Vesicular glutamate transporters play a role in neuronal differentiation of cultured SVZ-derived neural precursor cells.

The role of glutamate in the regulation of neurogenesis is well-established, but the role of vesicular glutamate transporters (VGLUTs) and excitatory amino acid transporters (EAATs) in controlling adult neurogenesis is unknown. Here we investigated the implication of VGLUTs in the differentiation of subventricular zone (SVZ)-derived neural precursor cells (NPCs). Our results show that NPCs express VGLUT1-3 and EAAT1-3 both at the mRNA and protein level. Their expression increases during differentiation closely associated with the expression of marker genes. In expression analyses we show that VGLUT1 and VGLUT2 are preferentially expressed by cultured SVZ-derived doublecortin+ neuroblasts, while VGLUT3 is found on GFAP+ glial cells. In cultured NPCs, inhibition of VGLUT by Evans Blue increased the mRNA level of neuronal markers doublecortin, B3T and MAP2, elevated the number of NPCs expressing doublecortin protein and promoted the number of cells with morphological appearance of branched neurons, suggesting that VGLUT function prevents neuronal differentiation of NPCs. This survival- and differentiation-promoting effect of Evans blue was corroborated by increased AKT phosphorylation and reduced MAPK phosphorylation. Thus, under physiological conditions, VGLUT1-3 inhibition, and thus decreased glutamate exocytosis, may promote neuronal differentiation of NPCs.

Methanol extract of Nigella sativa seed induces changes in the levels of neurotransmitter amino acids in male rat brain regions.

CONTEXT: Nigella sativa L. (Ranunculaceae) (NS) has been used for medicinal and culinary purposes. Different parts of the plant are used to treat many disorders. OBJECTIVE: This study investigates the effects of NS methanol extract on brain neurotransmitter amino acid levels. MATERIALS AND METHODS: We measured the changes in aspartate, glutamate, glycine and γ-aminobutyric acid in five brain regions of male Wistar rats after methanol extract treatment. Animals were injected intraperitoneally with saline solution (controls) or NS methanol extract (equivalent of 2.5 g/kg body weight) and sacrificed 1 h later or after administering 1 daily dose for 8 days. The neurotransmitters were measured in the hypothalamus, cortex, striatum, hippocampus and thalamus by HPLC. RESULTS AND DISCUSSION: Results showed significant changes in amino acids compared to basal values. Glutamate increased significantly (16-36%) in the regions analyzed except the striatum. Aspartate in the hypothalamus (50 and 76%) and glycine in hippocampus (32 and 25%), thalamus (66 and 29%) and striatum (75 and 48%) also increased with the two treatment intervals. γ-Aminobutyric acid significantly increased in the hippocampus (38 and 32%) and thalamus (22 and 40%) but decreased in the cortex and hypothalamus although in striatum only after eight days of treatment (24%). CONCLUSION: Our results suggest that injected methanol extract modifies amino acid levels in the rat brain regions. These results could be of interest since some neurodegenerative diseases are related to amino acid level imbalances in the central nervous system, suggesting the prospect for therapeutic use of NS against these disorders.

The nitric oxide donor SNAP-induced amino acid neurotransmitter release in cortical neurons. Effects of blockers of voltage-dependent sodium and calcium channels.

BACKGROUND: The discovery that nitric oxide (NO) functions as a signalling molecule in the nervous system has radically changed the concept of neuronal communication. NO induces the release of amino acid neurotransmitters but the underlying mechanisms remain to be elucidated. FINDINGS: The aim of this work was to study the effect of NO on amino acid neurotransmitter release (Asp, Glu, Gly and GABA) in cortical neurons as well as the mechanism underlying the release of these neurotransmitters. Cortical neurons were stimulated with SNAP, a NO donor, and the release of different amino acid neurotransmitters was measured by HPLC. The involvement of voltage dependent Na+ and Ca2+ channels as well as cGMP in its mechanism of action was evaluated. CONCLUSIONS: Our results indicate that NO induces release of aspartate, glutamate, glycine and GABA in cortical neurons and that this release is inhibited by ODQ, an inhibitor of soluble guanylate cyclase. Thus, the NO effect on amino acid neurotransmission could be mediated by cGMP formation in cortical neurons. Our data also demonstrate that the Na+ and Ca2+ voltage- dependent calcium channels are involved in the NO effects on cortical neurons.

Drugs for stroke: action of nitrone (Z)-N-(2-bromo-5-hydroxy-4-methoxybenzylidene)-2-methylpropan-2-amine oxide on rat cortical neurons in culture subjected to oxygen-glucose-deprivation.

The action of (Z)-N-(2-bromo-5-hydroxy-4-methoxybenzylidene)-2-methylpropan-2-amine oxide (RP6) on rat cortical neurons in culture, under oxygen-glucose-deprivation conditions, is reported. Cortical neurons in culture were treated during 1 h with OGD. After, they were placed under normal conditions during 24 h (reperfusion) in absence and presence of RP6. Different parameters were measured under each condition (control, 1 h OGD and 1 h OGD + reperfusion in absence and presence of RP6). RP6 protects neurons against ROS generation, lipid peroxidation levels, LDH release and mitochondrial membrane potential alteration, when administered during reperfusion after the OGD damage. Consequently, these results show that nitrone RP6 protects cells against ischemia injury produced during the reoxygenation, and could be a potential drug for the ictus therapy.

Nigella sativa L. seed extract modulates the neurotransmitter amino acids release in cultured neurons in vitro.

Nigella sativa L. (NS) has been used for medicinal purposes since ancient times. This study aimed to investigate the cytotoxicity of NS dry methanolic extract on cultured cortical neurons and its influence on neurotransmitter release, as well as the presence of excitatory (glutamate and aspartate) and inhibitory amino acids (gamma-aminobutyric acid-GABA-and glycine) in NS extract. Cultured rat cortical neurons were exposed to different times and concentrations of NS dry methanolic extract and cell viability was then determined by a quantitative colorimetric method. NS did not induce any toxicity. The secretion of different amino acids was studied in primary cultured cortical neurons by high-performance liquid chromatography (HPLC) using a derivation before injection with dansyl chloride. NS modulated amino acid release in cultured neurons; GABA was significantly increased whereas secretion of glutamate, aspartate, and glycine were decreased. The in vitro findings support the hypothesis that the sedative and depressive effects of NS observed in vivo could be based on changes of inhibitory/excitatory amino acids levels.

Transient focal cerebral ischemia significantly alters not only EAATs but also VGLUTs expression in rats: relevance of changes in reactive astroglia.

The involvement of plasma membrane glutamate transporters (EAATs - excitatory aminoacid transporters) in the pathophysiology of ischemia has been widely studied, but little is known about the role of vesicular glutamate transporters (VGLUTs) in the ischemic process. We analyzed the expression of VGLUT1-3 in the cortex and caudate-putamen of rats subjected to transient middle cerebral artery occlusion. Western blot and immunohistochemistry revealed an increase of VGLUT1 signal in cortex and caudate-putamen until 3 days of reperfusion followed by a reduction 7 days after the ischemic insult. By contrast, VGLUT2 and 3 were drastically reduced. Confocal microscopy revealed an increase in VGLUT2 and 3 immunolabelling in the reactive astrocytes of the ischemic corpus callosum and cortex. Changes in VGLUTs and EAATs expression were differently correlated to neurological deficits. Interestingly, changes in VGLUT1 and EAAT2 expression showed a significant positive correlation in caudate-putamen. Taken together, these results suggest a contribution of VGLUTs to glutamate release in these structures, which could promote neuroblast migration and neurogenesis during ischemic recovery, and a possible interplay with EAATs in the regulation of glutamate levels, at least in the first stages of ischemic recovery.

[The state of mental health primary care in the social services of El Alto, La Paz, Bolivia]. / Situación de la atención primaria de salud mental en servicios públicos de El Alto, La Paz, Bolivia.

OBJECTIVES: To determine the mental health and behavioral disorders (MHBD) treated by a Bolivian health network; and to gauge the perspective of the health professionals, community members, and care-providers in order to identify ways to better handle the issues. METHODS: A descriptive cross-sectional study was conducted from January to December 2005 in 15 public health centers in districts 2 and 3 of the Corea Network, one of four urban networks in the municipality of El Alto, province of Murillo, department of La Paz, Bolivia. The research and active participation methodology was employed through interviews, focus group sessions, review of external consultation logs and clinical histories, and active observation. RESULTS: Only 0.05% of primary care visits were for MHBD. Among the barriers identified by doctors were: lack of a specialized reference center (60.0%), not enough time (40.0%), a shortage of specialized personnel (33.3%), the drug supply (20.0%), and undertrained staff (16.6%). The departmental and federal programs have limited human resources training, standards of care are nonexistent, and the information system does not collect data on MHBD. Community members amply identified the mental health problems and care needs that, to date, have not been met by the social services. Conclusiones: Training and development of primary care services staff must be expanded so as to provide the proper care for mental health disorders. Improvements must be made in the management of health care services and the reporting of behavioral and mental health disorders. Another recommendation is to incorporate community participation in the model approach to mental health within the framework of primary health care.

Situación de la atención primaria de salud mental en servicios públicos de El Alto, La Paz, Bolivia / The state of mental health primary care in the social services of El Alto, La Paz, Bolivia

OBJETIVOS: Caracterizar los trastornos de salud mental o conductuales (TSMC) atendidos en una red de salud boliviana y conocer la percepción de profesionales sanitarios, representantes de la comunidad y responsables de brindar los servicios a fin de identificar los elementos necesarios para mejorar la respuesta a estos problemas. MÉTODO: Se realizó un estudio transversal descriptivo entre enero y diciembre de 2005 en los 15 centros públicos de salud de los distritos 2 y 3 pertenecientes a la Red Corea, una de las cuatro redes urbanas del municipio de El Alto, provincia de Murillo, departamento de La Paz, Bolivia. Se utilizó la metodología de investigación y acción participativa mediante entrevistas, sesiones en grupos focales, análisis de los cuadernos de registros de consultas externas e historias clínicas y la observación participante. RESULTADOS: Solo 0,05 por ciento de las consultas en los servicios de primer nivel correspondían a TSMC. Entre las dificultades percibidas por los médicos para la atención de esos pacientes están la falta de un centro de referencia especializado (60,0 por ciento), la falta de tiempo (40,0 por ciento), la ausencia de personal especializado (33,3 por ciento), la carencia de medicamentos (20,0 por ciento) y la insuficiente capacitación del personal (16,6 por ciento). Los programas departamentales y nacionales tienen limitaciones para la capacitación de los recursos humanos, no existen normas de atención y el sistema de información no registra variables sobre TSMC. Las personas de la comunidad identificaron adecuadamente los problemas de salud mental y las necesidades de atención que a la fecha no tienen respuesta de los servicios. CONCLUSIONES: Se deben fortalecer la formación y la capacitación del personal de los servicios de atención primaria de salud para lograr una adecuada atención de los trastornos de salud mental. Se debe mejorar la gestión de los servicios y el registro de los trastornos de comportamiento ...

OBJECTIVES: To determine the mental health and behavioral disorders (MHBD) treated by a Bolivian health network; and to gauge the perspective of the health professionals, community members, and care-providers in order to identify ways to better handle the issues. METHODS: A descriptive cross-sectional study was conducted from January to December 2005 in 15 public health centers in districts 2 and 3 of the Corea Network, one of four urban networks in the municipality of El Alto, province of Murillo, department of La Paz, Bolivia. The research and active participation methodology was employed through interviews, focus group sessions, review of external consultation logs and clinical histories, and active observation. RESULTS: Only 0.05 percent of primary care visits were for MHBD. Among the barriers identified by doctors were: lack of a specialized reference center (60.0 percent), not enough time (40.0 percent), a shortage of specialized personnel (33.3 percent), the drug supply (20.0 percent), and undertrained staff (16.6 percent). The departmental and federal programs have limited human resources training, standards of care are nonexistent, and the information system does not collect data on MHBD. Community members amply identified the mental health problems and care needs that, to date, have not been met by the social services. CONCLUSIONES: Training and development of primary care services staff must be expanded so as to provide the proper care for mental health disorders. Improvements must be made in the management of health care services and the reporting of behavioral and mental health disorders. Another recommendation is to incorporate community participation in the model approach to mental health within the framework of primary health care.

Sarcoma de células claras con toma ósea: presentación de un caso / Clear cell sarcoma with bony dose: a case report

Paciente femenina de 20 años, color de la piel negra, con antecedentes de salud que acude a consulta por dolor en la rodilla izquierda y tercio superior de la tibia izquierda de varios meses de evolución. La radiografía de hueso muestra una imágen osteolítica en la metáfisis superior de la tibia izquierda planteándose la posibilidad de tumor primario óseo. Se realiza biopsia por aspiración con aguja fina de la lesión y se informa como un tumor de células redondas, se encomienda biopsia la cual se concluye como un sarcoma de células claras, las técnicas de Inmunohistoquímica para HMB-45, S-100 y Vimentina fueron positivas, la ultraestructura informó la presencia de premelanosomas maduros. Se realiza amputación del miembro inferior a nivel del tercio medio del femur y se administra quimioterapia coadyuvante con Cisplatino y Adriamicina

Estudio anatomopatológico del cáncer de colon y recto en pacientes operados: año 2000-2001 / Anatomopathological study of colon and rectum cancer in operated patients: 2000-2001 year

El cáncer de colon y recto representa un gran problema de salud mundial, especialmente los de tipo epitelial. El advenimiento de nuevos conocimientos en este campo, la existencia de clasificaciones pronósticas, prefeccionadas con el desarrollo científico técnico incorporando hoy estudios genéticos y de biología molecular nos motivaron a realizar este estudio descriptivo en los años 2000 y 2001 sobre el comportamiento de esta enfermedad en pacientes intervenidos en nuestro centro a los cuales se logró realizar resección quirúrgica del tumor, su distribución por edad y sexo, sintomatología, morfología tumoral, determinamos los factores que permiten estudiar según las clasificaciones pronósticas más usadas que incluyen: estadificación de Astler y Coller, TNMp y estadíos anatomopatológicos de Rosai, correlacionamos las mismas. Se revisan ordenes de biopsias, expedientes clínicos y entrevistamos a los pacientes

Histiocitosis maligna: estudio clinicomorfológico e inmunohistoquímico de 3 casos / Malign histiocytosis: medical-morphological and immunohistochemical study of three cases

Se estudian 3 fallecidos por histiocitosis maligna, los cuales clinicamente evolucionaron con fiebre, íctero, hepatoesplenomegalia y pancitopenia con curso rápido hacia la muerte. Se encontró que la infiltración neoplásica afectò fundamentalmente la médula ósea, bazo, hígado y ganglios linfático, provocada por histiocitos morfológicamente típicos y atípicos, algunos de los cuales mostraban fagocitosisde elementos formes de la sangre. El carácter histiocitario se puso de manifiesto con el empleo de antisueros para lisozima, antiquimiotripsina y antitripsina

Duplicación intestinal retroperitoneal: presentación de dos casos / Retroperitoneal intestinal duplication: report of 2 cases

Se presentan dos casos operados de duplicidad intestinal a forma tumoral retroperitoneal sin conexión con el tracto digestivo en nuestro servicio de cirugía del Hospital Provincial Docente de Santa Clara. Se observa que la sintomatología de los dos casos referidos estaban en ralación con los fenómenos compresivos causados por el tamaño de la tumoración. Se hace énfasis en la poca frecuencia con que se presenta esta enfermedad en pacientes adultos, y se informan las anomálias congénitas vascular y urinaria que presentan. El tratamiento de elección es el quirúrgico