39 research outputs found

    Different Corticostriatal Integration in Spiny Projection Neurons from Direct and Indirect Pathways

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    The striatum is the principal input structure of the basal ganglia. Major glutamatergic afferents to the striatum come from the cerebral cortex and make monosynaptic contacts with medium spiny projection neurons (MSNs) and interneurons. Also: glutamatergic afferents to the striatum come from the thalamus. Despite differences in axonal projections, dopamine (DA) receptors expression and differences in excitability between MSNs from “direct” and “indirect” basal ganglia pathways, these neuronal classes have been thought as electrophysiologically very similar. Based on work with bacterial artificial chromosome (BAC) transgenic mice, here it is shown that corticostriatal responses in D1- and D2-receptor expressing MSNs (D1- and D2-MSNs) are radically different so as to establish an electrophysiological footprint that readily differentiates between them. Experiments in BAC mice allowed us to predict, with high probability (P > 0.9), in rats or non-BAC mice, whether a recorded neuron, from rat or mouse, was going to be substance P or enkephalin (ENK) immunoreactive. Responses are more prolonged and evoke more action potentials in D1-MSNs, while they are briefer and exhibit intrinsic autoregenerative responses in D2-MSNs. A main cause for these differences was the interaction of intrinsic properties with the inhibitory contribution in each response. Inhibition always depressed corticostriatal depolarization in D2-MSNs, while it helped in sustaining prolonged depolarizations in D1-MSNs, in spite of depressing early discharge. Corticostriatal responses changed dramatically after striatal DA depletion in 6-hydroxy-dopamine (6-OHDA) lesioned animals: a response reduction was seen in substance P (SP)+ MSNs whereas an enhanced response was seen in ENK+ MSNs. The end result was that differences in the responses were greatly diminished after DA depletion

    Dopaminergic Modulation of Corticostriatal Responses in Medium Spiny Projection Neurons from Direct and Indirect Pathways

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    Suprathreshold corticostriatal responses recorded from medium spiny neurons (MSNs) from the direct and indirect pathways of the basal ganglia are different. Their differences readily distinguish D1- and D2-type receptor expressing MSNs in both bacterial artificial chromosome-transgenic mice and their control littermates as well as in rats: indirect pathway neurons are more excitable than direct pathway neurons revealing autoregenerative spikes underlying their spike trains, whereas direct pathway neurons exhibit more prolonged plateau potentials and spike trains. SFK 81297, a selective agonist for D1-class receptors enhanced corticostriatal responses in direct pathway neurons, while quinelorane, a selective agonist for D2-class receptors reduced orthodromic and autoregenerative responses in indirect pathway neurons thus making both neuron classes similarly excitable. Because dopaminergic postsynaptic actions target CaV1 (L) class voltage-gated calcium channels in MSNs, we hypothesized that these channels are involved and can explain a part of the dopaminergic actions on corticostriatal integration. Both 2.5 μM nicardipine and 400 nM calciseptine, selective CaV1 channel blockers, reduced corticostriatal responses in both D1- and D2-receptor expressing neurons, respectively. A previous blockade of CaV1 channels occluded the actions of dopamine agonists in both neuronal classes. In contrast, a CaV1 (L) channel activator, 2.5 μM Bay K 8644, enhanced corticostriatal responses in neurons from both pathways. It is concluded that CaV1 intrinsic currents mediate a part of the dopaminergic modulation during orthodromic synaptic integration of cortical inputs in both classes of MSNs

    Extracorporeal membrane oxygenation improves survival in a novel 24-hour pig model of severe acute respiratory distress syndrome

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    Indexación: Web of Science; Pub Med CentralExtracorporeal membrane oxygenation (ECMO) is increasingly being used to treat severe acute respiratory distress syndrome (ARDS). However, there is limited clinical evidence about how to optimize the technique. Experimental research can provide an alternative to fill the actual knowledge gap. The purpose of the present study was to develop and validate an animal model of acute lung injury (ALI) which resembled severe ARDS, and which could be successfully supported with ECMO. Eighteen pigs were randomly allocated into three groups: sham, ALI, and ALI + ECMO. ALI was induced by a double-hit consisting in repeated saline lavage followed by a 2-hour period of injurious ventilation. All animals were followed up to 24 hours while being ventilated with conventional ventilation (tidal volume 10 ml/kg). The lung injury model resulted in severe hypoxemia, increased airway pressures, pulmonary hypertension, and altered alveolar membrane barrier function, as indicated by an increased protein concentration in bronchoalveolar fluid, and increased wet/dry lung weight ratio. Histologic examination revealed severe diffuse alveolar damage, characteristic of ARDS. Veno-venous ECMO was started at the end of lung injury induction with a flow > 60 ml/kg/min resulting in rapid reversal of hypoxemia and pulmonary hypertension. Mortality was 0, 66.6 and 16.6% in the SHAM, ALI and ALI + ECMO groups, respectively (p < 0.05). This is a novel clinically relevant animal model that can be used to optimize the approach to ECMO and foster translational research in extracorporeal lung support.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931177

    Caracterización geométrica y cinemática de un chorro pulverizado empleando la técnica óptica PTV

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    Los fenómenos naturales o inducidos que involucran el movimiento de gotas motivan análisis para determinar aspectos como la pérdida de suelo por erosión o los cambios que pudieran ocurrir en la tasa de infiltración debido a la energía con la que impactan sobre la superficie del suelo. El diámetro y la velocidad definen la magnitud del efecto. Para caracterizar estas variables se han aplicando diversas técnicas (papel sensible al agua, harina, inmersiones en aceite, ópticas y fotografía). En este sentido, la presente investigación emplea velocimetría por rastreo de partículas (PTV) en la caracterización de gotas emitidas por un pulverizador de flujo. PTV ha encaminado parte de su desarrollo al análisis de la velocidad de sedimentación en flujos bifásicos donde se requiere del sembrado de partículas trazadoras para evaluar el fenómeno; sin embargo, las características experimentales del trabajo obligaron a omitir el uso de estos elementos, por lo que fue indispensable hacer adecuaciones al esquema propuesto por Salinas et al. (2006). Las gotas se originaron a una presión hidráulica constante de 175 kPa, las fotografías se capturaron a una distancia de 4.5 m con tres alturas diferentes del pulverizador. La información recolectada (diámetros y velocidades) posibilitó la construcción de campos vectoriales de velocidad. Los resultados presentados derivan del análisis de 1 582 gotas, con las que se obtuvieron valores medios de 0.39, 0.55 y 0.34 mm en diámetro, y 4.02, 3.70 y 3.63 ms-1 en velocidad, para alturas de 0.5, 1.0 y 1.5 m, respectivamente

    Impairment of exogenous lactate clearance in experimental hyperdynamic septic shock is not related to total liver hypoperfusion

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    Introduction: Although the prognostic value of persistent hyperlactatemia in septic shock is unequivocal, its physiological determinants are controversial. Particularly, the role of impaired hepatic clearance has been underestimated and is only considered relevant in patients with liver ischemia or cirrhosis. Our objectives were to establish whether endotoxemia impairs whole body net lactate clearance, and to explore a potential role for total liver hypoperfusion during the early phase of septic shock. Methods: After anesthesia, 12 sheep were subjected to hemodynamic/perfusion monitoring including hepatic and portal catheterization, and a hepatic ultrasound flow probe. After stabilization (point A), sheep were alternatively assigned to lipopolysaccharide (LPS) (5 mcg/kg bolus followed by 4 mcg/kg/h) or sham for a three-hour study period. After 60 minutes of shock, animals were fluid resuscitated to normalize mean arterial pressure. Repeated series of measurements were performed immediately after fluid resuscitation (point B), and one (point C) and two hours later (point D). Monitoring included systemic and regional hemodynamics, blood gases and lactate measurements, and ex-vivo hepatic mitochondrial respiration at point D. Parallel exogenous lactate and sorbitol clearances were performed at points B and D. Both groups included an intravenous bolus followed by serial blood sampling to draw a curve using the least squares method. Results: Significant hyperlactatemia was already present in LPS as compared to sham animals at point B (4.7 (3.1 to 6.7) versus 1.8 (1.5 to 3.7) mmol/L), increasing to 10.2 (7.8 to 12.3) mmol/L at point D. A significant increase in portal and hepatic lactate levels in LPS animals was also observed. No within-group difference in hepatic DO2, VO2 or O2 extraction, total hepatic blood flow (point D: 915 (773 to 1,046) versus 655 (593 to 1,175) ml/min), mitochondrial respiration, liver enzymes or sorbitol clearance was found. However, there was a highly significant decrease in lactate clearance in LPS animals (point B: 46 (30 to 180) versus 1,212 (743 to 2,116) ml/min, P <0.01; point D: 113 (65 to 322) versus 944 (363 to 1,235) ml/min, P <0.01). Conclusions: Endotoxemia induces an early and severe impairment in lactate clearance that is not related to total liver hypoperfusion

    MAREJADAS RURALES Y LUCHAS POR LA VIDA, VOL. III: VAIVENES DEL ESTADO Y LA SOCIEDAD RURAL.

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    Volumen 3. Vaivenes del Estado y la Sociedad Rural, coordinado por: Francisco Herrera Tapia, Gladys Karina Sánchez Juárez, e Ignacio López Moreno, el texto está constituído por 12 capítulos, los autores abordan problemas derivados de la aplicación de las políticas públicas y reformas legislativas relacionadas con el campo, y con las instituciones de gobierno, la gobernabilidad, los acuerdos comunitarios y también los conflictos, son estudios de caso que evidencian estos procesos y las formas en que se complejizan o se resuelven en el medio rural.ASOCIACIÓN MEXICANA DE ESTUDIOS RURALES A.C., INSTITUTO DE CIENCIAS AGROPECUARIAS Y RURALES (ICAR), UNIVERSIDAD DE GUADALAJARA, EL COLEGIO DE MICHOACÁN A.C., UNIVERSIDAD MICHOACANA DE SAN NICOLAS HIDALGO, CUCOSTA SUR GRANA, ECOSUR, FACULTAD DE ESTUDIOS SUPERIORES ACATLÁN-UNA

    Caracterización geométrica y cinemáticade un chorro pulverizado empleando la técnica óptica PTV

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    SALINAS-TAPIA, H., ROBLES-ROVELO, C.O., CHÁVEZ-CARLOS, D. & BAUTISTA-CAPETILLO, C.F. Caracteriza-ción geométrica y cinemática de un chorro pulverizado em-pleando la técnica óptica PTV.Tecnología y Ciencias del Agua.Vol. V, núm. 3, mayo-junio de 2014, pp. 125-140.Los fenómenos naturales o inducidos que involucran elmovimiento de gotas motivan análisis para determinaraspectos como la pérdida de suelo por erosión o los cambiosque pudieran ocurrir en la tasa de infiltración debido a laenergía con la que impactan sobre la superficie del suelo.El diámetro y la velocidad definen la magnitud del efecto.Para caracterizar estas variables se han aplicando diversastécnicas (papel sensible al agua, harina, inmersiones enaceite, ópticas y fotografía). En este sentido, la presenteinvestigación emplea velocimetría por rastreo de partículas(PTV) en la caracterización de gotas emitidas por unpulverizador de flujo. PTV ha encaminado parte de sudesarrollo al análisis de la velocidad de sedimentación enflujos bifásicos donde se requiere del sembrado de partículastrazadoras para evaluar el fenómeno; sin embargo, lascaracterísticas experimentales del trabajo obligaron a omitirel uso de estos elementos, por lo que fue indispensable haceradecuaciones al esquema propuesto por Salinaset al.(2006).Las gotas se originaron a una presión hidráulica constantede 175 kPa, las fotografías se capturaron a una distanciade 4.5 m con tres alturas diferentes del pulverizador. Lainformación recolectada (diámetros y velocidades) posibilitóla construcción de campos vectoriales de velocidad. Losresultados presentados derivan del análisis de 1 582 gotas,con las que se obtuvieron valores medios de 0.39, 0.55 y 0.34mm en diámetro, y 4.02, 3.70 y 3.63 ms-1en velocidad, paraalturas de 0.5, 1.0 y 1.5 m, respectivamente

    Main functions and taxonomic distribution of virulence genes in Brucella melitensis 16 M.

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    Many virulence genes have been detected in attenuated mutants of Brucella melitensis 16 M; nevertheless, a complete report of these genes, including the main Cluster of Orthologous Groups (COG) represented as well as the taxonomical distribution among all complete bacterial and archaeal genomes, has not been analyzed. In this work a total of 160 virulence genes that have been reported in attenuated mutants in B. melitensis were included and analyzed. Additionally, we obtained 250 B. melitensis randomly selected genes as a reference group for the taxonomical comparisons. The COGs and the taxonomical distribution profile for 789 nonredundant bacterial and archaeal genomes were obtained and compared with the whole-genome COG distribution and with the 250 randomly selected genes, respectively. The main COGs associated with virulence genes corresponded to the following: intracellular trafficking, secretion and vesicular transport (U); cell motility (N); nucleotide transport and metabolism (F); transcription (K); and cell wall/membrane/envelope biogenesis (M). In addition, we found that virulence genes presented a higher proportion of orthologs in the Euryarchaeota and Proteobacteria phyla, with a significant decrease in Chlamydiae, Bacteroidetes, Tenericutes, Firmicutes and Thermotogae. In conclusion, we found that genes related to specific functions are more relevant to B. melitensis virulence, with the COG U the most significant. Additionally, the taxonomical distribution of virulence genes highlights the importance of these genes in the related Proteobacteria, being less relevant in distant groups of organisms with the exception of Euryarchaeota
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