Plasmoid Formation and Strong Radiative Cooling in a Driven Magnetic Reconnection Experiment.

We present the first experimental study of plasmoid formation in a magnetic reconnection layer undergoing rapid radiative cooling, a regime relevant to extreme astrophysical plasmas. Two exploding aluminum wire arrays, driven by the Z machine, generate a reconnection layer (S_{L}≈120) in which the cooling rate far exceeds the hydrodynamic transit rate (τ_{hydro}/τ_{cool}>100). The reconnection layer generates a transient burst of >1 keV x-ray emission, consistent with the formation and subsequent rapid cooling of the layer. Time-gated x-ray images show fast-moving (up to 50 km s^{-1}) hotspots in the layer, consistent with the presence of plasmoids in 3D resistive magnetohydrodynamic simulations. X-ray spectroscopy shows that these hotspots generate the majority of Al K-shell emission (around 1.6 keV) prior to the onset of cooling, and exhibit temperatures (170 eV) much greater than that of the plasma inflows and the rest of the reconnection layer, thus providing insight into the generation of high-energy radiation in radiatively cooled reconnection events.

Spanish Version of Teenagers' Quality of Life (T-QoL) for Adolescents with Skin Diseases: Translation, Cultural Adaptation and Validation.

BACKGROUND: Teenagers' Quality of Life (T-QoL) is an age-specific measure to assess QoL of teenagers suffering from different skin diseases. A validated Spanish language version is lacking. We present the translation, cultural adaptation and validation of the T-QoL into Spanish. METHODS: A prospective study with 133 patients (between 12 and 19 years old), attended at the dermatology department of Toledo University Hospital, Spain (September 2019-May 2020), was carried out for the validation study. The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines were used for the translation and cultural adaptation. We evaluated the convergent validity with the Dermatology Life Quality Index (DLQI), the Children's Dermatology Life Quality Index (CDLQI) and with a Global Question (GQ) on self-assessed disease severity. We also analysed internal consistency and reliability of the T-QoL tool and confirmed its structure with a factor analysis. RESULTS: Global T-QoL scores significantly correlated with the DLQI and the CDLQI (r=0.75) and with the GQ (r=0.63). The confirmatory factor analysis showed optimal fit for the bi-factor model and an adequate fit for the correlated three-factor model. Reliability indicators were high (Cronbach's α=0.89; Guttman's Lambda 6 index=0.91; Omega ω=0.91) and test-retest showed a high stability (ICC=0.85). The results were consistent with those found by the authors of the original test. CONCLUSION: Our Spanish version of the T-QoL tool is valid and reliable to assess QoL of Spanish-speaking adolescents with skin diseases.

Spanish Version of Teenagers' Quality of Life (T-QoL) for Adolescents with Skin Diseases: Translation, Cultural Adaptation and Validation. / [Artículo Traducido] Traducción, adaptación cultural y validación de la versión española del Teenagers' Quality of Life (T-QoL): cuestionario para adolescentes con enfermedades de la piel.

BACKGROUND: Teenagers' Quality of Life (T-QoL) is an age-specific measure to assess QoL of teenagers suffering from different skin diseases. A validated Spanish language version is lacking. We present the translation, cultural adaptation and validation of the T-QoL into Spanish. METHODS: A prospective study with 133 patients (between 12 and 19 years old), attended at the dermatology department of Toledo University Hospital, Spain (September 2019-May 2020), was carried out for the validation study. The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines were used for the translation and cultural adaptation. We evaluated the convergent validity with the Dermatology Life Quality Index (DLQI), the Children's Dermatology Life Quality Index (CDLQI) and with a Global Question (GQ) on self-assessed disease severity. We also analysed internal consistency and reliability of the T-QoL tool and confirmed its structure with a factor analysis. RESULTS: Global T-QoL scores significantly correlated with the DLQI and the CDLQI (r = 0.75) and with the GQ (r = 0.63). The confirmatory factor analysis showed optimal fit for the bi-factor model and an adequate fit for the correlated three-factor model. Reliability indicators were high (Cronbach's α = 0.89; Guttman's Lambda 6 index = 0.91; Omega ω = 0.91) and test-retest showed a high stability (ICC = 0.85). The results were consistent with those found by the authors of the original test. CONCLUSION: Our Spanish version of the T-QoL tool is valid and reliable to assess QoL of Spanish-speaking adolescents with skin diseases.

Treatment with intravenous immunoglobulins in systemic lupus erythematosus: a single-center experience with 63 patients.

BACKGROUND: Intravenous immunoglobulin (IVIG) is prepared using purified human plasma. IVIG therapy has immunomodulatory effects on autoimmune diseases, including severe systemic lupus erythematosus (SLE). However, reports of its effects on large cohorts are scarce. METHODS: This single-center retrospective study included SLE patients treated with at least one IVIG cycle for SLE complications. Demographic data, indications, cycle numbers, and clinical improvement with IVIG were evaluated. SLE Disease Activity Index 2000 (SLEDAI-2K) scores were calculated at admission and after IVIG treatment in order to measure clinical improvement. RESULTS: Sixty-three SLE patients treated with IVIG (median age: 29 years; interquartile range 21-36 years; 84.13% female) were included, who received 2 g/kg IVIG for two to five days. Main indications were immune thrombocytopenia, hypogammaglobulinemia, infection during a SLE flare, bicytopenia, and immune hemolytic anemia. Seven patients received more than one IVIG cycle without severe adverse effects. Significant differences were found in SLEDAI-2K scores when the indications were immune thrombocytopenia and hypogammaglobulinemia, with a trend for hemolytic anemia. Patients with concomitant infection, myopathy, and gastrointestinal involvement showed a considerable reduction in their last SLEDAI-2K scores. Fourteen patients died during hospitalization, mainly due to septic shock and active SLE. CONCLUSIONS: IVIG showed adequate tolerance and effectiveness in selected severe SLE manifestations, mainly hematological involvement. It was useful for concomitant infection.

Sludge reduction at low ozone doses: predictive effects and full-scale study.

The activated sludge process is the most widely used wastewater treatment. The main drawback of this technology is the excess sludge production (ESP). The ozonation of sludge of the recirculation line is used to reduce the ESP. In this study, ozonation was applied on a fraction of sludge of the recirculation line in a full-scale plant (50,000 population equivalent) at a lower-specific ozone dose (SOD) compared to previous studies. The results of batch tests to predict the main effect of the technology on the biomass activities are reported. Specifically, tests at 0.7-5 g O3/kg MLVSS (mixed liquor volatile suspended solids) doses were made to evaluate the changes of the nitrification and denitrification rates, the population of phosphate-accumulating organisms and the gravitational properties. A certain reduction of the impact of ozonation on the kinetic parameters of sludge for values of SOD over 2 g O3/kg MLVSS was found. The present study highlights also the use of the ratio of ozonated biomass to total biomass as an important operative parameter for ozonation in full-scale plants. Reduction in ESP in the wastewater treatment plant was equal to 10% as dry solids applying a SOD from 1.03 to 1.63 g O3/kg MLVSS. An analysis of the economic cost of the technique is also reported.

The physiology of ex vitro pineapple (Ananas comosus L. Merr. var MD-2) as CAM or C3 is regulated by the environmental conditions: proteomic and transcriptomic profiles.

KEY MESSAGE: Proteomic and transcriptomic profiles of key enzymes were monitored in pineapple plants propagated under C3 and CAM-inducing metabolisms to obtain insight into the CAM-facultative metabolism and the relationship of CAM plants with oxidative stress. ABSTRACT: Pineapple is one of the most important tropical crops worldwide. The use of temporary immersion bioreactors for the first stages of pineapple propagation enables precise control of plant growth, increases the rate of plant multiplication, decreases space, energy and labor requirements for pineapple plants in commercial micropropagation. Once the plantlets are ready to be taken from the reactors, they are carefully acclimatized to natural environmental conditions, and a facultative C3/CAM metabolism in the first 2 months of growth is the characteristic of pineapple plants, depending on environmental conditions. We subjected two sets of micropropagated pineapple plants to C3 and CAM-inducing environmental conditions, determined by light intensity/relative humidity (respectively 40 µmol m−2 s−1/85 % and 260 µmol m−2 s−1/50 %). Leaves of pineapple plants grown under CAM-inducing conditions showed higher leaf thickness and more developed cuticles and hypodermic tissue. Proteomic profiles of several proteins, isoenzyme patterns and transcriptomic profiles were also measured. Five major spots were isolated and identified, two of them for the first time in Ananas comosus (OEE 1; OEE 2) and the other three corresponding to small fragments of the large subunit of Rubisco (LSU). PEPC and PEPCK were also detected by immunobloting of 2DE at the end of both ex vitro treatments (C3/CAM) during the dark period. Isoenzymes of SOD and CAT were identified by electrophoresis and the transcript levels of OEE 1 and CAT were associated with CAM metabolism in pineapple plants.

Biochemical characterization of ecuadorian wild Solanum lycopersicum Mill. plants produced from non-cryopreserved and cryopreserved seeds.

This paper presents some of the effects of cryopreservation of wild Solanum lycopersicum Mill. seeds on the early stages of germination post liquid nitrogen exposure. Percentage of germination, conversion into plantlets and plant fresh mass were evaluated after cryostorage. Levels of chlorophyll pigments (a, b, total), malondialdehyde, other aldehydes, phenolics (cell wall-linked, free, and total) and proteins were determined. Peroxidase and superoxide dismutase activities were recorded. Liquid nitrogen exposure increased the percentage of seed germination at 5 days but at 7 days, the conversion into plantlets and the plant fresh mass were not statistically different between non-cryopreserved and cryopreserved samples. Several significant effects of cryopreservation were recorded at the biochemical level at 7 days of germination under controlled conditions. Highly significant effects due to liquid nitrogen exposure were observed in leaves: increased levels of peroxidase enzymatic and specific activities and cell wall-linked phenolics. Very remarkable effects were also recorded in roots: decreased contents of chlorophylls and cell wall-linked phenolics.

The physiology of ex vitro pineapple (Ananas comosus L. Merr. var MD-2) as CAM or C3 is regulated by the environmental conditions.

Many plant species grown under in vitro controlled conditions can be used as models for the study of physiological processes. Adult pineapple can display CAM physiology while in vitro it functions as a C3 plant. Ex vitro Ananas comosus has plastic morphology and physiology, both easy to modify from C3 to CAM by changing the environmental conditions. The yield of survival for a rentable propagation protocol of pineapple is closely related with the C3/CAM shift and the associated physiological characteristics. In the present work, ex vitro pineapple plants were divided in two sets and subjected to C3 and CAM-inducing environmental conditions, determined by light intensity and relative humidity, respectively, 40 µmol m(-2) s(-1)/85% and 260 µmol m(-2) s(-1)/50%. The results demonstrated that the stress imposed by the environmental conditions switched pineapple plants from C3 to CAM behavior. Comparing to CAM induced, C3-induced pineapple plants showed substandard growth parameters and morphological leaf characteristics but a better rooting process and a higher ABA production, a phenotype closer to adult plants, which are expected to produce fruits in a normal production cycle. We conclude that the upholding of these characteristics is conditioned by low light intensity plus high relative humidity, especially during the first 8 weeks of ex vitro growth. It is expected that the better understanding of pineapple acclimatization will contribute to the design of a protocol to apply as a rentable tool in the pineapple agronomic industry.

Three new teosintes (Zea spp., Poaceae) from México.

PREMISE OF THE STUDY: Teosinte species are the closest relatives of maize and represent an important but increasingly rare genetic resource for maize improvement and the study of evolution by domestication. Three morphologically and ecologically distinct teosinte populations were recently discovered in México. The taxonomic status of these rare and endangered populations was investigated by detailed comparisons to previously characterized wild Zea species. • METHODS: Three new teosinte populations were compared to known teosinte taxa on the basis of morphological, ecogeographic, cytological, and molecular characteristics. Phenetic and phylogenetic analyses were performed using morphological and molecular data, respectively. • KEY RESULTS: The newly discovered populations are distinct from each other and from other Zea species to represent three new entities based on their unique combinations of morphological, ecological, ploidy, and DNA markers. A perennial diploid population from Nayarit is distinguished by early maturing plants, and having male inflorescences with few tassel branches and long spikelets. A perennial tetraploid population from Michoacán is characterized by tall and late maturing plants, and having male inflorescences with many branches. An annual diploid population from Oaxaca is characterized by having male inflorescences with fewer branches and longer spikelets than those found in the sister taxa Z. luxurians and Z. nicaraguensis, plants with high thermal requirements, and very long seed dormancy. • CONCLUSIONS: Evidence from multiple independent sources suggests placement of the three new populations of teosinte as distinct entities within section Luxuriantes of the genus Zea. However, more extensive DNA marker or sequence data are required to resolve the taxonomy of this genus.

[Nutrition and anaemias in critical illness]. / Nutrición y anemias en pacientes graves.

INTRODUCTION: We made a clinical study, about nutrition in seriously ill patients, which includes a typical heterogeneous group of critical ill patients, with/without anaemia's, that have been admitted to Intensive Care Unit, ICU. It is difficult to individualize and to generalize the relative importance of all the factors that can contribute to these anaemia's in the admission to the Unit, including nutritional deficiencies, inflammatory alterations, the immune response to aggressions, inmunitary modifications and the complex relations existing between these clinic processes. OBJECTIVE: Indirect valuation of the nutritional situation and anaemia's, in a typical heterogeneous group of critical ill patients. METHOD/RESULTS: We studied 202 patients admitted to ICU, of varied and heterogeneous origin, classifying them in 3 groups: control, post surgery and septic group's, becoming the indirect valuation of the nutritional situation on the basis of: Global Subjective Valuation, (VGS) and the nutritional analytical determinations of total lymphocytes, albumin, and transferrin. Also we made hemogram and determinations of sideremia and ferritinemia to all of them. In 57% of the patients, we observed levels haemoglobin < 12.5 g/dl, basically in the post surgery groups, 68 patients and septic group's, 10 patients. And with levels haemoglobin < 10 g/dl, in 25 patient's (12.3%). There were 87 patients, 23 of them in the control group's, 58 in the post surgery and 5 septic group's, with levels haemoglobin > 12.5 g/dl. Regarding the nutritional prognoses indicators, (VGS + nutritional profile), in the control group's, they did not present anaemia nor analytical clinical under nourishment, in the post surgery group's, anaemia and slight under nourishment and in the septic group's, anaemia and moderate under nourishment. There were significant differences between the surgery and septic group and control group's, in values of haemoglobin, iron, total lymphocytes, transferrin and albumin. A statistical correlation between sideremia and albumin was significative. (Spearman's Rho 0,277). CONCLUSIONS: The evaluation of the anaemia and nutritional valuation. and the ferroterapic treatment, as immune-nutrient, can be beneficial for the integrity of the immune system and its defense's abilities against the aggressions in critically ills.

Use of microbial activity measurements for monitoring RBC biofilms.

Fixed biomass technologies, such as rotating biological contactors or biodiscs, have been applied for wastewater depuration both in large and medium-small-sized agglomerations. Biofilm's composition and microorganism activity are essential parameters for the successful operation and control of these systems. Biofilm's thickness and total dry weight have been widely used for biofilm's characterization but, actually, are not sufficient to describe biofilm activity. In fact, biofilm's activity is not proportional to the quantity of fixed biomass, but increases with the thickness of biofilm up to a determined level called the "active thickness". Above this level, the diffusion of nutrients through the film becomes a limiting factor. A stable, thin, and active biofilm thus offers numerous advantages in water and wastewater treatment. Different parameters have been used to evaluate biofilm's activity. The specific oxygen uptake rate, INT-dehydrogenase activity, and the ratio active/total cells have been applied for that purpose. These methods are not only simple and rapid but also sensitive, precise, and representative. The results obtained confirm the potential of the microbial activity measurements studied for an accurate biofilm's characterization and biomass activity estimation in fundamental research and for the practical operation and control of fixed biomass depuration systems.

Pharmacokinetics of an immediate and extended release oral morphine formulation utilizing the spheroidal oral drug absorption system in dogs.

This study investigated the pharmacokinetics of a human-labeled oral morphine formulation consisting of both immediate and extended release components in dogs. In a randomized design, 14 dogs were administered either 1 or 2 mg/kg morphine orally. Blood samples were collected up to 24 h post drug administration. Plasma concentrations of morphine were measured using high-pressure liquid chromatography with electrochemical coulometric detection. For both groups, maximal concentration occurred at 3 h post drug administration followed by a gradual decrease in morphine concentration over 24 h. There was substantial variability in morphine concentrations among dogs. The higher dose group produced a greater exposure (higher area-under-the-curve), higher peak concentration, longer half-life and a shorter time to peak concentration (t(max)). The specific oral morphine formulation used in this study produced sustained plasma morphine concentrations over 24 h compared with previous intravenous dosing and immediate-release oral morphine studies. However, the low morphine plasma concentrations and high variability produced from this formulation, suggest that the clinical application of this formulation at the doses evaluated in this study are limited.

Comparison of four chemical uncouplers for excess sludge reduction.

A substantial part of the operating costs of wastewater treatment plants (WWTP) is associated with the management and treatment of the excess sludge generated during the treatment process. Different strategies have been applied for excess sludge reduction, such as the oxic-settling-anaerobic process, the high dissolved oxygen process, the uncoupler-containing activated sludge process, the ozonation-combined activated sludge process, control of sludge retention time and biodegradation of sludge in a membrane-assisted reactor. Chemical uncouplers have been shown to reduce excess sludge production, disassociating the energy coupling between catabolism and anabolism. These metabolic uncouplers may be organic compounds, such as 2,4-dinitrophenol (2,4-DNP) or 3,3',4',5-tetrachlorosalicylanilide (TCS), or heavy metals. In this paper, four different chemicals (2,4-DNP, TCS, copper (Cu) and zinc (Zn)) were chosen for short-term tests for studying their ability to reduce sludge yield (Y(x/s)) and, consequently, their potential for reducing excess sludge production. According to the results obtained, only TCS seems to be very effective in reducing sludge production from the activated sludge process. Compared with the control test, Y(x/s) can be reduced by over 30% at 0.8 mg/l TCS. It was also found that the substrate removal capability was not adversely affected by the presence of TCS. Furthermore, an increase in the microbial activity of the system was observed.

Non-ionic surfactant biodegradation in lab-scale activated sludge.

The biodegradation of a non-ionic surfactant was evaluated by the evolution of the microbial activity and the determination of the soluble surfactant present in the effluent. Two lab-activated sludge reactors/systems were fed with synthetic sewage, one of which received in addition different concentrations--5 and 10 mg/L--of nonylphenol ethoxylates (NPEO). The parameters employed in this assay were: control parameters (COD and SS) and activity microbial parameters (specific oxygen uptake rate and dehydrogenase activity). The removal of NPEO and the production of secondary metabolites were monitored. Solid-phase extraction and HPLC with fluorescence detection were employed for sample preparation and analysis. The results suggest that the microbial activity was not inhibited when 5 mg/L of NPEO was added. Nevertheless, an important inhibition of the general metabolism was observed for 10 mg/L of NPEO.

E3 ubiquitin ligases LNX1 and LNX2 are major regulators of the presynaptic glycine transporter GlyT2.

The neuronal glycine transporter GlyT2 is an essential regulator of glycinergic neurotransmission that recaptures glycine in presynaptic terminals to facilitate transmitter packaging in synaptic vesicles. Alterations in GlyT2 expression or activity result in lower cytosolic glycine levels, emptying glycinergic synaptic vesicles and impairing neurotransmission. Lack of glycinergic neurotransmission caused by GlyT2 loss-of-function mutations results in Hyperekplexia, a rare neurological disease characterized by generalized stiffness and motor alterations that may cause sudden infant death. Although the importance of GlyT2 in pathology is known, how this transporter is regulated at the molecular level is poorly understood, limiting current therapeutic strategies. Guided by an unbiased screening, we discovered that E3 ubiquitin ligase Ligand of Numb proteins X1/2 (LNX1/2) modulate the ubiquitination status of GlyT2. The N-terminal RING-finger domain of LNX1/2 ubiquitinates a cytoplasmic C-terminal lysine cluster in GlyT2 (K751, K773, K787 and K791), and this process regulates the expression levels and transport activity of GlyT2. The genetic deletion of endogenous LNX2 in spinal cord primary neurons causes an increase in GlyT2 expression and we find that LNX2 is required for PKC-mediated control of GlyT2 transport. This work identifies, to our knowledge, the first E3 ubiquitin-ligases acting on GlyT2, revealing a novel molecular mechanism that controls presynaptic glycine availability. Providing a better understanding of the molecular regulation of GlyT2 may help future investigations into the molecular basis of human disease states caused by dysfunctional glycinergic neurotransmission, such as hyperekplexia and chronic pain.

Reduction in the anxiolytic effects of ethanol by centrally formed acetaldehyde: the role of catalase inhibitors and acetaldehyde-sequestering agents.

RATIONALE: Considerable evidence indicates that brain ethanol metabolism mediated by catalase is involved in modulating some of the behavioral and physiological effects of this drug, which suggests that the first metabolite of ethanol, acetaldehyde, may have central actions. Previous results have shown that acetaldehyde administered into the lateral ventricles produced anxiolysis in a novel open arena in rats. OBJECTIVES: The present studies investigate the effects of centrally formed acetaldehyde on ethanol-induced anxiolysis. MATERIALS AND METHODS: The effects of the catalase inhibitor sodium azide (SA; 0 or 10 mg/kg, IP) on ethanol-induced anxiolysis (0.0, 0.5, or 1.0 g/kg, IP) were evaluated in CD1 mice in two anxiety paradigms, the elevated plus maze and the dark/light box. Additional studies assessed the effect of the noncompetitive catalase inhibitor 3-amino-1,2,4-triazole (AT; 0.5 g/kg, IP) and the acetaldehyde inactivation agent D: -penicillamine (50 mg/kg, IP) on the plus maze. RESULTS: SA reduced the anxiolytic effects of ethanol on several parameters evaluated in the elevated plus maze and in the dark/light box. In the plus maze, AT completely blocked and D-penicillamine significantly reduced the anxiolytic properties of ethanol. CONCLUSIONS: Thus, when cerebral metabolism of ethanol into acetaldehyde is blocked by catalase inhibitors, or acetaldehyde is inactivated, there is a suppressive effect on the anxiolytic actions of ethanol. These data provide further support for the idea that centrally formed or administered acetaldehyde can contribute to some of the psychopharmacological actions of ethanol, including its anxiolytic properties.

[Traumatic rupture of the diaphragm]. / Rotura diafragmática traumática.

OBJECTIVE: Traumatic rupture of the diaphragm (TRD) is a rare occurrence, with variable morbidity and mortality. The aim of this study was to analyze cases of TRD in a tertiary hospital and assess prognostic factors associated with mortality. PATIENTS AND METHODS: A retrospective study was performed of patients diagnosed with TRD in Hospital Universitario La Fe, Valencia, Spain, between 1969 and 2006. The following variables were analyzed: sex, age, cause, diagnosis, associated lesions, surgical procedure, side and size of the lesion, visceral herniation, and postoperative morbidity and mortality. RESULTS: The study group comprised 132 patients (105 men, 79.5%) with a mean (SD) age of 39.64 (17.04) years. Traffic accidents were the most common cause of TRD. Rupture involved the left hemidiaphragm in 96 cases (72.7%), and 113 patients (85.6%) had associated lesions, most often affecting the abdomen. Thoracotomy was performed in 83 cases (62.9%) and laparotomy in 41 (31.1%). Visceral herniation was reported in 90 patients (68.3%), most often involving the stomach. The rates of perioperative morbidity and mortality were 62.8% and 20.5%, respectively. Diagnostic delay and the presence of morbidity and serious associated lesions all had a statistically significant impact on mortality (P< .05). In the case of serious associated lesions, the odds ratio was 2.898 (95% confidence interval, 1.018-8.250) and for perioperative morbidity it was 1.488 (95% confidence interval, 1.231-1.798). CONCLUSIONS: TRD is an infrequent occurrence in young men, is generally caused by traffic accidents, and is more common on the left side. Associated lesions are present in most cases and represent the main prognostic factor affecting morbidity and mortality. TRD can be considered a relative surgical emergency when not accompanied by other lesions that in themselves constitute surgical emergencies.

[Importance of artificial nutrition in the resolution and etiologic diagnosis of severe chronic diarrhea: a propos of a case]. / Importancia de la nutrición artificial en la resolución y diagnóstico etiológico de diarrea crónica severa: a propósito de un caso.

We present a case of severe chronic diarrhea requiring parenteral nutritional support to both cover the nutritional needs and allow for intestinal rest for later adaptation to enteral nutrition, altogether allowing for the etiologic diagnosis and disease healing.

[Pathophysiology of the glutamate and the glycine transporters: new therapeutic targets]. / Fisiopatologia de los transportadores de glutamato y de glicina: nuevas dianas terapeuticas.

INTRODUCTION: The amino acids glutamate and glycine, apart from their role in protein synthesis, are two fundamental neurotransmitters in the central nervous system of mammals. The first one is ubiquitous and is involved in excitatory pathways of the neocortex, the retina and the cerebellum, and the second is involved in inhibitory pathways of brain caudal areas. However, both share their way of acting by integrating into the functioning of glutamate receptors of the NMDA type fundamentals in the regulation of motor, sensory and cognitive systems. AIM: To highlight the need for a fine regulation of glutamate and glycine concentrations in the intracellular and extracellular spaces of the nervous system through the action of very specific transporters for both neurotransmitters located in the plasma membrane of neurons and glial cells. DEVELOPMENT: The role of the glutamate and glycine transporters in glutamatergic and glycinergic neurotransmission and in the functioning of the nervous system is described. The pathological consequences of imbalances in these signaling pathways are pointed out. We also describe its involvement in pathologies such as schizophrenia, chronic pain, cerebral ischemia, diseases such as hereditary hyperekplexia and the non-ketotic hyperglycinemia, and neurodegenerative disorders. CONCLUSIONS: The knowledge at molecular level of the way of acting of these transporters for glutamate and glycine is allowing the identification and development of new therapeutic strategies for pathologies such as those described above and the development of new drugs.

TITLE: Fisiopatologia de los transportadores de glutamato y de glicina: nuevas dianas terapeuticas.Introduccion. Los aminoacidos glutamato y glicina, aparte de su papel en la sintesis de proteinas, son dos neurotransmisores fundamentales en el sistema nervioso central de los mamiferos. El primero es ubicuo y esta implicado en vias excitatorias de la neocorteza, la retina y el cerebelo, y el segundo esta asociado a vias inhibitorias de zonas caudales del cerebro. Sin embargo, ambos comparten su manera de actuar al integrarse en el funcionamiento de los receptores de glutamato del tipo NMDA, fundamentales en la regulacion de sistemas motores, sensitivos y cognitivos. Objetivo. Evidenciar la necesidad de una regulacion exquisita de las concentraciones de glutamato y de glicina en los espacios intra y extracelulares del sistema nervioso mediante la actuacion de transportadores muy especificos para ambos neurotransmisores localizados en la membrana plasmatica de las neuronas y de las celulas de la glia. Desarrollo. Se describe el papel de los transportadores de glutamato y glicina en la neurotransmision glutamatergica y glicinergica, y en el funcionamiento del sistema nervioso. Se señalan las consecuencias patologicas de los desequilibrios en estas vias de señalizacion. Tambien se describe su participacion en patologias como la esquizofrenia, el dolor cronico, la isquemia cerebral, la hiperplexia hereditaria, la hiperglicinemia no cetosica o trastornos neurodegenerativos. Conclusiones. El conocimiento de la forma molecular de actuar de los transportadores de glutamato y de glicina esta permitiendo la identificacion y el desarrollo de nuevas estrategias terapeuticas para patologias como las descritas y el desarrollo de nuevos farmacos.