Ascorbic acid induces an oxidative stress in CCRF cells activating the transcription factors AP-1 and NFRB

We have previously tested the effects of high dose AA supplements on human volunteers in terms of reducing DNA damage, as a possible mechanism of the vitamin’s proposed protective effect against cancer and detected a transient, pro-oxidant effect at high doses (500 mg/day). Herein, we present evidence of a pro-oxidant effect of the vitamin when added to CCRF cells at extracellular concentrations which mimic those present in human serum in vivo (50–150AM). The activation of the transcription factor AP-1 was optimal at 100 AM AA following 3h exposure at 37jC. A minimum dose of 50 AM of AA activated NFnB but there appeared to be no dose-dependent effect. Increases of 2–3 fold were observed for both transcription factors when cells were exposed to 100 AM AA for 3h, comparing well with the pro-oxidant effect of H2O2 at similar concentrations. In parallel experiments the activation of AP-1 (binding to DNA) was potentiated when cells were pre-incubated with AA prior to exposure with H2O2. Cycloheximide pretreatment (10 Ag/ml for 15min) caused a 50% inhibition of AP-1 binding to DNA suggesting that it was due to a combination of increasing the binding of pre-existing Fos and Jun and an increase in their de novo synthesis. Cellular localisation was confirmed by immunocytochemistry using antibodies specific for c-Fos and c-Jun proteins. These results suggest that extracellular AA can elicit an intracellular stress response resulting in the activation of the oxidative stress-responsive transcription factors AP-1 and NFnB. These transcription factors are involved in the induction of genes associated with an oxidative stress response, cell cycle arrest and DNA repair confirmed by our cDNA microarray analysis (Affymetrix). This may explain the abilty for AA to appear to inhibit 8-oxodG, yet simultaneously generate another oxidative stress biomarker, 8-oxo-dA. These results suggest a completely novel DNA repair action for AA. Whether this action is relevant to our in vivo findings will be the subject of our future research.

Staying in nursing:what factors determine whether nurses intend to remain employed?

Aim. To test a model of eight thematic determinants of whether nurses intend to remain in nursing roles. Background. Despite the dramatic increase in the supply of nurses in England over the past decade, a combination of the economic downturn, funding constraints and more generally an ageing nursing population means that healthcare organizations are likely to encounter long-term problems in the recruitment and retention of nursing staff. Design. Survey. Method. Data were collected from a large staff survey conducted in the National Health Service in England between September-December 2009. A multi-level model was tested using MPlus statistical software on a sub-sample of 16,707 nurses drawn from 167 healthcare organizations. Results. Findings were generally supportive of the proposed model. Nurses who reported being psychologically engaged with their jobs reported a lower intention to leave their current job. The perceived availability of developmental opportunities, being able to achieve a good work-life balance and whether nurses' encountered work pressures were also influencing factors on their turnover intentions. However, relationships formed with colleagues and patients displayed comparatively small relationships with turnover intentions. Conclusion. The focus at the local level needs to be on promoting employee engagement by equipping staff with the resources (physical and monetary) and control to enable them to perform their tasks to standards they aspire to and creating a work environment where staff are fully involved in the wider running of their organizations, communicating to staff that patient care is important and the top priority of the organization. © 2012 Blackwell Publishing Ltd.

Survey of teacher stress in secondary schools in the local authority

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Conditional osmotic stress in yeast:a system to study transport through aquaglyceroporins and osmostress signaling

The accumulation and transport of solutes are hallmarks of osmoadaptation. In this study we have employed the inability of the Saccharomyces cerevisiae gpd1Δ gpd2Δ mutant both to produce glycerol and to adapt to high osmolarity to study solute transport through aquaglyceroporins and the control of osmostress-induced signaling. High levels of different polyols, including glycerol, inhibited growth of the gpd1Δ gpd2Δ mutant. This growth inhibition was suppressed by expression of the hyperactive allele Fps1-AΔ of the osmogated yeast aquaglyceroporin, Fps1. The degree of suppression correlated with the relative rate of transport of the different polyols tested. Transport studies in secretory vesicles confirmed that Fps1-Δ1 transports polyols at increased rates compared with wild type Fps1. Importantly, wild type Fps1 and Fps1-Δ1 showed similarly low permeability for water. The growth defect on polyols in the gpd1Δ gpd2Δ mutant was also suppressed by expression of a heterologous aquaglyceroporin, rat AQP9. We surmised that this suppression was due to polyol influx, causing the cells to passively adapt to the stress. Indeed, when aquaglyceroporin-expressing gpd1Δ gpd2Δ mutants were treated with glycerol, xylitol, or sorbitol, the osmosensing HOG pathway was activated, and the period of activation correlated with the apparent rate of polyol uptake. This observation supports the notion that deactivation of the HOG pathway is closely coupled to osmotic adaptation. Taken together, our "conditional" osmotic stress system facilitates studies on aquaglyceroporin function and reveals features of the osmosensing and signaling system. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.

Hydrogen sulfide:a novel mechanism for the vascular protection by resveratrol under oxidative stress in mouse aorta

Reactive oxygen species (ROS) decreases bioavailability of nitric oxide (NO) and impairs NO-dependent relaxations. Like NO, hydrogen sulfide (H2S) is an antioxidant and vasodilator; however, the effect of ROS on H2S-induced relaxations is unknown. Here we investigated whether ROS altered the effect of H2S on vascular tone in mouse aorta and determined whether resveratrol (RVT) protects it via H2S. Pyrogallol induced ROS formation. It also decreased H2S formation and relaxation induced by l-cysteine and in mouse aorta. Pyrogallol did not alter sodium hydrogensulfide (NaHS)-induced relaxation suggesting that the pyrogallol effect on l-cysteine relaxations was due to endogenous H2S formation. RVT inhibited ROS formation, enhanced l-cysteine-induced relaxations and increased H2S level in aortas exposed to pyrogallol suggesting that RVT protects against "H2S-dysfunctions" by inducing H2S formation. Indeed, H2S synthesis inhibitor AOAA inhibited the protective effects of RVT. RVT had no effect on Ach-induced relaxation that is NO dependent and the stimulatory effect of RVT on H2S-dependent relaxation was also independent of NO. These results demonstrate that oxidative stress impairs endogenous H2S-induced relaxations and RVT offers protection by inducing H2S suggesting that targeting endogenous H2S pathway may prevent vascular dysfunctions associated by oxidative stress.

Stress, burnout and coping strategies in the emergency and intensive care hospital departments

Doctors and nurses working at the accident and emergency (A&E), and intensive care departments are at risk of burnout. They often spend substantial time in intense interactions with other people, centered on patients? health problems (physical, psychological and social) that may lead to feelings of anger, anxiety and frustration, and eventually to burnout. Burnout is a syndrome of emotional exhaustion, depersonalization and reduced personal accomplishment (Maslach & Jackson, 1981) The purpose of this chapter is to assess work stressors, burnout and stress-coping mechanisms among doctors and nurses at the A&E and intensive care departments. A quantitative design using the survey approach was used to collect data from a sample of 200 participants with a response rate of 71% (n=154) Work stressors were associated with burnout in both doctors and nurses. Workload was the most salient work stressor in the sample. Nurses experienced more stress (M=1.5, SD=0.4) than doctors (M=1.2, SD=0.4) in all the work stressor variables examined. The A&E department was reported as more stressful than the intensive care department. Avoidance-oriented and task-oriented coping were the most and the least frequently reported coping strategies respectively. Additionally, only emotion-oriented coping strategy was significantly different between doctors and nurses, and this strategy was also significantly positively correlated with all the variables in the adapted nursing stress scale, and the three burnout variables. Death and dying was most strongly correlated with emotion-oriented coping. This chapter provides an assessment of stress, burnout and coping experienced by both doctors and nurses within the A&E and intensive care departments. Methods that may mitigate stress in these environments may be adequate staffing, supportive management, stress management programs, as well as improvement in communication strategies between doctors and nurses.

Cross-cultural variations in climate for autonomy, stress and organizational productivity relationships:A comparison of Chinese and UK manufacturing organizations

Cross-cultural researchers have questioned the extent to which European–American management practices can be transported to major markets in Asia, such as the People's Republic of China. Applying employee involvement theory, we examined the relationships between climate for autonomy, work demands climate, employee stress and organizational productivity in a cross-national study of 51 UK and 104 Chinese manufacturing organizations. We predicted and found that climate for autonomy was positively and negatively related to stress in the Chinese and UK contexts, respectively. The interaction of climate for autonomy and work demands climate was significant: climate for autonomy was positively related to organizational productivity only when work demands climate was low.

Differential birefringence in Bragg gratings in multicore fiber under transverse stress

We present experimental measurements of the peak splitting of the reflection spectra of fiber Bragg gratings as a result of birefringence induced by transverse loading of a multicore fiber. Measurements show that the splitting is a function of the applied load and the direction of the load relative to the azimuth of the fiber. A model for calculating the stress in the fiber that is due to an applied load is in good agreement with our experimental observations.

Dapsone induces oxidative stress and impairs antioxidant defenses in rat liver

Dapsone (DDS) is currently used in the treatment of leprosy, malaria and in infections with Pneumocystis jirovecii and Toxoplasma gondii in AIDS patients. Adverse effects of DDS involve methemoglobinemia and hemolysis and, to a lower extent, liver damage, though the mechanism is poorly characterized. We evaluated the effect of DDS administration to male and female rats (30 mg/kg body wt, twice a day, for 4 days) on liver oxidative stress through assessment of biliary output and liver content of reduced (GSH) and oxidized (GSSG) glutathione, lipid peroxidation, and expression/activities of the main antioxidant enzymes glutathione peroxidase, superoxide dismutase, catalase and glutathione S-transferase. The influence of DDS treatment on express ion/activity of the main DDS phase-II- metabolizing system, UDP-glucuronosyltransferase (UGT), was additionally evaluated. The involvement of dapsone hydroxylamine (DDS-NHOH) generation in these processes was estimated by comparing the data in male and female rats since N-hydroxylation of DDS mainly occurs in males. Our studies revealed an increase in the GSSG/GSH biliary output ratio, a sensitive indicator of oxidative stress, and in lipid peroxiclation, in male but not in female rats treated with DDS. The activity of all antioxidant enzymes was significantly impaired by DDS treatment also in male rats, whereas UGT activity was not affected in any sex. Taken together, the evidence indicates that DDS induces oxidative stress in rat liver and that N-hydroxylation of DDS was the likely mediator. Impairment in the activity of enzymatic antioxidant systems, also associated with DDS-NHOH formation, constituted a key aggravating factor.