c-Jun N-terminal kinase (JNK)-dependent internalization and Rab5-dependent endocytic sorting mediate long-distance retrograde neuronal death induced by axonal BDNF-p75 signaling.

During the development of the sympathetic nervous system, signals from tropomyosin-related kinase receptors (Trks) and p75 neurotrophin receptors (p75) compete to regulate survival and connectivity. During this process, nerve growth factor (NGF)- TrkA signaling in axons communicates NGF-mediated trophic responses in signaling endosomes. Whether axonal p75 signaling contributes to neuronal death and how signaling endosomes contribute to p75 signaling has not been established. Using compartmentalized sympathetic neuronal cultures (CSCGs) as a model, we observed that the addition of BDNF to axons increased the transport of p75 and induced death of sympathetic neurons in a dynein-dependent manner. In cell bodies, internalization of p75 required the activity of JNK, a downstream kinase mediating p75 death signaling in neurons. Additionally, the activity of Rab5, the key GTPase regulating early endosomes, was required for p75 death signaling. In axons, JNK and Rab5 were required for retrograde transport and death signaling mediated by axonal BDNF-p75 in CSCGs. JNK was also required for the proper axonal transport of p75-positive endosomes. Thus, our findings provide evidence that the activation of JNK by p75 in cell bodies and axons is required for internalization to a Rab5-positive signaling endosome and the further propagation of p75-dependent neuronal death signals.

Food protein-induced enterocolitis syndrome by fish: Not necessarily a restricted diet.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food hypersensitivity usually due to cow's milk or soy. Recent researches show that fish is 1 of the most important triggers of FPIES in the Mediterranean countries. Due to the risk of multiple-food FPIES, avoiding foods in the same category or that often occur together may be reasonable. The aim of this study was to evaluate the evolution and follow-up of FPIES related to fish over a period of 20 years. We describe the clinical features of our population, discuss different approaches to oral food challenges, and analyze the possibility of introducing the culprit fish or other nonrelated fish to avoid unnecessary restricted diets.

Interacciones farmacológicas de las hojas de Maytenus macrocarpa o ôchuchuhuasiõ con fármacos inhibitorios y estimuladores de la motilidad intestinal / Pharmacological interactions from the leaves of Maytenus macrocarpa \"chuchuhuasi\" with inhibitory and stimulating bowel motility drugs

Objetivo: Determinar las posibles interacciones farmacológicas de las hojas de Maytenus macrocarpa, con fármacos estimulantes e inhibitorios de la motilidad intestinal. Métodos: Se utilizaron 110 ratones albinos machos, con pesos medios de 25 g, se empleó el método de Arbos y col, se administró carbón activado al 5

vía oral, dosis de 0.1ml/10g, como marcador intestinal. Los grupos experimentales fueron: control (agua destilada 0,3ml), hojas de chuchuhuasi 1 (500mg/kg), hojas de chuchuhuasi 2 (3000mg/kg), atropina (1,5mg/kg), loperamida (5mg/kg), neostigmina (0,4mg/kg), metoclopramida (10mg/kg), hojas de chuchuhuasi 1 con metoclopramida, hojas de chuchuhuasi 1 con loperamida, hojas de chuchuhuasi 2 con metoclopramida y hojas de chuchuhuasi 2 con loperamida. Para la validación estadística se usó la prueba de Wilconxon, ANOVA y Tukey. Resultados: El porcentaje de recorrido intestinal de carbón activado fue de 27,04, 34,15, 31,66, 25,57, 15,89, 43,30, 33,99, 32,40, 27,90, 49,34 y 25,36 respectivamente, el test de ANOVA de dos colas revelo una p=0,0007. El test de Tukey indico p<0.05 versus el control para neostigmina, loperamida y la interacción chuchuhuasi 3000 mg/kg con metoclopramida, en este último, el test de Wilconxon presento un valor p<0,05. Conclusiones: Se observó interacciones farmacológicas de antagonismo sobre la motilidad intestinal, entre chuchuhuasi y Loperamida y sinergismo entre chuchuhuasi y metoclopramida.

Objectives: To determine the possible pharmacological interactions from the leaves of Maytenus macrocarpa with inhibitory and stimulating bowel motility drugs. Methods: We used 110 male albino mice with average weight of 25g, Arbos and others method was applied. Activated charcoal was administered at 5

at dose of 0.1ml/10g, as an intestinal marker. The experimental groups included 0.1 ml/10 g of distilled water, leave extract of M. macrocarpa 1 (500mg/kg), leave extract of M. macrocarpa 2 (3000 mg/kg), 1,5mg/kg of atropine, 5mg/kg of loperamide, 0.4mg/kg of neostigmine, 10mg/kg of metoclopramide, leave extract of M. macrocarpa 1 with metoclopramide, leave extract of M. macrocarpa 1 with loperamide, leave extract of M. macrocarpa 2 with metoclopramide and leave extract of M. macrocarpa 2 with loperamide. The statistical validation was based on Wilconxon, ANOVA and Tukey test. Results: The intestinal charcoal run percentage was 27.04, 34.15, 31.66, 25.57, 15.89, 43.30, 33.99, 32.40, 27.9, 49.34 and 25.36 respectively. The ANOVA test result in p= 0.0007. The Tukey test indicated p <0.05 versus the control group for neostigmine, loperamide, and the interaction between leave extract of M. macrocarpa 2 with metoclopramide, for the last the Wilcoxon test result in p <0.05. Conclusions: It was observed antagonism drug interactions on gastrointestinal motility between leaves extract of M. macrocarpa with loperamide and synergism interactions with metoclopramide.

Asociación de la deficiencia de cinc con factores inmunológicos y clínicos / Association between zinc deficiency and immunological and clinical factors

INTRODUCCIÓN: El cinc es un elemento imprescindible para el buen funcionamiento del organismo en todas las etapas de la vida, tanto para la síntesis celular, la reparación de tejidos y el desarrollo cerebral como para el crecimiento. Es cofactor de numerosas enzimas (lactato deshidrogenasa, fosfatasa alcalina, anhidrasa carbónica, carboxipeptidasa, SOD, etc.), siendo muy importante para el funcionamiento de la próstata, desarrollo de los órganos de reproducción, para buen funcionamientode la retina, y está involucrado en la regeneración de rodopsina. El sistema inmune requiere de Zn y es necesario para el mantenimiento de la integridad estructural del ADN y la síntesis de ácidos nucleicos y proteínas. OBJETIVO: El objetivo es estudiar el estado nutricional del cinc en una población sana y establecer la relación con otros factores como ejercicio físico, consumo de alcohol, y otros parámetros bioquímicos como GOT, FA, CPK, ASLO Inmunoglobulina G, Inmunoglobulina A, Alfa 1 anti tripsina, LDH, factor reumatoide. METODOLOGÍA: El estudio se realizó en un colectivo de personas de 21 a 59 años, 56 hombres y 61mujeres. Los criterios de inclusión se basaron en la aceptación de los sujetos a participar en el estudio y en que dichos sujetos no presentaran ningún tipo de patología que pudiera afectar su situación nutricional. El Zn se analizó mediante Espectrofotometría de Absorción Atómica (AAS) en muestras de eritrocitos y plasma mineralizadas por vía húmeda. Se aplicó un cuestionario de frecuencia de consumo, y mediante programa informático Nutriber® (Mataix, y Garcia Diz, 2006) se obtuvo el % RDA. Se contó con la aceptación del Comité ético y el consentimiento informado. Los parámetros clínicos analizados se determinaron en un equipo autoanalizador Hitachi mediante método colorimétrico(AU)

RESULTADOS: La recomendación de ingesta de Zn en la población adulta es de 7 a 15 mg/d. Nuestros resultados muestran una ingesta de Zn por debajo de los 2/3 de las RDA en un 56% de los individuos estudiados. En plasma, aparece deficiencia de Zn en el 17%, y en eritrocitos en un 35%. Se encontró una correlación significativa positiva entre los niveles de Zn y el consumo de alcohol, los niveles de GOT, FA, CPK, ASLO, IgG, IgA y α-1-Antitripsina, y negativa con la intensidad de ejercicio, LDH y factor reumatoide CONCLUSIÓN: según los resultados obtenidos, se hace necesario controlar tanto la ingesta como los niveles plasmáticos y eritrocitarios de Zn para que la población no sufra carencias en este mineral que derivan en el desarrollo de numerosas enfermedades, tal y como se demuestra con las asociaciones encontradas con los parámetros clínicos inmunológicos y enzimáticos que afectan a la integridad celular(AU)

INTRODUCTION: Zinc is an essential element for the proper functioning of the body at all stages of life, both for cell synthesis, tissue repair and brain development to growth. Cofactor of numerous enzymes (lactate dehydrogenase, alkaline phosphatase, carbonic anhydrase, carboxypeptidase, SOD, etc.), being very important for the functioning of the prostate, development of reproductive organs for proper functioning of the retina, and is involved in the regeneration of rhodopsin. The immune system requires Zn and is necessary for maintaining the structural integrity of DNA and the synthesis of nucleic acids and proteins. OBJECTIVE: The objective is to study the nutritional status of zinc in a healthy population and establish relationship with other factors such as exercise, alcohol consumption, and other biochemical parameters such as GOT, ALP, CPK, ALSO immunoglobulin G, immunoglobulin A, alpha 1antitrypsin, lactate dehydrogenase, rheumatoid factor. METHODS: The study was conducted in a group of people from 21 to 59 years, 56 men and 61women. Inclusion criteria were based on the acceptance of subjects to participate in the study and that these subjects did not display any pathology that could affect their nutritional status. Zn was analyzed by Atomic Absorption Spectrometry (AAS) in blood cells and plasma samples mineralized by wet. We applied a food frequency questionnaire, and through software Nutriben (Mataix, and Garcia Diz, 2006) won the% RDA. It was accepted by the Ethics Committee and informed consent. The clinical parameters analyzed were determined on a computer Hitachi autoanalyzer using a colorimetric method. RESULTS: The recommended intake of Zn in the adult population is 7 to 15 mg/d. Our results show that Zn intake below 2 / 3 of the RDA in 56% of individuals studied. In plasma, Zn deficiency occursin 17%. There was a significant positive correlation between Zn levels and alcohol consumption, levels of GOT, ALP, CPK, ASO, Immunogen, Inmuno A and alpha-1-antitrypsin, and negative with exercise intensity, LDH and rheumatoid factor CONCLUSION: According to the results, it is necessary to control both the intake and plasma and cellular levels of Zn for the population are deficient in this mineral that lead to the development of numerous diseases, as demonstrated by the association found with immunological and clinical parameters that affect enzymatic cell integrity (AU)

Deficiencia de cobre en un colectivo y factores asociados / Copper deficiency in a collective and associated factors

INTRODUCCIÓN: El cobre ejerce un papel esencial como nutriente en el organismo, se necesita un aporte diario mínimo a partir de alimentos o suplementos para el buen funcionamiento de la actividad celular. Está presente en todos los tejidos y participa activamente en la síntesis de la hemoglobina e influye sobre la absorción del hierro. Su deficiencia provoca anemia, diarrea, debilidad generalizada, alteraciones respiratorias y lesión cutánea, teniendo un papel esencial como protector frente el estrés oxidativo, un importante papel en el sistema inmunológico y una gran influencia sobre la expresión de numerosos genes. OBJETIVO: Valorar el estatus de cobre en un grupo de personas adultas sanas procedente de un colectivo de personas sanas adultas, estableciéndose tanto los niveles de ingesta como los niveles plasmáticos y eritrocitarios de este mineral, y estudiando una posible relación con otros parámetros. METODOLOGÍA: El estudio se realizó en una muestra de 90 sujetos de edades comprendidas entre 21 y 59 años (31 hombres y 53 mujeres), todos de la provincia de Granada. El criterio de inclusión se basó en la aceptación de los sujetos a participar en el estudio y no presentar ningún tipo de patología que pudiera afectar su situación clínico-nutricional. El Cu se analizó mediante Espectrofotometría de Absorción Atómica (AAS) en muestras de eritrocito y plasma mineralizadas por vía húmeda. Se aplicó un cuestionario de frecuencia de consumo, y mediante programa informático Nutriber (Mataix, yGarcia Diz 2006)1 se obtuvo el % de RDA. Se contó con la aceptación del Comité ético y el consentimiento informado(AU)

RESULTADOS: La ingesta media recomendada de cobre en la población adulta española es de 1,1mg/día. Los resultados obtenidos muestran ingestas del cobre <2/3 de IR en un 58,2% de la población estudiada, de los cuales el 53,6% son hombres y el 60,8% son mujeres. En plasma, se observaron valores deficientes en cobre en el 25% de la población total, siendo el 29% hombres y el 22,6 % mujeres. En eritrocito, el 21,4% de la población general presentaron deficiencia de cobre, siendo el 28,8% hombres y el 18,9% mujeres. Se encontró una correlación significativa positiva entre la ingesta de macronutrientes y los niveles de cobre en ingesta, así como entre la ingesta de cobre y la de hierro, cinc, magnesio, calcio y selenio. Igualmente, se observa una correlación positiva significativa entre los niveles de cobre en plasma y los niveles de cinc (p<0,02). CONCLUSIÓN: Según los resultados obtenidos, podemos concluir que son necesarios estudios recientes y detallados que aborden la valoración del estatus de cobre de una manera más integral, desde una evaluación pormenorizada de la ingesta hasta la determinación de biomarcadores específicos de cobre, teniendo en cuenta su participación en numerosas reacciones biológicas celulares que pueden alterarse por la deficiencia(AU)

INTRODUCTION: The copper has a crucial role as a nutrient in the body, you need a minimum daily intake from food or supplements for the proper functioning of cellular activity. Is present in all tissues and is actively involved in the synthesis of hemoglobin and influences iron absorption. Deficiency causes anemia, diarrhea, general weakness, respiratory and skin lesion, having an essential role as a protector against oxidative stress, an important role in the immune system and a great influence on the expression of numerous genes. OBJECTIVE: To assess copper status in a group of healthy adults from a group of healthy adults, establishing both the levels of intake and plasma and erythrocyte levels of this mineral, and isexploring a possible relationship with other parameters. METHOD: The study was conducted in a sample of 90 subjects aged between 21 and 59 years (31 men and 53 women), all of the province of Granada. The inclusion criteria was based on the acceptance of individuals to participate in the study and did not show any pathology that could affect clinical and nutritional status. Cu was analyzed by Atomic Absorption Spectrometry (AAS) in erythrocytes and plasma samples mineralized by wet. We applied a food frequency questionnaire, and through software Nutriben (Mataix, and Garcia Diz 2006)1 was obtained by the% of RDA. It was accepted by the Ethics Committee and informed consent(AU)

RESULTS: The average recommended intake of copper in the Spanish adult population is 1.1 mg /day. The results show copper intakes <2 / 3 of IR in 58'2% of the population studied, of which 53'6% are men and women 60'8%. In plasma, were found deficient in copper values in 25% of the total population, being 29% male and 22.6% women. In erythrocytes, 21.4% of the general population showed copper deficiency, with 28.8% men and 18.9% women. There was a significant positive correlation between macronutrient intake and levels of copper intake, as well as between dietary copper and iron, zinc, magnesium, calcium and selenium. Similarly, there is a significant positive correlation between plasma copper levels and zinc levels (p <0.02). CONCLUSION: According to the results, we conclude that studies are needed to address recent detailed assessment of copper status in a more comprehensive, since a thorough assessment of intake to the identification of specific biomarkers of copper, taking into account participation in numerous cellular biological reactions that may be altered by the deficiency(AU)

[Chronic progressive external ophthalmoplegia: clinical and electromyographic manifestations in a series of cases]. / Oftalmoplejía externa progresiva crónica: manifestaciones clínicas y electromiográficas en una serie de casos.

INTRODUCTION: Chronic progressive external ophthalmoplegia (CPEO) is a common mitochondrial disease. The different conditions in this group of diseases overlap clinically, enzymatically and genetically. There is no effective treatment. Ptosis improves with corrective surgery involving tarsorrhaphy as a palliative measure. CASE REPORTS: Code numbers were examined in a retrospective study conducted in order to search for patients with ptosis or ophthalmoplegia who had either visited or been admitted to the neurology department over the last 10 years. Data concerning these patients' clinical features and results of complementary tests were collected. Six patients with CPEO were identified, five of whom were females. Ages ranged from 44 to 72 years. All the patients had ptosis, although 50% were asymmetric. Half of them reported mild dysphagia while swallowing liquids. Levels of creatine phosphokinase and acetylcholine antireceptor antibodies were normal. Half the patients showed increased jitter and a muscle biopsy revealed that five of them had ragged red fibres. The most frequent enzyme deficit was complex I and IV deficiency. There were no familial forms; the most common genetic anomaly was single deletion in the mitochondrial deoxyribonucleic acid. CONCLUSIONS: In cases of ptosis and ophthalmoplegia that do not respond to anticholinesterases, knowledge of this condition makes it possible to avoid the use of immunosuppressant drugs, which have important side effects.

Oftalmoplejía externa progresiva crónica: manifestaciones clínicas y electromiográficas en una serie de casos / Chronic progressive external ophthalmoplegia: clinical and electromyographic manifestations in a series of cases

Introducción. La oftalmoplejía externa progresiva crónica(CPEO) es una enfermedad mitocondrial común. Este grupode enfermedades presenta solapamiento clínico, enzimático y genéticoentre las diferentes entidades. No existe un tratamiento eficaz.La ptosis mejora con cirugía correctora de tarsorrafia comouna medida paliativa. Casos clínicos. Estudio retrospectivo en elque se busca por codificación a pacientes con ptosis u oftalmoplejíaen consultas o ingresados en neurología durante los últimos 10años. Se recogieron datos de la clínica y pruebas complementariasde estos pacientes. Se identificó a seis pacientes con CPEO; cincode ellos fueron mujeres. Sus edades estaban comprendidas entrelos 44 y los 72 años. Todos los pacientes presentaban ptosis, aunqueel 50% era asimétrica. La mitad refería disfagia leve paralíquidos. Los niveles de creatinfosfocinasa y de anticuerpos antirreceptoresde acetilcolina fueron normales. Existía un aumentodel jitter en la mitad de los pacientes y fibras rojas rasgadas en labiopsia muscular de cinco de ellos. El déficit enzimático más frecuentefue el de los complejos I y IV. No existieron formas familiares;la anomalía genética más común fue la deleción única en elácido desoxirribonucleico mitocondrial. Conclusión. El conocimientode esta entidad permite, en casos de ptosis y oftalmoplejíaque no responden a anticolinesterásicos, evitar el uso de medicacionesinmunosupresoras con efectos secundarios importantes

Introduction. Chronic progressive external ophthalmoplegia (CPEO) is a common mitochondrial disease. Thedifferent conditions in this group of diseases overlap clinically, enzymatically and genetically. There is no effective treatment.Ptosis improves with corrective surgery involving tarsorrhaphy as a palliative measure. Case reports. Code numbers wereexamined in a retrospective study conducted in order to search for patients with ptosis or ophthalmoplegia who had eithervisited or been admitted to the neurology department over the last 10 years. Data concerning these patients' clinical featuresand results of complementary tests were collected. Six patients with CPEO were identified, five of whom were females. Agesranged from 44 to 72 years. All the patients had ptosis, although 50% were asymmetric. Half of them reported mild dysphagiawhile swallowing liquids. Levels of creatine phosphokinase and acetylcholine antireceptor antibodies were normal. Half thepatients showed increased jitter and a muscle biopsy revealed that five of them had ragged red fibres. The most frequentenzyme deficit was complex I and IV deficiency. There were no familial forms; the most common genetic anomaly was singledeletion in the mitochondrial deoxyribonucleic acid. Conclusions. In cases of ptosis and ophthalmoplegia that do not respondto anticholinesterases, knowledge of this condition makes it possible to avoid the use of immunosuppressant drugs, which haveimportant side effects

First seizure in adults: a prospective study from the emergency department.

A prospective study of 98 consecutive adults with a first seizure to determine the most important etiological factors and the optimum diagnostics. 27 were thought to have cryptogenic seizures. Main causes of symptomatic seizures were: cerebral infarction, alcohol-withdrawal, CNS infections, tumors, vascular malformations, traumatism and miscellanea. Eight were infected by human immunodeficiency virus (HIV-1) representing 8.2% of all the patients with a first seizure and 20% of the 15-45-year age group. CT disclosed structural lesions in 33 cases. MRI in those with normal CT and no other explanation of seizure revealed additional lesions in 22.2%, but did not change management in any. We conclude that CT is essential in evaluation of adults with first seizure. MRI may be useful in selected cases. The HIV-infected now represent an important group with a first seizure.

A fluorometric method for the determination of triglycerides in nanomolar quantities.

A fluorometric assay for triglycerides in nanomole quantities is described. Glycerol is liberated from triglycerides with lipase from Chromobacter viscosum, then converted by glycerol kinase to glycerol-3-phosphate, which is oxidized by glycerol-3-phosphate oxidase, producing H2O2. The H2O2 ultimately forms a peroxidase-catalyzed fluorogen with p-hydroxyphenylacetic acid. The excitation and emission wavelengths of the fluorogen are 325 and 415 nm, respectively. The assay is linear in the range 0.05-35 nmol of triglycerides using triolein as standard.

Sudden hearing loss in divers and fliers.

Many papers have been written about sudden sensory hearing loss and the effect of barotrauma on the inner ear. Fistulae of the round and oval window membranes have been implicated in the great majority of these cases. It has usually been recommended that the patient be treated with conservative therapy, such as bed rest, for a period of as long as 30 days and that the final hearing results are as good or better than those that have been surgically explored and corrected. In our experience immediate surgical exploration and correction of sudden severe or profound sensorineural deafness in the diver or flier is absolutely essential and the excellent results of hearing improvement in this select group certainly corroborates this theory. Other cases with the hearing loss limited to the high frequencies most notably have tinnitus and surgical exploration does not improve the hearing but may improve vertigo if present. Numerous cases are presented to support these supositions.