Features of alterations of igneous rocks from Sierras of Guadarrama and Malagon (Spanish Central Range)

[Resumen] Se describen las características-de las alteraciones desarrolladas sobre las rocas ígneas de un sector del Sistema Central. Criterios geomorfológicos y su distinta composición mineralógica permiten suponer su origen a partir de distintas etapas de alteración. Se discuten las condiciones climáticas durante su formación, realizada siempre bajo climas poco agresivos.[Abstract] The main features of the alterations developped on igneous rocks of Central System are described. From geomorphological criteria as well as mineralogical data, different stages of weathering are been inferred. Although weathering processes have not been strong, different conditions are discussed for each stage

Valor de la expresión del ARN mensajero de la isocitrato deshidrogenasa (IDH1) como predictor de agresividad en gliomas

Los gliomas son el tipo más común de tumor cerebral primario. En humanos, cinco genes codifican para la isocitrato deshidrogenasa: IDH1/2/3A/3B/3G. Mutaciones somáticas puntuales en el gen IDH1 son frecuentes en gliomas, la mayoría transiciones de una sola base: 395G-A y están asociadas a una mayor supervivencia de esos pacientes con glioma cuando los comparamos con aquellos que no tienen la mutación. Entre las consecuencias funcionales de la mutación de la IDH1, estudios demuestran un fuerte descenso en la producción de NADPH reducido dependiente de isocitrato en las células. Investigamos la expresión del ARNm del IDH1 y la presencia o ausencia de la mutación G395A en una serie de gliomas. En particular, estudiamos 38 casos de gliomas y 7 metástasis analizando el centro y la periferia de muestras en fresco y resección en bloque. No encontramos diferencias entre las regiones central y periférica con respecto a la expresión del ARNm y la mutación de IDH1. Sin embargo, podemos observar una mayor expresión del ARNm de IDH1 y una menor incidencia de la mutación en tumores de alto grado cuando los comparamos con aquellos de bajo grado. Este estudio muestra que los gliomas con IDH1 normal tienen una mayor expresión de ARNm independientemente de la zona del tumor. Esto podría conducir a un aumento en la actividad enzimática y mayor presencia de NADPH, lo cual se necesita para el crecimiento celular. Así, el mayor poder de reducción de estas células podría explicar la mayor agresividad de estos gliomas.Gliomas, are the most common type of primary brain tumors. In humans, five genes encode for isocitrate dehydrogenase: IDH1, IDH2, IDH3A, IDH3B, and IDH3G. Somatic point mutations in IDH1 are frequent in gliomas. Most mutations for IDH1 are single base transition substitutions: 395G_A and are associated with longer survival in patients with glioma when compared with those gliomas without IDH1 mutations. Among the functional consequences of IDH1 mutation, some studies have shown a strong decrease in the isocitrate dependent production of reduced NADPH production in the cells. We investigated mRNA expression of IDH1 and the presence or absence of the G395A mutation in a subset of gliomas. Specifically, we studied 38 cases of glioma and 7 methastasis analyzing central and peripheral regions from fresh and en block resection specimens. We found no differences between central and peripheral regions, in regard to IDH1 mRNA expression and G395A IDH1 mutation. However, we identified a significantly higher expression of IDH1 mRNA and a lesser incidence of mutation in high grade gliomas when compared with low grade ones. This study shows that those gliomas with IDH1 WT are associated with higher expression of IDH1 mRNA, independently of the tumor area. This could in turn lead to an increase in enzyme activity and more presence of NADPH which is needed for cellular growth. The greater reducing power in these cells could account for the greater aggressiveness of these gliomas

Pentobarbital versus thiopental in the treatment of refractory intracranial hypertension in patients with traumatic brain injury: a randomized controlled trial

Introduction: Experimental research has demonstrated that the level of neuroprotection conferred by the various barbiturates is not equal. Until now no controlled studies have been conducted to compare their effectiveness, even though the Brain Trauma Foundation Guidelines recommend that such studies be undertaken. The objectives of the present study were to assess the effectiveness of pentobarbital and thiopental in terms of controlling refractory intracranial hypertension in patients with severe traumatic brain injury, and to evaluate the adverse effects of treatment. Methods: This was a prospective, randomized, cohort study comparing two treatments: pentobarbital and thiopental. Patients who had suffered a severe traumatic brain injury (Glasgow Coma Scale score after resuscitation ≤ 8 points or neurological deterioration during the first week after trauma) and with refractory intracranial hypertension (intracranial pressure > 20 mmHg) first-tier measures, in accordance with the Brain Trauma Foundation Guidelines. Results: A total of 44 patients (22 in each group) were included over a 5-year period. There were no statistically significant differences in ' baseline characteristics, except for admission computed cranial tomography characteristics, using the Traumatic Coma Data Bank classification. Uncontrollable intracranial pressure occurred in 11 patients (50%) in the thiopental treatment group and in 18 patients (82%) in the pentobarbital group (P = 0.03). Under logistic regression analysis - undertaken in an effort to adjust for the cranial tomography characteristics, which were unfavourable for pentobarbital - thiopental was more effective than pentobarbital in terms of controlling intracranial pressure (odds ratio = 5.1, 95% confidence interval 1.2 to 21.9; P = 0.027). There were no significant differences between the two groups with respect to the incidence of arterial hypotension or infection. Conclusions: Thiopental appeared to be more effective than pentobarbital in controlling intracranial hypertension refractory to first-tier measures. These findings should be interpreted with caution because of the imbalance in cranial tomography characteristics and the different dosages employed in the two arms of the study. The incidence of adverse effects was similar in both groups

Absence of the MGMT protein as well as methylation of the MGMT promoter predict the sensitivity for temozolomide

The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) can cause resistance to the alkylating drug temozolomide (TMZ). The purpose of this study was to determine the relationship between the MGMT status, determined by means of several techniques and methods, and the cytotoxic response to TMZ in 11 glioblastoma multiforme (GBM) cell lines and 5 human tumour cell lines of other origins. Cell survival was analysed by clonogenic assay. The MGMT protein levels were assessed by western blot analysis. The MGMT promoter methylation levels were determined using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and quantitative real-time methylation-specific PCR (qMSP). On the basis of the results of these techniques, six GBM cell lines were selected and subjected to bisulphite sequencing. The MGMT protein was detected in all TMZ-resistant cell lines, whereas no MGMT protein could be detected in cell lines that were TMZ sensitive. The MS-MLPA results were able to predict TMZ sensitivity in 9 out of 16 cell lines (56%). The qMSP results matched well with TMZ sensitivity in 11 out of 12 (92%) glioma cell lines. In addition, methylation as detected by bisulphite sequencing seemed to be predictive of TMZ sensitivity in all six cell lines analysed (100%). The MGMT protein expression more than MGMT promoter methylation status predicts the response to TMZ in human tumour cell line

Resultados del estudio geológico a escala 1/25.000 del término municipal de Madrid.

Se exponen de forma abreviada los rasgos en cuanto a metodología y conclusiones del estudio geológico a escala 1/25000 realizado en el Municipio de Madrid en los años 1982/83. Las diferentes unidades expresadas en la cartografiase describen en función de las pautas mayores observables en los materiales que forman cada una de ellas, analizándose sus relaciones estratigráficas. El Proyecto «Estudio Geológico a escala 1/25000 del Término Municipal de Madrid ha sido llevado a cabo a lo largo de los años 1982-83 como resultado de la colaboración científica entre diversos organismos de la Administración (Facultad de CC. Geológicas-Universidad Complutense, Instituto Geológico y Minero. Ayuntamiento de Madrid, Instituto de Geología de Madrid-CSIC, y otros). Constituye una de las áreas de actuación definidas dentro del Convenio de Colaboración Técnica y Cultural para el conocimiento de las Características del Suelo y Subsuelo de Madrid», propiciado y patrocinado por el Excmo. Ayuntamiento. La financiación del proyecto especifico de Geología ha sido realizada íntegramente por el IGME, organismo encargado además de su supervisión. El desarrollo del Proyecto tiene un marcado carácter interdisciplinar, fruto del trasvase de información entre los distintos grupos que abarca el Convenio general (aparte de los ya referidos, el SGOP, COPLACO, Laboratorio «José Luis Escario» siendo precisamente uno de los objetivos del trabajo el servir de apoyo a las restantes áreas de investigación. Los estudios geológicos realizados se plasman en un total de siete mapas a escala 1/25000 elaborados según la normativa Magna de cartografía geológica mapas que toman como referencia, aunque en algunos casos no las completan y en otros adosan porciones de hojas adyacentes, las hojas 1/25000 de Madrid, Alcorcón, El Pardo, San Femando de Henares, Pozuelo de Alarcón, Alcobendas y Castillo de Viñuelas

Homogeneous MGMT Immunoreactivity Correlates with an Unmethylated MGMT Promoter Status in Brain Metastases of Various Solid Tumors

The O6-methylguanine-methyltransferase (MGMT) promoter methylation status is a predictive parameter for the response of malignant gliomas to alkylating agents such as temozolomide. First clinical reports on treating brain metastases with temozolomide describe varying effects. This may be due to the fact that MGMT promoter methylation of brain metastases has not yet been explored in depth. Therefore, we assessed MGMT promoter methylation of various brain metastases including those derived from lung (n = 91), breast (n = 72) kidney (n = 49) and from malignant melanomas (n = 113) by methylation-specific polymerase chain reaction (MS-PCR) and MGMT immunoreactivity. Fifty-nine of 199 brain metastases (29.6%) revealed a methylated MGMT promoter. The methylation rate was the highest in brain metastases derived from lung carcinomas (46.5%) followed by those from breast carcinoma (28.8%), malignant melanoma (24.7%) and from renal carcinoma (20%). A significant correlation of homogeneous MGMT-immunoreactivity (>95% MGMT positive tumor cells) and an unmethylated MGMT promoter was found. Promoter methylation was detected in 26 of 61 (43%) tumors lacking MGMT immunoreactivity, in 17 of 63 (27%) metastases with heterogeneous MGMT expression, but only in 5 of 54 brain metastases (9%) showing a homogeneous MGMT immunoreactivity. Our results demonstrate that a significant number of brain metastases reveal a methylated MGMT-promoter. Based on an obvious correlation between homogeneous MGMT immunoreactivity and unmethylated MGMT promoter, we hypothesize that immunohistochemistry for MGMT may be a helpful diagnostic tool to identify those tumors that probably will not benefit from the use of alkylating agents. The discrepancy between promoter methylation and a lack of MGMT immunoreactivity argues for assessing MGMT promoter methylation both by immunohistochemical as well as by molecular approaches for diagnostic purposes