Differential expression of CYP1A1 and CYP1B1 in human breast epithelial cells and breast tumor cells

OBJECTIVES: The aim of this study was to evaluate the tolerance and outcome of elderly cervical carcinoma patients treated with radiation therapy (RT). METHODS: Three hundred ninety-eight patients with stage I-III cervical carcinoma treated with definitive RT were analyzed. Patients were divided into nonelderly (ages 35-69) (n = 338) and elderly (ages >/= 70) (n = 60) groups. A comparison of patient, tumor and treatment factors, morbidity, and outcome was performed. Median follow-up was 81 months. RESULTS: Elderly patients had a higher rate of comorbid conditions including diabetes (P = 0. 02), coronary artery disease (P = 0.003), and hypertension (P = 0. 001) than younger patients. Comorbid conditions in the elderly resulted in more frequent treatment breaks and less ability to undergo definitive treatment with intracavitary RT (ICRT). While the 5-year actuarial disease-free (DFS) and cause-specific (CSS) survival rates were comparable between the two groups, disease recurrence and death from cervical cancer were more common beyond 5 years in the elderly group. When patients not undergoing ICRT and those with treatment protraction were excluded, differences in the DFS and CSS curves were no longer evident. The frequency and severity of acute and chronic sequelae were similar. CONCLUSIONS: Elderly cervical carcinoma patients have an equivalent overall outcome following radiation therapy to younger patients when comparable treatment is delivered. Age per se is not associated with a higher rate of acute or chronic sequelae. Comorbid conditions adversely impacted on the quality and delivery of RT in the elderly group and help explain observed differences in outcome based on age.     

Review of Package Warning Labels and Their Effect on Consumer Behaviour with Insights to Future Anticounterfeit Strategy of Label and Communication Systems

This paper investigates and reviews literature regarding a range of topics important to the research question – the themes apply across all the topics. The topics include label and package warnings, including tamper‐evident features, to review their effect on the consumer behaviour of changing usage or purchase decisions. This information was then applied to gain insight into anticounterfeit product/package efforts. Based on this research, it appears that there is value for brand marketers to enhance their anticounterfeit efforts and consumer confidence by utilizing warning labels and information labels on their labels or packages. Currently, consumer perception of a domestic counterfeit product threat (promoted as genuine products), even for pharmaceuticals by healthcare professionals, although increasing has still been very low. Generally, the consumers believe and expect that the product purchased from retailers is safe and genuine. The study reviewed many key warning and label communication areas: consumer behaviour review, technical specifications, anticounterfeit, tamper evidence/tamper resistance, over‐the‐counter drugs, alcohol, cigarette, nutrition food and nutrition supplements. To complete the insight on communicating with the consumer, a review of label legibility was included. Before brand marketers consider adding anticounterfeit warning labels, extensive consumer behaviour research should be conducted in areas such as fear appeals and involuntary risk outrage. Copyright © 2011 John Wiley & Sons, Ltd.     

Biotransformation of coumarin by rodent and human cytochromes P-450: metabolic basis of tissue-selective toxicity in olfactory mucosa of rats and mice

Coumarin was previously found to cause tissue-selective toxicity in the olfactory mucosa (OM) of rats and mice, with rats being the more sensitive species. The aim of this study was to explore the role of target tissue biotransformation in OM-selective toxicity and the metabolic basis of the species differences in coumarin toxicity. At least six coumarin metabolites were detected in OM microsomal reactions, with o-hydroxyphenylacetaldehyde (o-HPA) being the most abundant. Formation of o-HPA was inhibited by reduced glutathione, confirming its origin from a reactive intermediate. There were significant differences in the rates and metabolite profiles of coumarin metabolism in the livers of Wistar rats and C57BL/6 mice. The rates of metabolic activation of coumarin, as indicated by the formation of o-HPA, were comparable in OM microsomes of the two species but about 25- and 3-fold higher in OM than in liver microsomes of rats and mice, respectively. Thus, target tissue activation seems to play an important role in the tissue-selective toxicity, whereas differences in the rates of hepatic metabolism may be responsible for the species difference in olfactory toxicity. Purified, heterologously expressed mouse CYP2A5 and CYP2G1 produced 7-hydroxycoumarin and o-HPA as the predominant products, respectively. Kinetic analysis and immunoinhibition studies indicated that the OM-specific CYP2G1 plays the major role in metabolic activation of coumarin. Furthermore, of 13 human cytochrome P-450s (P-450s) examined, five (CYP1A1, CYP1A2, CYP2B6, CYP2E1, and CYP3A4) were active in the metabolic activation of coumarin, suggesting a potential risk of coumarin toxicity in humans.     

Evaluating a team building intervention in a youth exercise setting.

The purpose of this study was to examine the relationship between the mechanisms in an established team building (TB) activity intervention and cohesion, its proposed outcome as well as conduct a process evaluation of the intervention in a youth exercise setting. Participants (N = 100, 13–17 years) were members of school-based exercise clubs randomly assigned to either a TB or control condition. In the TB condition, trained leaders implemented an established TB protocol (Carron & Spink, 1993). Results revealed a positive association between the specified mechanisms in the TB intervention and the proposed outcome of task cohesion. The evaluation of the intervention also revealed that the TB components were implemented as prescribed, and the intervention appeared to be appropriate for a youth setting. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Metabolic activation of 2,6-dichlorobenzonitrile, an olfactory-specific toxicant, by rat, rabbit, and human cytochromes P450

The authors posit that cellular edema is the major contributor to brain swelling in diffuse head injury and that the contribution of vasogenic edema may be overemphasized. The objective of this study was to determine the early time course of blood-brain barrier (BBB) changes in diffuse closed head injury and to what extent barrier permeability is affected by the secondary insults of hypoxia and hypotension. The BBB disruption was quantified and visualized using T1-weighted magnetic resonance (MR) imaging following intravenous administration of the MR contrast agent gadolinium-diethylenetriamine pentaacetic acid. To avoid the effect of blood volume changes, the maximum signal intensity (SI) enhancement was used to calculate the difference in BBB disruption. A new impact-acceleration model was used to induce closed head injury. Forty-five adult Sprague-Dawley rats were separated into four groups: Group I, sham operated (four animals), Group II, hypoxia and hypotension (four animals), Group III, trauma only (23 animals), and Group IV, trauma coupled with hypoxia and hypotension (14 animals). After trauma was induced, a 30-minute insult of hypoxia (PaO2 40 mm Hg) and hypotension (mean arterial blood pressure 30 mm Hg) was imposed, after which the animals were resuscitated. In the trauma-induced animals, the SI increased dramatically immediately after impact. By 15 minutes permeability decreased exponentially and by 30 minutes it was equal to that of control animals. When trauma was coupled with secondary insult, the SI enhancement was lower after the trauma, consistent with reduced blood pressure and blood flow. However, the SI increased dramatically on reperfusion and was equal to that of control by 60 minutes after the combined insult. In conclusion, the authors suggest that closed head injury is associated with a rapid and transient BBB opening that begins at the time of the trauma and lasts no more than 30 minutes. It has also been shown that addition of posttraumatic secondary insult-hypoxia and hypotension-prolongs the time of BBB breakdown after closed head injury. The authors further conclude that MR imaging is an excellent technique to follow (time resolution 1-1.5 minutes) the evolution of trauma-induced BBB damage noninvasively from as early as a few minutes up to hours or even longer after the trauma occurs.     

Mediational effects of social cohesion on the leadership behavior–intention to return relationship in sport.

The purpose of the present study was to use A. V. Carron's (1982) conceptual model to determine whether social cohesion mediates relations between leadership behavior and intention to return to sport. Women competing in recreational leagues completed the Leadership Scale for Sports and the Group Environment Questionnaire after the completion of their season. Intention to return for another season also was assessed at this time. Mediation was tested by using the framework suggested by R. M. Baron and D. A. Kenny (1986). Results revealed that leadership behavior affected intention to return, but its effect was minimized when social cohesion was included in the predictive equation. This result supported the conclusion that specific aspects of social cohesion mediate the relationship between leadership behavior and intention to return to sport for another season. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regulation of spvR, the positive regulatory gene of Salmonella plasmid virulence genes

The regulation of the spvR promoter from the Salmonella dublin virulence plasmid was monitored using promoter-reporter gene fusion constructs. Activity was dependent upon the presence of the spv region and was affected by the number of copies of the spv region present within the cell. Activity remained constant throughout exponential growth, and increased rapidly with the onset of stationary phase, under both aerobic and anaerobic conditions. Additionally, the level of spvR expression was controlled by the availability of iron, activity being greatest under low iron conditions in stationary phase. The spvA gene product negatively regulated spvR expression in a dose-dependent manner, indicating that SpvA provides a negative feedback mechanism for this operon.     

Defining the Public Health Threat of Dietary Supplement Fraud

Adverse health events resulting from dietary supplement fraud (DSF)—fraud conducted for economic gain using dietary supplements—have received increased recognition from agencies and industry. There is a growing awareness that this issue represents a significant public health threat. With increasing consumption of supplements, there are increasing consequences—good and bad—for food science and food safety. “Dietary supplements” are a special category of food that consists of finished products (for example, a vitamin D tablet) that contain 1 or more dietary ingredients. “Dietary ingredients” are the components of those finished products (for example, vitamin D added to a food product such as breakfast cereal). Due to a number of factors, potentially harmful dietary supplements reach—and often remain—in the market. DSF is a type of product fraud, as is food fraud, which is often classified by the U.S. Food and Drug Administration as Economically Motivated Adulteration (EMA). Since the adulterants are unconventional, DSF may represent an even greater public health threat than traditional dietary supplement safety issues (though it is important to note that adulteration is only one type of fraud). Criminology concepts such as situational crime prevention and the crime triangle deepen understanding of the relationship of fraud opportunity as it relates to fraudsters and established hurdles to fraud. The purpose of this research is to provide a comprehensive overview on the public health threat of DSF, and to focus on altering current intervention and response‐based approaches that are prevention‐based.