Alteration of GSH level, gene expression and cell transformation in NIH3T3 cells by chronic exposure to low dose of arsenic

It is well established that arsenic toxicity is postulated to be primarily due to the binding of As(III) to sulfhydryl-containing enzymes. However, the mechanism of carcinogenesis induced by arsenic is still unclear. The interaction of arsenic with GSH and related enzymes seems a very important issue regarding mechanism of arsenical induced toxicity or carcinogenesis. The purpose of this work is to investigate the effect of chronic exposure to low dose of As(III) on GSH level, gene expression and cell transformation in NIH3T3 cells. The results showed that long-term, low dose arsenic treatment makes 3T3 cell more resistant to acute arsenic treatment. There were morphology changes after long-term arsenic treatment. First, partially immortalized 3T3 cell became immortalized. In addition, the cells were doubling more quickly than the control cells and attained higher density than the control cells at confluence. Second, cells treated with 0.1 µ.M As(III) exhibited anchorage-independent growth. Arsenic could enhance GSH level at 0.5 -10 µM dose of arsenic in 24 h treatment and decrease it at 25 µM and above. In long-term treatment with low dose of arsenic, GSH levels were decreased. As(I1I) can increase both glutathione S-transferase (GST) and glutathione reductase (GR) activities at low dose (0.5-10 M), but decreased GST and GR activities at 25 M and higher dose of arsenic, while in long-term As(III) treatment, GST and GR activities are increased. Both long-term and short-term treatments with As(III) can induce GR gene expression. GPx mRNA levels were decreased both in acute and chronic arsenic treated cells. Chronic treatment with As(III) also decreased the p53 mRNA level. Taken together, our results suggest that As(III) can alter GST, GR enzyme activities as well as GSH level and related gene expression both in long-term and short-term treatment but in a different manner in different doses. Alteration of cellular GSH level by As(III) might play all important role in gene expression and arsenic induced cell transformation.

Community integration or community exposure? A review and discussion in relation to people with an intellectual disability

Background: This paper reviews the issue of integration as it applies to people with an intellectual disability. A compelling finding is the almost exclusive orientation of the literature to physical integration within the general community of non-disabled people. Moreover, it seems to be generally assumed that the more frequently people experience such integration the better their lives will be. Methods: We question the validity of this assumption on several grounds. It is social, not physical integration, that has a reliable positive influence on well-being. This is an important conclusion as some disabled people find effective social integration with the general community extremely difficult to achieve. Because of this, the consequences of an overly enthusiastic program of integration for such people has more potential to be more stressful than beneficial. Results: We further argue that, as integration is being pursued to benefit the individual, the essential goal of service provision should be to achieve a sense of community connectedness, rather than being concerned with physical integration within the general community.
Conclusion: It is proposed that such connectedness is more likely to be achieved within the community of people with an intellectual disability.

Copper exposure induces trafficking of the Menkes protein in intestinal epithelium of ATP7A transgenic mice

The final steps in the absorption and excretion of copper at the molecular level are accomplished by 2 closely related proteins that catalyze the ATP-dependent transport of copper across the plasma membrane. These proteins, ATP7A and ATP7B, are encoded by the genes affected in human genetic copper-transport disorders, namely, Menkes and Wilson diseases. We studied the effect of copper perfusion of an isolated segment of the jejunum of ATP7A transgenic mice on the intracellular distribution of ATP7A by immunofluorescence of frozen sections. Our results indicate that ATP7A is retained in the trans-Golgi network under copper-limiting conditions, but relocalized to a vesicular compartment adjacent to the basolateral membrane in intestines perfused with copper. The findings support the hypothesis that the basolateral transport of copper from the enterocyte into the portal blood may involve ATP7A pumping copper into a vesicular compartment followed by exocytosis to release the copper, rather than direct pumping of copper across the basolateral membrane.

Mega-events and the "Showcase" effect: investigating the moderating influence of exposure to the 2004 Olympic games telecast and interest in the Olympic movement- an Australian perspective

Survey-based research explored the moderating effects of "exposure" to the Australian free-to-air telecast of Athens 2004 and "interest" in Olympic Games in developing behavioral intentions to visit Greece in the future. Differences were found between groups with low and high levels of exposure to the telecast, and also between groups with high levels of interest in the Olympic Games, but these were only marginal. When the combinatorial influences of these two variables were considered simultaneously, their effects were generally synergistic. The article calls for further research on this area of mega-events, as the results, while of significance, provide food to continue the broader debate on the role of mega-events in developing tourism to their host destinations after their staging.

Sun exposure and sun protection behaviours among Australian adolescents: trends over time

Background
This study compared the sun exposure and sun protection behaviours of adolescent students between 1993 and 1999.

Methods
Schools from all Australian states and the two territories participated in each of the 1993, 1996, and 1999 surveys and a sample of students from years 7 to 12 were surveyed. In each of the states and territories a random sample of schools was selected within each education sector (government, Catholic, independent). The questionnaire was a self-completed booklet with questions about sunburn history during the previous summer, tan preferences, skin-type, and usual reported behaviour. Data from a total of 78,032 students were available for analysis.

Results
From 1993 to 1999 there was a significant increase in the number of students reporting sunburn during the previous summer (χ2 = 225.77, df = 2, P < 0.01). However, the percentage of students who preferred no tan at all increased over the same period (χ2 = 184.47, df = 2, P < 0.01). The percentage of students who usually or always wore clothing that covered most of their body decreased between 1993 and 1999 (χ2 = 20.46, df = 2, P < 0.01); the percentage of students usually or always wearing maximum protection sunscreen decreased over time (χ2 = 27.71, df = 2, P < 0.01). Staying in the shade increased from 1993 (26%) to 1996 (32%) but decreased slightly in 1999 (30%). Across all survey years, only 11% of students routinely followed all three protective behaviours of wearing a hat, sunscreen, and clothes that cover the body.

Conclusions
Sun protection practices among adolescents are still below optimal levels. Future educational programs require innovative approaches that aims to change attitudes toward tanning as being healthy and attractive and modify adolescent behaviours in relation to sun exposure.

Can the use of foreign currency derivatives explain variations in foreign exchange exposure? Evidence from Australian companies

We investigate the role of foreign currency derivatives (FCD) in alleviating foreign exchange rate exposure of Australian firms. While there is some evidence that the use of FCD reduces the level of ex-post short-term exposure, such an effect is absent with regard to the degree of foreign operations. Our results support the view that FCDs are used to hedge existing exchange rate exposures and that Australian firms, generally, are extensively exposed to currency fluctuations in the long run. While monthly exposure appears to be a function of a firm's size and financial hedging, exchange rate exposure of shorter horizons (1 and 3 months) appears to be negatively related to a firm's price earnings ratio (proxying growth opportunities)—thereby supporting the ‘underinvestment’ hypothesis. Further, the exposure of longer horizons (12 and 24 months) is positively related to a firm's liquidity, supporting the view that liquidity is a substitute for hedging.

Learning opportunities for Australian prevocational hospital doctors: exposure, perceived quality and desired methods of learning.

Objective:

To survey prevocational doctors working in Australian hospitals on aspects of postgraduate learning.
Participants and setting:

470 prevocational doctors in 36 health services in Australia, August 2003 to October 2004.
Design:

Cross-sectional cohort survey with a mix of ordinal multicategory questions and free text.
Main outcome measures:

Perceived preparedness for aspects of clinical practice; perceptions of the quantity and usefulness of current teaching and learning methods and desired future exposure to learning methods.
Results:

64% (299/467) of responding doctors felt generally prepared for their job, 91% (425/469) felt prepared for dealing with patients, and 70% (325/467) for dealing with relatives. A minority felt prepared for medicolegal problems (23%, 106/468), clinical emergencies (31%, 146/469), choosing a career (40%, 188/468), or performing procedures (45%, 213/469). Adequate contact with registrars was reported by 90% (418/465) and adequate contact with consultants by 56% (257/466); 20% (94/467) reported exposure to clinical skills training and 11% (38/356) to high-fidelity simulation. Informal registrar contact was described as useful or very useful by 94% (433/463), and high-fidelity simulation by 83% (179/216). Most prevocational doctors would prefer more formal instruction from their registrars (84%, 383/456) and consultants (81%, 362/447); 84% (265/316) want increased exposure to high-fidelity simulation and 81% (283/350) to professional college tutorials.
Conclusion:

Our findings should assist planning and development of training programs for prevocational doctors in Australian hospitals.

Sun exposure and sun protection behaviours among young adult sport competitors

Objective: To explore the relationship between sun protection and physical activity in young adults (18-30 years) involved in four organised sports.

Methods: Participants (n=237) in field hockey, soccer, tennis and surf sports completed a self-administered survey on demographic and sun-protective behaviours while playing sport. Differences in sun-protective behaviour were explored by sport and by gender.

Results: Sunburn during the previous sporting season was high (69%). There were differences between sports for sunburn, sunscreen use and reapplication of sunscreen. Lifesaving had the highest rates compared with the other three sports. Hats and sunglasses worn by participants varied significantly by sports. A greater proportion of soccer and hockey players indicated they were not allowed to wear a hat or sunglasses during competition. For all sports, competition was played mainly in the open with no shade provision for competitors while they were playing. There were some gender differences within each of the sports. Female soccer and tennis players were more likely to wear sunscreen compared with males. Female hockey players were more likely to wear a hat compared with males.

Conclusions: Our findings highlight that there is still room for improvement in sun-protective behaviours among young adult sport competitors. There is a need for a systematic approach to sun protection in the sporting environments of young adults.

Implications: Health promotion efforts to increase physical activity need to be paired with sun protection messages.

Exchange rate exposure, foreign currency derivatives and the introduction of the euro: French evidence

We investigate the impact of the introduction of the Euro on exchange rate exposures for French corporations and examine the corporate use of foreign currency derivatives to hedge exchange rate exposure post-Euro. Our findings indicate that the introduction of the Euro is associated with both a reduction in the number of firms that have significant exchange rate exposure and the absolute size of exposure. Consistent with these reduced exposures, French firms use foreign currency derivatives less intensively. Furthermore, the use of foreign currency derivatives is found to be associated with lower exchange rate exposure but there is insufficient evidence that these instruments are more effective in the post-Euro environment.

Emotional reactions following exposure to idealized bodies predict unhealthy body change attitudes and behaviors in women and men

Objective: We explored the extent to which changes in emotional states following exposure to images of idealized bodies predict unhealthy body change attitudes and behaviors in women and men, and whether particular psychological traits mediate these effects. Method: One hundred thirty-three women and 93 men were assessed for unhealthy attitudes and behaviors related to body weight and muscles using the Eating Disorder Inventory-2 (EDI-2), the Obligatory Exercise Questionnaire, and the strategies to increase muscles subscale of the Body Change Inventory. Psychological traits assessed included body dissatisfaction (EDI-2), internalization of the thin/athletic ideal (Sociocultural Attitudes Towards Appearance Questionnaire-3), body comparison (Body Comparison Scale), self-esteem (Rosenberg Self-Esteem Inventory), depression (Beck Depression Inventory-II), and identity confusion (Self-Concept Clarity Scale). Participants were then exposed to photographs of thin female models and muscular male models, and visual analogue scales were used to measure changes in postexposure state body dissatisfaction, anger, anxiety, and depression.
Results: Postexposure increases in state anger, anxiety, depression, and body dissatisfaction correlated with drive for thinness and disordered eating symptomatology in women, while postexposure increases in state body dissatisfaction correlated with muscle development in men. Analyses revealed that internalization and body comparison mediated these relationships, with trait body dissatisfaction, trait depression, self-esteem, and self-concept/identity confusion serving as mediators for women only. Conclusion: These results are indicative of gender differences in: (a) reactions to idealized bodies; (b) psychological traits that predispose individuals to experience these reactions; and (c) types of body change behavior that are associated with these reactions.

Estimating mean exposures from censored data: exposure to benzene in the Australian petroleum industry

A retrospective assessment of exposure to benzene was carried out for a nested case control study of lympho-haematopoietic cancers, including leukaemia, in the Australian petroleum industry. Each job or task in the industry was assigned a Base Estimate (BE) of exposure derived from task-based personal exposure assessments carried out by the company occupational hygienists. The BEs corresponded to the estimated arithmetic mean exposure to benzene for each job or task and were used in a deterministic algorithm to estimate the exposure of subjects in the study. Nearly all of the data sets underlying the BEs were found to contain some values below the limit of detection (LOD) of the sampling and analytical methods and some were very heavily censored; up to 95% of the data were below the LOD in some data sets. It was necessary, therefore, to use a method of calculating the arithmetic mean exposures that took into account the censored data. Three different methods were employed in an attempt to select the most appropriate method for the particular data in the study. A common method is to replace the missing (censored) values with half the detection limit. This method has been recommended for data sets where much of the data are below the limit of detection or where the data are highly skewed; with a geometric standard deviation of 3 or more. Another method, involving replacing the censored data with the limit of detection divided by the square root of 2, has been recommended when relatively few data are below the detection limit or where data are not highly skewed. A third method that was examined is Cohen's method. This involves mathematical extrapolation of the left-hand tail of the distribution, based on the distribution of the uncensored data, and calculation of the maximum likelihood estimate of the arithmetic mean. When these three methods were applied to the data in this study it was found that the first two simple methods give similar results in most cases. Cohen's method on the other hand, gave results that were generally, but not always, higher than simpler methods and in some cases gave extremely high and even implausible estimates of the mean. It appears that if the data deviate substantially from a simple log-normal distribution, particularly if high outliers are present, then Cohen's method produces erratic and unreliable estimates. After examining these results, and both the distributions and proportions of censored data, it was decided that the half limit of detection method was most suitable in this particular study.

Leukemia risk associated with low-level benzene exposure

Background: Men who were part of an Australian petroleum industry cohort had previously been found to have an excess of lympho-hematopoietic cancer. Occupational benzene exposure is a possible cause of this excess.

Methods: We conducted a case-control study of lympho-hematopoietic cancer nested within the existing cohort study to examine the role of benzene exposure. Cases identified between 1981 and 1999 (N = 79) were age-matched to 5 control subjects from the cohort. We estimated each subject's benzene exposure using occupational histories, local site-specific information, and an algorithm using Australian petroleum industry monitoring data.

Results: Matched analyses showed that the risk of leukemia was increased at cumulative exposures above 2 ppm-years and with intensity of exposure of highest exposed job over 0.8 ppm. Risk increased with higher exposures; for the 13 case-sets with greater than 8 ppm-years cumulative exposure, the odds ratio was 11.3 (95% confidence interval = 2.85-45.1). The risk of leukemia was not associated with start date or duration of employment. The association with type of workplace was explained by cumulative exposure. There is limited evidence that short-term high exposures carry more risk than the same amount of exposure spread over a longer period. The risks for acute nonlymphocytic leukemia and chronic lymphocytic leukemia were raised for the highest exposed workers. No association was found between non-Hodgkin lymphoma or multiple myeloma and benzene exposure, nor between tobacco or alcohol consumption and any of the cancers.

Conclusions: We found an excess risk of leukemia associated with cumulative benzene exposures and benzene exposure intensities that were considerably lower than reported in previous studies. No evidence was found of a threshold cumulative exposure below which there was no risk.

Comparison of tissue dosimetry in the mouse following chronic exposure to arsenic compounds

Several chronic bioassays have been conducted in multiple strains of mice in which various concentrations of arsenate or arsenite were administered in the drinking water without a tumorigenic effect. However, one study (Ng et al., 1999) reported a significant increase in tumor incidence in C57Bl/6J mice exposed to arsenic in their drinking water throughout their lifetime, with no tumors reported in controls. A physiologically based pharmacokinetic model for arsenic in the mouse has previously been developed (Gentry et al., 2004) to investigate potential differences in tissue dosimetry of arsenic species across various strains of mice. Initial results indicated no significant differences in blood, liver, or urine dosimetry in B6C3F1 and C57Bl/6 mice for acute or subchronic exposure. The current work was conducted to compare model-predicted estimates of tissue dosimetry to additional kinetic information from the (C57Bl/6 x CBA)F1 and TgAc mouse. The results from the current modeling indicate that the pharmacokinetic parameters derived based on information in the B6C3F1 mouse adequately describe the measured concentrations in the blood/plasma, liver, and urine of both the (C57Bl/6 x CBA)F1 and TgAc mouse, providing further support that the differences in response observed in the chronic bioassays are not related to strain-specific differences in pharmacokinetics. One significant finding was that no increases in skin or lung concentrations of arsenic species in the (C57Bl/6 x CBA)F1 strain were observed following administration of low concentrations (0.2 or 2 mg/L) of arsenate in the drinking water, even though differences in response in the skin were reported. These data suggest that pharmacodynamic changes may be observed following exposure to arsenic compounds without an observable change in tissue dosimetry. These results provided further indirect support for the existence of inducible arsenic efflux in these tissues.