Postantifungal Effect of Micafungin against the Species Complexes of Candida albicans and Candida parapsilosis

Micafungin is an effective antifungal agent useful for the therapy of invasive candidiasis. Candida albicans is the most common cause of invasive candidiasis; however, infections due to non-C. albicans species, such as Candida parapsilosis, are rising. Killing and postantifungal effects (PAFE) are important factors in both dose interval choice and infection outcome. The aim of this study was to determinate the micafungin PAFE against 7 C. albicans strains, 5 Candida dubliniensis, 2 Candida Africana, 3 C. parapsilosis, 2 Candida metapsilosis and 2 Candida orthopsilosis. For PAFE studies, cells were exposed to micafungin for 1 h at concentrations ranging from 0.12 to 8 mu g/ml. Time-kill experiments (TK) were conducted at the same concentrations. Samples were removed at each time point (0-48 h) and viable counts determined. Micafungin (2 mu g/ml) was fungicidal (>= 3 log(10) reduction) in TK against 5 out of 14 (36%) strains of C. albicans complex. In PAFE experiments, fungicidal endpoint was achieved against 2 out of 14 strains (14%). In TK against C. parapsilosis, 8 mu g/ml of micafungin turned out to be fungicidal against 4 out 7 (57%) strains. Conversely, fungicidal endpoint was not achieved in PAFE studies. PAFE results for C. albicans complex (41.83 +/- 2.18 h) differed from C. parapsilosis complex (8.07 +/- 4.2 h) at the highest tested concentration of micafungin. In conclusion, micafungin showed significant differences in PAFE against C. albicans and C. parapsilosis complexes, being PAFE for the C. albicans complex longer than for the C. parapsilosis complex.

Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-beta 3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM.

La crisi presente. La autonomía de la voluntad La operatividad de la clausula Rebus sic Stantibus

La situación que emergió a partir del año 2008, hizo resurgir la necesidad de indagar sobre la posibilidad jurídica y la necesidad social de revisar los pactos contractuales vigentes. Por tanto se pretendía deducir si la situación de crisis económica permitía excepciones al principio de la autonomía de la voluntad, y llegados a este punto determinar si era posible la aplicación de la clausula rebus sic stantibus, es decir, si era posible modificar el contenido contractual inicialmente querido y pactado por las partes. Esta tarea se vio incentivada por varios pronunciamientos del Tribunal Supremo, que en términos generales consideraron la clausula como aplicación normalizada, dejando atrás la concepción de regla peligrosa para el sistema contractual.

Automatización de la adquisición y procesamiento de datos en microscopía electrónica tridimensional

257 P.

La jurisdicción voluntaria notarial. Su especial relevancia en el ámbito sucesorio

426 p.

Aspectos históricos de la mineria del hierro en Bizkaia hasta principios del siglo XX.

Búsqueda y recopilación de fuentes bibliográficas antiguas y comparación de las principales conclusiones geológicas propuestas a lo largo del tiempo.

Estudio del vulcanismo submarino de edad Cretácico en la transversal de Errigoiti: Implicaciones petrogenéticas y geodinámicas derivadas del estudio de los diques.

[ES] Estudio del vulcanismo submarino de edad Cretácico en la transversal de Errigoiti. Implicaciones petrogenéticas y geodinámicas derivadas del estudio de los diques, mediante láminas delgadas, "visu" de las rocas de campo y análisis geoquímicos con sus respectivos diagramas e interpretaciones.

Estimativa de espessura do concreto utilizando o método do eco - impacto

Nesta pesquisa utilizou-se um equipamento experimental que utiliza o método do eco-impacto produzido no Laboratório de Ensaios Físicos do Instituto Politécnico do Rio de Janeiro (UERJ/IPRJ), para estimar a espessuras de placas de concreto através da propagação de ondas de tensão geradas por um impacto. Para determinação dessa espessura, foram investigados vários mecanismos de estruturação do protótipo do equipamento com objetivo de se obter a melhor leitura possível, por meio das literaturas existentes. Entre parâmetros avaliados no estudo, estava o modelo de sensor a ser utilizado, o tipo de impactor, a precisão relacionada à aquisição de dados e o tratamento do mesmo, a distância entre o ponto de impacto e o transdutor (sensor), e o local de teste. Os resultados experimentais concordam com as previsões teóricas e revelam que este método é eficiente para análise de estrutura de concreto. A análise da espessura e resposta em frequência de um novo protótipo desenvolvido e os testes realizados possibilitou um erro médio de espessura real para amostras sem agregados de 0,39% e para as amostras com agregados com de 0,64%. Esses resultados apontam que o equipamento produzido tem potencial e que o mesmo pode ser utilizado para avaliação de estrutura de concreto.

Implicación de los microRNAs en la toxicidad del metotrexato en Leucemia Linfoblástica Aguda infantil

Analisis de la implicacion de los Polimorfismos de LLA en la respuesta al Metotrexato

Sintesi hidrotermal bidezko titanio dioxidozko nanohodien lorpena

[EUS] Gaur egun nanozientzia zientzia eta teknologia arlo guztietara zabaldu da, gizarte garapenean eragin handia izan du. Ikerkuntza arlo guztietara zabaldu da ezinezkoak ziruditen erronkak argitu eta ezezagunak ditugun ezagutzak garatzeko asmoz. Lan honetan TiO2 nanohagatxoen sintesia burutu da metodo hidrotermala erabiliz. Sintesi baldintzek lortutako produktuaren egituran eta forman duten eragina kontuan harturik, sintesia gertatzeko ezinbestekoak diren pHa, tenperatura eta denbora aztertu dira. Ondoren, tratamendu kimiko eta termiko ezberdinen bidez konposizio eta egitura ezberdinak lor daitezkeela frogatu da. Bereziki, surfaktante eta pHaren arabera egitura ezberdinak lortzen direla ikusirik. Sintetizatutako laginen karakterizazioa burutzeko X izpien difrakzioa, transmisio bidezko mikroskopia elektronikoa, infragorri espektroskopia, eta termograbimetria teknikak erabili dira. Hauen bidez NaTi3O6·(OH)x·(H2O)y , (TiO2)x(H2O)y , anatasa eta rutilo faseak identifikatu dira, eta nanohagatxoen lodiera eta morfologia ezberdinak ikusi dira.

Dipeptidyl-Peptidase IV Activity Is Correlated with Colorectal Cancer Prognosis

Background Dipeptidyl-peptidase IV (EC 3.4.14.5) (DPPIV) is a serine peptidase involved in cell differentiation, adhesion, immune modulation and apoptosis, functions that control neoplastic transformation. Previous studies have demonstrated altered expression and activity of tissue and circulating DPPIV in several cancers and proposed its potential usefulness for early diagnosis in colorectal cancer (CRC). Methods and principal findings The activity and mRNA and protein expression of DPPIV was prospectively analyzed in adenocarcinomas, adenomas, uninvolved colorectal mucosa and plasma from 116 CRC patients by fluorimetric, quantitative RT-PCR and immunohistochemical methods. Results were correlated with the most important classic pathological data related to aggressiveness and with 5-year survival rates. Results showed that: 1) mRNA levels and activity of DPPIV increased in colorectal neoplasms (Kruskal-Wallis test, p<0.01); 2) Both adenomas and CRCs displayed positive cytoplasmic immunostaining with luminal membrane reinforcement; 3) Plasmatic DPPIV activity was lower in CRC patients than in healthy subjects (Mann-U test, p<0.01); 4) Plasmatic DPPIV activity was associated with worse overall and disease-free survivals (log-rank p<0.01, Cox analysis p<0.01). Conclusion/significance 1) Up-regulation of DPPIV in colorectal tumors suggests a role for this enzyme in the neoplastic transformation of colorectal tissues. This finding opens the possibility for new therapeutic targets in these patients. 2) Plasmatic DPPIV is an independent prognostic factor in survival of CRC patients. The determination of DPPIV activity levels in the plasma may be a safe, minimally invasive and inexpensive way to define the aggressiveness of CRC in daily practice.