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Id: lil-790732
Autor: García-Corrochano, Pamela; Castañeda, Carlos A; Orrego, Enrique; Deza, Pedro; Heinicke, Hugo; Casavilca, Sandro; Castillo, Miluska; Cortez, Karen; Belmar, Carolina; Dolores, Ketty; Flores, Claudio; Ojeda, Luis.
Título: Resección microquirúrgica de glioblastoma guiada con fluoresceína intraoperatoria: evaluación retrospectiva / Microsurgical resection of glioblastoma guided with intraoperative fluorescein: a retrospective evaluation
Fonte: Rev. peru. med. exp. salud publica;32(3):471-478, jul.-sep. 2015. ilus, tab, graf.
Idioma: es.
Resumo: Evaluar la influencia del uso de fluoresceína sódica (FLS-Na) en la cirugía del glioblastoma (GB) sobre el grado de resección tumoral y la supervivencia en pacientes atendidos en el Instituto Nacional de Enfermedades Neoplásicas. Materiales y métodos. Se revisó un total de 238 casos de GB atendidos entre los años 2008 y 2013 y se seleccionó 150 casos de GB sometidos a resección quirúrgica, con información clínico-patológica y seguimiento adecuado. Resultados. La media de edad fue 51 años, el 58,7% de casos presento Karnofsky de al menos 90. Se administró FLS-Na en 80 casos (53,3%) y se obtuvo una resección subtotal y total en 69 (46%) y 81 (54%) de los casos, respectivamente. El grupo que recibió FLS-Na obtuvo mayores tasas de resección total que el grupo operado solo con luz blanca (77,5 vs 27,1%, p<0,001). La mediana de sobrevida global (SG) fue mayor en el grupo sometido a resección total que a subtotal (17 vs 7 meses, p<0,001). La mediana de SG en los que recibieron FLS-Na fue mayor que en los que no la recibieron (15,0 vs 8 meses, p=0,003). Otros factores que afectaron la SG fueron la edad (p=0,002), el Karnofsky (p=0,052) y la administración de radioterapia (p=0,016) y quimioterapia (p=0,011). Conclusiones. La técnica microquirúrgica con administración de FLS-Na se asoció con un aumento en la tasa de resecciones totales y de supervivencia...

To evaluate the influence of the use of sodium fluorescein (FLS-Na) in surgery of glioblastoma (GB) on the degree of tumor resection and survival in patients treated at the National Institute of Neoplastic Diseases. Materials and methods. A total of 238 cases of GB treated between 2008 and 2013 were reviewed and 150 cases of GB who underwent surgical resection with clinicopathological information and adequate follow-up were selected. Results. The mean age was 51 years, 58.7% of the cases presented a Karnofsky score of at least 90. FLS-Na was administered in 80 cases (53.3%) and a subtotal and total resection was obtained in 69 (46%) and 81 (54%) cases, respectively. The group that received FLS-Na obtained higher rates of total resection than the group operated with white light alone (77.5 vs 27.1%, p<0.001). The median overall survival (OS) was higher in the group subject to total compared to subtotal resection (17 vs 7 months, p<0.001). The median OS in those who received FLS-Na was higher than in those who did not (15.0 vs 8 months, p=0.003). Other factors affecting OS were age (p=0.002), the Karnofsky score (p=0.052) and radiation therapy (p=0.016) and chemotherapy (p=0.011). Conclusions. The microsurgical technique with administration of FLS-Na was associated with an increase in the rate of total resection and survival...
Descritores: Fluoresceínas
Glioblastoma/cirurgia
Análise de Sobrevida
Limites: Humanos
Masculino
Adolescente
Adulto
Feminino
Criança
Adulto Jovem
Pessoa de Meia-Idade
Responsável: PE14.1 - Biblioteca de la Sede Central


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Id: lil-766285
Autor: Guimarães, Roberto Eustáquio Santos; Stamm, Aldo Eden Cassol; Giannetti, Alexandre Varella; Crosara, Paulo Fernando Tormin Borges; Becker, Celso Gonçalves; Becker, Helena Maria Gonçalves.
Título: Chemical and cytological analysis of cerebral spinal fluid after intrathecal injection of hypodense fluorescein / Análise química e citológica do líquor após injeção intratecal de solução hipodensa de fluoresceína
Fonte: Braz. j. otorhinolaryngol. (Impr.);81(5):549-553, Sept.-Oct. 2015. tab, graf.
Idioma: en.
Resumo: ABSTRACT INTRODUCTION: Intrathecal fluorescein has been effective for topographic diagnosis of rhinoliquorrhea. Nonetheless, there are no reports on the study of cerebral spinal fluid (CSF) after use of intrathecal fluorescein. OBJECTIVE: A prospective study attempting to evaluate CSF through chemical and cytological analysis, after injection of fluorescein. METHODS: Prospective analysis of 24 samples of CSF after intrathecal injection of fluorescein for topographic diagnosis of CSF fistulae, collected at the time of puncture and after 24 and 48 h, divided by cellularity: Group 1, up to five cells, and Group 2, with more than five cells. RESULTS: The yellow-greenish color of CSF remained after 48 h in 36%, evidencing permanence of fluorescein. No changes in protein and glucose levels were observed between 0-24 h and 0-48 h. In group 2, an increase in cell count was observed between 24 h and 48 h (p = 0.019). In both groups, there was an increase of neutrophils between 0 and 48 h (p = 0.048) and a decrease between 24 and 48 h (p = 0.05). CONCLUSION: Intrathecal fluorescein provoked discreet meningeal reactions, such as an increase of cells between 24 and 48 h and an increase of neutrophils at 24 h, with a subsequent decrease at 48 h with no correlation with symptomatology.

RESUMO Introdução: A fluoresceína intratecal tem sido efetiva no diagnóstico topográfico da rinoliquorréia. Entretanto, não há estudos no líquor após o uso de fluoresceína intratecal. Objetivo: Estudo prospectivo visando avaliar o líquor, através de análise química e citológica, após injeção de fluoresceína. Método: Análise prospectiva de 24 punções após injeção intratecal de fluoresceína para diagnóstico topográfico de fístula liquórica, coletado no momento da punção, 24 e 48 horas, divididos pela celularidade: grupo 1, com até 5 células e grupo 2 com mais de 5 células. Resultado: A coloração amarelo-esverdeada do líquor permaneceu após 48 horas em 36%, evidenciando permanência de fluoresceína. Observou-se ausência de mudanças no nível de proteína e glicose entre 0-24 horas e 0-48 horas. No grupo 2, um aumento na contagem celular foi observado entre 24 e 48 horas (p = 0,019). No dois grupos juntos, observou-se um aumento de neutrófilos entre 0 e 48 horas (p = 0,048) e uma diminuição entre 24 e 28 horas (p = 0,05). Conclusão: Fluoresceína intratecal provocou discretas reações meníngeas, como o aumento de células entre 24 e 48 horas e aumento dos dos neutrófilos em 24 horas com uma subsequente dimi nuição em 48 horas sem correlação com sintomas.
Descritores: Líquido Cefalorraquidiano/efeitos dos fármacos
Fluoresceínas/administração & dosagem
Corantes Fluorescentes/administração & dosagem
-Proteínas do Líquido Cefalorraquidiano/análise
Proteínas do Líquido Cefalorraquidiano/efeitos dos fármacos
Rinorreia de Líquido Cefalorraquidiano/diagnóstico
Líquido Cefalorraquidiano/química
Líquido Cefalorraquidiano/citologia
Glucose/análise
Imuno-Histoquímica
Injeções Espinhais
Neutrófilos/efeitos dos fármacos
Estudos Prospectivos
Fatores de Tempo
Limites: Adolescente
Adulto
Criança
Pré-Escolar
Humanos
Pessoa de Meia-Idade
Adulto Jovem
Responsável: BR1.1 - BIREME


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Id: lil-689567
Autor: Céspedes, Ángel Enrique; Arango, César Augusto; Cardona, Gloria Patricia.
Título: Análisis comparativo de marcadores de lesión en modelos de isquemia cerebral focal y global en ratas / Injury markers in two models of cerebral ischemia
Fonte: Biomédica (Bogotá);33(2):283-291, abr.-jun. 2013. mapas, tab.
Idioma: es.
Resumo: Introducción. Los indicadores espacio-temporales de lesión son esenciales en el estudio neuropatológico y terapéutico de la isquemia cerebral. Objetivo. Optimizar la técnica de dos modelos de isquemia cerebral (focal y global) y hacer un análisis comparativo de la progresión del daño cerebral, mediante marcadores de neurodegeneración. Materiales y métodos. Se sometieron ratas Wistar a oclusión temporal de la arteria cerebral media o a oclusión de cuatro vasos, y se evaluaron comparativamente el tiempo quirúrgico, la tasa de supervivencia y la recuperación neurológica. Se utilizó trifenilo de tetrazolio para establecer la distribución del infarto y tinción con Fluoro - Jade B ® como marcador de neurodegeneración. La inmunorreacción de la astroglía se evaluó con el anticuerpo contra la proteína acídica fibrilar de la glía ( Glial Fibrillary Acidic Protein, GFAP) y el anticuerpo AT-8 contra la proteína tau hiperfosforilada, 24, 48 y 72 horas después de la isquemia. Resultados. Los modelos de isquemia utilizados requirieron menor tiempo quirúrgico y hubo menor riesgo de muerte, respecto a estudios previos. En el modelo focal, las células positivas con Fluoro - Jade B ® y los astrocitos reactivos, se evidenciaron en corteza e hipocampo a las 24 horas después de la isquemia. En el modelo global, se observó tinción Fluoro - Jade B ® positiva a las 24 horas, aumentando significativamente la reacción de la GFAP a las 72 horas en corteza y a las 48 horas en el hipocampo. La reacción contra la proteína tau hiperfosforilada aumentó progresivamente y fue máxima a las 72 horas en ambos modelos. Conclusiones. Los dos modelos de isquemia cerebral, oclusión temporal de la arteria cerebral media y oclusión de cuatro vasos, fueron optimizados. En estos modelos, los marcadores la tinción Fluoro - Jade B ® y la GFAP permitieron detectar procesos de neurodegeneración 24 horas después de la isquemia, en tanto el marcador de proteína tau hiperfosforilada (AT-8) incrementó progresivamente su reacción hasta las 72 horas, lo cual sugiere la propagación de la excitotoxicidad y la alteración de enzimas implicadas en la fosforilación de proteínas del citoesqueleto.

Introduction: Spatio-temporal indicators of injury are essential for the study of neuropathological processes and for developing therapeutic approaches for stroke. Objective: This study sought to optimize the techniques of two cerebral ischemia models (focal and global) and to comparatively evaluate the progression of brain damage by analyzing markers of neurodegeneration. Materials and methods: Wistar rats were subjected to temporary occlusion of the middle cerebral artery (t-MCAO) or four-vessel occlusion (4-VO), and surgical time, survival rate and neurological recovery were comparatively evaluated. Triphenyl tetrazolium was used to determine the distribution of the infarction, and Fluoro-Jade B was used as a marker of neurodegeneration. Astroglial immunoreactivity was assessed with an anti-glial fibrillary acidic protein (GFAP) antibody, and an anti-AT-8 antibody was used to detect hyperphosphorylated tau protein at 24, 48 and 72 hours post-ischemia. Results: The cerebral ischemia models employed (t-MCAO and 4-VO) required less surgical time and presented less of a death risk compared to those in previous studies. In the focal model, Fluoro-Jadepositive cells and reactive astrocytes were observed in the cerebral cortex and the hippocampus at 24 hours post-ischemia. In the global model, we observed Fluoro-Jade-positive cells at 24 hours, and a significant increase in the reactivity of GFAP was observed at 72 hours in the cortex and at 48 hours in the hippocampus. The immunoreactivity of hyperphosphorylated tau protein increased progressively, reaching a maximum at 72 hours post-ischemia in both models. Conclusions: These results suggest that in the t-MCAO and 4-VO ischemia models, the expression of Fluoro-Jade and GFAP indicates early neurodegeneration at 24 hours post-insult. In contrast, the immunoreactivity of the hyperphosphorylated tau protein marker (AT-8) progressively increases until 72 hours post-insult, which suggests that the progression of excitotoxicity and alteration of enzymes involves the phosphorylation of cytoskeletal proteins.
Descritores: Isquemia Encefálica
-Biomarcadores
Isquemia Encefálica/diagnóstico
Isquemia Encefálica/imunologia
Modelos Animais de Doenças
Progressão da Doença
Fluoresceínas
Proteína Glial Fibrilar Ácida
Fosforilação
Ratos Wistar
Fatores de Tempo
Proteínas tau/metabolismo
Limites: Animais
Feminino
Ratos
Tipo de Publ: Estudo Comparativo
Research Support, Non-U.S. Gov't
Responsável: CO332 - Facultad de Medicina


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Id: lil-654352
Autor: Balbino, Marcos; Silva, Gisele; Correia, Gabriela Cardoso Tostes Pimentel.
Título: Anafilaxia com convulsões após angiografia com fluoresceína em paciente ambulatorial / Anaphylaxis with convulsions following intravenous fluorescein angiography at an outpatient clinic
Fonte: Einstein (Säo Paulo);10(3):374-376, jul.-set. 2012.
Idioma: pt.
Resumo: A fluoresceína endovenosa é associada a pequenos efeitos adversos durante a angiografia da retina, a maioria deles sem gravidade e não relacionada a mecanismos imunológicos. Entretanto, em raras ocasiões, pode ocorrer reação anafilactoide; fatalidades envolvendo o uso de fluoresceína têm sido descritas. Complicações graves após injeção endovenosa de fluoresceína requerem ação imediata da equipe envolvida, assim como treinamento regular para padronizar o tratamento.

Fluorescein is associated with minor adverse effects during retinal angiography, and most of these effects are not severe and not related to immunological mechanism. However, on rare occasions, anaphylatoid reaction can occur, and fatalities involving fluorescein have been described. Life threatening complications after intravenous injection of sodium fluorescein require immediate intervention. Trainings for professionals are needed to standardize treatment for this event.
Descritores: Anafilaxia
Angiofluoresceinografia/efeitos adversos
Fluoresceínas/administração & dosagem
Convulsões
Tipo de Publ: Relatos de Casos
Responsável: BR1.1 - BIREME


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Id: lil-557103
Autor: Guskuma, Marcos Heidy; Hochuli-Vieira, Eduardo; Pereira, Flávia Priscila; Rangel-Garcia Junior, Idelmo; Okamoto, Roberta; Okamoto, Tetuo; Magro Filho, Osvaldo.
Título: Bone regeneration in surgically created defects filled with autogenous bone: an epifluorescence microscopy analysis in rats
Fonte: J. appl. oral sci;18(4):346-353, July-Aug. 2010. ilus, graf.
Idioma: en.
Resumo: Although the search for the ideal bone substitute has been the focus of a large number of studies, autogenous bone is still the gold standard for the filling of defects caused by pathologies and traumas, and mainly, for alveolar ridge reconstruction, allowing the titanium implants installation. OBJECTIVES: The aim of this study was to evaluate the dynamics of autogenous bone graft incorporation process to surgically created defects in rat calvaria, using epifluorescence microscopy. MATERIAL AND METHODS: Five adult male rats weighing 200-300 g were used. The animals received two 5-mm-diameter bone defects bilaterally in each parietal bone with a trephine bur under general anesthesia. Two groups of defects were formed: a control group (n=5), in which the defects were filled with blood clot, and a graft group (n=5), in which the defects were filled with autogenous bone block, removed from the contralateral defect. The fluorochromes calcein and alizarin were applied at the 7th and 30th postoperative days, respectively. The animals were killed at 35 days. RESULTS: The mineralization process was more intense in the graft group (32.09 percent) and occurred mainly between 7 and 30 days, the period labeled by calcein (24.66 percent). CONCLUSIONS: The fluorochromes showed to be appropriate to label mineralization areas. The interfacial areas between fluorochrome labels are important sources of information about the bone regeneration dynamics.
Descritores: Doenças Ósseas/cirurgia
Regeneração Óssea/fisiologia
Transplante Ósseo/fisiologia
Osso Parietal/cirurgia
-Antraquinonas
Coagulação Sanguínea
Transplante Ósseo/patologia
Calcificação Fisiológica/fisiologia
Fluoresceínas
Corantes Fluorescentes
Microscopia de Fluorescência
Osteogênese/fisiologia
Ratos Wistar
Fatores de Tempo
Transplante Autólogo
Limites: Animais
Masculino
Ratos
Responsável: BR1.1 - BIREME


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Id: lil-548496
Autor: Ramírez Benavides, Ginés Fernando; Osorio, José Henry.
Título: Niveles séricos de tetrayodotironina libre (T4L), mediante el método de electroquimioluminiscencia en caninos / Free tetraiodothyronine (FT4) serum levels by electrochemiluminescence method in canines
Fonte: Rev. cient. (Maracaibo);19(3):238-241, mayo-jun. 2009. tab.
Idioma: es.
Resumo: El presente estudio establece valores de referencia para niveles séricos de tetrayodotironina libre (T4L) en caninos mediante el método de electroquimioluminiscencia. Se utilizaron 180 caninos que fueron divididos en grupos según la edad y el sexo. Se encontraron diferencias altamente significativas (P<0,0001) relacionadas con la edad, sin encontrarse diferencias significativas con respecto al sexo para dicha hormona. Los resultados de este estudio sugieren que las concentraciones séricas de tetrayodotironina libre (ng/L) en caninos menores de 1año, de 1 a 7 años y mayores de 7 años, oscilan entre 9,90-11,74 ng/L, 8,51-11,74 ng/L y 7,48-8,64 ng/L, respectivamente. La determinación de T4L mediante electroquimioluminiscencia, puede considerarse útil como ayuda diagnóstica de posibles alteraciones tiroideas.

The present study establishes references values for free Tetraiodotironine (FT4) in canines using eletrochemiluminescence method. Blood samples from 180 canines divided in six groups of age (males and females), 30 animals for each group were used. Significant differences (P<0.0001) was found between age groups but not between sex groups. The canine average values for FT4 using this technique were as follow: younger than 1 year of age , 9.9 - 11.7 ng/L; from 1 to 7 years of age, 8.1 - 11.7 ng/L; older than 7 years of age 7.4- 8.6 ng/L. The electrochemiluminiscence method for measuring FT4 is valuable diagnostic tool in canine medicine.
Descritores: Eletroquimografia/veterinária
Fluoresceínas/análise
Biomarcadores/análise
Receptores dos Hormônios Tireóideos/análise
-Medicina Veterinária
Limites: Animais
Cães
Tipo de Publ: Estudo de Avaliação
Responsável: VE1.1 - Biblioteca Humberto Garcia Arocha


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Id: lil-517143
Autor: Uzcátegui, María; Rivas, Adriana; Rivas A., Pedro.
Título: Retinopatía diabética 5 años después / Diabetic retinophaty five years later
Fonte: Rev. oftalmol. venez;61(3):159-163, jul.-sept. 2005. graf.
Idioma: es.
Resumo: Determinar la evolución de la Retinopatía Diabética y sus efectos sobre la función visual en un período de 5 años. 76 pacientes diabéticos seguidos por un período de 5 años. Al grupo de 76 pacientes se les práctico una evaluación integral incluyendo agudeza visual, estado del fondo, angiografía fluoresceínica y niveles de Glicemia. El número de pacientes sin retinopatía diabética bajo de 29 por ciento en 1999 a 18.5 por ciento en el año 2005 con incremento de la RDPP de 20 por ciento a 31 por ciento y la RDP de 25 por ciento a 32 por ciento. Se aprecio un importante aumento de los ojos con visión peor a 20/400 de 35 por ciento a 46 por ciento. En el período de evaluación de 5 años, se nota un importante empeoramiento de la retinopatía diabética en la mayoría de los pacientes, así como también un importante deterioro de la visión.
Descritores: Catarata
Diabetes Mellitus
Glaucoma
Insulina
Retinopatia Diabética/etiologia
Retinopatia Diabética/terapia
-Cegueira
Fluoresceínas/análise
Limites: Humanos
Masculino
Feminino
Responsável: VE1.1 - Biblioteca Humberto Garcia Arocha


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Spada, Celso
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Id: lil-486310
Autor: Palma, Priscila F. R; Baggio, Giovana L; Spada, Celso; Silva, Renata da; Ferreira, Silvia Inês A. C. P; Treitinger, Aricio.
Título: Evaluation of annexin V and Calcein-AM as markers of mononuclear cell apoptosis during human immunodeficiency virus infection
Fonte: Braz. j. infect. dis;12(2):108-114, Apr. 2008. ilus.
Idioma: en.
Resumo: Evaluation of apoptosis by flow cytometry is generally accomplished by methods that use annexin V-FITC as vital dye, which access phosphatidylserine exposed on the external membrane at the beginning of this process. In addition, the concomitant use of propidium iodide makes possible to verify the characteristic nuclear alterations in the late stages of apoptosis, as a consequence of the increase in membrane permeability. On the other hand, the use of calcein-AM in association with ethidium homodimer (EthD-1) allows the evaluation of cell apoptosis through detection of esterase activity and cellular membrane physical and chemical alterations. The aim of this study was to compare the sensibility of calcein-AM and EthD-1 with annexin V-FITC and propidium iodide for early apoptosis evaluation in peripheral blood mononuclear cell culture, obtained from HIV-infected patients. Apoptosis and cellular viability were detected and quantified by flow cytometry after 24 and 48 hours incubation times. Our results showed that calcein-AM/EthD-1 was more sensitive for apoptotic cell quantification in both incubation times than annexin V-FITC/propidium iodide (mean of 46.95 percent ± 3.56, p < 0.0001, for 24 hours and mean of 37.67 percent ± 2.47, p < 0.0014 for 48 hours), besides allowing to clearly define viable, apoptotic and dead cell populations.
Descritores: Apoptose
/metabolismo
ANNEXIN AABDOMEN/metabolismo
Citometria de Fluxo/métodos
Fluoresceínas/metabolismo
Corantes Fluorescentes/metabolismo
Infecções por HIV/patologia
Linfócitos/fisiologia
-Biomarcadores/metabolismo
Permeabilidade da Membrana Celular
Etídio/análogos & derivados
Etídio/metabolismo
Propídio/metabolismo
Sensibilidade e Especificidade
Fatores de Tempo
Limites: Humanos
Tipo de Publ: Estudo Comparativo
Estudo de Avaliação
Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


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Malnic, G
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Id: lil-449084
Autor: Tararthuch, A. L; Fernandez, R; Malnic, G.
Título: Cl- and regulation of pH by MDCK-C11 cells
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;40(5):687-696, May 2007. graf, tab.
Idioma: en.
Projeto: FAPESP; . CNPq.
Resumo: The interaction between H+ extrusion via H+-ATPase and Cl- conductance was studied in the C11 clone of MDCK cells, akin to the intercalated cells of the collecting duct. Cell pH (pHi) was measured by fluorescence microscopy using the fluorescein-derived probe BCECF-AM. Control recovery rate measured after a 20 mM NH4Cl acid pulse was 0.136 ± 0.008 pH units/min (dpHi/dt) in Na+ Ringer and 0.032 ± 0.003 in the absence of Na+ (0 Na+). With 0 Na+ plus the Cl- channel inhibitor NPPB (10 æM), recovery was reduced to 0.014 ± 0.001 dpHi/dt. 8-Br-cAMP, known to activate CFTR Cl- channels, increased dpHi/dt in 0 Na+ to 0.061 ± 0.009 and also in the presence of 46 nM concanamycin and 50 æM Schering 28080. Since it is thought that the Cl- dependence of H+-ATPase might be due to its electrogenic nature and the establishment of a +PD (potential difference) across the cell membrane, the effect of 10 æM valinomycin at high (100 mM) K+ was tested in our cells. In Na+ Ringer, dpHi/dt was increased, but no effect was detected in 0 Na+ Ringer in the presence of NPPB, indicating that in intact C11 cells the effect of blocking Cl- channels on dpHi/dt was not due to an adverse electrical gradient. The effect of 100 æM ATP was studied in 0 Na+ Ringer solution; this treatment caused a significant inhibition of dpHi/dt, reversed by 50 æM Bapta. We have shown that H+-ATPase present in MDCK C11 cells depends on Cl- ions and their channels, being regulated by cAMP and ATP, but not by the electrical gradient established by electrogenic H+ transport.
Descritores: Canais de Cloreto/metabolismo
ATPases Translocadoras de Prótons/metabolismo
-Linhagem Celular
Células Clonais
Fluoresceínas
Corantes Fluorescentes
Concentração de Íons de Hidrogênio
Microscopia de Fluorescência
Limites: Animais
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


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Cunha, F. Q
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Id: lil-421363
Autor: Romão, P. R. T; Tovar, J; Fonseca, S. G; Moraes, R. H; Cruz, A. K; Hothersall, J. S; Noronha-Dutra, A. A; Ferreira, S. H; Cunha, F. Q.
Título: Glutathione and the redox control system trypanothione/trypanothione reductase are involved in the protection of Leishmania spp. against nitrosothiol-induced cytotoxicity
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;39(3):355-363, Mar. 2006. tab.
Idioma: en.
Projeto: Fundação de Amparo à Pesquisa do Estado de São Paulo.
Resumo: Glutathione is the major intracellular antioxidant thiol protecting mammalian cells against oxidative stress induced by oxygen- and nitrogen-derived reactive species. In trypanosomes and leishmanias, trypanothione plays a central role in parasite protection against mammalian host defence systems by recycling trypanothione disulphide by the enzyme trypanothione reductase. Although Kinetoplastida parasites lack glutathione reductase, they maintain significant levels of glutathione. The aim of this study was to use Leishmania donovani trypanothione reductase gene mutant clones and different Leishmania species to examine the role of these two individual thiol systems in the protection mechanism against S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a nitrogen-derived reactive species donor. We found that the resistance to SNAP of different species of Leishmania was inversely correlated with their glutathione concentration but not with their total low-molecular weight thiol content (about 0.18 nmol/10(7) parasites, regardless Leishmania species). The glutathione concentration in L. amazonensis, L. donovani, L. major, and L. braziliensis were 0.12, 0.10, 0.08, and 0.04 nmol/10(7) parasites, respectively. L. amazonensis, that have a higher level of glutathione, were less susceptible to SNAP (30 and 100 µM). The IC50 values of SNAP determined to L. amazonensis, L. donovani, L. major, and L. braziliensis were 207.8, 188.5, 160.9, and 83 µM, respectively. We also observed that L. donovani mutants carrying only one trypanothione reductase allele had a decreased capacity to survive (40 percent) in the presence of SNAP (30-150 µM). In conclusion, the present data suggest that both antioxidant systems, glutathione and trypanothione/trypanothione reductase, participate in protection of Leishmania against the toxic effect of nitrogen-derived reactive species.
Descritores: Glutationa/metabolismo
Leishmania/efeitos dos fármacos
NADH NADPH Oxirredutases/metabolismo
Penicilamina/análogos & derivados
-Fluoresceínas
Leishmania/enzimologia
Peso Molecular
NADH NADPH Oxirredutases/genética
Ouabaína/análogos & derivados
Penicilamina/toxicidade
Especificidade da Espécie
Limites: Animais
Responsável: BR1.1 - BIREME



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