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Id: biblio-1131007
Autor: Herrera-Rodríguez, Diana L; Totomoch-Serra, Armando; Rosas-Madrigal, Sandra; Luna-Limón, Claudia; Marroquín-Ramírez, Daniel; Carnevale, Alessandra; Rosendo-Gutiérrez, Rigoberto; Villarreal-Molina, María T; Márquez-Murillo, Manlio F.
Título: Genes frequently associated with sudden death in primary hypertrophic cardiomyopathy / Genes frecuentemente asociados con muerte súbita en miocardiopatía hipertrófica primaria
Fonte: Arch. cardiol. Méx;90(1):59-68, Jan.-Mar. 2020. tab, graf.
Idioma: en.
Resumo: Abstract Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy without apparent cardiac justification. Sudden cardiac death may be the first manifestation of the disease. It occurs mainly in adulthood and can be seen in childhood and adolescence where genetic origin predominates. Primary HCM (“familial”) is inherited in an autosomal dominant pattern in the 25 subtypes informed in Online Mendelian Inheritance in Man. The proteins encoded by the mutated genes are part of the sarcomere in the cardiac cells, being the thick filament the most frequently affected, with the worst prognosis. In the present article, we describe the Mendelian inheritance of the disease and the two most associated genes with sudden death: MYBPC3 and MYH7.

Resumen La miocardiopatía hipertrófica (MCH) es el aumento de grosor de la pared ventricular izquierda no relacionada con otras alteraciones cardíacas. Es una enfermedad que puede presentar como primera manifestación clínica la muerte súbita y de ahí su relevancia clínica. Aunque se presenta sobre todo en la edad adulta, puede aparecer durante la infancia y adolescencia, en las que predominan los casos de origen hereditario. La MCH primaria, de causa genética, muestra en particular un patrón de herencia autosómico dominante en los 25 subtipos reconocidos en OMIM (Online Mendelian Inheritance in Man). Las proteínas codificadas por los genes mutantes forman parte del sarcómero en células musculares cardíacas, y las variantes patogénicas de filamentos gruesos son las de mayor frecuencia y peor pronóstico. En este artículo se describen la herencia mendeliana de la enfermedad y la relación con muerte súbita de los genes más frecuentemente encontrados en ella: MYBPC3 y MYH7.
Descritores: Cardiomiopatia Hipertrófica/genética
Proteínas de Transporte/genética
Cadeias Pesadas de Miosina/genética
Miosinas Cardíacas/genética
-Cardiomiopatia Hipertrófica/fisiopatologia
Limites: Humanos
Pré-Escolar
Adolescente
Adulto
Tipo de Publ: Revisão
Responsável: BR1.1 - BIREME


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Id: biblio-1358665
Autor: Marín, José J. G.
Título: Bases moleculares de la función excretora de tipo hepatobiliar de la placenta / Molecular basis of excretory function placental hepatobiliary type
Fonte: Salud(i)ciencia (Impresa) = Salud(i)ciencia (En linea);13(2):31-32, 2005.
Idioma: es.
Resumo: The liver plays an important excretory role eliminating from the body potentially toxic compounds that are xenobiotics or produced endogenously, such as bile acids and biliary pigments. This involves both transport and biotransformation processes. During intrauterine life, the inmature fetal liver cannot carry out this function. Therefore, the placenta performs a hepatobiliary-like excretory role, transferring cholephilic compounds from the fetus to the mother. The similarity of this function in the placenta and the adult liver is probably accounted for by the presence in both organs of proteins of the OATP family, involved in the uptake of organic anions across the basolateral membrane of several epithelia, and of members of the superfamily of ATP-binding cassette (ABC) proteins, which are involved in the export of substances out of many different cells. Thus, several studies have shown that, in addition to a difussional component, that may become particularly important for unconjugated bilirubin, the main mechanisms for bile acids and bilirubin transplacental transfer from the fetus to the mother are carrier-mediated transport systems, which have vectorial properties and also play an important role in the placental barrier by preventing or reducing the net flux of noxious substances from the mother to the fetus.

El hígado juega un papel determinante en la excreción de sustancias potencialmente tóxicas de origen externo o producidas por el organismo, como ácidos biliares y bilirrubina. Esta función implica tanto procesos de transporte como de biotransformación. Durante la vida intrauterina, el hígado fetal no es aún capaz de realizar esta función, por lo que es la placenta la que asume un papel excretor similar al que desempeña el sistema hepatobiliar en el adulto. La similitud entre ambas funciones se debe a la presencia en ambos órganos de proteínas transportadoras de la familia OATP, que llevan a cabo la captación de aniones orgánicos en varios epitelios, y de miembros de la superfamilia de proteínas ABC ("ATP-binding cassette"), capaces de bombear al exterior celular una gran variedad de sustancias. Estudios recientes demostraron que, además de un componente difusional, que es más relevante en el caso de la bilirrubina no conjugada, la vía mayoritaria en la transferencia placentaria de ácidos biliares y bilirrubina está mediada por sistemas de transporte que, en conjunto, presentan características de vectorialidad feto-materna, y que por ello también juegan un papel en la barrera placentaria reduciendo el flujo de sustancias nocivas desde la madre al feto.
Descritores: Placenta
Biotransformação
Eliminação Hepatobiliar
Fígado
-gama-Glutamil Hidrolase
Xenobióticos
Proteínas
Proteínas de Transporte
Trifosfato de Adenosina
Feto
Ânions
Mães
Responsável: AR392.1 - Biblioteca


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Texto completo SciELO Saúde Pública
Texto completo
Id: lil-793000
Autor: Pineda-Belmontes, Cristina P; Hernández-Ramírez, Raúl U; Hernández-Alcaraz, César; Cebrián, Mariano E; López-Carrillo, Lizbeth.
Título: Genetic polymorphisms of PPAR gamma, arsenic methylation capacity and breast cancer risk in Mexican women / Polimorfismos genéticos de PPAR gamma, capacidad de metilación del arsénico y riesgo de cáncer de mama en mujeres mexicanas
Fonte: Salud pública Méx;58(2):220-227, Mar.-Apr. 2016. tab.
Idioma: en.
Projeto: National Science and Technology Council (Consejo Nacional de Ciencia y Tecnología - Conacyt); . Sectorial Fund for Research in Health and Safety (Fondo Sectorial de Investigación en Salud y Seguridad.
Resumo: Abstract Objective: To evaluate whether the presence of polymorphisms of peroxisome proliferator-activated receptor gamma PPARγ (Pro 1 2Ala) and PPARGC1B (Ala203Pro) modifies the association between the inorganic arsenic (iAs) methylation capacity and breast cancer (BC). Materials and methods: Mexican women were interviewed, and blood and urine samples were collected from them (cases/controls= 197/220). The concentration of urinary arsenic species and the polymorphisms of interest were determined by high-performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and polymerase chain reaction (PCR), respectively. Results: In women with a high %MMA (urinary monomethyl arsenic) and high primary methylation ratio (PM = MMA/iAs), the risk of BC was increased (odds ratio [OR]%MMA T3 vs.T1= 3.60: 95% confidence interval [CI] 2.02-6.41, ORPMI T3 vs.T1= 3.47: 95%CI 1.95-6.17), which was maintained after adjusting for polymorphisms. No significant interactions were observed between the polymorphisms and the arsenic variables on the risk of BC. Conclusion: Pro 12Ala and Ala203Pro polymorphisms did not modify the association between the iAs methylation capacity and BC.

Resumen Objetivo: Evaluar si la presencia de polimorfismos de PPARγ (Pro 1 2Ala) y PPARGC1B (Ala203Pro) modifica la asociación entre la capacidad de metilación del arsénico inorgánico (Asi) y el cáncer de mama (CM). Material y métodos: Se entrevistaron mujeres mexicanas y recolectaron muestras de sangre y orina de (casos/controles=197/220). La concentración de especies de arsénico urinario y los polimorfismos de interés se determinaron mediante cromatografía líquida de alta resolución acoplada a espectrometría de masas (HPLC-ICP-MS) y reacción en cadena de la polimerasa (PCR), respectivamente. Resultados: En mujeres con %MMA (monometilarsénico urinario) y razón de primera metilación altas (PM=MMA/Asi) se incrementó el riesgo de CM (RM%MMAT3vsT1=3.60: intervalo de confianza [IC]95%2.02-6.41, RMPMT3vs.T1=3.47:IC95%1.95-6.17), que se mantuvo, respectivamente, al ajustar por polimorfismos. No se observaron interacciones significativas entre los polimorfismos y las variables arsenicales sobre el riesgo de CM. Conclusión: Los polimorfismos Pro 12Ala y Ala203Pro no modificaron la asociación entre la capacidad de metilación del Asi y el CM.
Descritores: Arsenicais/metabolismo
Neoplasias da Mama/epidemiologia
Proteínas de Transporte/genética
Polimorfismo de Nucleotídeo Único
PPAR gama/genética
-Arsênio/toxicidade
Arsenicais/urina
Espectrometria de Massas
Neoplasias da Mama/genética
Estudos de Casos e Controles
Reação em Cadeia da Polimerase
Risco
Cromatografia Líquida de Alta Pressão
Proteínas de Ligação a RNA
Predisposição Genética para Doença
Exposição Ambiental
Metilação
Limites: Humanos
Feminino
Adulto
Pessoa de Meia-Idade
Idoso
Adulto Jovem
Responsável: BR1.1 - BIREME


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Id: biblio-1346509
Autor: Perez Garrido, Natalia; Pujana, Matías; Berger, Malena; Ramírez, Pablo; Guercio, Gabriela; Belgorosky, Alicia; Marino, Roxana.
Título: Growth hormone receptor gene polymorphism. Spontaneous catch up growth in small for gestational age patients / Polimorfismo del gen del receptor de la hormona de crecimiento. Crecimiento postnatal espontáneo en niños pequeños para la edad gestacional
Fonte: Medicina (B.Aires);81(4):574-580, ago. 2021. graf.
Idioma: en.
Resumo: Abstract The growth hormone receptor (GHR) mediates the effect of growth hormone (GH) on linear growth and metabolism. In humans, it exists as two isoforms differing by the retention or exclusion of exon 3; a full-length GHR isoform (GHRfl) and the exon 3-deleted isoform (GHRd3). The genotypic frequency of this polymorphism was analyzed in several studies and in different human populations. However scarce information in Argentinean population is available. Associations between GHRd3 and growth have been reported previously. Some studies have shown that the presence of GHRd3 polymorphism might be a potential variant that improves growth response to recombinant human GH (rhGH) therapy in patients born small for gestational age (SGA), among others. However, over the years the results have been controversial and inconclusive. Based on this, it would be proposed that variants at the genomic level are not completely reflected at the mRNA level. Our aim was to evaluate the genotypic frequencies (%) of the GHR gene polymorphism (GHRfl/GHRfl; GHRfl/GHRd3; GHRd3/GHRd3) in normal Argentinean population (n = 94) and SGA patients (n = 65), and the expression of these polymorphisms at mRNA level in the fetal side of placenta tissues was analyzed. In addition, their asso ciation with spontaneous postnatal catch-up growth in SGA patients was also evaluated. In this study, we show a significant increment of compensatory growth in small for gestational age children (SGA) associated to the presence of the GHRd3 allele polymorphism. In addition, the expression of GHR in healthy placentas revealed that no alternative splicing mechanism occurs.

Resumen El receptor de la hormona de creci miento (GHR) media la acción de la hormona de crecimiento (GH) en el crecimiento lineal y el metabolismo. En los seres humanos, existen dos isoformas que difieren en la retención (GHRfl) o exclusión del exón 3 (GHRd3). La frecuencia genotípica de este polimorfismo fue analizada en varios estudios y en diferentes poblaciones. Sin embargo, la información disponible en la población argentina es escasa. Se ha reportado anteriormente asociación entre el polimorfismo GHRd3 y el crecimiento. Varios estudios ha n demostrado que la presencia del polimorfismo GHRd3 podría mejorar, en pacientes nacidos pequeños para la edad gestacional, entre otros, la respuesta a la terapia con GH humana recombinante (rhGH). Sin embargo, a lo largo de los años los resultados han sido con trovertidos y no concluyentes. En base a esto, se propondría que las variantes a nivel genómico no se reflejan completamente a nivel del ARNm. Nuestro objetivo fue evaluar la frecuencia genotípica de los polimorfismos del gen del GHR (GHRfl/GHRfl; GHRfl/GHRd3; GHRd3/GHRd3) en la población argentina normal (n = 94) y en niños pequeños para la edad gestacional (n = 65), y se analizó la expresión de estos polimorfismos a nivel de ARNm en la porción fetal de placentas sanas. Además, se evaluó la asociación de este polimorfismo con el cre cimiento postnatal espontáneo en pacientes pequeños para la edad gestacional. En este estudio, mostramos un incremento significativo del crecimiento compensatorio en niños pequeños para la edad gestacional asociado a la presencia del polimorfismo del alelo GHRd3. Además, los ensayos de expresión de GHR en placentas sanas revelaron que no se produciría ningún mecanismo de splicing alternativo.
Descritores: Receptores da Somatotropina/genética
Hormônio do Crescimento Humano
-Polimorfismo Genético
Proteínas de Transporte
Éxons
Idade Gestacional
Limites: Humanos
Feminino
Gravidez
Criança
Responsável: BR1.1 - BIREME


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Texto completo SciELO Brasil
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Id: biblio-1011609
Autor: Guo, Wan-Liang; Geng, Jia; Zhao, Jun-gang; Fang, Fang; Huang, Shun-Gen; Wang, Jian.
Título: Gene expression profiling reveals upregulated FUT1 and MYBPC1 in children with pancreaticobiliary maljunction
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;52(8):e8522, 2019. tab, graf.
Idioma: en.
Resumo: Pancreaticobiliary maljunction (PBM) is associated with high risk of epithelial atypical growth and malignant transformation of the bile duct or gallbladder. However, overall changes in genetic expression have not been examined in children with PBM. Genome-wide expression was analyzed using peripheral blood samples from 10 children with PBM and 15 pediatric controls. Differentially expressed genes (DEGs) were identified using microarray. Bioinformatics analysis was conducted using Gene Ontology and KEGG analyses. The top 5 in the up-regulated genes in PBM were verified with qRT-PCR. Receiver operator characteristic curve analysis was conducted to evaluate the predictive accuracy of selected genes for PBM. The microarray experiments identified a total of 876 DEGs in PBM, among which 530 were up-regulated and the remaining 346 were down-regulated. Verification of the top 5 up-regulated genes (TYMS, MYBPC1, FUT1, XAGE2, and GREB1L) by qRT-PCR confirmed the up-regulation of MYBPC1 and FUT1. Receiver operating characteristic curve analysis suggested that FUT1 and MYBPC1 up-regulation could be used to predict PBM, with the area under the curve of 0.873 (95%CI=0.735−1.000) and 0.960 (95%CI=0.891−1.000), respectively. FUT1 and MYBPC1 were up-regulated in children with PBM, and could be used as potential biomarkers for PBM.
Descritores: Ductos Pancreáticos/anormalidades
Ductos Biliares/anormalidades
Regulação para Cima/genética
Perfilação da Expressão Gênica
Fucosiltransferases/genética
-Neoplasias dos Ductos Biliares/etiologia
Proteínas de Transporte/genética
Estudos de Casos e Controles
Análise em Microsséries
Dilatação Patológica/complicações
Dilatação Patológica/congênito
Neoplasias da Vesícula Biliar/etiologia
Limites: Humanos
Masculino
Lactente
Pré-Escolar
Criança
Responsável: BR1.1 - BIREME


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Texto completo SciELO Brasil
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Id: biblio-1249340
Autor: Qi, Moci; Li, Lingyu; Tang, Xiaofei; Lu, Yunping; Wang, Min; Yang, Jing; Zhang, Min.
Título: Nicotine promotes the development of oral leukoplakia via regulating peroxiredoxin 1 and its binding proteins
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;54(9):e10931, 2021. tab, graf.
Idioma: en.
Projeto: National Natural Science Foundation of China; . Scientific Research Common Program of Beijing Municipal Commission of Education.
Resumo: Tobacco can induce reactive oxygen species (ROS) production extensively in cells, which is a major risk factor for oral leukoplakia (OLK) development. Peroxiredoxin 1 (Prx1) is a key antioxidant protein, upregulated in a variety of malignant tumors. We previously found that nicotine, the main ingredient of tobacco, promotes oral carcinogenesis via regulating Prx1. The aim of the present study was to screen and identify the Prx1 interacting proteins and investigate the mechanisms of nicotine on the development of OLK. Through liquid chromatography-tandem mass spectrometry combined with bioinformatics analysis, the candidate Prx1 interacting proteins of cofilin-1 (CFL1), tropomyosin alpha-3 chain (TPM3), and serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (PPP2R1A) were screened in human dysplastic oral keratinocyte cells treated with nicotine. CFL1, TPM3, and PPP2R1A were highly expressed in human OLK tissues. The expression of CFL1 increased and the expression of PPP2R1A decreased in OLK of smokers compared to that in OLK of non-smokers. Nicotine upregulated CFL1 and downregulated PPP2R1A in 4-nitro-quinoline-1-oxide (4NQO)-induced OLK tissues in mice in part dependent on Prx1. Furthermore, the in-situ interaction of CFL1, TPM3, and PPP2R1A with Prx1 were validated in human OLK tissues. Our results suggested that tobacco might promote the development of OLK via regulating Prx1 and its interacting proteins CFL1 and PPP2R1A.
Descritores: Leucoplasia Oral/induzido quimicamente
Peroxirredoxinas/metabolismo
Nicotina
-Proteínas de Transporte
Proteínas de Homeodomínio
Carcinogênese
Limites: Animais
Camundongos
Responsável: BR1.1 - BIREME


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Id: biblio-1045581
Autor: Justiz-Vaillant, AA; Akpaka, PE; McFarlane-Anderson, N; Smikle, MF.
Título: Comparison of techniques of detecting immunoglobulin-binding protein reactivity to immunoglobulin produced by different avian and mammalian species / Comparación de las técnicas de detección de la reactividad de la proteína de unión de la inmunoglobulina frente a la inmunoglobulina producida por diferentes especies aviarias y mamíferas
Fonte: West Indian med. j;62(1):12-20, Jan. 2013. ilus, tab.
Idioma: en.
Resumo: The rationale of this study was to use several immunological assays to investigate the reactivity of immunoglobulin binding protein (IBP) to immunoglobulins from various avian and mammalian species. The IBP studied were Staphylococcal protein A (SpA), Streptococcal protein G (SpG), Peptostreptococcal protein L (SpL) and recombinant protein LA (SpLA). The various immunological techniques used were double immunodiffusion (Ouchterlony technique) that tested positive high protein reactivities, direct and competitive enzyme-linked immunosorbent assays (ELISAs) that tested moderate and low positive protein binding capacities, respectively. In addition to sandwich ELISAs, immunoblot analyses and Ig-purification by SpA-affinity chromatography, which were sensitive tests and helpful in the screening and confirmatory tests were also used. The Ouchterlony technique showed that compared to the other proteins, SpLA had the highest range of reactivity with animal sera and purified immunoglobulins while SpL was least reactive. With the direct ELISA, SpL reacted with the raccoon sera, rabbit IgG and with IgY from bantam hens and pigeons. While with the direct ELISA, SpA reacted with sera from skunk, coyote, raccoon, mule, donkey and human. The sandwich ELISA revealed high reactivity of both SpG and SpLA with mammalian sera titres ranging from 1:32 (raccoon serum) to 1:1024 (mule and donkey sera).These results suggest that IBP can be used for the detection of immunoglobulin using various immunological assays and this is important for the diagnosis of infectious diseases in animal and bird populations studied and in the purification of immunoglobulins.

El fundamento de este estudio radica en el uso de varios ensayos inmunológicos para investigar la reactividad de la proteína de unión de la inmunoglobulina (IBP) frente a las inmunoglobulinas de varias especies aviarias y mamíferas. Las proteínas IBP estudiadas fueron la proteína estafilocócica A (SpA), la proteína estreptocócica G (SpG), la proteína peptoestreptocócica L (SpL), y la proteína recombinante LA (SpLA). Las varias técnicas inmunológicas usadas fueron: la inmunodifusión doble (técnica de Ouchterlony) para examinar las reactividades positivas de la proteína alta; el ensayo por inmunoabsorción ligado a enzimas(ELISA), de tipo directo y competitivo, para examinar la capacidad de realizar uniones positivas de proteína moderada y baja, respectivamente, además del ensayo ELISA 'Sándwich', los análisis inmunoblot, yla purificación de IgG, mediante cromatografía de afinidad, los cuales fueron pruebas sensibles y útiles en el tamizaje y las pruebas de confirmación. La técnica de Ouchterlony mostró que - en comparación con otras proteínas - la SpLA tenía el grado más alto de reactividad con los sueros animales y las inmunoglobulinas purificadas, mientras que la SpL fue la menos reactiva. Con el ELISA directo, la SpL reaccionó con los sueros de mapache, la IgG de conejo, así como con la IgY de palomas y gallinas de Bantam, en tanto con el ELISA directo, la SpA reaccionó con sueros de mofeta, coyote, mapache, mula, asno y seres humanos. ELISA "sándwich" reveló una alta reactividad tanto de SpG como de SpLA, con títulos séricos mamíferos que iban desde 1:32 (suero de mapache) hasta 1:1024 (sueros de mula y de asno). Estos resultados sugieren que la proteína de unión IBP puede usarse en la detección de la inmunoglobulina usando varios ensayos inmunológicos, lo cual es importante para el diagnóstico de enfermedades infecciosas en las poblaciones animales y aviarias bajo estudio, así como para la purificación de inmunoglobulinas.
Descritores: Proteínas de Bactérias/imunologia
Aves/imunologia
Imunoglobulinas/biossíntese
Cromatografia de Afinidade
Técnicas Imunoenzimáticas/métodos
Mamíferos/imunologia
-Proteínas Recombinantes/imunologia
Proteínas de Transporte/imunologia
Doenças Transmissíveis/diagnóstico
Limites: Humanos
Animais
Tipo de Publ: Estudo Comparativo
Responsável: BR1.1 - BIREME


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Id: biblio-1254916
Autor: Silva, Maria Cecília de Mattos Alves; Rezende, Thayane Rosas Batista; Carneiro, Zumira Aparecida; Lourenço, Charles Marques.
Título: BPAN manifesting with febrile seizures and language delay: a case report from Brazil
Fonte: Clin. biomed. res;41(1):91-93, 2021. ilus.
Idioma: en.
Resumo: Neurodegeneration with brain iron accumulation (NBIA) is a complex group of hereditary progressive neurodegenerative diseases characterized by deposition of iron in the basal ganglia. Twelve genetic forms of this disorder have been identified in previous studies. Though they have different inheritance mechanisms all are usually associated with abnormal brain MRI findings. One of NBIA types is an X-linked disorder known as Beta-propeller Protein Associated Neurodegeneration (BPAN). Herein we describe the case of a 4-year-old girl with 2 episodes of febrile seizures, a brain MRI showing nonspecific hyperintense signal in the dentate nucleus area, and delays in language and communication development. Her diagnosis was made based on a genetic evaluation where exome sequencing revealed a mutation in the position chrX:48.933.022 region of the WDR45 gene. The literature describes different clinical presentations for BPAN, each with a different prognosis, suggesting a wide range of possible symptoms of BPAN, including mild cognitive delay and even epileptic encephalopathy (EE). (AU)
Descritores: Distrofias Neuroaxonais/diagnóstico
Distúrbios do Metabolismo do Ferro/diagnóstico
Convulsões Febris
Transtornos do Desenvolvimento da Linguagem
-Proteínas de Transporte/genética
Distrofias Neuroaxonais/genética
Distúrbios do Metabolismo do Ferro/genética
Limites: Humanos
Feminino
Pré-Escolar
Tipo de Publ: Relatos de Casos
Responsável: BR18.1 - Biblioteca FAMED/HCPA


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Texto completo SciELO Chile
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Id: biblio-950735
Autor: Repsold, Lisa; Mqoco, Thandi; Wolmarans, Elize; Nkandeu, Sandra; Theron, Joji; Piorkowski, Tomek; du Toit, Peet; van Papendorp, Dirk; Joubert, Annie Margaretha.
Título: Ultrastructural changes of erythrocytes in whole blood after exposure to prospective in silico-designed anticancer agents: a qualitative case study
Fonte: Biol. Res;47:1-7, 2014. ilus, graf.
Idioma: en.
Resumo: BACKGROUND: Novel, in silico-designed anticancer compounds were synthesized in our laboratory namely, 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16). These compounds were designed to have improved bioavailability when compared to their source compound, 2-methoxyestradiol. This theoretically would be due to their increased binding affinity to carbonic anhydrase II, present in erythrocytes. Since the novel compounds under investigation are proposed to be transported within erythrocytes bound to carbonic anhydrase II, the morphological effect which they may exert on whole blood and erythrocytes is of great significance. A secondary outcome included revision of previously reported procedures for the handling of the whole blood sample. The purpose of this study was twofold. Firstly, the ultrastructural morphology of a healthy female's erythrocytes was examined via scanning electron microscopy (SEM) after exposure to the newly in silico-designed compounds. Morphology of erythrocytes following exposure to ESE-15-ol and ESE-16 for 3 minutes and 24 hours at 22°C were described with the use of SEM. The haemolytic activity of the compounds after 24 hours exposure were also determined with the ex vivo haemolysis assay. Secondly, storage conditions of the whole blood sample were investigated by determining morphological changes after a 24 hour storage period at 22°C and 37°C. RESULTS: No significant morphological changes were observed in the erythrocyte morphology after exposure to the novel anticancer compounds. Storage of the whole blood samples at 37°C for 24 hours resulted in visible morphological stress in the erythrocytes. Erythrocytes incubated at 22°C for 24 hours showed no structural deformity or distress. CONCLUSIONS: From this research the optimal temperature for ex vivo exposure of whole blood samples to ESE-15-ol and ESE-16 for 24 hours was determined to be 22°C. Data from this study revealed the potential of these compounds to be applied to ex vivo study techniques, since no damage occurred to erythrocytes ultrastructure under these conditions. As no structural changes were observed in erythrocytes exposed to ESE-15-ol and ESE-16, further ex vivo experiments will be conducted into the potential effects of these compounds on whole blood. Optimal incubation conditions up to 24 hours for whole blood were established as a secondary outcome.
Descritores: Sulfonamidas/farmacologia
Simulação por Computador
Inibidores da Anidrase Carbônica/farmacologia
Eritrócitos/efeitos dos fármacos
Estradiol/análogos & derivados
Estrenos/farmacologia
Antineoplásicos/farmacologia
-Sulfonamidas/toxicidade
Sulfonamidas/farmacocinética
Temperatura
Inibidores da Anidrase Carbônica/farmacocinética
Disponibilidade Biológica
Microscopia Eletrônica de Varredura
Proteínas de Transporte/farmacologia
Proteínas de Transporte/farmacocinética
Anidrase Carbônica II/efeitos dos fármacos
Pesquisa Qualitativa
Eritrócitos/ultraestrutura
Estradiol/toxicidade
Estradiol/farmacologia
Estradiol/farmacocinética
Estrenos/farmacocinética
Descoberta de Drogas
Hemólise/efeitos dos fármacos
Antineoplásicos/farmacocinética
Limites: Humanos
Feminino
Pessoa de Meia-Idade
Responsável: CL1.1 - Biblioteca Central


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Id: biblio-958403
Autor: Carmo, Helison Pereira do; Reichert, Karla; Carvalho, Daniela Diógenes de; Silveira-Filho, Lindemberg da Mota; Vilarinho, Karlos; Oliveira, Pedro; Petrucci, Orlando.
Título: Lidocaine and pinacidil added to blood versus crystalloid cardioplegic solutions: study in isolated hearts
Fonte: Rev. bras. cir. cardiovasc = Braz. j. cardiovasc. surg. (impr.);33(3):211-216, May-June 2018. tab, graf.
Idioma: en.
Projeto: Fundação de Amparo à Pesquisa do Estado de São Paulo.
Resumo: Abstract Objective: The present study aimed the functional recovery evaluation after long term of cardiac arrest induced by Custodiol (crystalloid-based) versus del Nido (blood-based) solutions, both added lidocaine and pinacidil as cardioplegic agents. Experiments were performed in isolated rat heart perfusion models. Methods: Male rat heart perfusions, according to Langendorff technique, were induced to cause 3 hours of cardiac arrest with a single dose. The hearts were assigned to one of the following three groups: (I) control; (II) Custodiol-LP; and (III) del Nido-LP. They were evaluated after ischemia throughout 90 minutes of reperfusion. Left ventricular contractility function was reported as percentage of recovery, expressed by developed pressure, maximum dP/dt, minimum dP/dt, and rate pressure product variables. In addition, coronary resistance and myocardial injury marker by alpha-fodrin degradation were also evaluated. Results: At 90 minutes of reperfusion, both solutions had superior left ventricular contractile recovery function than the control group. Del Nido-LP was superior to Custodiol-LP in maximum dP/dt (46%±8 vs. 67%±7, P<0.05) and minimum dP/dt (31%±4 vs. 51%±9, P<0.05) variables. Coronary resistance was lower in del Nido-LP group than in Custodiol-LP (395%±50 vs. 307%±13, P<0.05), as well as alpha-fodrin degradation, with lower levels in del Nido-LP group (P<0.05). Conclusion: Del Nido-LP cardioplegia showed higher functional recovery after 3 hours of ischemia. The analysis of alpha-fodrin degradation showed del Nido-LP solution provided greater protection against myocardial ischemia and reperfusion (IR) in this experimental model.
Descritores: Soluções Cardioplégicas/farmacologia
Reperfusão Miocárdica/métodos
Compostos de Potássio/farmacologia
Pinacidil/farmacologia
Parada Cardíaca Induzida/métodos
Lidocaína/farmacologia
-Fatores de Tempo
Resistência Vascular/fisiologia
Soluções Cardioplégicas/química
Proteínas de Transporte/análise
Western Blotting
Ratos Wistar
Vasos Coronários/fisiopatologia
Glucose/farmacologia
Glucose/química
Coração/efeitos dos fármacos
Manitol/farmacologia
Manitol/química
Proteínas dos Microfilamentos/análise
Limites: Animais
Masculino
Tipo de Publ: Estudo de Avaliação
Responsável: BR1.1 - BIREME



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