The role of endocrine factors in the alteration of cytochromes P450 by cyclosporine

textCyclosporine is an immunosuppressant whose side effects include suppressing cytochrome P450 (P450) levels and activity in the liver. This effect may be one of the underlying causes in the difficulties in relating cyclosporine blood levels with efficacy and toxicity. Growth hormone (GH) is known to pretranslationally regulate P450 expression, while prolactin can interact directly with cyclosporine as an immunomodulator. Thus, the suppression of P450 by cyclosporine may involve GH or prolactin as intermediates. In order to address these hypotheses, the effect of exogenous GH and prolactin, separately and in combination with cyclosporine, on P450 3A1/2 (CYP3A1/2) and 2C11 (CYP2C11) was investigated. In addition, the direct effects of cyclosporine on GH-related cellular signaling factors were examined in vitro. Results from in vivo studies revealed that cyclosporine does not alter GH levels as a mediating event in suppressing P450s, although GH is a dominating factor over cyclosporine in determining hepatic P450 expression. The additive suppression in P450 activity seen with the concomitant administration of cyclosporine and GH suggests that changes in hormonal status is likely to be one of many factors that is responsible for the lack of a clear association between cyclosporine dose and toxicity. In the context of prolactin as a mediating factor in the suppression of P450 by cyclosporine, bromocriptine caused a significant suppression of CYP3A1/2 and CYP2C11 protein and activity levels when it was administered alone and in combination with cyclosporine. While cyclosporine and bromocriptine, separately, can significantly alter the fate of hepatic P450 enzymes, the suppression is likely not due to an alteration in prolactin levels. In vitro studies indicate that P450s are differentially modulated by cyclosporine. While CYP3A1/2 is decreased at specific concentrations, CYP2C11 is increased in a dose-dependent manner. This increase in CYP2C11 correlated with increases in Stat5b binding activity, which initiates transcription of P450 genes in the nucleus. Taken together, these studies indicate that while cyclosporine does not suppress P450 enzymes by altering GH or prolactin levels, one of the avenues of suppression is through modifying intracellular signaling elements.Pharmac

Priority Hypertension Management Strategies for At-risk African Americans as Perceived by Medical Clinicians and Academic Scholars

African American adults, in the United States (US), bear the greatest burden of high blood pressure (HBP)--a primary risk factor for cardiovascular disease and premature death. Current research does not adequately inform the design of multi-level interventions that work to control HBP in this at-risk population. The purpose of this study was to uncover information about priority strategies recommended for HBP control in African American adults. Research questions are 1) what are factors that reduce or manage HBP in at-risk African Americans and 2) what factors are important to the design and implementation of successful HBP interventions in at-risk African Americans? A qualitative interpretive descriptive design and in-depth interview were used with a purposive sample (n=10) of doctorate-educated healthcare clinicians (i.e., physicians) and academicians (i.e., researchers) based on eligibility criteria: a) experience in treating or conducting research about HBP in African American adults, b) located within the Southern US, and c) consent to participate. Thematic analysis of audio-taped interview transcripts yielded a theoretical framework that consists of three multi-level elements believed to be critical components of interventions that can successfully manage HBP in at-risk African Americans: 1) social support, 2) lifestyle coaching, and 3) personalized medical management. Unique domains within the each element were revealed that ranged from stress management and holism to emotional resonant patient-caregiver partnership and experiential learning. Our findings were consistent with the social ecological model and have the potential to help address racial/ethnic-based health disparities through the design of patient-centered interventions. Findings will also be used to identify parameters available to simulation modelers in the design of models for optimal population level HBP control policy

Dancing and Drawing in Trisha Brown’s Work: A Conversation Between Choreography and Visual Art

This Art History and Dance combined, interdisciplinary thesis explores the connections between choreographic approaches and creative processes in dance and visual art. It develops from a postmodern, historical foundation and looks at choreographer Trisha Brown’s drawing and dancing in 1970s, a crucial period when Brown constantly investigated fundamental questions about choreography. It was through her drawing and choreography that Brown was able to examine structure from both choreographic and visual perspectives. Chapter Two uses Wassily Kandinsky’s theory of line to analyze Brown’s 1973 linear drawings as well as her notion of the body-making line in space. Chapter Three compares Brown’s Locus (1975) to conceptual artist Sol LeWitt’s sculpture Incomplete Open Cubes (1974). Both Brown and LeWitt emphasized the conceptual idea behind a work of art, and both adopted the cubic form as a visual strategy to actualize their conceptual ideas

Cyber-Physical Codesign of Distributed Structural Health Monitoring with Wireless Sensor Networks

Our Deteriorating Civil Infrastructure Faces the Critical Challenge of Long-Term Structural Health Monitoring for Damage Detection and Localization. in Contrast to Existing Research that Often Separates the Designs of Wireless Sensor Networks and Structural Engineering Algorithms, This Paper Proposes a Cyber-Physical Co-Design Approach to Structural Health Monitoring based on Wireless Sensor Networks. Our Approach Closely Integrates (1) Flexibility-Based Damage Localization Methods that Allow a Tradeoff between the Number of Sensors and the Resolution of Damage Localization, and (2) an Energy-Efficient, Multi-Level Computing Architecture Specifically Designed to Leverage the Multi-Resolution Feature of the Flexibility-Based Approach. the Proposed Approach Has Been Implemented on the Intel Imote2 Platform. Experiments on a Physical Beam and Simulations of a Truss Structure Demonstrate the System\u27s Efficacy in Damage Localization and Energy Efficiency. © 2010 ACM

Cyber-Physical Codesign of Distributed Structural Health Monitoring with Wireless Sensor Networks

Our Deteriorating Civil Infrastructure Faces the Critical Challenge of Long-Term Structural Health Monitoring for Damage Detection and Localization. in Contrast to Existing Research that Often Separates the Designs of Wireless Sensor Networks and Structural Engineering Algorithms, This Paper Proposes a Cyber-Physical Codesign Approach to Structural Health Monitoring based on Wireless Sensor Networks. Our Approach Closely Integrates 1) Flexibility-Based Damage Localization Methods that Allow a Tradeoff between the Number of Sensors and the Resolution of Damage Localization, and 2) an Energy-Efficient, Multilevel Computing Architecture Specifically Designed to Leverage the Multiresolution Feature of the Flexibility-Based Approach. the Proposed Approach Has Been Implemented on the Intel Imote2 Platform. Experiments on a Simulated Truss Structure and a Real Full-Scale Truss Structure Demonstrate the System\u27s Efficacy in Damage Localization and Energy Efficiency

Unlocking the key to successful commercialization by coupling the power of biocatalysis, strain engineering, and application studies

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Relación entre el nivel de conocimiento de salud bucal y grado de instrucción de padres de dos instituciones educativas, 2021

El objetivo de este estudio fue determinar la relación entre el nivel de conocimiento de salud bucal y grado de instrucción de padres de dos instituciones educativas 2021 , fue una investigación de tipo descriptivo, transversal y de diseño no experimental, teniendo una muestra total de 353 padres de familia, el instrumento fue un cuestionario virtual de 20 preguntas cerradas con respuesta única. Se obtuvo que existe relación entre el nivel de conocimiento de salud bucal con el grado de instrucción de padres; asimismo, no existió relación entre el nivel de conocimiento de salud bucal y grado de instrucción de la I.E. de Lima; de igual manera en la I.E. de Huancavelica no se encontró relación entre el nivel de conocimiento de salud bucal y grado de instrucción. Se concluyó que existe relación entre el nivel de conocimiento de salud bucal y grado de instrucción de padres de dos instituciones educativas