As and S speciation in a submarine sulfide mine tailings deposit and its environmental significance: The study case of Portmán Bay (SE Spain).

The dumping of an estimated amount of 57 million tons of hazardous sulfide mine waste from 1957 to 1990 into Portmán's Bay (SE Spain) caused one of the most severe cases of persistent anthropogenic impact in Europe's costal and marine environments. The resulting mine tailings deposit completely infilled Portmán's Bay and extended seawards on the continental shelf, bearing high levels of metals and As. The present work, where Synchrotron XAS, XRF core scanner and other data are combined, reveals the simultaneous presence of arsenopyrite (FeAsS), scorodite (FeAsO4·2H2O), orpiment (As2S3) and realgar (AsS) in the submarine extension of the mine tailings deposit. In addition to arsenopyrite weathering and scorodite formation, the, the presence of realgar and orpiment is discussed, considering both potential sourcing from the exploited ores and in situ precipitation from a combination of inorganic and biologically mediated geochemical processes. Whereas the formation of scorodite relates to the oxidation of arsenopyrite, we hypothesize that the presence of orpiment and realgar is associated to scorodite dissolution and subsequent precipitation of these two minerals within the mine tailings deposit under moderately reducing conditions. The occurrence of organic debris and reduced organic sulfur compounds evidences the activity of sulfate-reducing bacteria (SRB) and provides a plausible explanation to the reactions leading to the formation of authigenic realgar and orpiment. The precipitation of these two minerals in the mine tailings, according to our hypothesis, has important consequences for As mobility since this process would reduce the release of As into the surrounding environment. Our work provides for the first time valuable hints on As speciation in a massive submarine sulfide mine tailings deposit, which is highly relevant for similar situations worldwide.

Calibrating high resolution XRF core scanner data to obtain absolute metal concentrations in highly polluted marine deposits after two case studies off Portmán Bay and Barcelona, Spain.

X-ray fluorescence core scanners (XRF-CS) allow rapid, non-destructive, continuous and high-resolution analyses of the elemental composition of sediment cores, providing large sets of semi-quantitative data. These data can be converted to quantitative data through the linear regression approach using a relatively small number of discrete samples analyzed by techniques providing absolute concentrations. However, a precise characterization of the errors associated with the linear function is required to evaluate the quality of the calibrated element concentrations. Here we present a calibration of high-resolution XRF-CS for six metals (Ti, Mn, Fe, Zn, Pb and As) measured in heavily contaminated marine deposits so that absolute concentrations are obtained. In order to determine the best linear function for conversion of XRF data, we have tested three regression methods: the ordinary least-squares (OLS), which does not consider the standard error in any variable (x and y), the weighted ordinary least-squares (WOLS), which considers the weighted standard error of the vertical variable (y), and the weighted least-squares (WLS), which incorporates the standard error in both x and y variables. We demonstrate that the calibration method presented in this study significantly increases the correlation coefficient, higher than r2 = 0.94, and reduces both the data deviation and the errors of the linear function for the three regression methods. Nonetheless, the WLS appears as the best regression method to minimize errors in the calibrated element concentrations. Our results open the door to use calibrated XRF-CS data to evaluate marine sediment pollution according to the levels of the strictest sediment quality guidelines (SQG) with errors lower than 0.4%-2% for Fe, 1%-7% for Zn, 3-14% for Pb and 5%-16% for Mn. They highlight the robustness of the calibration procedure here presented for accurate and precise quantification of element concentrations from XRF-CS semi-quantitative data.

X-ray microtomographic characterization of highly rough titanium cold gas sprayed coating for identification of effective surfaces for osseointegration.

A highly rough titanium coating obtained by Cold Gas Spray (CGS) has been characterized by means of high-resolution 3D microtomography (micro-CT) with the aim to evaluate its open and close porosity for possible use in orthopaedic implants to promote osseointegration. Micro-CT allowed a qualitative and quantitative description of the main features, morphology of the pores and surface roughness of the coating. Several numerical values were obtained to describe size, form and distribution of the closed/inner and open/outer pores. Additionally, surface roughness and open porosity were image-analyzed to find the effective surface for osseointegration.

Síndrome de Guillain-Barré / Guillain-Barre Syndrome

No disponible

Enantioseparation of basic pharmaceutical compounds by capillary electrophoresis using sulfated cyclodextrins. Application to E-6006, a novel antidepressant.

In this study, a chiral capillary electrophoresis method was optimized and validated for E-6006, a thienylpyrazolylethanamine derivative (pKa 8.9). Enantioselectivity of neutral and anionic cyclodextrins (CDs) was evaluated at acid pH (3), obtaining cathodic and anodic migration, respectively. Hydroxypropyl-beta-CD, carboxymethyl-beta-CD and sulfobutyl ether-beta-CD led to similar and partial selectivity, whereas sulfate (S)-beta-CD produced baseline separation of the enantiomers. Four types of sulfated CDs were compared considering: cavity size (alpha, beta, gamma) and random substitution versus unique derivative (S-beta-CD, 6-heptakis-S-beta-CD). Complete peak separation was obtained in all cases, but with different affinity and binding strength. Some factors that play a role in the complex formation include: position/region/degree of substitution, size of CD cavity and proportion of derivatives in mixtures. Enantioaffinity and enantioselectivity increased with the average of sulfate groups/mol. Beta cavity size complexed better, although alpha and gamma cavities did not compromise separation. 6-Heptakis-S-beta-CD had less affinity and separation efficiency, attributed to its lower degree and unique position of substitution. The method was optimized with S-beta-CD (Aldrich, randomly substituted, 7-11 groups/mol). With this selector, the effect of pH value (3-9) was evaluated. Around pH 7 the cross-over point with change in the direction and order of migration was observed, associated with great enantioselectivity and long migration times. Fine tuning was done by adjusting the CD concentration and the buffer counterion. Definitive conditions were: uncoated silica capillary, 10 mM S-beta-CD-25 mM sodium phosphate, pH 3. Validation parameters are included.

Síndrome de West: factores etiológicos / West syndrome: etiological factors

Introducción: El síndrome de West (SW) se caracteriza por la presencia de espasmos en salvas, trazado electroencefalográfico hipsarrítmico y detención o regresión en el desarrollo psicomotor. El objetivo de este estudio es conocer la distribución etiológica del SW en nuestro medio y su evolución en el tiempo. Método: Estudio retrospectivo de 20 niños diagnosticados de SW entre 1993 y 2001. Se analizan las causas y se describen los métodos diagnósticos empleados, tratamiento y evolución. Se comparan los resultados con otro estudio realizado entre 1975 y 1986 en el mismo hospital. Resultados: Relación varón:mujer de 1,5:1. La edad media al comenzar los espasmos fue de 7,4 meses (rango 2-14 meses), con una demora hasta el diagnóstico igual o superior al mes en el 60 por ciento de los casos. Se identificaron 16 casos sintomáticos (11 de origen prenatal, 4 perinatal y 1 postnatal), 3 criptogénicos y 1 idiopático. La hipsarritmia y los espasmos desaparecieron en todos los pacientes, pero en la mitad de los casos sintomáticos persistieron otros tipos de crisis. Se registraron 3 exitus, todos sintomáticos. La proporción de casos sintomáticos fue significativamente mayor en el período 1993-2001 (16/20, 80 por ciento) respecto a 1975-1986 (15/30, 50 por ciento). Conclusiones: Las nuevas tecnologías permiten identificar como sintomáticos una mayor proporción de pacientes con SW. Persiste una importante demora en el diagnóstico por la confusión de los 'espasmos' con otros episodios paroxísticos no epilépticos. Ante la sospecha clínica debe practicarse un electroencefalograma con urgencia para confirmar o descartar hipsarritmia. Las lesiones preexistentes condicionan la evolución de los SW sintomáticos (AU)

[Epilepsy and sleep as seen on video encephalographic recordings]. / Epilepsia y sueño a través de la evidencia del registro vídeo-EEG

INTRODUCTION: The relation between epilepsy and sleep has been known for some time. Seizures are often not observed by the examiner and it is necessary to make prolonged recordings during sleep, both slow or no REM sleep and paradoxical or REM sleep. Objective. To show the way in which a video recording may be made of a patient s seizures, together with an electroencephalogram recorded on a suitable disk and both sets of data be synchronised and studied as often as necessary. PATIENTS AND METHODS: We describe some of the epileptic seizures, recorded by this technique, during sleep. At the same time we show other paroxystic non epileptic episodes occurring during sleep which may be needed to be ruled out of the differential diagnosis. CONCLUSIONS: We show that as a general rule the basic activity of paroxystic disorders seen on an electroencephalogram occurs during slow sleep phases and particularly during their early stages. These studies are especially relevant in children and in neonates a prolonged recording is essential

Epilepsia y sueño a través de la evidencia del registro vídeo-EEG / Epilepsy and sleep as seen on video-encephalographic recordings

Introducción. Desde hace tiempo es conocida la relación existente entre la epilepsia y el sueño. En muchas ocasiones los episodios críticos pasan desapercibidos al ojo del explorador, y es necesario realizar trazados de larga duración durante las etapas de sueño, tanto en las fases de sueño lento o no REM, como en las de sueño paradójico o REM. Objetivo. Destacar la forma en que podemos recoger en una cinta de vídeo las crisis del enfermo y en un disco adecuado el trazado electro-encefalográfico y que podamos sincronizar ambos datos para repetirlos cuantas veces consideremos oportuno. Pacientes y métodos. Describimos algunos tipos de crisis epilépticas obtenidas durante el sueño con esta técnica de registro. Al mismo tiempo mostramos otros tipos de episodios paroxísticos no epilépticos que acontecen también en el sueño y que precisan de un diagnóstico de exclusión. Conclusiones. Señalamos como regla general que la activación fundamental de los paroxismos en el electroencefalograma ocurren durante las fases de sueño lento y muy especialmente en los primeros periodos de dicho sueño. En los niños estos estudios adquieren especial relevancia y en los neonatos se hace del todo imprescindible un registro de larga duración (AU)

Simultaneous separation of the enantiomers of cizolirtine and its degradation products by capillary electrophoresis.

The simultaneous enantioselective separation of (+/-)-cizolirtine and its impurities: (+/-)-N-desmethylcizolirtine, (+/-)-cizolirtine-N-oxide and (+/- )-5-(alpha-hydroxybenzyl)-1-methylpyrazole was investigated by capillary electrophoresis. Electrokinetic chromatography with carboxymethyl-beta-CD (CM-beta-CD) and sulfobutyl-ether-beta-CD was tried, showing good enantioseparation but poor chemical selectivity. The four racemic pairs were baseline separated, in a single run, by cyclodextrin-modified micellar electrokinetic chromatography. The migration buffer composition was: (60 mM hydroxypropyl-beta-cyclodextrin-150 mM sodium dodecyl sulfate-50 mM disodium tetraborate, pH 9.2, in water)-butanol 95:5, v/v). Work was done to determine the effect of buffer components and their optimal concentration on selectivity. The method was validated with respect to enantioselectivity of cizolirtine as well as its degradation products and separation selectivity between the different components. Linearity, limit of detection, limit of quantitation and precision were also determined. This method is suitable for the enantiomeric purity determination and stability control of cizolirtine (racemic mixture or enantiomers) and its degradation products. Examples of electropherograms of (R)-cizolirtine degraded under stressed conditions are shown.

Afasia epiléptica adquirida (síndrome de Landau-Kleffner) / Acquired epileptic aphasia (Launda-Kleffner syndrome)

Se describe el caso clínico de una niña de 5 años con ausencia total del lenguaje, hiperactividad y crisis paroxísticas compatibles con crisis epilépticas parciales complejas con automatismos orofaríngeos. En el EEG de vigilia se constataron puntas y complejos punta-onda bifrontales y, en el videoEEG durante sueño fisiológico, se objetivó actividad continua generalizada de complejos punta-onda, especialmente durante el sueño lento (fases III-IV), confirmando el diagnóstico de afasia epiléptica adquirida. En este síndrome se asocian la agnosia auditiva verbal y la epilepsia, confirmándose el diagnóstico con el hallazgo en el EEG de punta-onda continua durante más del 80 por ciento del sueño lento. La evolución es desfavorable, porque se asocian graves trastornos de la conducta y afectación cognitiva, y por la resistencia de este cuadro electroclínico a todo tipo de terapias. El interés de este caso clínico reside en confirmar la remisión espectacular de sus síntomas al asociar valproato y etosuximida, pauta terapéutica descrita por nosotros anteriormente (AU)

Epilepsia con punta-onda continua durante el sueño lento (EPOCS) / Epilepsy with continuous spike and waves in slow sleep (SPWSS)

El estatus eléctrico durante el sueño lento, es un cuadro electroclínico raro que se caracteriza por la asociación de varios tipos de crisis epilépticas, parciales o generalizadas casi siempre en el transcurso del sueño, así como por la existencia de ausencias atípicas en vigilia y un patrón electroencefalográfico formado por complejos punta-onda difusos y continuos, debiendo de ocupar por lo menos el 85 por ciento del trazado y que aparecen meses o años después de la primera crisis, es decir, debe de producirse durante el sueño un estado de mal eléctrico sin clínica acompañante. Se acompaña el cuadro de trastornos neuropsicológicos diversos que suelen regresar al igual que la desaparición de las crisis y la normalización del EEG entre los 8 y 15 años de edad. Describimos el caso de una niña que ingresa por sufrir una crisis convulsiva generalizad y en cuya evolución, se registran al inicio crisis parciales, crisis unilaterales y ausencias atípicas con anomalías tanto focales como generalizadas en el EEG y un status eléctrico con punta-onda continua y generalizada en el sueño que configura el diagnóstico de epilepsia con punta-onda continua durante sueño (EPOCS) (AU)

Pérdida de conciencia / Loss of consciousness

No disponible

[The use of oral amiodarone as a chronic treatment in a patient with prior fulminant hepatitis due to intravenous amiodarone]. / Uso de amiodarona oral como tratamiento crónico en un paciente con hepatitis fulminante previa por amiodarona intravenosa.

Acute hepatitis for intravenous amiodarone is an uncommon problem with scarce appearances in medical literature. Sometimes, it has postulated that the vehicle of the intravenous preparation and not the active principle is the possible cause of this complication. We report a patient with fulminating hepatitis and severe encephalopathy following the administration of intravenous amiodarone. We present also the clinical evolution of the patient after reintroduction of oral amiodarone. In the end, we make a review of the associated literature with our case.

Synthesis and structure-activity relationships of a new series of benzimidazoles as H1-antihistaminic agents.

New 2-(4-(4-azolylbutyl)piperazinyl)-, 2-(4-(4-azolylbutyl) piperazinylmethyl)-, 2-(4-(-azolylbutyl)homopiperazinyl)- and 2-(4-(4-azolylbutyl)homopiperazinylmethyl)benzimidazoles were synthesized, characterized and tested for in vitro and in vivo H1-antihistaminic activity. Structure-activity relationships implied that the best antihistaminic activity required the simultaneous presence of a homopiperazinylbenzimidazole system (or a methylene linker between the benzimidazole and the piperazine rings) and an unsubstituted pyrazole ring. 1-(2-Ethoxyethyl)-2-¿4-[4-(pyrazol-1-yl)butyl] homopiperazin-1-yl¿benzimidazole (17), as its dimaleate salt, has been chosen for further development.

[The effects of phenobarbital, valproic acid and carbamazepine on the serum lipids and lipoproteins in a pediatric population]. / Efectos del fenobarbital, ácido valproico y carbamazepina sobre lípidos y lipoproteínas séricas en población infanto-juvenil.

Lipids and serum lipoproteins were analyzed in 432 epileptic children younger than 14 years of age who received chronic treatment (more than 6 months) with anticonvulsive drugs: phenobarbital (n = 255), valproic acid (n = 92) and carbamazepine (n = 85). The children were grouped according to sex, age and the drug administered and compared with 490 healthy children from the same social environment. The biochemical findings significantly different (p < 0.05) from the control population were as follows: phenobarbital increased serum total cholesterol levels in females and high density lipoproteins in both sexes. Valproic acid raised serum A-II apoprotein levels in every group and serum C-HDL levels in the 6 to 13 year old male group. Treatment with carbamazepine raised serum total cholesterol levels, C-HDL, phospholipid and A-I apoprotein in all groups, low density lipoproteins in females and B apoprotein males. The total cholesterol/LDL ratio was significantly lower in the 6 to 13 year old male group with any of the drugs used when compared to the control population.

7-Azetidinylquinolones as antibacterial agents. 3. Synthesis, properties and structure-activity relationships of the stereoisomers containing a 7-(3-amino-2-methyl-1-azetidinyl) moiety.

A series of stereochemically pure 7-(3-amino-2-methyl-1-azetidinyl)-1,4- dihydro-6-fluoro-4-oxoquinoline- and -1,8-naphthyridine-3-carboxylic acids, with varied substituents at the 1-, 5-, and 8-positions, was prepared to determine the effects of chirality on potency and in vivo efficacy relative to the racemic mixtures (for part 2, see: J. Med. Chem. 1994, 37, 4195-4210). A series of chiral 9-fluoro-2,3-dihydro-3-methyl-7-oxo-10-(substituted-1- azetidinyl)-7H-pyrido[1,2,3- de]-1,4-benzoxazine-6-carboxylic acids was synthesized to study the effect of the azetidine moiety on tricyclic quinolone antibacterial agents. A series of amino acid prodrugs of chiral naphthyridines 24a and 24b and quinolone 33a (cetefloxacin) was prepared and evaluated for antibacterial activity, solubility, and pharmacokinetic behavior. The absolute configuration of the new azetidinylquinolones was established by X-ray analysis of one of the diastereomeric salts of the resolved azetidinols (15) and of compound 25a (E-4767), which showed the best in vitro and in vivo overall profile. Structure-activity relationship studies indicated that the absolute stereochemistry at the asymmetric centers of both the azetidine and the oxazine rings was critical to increase in vitro activity and oral efficacy. The 3S configuration in the pyridobenzoxazine series and the (2S,3R) configuration of the 3-amino-2-methylazetidine moiety for all new compounds conferred the best antibacterial activity.

Heterocyclic betaines. XXII. Azinium(azolium) 4-nitrobenzimidazolate inner salts and their derivatives with several interannular spacers. Synthesis, characterization and antitrichomonal activity.

The synthesis of an ensemble of pyridinium(imidazolium) 4-nitrobenzimidazolate betaines and their derivatives with several interannular linkages has been explored. Their antiprotozoal activity has also been examined.

7-azetidinylquinolones as antibacterial agents. 2. Synthesis and biological activity of 7-(2,3-disubstituted-1-azetidinyl)-4-oxoquinoline- and -1,8-naphthyridine-3-carboxylic acids. Properties and structure-activity relationships of quinolones with an azetidine moiety.

A series of 7-(2,3-disubstituted-1-azetidinyl)-1,4-dihydro-6-fluoro-4- oxoquinoline- and -1,8-naphthyridine-3-carboxylic acids, with varied substituents at the 1-, 5-, and 8-positions, was prepared to study the effects on potency and physicochemical properties of the substituent at position 2 of the azetidine moiety. The activity of the title compounds was determined in vitro against Gram-positive and Gram-negative bacteria, and the in vivo efficacy of selected derivatives was determined using a mouse infection model. The X-ray crystal structures of 6b, 6c, and 6d were found to be in reasonable agreement with the corresponding AM1 calculated geometries. Correlations between antibacterial potency of all the synthesized 7-azetidinylquinolones and naphthyridines and their calculated electronic properties and experimental capacity factors were established. Antibacterial efficacy and pharmacokinetic and physicochemical properties of selected derivatives were compared to the relevant 7-(3-amino-1-azetidinyl) and 7-(3-amino-3-methyl-1-azetidinyl) analogues (for Part 1, see: J. Med. Chem. 1993, 36, 801-810). A combination of a cyclopropyl or a substituted phenyl group at N-1 and a trans-3-amino-2-methyl-1-azetidinyl group at C-7 conferred the best overall antibacterial, pharmacokinetic, and physicochemical properties to the azetidinylquinolones studied.

7-Azetidinylquinolones as antibacterial agents. Synthesis and structure-activity relationships.

A series of novel antibacterial quinolones and naphthyridones has been prepared which contain 7-azetidinyl substituents in place of the usual piperazine or aminopyrrolidine groups. These azetidinyl derivatives were evaluated for in vitro activity by determining minimum inhibitory concentrations against a variety of bacteria. In vivo efficacy in the mouse infection model and blood levels in the mouse were determined for several compounds. The influence on the structure-activity relationships of varying substituents in the azetidine ring and at position 8 (CH, CF, CCl, N) and N-1 (ethyl, fluoroethyl, cyclopropyl, tert-butyl, 4-fluorophenyl, and 2,4-difluorophenyl) was also studied. Compounds with outstandingly broad-spectrum activity, particularly against Gram-positive organisms, improved in vivo efficacy, and high blood levels were identified in this work. 7-Azetidinyl-8-chloroquinolones were considered as warranting further development.