The Urinary Metabolome of Healthy Newborns.

The knowledge of normal metabolite values for neonates is key to establishing robust cut-off values to diagnose diseases, to predict the occurrence of new diseases, to monitor a neonate's metabolism, or to assess their general health status. For full term-newborns, many reference biochemical values are available for blood, serum, plasma and cerebrospinal fluid. However, there is a surprising lack of information about normal urine concentration values for a large number of important metabolites in neonates. In the present work, we used targeted tandem mass spectrometry (MS/MS)-based metabolomic assays to identify and quantify 136 metabolites of biomedical interest in the urine from 48 healthy, full-term term neonates, collected in the first 24 h of life. In addition to this experimental study, we performed a literature review (covering the past eight years and over 500 papers) to update the references values in the Human Metabolome Database/Urine Metabolome Database (HMDB/UMDB). Notably, 86 of the experimentally measured urinary metabolites are being reported in neonates/infants for the first time and another 20 metabolites are being reported in human urine for the first time ever. Sex differences were found for 15 metabolites. The literature review allowed us to identify another 78 urinary metabolites with concentration data. As a result, reference concentration values and ranges for 378 neonatal urinary metabolites are now publicly accessible via the HMDB.

Effects of cytomegalovirus infection in human neural precursor cells depend on their differentiation state.

Cytomegalovirus (CMV) is the most common cause of congenital infection in developed countries and a major cause of neurological disability in children. Although CMV can affect multiple organs, the most important sequelae of intrauterine infection are related to lesions of the central nervous system. However, little is known about the pathogenesis and the cellular events responsible for neuronal damage in infants with congenital infection. Some studies have demonstrated that neural precursor cells (NPCs) show the greatest susceptibility to CMV infection in the developing brain. We sought to establish an in vitro model of CMV infection of the developing brain in order to analyze the cellular events associated with invasion by this virus. To this end, we employed two cell lines as a permanent source of NPC, avoiding the continuous use of human fetal tissue, the human SK-N-MC neuroblastoma cell line, and an immortalized cell line of human fetal neural origin, hNS-1. We also investigated the effect of the differentiation stage in relation to the susceptibility of these cell lines by comparing the neuroblastoma cell line with the multipotent cell line hNS-1. We found that the effects of the virus were more severe in the neuroblastoma cell line. Additionally, we induced hNS-1 to differentiate and evaluated the effect of CMV in these differentiated cells. Like SK-N-MC cells, hNS-1-differentiated cells were also susceptible to infection. Viability of differentiated hNS-1 cells decreased after CMV infection in contrast to undifferentiated cells. In addition, differentiated hNS-1 cells showed an extensive cytopathic effect whereas the effect was scarce in undifferentiated cells. We describe some of the effects of CMV in neural stem cells, and our observations suggest that the degree of differentiation is important in the acquisition of susceptibility.

Application of Focused Ultrasound-Assisted Extraction to the Determination of Persistent Organic Pollutants (POPs) in Soil Samples.

A simple and rapid focused ultrasound extraction (FU) based method is presented for the determination of persistent organic pollutants (POPs) in soil using a gas chromatography coupled to a mass detector with electron impact ionization. The main experimental parameters affecting the FU step have been optimized by applying a PERMANOVA and PCO analysis allowing us to obtain a maximum amount of information with a minimum number of assays. The limits of detection for POPs fell within the 0.9-6.8 ng/g d.w. interval; a linear method was used with correlation coefficients (r) higher than 0.99. Recovery percentages at low concentrations (25 ng/g d.w.) were 75.8%-110%, and at high concentrations (75 ng/g d.w.) 82.3%-109%; the evaluated precision as RSD% of repeatability and reproducibility were within a range of 0.5%-11% and 0.3%-18%, respectively.

Rapid analysis of persistent organic pollutants by solid phase microextraction in serum samples.

A simple and rapid headspace solid-phase microextraction (HS SPME) based method is presented for the determination of Persistent Organic Pollutants (POPs) in human serum by gas chromatography (GC) coupled to mass detector (MS) with electron impact ionization (EI). As an outcome of the assessment of several polymer phases; the one with the best result was the PDMS fiber (100 µm). A multivariate analysis of variance by permutations (PERMANOVA) was performed to establish the optimal extraction conditions as a function of temperature and time variables. The results were 1 mL serum+200 µL H2SO4 9M+1 mL of deionized water at 600 rpm with a temperature of 80°C for 50 min to expose the fiber. The limits of detection (LOD) for POPs pesticides fell within the 0.22-5.41 ng/mL interval, and within 0.07-1.79 ng/mL for PCBs; a linear method was used with correlation coefficients (r) higher than 0.99. Recovery percentages at low concentrations (15 ng/mL) were 67.8-120.2%, and at high concentrations (75 ng/mL) 80.2-119.2%. Evaluated precision as percentage Relative Standard Deviation (RSD%) of repeatability and reproducibility was within a range of 0.5-9% and 0.3-21%, respectively. This analytical method prevents some of the main problems for quantifying POPs in human serum, such as the elimination of the solvents, sample handling, integration of extraction steps, pre-concentration and introduction of samples; consequently, the time and cost of analyzing the sample can be significantly reduced. The method developed was applied to determine exposure to POPs in samples of children living in different polluted sites in Mexico. In children living in indigenous communities results show exposure to DDE (median 29.2 ng/mL range 17.4-52.2 ng/mL) and HCB (median 2.53 ng/mL range 2.50-2.64 ng/mL); whereas in the industrial scenario, exposure to HCB (median 2.81 ng/mL range 2.61-3.4 ng/mL) and PCBs (median Σ-PCBs 22.2 ng/ml range 8.2-74.6 ng/mL) and finally in petrochemical scenario was demonstrated exposure to HCB (median 2.81 ng/mL range 2.61-3.4 ng/mL) and PCBs (Σ-PCBs median 7.9 ng/mL range 5.4-114.5 ng/mL).

Anestesia para cesárea en una paciente con hígado graso agudo del embarazo / No disponible

No disponible

[Epidural anesthesia for cesarean section in a patient with von Hippel-Lindau disease]. / Anestesia epidural para cesárea en una paciente con enfermedad de von Hippel-Lindau.

Von Hippel-Lindau disease is a dominant autosomal genetic condition with variable penetrance and expressivity. It is characterized by hemangioblastomas in multiple organs but mainly in the retina and cerebellum. There is a predisposition to carcinoma. We report a cesarean section in a 28-year-old woman with von Hippel-Lindau disease. She had no neurologic symptoms at the time of the operation but a history of ocular and cerebellar involvement and several procedures to remove cerebellar hemangioblastomas. Epidural anesthesia was chosen given that there was no nervous system involvement at the time of surgery.

Anestesia epidural para cesárea en una paciente con enfermedad de Von Hippel-Lindau / Epidural anesthesia for cesarean section in a patient with von Hippel-Lindau disease

La enfermedad de von Hippel Lindau es un transtornogenético autosómico dominante con penetranciavariable, caracterizado por hemangioblastomas multiorgánicosprincipalmente en la retina y cerebelo y con predisposicióna desarrollar carcinoma. Se comunica el casode una gestante a término de 28 años de edad, portadorade la enfermedad de von Hippel Lindau, sin clínicaneurológica en el momento de la cesárea, con historia deafectación ocular y cerebelosa, a quien se le habían extirpadohemangioblastomas cerebelosos en varias ocasiones.Se eligió anestesia epidural por no presentar afectacióndel sistema nervioso, en el momento de la cirugía(AU)

Von Hippel-Lindau disease is a dominant autosomalgenetic condition with variable penetrance and expre -ssivity. It is characterized by hemangioblastomas inmultiple organs but mainly in the retina and cerebellum.There is a predisposition to carcinoma. We report acesarean section in a 28-year-old woman with von Hippel-Lindau disease. She had no neurologic symptoms at thetime of the operation but a history of ocular and cerebellarinvolvement and several procedures to remove cerebellarhemangioblastomas. Epidural anesthesia was chosen giventhat there was no nervous system involvement at the timeof surgery(AU)

Terapia celular y terapia génica ex vivo: avances en el tratamiento de enfermedades del sistema nervioso central / Cell and ex ivo gene Therapy: Avances in the treatment of Central nervous system disorders

Introducción. La aplicación directa de diversos tipos celulares al sistema nervioso central (SNC) por medio de trasplantes, la conocida terapia celular, es un acercamiento experimental que promueve la caracterización de los mecanismoscelulares y moleculares involucrados en el desarrollo, plasticidad y regeneración del SNC dañado. El conocimiento de la patología y etiología de las enfermedades neurodegenerativas, asociadas frecuentemente a la neurodegeneración de tipos celularesselectivos y/o deficiencia de neurotransmisores particulares, ha dirigido las investigaciones hacia la obtención de líneas celulares con características específicas. Desarrollo. En algunos casos, dichas células se transforman genéticamente paraproducir neurotransmisores o factores neurotróficos en grandes cantidades, la conocida terapia génica ex vivo, con la finalidad de ser utilizadas como alternativas terapéuticas en padecimientos del SNC. Por ejemplo, se ha notificado el efecto benéficode estas terapias en estudios con humanos y en diversos modelos de enfermedades neurodegenerativas, como la enfermedad de Huntington y la enfermedad de Parkinson, y en la epilepsia. El objetivo de este trabajo es realizar una revisión de diversos trabajos en los cuales se han utilizado trasplantes de células neuronales y no neuronales que han servido de base paraampliar nuestro conocimiento del SNC, de las enfermedades que lo afectan y de posibles alternativas terapéuticas. Conclusión. La terapia celular y la terapia génica ex vivo han contribuido a ampliar el conocimiento sobre la plasticidad, los mecanismos y los factores que promueven la integración celular en el sistema nervioso central. Si bien se han notificado mejoríasconductuales en modelos animales y humanos, estos estudios continúan arrojando incógnitas (AU)

Introduction. The direct application of different types of cells to the central nervous system (CNS) by means of transplants, so-called cell therapy, is an experimental approach that promotes the characterisation of the cell and molecularmechanisms involved in the development, plasticity and regeneration of damage to the CNS. Knowledge of the pathology andaetiology of neurodegenerative diseases, which are frequently related to the neurodegeneration of selected types of cells and/or deficiency of particular neurotransmitters, has led to research on means to obtain cell lines with specific characteristics. Development. In some cases these cells become genetically transformed to produce large amounts of neurotransmitters or neurotrophic factors, the well-known ex vivo gene therapy, so that they can be used as therapeutic alternatives in pathologies affecting the CNS. For example, reports have been published of the beneficial effects of these therapies in studies with humans and in different models of neurodegenerative diseases, such as Huntington’s disease and Parkinson’s disease, and in epilepsy. The aim of this work is to review the different studies in which transplants of neuronal and non-neuronal cells have been used and which have served to further our knowledge of the CNS, of diseases that affect it and of possible therapeutic alternatives. Conclusions. Ex vivo cell therapy and gene therapy have helped to expand ourknowledge about plasticity and the mechanisms and factors that promote cell integration within the central nervous system.Although behavioural improvements have been reported in animal and human models, further work is still required on these studies to clear up a number of dubious points. Ex vivo cell therapy and gene therapy in the nervous system constitute an important methodological tool with therapeutic possibilities that deserve further study (AU)

[Cell and ex vivo gene therapy: advances in the treatment of central nervous system disorders]. / Terapia celular y terapia génica ex vivo: avances en el tratamiento de enfermedades del sistema nervioso central.

INTRODUCTION: The direct application of different types of cells to the central nervous system (CNS) by means of transplants, so-called cell therapy, is an experimental approach that promotes the characterisation of the cell and molecular mechanisms involved in the development, plasticity and regeneration of damage to the CNS. Knowledge of the pathology and aetiology of neurodegenerative diseases, which are frequently related to the neurodegeneration of selected types of cells and/or deficiency of particular neurotransmitters, has led to research on means to obtain cell lines with specific characteristics. DEVELOPMENT: In some cases these cells become genetically transformed to produce large amounts of neurotransmitters or neurotrophic factors, the well-known ex vivo gene therapy, so that they can be used as therapeutic alternatives in pathologies affecting the CNS. For example, reports have been published of the beneficial effects of these therapies in studies with humans and in different models of neurodegenerative diseases, such as Huntington's disease and Parkinson's disease, and in epilepsy. The aim of this work is to review the different studies in which transplants of neuronal and non-neuronal cells have been used and which have served to further our knowledge of the CNS, of diseases that affect it and of possible therapeutic alternatives. CONCLUSIONS: Ex vivo cell therapy and gene therapy have helped to expand our knowledge about plasticity and the mechanisms and factors that promote cell integration within the central nervous system. Although behavioural improvements have been reported in animal and human models, further work is still required on these studies to clear up a number of dubious points. Ex vivo cell therapy and gene therapy in the nervous system constitute an important methodological tool with therapeutic possibilities that deserve further study.

Neuronal activity of aromatase enzyme in non-copulating male rats.

There are apparently normal male rats that fail to initiate copulation; these animals are called non-copulating (NC) males. Several research groups have demonstrated that conversion of testosterone to oestradiol (aromatisation) in specific brain areas known to be involved in the control of masculine sexual behaviour is fundamental in the control of masculine sexual behaviour. The aim of the present study was to test the hypothesis that the concentration of aromatase activity (AA) in the brain is lower in NC males than in copulating males (C). We quantified AA in several brain nuclei and also evaluated whether NC rats have altered concentrations of testosterone in their plasma. We found that AA was reduced in the medial preoptic nuclei (MPN) of NC male rats vs C males. In addition, NC and C male rats had similar plasma levels of testosterone. These data suggest that reduced levels of AA in the MPN could be a crucial factor associated with lack of male coital behaviour in rats.

Behavioral effects of exposure to endosulfan and methyl parathion in adult rats.

Endosulfan (ES) and methyl parathion (MP) are widely used in Latin America, and simultaneous exposure to both products is documented. This exposure may have effects on the nervous system because their targets include the GABAergic and cholinergic systems, which are main modulators of neuronal excitability in the cortex and hippocampus. We tested whether low-level, repeated exposure of adult rats to commercial formulations containing ES and MP disrupts spatial learning in the water maze. Five groups of eight animals received subcutaneously appropriate dilutions of the commercial formulations to yield the following treatments during 10 days: saline, 25 mg/kg ES, 2 mg/kg MP (MP(2)), 25 mg/kg ES plus 1 mg/kg MP (ES+MP(1)) and 25 mg/kg ES plus 2 mg/kg MP (ES+MP(2)). In addition, markers of neurological function, renal and hepatic damage were explored as potential consequences of exposure. In the absence of overt toxicity, the groups exposed to the ES plus MP showed significantly longer escape latencies, higher number of failures to reach the platform and more time in the periphery of the tank than the control and single-exposed groups. This finding shows that commercial formulations of ES and MP have marginal effects when administered individually but can produce behavioral alterations when given in combination.

Nature and localization of avian lens glycogen by electron microscopy and Raman spectroscopy.

Electron microscopy confirms the presence of a high concentration of glycogen particles in the lens nuclear region of birds of flying habit such as the ring-neck dove and pigeon. This observation is consistent with Raman spectroscopy. The glycogen particles in the dove lens, which are approximately 35 nm in diameter, are classified as beta type particles. Although this type has been previously characterized by high rates of glycogen turnover in other tissues, its localization in the lens nucleus indicates that it may serve a structural function rather than as a storage depot of carbohydrate in the lens. In a comparative electron microscopy study, glycogen particles were not observed in the chicken lens.