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1.
Hum Mutat ; 41(7): 1329-1338, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32333439

RESUMO

Biallelic variants of the gene DNAJC12, which encodes a cochaperone, were recently described in patients with hyperphenylalaninemia (HPA). This paper reports the retrospective genetic analysis of a cohort of unsolved cases of HPA. Biallelic variants of DNAJC12 were identified in 20 patients (generally neurologically asymptomatic) previously diagnosed with phenylalanine hydroxylase (PAH) deficiency (phenylketonuria [PKU]). Further, mutations of DNAJC12 were identified in four carriers of a pathogenic variant of PAH. The genetic spectrum of DNAJC12 in the present patients included four new variants, two intronic changes c.298-2A>C and c.502+1G>C, presumably affecting the splicing process, and two exonic changes c.309G>T (p.Trp103Cys) and c.524G>A (p.Trp175Ter), classified as variants of unknown clinical significance (VUS). The variant p.Trp175Ter was detected in 83% of the mutant alleles, with 14 cases homozygous, and was present in 0.3% of a Spanish control population. Functional analysis indicated a significant reduction in PAH and its activity, reduced tyrosine hydroxylase stability, but no effect on tryptophan hydroxylase 2 stability, classifying the two VUS as pathogenic variants. Additionally, the effect of the overexpression of DNAJC12 on some destabilizing PAH mutations was examined and a mutation-specific effect on stabilization was detected suggesting that the proteostasis network could be a genetic modifier of PAH deficiency and a potential target for developing mutation-specific treatments for PKU.

2.
Materials (Basel) ; 10(6)2017 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-28773001

RESUMO

Bacterial cellulose (BC) is a polymer obtained by fermentation with microorganism of different genera. Recently, new producer species have been discovered, which require identification of the most important variables affecting cellulose production. In this work, the influence of different carbon sources in BC production by a novel low pH-resistant strain Komagataeibacter medellinensis was established. The Hestrin-Schramm culture medium was used as a reference and was compared to other media comprising glucose, fructose, and sucrose, used as carbon sources at three concentrations (1, 2, and 3% w/v). The BC yield and dynamics of carbon consumption were determined at given fermentation times during cellulose production. While the carbon source did not influence the BC structural characteristics, different production levels were determined: glucose > sucrose > fructose. These results highlight considerations to improve BC industrial production and to establish the BC property space for applications in different fields.

3.
Pediátr. Panamá ; 42(2): 6-16, Agosto-Septiembre 2013.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-848913

RESUMO

El abuso sexual se refiere a las conductas sexuales coercitivas , impuestas a una persona menor de edad, por otra persona, que puede ser físicamente superior, con más experiencia y recursos, que utiliza incorrectamente su poder o autoridad. Es un hecho significativo que cada día emerge con más fuerza e involucra la vulneración de los derechos humanos. Por esta razón ante el creciente interés en el tema a nivel mundial, ante las devastadoras consecuencias sobre el niño, su entorno, salud física, emocional y posterior desempeño escolar y social, hemos decidido abordarlo. Objetivo: Identificar las características sociodemográficas, consecuencias físicas en niños de 4 a 15 años con sospecha de abuso sexual, atendidos en el Hospital del Niño entre los años 2009 al 2011 y determinar si existe relación a corto y largo plazo entre la agresión y alteraciones psicoemocionales. Metodología: Se realizó un estudio en dos fases: La primera fase un estudio descriptivo retrospectivo simple y la segunda fase, analítica de seguimiento, en un periodo de 18 a 24 meses posterior a sufrir agresión sexual, de los casos referidos a los Juzgados de Niñez y Adolescencia del Distrito de Panamá, mediante la aplicación de La Escala Children's Depression Inventory y la Escala de Ansiedad de Spence. La muestra fue de 92 casos. Se analizaron los datos con Excel 2010. Resultados: El mayor número de casos de abuso sexual se encontró en la adolescencia temprana 36 %, con una media de edad de 9.6 años, encontrando un factor de asociación de ocurrencia en el ámbito extra familiar con 21 %; en donde el 79 % el agresor era conocido por las víctimas. Sólo un 45 % de los casos referidos se considero abuso según juzgados. Sólo un 26 % cumplió la ruta crítica de forma integral. Conclusiones: Encontramos la mayor afectación en el grupo de adolescencia intermedia. La agresión se realizó por un conocido de la víctima y el examen físico no fue concluyente para el dictamen de abuso. En los casos a quienes se aplicaron las herramientas de evaluación psicoemocionales se evidenció predominio de alteraciones de tipo emocionales.


The sexual abuse refers to coercive sexual behaviors imposed to a minor by another person who can be physically superior, with more experience, resources, using in a wrong way his authority. It is significant fact that every day more strongly emerges and involves the violation of human rights. For this reason at the global increase of the topic with devastating consequences for the child, their environment, physical and emotional health and subsequent school and social performance, we decide to address this issue. Objective: Identify the sociodemographic characteristics and physical consequences in children from 4 to15 years with suspected sexual abuse, attended in Hospital del Niño between years 2009-2011 and determine if there exists association in a short or long term between the aggression and psycho-emotional disorders. Methods: The study was conducted in two phases: the first one was a single retrospective study and the second phase was a follow-up analysis in a period from 18 to 24 months after the sexual attack, in those cases referred to the courts for Childhood and Adolescence Panama District, through the application of Children's Depression Inventory Scale and the Spence Anxiety Scale. The sample was 92 cases. Data were analyzed with excel 2010. Results: The most cases of child sexual abuse were in the middle adolescence (36%), with a mean age of 9.6 years. We found association of occurrence in the extra-familiar environment with 21%, where the 79% of the aggressors were known people from the victim. 45% of the cases were considered sexual abuse by the Tribunals. Just 26% complete the entire process (Critical Route). The psycho-emotional disturbances were seen in a short term with 16% in adolescents. Conclusions: the most affected group was the middle adolescence. The attack was done by a known person of the victim and the physical examination was not conclusive to determine sexual abuse. In the cases evaluated with the anxiety and depression scales the most resulted in emotional disturbances.

4.
Epilepsia ; 54(2): 239-48, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23350806

RESUMO

PURPOSE: Pyridoxine-dependent epilepsy seizure (PDE; OMIM 266100) is a disorder associated with severe seizures that can be controlled pharmacologically with pyridoxine. In the majority of patients with PDE, the disorder is caused by the deficient activity of the enzyme α-aminoadipic semialdehyde dehydrogenase (antiquitin protein), which is encoded by the ALDH7A1 gene. The aim of this work was the clinical, biochemical, and genetic analysis of 12 unrelated patients, mostly from Spain, in an attempt to provide further valuable data regarding the wide clinical, biochemical, and genetic spectrum of the disease. METHODS: The disease was confirmed based on the presence of α-aminoadipic semialdehyde (α-AASA) in urine measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and pipecolic acid (PA) in plasma and/or cerebrospinal fluid (CSF) measured by high performance liquid chromatography (HPLC)/MS/MS and by sequencing analysis of messenger RNA (mRNA) and genomic DNA of ALDH7A1. KEY FINDINGS: Most of the patients had seizures in the neonatal period, but they responded to vitamin B6 administration. Three patients developed late-onset seizures, and most patients showed mild-to-moderate postnatal developmental delay. All patients had elevated PA and α-AASA levels, even those who had undergone pyridoxine treatment for several years. The clinical spectrum of our patients is not limited to seizures but many of them show associated neurologic dysfunctions such as muscle tone alterations, irritability, and psychomotor retardation. The mutational spectrum of the present patients included 12 mutations, five already reported (c.500A>G, c.919C>T, c.1429G>C c.1217_1218delAT, and c.1482-1G>T) and seven novel sequence changes (c.75C>T, c.319G>T, c.554_555delAA, c.757C>T, c.787 + 1G>T, c.1474T>C, c.1093-?_1620+?). Only one mutation, p.G477R (c.1429G>C), was recurrent; this was detected in four different alleles. Transcriptional profile analysis of one patient's lymphoblasts and ex vivo splicing analysis showed the silent nucleotide change c.75C>T to be a novel splicing mutation creating a new donor splice site inside exon 1. Antisense therapy of the aberrant mRNA splicing in a lymphoblast cell line harboring mutation c.75C>T was successful. SIGNIFICANCE: The present results broaden our knowledge of PDE, provide information regarding the genetic background of PDE in Spain, afford data of use when making molecular-based prenatal diagnosis, and provide a cellular proof-of concept for antisense therapy application.


Assuntos
Epilepsia/tratamento farmacológico , Epilepsia/genética , Terapia Genética/métodos , Oligonucleotídeos Antissenso/uso terapêutico , Deficiência de Vitamina B 6/complicações , Aldeído Desidrogenase/genética , Linhagem Celular , Análise Mutacional de DNA , Epilepsia/etiologia , Éxons/genética , Feminino , Humanos , Hiperlisinemias/urina , Lactente , Recém-Nascido , Linfócitos/efeitos dos fármacos , Masculino , Mutação/genética , Polimorfismo de Nucleotídeo Único , Processamento de RNA , Sacaropina Desidrogenases/deficiência , Sacaropina Desidrogenases/urina , Espectrometria de Massas em Tandem
7.
Enferm. clín. (Ed. impr.) ; 21(4): 196-201, jul.-ago. 2011.
Artigo em Espanhol | IBECS | ID: ibc-98564

RESUMO

Objetivo. Conocer la actitud y el comportamiento de las mujeres hacia las actividades preventivas relacionadas con la enfermedad cardiovascular. Método. Estudio descriptivo transversal, mediante encuesta autoadministrada sobre actitudes y comportamientos en prácticas preventivas, realizado en 3 centros de salud de Toledo, en 539 mujeres de 18-65 años. Resultados. Edad 40,4 años. Proceden del medio urbano 361 (66,7%); 354 (65,4%) están casadas; 221 (40,8%) son universitarias; trabajan 382 (70,8%). Creen que la principal causa de muerte en las mujeres es el cáncer 432 (83,2%); 174 (32,4%) dicen realizarse anualmente un chequeo médico preventivo; 411 (76,8%) consideran muy peligroso fumar, pero fuman actualmente 159 (30,0%). El consumo de alcohol es considerado muy peligroso por 232 (43,4%); son consumidoras habituales (casi todas las semanas) 92 (17,2%). Sólo 128 (23,8%) hace ejercicio habitualmente. Hacen algún tipo de dieta 127 (24,0%). Se realizan al menos una vez al año una toma de PA y analítica (colesterol y glucemia) el 68,4, el 64,1 y el 53,9%, respectivamente. Recuerdan haber sido aconsejadas alguna vez sobre el estilo de vida por un profesional sanitario 266 (51,7%). Conclusiones. La repercusión de las enfermedades cardiovasculares en la mujer está infravalorada. Nuestra población parece concienciada del riesgo de determinados hábitos, pero eso no se traduce siempre en un estilo de vida saludable. Parece que nuestros consejos no consiguen modificar la conducta de las mujeres en muchos casos, pero sí «medicalizar» su vida, aumentando la realización de controles analíticos y clínicos. Debemos insistir en la prevención del riesgo cardiovascular en la mujer y mejorar la efectividad de nuestras intervenciones (AU)


Objective. To find out the attitudes and behaviour of women towards preventive activities related to cardiovascular disease. Method. Cross-sectional descriptive study, through a self-completion questionnaire, in three Health Centres in Toledo (Spain). A total of 539 women between 18 and 65 years old answered an ad hoc developed questionnaire that contained items on knowledge, attitudes, and behaviours in preventive practices. Results. The mean age was 40.4 years age; 361 (66.7%) came from urban areas; 354 (65.4%) were married; 221 (40.8%) had university studies; 382 (70.8%) were working; 432 (83.2%) believed that the leading cause of death in women was cancer; 174 (32.4%) said they had annual preventive medical check-ups; 411 (76.8%) considered it very dangerous to smoke, but 159 (30.0%) currently smoked. Alcohol consumption was considered very dangerous by 232 (43.4%); 92 (17.2%) were regular consumers (almost every week). Only 128 (23.8%) did exercise one or more times per week. Only 127 (24.0%) followed some type of diet. At least one annual BP and laboratory tests (cholesterol and blood sugar) were measured in 68.4%, 64.1% and 53.9%, respectively. A total of 266 (51.7%) had been advised once on their lifestyle by a healthcare professional. Conclusions. The impact of cardiovascular disease in women is underestimated. Our population seemed concerned about the risk of certain habits but this was not always translated into a healthy lifestyle. It seems that our advice may not change the behaviour of women in many cases, but it does increase the number of clinical and analytical controls. We must insist on the prevention of cardiovascular risk in women and improve the effectiveness of our interventions (AU)


Assuntos
Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Doenças Cardiovasculares/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Estudos Transversais , Inquéritos e Questionários
8.
Enferm Clin ; 21(4): 196-201, 2011.
Artigo em Espanhol | MEDLINE | ID: mdl-21723175

RESUMO

OBJECTIVE: To find out the attitudes and behaviour of women towards preventive activities related to cardiovascular disease. METHOD: Cross-sectional descriptive study, through a self-completion questionnaire, in three Health Centres in Toledo (Spain). A total of 539 women between 18 and 65 years old answered an ad hoc developed questionnaire that contained items on knowledge, attitudes, and behaviours in preventive practices. RESULTS: The mean age was 40.4 years age; 361 (66.7%) came from urban areas; 354 (65.4%) were married; 221 (40.8%) had university studies; 382 (70.8%) were working; 432 (83.2%) believed that the leading cause of death in women was cancer; 174 (32.4%) said they had annual preventive medical check-ups; 411 (76.8%) considered it very dangerous to smoke, but 159 (30.0%) currently smoked. Alcohol consumption was considered very dangerous by 232 (43.4%); 92 (17.2%) were regular consumers (almost every week). Only 128 (23.8%) did exercise one or more times per week. Only 127 (24.0%) followed some type of diet. At least one annual BP and laboratory tests (cholesterol and blood sugar) were measured in 68.4%, 64.1% and 53.9%, respectively. A total of 266 (51.7%) had been advised once on their lifestyle by a healthcare professional. CONCLUSIONS: The impact of cardiovascular disease in women is underestimated. Our population seemed concerned about the risk of certain habits but this was not always translated into a healthy lifestyle. It seems that our advice may not change the behaviour of women in many cases, but it does increase the number of clinical and analytical controls. We must insist on the prevention of cardiovascular risk in women and improve the effectiveness of our interventions.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
9.
Neurogenetics ; 12(3): 183-91, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21431957

RESUMO

Sepiapterin reductase (SR) catalyzes the final step in the de novo synthesis of tetrahydrobiopterin, essential cofactor for phenylalanine, tyrosine, and tryptophan hydroxylases. SR deficiency is a very rare disease resulting in monoamine neurotransmitter depletion. Most patients present with clinical symptoms before the first year of age corresponding to a dopa-responsive dystonia phenotype with diurnal fluctuations, although some patients exhibit more complex motor and neurological phenotypes. Herein, we describe four new cases from Spain, their clinical phenotype and the biochemical and genetic analyses. Two mutations in the SPR gene were functionally expressed to provide a basis to establish genotype-phenotype correlations. Mutation c.751A>T is functionally null, correlating with the severe phenotype observed. The novel mutation c.304G>T was identified in three siblings with a strikingly mild phenotype without cognitive delay and close to asymptomatic in the eldest sister. Minigene analysis demonstrated that this mutation located in the last nucleotide of exon 1 affects splicing although some normal transcripts can be produced, resulting in the missense mutant p.G102C that retains partial activity. These results may account for the mild phenotype and the variable clinical presentations observed, which could depend on interindividual differences in relative abundance of correctly spliced and aberrant transcripts.


Assuntos
Oxirredutases do Álcool/genética , Processamento Alternativo/genética , Erros Inatos do Metabolismo/genética , Polimorfismo Genético/fisiologia , Adolescente , Oxirredutases do Álcool/deficiência , Oxirredutases do Álcool/metabolismo , Criança , Pré-Escolar , Feminino , Estudos de Associação Genética , Humanos , Isoenzimas/genética , Erros Inatos do Metabolismo/etiologia , Proteínas Mutantes/genética , Fenótipo
10.
Med Clin (Barc) ; 131(3): 81-8, 2008 Jun 21.
Artigo em Espanhol | MEDLINE | ID: mdl-18590621

RESUMO

BACKGROUND AND OBJECTIVE: Studies on different populations have shown a great variability of the frequencies of different polymorphisms in genes acting in the folate cycle. The present study was aimed to analyze the frequency in the Spanish population of each genotype combination of four polymorphisms, one of them -1561C-T of the glutamate carboxypeptidase II (GCPII) gene- being the first time that is studied in Spain. The study included a meta-analysis of the published data. SUBJECTS AND METHOD: Using the Spanish Collaborative Study of Congenital Malformations (ECEMC) Network, blood samples of 190 mother-child couples with newborns without any congenital defect, were obtained from 15 Spanish autonomous regions. The study polymorphisms were the 677C-T and 1298A-C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR), the 66A-G of the methionine synthase reductase (MTRR), and the 1561C-T polymorphism of the GCPII gene. To estimate the range for the population frequencies, 99% confidence intervals were calculated. RESULTS: The frequencies observed in our country were significantly different from others, being similar to those obtained in countries of the Mediterranean European area. The 1561C-T polymorphism of the GCPII gene has a frequency in Spain of 5.11%, which is also similar to the values observed in France (5%) and in Italy (6%). On the other hand, the frequency of the genotypes CTCC, TTAC is quite few, while the genotype TTCC was not observed in any mother or infants. A meta-analysis was performed for a big sample (23,612 individuals) and the results showed that with a 99% of probability the values for the genotype combinations CTCC, TTAC, and TTCC were within 0.10-0.24; 0.20-0.36; and 0.003-0.05, respectively. CONCLUSIONS: Our results are important to further analyze the relationship with some health problems and individual susceptibilities. Indeed, considering the published observations of the structure and function of the MTHFR enzyme, it is understandable that those genotype combinations that are quite little frequent, may be related to the embryo-fetal viability, and to the life style of each population.


Assuntos
Antígenos de Superfície/genética , Ferredoxina-NADP Redutase/genética , Ácido Fólico/metabolismo , Glutamato Carboxipeptidase II/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Feminino , Genótipo , Humanos , Recém-Nascido , Mães
11.
Med. clín (Ed. impr.) ; 131(3): 81-88, jun. 2008. tab
Artigo em Espanhol | IBECS | ID: ibc-178290

RESUMO

Fundamento y objetivo: Distintas poblaciones muestran diferencias en cuanto a las frecuencias de polimorfismos de genes del ciclo del folato. El objetivo de este estudio ha sido analizar las frecuencias genotípicas de 4 polimorfismos, uno de los cuales -1561C-T del gen de la glutamato carboxipeptidasa II (GCPII)- se analiza por primera vez en España, así como realizar un metaanálisis de los datos publicados. Sujetos y método: Utilizando la Red del Estudio Colaborativo Español de Malformaciones Congénitas (ECEMC) se obtuvieron, en 15 comunidades autónomas, muestras de sangre de 190 parejas madres-recién nacidos sin defectos. Se analizaron los polimorfismos 677C-T y 1298A-C del gen de la metilentetrahidrofolato reductasa (MTHFR); 66A-G del gen de la metionina sintasa reductasa (MTRR), y 1561C-T del gen de la GCPII. Los valores poblaciones se calcularon por los intervalos de confianza del 99%. Resultados: Las frecuencias en nuestro país difieren de las de otras poblaciones, excepto las del área mediterránea europea. La frecuencia del polimorfismo 1561C-T (gen GCPII) en España es del 5,11%, igual que en Francia (5%) e Italia (6%). Las de MTHFR, CTCC y TTAC en España son muy bajas y no se observó ninguna madrehijo con TTCC. El metaanálisis (23.612 individuos) mostró que, con un 99% de probabilidad, las frecuencias poblacionales de CTCC, TTAC y TTCC serían de 0,10-0,24; 0,20-0,36, y 0,003-0,05, respectivamente. Conclusiones: Estos resultados son importantes para estudios sobre la relación de dichos polimorfismos con problemas de salud y susceptibilidad individuales, así como para investigar sus implicaciones biológicas. Tras los últimos hallazgos estructurales y funcionales en la MTHFR pueden entenderse las diferencias, porque los genotipos infrecuentes podrían relacionarse con la viabilidad fetal, las concentraciones de homocisteína materno/ fetal y los estilos de vida


Background and objective: Studies on different populations have shown a great variability of the frequencies of different polymorphisms in genes acting in the folate cycle. The present study was aimed to analyze the frequency in the Spanish population of each genotype combination of four polymorphisms, one of them -1561CT of the glutamate carboxypeptidase II (GCPII) gene- being the first time that is studied in Spain. The study included a meta-analysis of the published data. Subjects and method: Using the Spanish Collaborative Study of Congenital Malformations (ECEMC) Network, blood samples of 190 mother-child couples with newborns without any congenital defect, were obtained from 15 Spanish autonomous regions. The study polymorphisms were the 677C-T and 1298A-C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR), the 66A-G of the methionine synthase reductase (MTRR), and the 1561C-T polymorphism of the GCPII gene. To estimate the range for the population frequencies, 99% confidence intervals were calculated. Results: The frequencies observed in our country were significantly different from others, being similar to those obtained in countries of the Mediterranean European area. The 1561C-T polymorphism of the GCPII gene has a frequency in Spain of 5.11%, which is also similar to the values observed in France (5%) and in Italy (6%). On the other hand, the frequency of the genotypes CTCC, TTAC is quite few, while the genotype TTCC was not observed in any mother or infants. A meta-analysis was performed for a big sample (23,612 individuals) and the results showed that with a 99% of probability the values for the genotype combinations CTCC, TTAC, and TTCC were within 0.10-0.24; 0.20-0.36; and 0.003-0.05, respectively. Conclusions: Our results are important to further analyze the relationship with some health problems and individual susceptibilities. Indeed, considering the published observations of the structure and function of the MTHFR enzyme, it is understandable that those genotype combinations that are quite little frequent, may be related to the embryo-fetal viability, and to the life style of each population


Assuntos
Humanos , Feminino , Gravidez , Recém-Nascido , Antígenos de Superfície/genética , Ferredoxina-NADP Redutase/genética , Ácido Fólico/metabolismo , Glutamato Carboxipeptidase II/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Genótipo , Mães , Espanha
13.
Am J Med Genet A ; 140(9): 987-97, 2006 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-16575899

RESUMO

This study was aimed at analyzing the effect of mutations in three non-synonymous SNP genes (677C > T and 1298A > C of the methylenetetrahydrofolate reductase (MTHFR) gene, and 66A > G in the MTRR gene) on total plasmatic homocysteine (Hcy), in 91 mothers of Down syndrome (DS) infants and 90 control mothers. The comparison of both groups of mothers is a new way to determine if those mutations and their interactions increase the risk for DS. Material came from the case-control network of the Spanish Collaborative Study of Congenital Malformations (ECEMC). Using a general lineal model in a backwards step, we performed the analyses including the different mutations, maternal age, the fact that each mother had a DS or a control infant, and all possible interactions of these variables, in the models, being maternal Hcy the continuous dependent variable. In another model, maternal folic acid intake during the third trimester of pregnancy was added. The results from both models were essentially the same: Hcy levels variability differs from case mothers to control ones, the presence of the MTHFR1298A > C polymorphism also affects significantly the Hcy variance, as it does the statistical interaction between the mutations MTRR66A > G and MTHFR1298A > C in the mother. In this sense, the interaction between different polymorphisms may totally modify their individual effects, and some of those effects are different in mothers of DS children and in controls' mothers. For instance, only two mutations in MTRR66 (GGAA) in mothers of control infants increase the reference maternal Hcy level in 4.66 units, and the individual effect of the genotype with only two mutations in the MTHFR1298 gene (AACC) increases the reference Hcy level in 12.74 units. However, the presence of the four mutations (GGCC) interacts giving a statistically significant decrease in 6.00 units in the level of Hcy in control mothers. On the contrary, in mothers of DS infants, the sole presence of two mutations in one of these two genes decreases the levels of Hcy (-2.31 units for GGAA genotype, and -3.43 units for AACC genotype), while the presence of the four mutations (GGCC) increases Hcy in 9.53 units. Taking into consideration that in the one-carbon metabolism cystathionine beta-synthase (CBS) catalyzes Hcy in an irreversible way, and that CBS gene is located in chromosome 21, fetuses and infants with DS have functional folate deficiency due to overexpression of CBS. This fact, as well as others influencing Hcy levels (such as nutrients interactions and lifestyle), together with the fetal genotype, suggest that their relationship with DS could be through an effect on fetal survival up to birth. Three possible mechanisms are considered by evaluating the results in the light of the present knowledge on cytology and molecular biology.


Assuntos
Síndrome de Down/genética , Ferredoxina-NADP Redutase/genética , Homocisteína/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Feminino , Ferredoxina-NADP Redutase/metabolismo , Ácido Fólico/administração & dosagem , Genótipo , Humanos , Lactente , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Mães , Mutação , Análise de Regressão , Fatores de Risco , S-Adenosil-Homocisteína/sangue , S-Adenosilmetionina/sangue
14.
Mol Genet Metab ; 86 Suppl 1: S61-6, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16165389

RESUMO

A novel subtype of patients with mutations in the phenylalanine hydroxylase (PAH) gene that show a positive response during a tetrahydrobiopterin (BH4) loading test has recently been recognized. These studies suggest that a number of phenylketonuric (PKU) patients may benefit from BH4 substitution, eliminating the need of life-long dietary restrictions. In our unit, we performed BH4 overload tests in 50 PAH-deficient patients. Overall, 38% of the patients had a positive response, mostly MHP and mild PKU patients, all with at least one missense mutation with presumed residual activity. Seven of the patients that required dietary restrictions have received treatment with BH4 from 5 to 18 months. All the patients included in the long-term treatment protocol had a mild PKU phenotype. BH4 therapy began at 10 mg/kg/day and changes were made over time depending on Phe levels. All patients at least doubled their protein ingestion and some could follow a completely free diet. Patients with a smaller decrease in Phe levels during the BH4 overload required higher BH4 doses and/or dietary restrictions to maintain adequate Phe levels over time. The genotype and the potential mechanisms underlying BH4 responsiveness and interindividual differences in pharmacokinetics of the administered cofactor are probably the basis for the differences in prolonged treatment.


Assuntos
Biopterina/análogos & derivados , Fenilalanina Hidroxilase/deficiência , Fenilcetonúrias/tratamento farmacológico , Administração Oral , Adolescente , Biopterina/uso terapêutico , Criança , Pré-Escolar , Genótipo , Humanos , Lactente , Mutação de Sentido Incorreto , Fenilalanina/sangue , Fenilalanina Hidroxilase/genética , Fenilcetonúrias/sangue , Fenilcetonúrias/dietoterapia , Fenilcetonúrias/genética
15.
Mol Genet Metab ; 83(1-2): 157-62, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15464430

RESUMO

Tetrahydrobiopterin (BH4) responsiveness in patients with mutations in the phenylalanine hydroxylase (PAH) gene is a recently recognized subtype of hyperphenylalaninemia characterized by a positive BH4 loading test. According to recent estimates, this phenotype may be quite common, suggesting that a large group of individuals may benefit from BH4 substitution, eliminating the need of life-long dietary restrictions. This underscores the importance of identifying BH4-responsive patients in each population, establishing the association with specific PAH mutations. In this work, we describe the results of a pilot study performed with 31 Spanish PAH-deficient patients subjected to a BH4 loading test. Overall, 11/31 (37%) showed a positive response with a 30% decrease in blood Phe levels 8 h after the BH4 challenge, and three additional patients, considered slow responders, showed this decrease only after 12-16 h. We report for the first time a patient homozygous for a splicing mutation with a slow response, suggesting an effect of BH4 supplementation on PAH gene expression. Most of the responsive patients belong to the mild hyperphenylalaninemia (MHP) or mild phenylketonuria phenotypic groups. In MHP patients we report for the first time the results of parallel single Phe doses confirming the utility of these analyses for a better evaluation of the response. Genotype analysis confirms the involvement in the response of specific mutations (D415N, S87R, R176L, E390G, and A309V) present in hemizygous patients, and provide relevant information for the discussion of the potential mechanisms underlying BH4 responsiveness.


Assuntos
Biopterina/análogos & derivados , Biopterina/farmacologia , Testes Respiratórios/métodos , Mutação , Fenilalanina Hidroxilase/deficiência , Fenilalanina Hidroxilase/genética , Fenilcetonúrias/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Homozigoto , Humanos , Lactente , Projetos Piloto , Espanha
16.
Biochem Pharmacol ; 66(10): 1915-24, 2003 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-14599549

RESUMO

Li(+)/Mg(2+) competition has been implicated in the therapeutic action of Li(+) treatment in bipolar illness. We hypothesized that this competition depended on cell-specific properties. To test this hypothesis, we determined the degree of Li(+) transport, immobilization, and Li(+)/Mg(2+) competition in lymphoblastomas, neuroblastomas, and erythrocytes. During a 50 mM/L Li(+)-loading incubation, Li(+) accumulation at 30 min (mmoles Li(+)/L cells) was the greatest in lymphoblastomas (11.1+/-0.3), followed by neuroblastomas (9.3+/-0.5), and then erythrocytes (4.0+/-0.5). Li(+) binding affinities to the plasma membrane in all three cell types were of the same order of magnitude; however, Li(+) immobilization in intact cells was greatest in neuroblastomas and least in erythrocytes. When cells were loaded for 30 min in a 50 mM/L Li(+)-containing medium, the percentage increase in free intracellular [Mg(2+)] in neuroblastoma and lymphoblastoma cells ( approximately 55 and approximately 52%, respectively) was similar, but erythrocytes did not exhibit any substantial increase ( approximately 6%). With the intracellular [Li(+)] at 15 mM/L, the free intracellular [Mg(2+)] increased by the greatest amount in neuroblastomas ( approximately 158%), followed by lymphoblastomas ( approximately 75%), and then erythrocytes ( approximately 50%). We conclude that Li(+) immobilization and transport are related to free intracellular [Mg(2+)] and to the extent of Li(+)/Mg(2+) competition in a cell-specific manner.


Assuntos
Eritrócitos/metabolismo , Transporte de Íons/fisiologia , Lítio/metabolismo , Magnésio/metabolismo , Ligação Competitiva , Transporte Biológico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/metabolismo , Humanos , Lítio/uso terapêutico , Neuroblastoma/patologia , Células Tumorais Cultivadas
17.
Rev. calid. asist ; 18(4): 244-248, jun. 2003. tab
Artigo em Espanhol | IBECS | ID: ibc-26225

RESUMO

Objetivo: Estimar el porcentaje de ingresos generales urgentes inadecuados e identificar los factores relacionados, en el Complexo Hospitalario de Ourense, donde se detecta una elevada presión de urgencias. Material y métodos: Muestreo aleatorio simple: 550 ingresos generales urgentes, excluidos los pediátricos y ginecológico-obstétricos, seleccionados de los producidos durante el año 2000. Las variables analizadas fueron los datos de identificación, la atención o el ingreso urgente, la estancia y la adecuación. Se aplicó el protocolo AEP (Universidad de Boston, distribuido por la Fundación Avedis Donavedian). La fuente de los datos fue la historia clínica. Se llevó a cabo un análisis descriptivo y de regresión logística. Resultados: El porcentaje de inadecuación fue del 7,3 por ciento (intervalo de confianza [IC] del 95 por ciento, 5,3-9,9). El día de la semana (lunes) influye significativamente en el aumento de la inadecuación, con independencia del resto de las variables introducidas. Conclusiones: No se confirma la hipótesis de que un porcentaje elevado de ingresos inadecuados justifique la elevada presión de urgencias en nuestro centro. Es necesario investigar otros factores (AU)


Assuntos
Adolescente , Adulto , Idoso , Feminino , Masculino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Humanos , Medicina de Emergência/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Qualidade da Assistência à Saúde/estatística & dados numéricos , Hospitais Gerais , Espanha
18.
Rev. cient. (Bogotá) ; 5(1/2): 52-60, ene.-dic. 1999. tab, graf
Artigo em Espanhol | LILACS | ID: lil-385838

RESUMO

Con el fin de describir los patrones esqueléticos para la maclusión clase III se tomó una muestra de 72 pacientes entre 6 y 12 años de las clínicas odontológicas de la Universidad El Bosque y el CIEO; con padres y abuelos Colombianos, características raciales de mestizos, sin historia de hábitos orales, ni patologías craneofaciales y sin antecedentes de tratamientos de ortodonciau ortopedia. Se les tomó una radiografía de perfil y se estudiaron 24 variables cefalométricas mediante los análisis de Harvord, Steiner, Mc Namara y Downs. Éstas fueron comparadas con un patrón de normalidad (clase I) de una muestra representativa para Santafé de Bogotá. Las variables que presentaron mayores diferencias significativas en cuanto a sexo fueron: longitud maxilar, diferencia maxilo-mandibular y altura facial inferior "Harvord", ángulos interincisal y goniaco "Steiner" y altura facial inferior "Mc Namara". Se observaron diferencias estadísticamente significativas según la edad para las siguientes variables: longitud maxilar, mandibular y diferencia maxilo-mandibular "Harvord", SNB "Steiner", longitud mandibular y diferencia maxilo-mandibular "McNamara" y ángulo de la converjidad "Downs". Los sujetos de maloclusión clase III presentan una combinación de mandíbula normal con un maxilar normal en un 20.4, retrusión maxilar y protrusión mandibular en un 23.6 y 19 con retrusión mandibular y maxilar.


Assuntos
Criança , Cefalometria , Dentição Mista , Má Oclusão de Angle Classe III
19.
Rev. ADM ; 54(1): 33-6, ene.-feb. 1997. tab
Artigo em Espanhol | LILACS | ID: lil-200154

RESUMO

Se estudiaron 26 laminillas con citología exfoliativa bucal de 17 pacientes, ambos sexos, con rangos de edad entre 5-65 años, que presentaban úlceras aftosas con un máximo de 36 horas de evolución y sin aplicación previa de tratamiento. Se observaron todas las laminillas, determinando los siguientes índices: maduración de Frost, eosinófilo, plegamiento, aglutinación, además de los valores estrogénicos y cariopicnóticos, con el propósito de comparar, mediante estos índices, los cambios ocurridos antes y después de la aplicación durante tres minutos del rayo láser blando galio-aluminio-arsenurio, a longitud de onda de 790 nanómetros, 115 volts de entrada, 6 volts de salida y 30 microwatts de potencia. Se aplicó la prueba "t" de Student en muestras apareadas con un nivel de confianza P=0.05, para establecer la significancia estadística de los cambios detectados. Las úlceras aftosas presentaron significancia en células intermedias del índice de maduración, en células no cariopicnóticas y en el índice de aglutinación. Por lo tanto, para este estudio se demuestra que el tratamiento con rayo láser acelera el metabolismo celular epitelial, con una menor descamación, observándose un proceso de reparación uniforme, estable y predecible


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Adolescente , Adulto , Pessoa de Meia-Idade , Citodiagnóstico/métodos , Lasers/uso terapêutico , Estomatite Aftosa/radioterapia , Distribuição por Idade , Microscopia de Polarização , Mucosa Bucal/ultraestrutura , Radioisótopos de Gálio/uso terapêutico , Distribuição por Sexo , Análise Estatística , Testes de Aglutinação
20.
México, D.F; Fernández Editores; 20 nov. 1996. 279 p. ilus, mapas.
Monografia em Espanhol | LILACS | ID: lil-217494

RESUMO

Material didáctico elaborado por la Comisión Ambiental Metropolitana, dirigido a los estudiantes que cursan el tercer grado de educación secundaria en México, con el objetivo principal de dar a conocer los problemas ambientales del país y proponer algunas estrategias para prevenir y controlar la contaminación. Los temas se dan a conocer de manera práctica y sencilla, conteniendo algunos términos científicos de fácil comprensión y tomando en cuenta estadísticas recientes que permiten actualizar los datos acerca del tema, así como información acerca de las áreas ecológicas y las zonas chinamperas, su concepto y distribución geográfica. Se anexan al final de cada capítulo actividades y un glosario. Contenido: 1. La contaminación producida por desechos materiales 2. La contaminación por combustión, ruido, medios de transporte e industrias 3. Alteraciones en el equilibrio ecológico por la deforestación 4. La contaminación social


Assuntos
Poluição Ambiental , Ecologia , Meio Ambiente , Educação em Saúde
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