[Maintenance of chest compressions skill in cardiopulmonary resuscitation in primary health care professionals: Quasi-experimental study]. / Mantenimiento de la habilidad de las compresiones torácicas en reanimación cardiopulmonar en profesionales de la atención primaria de salud: estudio cuasiexperimental.

OBJECTIVE: To validate the efficacy of brief CPR training with dual feedback to maintain the ability to perform quality chest compressions. MATERIALS AND METHODS: Quasi-experimental study with two groups to evaluate a brief theoretical training followed by a practice with manikin with feedback; Participants: 155 health and non-health professionals from 5 primary care health centers of urban area (43 losses); Main measurements: Characteristics of compressions that were measured before and after the brief training and their maintenance at 3 and 6 months according to the study group. The effect of training and maintenance of skills were analyzed using multiple linear regression models. RESULTS: 155 participants were included, mean age 39.7 years (SD=12.0) with 82.7% female. The training effect had an improvement in mean compression depth (pre-post difference: 3.5, P<.001), total compressions with adequate depth (pre-post difference: 0.2, P<.001) and Total Compressions with Adequate Rhythm (pre-post difference: 0.4, P<.001). The second phase was completed by 112 participants (72.2%). Compression skills declined at 3 months and were lower at 6 months, although the loss of skills was not statistically significant between the two groups. CONCLUSIONS: An individualized, brief training action with feedback immediately improves the quality of compressions. The progressive loss of skills from 3 to 6 months is not relevant.

Arterial hypertension and smoking in pregnant women in the Valencian Community: maternal and neonatal outcomes.

OBJECTIVE: Hypertension and smoking during pregnancy have been linked to various adverse maternal and fetal outcomes. The objective of this work is to study how the smoking influences the development of hypertension, its effects on the pregnant woman, and on the newborn. MATERIALS AND METHODS: An observational study in two phases was carried out: the descriptive first phase allows characterization of the sample and the analytical second phase is a case-control nested in a retrospective cohort corresponding to pregnancy. RESULTS: A total of 712 women were included in the study. Of the 672 (94.4%) non-hypertensive women, 533 (79.3%) were non-smoking and 139 (20.7%) smoking. For the 40 (5.6%) hypertensive women, 30 (75.0%) were non-smoking and 10 (25.0%) smoking. The prevalence of hypertension was of 5.6%. Women who quit smoking before pregnancy saw a reduced risk of hypertension. For women who smoke during pregnancy, those of younger ages, with a normal body mass index, who are primiparous, employed and with a low-medium level of education have higher risk of hypertension. The risk of hypertension according to the level of physical activity during leisure time follows a "U" shape, with those who perform light physical activity at the lowest risk of hypertension. Hypertensive women have a higher risk of small for gestational age newborns. Smoking does not pose an additional risk for adverse outcomes once hypertension is diagnosed. CONCLUSIONS: Future studies should aim to determine the role of smoking habit in the appearance of hypertension in pregnancy in order to establish adequate intervention guidelines that may aid in reducing the prevalence of hypertension.

Sedentarismo en el embarazo: efectos sobre la madre y el recién nacido / Sedentary lifestyle in pregnancy: Effects on the mother and the newborn

Objetivo Identificar el estado de sedentarismo durante el embarazo y los factores asociados a este comportamiento, los posibles factores, su situación de salud y del recién nacido. Material y métodos Este estudio observacional transversal de 2 fases se desarrolló en el Hospital Universitario y Politécnico de La Fe, y participaron 228 mujeres embarazadas. Las características sociodemográficas maternas se obtuvieron mediante cuestionario estructurado e información de salud de la historia clínica electrónica, así como los resultados perinatales del recién nacido. Para evaluar el sedentarismo se valoró el ejercicio en el tiempo libre y el ejercicio en horario laboral, categorizándolos en función de la intensidad (sedentarismo, actividad leve, actividad moderada e intenso). Resultados En total, la prevalencia de sedentarismo fue del 31,14%. El perfil de este grupo tiene menor nivel educativo y desempleo (p<0,05), presentando una mayor prevalencia de problemas durante el parto, que requirió cesárea, así como problemas posparto en el recién nacido (p<0,05). Conclusiones La inactividad física es altamente prevalente entre las mujeres embarazadas. Debido a los beneficios (o no daños) atribuidos al ejercicio durante el embarazo. Se deben realizar mayores esfuerzos para superar las barreras para promover actividades entre las mujeres embarazadas que son más jóvenes, menos educadas y desempleadas, y aquellas con varios hijos y menores ingresos tienen menos probabilidades de participar en una cantidad adecuada de actividad física, conscientes de la importancia de hacerlo, resolviendo dudas y disipando temores que puedan surgir por una mala comprensión del mecanismo de su beneficio (AU)

Objective Identify the state of sedentary lifestyle during pregnancy and the factors associated with this behavior, the possible factors of your health situation and that of the newborn. Material and methods This two-phase, cross-sectional observational study was developed at the La Fe University and Polytechnic Hospital and 228 pregnant women participated. Maternal sociodemographic characteristics were obtained using structured questionnaire and health information from the electronic medical records, as well as perinatal results of the newborn. To assess sedentary lifestyle, exercise in free time and exercise during working hours were assessed, categorizing them based on intensity (sedentary lifestyle, light activity, moderate and intense activity). Results In total, the prevalence of physical inactivity was 31.14%. The profile of this group has a lower level of education and unemployment (P<.05), presenting a higher prevalence of problems during childbirth, which required a caesarean section, as well as problems after birth in the newborn (P<.05). Conclusions Physical inactivity is highly prevalent among pregnant women. Due to the benefits (or non-harm) attributed to exercise during pregnancy. Further efforts should be taken to overcome the barriers to promote activities among pregnant women who are younger, less well educated, and unemployed and those with multiple children and a lower income are less likely to engage in an adequate amount of physical activity, aware of the importance of doing it, resolving doubts and allaying fears that may arise from a poor understanding of the mechanism of its benefit (AU)

Fish intake in pregnant women and its impact on maternal-fetal health status / Ingesta de pescado en mujeres embarazadas y su impacto en el estado de salud materno-fetal

Objective The objective was to evaluate the consumption of fish in pregnant women and its association with maternal and infant outcomes. Material and methods In this observational study carried out at the La Fe University and Polytechnic Hospital in Valencia, 300 pregnant women participated. The participants were divided into 2 groups according to their fish consumption during pregnancy for comparison. The χ2 test or ANOVA test were applied for comparisons for qualitative and quantitative variables respectively. Results It was observed that 49% of women consumed adequate amounts of fish during pregnancy (2 or 3 weekly servings). Significant differences were observed for iron supplementation (higher in women with inadequate fish consumption), threatened pregnancy loss (higher in women with inadequate fish consumption), infant size (better in women with adequate fish consumption), and arterial O2 pressure (better in women with adequate fish consumption). In regard to the other components of the dietary pattern, no differences were observed but the adequacy of intake for grains and white meat was very poor (less than 5.0%). Conclusions Half of the women met the recommendations for fish intake during pregnancy and presented an overall healthier eating pattern but without statistical significance (AU)

Objetivo Evaluar el consumo de pescado en mujeres embarazadas y su asociación con la salud materno-infantil. Material y métodos En este estudio observacional llevado a cabo en el Hospital Universitario y Politécnico La Fe de Valencia participaron 300 mujeres embarazadas. Las participantes se dividieron en dos grupos según su consumo de pescado durante el embarazo para comparar. Para las comparaciones de variables cualitativas y cuantitativas se aplicaron la prueba de χ2 o la ANOVA, respectivamente. Resultados Se observó que el 49% de las mujeres consumieron cantidades adecuadas de pescado durante el embarazo (2 o 3 raciones semanales). Se observaron diferencias significativas para la suplementación con hierro (mayor en mujeres con consumo inadecuado de pescado), amenaza de pérdida del embarazo (mayor en mujeres con consumo inadecuado de pescado), tamaño del bebé (mejor en mujeres con consumo adecuado de pescado) y presión arterial de O2 (mejor en mujeres con consumo adecuado de pescado). En cuanto a los demás componentes del patrón dietético, no se observaron diferencias, pero la adecuación del consumo de cereales y de carnes blancas fue muy pobre (menos del 5,0%). Conclusiones La mitad de las mujeres cumplían con las recomendaciones de consumo de pescado durante el embarazo y presentaban un patrón alimentario globalmente más saludable, pero sin significación estadística (AU)

Fish intake in pregnant women and its impact on maternal-fetal health status.

OBJECTIVE: The objective was to evaluate the consumption of fish in pregnant women and its association with maternal and infant outcomes. MATERIAL AND METHODS: In this observational study carried out at the La Fe University and Polytechnic Hospital in Valencia, 300 pregnant women participated. The participants were divided into 2 groups according to their fish consumption during pregnancy for comparison. The χ2 test or ANOVA test were applied for comparisons for qualitative and quantitative variables respectively. RESULTS: It was observed that 49% of women consumed adequate amounts of fish during pregnancy (2 or 3 weekly servings). Significant differences were observed for iron supplementation (higher in women with inadequate fish consumption), threatened pregnancy loss (higher in women with inadequate fish consumption), infant size (better in women with adequate fish consumption), and arterial O2 pressure (better in women with adequate fish consumption). In regard to the other components of the dietary pattern, no differences were observed but the adequacy of intake for grains and white meat was very poor (less than 5.0%). CONCLUSIONS: Half of the women met the recommendations for fish intake during pregnancy and presented an overall healthier eating pattern but without statistical significance.

[Sedentary lifestyle in pregnancy: Effects on the mother and the newborn]. / Sedentarismo en el embarazo: efectos sobre la madre y el recién nacido.

OBJECTIVE: Identify the state of sedentary lifestyle during pregnancy and the factors associated with this behavior, the possible factors of your health situation and that of the newborn. MATERIAL AND METHODS: This two-phase, cross-sectional observational study was developed at the La Fe University and Polytechnic Hospital and 228 pregnant women participated. Maternal sociodemographic characteristics were obtained using structured questionnaire and health information from the electronic medical records, as well as perinatal results of the newborn. To assess sedentary lifestyle, exercise in free time and exercise during working hours were assessed, categorizing them based on intensity (sedentary lifestyle, light activity, moderate and intense activity). RESULTS: In total, the prevalence of physical inactivity was 31.14%. The profile of this group has a lower level of education and unemployment (P<.05), presenting a higher prevalence of problems during childbirth, which required a caesarean section, as well as problems after birth in the newborn (P<.05). CONCLUSIONS: Physical inactivity is highly prevalent among pregnant women. Due to the benefits (or non-harm) attributed to exercise during pregnancy. Further efforts should be taken to overcome the barriers to promote activities among pregnant women who are younger, less well educated, and unemployed and those with multiple children and a lower income are less likely to engage in an adequate amount of physical activity, aware of the importance of doing it, resolving doubts and allaying fears that may arise from a poor understanding of the mechanism of its benefit.

Enfermedad periodontal y diabetes mellitus gestacional: estudio caso-control / Periodontal disease and gestational diabetes mellitus: a case-control study

Antecedentes: Los estudios que relacionan la enfermedad periodontal (EP) y la diabetes mellitus gestacional (DMG) no son concordantes. Nuestro objetivo principal es evaluar la posible asociación entre la EP y la DMG. Además, analizamos los factores de riesgo para la DMG en nuestra muestra. Métodos: Participaron 180 gestantes, 90 con DMG y 90 controles, del Hospital La Fe de Valencia. Se pasó un cuestionario y realizo un examen periodontal, valorándose los siguientes parámetros: número de dientes, índices de placa y sangrado al sondaje, profundidad de sondaje (PS) y nivel de inserción de clínica (NIC). La periodontitis se definió según criterios de la CDC-AAP. Resultados: Las DMG tuvieron mayor valor promedio de PS (p = 0,001) y NIC (p = 0,028). Un 74,4% de las pacientes con DMG presentaron inflamación gingival vs. 57,8% de las no diabéticas. La periodontitis fue más prevalente en las pacientes con DMG (p < 0,05). La edad materna, el nivel de estudios y la presencia de periodontitis son factores independientes de riesgo para la DMG (OR = 1,16, IC 95% 1,07 a 1,25, p < 0,001), (OR = 0,37, IC 95% 0,19 a 0,72, p < 0,005) y (OR = 2,79, IC 95% 1,40 a 5,59, p < 0,005), respectivamente. Conclusiones: Los resultados sugieren que las embarazadas con diabetes gestacional asocian más enfermedad periodontal que aquellas sin dicha enfermedad gestacional. En nuestra muestra el riesgo de DMG puede estimarse a partir de la periodontitis, la edad y el nivel de estudios.(AU)

Background: Studies linking periodontal disease (PD) and gestational diabetes mellitus (GDM) are not consistent. Our main objective is to evaluate the possible association between PD and GDM. We also analysed the risk factors for GDM in our sample. Methods: 180 pregnant women participated, 90 with GDM and 90 controls, from Valencia's Hospital La Fe. A questionnaire was completed and a periodontal examination was performed, assessing the following parameters: number of teeth, plaque and bleeding on probing indices, probing depth (PD) and clinical attachment level (CAL). Periodontitis was defined according to the criteria of CDC-AAP. Results: The GDM group had a higher mean value of PD (p = .001) and CAL (p = .028). Of the patients with GDM, 74.4% had gingival inflammation compared to 57.8% of the non-diabetic patients. Periodontitis was more prevalent in patients with GDM (p < .05). Maternal age, educational level and periodontitis are independent risk factors for GDM (OR = 1.16, 95% CI 1.07 to 1.25, p < .001), (OR = .37, 95% CI .19 to .72, p < .005) and (OR = 2.79, 95% CI 1.40 to 5.59, p < .005) respectively. Conclusions: The results suggest that pregnant women with gestational diabetes have more associated periodontal disease than those without gestational diabetes. In our sample, the risk for GDM can be estimated from periodontitis, age, and educational level.(AU)

Toxicidad por rodenticidas anticoagulantes / No disponible

No disponible

Encuesta a urgenciólogos sobre el papel del laboratorio en el manejo de las intoxicaciones agudas / Role of laboratory tests in managing acute poisonings: a survey of emergency physicians

Objetivo: Evaluar mediante una encuesta la percepción que los facultativos que atienden a pacientes intoxicados agudos tienen sobre el papel del laboratorio y conocer la importancia subjetiva que otorgan a determinadas pruebas para realizar el manejo clínico de las intoxicaciones agudas frecuentes. Método: La encuesta se dirigió a urgenciólogos que trabajan en servicios de urgencias(SU) de dos hospitales con Unidades de Toxicología Clínica (UTC) y médicos asistentes a cursos de formación toxicológica. Se solicitaba: datos profesionales, grado de importancia atribuida a las pruebas del laboratorio para las diferentes etapas asistenciales, un máximo de tres pruebas fundamentales para el cuidado de 17 intoxicaciones agudas e indicar una determinación de analítica básica y que no se realizase en su laboratorio. Resultados: Ochenta y ocho encuestas se consideraron válidas, de las cuales 69 (78%)se recogieron en cursos y 19 (22%) en 2 SU. La etapa asistencial a la cual los facultativos encuestados otorgan una mayor importancia al laboratorio es la etapa diagnóstica, independientemente del grupo al que pertenecen (62% si pertenecen a SU y 58% si asistieron a cursos). El papel del laboratorio es más relevante (p < 0,05) para aquellos médicos encuestados que trabajan en SU de los hospitales con UTC (52%) que para los (..) (AU)

Objective: To survey physicians who treat acute poisoning cases to determine their attitudes toward laboratory testing in these cases and also toward certain tests for the management of common poisonings. Methods: A questionnaire was sent to physicians working in the emergency departments of 2 hospitals with toxicology units and to physicians attending toxicology training courses. Survey items asked about professional data; the degree of importance the physicians attached to laboratory testing at different stages in the care process; which 3 tests the respondents considered important in 17 different acute poisoning scenarios; and which laboratory test they considered highly important was unavailable at the hospitals where the physicians worked. Results: Eighty-eight valid questionnaires were returned; 69 of them (78%) were from physicians attending toxicology courses and 19 (22%) were from emergency room physicians. The respondents in both groups believed that laboratory tests were most important when cases of acute poisoning were being diagnosed; 62% of the emergency department physicians and 58% of the trainee physicians expressed that opinion. More emergency department physicians at(..)(AU)

Manejo de los pacientes con fibrilación auricular en los servicios de urgencias hospitalarios (actualización 2012) / Atrial fibrillation management in the hospital emergency department: 2012 update

La fibrilación auricular (FA) es la arritmia sostenida de mayor prevalencia en los servicios de urgencias (SHU), que presentan una frecuentación elevada y creciente en España. La FA es una enfermedad grave, que incrementa la mortalidad y asocia una relevante morbilidad e impacto en la calidad de vida de los pacientes y en el funcionamiento de los servicios sanitarios. La diversidad de aspectos clínicos a considerar y el elevado número de opciones terapéuticas posibles justifican la implementación de estrategias de actuación coordinadas entre los diversos profesionales implicados, con el fin de incrementar la adecuación del tratamiento y optimizar el uso de recursos. Este documento recoge las recomendaciones para el manejo de la FA, basadas en la evidencia disponible, y adaptadas a las especiales circunstancias de los SUH. En él se analizan con detalle las estrategias de tromboprofilaxis, control de frecuencia y control del ritmo, y los aspectos logísticos y diagnósticos relacionados (AU)

Atrial fibrillation is the most frecuently sustained arrhythmia managed in emergency departments, and accounts for a high and increasing prevalence in Spain. Atrial fibrillation is increases mortality, is associated with substantial complications and, therefore, has a relevant impact in running of the health care system. Management requires consideration of diverse clinical variables and a large number of possible therapeutic approaches, justifying action plans that coordinate the work of medical staff in the interest of providing appropriate care and optimizing resources. These evidence-based guidelines contain recommendations for managing atrial fibrillation in the special circumstances of hospital emergency departments. Stroke prohylaxis, rate control, rhtyhm control, and related diagnostic and logistic issues are discussed in detail (AU)

Síndrome de bridas amnióticas: caso clínico y revisión del tema / Amniotic band syndrome: case report and review of the literatura

El síndrome de bridas amnióticas (SBA) es un conjunto de anomalías congénitas, que asocia lesiones por constricción o amputación de miembros o dedos, asociado a la presencia de bridas amnióticas. Es una entidad con baja incidencia y suele ser de aparición esporádica. Suele cursar con anillos de constricción en la parte distal de los miembros o en los dedos o en casos más graves presentar amputación completa de miembros u asociación con otras malformaciones. El diagnóstico prenatal se produce sólo en el 29-50% de los casos. Presentamos el caso de una paciente con diagnóstico ecográfico de brida amniótica en la semana 12 de gestación (AU)

Amniotic band syndrome is a set of congenital birth defects consisting of constriction rings and limb or digit amputations, associated with the presence of amniotic bands. The incidence of this complication is low and its occurrence is sporadic. This syndrome usually causes constriction rings in the distal end of limbs or digits, which, in severe cases, can lead to complete amputation of the limbs or other malformations. Only 29-50% of cases are diagnosed prenatally. We report the case of a patient with an ultrasonographic diagnosis of amniotic band syndrome in week 12 of pregnancy (AU)

Características de los recién nacidos tras fecundación in vitro / Birth characteristics due to in vitro fertilization (IVF) techniques

Objetivo: determinar en una unidad neonatal de nivel II la frecuencia de nacimientos tras fecundación in vitro (FIV) incluyendo FIV-ICSI (intracytoplasmic sperm injection) y comparar sus características con los de fecundación natural (FN), según sean gemelares o únicos. Pacientes y método: estudio prospectivo mediante revisiones fetales desde la semana 12 de gestación tras FIV, al nacer y al año de vida. Del 1 de enero de 2004 al 31 de marzo de 2007 nacieron 7.008 recién nacidos (RN), 113 tras FIV y 6.895 por FN. Resultados: la gemelaridad es del 2,4% en FN y el 56,6% en FIV (p<0,001). La edad materna media en únicos es 28±9 años en FN y 36±4 en FIV (p<0,05); en gemelares es 29±10 años en FN y 35±4 en FIV (p<0,05). La edad gestacional media en únicos es 38±4 semanas en FN y 39±2 en FIV y 36±1 semanas en gemelares FN y FIV. La tasa de prematuridad (<37 semanas) y la de bajo peso (<2.500g) no difiere estadísticamente entre únicos y gemelares FN y FIV. El 23,13% de los únicos FN y el 51,02% de los únicos FIV nacieron por cesárea (p<0,001), pero la diferencia entre gemelares FN (71,42%) y FIV (79,69%) no es estadísticamente significativa. El 5,3% de los RN vivos FIV y el 1,1% de los FN nacieron con defectos congénitos (p<0,002). El riesgo relativo (RR) de defectos congénitos de los FIV frente a los FN es 4,83 (intervalo de confianza del 95%, 2,14-10,83). Conclusiones: si se comparan según número de fetos, los FIV suponen el 1,61% de los RN, difieren de los FN en edad materna, gemelaridad, cesáreas (únicos) y defectos congénitos, pero no en prematuridad ni bajo peso (AU)

Objective: To determine the number of deliveries after 31 weeks gestation (w), from in vitro fertilization (IVF), including Intracytoplasmic Sperm Injection (ICSI), and to compare characteristics with those achieved by natural fertilization (NF). We analyse twin and singleton pregnancies separately. Patients and method: This descriptive and prospective study monitors children from foetus, from 12 weeks after IVF, to 12 months of age, including the newborn period. There were 7008 newborns between 1st January 2004 and 31st March 2007 of which there were 113 from IVF and 6895 from NF. Results: Twin-pregnancies in NF is 2.4%, whereas in IVF it is 56.6%, (p<0.001). Mean mother age is 28±9 years (y) in NF and 36±4y in IVF singletons (p<0.05), and 29±10 y in NF and 35±4 y in IVF twins (p<0.05). Mean gestational age is 38±4 w and 39±2w in NF and IVF singletons and 36±1 w in NF and IVF twins. No statistically significant differences were found in prematurity rate (<37 w) and low birth weight (< 2500g) between singletons and twins from IVF or NF. Caesarean sections were 23.13% and 51.02% from singleton NF and IVF (p<0.001). No statistically differences were found between twins NF (71.42%) and IVF (79.69%). Malformations at birth were observed in 5.3% of IVF and in 1.1% of NF newborns (p<0.002). Relative risk of malformations (RR) IVF versus NF is 4.83 (95% CI, 2.14-10.83). Conclusions: Only 1.61% of newborns comes from IVF techniques. There are significant differences in age of mother, twin- pregnancies, caesarean sections (singletons) and congenital defects between them and NF newborns. There were no differences found in prematurity and low birth weight between them and NF newborns, when compared by number of foetus (AU)

[Birth characteristics due to in vitro fertilization (IVF) techniques]. / Características de los recién nacidos tras fecundación in vitro.

OBJECTIVE: To determine the number of deliveries after 31 weeks gestation (w), from in vitro fertilization (IVF), including Intracytoplasmic Sperm Injection (ICSI), and to compare characteristics with those achieved by natural fertilization (NF). We analyse twin and singleton pregnancies separately. PATIENTS AND METHOD: This descriptive and prospective study monitors children from foetus, from 12 weeks after IVF, to 12 months of age, including the newborn period. There were 7008 newborns between 1st January 2004 and 31st March 2007 of which there were 113 from IVF and 6895 from NF. RESULTS: Twin-pregnancies in NF is 2.4%, whereas in IVF it is 56.6%, (p<0.001). Mean mother age is 28+/-9 years (y) in NF and 36+/-4y in IVF singletons (p<0.05), and 29+/-10 y in NF and 35+/-4 y in IVF twins (p<0.05). Mean gestational age is 38+/-4 w and 39+/-2w in NF and IVF singletons and 36+/-1 w in NF and IVF twins. No statistically significant differences were found in prematurity rate (<37 w) and low birth weight (< 2500g) between singletons and twins from IVF or NF. Caesarean sections were 23.13% and 51.02% from singleton NF and IVF (p<0.001). No statistically differences were found between twins NF (71.42%) and IVF (79.69%). Malformations at birth were observed in 5.3% of IVF and in 1.1% of NF newborns (p<0.002). Relative risk of malformations (RR) IVF versus NF is 4.83 (95% CI, 2.14-10.83). CONCLUSIONS: Only 1.61% of newborns comes from IVF techniques. There are significant differences in age of mother, twin- pregnancies, caesarean sections (singletons) and congenital defects between them and NF newborns. There were no differences found in prematurity and low birth weight between them and NF newborns, when compared by number of foetus.

Oxidative damage of 14-3-3 zeta and gamma isoforms in Alzheimer's disease and cerebral amyloid angiopathy.

Previous studies have shown oxidative damage resulting from amyloid Abeta exposure to cultured cells and in murine models. A target of oxidation is 14-3-3 which comprises a group of proteins involved in kinase activation and chaperone activity. The present study shows glycoxidative damage, as revealed with mono and bi-dimensional gel electrophoresis and Western blotting, followed by in-gel digestion and mass spectrometry, in the frontal cortex in Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA), a neurodegenerative disease with deposition of Abeta in cerebral blood vessels and in diffuse plaques unaccompanied by intraneuronal hyper-phosphorylated tau deposition. malondialdehyde-lysine (MDA-Lys)-, but not 4-hydroxy-2-nonenal (HNE)-immunoreactive adducts, and N-carboxyethyl-lysine (CEL), but not N-carboxymethyl-lysine (CML)-products, were present in 14-3-3 involving zeta and gamma isoforms in both AD and CAA. These findings demonstrate that 14-3-3 glyco- and lipoxidation occurs in AD and CAA, probably as a direct consequence of Abeta deposition.

Abnormal Sp1 transcription factor expression in Alzheimer disease and tauopathies.

Sp1 transcription factor expression was examined by immunohistochemistry, immunofluorescence and confocal microscopy in Alzheimer disease (AD), Pick disease (PiD), progressive supranuclear palsy (PSP), Parkinson disease (PD) and Dementia with Lewy bodies (DLB). Sp1 partly co-localizes with hyper-phosphorylated tau deposits in neurofibrillary tangles, dystrophic neurites of senile plaques and neuropil threads in AD, and in neurons, astrocytes and oligodendrocytes bearing hyper-phosphorylated tau in PiD and PSP. Sp1 is not found in alpha-synuclein inclusions in PD and DLB. These modifications are not associated with changes in the total expression levels of Sp1, as revealed with gel electrophoresis and Western blotting of brain homogenates. Furthermore, no co-immunoprecipitation of Sp1 and phospho-tau was observed in AD and PiD cases. Since Sp1 binding sites are present in the promoters of several genes involved in amyloid and tau, and Sp1 is regulated by oxidative stress, the present findings suggest that Sp1 deposition in hyper-phosphorylated tau deposits may have functional consequences in the pathology of AD and other tauopathies.

BetaII-tubulin and phospho-tau aggregates in Alzheimer's disease and Pick's disease.

The expression of betaI-, betaII- and betaIII-tubulin isotypes was examined by immunohistochemistry in the entorhinal and transentorhinal cortices, hippocampus and dentate gyrus in normal human brains and in cases with Alzheimer's disease (AD), Pick's disease (PiD) and in argyrophilic grain disease (AGD). The results showed that betaII-tubulin predominated in the upper layers (mainly layer II) and betaIII-tubulin in the inner layers of the entorhinal and transentorhinal cortices in control brains. betaII-tubulin immunoreactivity was higher than betaIII-tubulin immunoreactivity in granular neurons of the dentate gyrus, whereas pyramidal neurons of the hippocampus proper were stained equally with anti-betaII-tubulin andbetaIII-tubulin antibodies. No preferential layering distribution was observed for betaI-tubulin. Polymerization assays with tubulin peptides following the method of microtubule-associated protein displacement demonstrated that the betaI and betaIII isotypes have a higher binding capacity for tau than does the betaII isotype. Interestingly, about 60% of neurons with neurofibrillary tangles in layer II of the entorhinal and transentorhinal cortices in AD were selectively stained with anti-betaII-tubulin antibodies. Moderate betaII-tubulin immunoreactivity was also observed in Pick bodies in PiD. Taken together, these findings support the view that high betaII-tubulin content is a contributing factor in the formation of abnormal hyper-phosphorylated tau aggregates.

Current advances on different kinases involved in tau phosphorylation, and implications in Alzheimer's disease and tauopathies.

Hyperphosphorylation and accumulation of tau in neurons (and glial cells) is one the main pathologic hallmarks in Alzheimer's disease (AD) and other tauopathies, including Pick's disease (PiD), progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease and familial frontotemporal dementia and parkinsonism linked to chromosome 17 due to mutations in the tau gene (FTDP-17-tau). Hyperphosphorylation of tau is regulated by several kinases that phosphorylate specific sites of tau in vitro. GSK-3-immunoprecipitated sarcosyl-insoluble fractions in AD have the capacity to phosphorylate recombinant tau. In addition, GSK-3 phosphorylated at Ser9, that inactivates GSK-3, is found in the majority of neurons with neurofibrillary tangles and dystrophic neurites of senile plaques in AD, and in Pick bodies and other phospho-tau-containing neurons and glial cells in other tauopathies. Increased expression of active kinases, including stress-activated kinase, c-Jun N-terminal kinase (SAPK/JNK) and kinase p38 has been found in brain homogenates in all the tauopathies. Strong active SAPK/JNK and p38 immunoreactivity has been observed restricted to neurons and glial cells containing hyperphosphorylated tau, as well as in dystrophic neurites of senile plaques in AD. Moreover, SAPK/JNK- and p38-immunoprecipitated sub-cellular fractions enriched in abnormal hyperphosphorylated tau have the capacity to phosphorylate recombinant tau and c-Jun and ATF-2 which are specific substrates of SAPK/JNK and p38 in AD and PiD. Interestingly, increased expression of phosphorylated (active) SAPK/JNK and p38 and hyperphosphorylated tau containing neurites have been observed around betaA4 amyloid deposits in the brain of transgenic mice (Tg 2576) carrying the double APP Swedish mutation. These findings suggest that betaA4 amyloid has the capacity to trigger the activation of stress kinases which, in turn, phosphorylate tau in neurites surrounding amyloid deposits. Complementary findings have been reported from the autopsy of two AD patients who participated in an amyloid-beta immunization trial and died during the course of immunization-induced encephalitis. The neuropathological examination of the brain showed massive focal reduction of amyloid plaques but not of neurofibrillary degeneration. Activation of SAPK/JNK and p38 were reduced together with decreased tau hyperphosphorylation of aberrant neurites in association with decreased amyloid plaques in both Tg2576 mice and human brains. These findings support the amyloid cascade hypothesis of tau phosphorylation mediated by stress kinases in dystrophic neurites of senile plaques but not that of neurofibrillary tangles and neuropil threads in AD.

A novel mutation (K317M) in the MAPT gene causes FTDP and motor neuron disease.

BACKGROUND: Frontotemporal dementia with parkinsonism is often linked to chromosome 17 and is related to mutations in the MAPT gene. In some families the genetic basis is still unknown. The authors report two pedigrees with FTDP-17 harboring a novel mutation (K317M) in exon 11 in the MAPT gene. METHODS: The authors identified two apparently unrelated pedigrees with an autosomal dominant neurodegenerative condition. Thirteen patients were examined and eight autopsies were performed. RESULTS: Mean age at onset was 48 years. Mean disease duration was 6 years. Dysarthria often heralded the disease. All cases had parkinsonism and pyramidalism and half of them had amyotrophy. Behavioral or personality changes were not a prominent feature. Cognitive decline appeared late in the evolution. Neuropathologically, a massive degeneration of the substantia nigra without Lewy bodies was a constant finding. A variable degree of frontotemporal atrophy was found. Corticospinal tract degeneration and anterior horn neuron loss were present in six of seven autopsies in which the spinal cord was examined. An extensive deposition of abnormal tau protein in a mixed pattern (neuronal, glial) was observed. Pick's bodies were not seen. Biochemical analysis of tau revealed two bands of 64 and 68 kDa. CONCLUSION: Genetic analysis revealed the same novel mutation (K317M) in exon 11 of the MAPT gene in both pedigrees. A common haplotype between members of the two pedigrees suggests that they belong to the same family.

Metabotropic glutamate receptor/phospholipase C pathway: a vulnerable target to Creutzfeldt-Jakob disease in the cerebral cortex.

Glutamate is the main excitatory neurotransmitter in the cerebral cortex. Altered glutamatergic transmission has been suggested as having a central role in many neurodegenerative diseases. Metabotropic glutamate receptors (mGluRs) are coupled to intracellular signal transduction via G proteins, and they mediate slower responses than ionotropic glutamate receptors. Group I mGluRs are positively coupled to phospholipase C beta1 (PLCbeta1). Creutzfeldt-Jakob disease (CJD) is a human transmissible spongiform encephalopathy associated with a dysfunction in the membrane glycoprotein PrP which is converted into an abnormal isoform, with a predominant beta-sheet structure, that is pathogenic and partially resistant to protease digestion. Proteins associated with the signal transduction of group I mGluRs were examined in the frontal cortex (area 8) of 12 cases with sCJD and four age-matched controls, by means of gel electrophoresis and Western blotting of total homogenates. Densitometric analysis of the bands demonstrated decreased expression levels of PLCbeta1 and PLCgamma, a non-related phospholipase which is a substrate of tyrosine kinase, in CJD cases when compared with controls. Novel protein kinase C delta (nPKCdelta) has also been found to be significantly decreased in CJD cases. However, no modifications in mGluR1 cPKCalpha expression levels are found in CJD when compared with controls. No modifications in PLCbeta1 solubility in PBS-, deoxycholate- and sodium dodecylsulphate-soluble fractions have been observed in CJD when compared with controls. Finally, no interactions between PLCbeta1 and PrP, as revealed by immunoprecipitation assays, have been found in CJD and controls. The present results show, for the first time, reduced expression levels of phospholipases, particularly PLCbeta1, which may interfere with group I mGluR signaling in the cerebral cortex in CJD. These abnormalities are not the result of abnormal PLC solubility or interactions with PrP. Selective involvement of group I mGluRs may have functional effects on glutamatergic transmission modulation and processing in CJD.