Ecografía de los troncos supraaórticos / Ultrasonography of supra-aortic trunks

La ecografía es un recurso del que disponemos de primera mano los médicos de familia y al que cada vez más frecuentemente recurrimos, hasta el punto de formar ya parte de nuestra exploración física. Es una técnica diagnóstica de fácil acceso, asequible, versátil y no invasiva que emplea los ultrasonidos para definir las estructuras anatómicas de nuestro cuerpo sin necesidad de radiación y que se realiza en tiempo real, pudiendo permitir una exploración dinámica. Pese a todo lo mencionado, la ecografía vascular y, en concreto, la de los troncos supraaórticos no está tan extendida en nuestro ámbito, pese a su importante papel en el ámbito de la prevención cardiovascular, fundamental en la atención primaria. Por este motivo en este artículo se pretende llevar a cabo una breve y clara descripción de la técnica con el objetivo de extender su uso en la práctica cotidiana (AU)

Ultrasound is a resource that family doctors have first-hand and that we use more and more frequently, to the point of becoming part of our physical examination. It is an easily accessible, affordable, versatile and non-invasive diagnostic technique that uses ultrasound to define the anatomical structures of our body without radiation and is performed in real time, allowing a dynamic exploration. Despite all the above, vascular ultrasound and, specifically, the supra-aortic trunks ultrasound is not as widespread in our setting, despite its important role in the field of cardiovascular prevention, which is essential in primary care. For this reason, this article aims to carry out a brief-and-clear description of the technique with the aim of extending its use in daily practice (AU)

[Ultrasonography of supra-aortic trunks]. / Ecografía de los troncos supraaórticos.

Ultrasound is a resource that family doctors have first-hand and that we use more and more frequently, to the point of becoming part of our physical examination. It is an easily accessible, affordable, versatile and non-invasive diagnostic technique that uses ultrasound to define the anatomical structures of our body without radiation and is performed in real time, allowing a dynamic exploration. Despite all the above, vascular ultrasound and, specifically, the supra-aortic trunks ultrasound is not as widespread in our setting, despite its important role in the field of cardiovascular prevention, which is essential in primary care. For this reason, this article aims to carry out a brief-and-clear description of the technique with the aim of extending its use in daily practice.

In vivo oncogenic conflict triggered by co-existing KRAS and EGFR activating mutations in lung adenocarcinoma.

Activating mutations in KRAS and EGFR, the two most frequent oncogenes in human lung adenocarcinoma, are mutually exclusive, a phenotype attributed to functional redundancy implying lack of positive selection. Employing a mouse model expressing EGFRL858R in advanced KrasG12V-driven tumors we show that their mutual exclusivity can be explained by detrimental effects of their co-expression in lung adenocarcinoma. In vivo, expression of EGFRL858R in KrasG12V-driven tumors triggers replicative stress and apoptosis, while the surviving cells enter a transient cytostatic state incompatible with tumor development that is fully reversible upon discontinued EGFRL858R expression. Eventually, sustained expression of both mutants induces attenuation of oncogenic signaling to levels compatible with proliferation and tumor growth resulting in high sensitivity to Mek inhibition. Our results indicate that the mutual exclusivity of KRAS and EGFR mutations occurs as a combination of cellular toxicity and signal adjustment resulting in lack of selective advantage for cells expressing both oncogenes.

Análisis del tiempo de vida útil en la elaboración de mermelada de higuerón (Cucúrbita Odorífera Vell) con zanahoria (Daucus Carota) / Time analysis of life in the development of marmalade higuerón (Cucurbita Odorifera Vell) with carrot (Daucus Carota)

The aim of this study was to determine the lifespan in making jam by higueron and carrot mixture, motivated by the lack of a number of species of tubers and vegetables, as evidenced by the low consumption of these foods and the lack of appropriate technology for processing the same. The two raw materials are high in vitamins and minerals, higueron suitable for their characteristics and chemical composition is considered a fruit-vegetable, it is possible it industrialization similar to those made with fruits, like the carrot is a food products excellent from the nutritional point of view, contributing to improve the quality of the jam. The treatments were kept under ambient conditions for 40 days when pH were recorded - soluble solids (° Brix) - Heartburn - Microbiological and organoleptic analysis in order to identify the best experimental treatment tests. According to the results obtained and microbiological analysis establishes a lifetime about 6 months.

El objetivo de este estudio fue conocer el tiempo de vida útil en la elaboración de mermelada mediante una mezcla higuerón y zanahoria, motivado por el desconocimiento de un sinnúmero de especies de tubérculos y hortalizas, evidenciado por el bajo consumo de estos alimentos y la carencia de tecnología adecuada para el procesamiento del mismo y aprovechamiento de sus nutrientes. Las dos materias primas de alto contenido de vitaminas y minerales; el higuerón se considera como fruta-hortaliza por sus características y composición química, siendo posible la industrialización en productos semejantes a los elaborados con las frutas. La zanahoria es un alimento excelente desde el punto de vista nutricional por lo que aporta al mejoramiento de la calidad de la mermelada. Los tratamientos se mantuvieron bajo condiciones ambientales durante 40 días en los que se registró pH - sólidos solubles (°Brix) - acidez - análisis microbiológicos y pruebas organolépticas con la finalidad de identificar el mejor tratamiento experimental. De acuerdo a los resultados obtenidos y al análisis microbiológico se establece un tiempo de vida útil alrededor de 6 meses.

Characterization and follow-up of esophagogastric junction outflow obstruction detected by high resolution manometry.

BACKGROUND: Esophagogastric junction outflow obstruction (EGJOO) is a newly described diagnostic entity growing in importance due to the use of high resolution manometry (HRM). There is little knowledge regarding its incidence, etiopathogeny, long-term evolution, and most suitable treatment. Our objective was to increase the awareness of EGJOO to optimize the management of these patients. METHODS: We conducted a historical (retrospective and prospective) study of patients diagnosed with EGJOO using HRM combined with multichannel intraluminal impedance, comparing their manometric and impedance characteristics with those of a control group. Symptoms, etiology of obstruction, acid exposure, clinical course (and its associated factors), and response to treatment were also evaluated in the EGJOO group. KEY RESULTS: Forty-four subjects were included (28 patients and 16 controls). Esophagogastric junction outflow obstruction patients presented incomplete esophageal transit more frequently than controls. Patients with structural obstruction had dysphagia more frequently than patients with functional obstruction, and different manometric, impedance, and pH-metric patterns. Over one-third of the EGJOO patients presented a spontaneous resolution of symptoms without EGJOO treatment. In the multivariate analysis, the variables associated with this spontaneous symptomatic resolution included typical symptoms of gastro-esophageal reflux disease or epigastralgia as the main symptom and resting or basal pressure of the upper esophageal sphincter <50 mmHg. CONCLUSIONS & INFERENCES: The majority of EGJOO patients presented intact peristalsis which may compensate for the lack of EGJ relaxation. In the EGJOO patients presenting favorable factors associated with a spontaneous resolution of symptoms, invasive treatments should be considered with special caution. Structural etiologies are more amenable to management, while the remainder may improve without intervention.

The chronology of the earliest Upper Palaeolithic in northern Iberia: New insights from L'Arbreda, Labeko Koba and La Viña.

Since the late 1980s, northern Iberia has yielded some of the earliest radiocarbon dated Aurignacian assemblages in Western Europe, probably produced by anatomically modern humans (AMHs). This is at odds with its location furthest from the likely eastern entry point of AMHs, and has also suggested to some that the Châtelperronian resulted from cultural transfer from AMHs to Neanderthals. However, the accuracy of the early chronology has been extensively disputed, primarily because of the poor association between the dated samples and human activity. Here, we test the chronology of three sites in northern Iberia, L'Arbreda, Labeko Koba and La Viña, by radiocarbon dating ultrafiltered collagen from anthropogenically modified bones. The published dates from Labeko Koba are shown to be significant underestimates due to the insufficient removal of young contaminants. The early (c.44 ka cal BP [thousands of calibrated years before present]) Aurignacian chronology at L'Arbreda cannot be reproduced, but the reason for this is difficult to ascertain. The existing chronology of La Viña is found to be approximately correct. Together, the evidence suggests that major changes in technocomplexes occurred contemporaneously between the Mediterranean and Atlantic regions of northern Iberia, with the Aurignacian appearing around 42 ka cal BP, a date broadly consistent with the appearance of this industry elsewhere in Western Europe.

Structure, metastability, and electron density of Al lattices in light of the model of anions in metallic matrices.

This paper reports a theoretical investigation of the structure, stability, and electron charge density of cubic, rhombohedral, hexagonal, and monoclinic Al lattices. The equations of state and the elastic constants are computed from total energy calculations at different volumes and unit cell strains using the density functional theory approximation. The topology of the electron density is analyzed within the crystalline implementation of the atoms in molecules formalism. The results are discussed in light of the so-called anions in metallic matrices model, which permits the interpretation of the chemical bonding and the explanation of the existence of particular symmetries of inorganic crystals. First, the Al sublattices are identified as the reference building blocks of AlX(3) (X = F, Cl, OH) compounds. The calculations reveal that the equilibrium zero-pressure Al-Al shortest distance is around 2.75 A in all of the Al matrixes, similar to the value observed in the stable face centered cubic structure of Al at room conditions. Second, at their zero-pressure equilibrium geometries, the Al sublattices are found to fulfill the mechanical stability criteria or, alternatively, to show mechanical instabilities that are compatible with the distortions observed for the structures in AlX(3) crystals. However, at the equilibrium volumes of the AlX(3) crystals, all of the Al matrices violate the spinodal condition, and the cohesion and stabilization are provided by the nonmetallic X atoms. Third, the structural anisotropy of the Al sublattices seems to be the main factor to discriminate metallic matrices able to host nonmetallic elements. The inhomogeneities of the electron charge density, which favor the arrival of nonmetallic elements and the crystal formation, are notably enhanced in passing from the fcc structure of pure Al to the less isotropic Al matrices observed in AlX(3) compounds.

Cell cycle and cancer: genetic analysis of the role of cyclin-dependent kinases.

Most human tumors harbor mutations that misregulate the early phases of the cell cycle. Here, we summarize genetic evidence, mostly obtained in our laboratory using strains of gene-targeted mice, that provides direct experimental support for a role of Cdk4 in tumor development. Moreover, these genetic studies challenge some well-established concepts regarding the role of Cdks during the early phases of the cell cycle. For instance, they have illustrated that Cdk4 and Cdk6 are not essential for cell division during embryonic development except in the hematopoietic system. More surprisingly, mice lacking Cdk2 survive for over 2 years without detectable abnormalities except in their germ cells, indicating that Cdk2 is essential for meiosis but dispensable for the normal mitotic cell cycle. Cdk2 is also dispensable for cell cycle inhibition and tumor suppression by the Cip/Kip inhibitors, p21(Cip1) and p27(Kip1). These observations have important implications not only to understand cell cycle regulation, but also to validate Cdks as potential targets for the development of therapeutic strategies to block proliferation of tumor cells.

A continuous spectrum of neutrophilic dermatoses in Crohn's disease.

UNLABELLED: The inflammatory bowel disease is accompanied by cutaneous manifestations in approximately 10% of the cases. Neutrophilic dermatoses are located on the dermis and/or epidermis and are characterised on histological examination by the presence of an infiltrate that consists largely of neutrophils. The prototype of neutrophilic dematoses is Sweetacute;s syndrome; which is rarely associated with Crohns disease. CASE REPORT: A 63 year old woman was admitted to hospital with pyrexia, abdominal pain, episcleritis and skin lesions. She presented erythematous lesions on trunk, legs and arms, with tendency towards formation of plaques, nodules and vesicular pustular lesions. Both the colonoscopy and colonic biopsies confirmed the diagnosis of colonic Crohns disease. Cutaneous biopsies re-vealed an infiltrate consisting mainly of neutrophils. These biopsies, together with clinical details led to the diagnosis of Sweetacute;s syndrome. A methylprednisolone treatment rapidly improved the skin lesions and clinical symptoms. The different clinical forms of neutrophilic dermatosis are an extra intestinal manifestation of Crohns disease, and are some-times found concurrently in the same patient, which would indicate a common pathogenesis with different clinical presentations (spectrum of neutrophilic dermatoses).

Prevalence of mutations of the NOD2/CARD15 gene and relation to phenotype in Spanish patients with Crohn disease.

BACKGROUND: We assessed the prevalence of R702W, G908R, and L1007fs coding mutations in the NOD2/CARD15 gene and the genotype-phenotype relation in Spanish patients with Crohn disease. METHODS: A cohort of 204 unrelated patients with Crohn disease and 140 healthy controls were studied. The phenotype was established before commencement of genotyping. Genotyping of the R702W, G908R, and L1007fs gene polymorphisms of NOD2/CARD15 was performed by two independent laboratories using different techniques. In the case of discordant results, specific sequencing of DNA strands was performed. RESULTS: At least one mutation was present in 32.8% of patients compared to 10.7% in controls (OR = 4.08, 95% CI 2.21 to 7.50). In patients with Crohn disease, the frequency of R702W, G908R, and L1007fs carriers was 13.7%, 8.3%, and 14.2%, respectively. Compound heterozygotes and homozygotes occurred in 3.4% and 2.9% of patients and in none of the controls. The correlation of genotype-Vienna classification showed a significant association with ileal disease (RR = 1.61, 95% CI 1.21-2.15, P = 0.001) and an inverse association with colonic localization (RR = 0.29, 95% CI 0.11-0.80, P = 0.007). There was a significant association between G908R carriership and previous appendectomy, surgical interventions, and stricturing behavior. A gene-dosage effect on phenotypic characteristics was not observed. CONCLUSIONS: In a Spanish population from Madrid, mutations of the NOD2/CARD15 gene were a marker of susceptibility to Crohn disease and were associated with ileal disease. Carriers of the G908R mutation showed a stricturing disease behavior, history of appendectomy, and surgical interventions over the course of the disease.

Infliximab treatment and prognostic factors for response in patients with Crohn's disease.

OBJECTIVE: The aim of this study is to report our experience with infliximab and analyse prognostic factors for response in Crohn's disease (CD). MATERIAL AND METHODS: Consecutive patients were prospectively enrolled in the study when referred for infliximab infusion. Data collected included indication for infusion, patient epidemiological characteristics, Vienna classification, previous surgery, previous medications and extra-intestinal manifestations. Adverse events and clinical response were tabulated separately for patients with luminal or fistulous Crohn's disease. RESULTS: 28 patients were treated (7 with inflammatory and 21 with fistulizing disease). Patients received a total of 116 infusions of infliximab: 57.1% (4 of 7) of patients with luminal disease had complete response within a median of 17.5 days (range 15-28 days), and 62% (13 of 21) of patients with fistulizing disease had complete response within a median of 9 days (range 6-51 days). All patients (5) without relapse received concomitant treatment with immune modifiers. The group of patients with previous resection or perianal fistula repair had complete response more frequently p = 0.03 (OR = 30; IC 95% = 1.47-119.8). CONCLUSIONS: Infliximab is safe and beneficial in clinical practice for Crohn's disease. The re-treatment regimen of infliximab is effective in maintaining clinical response. Immunosuppressant therapy may have a role in the duration of maintained clinical remission in patients with fistulizing disease. In patients with perianal fistulizing disease infliximab treatment is more effective when previous resection or fistula repair is present.

Hidatidosis intraportal como causa de hipertensión portal / Intraportal hydatidosis as manifestation of portal hypertension

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Tratamiento con infliximab y factores predictivos de respuesta en la enfermedad de Crohn / In fliximab treatment and prognostic factors for response in patients with Crohn's disease

Objetivo: describir nuestra experiencia con el infliximab y analizar la existencia de factores predictivos de respuesta en pacientes con enfermedad de Crohn (EC).Material y métodos: estudio longitudinal prospectivo donde se incluyeron consecutivamente a los pacientes tratados con infliximab. Se clasificaron según la indicación del tratamiento, características epidemiológicas, clasificación de Viena, antecedentes de cirugía, tratamientos concomitantes y manifestaciones extraintestinales. Se recogieron los efectos secundarios derivados del tratamiento y los resultados obtenidos durante el seguimiento clínico Resultados: se incluyeron 28 pacientes (7 con enfermedad intraluminal y 21 con enfermedad fistulosa) y se realizaron en total 116 infusiones de infliximab. En el grupo de enfermedad intraluminal respondieron 4 (57,1 por ciento), con una mediana de 17,5 días (15-28). En los enfermos con indicación por enfermedad fistulosa respondieron completamente 13 (62 por ciento) con una mediana de tiempo de 9 días (6-51). Los 5 pacientes en los que no se produjo la reapertura de la enfermedad fistulosa durante el seguimiento estaban concomitantemente con inmunosupresores. No encontramos factores predictivos de respuesta excepto en el grupo de enfermos con enfermedad perianal y antecedentes de cirugías prevías que presentaron con más frecuencia respuesta completa p=0,03 (OR=30; IC 95 por ciento= 1,47-119,8).Conclusiones: el tratamiento con infliximab benefició a un alto porcentaje de pacientes. Es un tratamiento seguro y eficaz. Tiene un importante papel en el mantenimiento de la respuesta en la EC. Los inmusupresores podrían tener un papel en la duración del mantenimiento de la respuesta en la enfermedad fistulizante. En la enfermedad fistulizante perianal se obtienen mejores resultados en la inducción, cuando se ha realizado cirugía previamente (AU)

Premature termination of DNA replication in plasmids carrying two inversely oriented ColE1 origins.

In Escherichia coli plasmids carrying two inversely oriented ColE1 origins, DNA replication initiates at only one of the two potential origins. The other silent origin acts as a replication fork barrier. Whether this barrier is permanent or simply a pausing site remains unknown. Here, we used a repeated primer extension assay to map in vivo, at the nucleotide level, the 5' end of the nascent strand where initiation and blockage of replication forks occurs. Initiation occurred primarily at the previously defined origin, however, an alternative initiation site was detected 17 bp upstream. At the barrier, the lagging strand also terminated at the main initiation site. Therefore, the 5' end of the nascent strand at the barrier was identical to that generated during initiation. This observation strongly suggests that blockage of the replication fork at the silent origin is not just a pausing site but permanent, and leads to a premature termination event.

Bi-directional replication and random termination.

Two-dimensional (2D) agarose gel electrophoresis was used to study termination of DNA replication in a shuttle vector, YRp7', when it replicated in Escherichia coli, Saccharomyces cerevisiae and Xenopus egg extracts. In E. coli, the 2D gel patterns obtained were consistent with uni-directional replication initiated at a specific site, the ColE1 origin. In consequence, termination also occurred precisely at the ColE1 origin. In Xenopus egg extracts, the particular shape of the bubble arc as well as the triangular smear detected to the left of the simple-Y pattern indicated random initiation and termination. In S.cerevisiae, initiation occurred at the ARS1 origin and replication proceeded in a bi-directional manner. However, termination did not always occur at a specific site 180 degrees across from the origin, but almost all along the south hemisphere of the plasmid. Inversion, deletion or replacement of DNA sequences located throughout this hemisphere did not eliminate random termination. Analysis of the replication intermediates of another yeast plasmid bearing a different origin, ARS305, also exhibited random termination. We propose that the random termination events observed in S.cerevisiae could be due to an asynchronous departure of both forks from the bi-directional origin in addition to differences in the rate of fork progression. These observations could be extended to all bi-directional origins.

Effect of quinolinic acid on endogenous antioxidants in rat corpus striatum.

The response of endogenous antioxidants to the N-methyl-D-aspartate (NMDA) receptor agonist and excitotoxin, quinolinic acid (QUIN), was investigated in rat corpus striatum. Animals treated with QUIN (240 nmol/microl), were sacrificed at 120 min after a single intrastriatal injection to examine the alterations in the levels of both reduced (GSH) and oxidized (GSSG) glutathione, and the activities of the antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (Gpx). Changes in the rate of lipid peroxidation (LP) were also measured after exposure to different doses of QUIN (60, 120, 240 and 480 nmol/microl) as an index of oxidative stress. When compared to control, lipid peroxidation was increased at QUIN doses of 240 and 480 nmol/microl. Striatal levels of GSH and GSSG were decreased and increased, respectively, after QUIN injection; whereas GPx activity was unchanged. Cytosolic copper/zinc SOD (CuZn-SOD) activity decreased after treatment, while mitochondrial manganese SOD (Mn-SOD) was unchanged. The alterations observed on these antioxidant systems suggest that QUIN toxicity is mediated by specific mechanisms leading to oxidative stress.

Correlación entre enzimoinmunoensayos anti-HCV de segunda generación y tercera generación en donantes de sangre / Correlation between second and third generation anti-HCV ELISA in blood donors

En los enzimoinmunoensayos de segunda generación (EIA 2.0) se incrementó la sensibilidad y especificidad respecto de los de primera generación. Actualmente se emplean los equipos de tercera generación (EIA3.0) con el fin de acortar el período de ventana y mejorar el comportamiento de sus versiones anteriores. El objetivo de este trabajo es evaluar el comportamiento de EIA 3.0 y EIA 2.0 en la población de dadores de sangre (DS) de nuestro hospital y relacionarlos con un ensayo suplementario (LIA III), con especial énfasis en las distintas intensidades de reacción (RP) de ambos EIAs. Fueron estudiados 15.898 DS con reactivos Abbott HCV EIA 2.0 y 4.147 con Abbott HCV EIA 3.0 (Abbott Laboratoires, Wiesbaden, Alemania). Las muestras doblemente reactivas fueron evaluadas por InnoLIA III (Innogenetics, Bélgica). La prevalencia de DS seropositivos para HCV fue 1,17 por ciento por EIA 2.0 y 1,83 por ciento por EIA 3.0. Independientemente del valor de RP, el EIA 3.0 mostró una mayor frecuencia de muestras LIA III negativas e indeterminadas que el EIA 2.0 (negativas 44 por ciento versus 38 por ciento; indeterminadas 14 por ciento versus 4 por ciento). Este comportamiento fue similar en todos los valores de RP. Para DS EIA reactivos con RP>=4.0 el 100 por ciento fue LIA III positivo cuando se empleó EIA 2.0 y el 68 por ciento en los analizados con EIA 3.0. El perfil de bandas reactivas en LIA III fue similar para ambos equipos y se hace más completo e intenso al aumentar el RP. De estas observaciones se concluye que el EIA 3.0 posee una perfomance más pobre respecto de su versión anterior, con mayor porcentaje de resultados LIA III indeterminados y negativos, en casi todos los valores de RP. Esta elevada frecuencia de datos falso-positivos crea en el dador de sangre una preocupación innecesaria y hace necesario el empleo de pruebas suplementarias para su certificación, con el consiguiente incremento en el costo de la unidad de sangre estudiada y su posterior descarte. (AU)

Correlación entre enzimoinmunoensayos anti-HCV de segunda generación y tercera generación en donantes de sangre / Correlation between second and third generation anti-HCV ELISA in blood donors

En los enzimoinmunoensayos de segunda generación (EIA 2.0) se incrementó la sensibilidad y especificidad respecto de los de primera generación. Actualmente se emplean los equipos de tercera generación (EIA3.0) con el fin de acortar el período de ventana y mejorar el comportamiento de sus versiones anteriores. El objetivo de este trabajo es evaluar el comportamiento de EIA 3.0 y EIA 2.0 en la población de dadores de sangre (DS) de nuestro hospital y relacionarlos con un ensayo suplementario (LIA III), con especial énfasis en las distintas intensidades de reacción (RP) de ambos EIAs. Fueron estudiados 15.898 DS con reactivos Abbott HCV EIA 2.0 y 4.147 con Abbott HCV EIA 3.0 (Abbott Laboratoires, Wiesbaden, Alemania). Las muestras doblemente reactivas fueron evaluadas por InnoLIA III (Innogenetics, Bélgica). La prevalencia de DS seropositivos para HCV fue 1,17 por ciento por EIA 2.0 y 1,83 por ciento por EIA 3.0. Independientemente del valor de RP, el EIA 3.0 mostró una mayor frecuencia de muestras LIA III negativas e indeterminadas que el EIA 2.0 (negativas 44 por ciento versus 38 por ciento; indeterminadas 14 por ciento versus 4 por ciento). Este comportamiento fue similar en todos los valores de RP. Para DS EIA reactivos con RP>=4.0 el 100 por ciento fue LIA III positivo cuando se empleó EIA 2.0 y el 68 por ciento en los analizados con EIA 3.0. El perfil de bandas reactivas en LIA III fue similar para ambos equipos y se hace más completo e intenso al aumentar el RP. De estas observaciones se concluye que el EIA 3.0 posee una perfomance más pobre respecto de su versión anterior, con mayor porcentaje de resultados LIA III indeterminados y negativos, en casi todos los valores de RP. Esta elevada frecuencia de datos falso-positivos crea en el dador de sangre una preocupación innecesaria y hace necesario el empleo de pruebas suplementarias para su certificación, con el consiguiente incremento en el costo de la unidad de sangre estudiada y su posterior descarte.

Nomega-nitro-L-arginine, a nitric oxide synthase inhibitor, antagonizes quinolinic acid-induced neurotoxicity and oxidative stress in rat striatal slices.

Nitric oxide (NO) is a potential contributor to neurotoxicity following overactivation of N-methyl-D-aspartate (NMDA) receptors. In this work we investigated the effect of Nomega-nitro-L-arginine (L-NARG 25, 50, or 100 microM), a selective inhibitor of nitric oxide synthase (NOS) -the synthetic enzyme of NO- on quinolinic acid (QUIN 100 microM)-induced neurotoxicity (measured as lactate dehydrogenase (LDH) leakage) in rat striatal slices. Oxidative stress was also measured both as lipid peroxidation and as the levels of reduced (GSH) and oxidized (GSSG) glutathione, in an effort to elucidate a possible participation of NO in the toxic mechanisms involved in NMDA receptor-mediated neuronal injury. The action of L-arginine (L-ARG 100 or 200 microM), a well-known NO precursor, was also tested on QUIN-induced neurotoxicity and oxidative stress. Results showed that QUIN produced significant changes in both cell damage (177%) and oxidative injury (203% in lipid peroxidation, 68% in GSH, and 123% in GSSG) as compared to control values. All these effects were antagonized by adding L-NARG to the incubation media, whereas L-ARG alone, or in combination with QUIN, significantly enhanced both lipid peroxidation and LDH leakage. Moreover, the protective effects of L-NARG on QUIN-induced lipid peroxidation were reversed by addition of an excess of L-ARG to the media. These findings indicate that NO is probably mediating the mechanism of neurotoxicity produced by QUIN, which may be of potential value to explain the molecular basis of neurodegenerative processes linked to QUIN-mediated NMDA receptor overactivation.