Human and environmental health challenges for the next decade (2010–2020).

The public health and environmental communities will face many challenges during the next decade. To identify significant issues that might be addressed as part of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) scientific portfolio, an expert group of key government, academic, and industry scientists from around the world were assembled in 2009 to map the current and future landscape of scientific and regulatory challenges. The value of the scientific mapping exercise was the development of a tool which HESI, individual companies, research institutions, government agencies, and regulatory authorities can use to anticipate key challenges, place them into context, and thus strategically refine and expand scientific project portfolios into the future.

Maximizing safe design of engineered nanomaterials: the NIH and NIEHS research perspective.

Estimating potential risk of an emerging technology as its products are being developed offers the greatest potential for success of the technology. The National Nanotechnology Initiative was launched in 2000 to provide a federal framework to support safe and responsible development of nanotechnology.Within this framework, the National Institutes of Health (NIH) focuses resources and expertise on both the biomedical applications of nanotechnology and the possibility of adverse health effects, or implications research.

Genetic determinants of sensitivity to beryllium in mice.

Chronic beryllium disease (CBD), an irreversible, debilitating granulomatous lung disease is caused by exposure to beryllium. This occupational hazard occurs in primary production and machining of Be-metal, BeO, beryllium - containing alloys, and other beryllium products. CBD begins as an MHC Class II-restricted, T(H)1 hypersensitivity, and the Human Leukocyte Antigen, HLA-DPB1E(69), is associated with risk of developing CBD.

Determination of in vivo dose response and allergen-specific T cells in subjects contact-sensitized to squaric acid dibutyl ester.

Background: Squaric acid dibutyl ester (SADBE) is a known contact sensitizer, but dose-response data are not defined.

Objective: To determine the relationship between sensitization dose and contact hypersensitivity (CHS) response to SADBE in human volunteers. The study also aimed to investigate whether SADBE-reactive blood T cells could be detected using ex vivo mature dendritic cells (DCs) as antigen-presenting cells.

Ethics in nanomedicine.

As the science and technology of nanomedicine speed ahead, ethics, policy and the law are struggling to keep up. It is important to proactively address the ethical, social and regulatory aspects of nanomedicine in order to minimize its adverse impacts on the environment and public health and also to avoid a public backlash. At present, the most significant concerns involve risk assessment, risk management of engineered nanomaterials and risk communication.

Ethical issues in clinical trials involving nanomedicine.

Nanomedicine shows tremendous promise for improving medical diagnosis, treatment, and prevention, but it also raises a variety of ethical concerns. Because of the paucity of data on the physicochemical properties of nanoscale materials in biological systems, clinical trials of nanomedicine products present some unique challenges related to risk minimization, management and communication involving human subjects. Although these clinical trials do not raise any truly novel ethical issues, the rapid development of nanotechnology and its potentially profound social and environmental impacts, add a sense of urgency to the problems that arise.

Beryllium exposure: dermal and immunological considerations.

Objective: People exposed to beryllium compounds are at increased risk of developing beryllium sensitization and chronic beryllium disease (CBD). The purpose of this short communication is to present information regarding the potential importance of skin exposure to beryllium, an exposure and alternate immune response pathway to the respiratory tract, which has been largely overlooked in epidemiologic and exposure assessment studies.

Methods: We reviewed the published literature, including epidemiologic, immunologic, genetic, and laboratory-based studies of in vivo and in vitro models, to assess the state of knowledge concerning skin exposure to beryllium.

Genetic factors modify the risk of developing beryllium disease.

Chronic beryllium disease (CBD) is a debilitating, granulomatous lung disease that occurs in 1 to 5% of exposed workers. Beryllium stimulates a major histocompatibility Class II-restricted, TH1, CD4+ T cell-mediated immune response. The immunological component of the illness, coupled with the small subset of beryllium workers who develop disease, led researchers to hypothesize that genetic factors modify risk of disease.

Electrostatic potential on human leukocyte antigen: implications for putative mechanism of chronic beryllium disease.

The pathobiology of chronic beryllium disease (CBD) involves the major histocompatibility complex class II human leukocyte antigen (HLA). Although occupational exposure to beryllium is the cause of CBD, molecular epidemiologic studies suggest that specific (Italic)HLA-DPB1(/Italic) alleles may be genetic susceptibility factors. We have studied three-dimensional structural models of HLA-DP proteins encoded by these genes.

Differential regulation of sensitizer-induced inflammation and immunity by acute restraint stress in allergic contact dermatitis.

Previously, we demonstrated that restraint stress applied before chemical sensitization modulates allergic contact dermatitis (ACD) differently than restraint applied before challenge. In this study, we asked if these dichotomous restraint-induced changes reflect modulation of the cutaneous microenvironment or changes in development of antigen-specific immunity in the lymph node (LN) of BALB/c mice. Our data confirm that restraint suppresses T cell-dependent immunity in ACD when applied prior to sensitization or prior to challenge and demonstrate that the stress-induced increase in ear swelling is due to heightened inflammation associated with ACD and is dependent upon the sensitization status of the mouse.

Skin as a route of exposure and sensitization in chronic beryllium disease.

Chronic beryllium disease is an occupational lung disease that begins as a cell-mediated immune response to beryllium. Although respiratory and engineering controls have significantly decreased occupational beryllium exposures over the last decade, the rate of beryllium sensitization has not declined. We hypothesized that skin exposure to beryllium particles would provide an alternative route for sensitization to this metal.

Acute stress modulates the irritant component of sensitizers in allergic contact dermatitis: implications for exposure assessment.

Exposure of skin to noxious environmental stimuli can cause allergic contact dermatitis (ACD), which is a major health risk. Epidemiological studies have determined that 40% of workers report that their jobs are very, or extremely, stressful, and the number of chemicals to which workers are exposed increases each year. We hypothesized that combined exposure to a workplace stressor and a sensitizing chemical would alter the time course and magnitude of the skin immune response.

Restraint stress and corticotropin releasing hormone modulation of murine cutaneous POMC mRNA.

The skin is a unique immunological defense barrier that protects the organism from occupational and environmental exposures and provides a model system in which to evaluate the interaction of the central nervous system with the peripheral immune response. In the studies presented here, we tested mild, acute restraint stress activation of the cutaneous corticotropin releasing hormone-pro-opiomelanocortin (CRH-POMC) axis. We verified that 2 h restraint stress increased the serum concentration of corticosterone and alpha-melanocyte stimulating hormone.

Insights into the quantitative relationship between sensitization and challenge for allergic contact dermatitis reactions.

The ability of chemical or pharmaceutical agents to induce allergic contact dermatitis (ACD) is of major health and regulatory concern. As such, tests to identify their sensitizing capacity, such as the guinea pig maximization test and the more recently developed local lymph node assay, are broadly used. Ideally, for risk assessment it is useful to translate results from animal data into establishing safe or no-effect levels for occupational or environmental agents.