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In this study, we focused on the fluorous affinity acting among fluorine compounds, and then developed a new separation medium and evaluated their performance. We prepared the stationary phases for a column using silica gel-modified alkyl fluoride and investigated the characteristics of fluorous affinity by comparing them with a typical stationary phase, which does not contain fluorine, using high-performance liquid chromatography (HPLC). In HPLC measurements, we confirmed that while all non-fluorine compounds were not retained, retention of fluorine compounds increased as the number of fluorine increased with the stationary phase. It also revealed that the strength of fluorous affinity changes depending on the types of the organic solvent; the more polar the solvent, the stronger the effect. Additionally, the stationary phase was employed to compare the efficiency of our column with that of a commercially available column, Fluofix-II. The retention selectivity was almost the same, but the absolute retention strength was slightly higher on our column, indicating that the column is available for practical use.
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Pseudohypoparathyroidism (PHP) is a rare disorder characterized by convulsions, tetany, and sensory abnormalities caused by hypocalcemia due to parathyroid hormone (PTH) resistance. Only few patients present with involuntary movements. We report the case of a 7-yr-old girl with PHP and involuntary movements triggered by running. Initially, she was suspected of having paroxysmal kinesigenic dyskinesia and was treated with carbamazepine (CBZ). Involuntary movements were reduced. However, 2 months post-treatment, she experienced convulsions during a fever. Blood tests and brain computed tomography revealed hypocalcemia, hyperphosphatemia, elevated intact PTH, and calcifications in the frontal cortex and basal ganglia. The patient showed no features of Albright's hereditary osteodystrophy. The involuntary movements disappeared after the discontinuation of CBZ and initiation of calcium and active vitamin D preparations. Methylation-specific multiplex ligation-dependent probe amplification for the GNAS region and microsatellite analysis of chromosome 20 led to the diagnosis of PHP1B caused by epimutation. In 15 reported cases, with or without intracranial calcification, PHP-associated involuntary movements disappeared or became less severe with treatment for hypocalcemia; in eight of 11 cases, they were triggered by exercise or movement. PHP-associated hypocalcemia can trigger exercise-induced involuntary movements owing to lowered serum ionized calcium levels. In such patients, early blood tests are vital for the differential diagnosis of PHP.
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Particle packed columns used for liquid chromatography (LC) can suppress a column internal band broadening (hereinafter referred to as band broadening) by packing monodisperse particles homogenously. However, a quantitative evaluation for the effects of particle shape and packed state on band broadening needs to be more investigated. In this study, we fabricated a model of particle packed bed using microfluid LC columns that have pillar array structure prepared by microfabrication technology, evaluating how structural factors inside of a column affect its band broadening. At first, microfluid LC columns was prepared using Si-quartz glass (Si-Q column) for the optimization of LC measurement system. Through the evaluation, it showed 11.6 times higher pressure tolerance compared to that of PDMS-soda lime glass (PDMS-g column). Then, an optimized LC measurement system was constructed using a microfluidic LC column made of Si-Q column, and it was confirmed that the measurement error was small enough and the LC measurement could be performed with high repeatability. Additionally, the effect of a distribution of structural size on band broadening was evaluated. It was confirmed that wide distribution of the structural size provided large band broadening in actual measurements. Comparing two columns having different structural log-normal distributions of 0 and 0.22 showed approximately 1.8 times difference in both real LC measurement. Lastly, the relationship between packed state and band broadening was evaluated. As packed state, we employed void arrangement and structural arrangement in the columns. Different location arrangements of 50 and 100 µm pillar sizes afforded different band broadening. Well-homogenized array showed approximately two times worse band broadening compared to that of delocalized array. Based on these results, the developed packed bed of particles model was able to evaluate the relation between structural factors and band broadening.
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Cuarzo , Cromatografía Liquida , Tamaño de la Partícula , Cromatografía Líquida de Alta Presión/métodosRESUMEN
Reset osmostat (RO) is classified as type C among the four subtypes of the syndrome of inappropriate secretion of antidiuretic hormone based on antidiuretic hormone (ADH) secretion. It is characterized by a lower plasma osmolality threshold for ADH excretion when plasma sodium concentration is reduced. We report the case of a boy with RO and a giant arachnoid cyst (AC). The patient had been suspected of having AC since the fetal period, and a giant AC in the prepontine cistern was confirmed by brain magnetic resonance imaging 7 days after birth. During the neonatal period, there were no abnormalities in the general condition or blood tests, and he was discharged from the NICU at the 27 after birth. He was born with a -2 standard deviation short stature and mild mental retardation. When he was 6 years old, he was diagnosed with infectious impetigo and had hyponatremia of 121 mmol/L. Investigations revealed normal adrenal and thyroid functions, plasma hyposmolality, high urinary sodium, and high urinary osmolality. The 5% hypertonic saline and water load tests confirmed that ADH was secreted under low sodium and osmolality conditions, and the ability to concentrate urine and excrete a standard water load; therefore, RO was diagnosed. In addition, an anterior pituitary hormone secretion stimulation test was performed, which confirmed growth hormone secretion deficiency and gonadotropin hyperreactivity. Hyponatremia was untreated, but fluid restriction and salt loading were started at age 12 because of the risk of growth obstacles. The diagnosis of RO is important from the viewpoint of clinical hyponatremia treatment options.
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To date, an identification protocol for endocrine disruptors that bind to the thyroid hormone receptor (TR) has not been established. A method for screening and identifying TR-binding substances is highly required due to the existence of unknown TR-binding substances from the environment. Here, we conceived a chromatographic method using a molecularly imprinted polymer (MIP) to create a novel screening protocol for the endocrine disruptors. A receptor-imitating MIP was prepared using N-acetylthyroxine (AcetylT4) and 4-vinylpyridine as a pseudo-template and a functional monomer, respectively, based on the existing molecular recognition mechanism of the TR. The receptor-imitating MIP provided molecular recognition ability for all the TR-binding substances that were employed in this study. The prepared MIPs were packed into a high-performance liquid chromatography column for the simultaneous analysis of TR-binding and non-binding substances. The former was strongly retained, while the latter was not. The presence or absence of TR-binding/non-binding activity resulted in successful dichotomous separation. Additionally, the surface imprinting technique was applied to improve the separation performance of the MIP packing material. MIP-coated uniformly sized silica-based particles of 5 µm were successfully prepared, and the MIP-coated silica column enabled more efficient dichotomous separation of TR-binding and non-binding substances.
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Disruptores Endocrinos , Impresión Molecular , Impresión Molecular/métodos , Polímeros Impresos Molecularmente , Polímeros/química , Glándula Tiroides , Dióxido de Silicio/química , HormonasAsunto(s)
Atresia Intestinal/diagnóstico , Choque Hemorrágico/etiología , Úlcera/etiología , Arterias Umbilicales/patología , Cordón Umbilical/patología , Femenino , Humanos , Recién Nacido , Atresia Intestinal/complicaciones , Atresia Intestinal/fisiopatología , Choque Hemorrágico/diagnóstico , Úlcera/diagnóstico , Cordón Umbilical/irrigación sanguíneaRESUMEN
We report here a very rare case of de novo inversion-duplication chromosomal abnormality with a pure 3qter duplication syndrome. Interestingly, the 3q duplication includes an overlap of the syndromes critical region. Although there have only been 9 cases of this syndrome reported in the past, our patient had more severe neurological abnormalities than anticipated. In this regard, we have gathered the 3q chromosomal duplication abnormalities known to cause pure 3q duplication syndrome to date as a reference for comparisons and we discuss the particulars of our case.
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We describe four families with affected siblings showing unique clinical features: early-onset (before 1 year of age) progressive diffuse brain atrophy with regression, postnatal microcephaly, postnatal growth retardation, muscle weakness/atrophy, and respiratory failure. By whole-exome sequencing, we identified biallelic TBCD mutations in eight affected individuals from the four families. TBCD encodes TBCD (tubulin folding co-factor D), which is one of five tubulin-specific chaperones playing a pivotal role in microtubule assembly in all cells. A total of seven mutations were found: five missense mutations, one nonsense, and one splice site mutation resulting in a frameshift. In vitro cell experiments revealed the impaired binding between most mutant TBCD proteins and ARL2, TBCE, and ß-tubulin. The in vivo experiments using olfactory projection neurons in Drosophila melanogaster indicated that the TBCD mutations caused loss of function. The wide range of clinical severity seen in this neurodegenerative encephalopathy may result from the residual function of mutant TBCD proteins. Furthermore, the autopsied brain from one deceased individual showed characteristic neurodegenerative findings: cactus and somatic sprout formations in the residual Purkinje cells in the cerebellum, which are also seen in some diseases associated with mitochondrial impairment. Defects of microtubule formation caused by TBCD mutations may underlie the pathomechanism of this neurodegenerative encephalopathy.
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Alelos , Encefalopatías/genética , Proteínas Asociadas a Microtúbulos/genética , Mutación/genética , Enfermedades Neurodegenerativas/genética , Adolescente , Edad de Inicio , Secuencia de Aminoácidos , Animales , Encefalopatías/patología , Encefalopatías/fisiopatología , Niño , Preescolar , Drosophila melanogaster/genética , Exoma , Femenino , Mutación del Sistema de Lectura/genética , Proteínas de Unión al GTP/metabolismo , Humanos , Lactante , Recién Nacido , Masculino , Proteínas Asociadas a Microtúbulos/química , Proteínas Asociadas a Microtúbulos/metabolismo , Microtúbulos/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Enfermedades Neurodegenerativas/patología , Enfermedades Neurodegenerativas/fisiopatología , Linaje , Sitios de Empalme de ARN/genética , Tubulina (Proteína)/metabolismo , Adulto JovenRESUMEN
BACKGROUND: The aim of this study was to verify whether lipid emulsion treatment aggravates infection and inflammation in very low-birthweight (VLBW) infants. STUDY DESIGN: Very low-birthweight (<1500 g) infants born at <32 weeks gestational age between October 2013 and October 2014 at Dokkyo Medical University Hospital (Mibu, Tochigi, Japan) were treated with or without i.v. nutrition with a lipid emulsion. Infants were excluded who had congenital abnormalities, could not receive i.v. nutrition because of poor general condition, or on physician decision. Lipid emulsion with purified soybean oil was initiated at 0.5 g/kg/day on postnatal day 1. The dose was increased to 1 g/kg/day, and then to 1.5 g/kg/day (maximum dose). Blood tests were performed before (day 1) and after (day 8) initiation of lipid emulsion treatment. Interleukin (IL)-6, IL-8, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), total bilirubin (T-Bil), direct bilirubin (D-Bil) and insulin were measured. Changes in respiratory condition, amount of oxygen used, and phototherapy duration were investigated. RESULTS: A total of 17 treated and 15 untreated VLBW infants were enrolled. IL-6, IL-8, MCP-1, TNF-α, CRP, T-Bil, D-Bil and insulin on days 1 and 8; respirator or surfactant use; amount of oxygen used; and phototherapy duration were not significantly different between the two groups. CONCLUSIONS: Lipid emulsion treatment did not increase inflammatory cytokine levels or aggravate respiratory disorders. Lipid emulsions, if proven safe, could be used to treat VLBW infants soon after birth, which may prevent extrauterine growth restriction and improve intellectual development prognosis.
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Citocinas/sangre , Emulsiones Grasas Intravenosas/administración & dosificación , Enfermedades del Prematuro/tratamiento farmacológico , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Nutrición Parenteral/métodos , Femenino , Estudios de Seguimiento , Edad Gestacional , Humanos , Recién Nacido , Enfermedades del Prematuro/sangre , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is produced in response to tubular epithelial injury and is a biomarker of tubulointerstitial injury. The aim of the present study was to examine whether acute kidney injury (AKI) could be predicted by measuring uNGAL in very low-birth weight (VLBW) infants. Forty VLBW infants with birthweight below 1,500 g were enrolled in the present study. uNGAL and serum creatinine (sCre) were measured daily from postnatal days 0 to 8. Infants with sCre ≥1.2 mg/dl were diagnosed with AKI. The relationship of uNGAL with sCre was measured on the day after uNGAL measurement (next-day sCre) was examined. The results showed that 16 infants had sCre ≥1.2 mg/dl in this period. Logistic regression analysis revealed that uNGAL on postnatal days 2, 3, 4, 5 and 6 was correlated with next-day sCre (P<0.05). uNGAL corrected by urinary Cre (uCre) (uNGAL/uCre) was only correlated with an increase in next-day sCre on postnatal days 5 and 6 (P<0.05). For the logistic analysis, subjects with high and low uNGAL levels based on the median value for each day, uNGAL on postnatal days 2, 3 and 6 in the high uNGAL group was correlated with an increase in next-day sCre. Thus, AKI may be predicted by measuring uNGAL in VLBW infants. This measurement was non-invasive, and is potentially useful for the evaluation of renal function in VLBW infants.
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A novel on-line pretreatment pump-injection HPLC system for polycyclic aromatic hydrocarbons is proposed. We report novel pump-injection HPLC-based on-line SPE with a specially designed pretreatment column for the determination of trace amounts of chemical substances in surface water. Polycyclic aromatic hydrocarbons are well known for strong carcinogenicity and thus a severe concentration control is required for drinking water and/or river water, which is the main resource of tap water. We found it possible to detect ng/L levels of polycyclic aromatic hydrocarbons by using pump-injection column switching HPLC with fluorescence detection. To avoid the phenomenon, in which polycyclic aromatic hydrocarbons can be often adsorbed on the surface of flow lines of HPLC by their highly hydrophobicity especially resin-made parts in sample delivery pump, we employed "autodilution" device that provides reliable recovery and repeatability. Additionally, real water samples were collected and then the spiked polycyclic aromatic hydrocarbons were determined at ng/L levels.
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Cromatografía Líquida de Alta Presión/métodos , Hidrocarburos Policíclicos Aromáticos/análisis , Ríos/química , Contaminantes Químicos del Agua/análisis , Adsorción , Hidrocarburos Policíclicos Aromáticos/aislamiento & purificación , Contaminantes Químicos del Agua/aislamiento & purificaciónRESUMEN
OBJECTIVES: To investigate the risk of hypophosphatemia and hypercalcemia in small for gestational age (SGA) extremely low birth weight infants (ELBWI) receiving parenteral nutrition. METHODS: A retrospective review of 58 ELBWI was conducted. Serum calcium (Ca) and phosphate (PO4) concentrations on days 1 and 8 after birth were examined for associations with body measurements and nutritional factors in the 1st week of life. RESULTS: Lower birth weight standard deviation (SD) scores were correlated with hypophosphatemia and hypercalcemia in SGA ELBWI on day 8. Higher parenteral amino acid (AA) administration was correlated with hypophosphatemia on day 8. SGA ELBWI exhibited lower serum PO4 concentrations compared to appropriate for gestational age (AGA) ELBWI on day 8. CONCLUSIONS: This is the 1st study to report that parenteral nutrition, in the first 7 days after birth for the treatment of SGA ELBWI, was correlated with hypophosphatemia and hypercalcemia. It is important to determine an ideal nutrition protocol for treatment of SGA ELBWI.
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Hipercalcemia/etiología , Hipofosfatemia/etiología , Recien Nacido con Peso al Nacer Extremadamente Bajo/crecimiento & desarrollo , Recien Nacido con Peso al Nacer Extremadamente Bajo/metabolismo , Recién Nacido Pequeño para la Edad Gestacional/crecimiento & desarrollo , Recién Nacido Pequeño para la Edad Gestacional/metabolismo , Nutrición Parenteral/efectos adversos , Peso al Nacer , Femenino , Humanos , Hipercalcemia/sangre , Hipercalcemia/diagnóstico , Hipofosfatemia/sangre , Hipofosfatemia/diagnóstico , Recién Nacido , Masculino , Pronóstico , Estudios RetrospectivosRESUMEN
A practical way for reducing contaminants, such as humic acids, and solving column-clogging problem in environmental water analysis with liquid chromatography is proposed. Detection interference by contamination is one of the most important issues of the environmental analyses. Moreover, due to the recent smaller diameter and fine particle size of an analytical column for HPLC system, a column-clogging problem is another practical difficulty as well. We found it possible to solve these problems by employing column-switching HPLC, which consists of a pretreatment column containing surface-modified polymer particles and flow changeover valves for cleaning the remaining matrices in the pretreatment column prior to analysis. This method was successfully applied to actual HPLC-fluorescence detection of bisphenol A. Limit of detection (LOD) in real sample was <0.7 ng/L. Repeatability was around 1.4% and recovery was around 97% or more. A particular pressure increase was not observed in 150 repeated analyses of real river water samples.
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Métodos Analíticos de la Preparación de la Muestra/métodos , Cromatografía Líquida de Alta Presión/métodos , Disruptores Endocrinos/análisis , Fenoles/análisis , Contaminantes Químicos del Agua/análisis , Métodos Analíticos de la Preparación de la Muestra/instrumentación , Compuestos de Bencidrilo , Cromatografía Líquida de Alta Presión/instrumentación , Fluorescencia , Límite de Detección , Ríos/químicaRESUMEN
We report the fundamental chromatographic retention properties of spongy monolith that was previously reported as a novel separation medium for the effective pretreatment of environmental pollutants. According to the detailed examination on liquid chromatographic evaluations using hydrophobic, hydrophilic, and polyaromatic compounds as solutes, the spongy monolith consisted of poly(ethylene-co-vinyl acetate) and having macroporous co-continuous structures showed the selective retention ability for polyaromatic hydrocarbons (PAHs), especially coplanar compounds, whereas lower selectivity was observed for typical hydrophobic and hydrophilic compounds compared with the commonly used C18 medium. Moreover, we demonstrate the effective preconcentration of benzo[a]pyrene using a spongy monolith as a pretreatment column of an online column switching HPLC system.
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BACKGROUND: The relationship of thyroxine supplementation for transient hypothyroxinemia of prematurity to the incidence of cerebral palsy (CP) in infants <28 weeks of gestation is unclear. METHODS: The incidence of CP at a corrected age of 18 months was compared between infants born in a 3-year period in which routine measurement of free T4 (FT4) in the blood was not performed (first period, n= 54), and those born in a later 3-year period in which FT4 was measured (second period, n= 60; mainly at 7 days old), and in which l-thyroxine 5-10 µg/kg per day (mean, 9 µg/kg/day) was administered for FT4 levels <0.8 ng/dL. Incidence of CP at 3 years of age was also compared between the same groups. RESULTS: Background clinical factors between the two groups were comparable except for prenatal steroid administration, which was reduced in the second period. Incidence of CP at a corrected age of 18 months was significantly lower in the second period (3.3%) than in the first period (16.6%). Incidence of CP at 3 years of age was also significantly lower in the second period. Multiple logistic regression analysis using factors except thyroxine supplementation, for the total of 114 infants from both groups, found no perinatal factors related to the development of CP at a corrected age of 18 months. CONCLUSIONS: Thyroxine supplementation for transient hypothyroxinemia of prematurity may reduce the incidence of CP in extremely preterm infants. Large-scale randomized controlled trials are essential to determine the effects of thyroxine supplementation in reducing the incidence of CP among extremely preterm infants.
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Parálisis Cerebral/prevención & control , Enfermedades del Prematuro/tratamiento farmacológico , Tiroxina/deficiencia , Tiroxina/uso terapéutico , Parálisis Cerebral/etiología , Preescolar , Hipotiroidismo Congénito/sangre , Hipotiroidismo Congénito/tratamiento farmacológico , Esquema de Medicación , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/sangre , Modelos Logísticos , Tirotropina/sangre , Tiroxina/sangreRESUMEN
Human chromosome 14q32.2 harbors the germline-derived primary DLK1-MEG3 intergenic differentially methylated region (IG-DMR) and the postfertilization-derived secondary MEG3-DMR, together with multiple imprinted genes. Although previous studies in cases with microdeletions and epimutations affecting both DMRs and paternal/maternal uniparental disomy 14-like phenotypes argue for a critical regulatory function of the two DMRs for the 14q32.2 imprinted region, the precise role of the individual DMR remains to be clarified. We studied an infant with upd(14)pat body and placental phenotypes and a heterozygous microdeletion involving the IG-DMR alone (patient 1) and a neonate with upd(14)pat body, but no placental phenotype and a heterozygous microdeletion involving the MEG3-DMR alone (patient 2). The results generated from the analysis of these two patients imply that the IG-DMR and the MEG3-DMR function as imprinting control centers in the placenta and the body, respectively, with a hierarchical interaction for the methylation pattern in the body governed by the IG-DMR. To our knowledge, this is the first study demonstrating an essential long-range imprinting regulatory function for the secondary DMR.
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Cromosomas Humanos Par 14 , Metilación de ADN , Proteínas/genética , Secuencia de Bases , Factor de Unión a CCCTC , Deleción Cromosómica , Femenino , Humanos , Lactante , Recién Nacido , Datos de Secuencia Molecular , ARN Largo no Codificante , Proteínas Represoras/genética , Alineación de SecuenciaRESUMEN
Congenital high airway obstruction syndrome (CHAOS) is a rare life-threatening syndrome. Most cases are diagnosed prenatally by US. We report a fetus with this syndrome that showed a unique course revealed on MRI. Ultrasonography at 22 weeks demonstrated that the fetus had ascites and bilaterally enlarged hyperechoic lungs. Congenital infection, congenital cystic adenomatoid malformation or CHAOS was suspected. Subsequent MRI performed at 24 weeks demonstrated bilaterally enlarged high-signal lungs, dilated bronchi, massive ascites, subcutaneous oedema and polyhydramnios. MRI confirmed the diagnosis of CHAOS. A second MRI at 35 weeks showed that the bilateral lung enlargement, ascites, oedema and polyhydramnios had resolved, but that the appearance of the airway was unchanged. The infant was delivered by caesarean section at 38 weeks of gestation and immediate tracheostomy was performed. This spontaneous regression was explained by a tracheo-oesophageal fistula that may have decreased the intrathoracic pressure.
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Obstrucción de las Vías Aéreas/diagnóstico , Enfermedades Fetales/diagnóstico , Laringe/anomalías , Imagen por Resonancia Magnética , Adulto , Obstrucción de las Vías Aéreas/congénito , Obstrucción de las Vías Aéreas/cirugía , Cesárea , Femenino , Enfermedades Fetales/cirugía , Humanos , Recién Nacido , Masculino , Embarazo , Remisión Espontánea , Síndrome , Traqueostomía , Ultrasonografía PrenatalAsunto(s)
Anomalías Múltiples/diagnóstico , Recien Nacido Prematuro , Linfohistiocitosis Hemofagocítica/diagnóstico , Diagnóstico Prenatal , Adulto , Ascitis/diagnóstico , Autopsia , Biopsia con Aguja , Progresión de la Enfermedad , Resultado Fatal , Femenino , Edad Gestacional , Humanos , Hiponatremia/diagnóstico , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Insuficiencia Multiorgánica , Oligohidramnios/diagnóstico , Embarazo , Trombocitopenia/diagnósticoRESUMEN
Surface modified molecularly imprinted polymers (SM-MIPs) for 17beta-estradiol (E2), utilizing 6-ketoecradiol as a pseudo template were prepared. MIPs for E2 were synthesized using 4-vinyl pyridine and ethylene dimethacrylate as a functional monomer and cross-linking agent, respectively. MIPs selectively retained E2 and provided excellent chromatographic resolution from interfering compounds inherent in river water sample matrices. Therefore, freshly prepared MIPs were applied to quantitative mass spectrometric (negative electrospray ionization mode) detection of low levels of E2 in river water sample. In order to pre-concentrate the target compound for HPLC analysis, column switching was coupled with a pretreatment column packed with the MIPs. The repeatability of actual determinations of river water sample, in which background E2 was not detected, spiked with 50 ng/L of E2 was 2.2% RSD with a detection limit and qualification limit of 1.8 and 5.4 ng/L, respectively. Surface modification of MIP particlefs packed in the pretreatment column provided selective affinity and on-line concentration of low levels of E2 while simultaneously eliminating sample matrix interference, resulting in a significant increase in sensitivity and reproducibility for liquid chromatography-mass spectrometry analysis of E2 in river water sample.
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Cromatografía Líquida de Alta Presión/métodos , Estradiol/análisis , Ríos/química , Espectrometría de Masa de Ion Secundario/métodos , Contaminantes Químicos del Agua/análisis , Estradiol/química , Estradiol/aislamiento & purificación , Estructura Molecular , Polímeros/química , Reproducibilidad de los Resultados , Espectrofotometría UltravioletaRESUMEN
Age-related changes in the monoaminergic neuron systems in the brains of methylazoxymethanol acetate (MAM)-induced micrencephalic rats were studied. Neurochemical analysis revealed high levels of serotonin, norepinephrine and associated metabolites in several brain areas of MAM-treated rats. In particular, serotonin levels in the frontal cortex, cingulate cortex and hippocampus of 12-month-old (12 M) MAM-treated rats were significantly higher than in corresponding age-matched controls. Immunohistochemical analysis demonstrated numerous aberrant serotonin-immunoreactive fibers and small numbers of aberrant tyrosine hydroxylase-immunoreactive fibers in the septum, caudate putamen, thalamus, cerebral cortex, hippocampus and midbrain tegmentum of 12 M MAM-treated rats. Aberrant monoaminergic fibers characterized by swollen varicosities and thickening of intervaricose segments were common compared to 12 M control rats. In the cortex and hippocampus of 12 M MAM-treated rats, aberrant fibers were observed near cortical heterotopic tissue. These results indicate early onset of age-related degeneration of monoaminergic fibers in micrencephalic rats. Aged MAM-treated rats may thus offer a good model for studying age-related monoaminergic changes in the cortical heterotopic tissue of human cortical malformations.