Cytokine production induced by low-molecular-weight chemicals as a function of the stimulation index in a modified local lymph node assay: an approach to discriminate contact sensitizers from respiratory sensitizers

In general, contact sensitizers have been shown to selectively induce Th1 immune responses, such as interferon-gamma (IFN-gamma) production, whereas Th2 responses, such as interleukin (IL)-4 production, were seen after exposure to respiratory allergens. However, these features may be dependent on the dose of the particular allergen. Therefore, the aim of the present study was to investigate the distinction between contact sensitizers and respiratory allergens, by establishing dose-dependent cytokine profiles. The contact allergens 2,4- dinitrochlorobenzene (DNCB), hexyl cinnamic aldehyde (HCA), and oxazolone (OXA, 4-ethoxymethylene 2-phenyloxazol-5-one) as well as the respiratory allergens fluorescein 5-isothiocyanate, phthalic anhydride, toluene diisocyanate, and trimellitic anhydride were tested. For a range of concentrations, both proliferative responses and cytokine production were established. Estimated concentrations were derived at several stimulation indices (SIs). From the estimated concentrations, IFN-gamma, IL-4, and IL-10 production as a function of stimulation indices were plotted. All four respiratory allergens showed significantly higher IL-4 and IL-10 production patterns compared to the contact allergens. Positive identification of DNCB, HCA, and OXA as contact allergens on the basis of IFN-gamma production was observed only at very high stimulation indices (SI >or= 35) for DNCB and OXA and at low SIs (SI 相似文献   

Intrarenal detection of nitric oxide using electron spin resonance spectroscopy in hypertensive lipopolysaccharide-treated rats

The inhibition of nitric oxide (NO) synthesis by chronic administration of NG-nitro-l-arginine methyl ester (l-NAME) in rats is responsible for systemic hypertension. However, the mechanisms involved in this hypertension remain unclear. The effects of chronic l-NAME on kidney and blood NO production were studied in rats in a state of endotoxic shock due to lipopolysaccharide (LPS). A nitric oxide spin trapping technique using electron spin resonance (ESR) spectroscopy has been used to identify and measure the production of NO in the kidney. This method is based on the trapping of nitric oxide by a metal-chelator complex consisting of N-methyl-d-glucamine dithiocarbamate (MGD) and reduced iron (Fe2+) forming a water-soluble NO-FeMGD complex detected by ESR. After LPS injection (14 mg/kg, IV, 6 h before the sacrifice) to rats pretreated with l-NAME (10 mg/kg/d over 14 days), the NO-FeMGD complex was evaluated in the kidney (arbitrary units [AU]/g of kidney) and the density of polynuclear neutrophils was counted by light microscopy. Chronic inhibition of NO synthase by l-NAME, a nonspecific inhibitor, was responsible for a decrease of the NO-FeMGD complex levels in the kidney (24.9 +/- 1.6 AU versus 13.8 +/- 1.3 AU). LPS administration was responsible for a large increase in both NO-FeMGD complex and neutrophil levels in the kidney of normotensive rats (332.6 +/- 12.8 AU versus 24.9 +/- 1.6 AU for NO-FeMGD complex and 1.36 +/- 0.41 versus 0.11 +/- 0.03 for neutrophils). Conversely, LPS administration in hypertensive, l-NAME-pretreated rats was linked to a smaller increase in the NO-FeMGD complex (85.1 +/- 7.9 AU versus 332.6 +/- 12.8 AU) and a larger increase in glomerular neutrophils (2.48 +/- 0.36 versus 1.36 +/- 0.41) compared with normotensive rats. These results are in agreement with a direct implication of NO during LPS-and l-NAME-induced kidney injuries.     

Assessing the estrogenic potential of organochlorine pesticides in primary cultures of male rainbow trout (Oncorhynchus mykiss) hepatocytes using vitellogenin as a biomarker

Many organochlorine pesticides are suspected of impairing natural hormonal function in organisms by mimicking endogenous estrogen. The aim of this study was to assess the estrogenic activity of the organochlorine pesticides o,p'-DDT, dieldrin, aldrin, heptachlor, mirex and DDT in rainbow trout hepatocyte cultures using vitellogenin (Vtg) as the biomarker. A wide range of pesticide concentrations (0.0001-100 microM) was evaluated. Among the pesticides tested, o,p'-DDT was the most potent inducer of Vtg. The lower potency of technical grade DDT relative to o,p'-DDT could be explained by the fact that this pesticide is a mixture of two different pesticides (18% o,p'-DDT and 77% p,p'-DDT). This suggests that o,p'-DDT is a stronger inducer of Vtg than p,p'-DDT. A simple hypothesis could be that pesticides mixed together competed for the same receptor to favor the formation of a complex with reduced activity towards EREs. If these compounds are classified according to the level of Vtg secreted, we observed the following decreasing order: 17beta-estradiol (E(2))>o,p'-DDT>dieldrin>aldrin>DDT. Non-toxic levels of these compounds competed with E(2) for binding to the estrogen receptor. Heptachlor and mirex did not induce Vtg. Since the latter compounds failed to stimulate Vtg production, the possibility that they could interfere with the estrogenic response by inhibiting E(2) action was tested. In the presence of heptachlor, Vtg production triggered by E(2) significantly decreased. The EC50 value for inhibition of ER binding by heptachlor was cytotoxic for hepatocytes in culture, and this could in part explain the lack of Vtg response observed with this compound at the concentrations tested. Our results indicate that organochlorine pesticides can act as positive or negative modulators of estrogenic function in rainbow trout.     

'Opportunity structures': urban landscape,social capital and health promotion in Australia

This paper presents data from 40 in-depth interviews that were conducted as part of a study of social capital and health in relation to people's perceptions of the influence of 'place' on their participation levels and health. These data were used to examine features of the western suburbs of Adelaide that were perceived as health damaging and health promoting. The paper demonstrates that our Australian suburban respondents expressed a considerable concern about these features and the impact they have on their perception of community and their ability to participate in it. Safety, connectedness to the area, the reputation of an area and the extent and nature of community facilities are all seen as important to a healthy community. The research found that in the more deprived socioeconomic areas within the study area, there was a significant degree of dissatisfaction with features of the urban environment, such as availability of amenities, provision of public transport, and proximity of industry to private dwellings. The paper concludes by considering certain features of urban environments that might make them more supportive of health through encouraging contact between people. We conclude that these environments could be improved using the following measures: a subsidy scheme to support the viability of local shops and cafés (thereby providing meeting places and employment); parks with facilitators (who could play a role in increasing safety in the park but also encouraging community development); attractive places to walk; and a general environmental improvement program.     

Learning about interagency collaboration: trialling collaborative projects between hospitals and community health services

Interagency collaboration has increasingly been viewed as an important strategy to encourage the co-ordination of healthcare. It is seen to have a number of positive outcomes, including: improved service delivery for people requiring multiple services; more efficient use of healthcare resources; and a means for managers to share the responsibility of community care and reduce organizational stress caused by pressures of increasing demand for services within a climate of cost containment. However, establishing collaborative interagency relationships can be a challenging, long-term and complex process. The present article describes some of the findings of a research project that evaluated collaborative strategies adopted and trialed by a group of four publicly funded healthcare agencies in the southern metropolitan area of Adelaide, South Australia. Key findings from the literature about the factors supporting and impeding collaboration are discussed in the light of some of the findings from the evaluation project. Some of the themes emerging from the Adelaide study include: the need for resources for change; experience of multidisciplinary work; professional barriers to collaboration; the importance of agreed aims, agendas and project ownership; and the importance of supportive leadership. This article concludes with a discussion of the difficulties and opportunities for collaboration between community-based primary healthcare agencies and acute care hospitals. The development of partnerships which are either based on trust, or on the open negotiation of power differences and professional territories, and the management of mistrust are found to be important foundations for achieving greater genuine collaboration between primary and tertiary level healthcare.     

Long-term air pollution indicator assessment: example of black smoke in Bordeaux,France

The aim of the second phase of the Pollution Atmosphérique et Affections Respiratoires Chroniques (PAARC) study, started in 1974, was to compare the long-term mortality between populations living in areas with different air pollution levels. In Bordeaux (France), four different areas were concerned by the study. The black smoke measures were realized between 1974 and 1981. After 1981, the stations set specifically for the study were not used any more. The purpose of this study was to estimate the evolution of air pollution in those areas between 1982 and 1997 using the measures of 12 Association de Prévention de la Pollution Atmosphérique (APPA) stations located in Bordeaux city but not in the PAARC areas. The method used was divided in three phases: a correlation study between the stations of the different networks, a selection of the pertinent stations and the setting up of indicators using the arithmetic means method. Monthly means concentrations were estimated from January 1982 to December 1997. Models showed a decrease in black smoke levels whatever the area. The difference in level from one area to another, existing between the areas in 1974, was still with predicted values in 1997, but less important. Black smoke mean concentration for 1982-1997 was, respectively, 16.4 and 16.2 microg/m3, in areas 1 and 2. It was a little bit higher in area 3 with 18.9 microg/m3. Area 4 still has the highest level with 26.3 microg/m3. To conclude, this method enabled to assess different air pollution levels at different times in the four areas of the PAARC study in Bordeaux. Those levels could be used to study the impact of the air pollution on long-term mortality on populations living in the areas considered.     

Disasters in urban context

This article provides a brief overview of the field of disaster research, summarizing what is known at present about the prevalence of disasters, the range of stressors and outcomes experienced, and sample-, event-, and individual-level risk factors for poor health and mental health outcomes. Prior research does not suggest that an urban context either enhances or reduces risk for individual survivors. It is argued, however, that the influence of extraindividual exposure, ethnic diversity, and support deterioration may be especially salient for understanding urban disasters. Investigators of urban disasters are especially well situated to expand knowledge of ecological and collective aspects of disaster response and recovery.