Modeling Receptor-Mediated Processes with Dioxin: Implications for Pharmacokinetics and Risk Assessment

Dioxin (2,3,7,8-tetrachlorodibenzo- p -dioxin; TCDD), a widespread polychlorinated aromatic hydrocarbon, caused tumors in the liver and other sites when administered chronically to rats at doses as low as 0.01 μg/kg/day. It functions in combination with a cellular protein, the Ah receptor, to alter gene regulation, and this resulting modulation of gene expression is believed to be obligatory for both dioxin toxicity and carcinogenicity. The U.S. EPA is reevaluating its dioxin risk assessment and, as part of this process, will be developing risk assessment approaches for chemicals, such as dioxin, whose toxicity is receptor-mediated. This paper describes a receptor-mediated physiologically based pharmacokinetic (PB-PK) model for the tissue distribution and enzyme-inducing properties of dioxin and discusses the potential role of these models in a biologically motivated risk assessment. In this model, ternary interactions among the Ah receptor, dioxin, and DNA binding sites lead to enhanced production of specific hepatic proteins. The model was used to examine the tissue disposition of dioxin and the induction of both a dioxin-binding protein (presumably, cytochrome P4501A2), and cytochrome P4501A1. Tumor promotion correlated more closely with predicted induction of P4501A1 than with induction of hepatic binding proteins. Although increased induction of these proteins is not expected to be causally related to tumor formation, these physiological dosimetry and gene-induction response models will be important for biologically motivated dioxin risk assessments in determining both target tissue dose of dioxin and gene products and in examining the relationship between these gene products and the cellular events more directly involved in tumor promotion.     

躲不掉的冷枪暗箭

在月末的公司经营销售总结会上,几个部门主管大倒苦水,均反映本部门的业务难以开展,他们说了种种理由,都有道理。看着各部门呈上来的销售记录,总经理紧锁眉头,低头不语。过了—会儿,总经理便吩咐秘书小姐拿来一杯水。玻璃杯里的水满满的,清澈见底。总经理对大家说:“现在谁能告诉我.这杯水满了没有?”对于总经理的提问,大家显得有些疑惑不解。这时,总经理身边的设计部主管非常确定地说:“还有两毫     

HIV/AIDS and homelessness

This article describes the results of research on the demographic, housing, psychosocial characteristics, and service needs of a sample of homeless people with HIV disease. Results show that respondents are similar in demographic and housing characteristics to the general homeless population. On average, respondents report high levels of stress and depression, moderate satisfaction with perceived social support availability, moderate beliefs in their ability to influence health related outcomes, moderate levels of self-efficacy, and low levels of physical and psychosocial disability. A range of services was identified as both helpful and useful in supporting a stable living arrangement. Implications for social policy, service provision, and research are discussed.     

Productivity of women scholars and gender researchers: Is funding a factor?

Articles by women scholars and proportions of articles focused on gender have increased steadily in major sociology journals since 1974. Women are more heavily represented as journal authors than as members of graduate-program departments, the institutional bases where most published work originates. We consider whether funding might account for these patterns by examining acknowledgement of support in published articles. We find no significant relationships among author gender, article topic, and notation of internal funding. Male-authored articles focused on nongender topics acknowledge external funding significantly more often than women-authored works and articles focused on gender written by women or men. Funding patterns therefore do not appear to account for increased productivity by women and gender researchers. She is currently studying the educational achievement of immigrant students. Linda Grant is an assistant professor of sociology and faculty associated of the Institute of Behavioral Research at the University of Georgia. Her current research focuses on gender and academic careers and gender relationships in schools. Her current research includes the feminist critique of sociology and publishing, and the U.S. women’s movement.     

Essay Review: The Legacy of Heinz Kohut: A Twentieth Anniversary Retrospective

HEINZ KOHUT: THE MAKING OF A PSYCHOANALYST. Charles B. Strozier. New York: Farrar, Straus and Giroux, 2001, 495 pp., $35.00.     

Teaching Sociological Theory Through Organizational Cases

Concepts developed by classical and contemporary thinkers serve as guides to the details of organizational environments and help investigators determine the efficacy of given organizational patterns. Students of sociology develop the application component of the major, in part, when provided the opportunity to gain experience with real organizational cases. The organizational projects conducted by students are founded upon four theoretical perspectives: functionalist, interactionist, exchange, and conflict.     

In-home family therapy: indicators of success

In this study, we explore how specific individual, family, and family-within-community characteristics, as well as aspects of in-home family therapy, relate to responses to treatment. The Child and Adolescent Functional Assessment Scale scores and Global Assessment of Functioning scores were used as outcome measures. Results revealed significant differences between pre- and post-scores for clients receiving in-home family therapy services, providing an initial indicator of treatment success. In addition, primary family caregiver social support, role performance in school/work, and self-harmful behavior were indicative of successful outcomes. Clients with higher problem levels had the greatest rates of change, and clients receiving more hours of services fared better in therapy.     

Cryotherapy for treatment of ECT-induced headache

Because headache is a common side effect of electroconvulsive therapy (ECT), this study sought to determine the effectiveness of cryotherapy (i.e., a frozen gel band) in relieving pain in patients with post-ECT headaches, and whether headache intensity and physiological measurements could predict use of an alternative analgesic (rescue medication). We used a quasi-experimental, crossover design to collect data from 31 patients ages 24 to 85 who had been referred for ECT at two medical facilities in San Diego, California. Measurements of patients' pain intensity were made at three intervals: upon perceiving headache, and at 30 and 60 minutes following the cryotherapy or acetaminophen interventions, based on the order of the crossover design. Data were analyzed using Hotelling's T2 and logistic regression. No significant difference was found between cryotherapy and acetaminophen in relieving ECT-induced headaches (p = .420). There was no influence due to the crossover design (p = .313), nor where there significant changes in physiological measures from treatment (p = .420). Logistic regression showed that 50% of patients required rescue medication after 60 minutes for both treatments (R2 = .498, p = .001), and 66% required rescue medication based on pain level and physiological measures (R2 = .662, p < .008). Based on these results, cryotherapy is an alternative treatment that may be helpful to some patients with ECT-induced headaches.