Environmental exposure assessment of fluoroquinolone antibacterial agents in sewage, river water and soil

Sancho, Eva Maria Golet Swiss Federial Institute of Technology Zu@rich 2002 국내박사

PHYSIOLOGICAL PERTURBATIONS IN PHARMACOKINETIC ANIMAL STUDIES (MICROVASCULAR SPACE, INTERSTISIAL FLUID, ANTINEOPLASTIC AGENTS)

SANCHO, ALFREDO R UNIVERSITY OF SOUTHERN CALIFORNIA 1999 해외박사(DDOD)

Optimization of an individual's antineoplastic drug regimen is dependent on understanding of that individual's unique physiology and tumor pathophysiology. Noninvasive methods of measurement, when combined with pharmacokinetic methods of analysis, such as pharmacokinetic imaging, can estimate the amount of antineoplastic agent reaching the target site as well as identifying and quantifying the pathophysjological factors affecting the delivery of the drug. The animal model utilized for this work were female Sprague Dawley rats bearing subcutaneous Walker 256 carcinosarcoma, tumors implanted in the rear right flank. All studies were performed using nuclear imaging. These studies were undertaken using radiolabelled <super>195m</super>Pt-carboplatin. The microvascular space (<bold>MV</bold>) was measured using red blood cells labeled with <super>99m</super>Tc and the interstitial fluid (<bold>IF</bold>) space using <super>111</super>In-DTPA. The data obtained suggests that MV and IF increase gradually as the Walker 256 tumors become larger, this relationship breaks down when the tumor reaches 2 grams. The results obtained in this work support the proposal that once a critical mass is reached (2 grams or larger), the ability of the tumor to maintain an internal balance collapses and the various forces involved in the movement of fluid and particles—large and small—within the IF, <italic>e.g</italic>. diffusion and convection, have different effects. Thus, to perform reliable studies of drug pharmacokinetics in tumors, the tumor size needs to be carefully controlled. Another parameter that needs to be properly controlled is the effect of co-administered drugs, including anesthetics. We postulated that the pharmacokinetics of <super>195m</super>Pt-carboplatin would vary significantly depending on the anesthetic used. A systematic analysis on the effect of different anesthesia on the pharmacokinetics of <super>195m</super>Pt-carboplatin was compared to the pharmacokinetics of <super>195m</super>Pt-carboplatin in the conscious rat. These results lead to the conclusion that the efficacy of the antineoplastic agent is dependent both on its tumoral pharmacokinetics as well as on the status of the microvasculature and interstitial fluid volumes found in and around the. tumor masses targeted. These two physiological compartments directly influence the ability of the drug to reach the active tumors cells in therapeutic levels.

Regulation of cardiac myofilament function by 5'-AMP activated protein kinase (AMPK)

Sancho Solis, Raquel M The University of Wisconsin - Madison 2010 해외박사(DDOD)

AMPK is a serine/threonine protein kinase that becomes activated when cellular AMP:ATP ratios rise, thereby serving as a key regulator of cellular energetics. Among the known target proteins phosphorylated by AMPK are catabolic and anabolic enzymes, but little is known about its ability to regulate the cardiac contractile apparatus. This study demonstrates that cTnI, a subunit of the cardiac troponin (cTn) complex, is readily phosphorylated by AMPK. Heterotrimeric cardiac troponin (cTn) is a critical component of the thin filament regulatory complex in cardiac muscle. Two of the three subunits, cTnI and cTnT, are subject to post-translational modifications such as proteolysis and phosphorylation. To obtain a global view of the biochemical state of cTn in native tissue, we performed high resolution top-down mass spectrometry of cTn heterotrimers from healthy adult rat hearts. High resolution top-down mass spectrometry revealed naturally occurring single amino acid sequence variants co-existing within a single rat heart. To study the effects of AMPK on cardiac contracile function, the kinase domain of AMPK was expressed and purified. Using a combination of recombinant mouse cTnI with candidate sites mutated to Alanine, screening of synthetic peptides mimicking selected regions of cTnI, phosphospecific antibodies and high resolution mass spectrometry analysis of synthetic peptide substrates, Ser22 and Ser149 were identified as the targeted sites by AMPK. Top-down MS analysis of purified rat cTn complexes confirmed that Ser149 and the PKA sites were phosphorylated by AMPK. Time course of phosphorylation experiments revealed that Ser149 is the preferred site. Experiments with skinned myocytes determined that AMPK can phosphorylate cTnI while assembled in the myofilament and that Ser 149 was a target site under these conditions. To determine the physiological consequences of AMPK-mediated phosphorylation of cTnI, myofilament contractile function was studied in skinned and intact cardiomyocytes. In addition, the phosphorylation pattern of cTnI in the exercise-trained state was examined, as exercise is associated with both activation of AMPK. Finally, fast skeletal troponin was found to be a good substrate for AMPK making it a possibly useful model to study the physiological consequences of phosphorylating Ser149 independent of the phosphorylation of Ser22.

The legacy of genius: Improvisation, Romantic imagination, and the Western musical canon

Sancho-Velazquez, Angeles University of California, Los Angeles 2001 해외박사(DDOD)

This dissertation addresses the question of the decline of improvisation in Western classical music, investigating both its disappearance from performance practice and the scholarly neglect of this phenomenon in music histories and theories. Music historians have traditionally situated the disappearance of improvisation at the end of the Baroque, but improvisation continued to be an important part of Western classical music until well into the nineteenth century. The failure to account for its importance in the Classical and Romantic periods raises questions concerning the methodological limitations of early music scholarship and the scholarly tradition that ensued. The decline of the practice of improvisation coincides with the period around the middle of the nineteenth century when this musical tradition underwent a process of formalization and canonization. This process went hand in hand with a post-Romantic recontextualization of historicism, the aesthetics of genius, and music scholarship. The disappearance of improvisation was caused by the confluence of these developments and the impact each had on the others. The Classical musical tradition then became synonymous with the preservation, study, and reproduction of a body of fixed works conceived as the metaphysically-charged legacy of genius. An underlying goal of this dissertation is to question some central aspects of the received concept of “Western Classical music.” A reflection on the role played by improvisation in the history of this music makes it evident that this is a rich tradition of music-making and musical aesthetics that is not reducible to the narrow, formalist concept of work with which it is largely identified. This reflection opens up theoretical and practical possibilities that might help us to think about and experience Western Classical music from exciting new perspectives that are nevertheless firmly rooted in tradition.

Migration in the age of globalization: Transnationalism, identity, social class, and education of Latino families

Crespo Sancho, Catalina State University of New York at Buffalo 2009 해외공개박사

This dissertation addresses the connections between migration, identity, social class, and education, and how these relations create contemporary transnational individuals. I closely examine how Latino migrant families live their every day lives within a transnational context. Specifically, I compare the migration experience of middle and poor class Latinos from varying nationality and look at how they live and narrate concepts of belonging, ethnic identity, and social class. In addition, I examine how families and schools give advantages and/or disadvantages to Latino migrant children. Over a 12-month period, I conducted in-depth ethnographic case studies of 4 Latino families of varying nationalities and social class. The research design includes interviews with family members and school teachers, field observations at homes and schools, document collection, and field notes. The comparative ethnographic design of this research offers a detailed understanding of the processes through which families of diverse background cope with migration. This work shows how Latino families simultaneously engage in different social practices within multiple locations. In particular, it shows how social class is being transformed by to the movement of people and the shifting global economy. The findings reveal that there are important differences in how Latinos of different background settle and adapt to a new country, create networks of support, navigate the educational system, and relate to other ethnic and racial groups, including other Latinos. It also uncovers that differences in uses and access to technology leads to inequality between schools and families; this digital divide is in many ways related to race and ethnicity. In conclusion, I point out the need to adopt a multidimensional approach when studying transnational migrants. This approach helps us understand the often contradictory set of forces operating in these families. Implications of this study highlight the need for teachers and schools to look at the culture and the home environment of their students. The findings show that schools need to be active participants in the development of parental involvement programs that take into account the families' cultural background. In addition, schools need to look more closely at the instruction on uses of technology needed to compete in the globalized world. For policy-makers, this study reveals that a new type of nation building is occurring; one that is based on multiple belongings and loyalties. Thus, this study suggests that the United States should adopt a migration agenda based on the possibility of having double loyalty, where migrants living in the U.S. are allowed to feel a sense of responsibility and duty to several countries.