrograms. Three areas were recorded in the right atrium, each of them with different electrophysiological properties: (1) persistent atrial standstill, (2) irregular atrial activity with a rate of 50/minute, and (3) fibrilloflutter waves with a rate of 450/minute. The latter were also registered in the left atrium. This case illustrates another form of dissimilar atrial rhythms, and provides additional evidence of the importance of recording multiple electrograms from each atrium in the evaluation of the atrial events in atypical atrial arrhythmias.
Asunto(s)
Fibrilación Atrial/diagnóstico , Electrocardiografía , Bloqueo Cardíaco/diagnóstico , Cateterismo Cardíaco , Electrofisiología , Atrios Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
The underlying mechanism of bradycardia-dependent bundle-branch and paroxysmal atrioventricular block appears to be enhancement of phase-4 depolarization in a branch or in a natural or acquired monofascicular pathway. Clinical records of these forms of impaired conduction occurring in the bundle-branches, with either longer or shorter cardiac cycle lengths, are presented and analysed. These also include the combination of Mobitz typw I atrioventricular block with variable degrees of bundle-branch block, as a representative example of narrow ventricular escape beats firing in the zone where prominent diastolic depolarization is present.
Asunto(s)
Bradicardia/fisiopatología , Bloqueo Cardíaco/fisiopatología , Sistema de Conducción Cardíaco/fisiopatología , Síndrome de Adams-Stokes/complicaciones , Adulto , Anciano , Angina de Pecho/complicaciones , Enfermedades de la Aorta/complicaciones , Fascículo Atrioventricular/fisiopatología , Bloqueo de Rama/complicaciones , Bloqueo de Rama/fisiopatología , Cateterismo Cardíaco , Cardiomegalia/complicaciones , Electrocardiografía , Femenino , Bloqueo Cardíaco/complicaciones , Humanos , Masculino , Potenciales de la Membrana , Persona de Mediana Edad , Ramos Subendocárdicos/fisiopatología , VectorcardiografíaRESUMEN
The results from OCTOPUS-I indicate that combined metabolic activities could be maintained under the optimal conditions provided for a prolonged period of time, but most effectively up to 14 hrs. The results of OCTOPUS-II and -III are lower than those in OCTOPUS-I. However, the activity in these systems is still higher than those previously reported((18)), which had urea production of 0.47 mg/Gm of liver. As imposed by any mass transfer device rate limitation, 60% efficacy of OCTOPUS-I brought into OCTOPUS-II, calculated by urea level, is acceptable. What is required for further improvement is mainly oriented to device rather than procurement andpreparation stages. The obstacles in the OCTOPUS-II and -III were, 1) the long time consumed for mounting the slices and assembling the devices before initiation of incubation, 2) inadequate control of incubation media, particularly blood, for oxygenation and pH, which was only for a short period of time but in the critical early stage of operation, 3) possible inadequate flow geometry in the device resulting in mass transfer resistance between the medium and the slices, 4) decrease in effective surface area of the slices, especially in OCTOPUS-III in which only one side of the slice faced the blood, and 5) in OCTOPUS-II, sagging of the slices due to the vertical position of the frames, with eventual reduction of effective surface area. Could a hepatic assist device utilizing liver slices be practical? Daily excretion of urea in dogs is 0.3-0.5 Gm/Kg((31)). Should the urea productivity in OCTOPUS-I(7.2 mg/Gm of liver/24 hrs) be successfully incorporated in a system, 600 Gm of slices can produce the amount of urea equivalent to the daily excretion in a 15 Kg dog. This volume of slices should not be considered unrealistic. Even though it is realized that in the practical situation 60% efficiency is expected, substitution of liver functions does not appear impossible. Further exploration for optimal conditions and practical considerations for improvement of devices will bring the goal closer to reality.
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Órganos Artificiales , Hígado/metabolismo , Animales , Análisis Químico de la Sangre , Perros , Estudios de Evaluación como Asunto , Femenino , MasculinoRESUMEN
Samples of cambial sap from each of the three coniferous species Pinus sylvestris L., Picea Abies Karst. and Abies alba Mill. were taken at the time the trees were coming into bud and analysed for low molecular weight carbohydrates, cyclitols and organic acids. They all contained the same free sugars and cyclitols, but in markedly different proportions. Quantitative analyses were carried out for glucose, fructose, sucrose, raffinose, myo-inositol, D-inositol, pinitol, sequoyitol and coniferin.The three main components of the organic acid fractions-quinic acid, shikimic acid and malic acid-were determined quantitatively. The amount of quinic acid greatly exceeded the amount of all the other acids in all three species. (14)C-labelled quinic acid applied to the cut ends of Pinus sylvestris needles was transported to the twig. There was no conversion of quinic acid to shikimic acid over short periods of time.