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INTRODUCTION: Designs for determining nociceptive response in rodents are of great use in neurology and experimental neuroscience. Immersing mice's tails in warm water is one of the most widely used procedures to evaluate this response; however, a wide range of temperatures are used in different studies. Knowing the temperature that produces a powerful nociceptive response in the tail of BALB/c mice is extremely useful. METHODS: Eight 2-month-old male BALB/c mice were used. A 14-cm high beaker was filled with water up to 13cm. The animals' tails were immersed in the container with a starting temperature of 36°C. The water temperature was raised in 1°C increments until we identified the temperatures that produced nociceptive responses. That response was determined by counting the time taken before the mouse shook its tail to remove it from the water. RESULTS: Six of the 8 mice began shaking their tails at the temperature of 51°C. All animals removed their tails from the water at the temperatures of 54°C, 55°C, and 56°C, taking a mean time of 8.54, 7.99, and 5.33seconds, respectively. ANOVA applied to the response times for each of the 3 temperatures indicated revealed a value of F=2.8 (P=.123). CONCLUSIONS: The response time was statistically similar for the temperatures of 54°C, 55°C, and 56°C; however, the data were less dispersed for the latter temperature.
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Nocicepción , Animales , Masculino , Ratones , Ratones Endogámicos BALB C , Tiempo de Reacción , TemperaturaRESUMEN
Introducción: Los diseños para determinar la respuesta nociceptiva en roedores son de gran utilidad en neurología y en neurociencias experimentales. El paradigma de inmersión de la cola de ratón en agua temperada es uno de los más empleados para evaluar dicha respuesta; sin embargo, existe amplia variación en la temperatura utilizada en las diversas investigaciones. Resulta sumamente útil determinar la temperatura que produce una mejor respuesta nociceptiva sobre la cola de ratones de la cepa Balb/c.MétodosSe emplearon 8 ratones machos Balb/c de 2 meses de edad. Un beaker de 14 cm de alto se llenó de agua hasta 13 cm. Partiendo desde los 36 °C se empezó a sumergir la cola del animal dentro del recipiente. Se comenzó a elevar en 1 °C el agua hasta encontrar las temperaturas que produzcan las respuestas nociceptivas. Dicha respuesta se determinó contabilizando el tiempo que el ratón tardó en sacudir su cola retirándola del agua.ResultadosLos ratones empezaron a sacudir su cola a los 51 °C (6 de los 8 roedores). El total de la muestra retiró su cola del agua a los 54, 55 y 56 °C en el tiempo promedio de 8,54, 7,99 y 5,33 s, respectivamente. Al aplicar ANOVA a los tiempos de las 3 temperaturas señaladas se obtuvo el valor F = 2,8 y p = 0,123.ConclusionesEl tiempo de respuesta fue similar estadísticamente ante las temperaturas de 54, 55 y 56 °C; sin embargo se encontró menor dispersión de los datos ante esta última. (AU)
Introduction: Designs for determining nociceptive response in rodents are of great use in neurology and experimental neuroscience. Immersing mice's tails in warm water is one of the most widely used procedures to evaluate this response; however, a wide range of temperatures are used in different studies. Knowing the temperature that produces a powerful nociceptive response in the tail of BALB/c mice is extremely useful.MethodsEight 2-month-old male BALB/c mice were used. A 14-cm high beaker was filled with water up to 13 cm. The animals tails were immersed in the container with a starting temperature of 36 °C. The water temperature was raised in 1 °C increments until we identified the temperatures that produced nociceptive responses. That response was determined by counting the time taken before the mouse shook its tail to remove it from the water.ResultsSix of the 8 mice began shaking their tails at the temperature of 51 °C. All animals removed their tails from the water at the temperatures of 54 °C, 55 °C, and 56 °C, taking a mean time of 8.54, 7.99, and 5.33 seconds, respectively. ANOVA applied to the response times for each of the 3 temperatures indicated revealed a value of F=2.8 (P=.123).ConclusionsThe response time was statistically similar for the temperatures of 54 °C, 55 °C, and 56 °C; however, the data were less dispersed for the latter temperature. (AU)
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Humanos , Animales , Ratones , Ratones Endogámicos BALB C , Nocicepción , Tiempo de Reacción , TemperaturaRESUMEN
INTRODUCTION: Household cleaning products and cosmetics are necessary for daily life and widely used by the population. However, their use may not be risk-free, especially when they are not used or stored as recommended. It is important to characterize exposures, as this is useful for developing stra tegies to reduce morbidity, mortality, and health costs associated, especially in the child population. OBJECTIVE: To describe reports associated with household cleaning products and cosmetics exposure in patients under the age of 12, reported to the Poison Information Center of the Catholic University of Chile (CITUC). PATIENTS AND METHOD: Descriptive cross-sectional study of phone calls to CITUC during 2016. The analyzed variables were age, sex, product, caller, caller and incident location, ex posure circumstances, exposure route(s), symptoms, and severity from manual records and from the WHO's electronic record software 'INTOX Data Management System'. RESULTS: 3,415 cases met the inclusion criteria. Children under the age of five represented 91% of the exposures, and 58.5% were male. 99.4% were accidental exposures, and 98.6% occurred at home. Family members (57%) and health personnel (42%) made the calls. 68.3% of the patients had no symptoms after exposure. The four products with the highest incidence were household bleach (27.6%), floor cleaners and polishers (13.1%), dish soap (7.9%), and perfume/cologne (5.8%). The main exposure route was by ingestion (89.4%). CONCLUSIONS: Household cleaning products and cosmetics are common causes of exposures especially in children under the age of five. Although these products have a low morbidity and mortality rate, it is important to educate the population to prevent possible poisonings in the child population.
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Cosméticos/envenenamiento , Productos Domésticos/envenenamiento , Centros de Control de Intoxicaciones/estadística & datos numéricos , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , MasculinoRESUMEN
INTRODUCCIÓN: Los productos de aseo y cosméticos son necesarios en el diario vivir y ampliamente utilizados por la población. Sin embargo, su uso puede no estar exento de riesgos, especialmente cuando no se utilizan o almacenan según lo recomendado. Es importante caracterizar las exposiciones, ya que eso es útil para implementar estrategias para reducir la morbilidad, mortalidad y costos asociados, especialmente en la población infantil. OBJETIVO: Caracterizar los reportes asociados a exposiciones a productos de aseo y productos cosméticos en pacientes menores de 12 años reportados al Centro de Información Toxicológica de la Universidad Católica de Chile (CITUC). PACIENTES Y MÉTODO: Estudio descriptivo transversal de llamados telefónicos reportados a CITUC durante el año 2016. Se analizaron las variables: edad, sexo, agente, interlocutor, localización del interlocutor e inciden te, circunstancia de exposición, vía(s) de exposición, sintomatología, y severidad, mediante fichas de registro manual y desde el software de registro electrónico denominado "INTOX Data Manage ment System" de la OMS. RESULTADOS: Cumplieron criterios de inclusión 3.415 casos. Los menores de 5 años representaron el 91% de las exposiciones y el 58,5% correspondió al sexo masculino. Un 99,4% correspondió a exposiciones accidentales y el 98,6% ocurrieron en el hogar. El 68,3% no presentó síntomas, tras la exposición. Las llamadas fueron realizadas por familiares (57%) y personal de salud (42%). Los 4 agentes con mayor incidencia fueron cloro doméstico (27,6%), limpiadores y lustres de pisos (13,1%), lavalozas (7,9%) y perfumes/colonias (5,8%). La principal vía de exposición fue digestiva (89,4%). CONCLUSIONES: Los productos de aseo y cosméticos son causas comunes de exposiciones especialmente en menores de 5 años. Si bien son productos de baja mortalidad y morbilidad, es importante educar a la población para prevenir posibles intoxicaciones en la población infantil.
INTRODUCTION: Household cleaning products and cosmetics are necessary for daily life and widely used by the population. However, their use may not be risk-free, especially when they are not used or stored as recommended. It is important to characterize exposures, as this is useful for developing stra tegies to reduce morbidity, mortality, and health costs associated, especially in the child population. OBJECTIVE: To describe reports associated with household cleaning products and cosmetics exposure in patients under the age of 12, reported to the Poison Information Center of the Catholic University of Chile (CITUC). PATIENTS AND METHOD: Descriptive cross-sectional study of phone calls to CITUC during 2016. The analyzed variables were age, sex, product, caller, caller and incident location, ex posure circumstances, exposure route(s), symptoms, and severity from manual records and from the WHO's electronic record software 'INTOX Data Management System'. RESULTS: 3,415 cases met the inclusion criteria. Children under the age of five represented 91% of the exposures, and 58.5% were male. 99.4% were accidental exposures, and 98.6% occurred at home. Family members (57%) and health personnel (42%) made the calls. 68.3% of the patients had no symptoms after exposure. The four products with the highest incidence were household bleach (27.6%), floor cleaners and polishers (13.1%), dish soap (7.9%), and perfume/cologne (5.8%). The main exposure route was by ingestion (89.4%). CONCLUSIONS: Household cleaning products and cosmetics are common causes of exposures especially in children under the age of five. Although these products have a low morbidity and mortality rate, it is important to educate the population to prevent possible poisonings in the child population.
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Humanos , Masculino , Femenino , Recién Nacido , Lactante , Preescolar , Niño , Centros de Control de Intoxicaciones/estadística & datos numéricos , Cosméticos/envenenamiento , Productos Domésticos/envenenamiento , Incidencia , Estudios TransversalesRESUMEN
INTRODUCTION: Designs for determining nociceptive response in rodents are of great use in neurology and experimental neuroscience. Immersing mice's tails in warm water is one of the most widely used procedures to evaluate this response; however, a wide range of temperatures are used in different studies. Knowing the temperature that produces a powerful nociceptive response in the tail of BALB/c mice is extremely useful. METHODS: Eight 2-month-old male BALB/c mice were used. A 14-cm high beaker was filled with water up to 13 cm. The animals' tails were immersed in the container with a starting temperature of 36°C. The water temperature was raised in 1°C increments until we identified the temperatures that produced nociceptive responses. That response was determined by counting the time taken before the mouse shook its tail to remove it from the water. RESULTS: Six of the 8 mice began shaking their tails at the temperature of 51°C. All animals removed their tails from the water at the temperatures of 54°C, 55°C, and 56°C, taking a mean time of 8.54, 7.99, and 5.33seconds, respectively. ANOVA applied to the response times for each of the 3 temperatures indicated revealed a value of F=2.8 (P=.123). CONCLUSIONS: The response time was statistically similar for the temperatures of 54°C, 55°C, and 56°C; however, the data were less dispersed for the latter temperature.
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The toxicity assessment of chemicals is one of the main issues in the current policies in order to protect the health of the environment and human beings. Food and cosmetic additives have been extensively studied in relation to their toxicity to humans, but data about their ecotoxicological effects are scarce. The aim of this study was to evaluate the toxic effects of the additive 6-methylcoumarine in the aquatic milieu using a test battery comprising experimental model systems from different trophic levels. The inhibition of bioluminiscence was studied in the bacteria Vibrio fischeri (decomposer), the inhibition of growth was evaluated in the alga Chlorella vulgaris (producer) and immobilization was studied in the cladoceran Daphnia magna (first consumer). Finally, several end points were evaluated in the RTG-2 salmonid fish cell line, including neutral red uptake, protein content, methylthiazol tetrazolium salt metabolization, glucose-6-phosphate dehydrogenase activity, lactate dehydrogenase activity and leakage, and morphology. The sensitivity of the test systems employed was as follows: V. fischeri > D. magna > C. vulgaris > RTG-2 cell line. The results show that 6-methylcoumarine is not expected to produce acute toxic effects on the aquatic biota. However, chronic and synergistic effects with other chemicals cannot be excluded and should be further investigated.
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Cumarinas/toxicidad , Contaminantes Químicos del Agua/toxicidad , Aliivibrio fischeri/efectos de los fármacos , Aliivibrio fischeri/crecimiento & desarrollo , Animales , Apoptosis/efectos de los fármacos , Línea Celular/citología , Línea Celular/efectos de los fármacos , Línea Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Chlorella vulgaris/efectos de los fármacos , Chlorella vulgaris/crecimiento & desarrollo , Cosméticos/efectos adversos , Daphnia/efectos de los fármacos , Daphnia/crecimiento & desarrollo , Relación Dosis-Respuesta a Droga , Gónadas/efectos de los fármacos , Gónadas/metabolismo , Gónadas/patología , Luminiscencia , Oncorhynchus mykiss , Valor Predictivo de las Pruebas , Pruebas de Toxicidad Aguda/métodosRESUMEN
Little is known about the pathogenesis of Leydig cell tumours (LCTs) of the testis. The observation of several associated dysgenetic features in the non-tumoural parenchyma and in the contralateral testes of men with testicular germ cell neoplasms has served as the basis to propose that there may be a common mechanism for different male reproductive disorders. However, the possible relationship between LCTs and other testicular lesions has not been explored. Here we describe the presence of primary lesions in the non-tumoural parenchyma of testes with LCT, from which we try to establish possible pathogenetic associations. We studied the non-tumoural parenchyma adjacent to 16 LCT specimens. Parameters as Leydig cell hyperplasia (LCHY), qualitative evaluation of the germinal epithelium and spermatogenesis, the presence of Sertoli cell-only tubules (SCOT), and the Sertoli cell nuclear morphology were consistently assessed in all cases. SCOT associated with Sertoli cell dysgenetic morphology was the most frequent finding, present in 50% of the cases. Another interesting finding was the presence of LCHY in four cases (25%). Abnormal spermatogenesis was found in 81.25% of the cases, and it consisted of lesions of the adluminal or basal compartments of seminiferous tubules. The occurrence of either dysgenetic Sertoli cells or LCHY adjacent to LCTs could represent primary anomalies, resulting from a common insult also involved in tumourigenesis. The abnormalities in spermatogenesis observed here are likely to represent consequences of either tumour compression or abnormal hormonal production. The significance of these associations merits further investigation regarding a common pathogenesis.
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Tumor de Células de Leydig/patología , Neoplasias Testiculares/patología , Testículo/patología , Adulto , Anciano , Anciano de 80 o más Años , Forma del Núcleo Celular , Humanos , Hiperplasia , Tumor de Células de Leydig/fisiopatología , Células Intersticiales del Testículo/patología , Masculino , Persona de Mediana Edad , Células de Sertoli/patología , Espermatogénesis , Neoplasias Testiculares/fisiopatología , Testículo/fisiopatologíaRESUMEN
The cytotoxic effects of the herbicide alachlor were compared on rainbow trout gonadal RTG-2 and human neuroblastoma SH-SY5Y cell lines. The end points evaluated in both cells after 24, 48, and 72 h of exposure were total protein content (PC), lysosomal function, and mitochondrial's integrity by mitochondrial succinate dehydrogenase (SDH) activity. After 24 h, cytoplasmic membrane integrity by cytosolic lactate dehydrogenase (LDH) leakage and LDH intracellular activity were also studied. In addition, acetylcholinesterase activity (AChE) was quantified in SH-SY5Y cells. The possible biotransformation of alachlor by RTG-2 cells was investigated by analyzing the exposure culture medium by liquid chromatography-mass spectrometry. In RTG-2, EC50 values on PC, lysosomal function, and SDH activity after 24 h exposure ranged from 80 to 95 microM and decreased to approximately 40 microM for longer exposure time periods. SH-SY5Y cells were slightly more sensitive than RTG-2 cells, with EC50 values on PC and lysosomal function ranging from 87 to 75 microM at 24 h and decreasing to 47 microM and 34 microM at 72 h, respectively. AChE activity was increased, being the most sensitive marker for SH-SY5Y with an EC50 of 20 microM at 24 h. The metabolic enzyme SDH was stimulated in SH-SY5Y and reduced in RTG-2 cells. At the studied conditions, no metabolites of alachlor were detected in RTG-2 cultures. In conclusion, the proposed battery approach is an effective screening tool for the safety assessment of environmental contaminants as a complement to fish and animal toxicity procedures.
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Acetamidas/toxicidad , Herbicidas/toxicidad , Acetilcolinesterasa/metabolismo , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , L-Lactato Deshidrogenasa/metabolismo , Oncorhynchus mykiss , Succinato Deshidrogenasa/metabolismoRESUMEN
Due to the current controversy about the real effectiveness of the oximes in the treatment of organophosphate poisoning, the reactivation capacity of pralidoxime has been evaluated in vitro on human erythrocyte acetylcholinesterase inhibited by dimethoate. In the in vitro model, a partial recovery of acetylcholinesterase activity was observed with concentrations from 0.066 mM pralidoxime, probably useful enough to prevent death in most cases in vivo. However, much more effectiveness was observed with concentrations up to 0.70 mM pralidoxime. Although pralidoxime should be applied as soon as possible after organophosphate exposure, the application of the antagonist can be useful even 24h after, particularly for organophosphates with biological half-life longer than one day. The protective capacity of pralidoxime after the application was reduced up to 50% in 6h and disappeared almost completely in 24h. Furthermore, the pesticide and its metabolites remained active and were able to inhibit the enzyme as soon as pralidoxime reduced its antagonist capacity. Our results in conjunction with the short half-life of pralidoxime suggest that the maintenance of higher plasmatic concentrations than the currently used should be considered in the management of severe poisoned patients, although adverse effects could be expected.
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Acetilcolinesterasa/metabolismo , Reactivadores de la Colinesterasa/farmacología , Eritrocitos/efectos de los fármacos , Compuestos de Pralidoxima/farmacología , Acetilcolinesterasa/sangre , Inhibidores de la Colinesterasa/farmacología , Dimetoato/farmacología , Relación Dosis-Respuesta a Droga , Eritrocitos/metabolismo , Humanos , Concentración 50 Inhibidora , Factores de TiempoRESUMEN
The occurrence of pharmaceutically active compounds in the aquatic environment has been recognized as one of the emerging issues in environmental chemistry. However, the ecotoxicological effects of pharmaceuticals have still not been researched adequately. Carbamazepine, an anticonvulsant commonly present in surface and groundwater, was studied, using six ecotoxicological model systems with eighteen endpoints evaluated at different exposure time periods. The battery included the immobilization of Daphnia magna, bioluminescence inhibition in the bacterium Vibrio fischeri, growth inhibition of the alga Chlorella vulgaris, and micronuclei induction and root growth inhibition in the plant Allium cepa. Cell morphology, neutral red uptake, total protein content, MTS metabolization, lactate dehydrogenase leakage and activity and glucose-6-phosphate dehydrogenase activity were studied in the salmonid fish cell line RTG-2. The total protein content, LDH activity, neutral red uptake and MTT metabolization in Vero monkey kidney cells were also investigated. The most sensitive system to carbamazepine was the Vero cell line, followed by Chlorella vulgaris, Vibrio fischeri, Daphnia magna, Allium cepa, and RTG-2 cells. EC50 values from 19 microM in Vero cells at 72 h to more than 1200 microM in other systems, were obtained. Comparing the concentrations in water and the toxicity quantified in our assay systems, carbamazepine is not expected to produce acute toxic effects in the aquatic biota under these circumstances, but chronic and synergistic effects with other chemicals cannot be excluded.
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Anticonvulsivantes/toxicidad , Carbamazepina/toxicidad , Ecosistema , Determinación de Punto Final/métodos , Pruebas de Toxicidad/métodos , Alternativas al Uso de Animales , Animales , Biomarcadores/análisis , Línea Celular , Chlorella/efectos de los fármacos , Chlorella/crecimiento & desarrollo , Chlorocebus aethiops , Daphnia/efectos de los fármacos , Daphnia/fisiología , Relación Dosis-Respuesta a Droga , Micronúcleos con Defecto Cromosómico/efectos de los fármacos , Oncorhynchus mykiss , Cebollas/efectos de los fármacos , Cebollas/genética , Células Vero , Vibrio/efectos de los fármacos , Vibrio/fisiología , Contaminantes Químicos del Agua/toxicidadRESUMEN
Tribromophenol is a pesticide with fungicide activity, presently used as a replacement of pentachlorophenol as a wood preservative, and as a flame retardant in electronic and electrotechnical devices. Retinoic acid differentiated and non-differentiated SH-SY5Y human neuroblastoma cell cultures were exposed to a range of concentrations of tribromophenol for 24, 48 and 72 h and the effects evaluated at morphological, basal cytotoxicity and biochemical levels. Neuroblastoma cell number, evaluated by quantification of total protein content, was increasingly inhibited in accordance with the concentration of tribromophenol and the exposure time period. According to the mean effective concentrations, differentiated cultures were nearly three times more sensitive than naive cells. Lysosomal function evaluated by the neutral red uptake was stimulated, particularly in non-differentiated cells. MTS metabolization was stimulated by all the treatments, with more potency at 24 h for differentiated cells. Acetylcholinesterase activity increased with the time of exposure in non-differentiated cells, while in differentiated cells the activity was doubled at 24 h. Morphological alterations were evident from 12.5 microM, showing hydropic degeneration and reduction in cell number, and from that concentration, piknosis and apoptotic bodies were observed. In conclusion, the main effects detected for tribromophenol were the induction of neuroblastoma cell differentiation, as expressed by the inhibition of cell growth and the increase in acetylcholinesterase activity with a critical cell concentration of 0.1 microM. Apoptosis was observed at high concentrations. The induction of cell differentiation and the special sensitivity of differentiated cells can explain some mechanisms involved in the embryotoxic and foetotoxic potential of tribromophenol.
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Transformación Celular Neoplásica/efectos de los fármacos , Neuroblastoma/tratamiento farmacológico , Plaguicidas/toxicidad , Fenoles/toxicidad , Biomarcadores/análisis , Recuento de Células , División Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Neuroblastoma/metabolismo , Neuroblastoma/patologíaRESUMEN
Myelinated fibers are organized into distinct domains that are necessary for saltatory conduction. These domains include the nodes of Ranvier and the flanking paranodal regions where glial cells closely appose and form specialized septate-like junctions with axons. These junctions contain a Drosophila Neurexin IV-related protein, Caspr/Paranodin (NCP1). Mice that lack NCP1 exhibit tremor, ataxia, and significant motor paresis. In the absence of NCP1, normal paranodal junctions fail to form, and the organization of the paranodal loops is disrupted. Contactin is undetectable in the paranodes, and K(+) channels are displaced from the juxtaparanodal into the paranodal domains. Loss of NCP1 also results in a severe decrease in peripheral nerve conduction velocity. These results show a critical role for NCP1 in the delineation of specific axonal domains and the axon-glia interactions required for normal saltatory conduction.
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Axones/fisiología , Moléculas de Adhesión Celular Neuronal , Proteínas de Drosophila , Glicoproteínas de Membrana/fisiología , Proteínas de la Membrana/fisiología , Fibras Nerviosas Mielínicas/fisiología , Proteínas del Tejido Nervioso/fisiología , Neuroglía/fisiología , Neuropéptidos/fisiología , Nervio Óptico/fisiología , Receptores de Superficie Celular/fisiología , Nervio Ciático/fisiología , Envejecimiento , Animales , Clonación Molecular , Drosophila , Femenino , Biblioteca Genómica , Heterocigoto , Homocigoto , Humanos , Masculino , Glicoproteínas de Membrana/deficiencia , Glicoproteínas de Membrana/genética , Proteínas de la Membrana/genética , Ratones , Ratones Noqueados , Fibras Nerviosas Mielínicas/ultraestructura , Proteínas del Tejido Nervioso/genética , Neuropéptidos/deficiencia , Neuropéptidos/genética , Canales de Potasio/fisiología , Receptores de Superficie Celular/genética , Mapeo RestrictivoRESUMEN
In the adult peripheral nerve, microvillous processes of myelinating Schwann cells project to the nodes of Ranvier; their composition and physiologic function have not been established. As the ezrin-radixin-moesin (ERM) proteins are expressed in the microvilli of many epithelial cells, we have examined the expression and distribution of these proteins in Schwann cells and neurons in vitro and in vivo. Cultured Schwann cells express high levels of all three proteins and the ezrin-binding protein 50, whereas neurons express much lower, although detectable, levels of radixin and moesin. Ezrin is specific for Schwann cells. All three ERM proteins are expressed predominantly at the membrane of cultured Schwann cells, notably in their microvilli. In vivo, the ERM proteins are concentrated strikingly in the nodal processes of myelinating Schwann cells. Because these processes are devoid of myelin proteins, they represent a unique compartment of the myelinating Schwann cell. During development, the ERM proteins become concentrated at the ends of Schwann cells before myelin basic protein expression, demonstrating that Schwann cells are polarized longitudinally at the onset of myelination. ERM-positive Schwann cell processes overlie and are associated closely with nascent nodes of Ranvier, identified by clusters of ankyrin G. Ankyrin accumulation at the node precedes that of Caspr at the paranodes and therefore does not depend on the presence of mature paranodal junctions. These results demonstrate that nodes of Ranvier in the peripheral nervous system form in contact with specialized processes of myelinating Schwann cells that are highly enriched in ERM proteins.
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Proteínas Sanguíneas/fisiología , Proteínas del Citoesqueleto/fisiología , Proteínas de la Membrana/fisiología , Proteínas de Microfilamentos/fisiología , Neuronas/fisiología , Nervio Óptico/fisiología , Fosfoproteínas/fisiología , Nódulos de Ranvier/fisiología , Células de Schwann/fisiología , Nervio Ciático/fisiología , Envejecimiento , Animales , Ancirinas/análisis , Ancirinas/fisiología , Proteínas Sanguíneas/análisis , Células Cultivadas , Proteínas del Citoesqueleto/análisis , Ganglios Espinales/citología , Ganglios Espinales/fisiología , Proteínas de la Membrana/análisis , Proteínas de Microfilamentos/análisis , Microscopía Confocal , Microvellosidades/fisiología , Microvellosidades/ultraestructura , Vaina de Mielina/fisiología , Fosfoproteínas/análisis , Ratas , Ratas Sprague-DawleyRESUMEN
Specialized paranodal junctions form between the axon and the closely apposed paranodal loops of myelinating glia. They are interposed between sodium channels at the nodes of Ranvier and potassium channels in the juxtaparanodal regions; their precise function and molecular composition have been elusive. We previously reported that Caspr (contactin-associated protein) is a major axonal constituent of these junctions (Einheber et al., 1997). We now report that contactin colocalizes and forms a cis complex with Caspr in the paranodes and juxtamesaxon. These proteins coextract and coprecipitate from neurons, myelinating cultures, and myelin preparations enriched in junctional markers; they fractionate on sucrose gradients as a high-molecular-weight complex, suggesting that other proteins may also be associated with this complex. Neurons express two contactin isoforms that differ in their extent of glycosylation: a lower-molecular-weight phosphatidylinositol phospholipase C (PI-PLC)-resistant form is associated specifically with Caspr in the paranodes, whereas a higher-molecular-weight form of contactin, not associated with Caspr, is present in central nodes of Ranvier. These results suggest that the targeting of contactin to different axonal domains may be determined, in part, via its association with Caspr. Treatment of myelinating cocultures of Schwann cells and neurons with RPTPbeta-Fc, a soluble construct containing the carbonic anhydrase domain of the receptor protein tyrosine phosphatase beta (RPTPbeta), a potential glial receptor for contactin, blocks the localization of the Caspr/contactin complex to the paranodes. These results strongly suggest that a preformed complex of Caspr and contactin is targeted to the paranodal junctions via extracellular interactions with myelinating glia.
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Moléculas de Adhesión Celular Neuronal/metabolismo , Uniones Intercelulares/metabolismo , Vaina de Mielina/metabolismo , Nódulos de Ranvier/metabolismo , Receptores de Superficie Celular/metabolismo , Animales , Moléculas de Adhesión Celular Neuronal/química , Células Cultivadas , Centrifugación por Gradiente de Densidad , Técnicas de Cocultivo , Contactinas , Ganglios Espinales/citología , Ganglios Espinales/metabolismo , Humanos , Fragmentos Fc de Inmunoglobulinas/genética , Peso Molecular , Proteínas del Tejido Nervioso/genética , Neuronas/citología , Neuronas/metabolismo , Fosfatidilinositol Diacilglicerol-Liasa , Fosfoinositido Fosfolipasa C , Estructura Terciaria de Proteína/genética , Proteínas Tirosina Fosfatasas/genética , Ratas , Proteínas Tirosina Fosfatasas Clase 5 Similares a Receptores , Receptores de Superficie Celular/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Células de Schwann/citología , Células de Schwann/metabolismo , Fracciones Subcelulares/química , Fosfolipasas de Tipo C/metabolismoRESUMEN
Calcium channel blockers are widely used in all-aged populations. The drugs are generally safe in therapeutic dosage, but severe side effects with elevated intake are increasingly described, mainly in adult patients. We report an adolescent girl who intentionally ingested an overdose of nifedipine.
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Bloqueadores de los Canales de Calcio/envenenamiento , Nifedipino/envenenamiento , Intento de Suicidio , Adolescente , Femenino , Hemodinámica/efectos de los fármacos , HumanosRESUMEN
We report the case of a previously healthy girl who developed a multi-systemic failure after an inappropriate dose of colchicine. The patient recovered completely and had no residual effects.
Asunto(s)
Sistema Nervioso Central/efectos de los fármacos , Colchicina/envenenamiento , Insuficiencia Multiorgánica/inducido químicamente , Médula Ósea/efectos de los fármacos , Preescolar , Colchicina/administración & dosificación , Coagulación Intravascular Diseminada/inducido químicamente , Sobredosis de Droga , Servicio de Urgencia en Hospital , Enzimas/sangre , Femenino , Humanos , Unidades de Cuidados Intensivos , Enfermedades Metabólicas/inducido químicamente , Neutropenia/inducido químicamente , Trombocitopenia/inducido químicamenteRESUMEN
Serotonin and dexamethasone act as differentiating agents during development. Reducing circulating adrenal steroids or central 5-HT levels via adrenalectomy (ADX) or the tryptophan hydroxylase inhibitor, para-chlorophenylalanine (PCPA), respectively, has been shown to have de-differentiating effects in the adult brain. Morphometric analysis of 5-HT, S100 beta, MAP-2 and synaptophysin immunoreactivity (IR) was used to follow the molecular plasticity of several brain regions after lesioning of 5-HT nerve terminals by para-chloroamphetamine (PCA; 2 x 10 mg/kg s.c.), a serotonin neurotoxin. Two weeks after PCA treatment we observed reductions of 5-HT, S100 beta, and MAP-2 IR in parietal and temporal cortex, temporal pole, hippocampus and hypothalamus. The reductions in MAP-2 and synaptophysin-IR were reversed by 3 days of treatment with dexamethasone (10 mg/l drinking water) or ipsapirone, a 5-HT1A agonist (1 mg/kg s.c.). The loss of S100-IR was reversed only by the 5-HT1A agonist. These results indicate that both dexamethasone and serotonin have effects on adult neuronal plasticity but may work via different mechanisms. The implications of these findings to the loss of synaptophysin and MAP-2 staining in Alzheimer's disease are discussed.
Asunto(s)
Dexametasona/farmacología , Proteínas Asociadas a Microtúbulos/efectos de los fármacos , Proteínas Asociadas a Microtúbulos/inmunología , Neuronas/efectos de los fármacos , Agonistas de Receptores de Serotonina/farmacología , Sinaptofisina/efectos de los fármacos , Sinaptofisina/inmunología , Factores de Edad , Animales , Astrocitos/efectos de los fármacos , Química Encefálica/inmunología , Corteza Cerebral/química , Corteza Cerebral/citología , Hipocampo/química , Hipocampo/citología , Inmunohistoquímica , Masculino , Ratas , Ratas Sprague-Dawley , Proteínas S100/efectos de los fármacos , Proteínas S100/inmunología , p-Cloroanfetamina/farmacologíaRESUMEN
The prevalence of cardiac abnormalities in the spectrum of human immunodeficiency virus (HIV) infection is unknown. Sixty consecutive HIV-infected patients were studied using echocardiograms, electrocardiograms (50 patients) and ambulatory electrocardiographic monitoring (43 patients). Group A (25 patients) were seropositive but pre-AIDS, whereas group B (35 patients) had AIDS and included 24 with an active opportunistic infection (group B1) and 11 without it (group B2). Abnormalities were identified in 32 of 60 patients (53%) and were more frequent in group B (23 of 35, 66%) than in group A (9 of 25, 36%, p less than 0.05) but independent of active opportunistic infection (15 of 24, 62%, in group B1 vs 8 of 11, 73%, in group B2). Echocardiographic abnormalities were identified in 21 of 60 patients (35%), including 7 of 25 (28%) in group A vs 14 of 35 (40%) in group B (difference not significant), and 7 of 24 (29%) in group B1 vs 7 of 11 (64%) in group B2 (difference not significant). Those patients with an absolute CD4 lymphocyte count less than or equal to 100/mm3 had a higher prevalence of echocardiographic abnormalities (12 of 22) than those with CD4 counts greater than 100/mm3 (1 of 14, p less than 0.01). Left ventricular dilation or hypokinesis was identified in 14 of 60 patients (23%), including 4 of 25 (16%) in group A and 10 of 35 (29%) in group B. Electrocardiographic abnormalities were seen in 22 of 50 patients (44%) including 5 of 18 (28%) in group A and 17 of 32 (53%) in group B (difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Cardiopatías/complicaciones , Adulto , Linfocitos T CD4-Positivos , Ecocardiografía , Electrocardiografía , Femenino , Cardiopatías/diagnóstico , Humanos , Recuento de Leucocitos , Masculino , Monitoreo Fisiológico , Infecciones Oportunistas/complicacionesRESUMEN
Precordial maps have been used for some 15 years to estimate the extent of myocardial injury in patients with acute anterior or lateral wall infarction. Estimates have been based on various QRS- and ST-T-derived parameters, including amplitude sum of ST elevations. Application of the electrodes, commonly 35, is cumbersome and time-consuming with the critically ill. A subset of 5 or 7 selected leads can be applied instead, and the remaining leads calculated from that subset with minimal loss of QRS and ST-T information. Maps were recorded from 100 patients within 72 hours of onset of anterior or lateral infarct. Optimal lead subsets for QRS and ST-T feature extraction were found by the sequential selection method of Lux. Subsets numbering between 2 and 15 leads were derived, with their lead-transform coefficients. Measures to estimate goodness of fit for reconstructed leads included correlations, error-to-signal ratios and root-mean-square errors. These measures were calculated separately over the QRS and ST-T complexes. Reconstructions from a 7-lead subset had a mean 0.92 correlation with ST-T in the original leads and root-mean-square error of only 0.04 mV. Sum of ST elevation differed by only 2% between original leads and reconstructions based on 5 or more leads. To confirm repeatability, lead-transform coefficients were also calculated from a training population of 50 patients and applied to the maps of the other 50.