RESUMO
Many naturally occurring proteins, peptides, carbohydrates, nucleic acids, and lipids, as well as synthetic peptides, are successful immunogens. To elicit an immune response, a compound must contain an antigenic determinant or epitope and must be of sufficient size to initiate lymphocyte activation necessary for an antibody response. In practice, small chemical compounds (haptens) are generally not good immunogens. However, when attached to macromolecules (carriers), they can become immunogenic. An immunogen must have epitopes that can be recognized by antigen-presenting cells and a T-cell receptor, and it must be degradable. Haptens and corresponding hapten-carrier conjugates have been essential to the development of sensitive quantitative and qualitative immunoassays. In the design of hapten conjugates, consideration must be given to the hapten, the carrier, the coupling strategy, and the hapten density because the amount of hapten attached to the carrier influences the strength of the immune response directed toward the newly created antigenic determinant. Hence the haptenic density of the conjugate is also important in the development of immunoassays. The optimal epitope density of a conjugate to elicit either a strong immune response or provide the best immunoassay is dependent on the structure of the epitope and the nature of the immunoassay. The aim of this chapter is to describe the diverse techniques used to couple haptens to carriers and provide guidance in the selection of the most appropriate procedure for a particular hapten.
Assuntos
Antígenos/química , Reagentes de Ligações Cruzadas/química , Haptenos/química , Proteínas/química , Animais , Antígenos/imunologia , Haptenos/imunologia , Humanos , Proteínas/imunologiaRESUMO
BACKGROUND: People in modern societies spend more than 90% of their time indoors. Hence, indoor environmental quality (IEQ) has a significant impact on public health. In this article we describe health risks associated with indoor environments, illuminate barriers to overcoming these risks, and provide policy recommendations to achieve healthier indoor environments. OBJECTIVES: The weight of evidence suggests that indoor environmental contaminants pose significant public health risks, particularly among children and the poor, and the societal costs of illnesses related to indoor environments are considerable. Despite the evidence of harm to human health, poor indoor environments are generally difficult to regulate and not of sufficient concern to the general public. We discuss several reasons for this lack of concern about IEQ, focusing specifically on home environments. DISCUSSION: Economics plays a large role both in political inaction and individual-level indifference. Because little effort has been made to quantify the value of the societal and individual costs of poor housing quality, as well as the benefits achievable by simple interventions, policymakers lack motivation to act on IEQ. Similarly, individual homeowners lack the incentive to remediate homes, as other problems may be more pressing than home environmental quality. CONCLUSIONS: Although the problem of IEQ involves multiple stakeholders and multiple levels of governance, it is possible to establish economic incentives that would set the wheels in motion for action at all levels to achieve healthy home environments. Also important are education and information dissemination on the public health risks associated with indoor environments. These recommendations are intended for all decision makers who have an influence in developing policy to improve indoor environmental quality.
Assuntos
Poluição do Ar em Ambientes Fechados/economia , Exposição Ambiental , Doença Ambiental/prevenção & controle , Habitação/normas , Política Pública , Poluição do Ar em Ambientes Fechados/legislação & jurisprudência , Educação em Saúde , Humanos , Fatores de RiscoRESUMO
Our understanding of the relationship between human health and the indoor environment continues to evolve. Previous research on health and indoor environments has tended to concentrate on discrete pollutant sources and exposures and on specific disease processes. Recently, efforts have been made to characterize more fully the complex interactions between the health of occupants and the interior spaces they inhabit. In this article we review recent advances in source characterization, exposure assessment, health effects associated with indoor exposures, and intervention research related to indoor environments. Advances in source characterization include a better understanding of how chemicals are transported and processed within spaces and the role that other factors such as lighting and building design may play in determining health. Efforts are under way to improve our ability to measure exposures, but this remains a challenge, particularly for biological agents. Researchers are also examining the effects of multiple exposures as well as the effects of exposures on vulnerable populations such as children and the elderly. In addition, a number of investigators are also studying the effects of modifying building design, materials, and operations on occupant health. Identification of research priorities should include input from building designers, operators, and the public health community.
Assuntos
Poluição do Ar em Ambientes Fechados/análise , Exposição Ambiental , Doença Ambiental/prevenção & controle , Habitação/normas , Códigos de Obras , Materiais de Construção , Planejamento Ambiental , Humanos , Material Particulado/análiseRESUMO
Asthma research has traditionally focused on children and the elderly, the two populations considered most susceptible to complications. The prevalence of asthma in the adult population (19-64 years of age) is, however, gaining recognition as a formidable clinical and public health problem. Few studies have compared the incidence of adult asthma hospitalizations in urban and nonurban areas. The study reported here, using population size, population density, and traffic-related factors to define urban versus nonurban environments, selected six Pennsylvania counties to test the hypothesis that the degree of urbanization influences the asthma hospitalization rate for adults. The study group comprised adults 19-64 years of age who were hospitalized for asthma (as the primary diagnosis) from 1999 to 2001. To define urbanization in relation to traffic, the study used daily vehicular traffic count and miles of roads/highways for each of the six counties. The authors found a decrease in the adult asthma hospitalization rate as urbanization decreased in some of the counties. For other counties, however, the rate increased as urbanization decreased. The counties in which the latter was observed had depressed measures of socioeconomic status. These findings suggest that depressed socioeconomic conditions may supersede exposure to traffic-related pollution as a factor associated with asthma hospitalizations.
Assuntos
Hospitalização/tendências , Urbanização , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pennsylvania/epidemiologia , Estados Unidos/epidemiologiaRESUMO
There is significant public concern about the potential health effects of exposure to mercury vapour (Hg(0)) released from dental amalgam restorations. The purpose of this article is to provide information about the toxicokinetics of Hg(0), evaluate the findings from the recent scientific and medical literature, and identify research gaps that when filled may definitively support or refute the hypothesis that dental amalgam causes adverse health effects. Dental amalgam is a widely used restorative dental material that was introduced over 150 years ago. Most standard dental amalgam formulations contain approximately 50% elemental mercury. Experimental evidence consistently demonstrates that Hg(0) is released from dental amalgam restorations and is absorbed by the human body. Numerous studies report positive correlations between the number of dental amalgam restorations or surfaces and urine mercury concentrations in non-occupationally exposed individuals. Although of public concern, it is currently unclear what adverse health effects are caused by the levels of Hg(0) released from this restoration material. Historically, studies of occupationally exposed individuals have provided consistent information about the relationship between exposure to Hg(0) and adverse effects reflecting both nervous system and renal dysfunction. Workers are usually exposed to substantially higher Hg(0) levels than individuals with dental amalgam restorations and are typically exposed 8 hours per day for 20-30 years, whereas persons with dental amalgam restorations are exposed 24 hours per day over some portion of a lifetime. This review has uncovered no convincing evidence pointing to any adverse health effects that are attributable to dental amalgam restorations besides hypersensitivity in some individuals.
Assuntos
Amálgama Dentário/efeitos adversos , Restauração Dentária Permanente/efeitos adversos , Mercúrio/efeitos adversos , Mercúrio/farmacocinética , Quimioterapia Combinada , Humanos , Compostos de Metilmercúrio/efeitos adversosRESUMO
Diisocyanates, highly reactive chemicals used in the production of polyurethanes, are currently the most frequently reported cause of chemically induced occupational asthma and their use continues to rise. The prevalence of diisocyanate asthma among exposed workers is estimated to range from 5% to 15%. Routes of exposure include the respiratory tract and skin. Workplace exposures are difficult to quantify and control, and there is no simple diagnostic test for the disease. This review considers recent concepts in exposure. clinical aspects and pathogenesis of the disease. The pathogenesis of diisocyanate asthma remains unclear, with evidence supporting both immunological and nonimmunological mechanisms. Knowledge of the chemical reactivity of diisocyanates, the target biomolecules, and the cellular sites of reaction are fundamental to understanding diisocyanate toxicity and disease. Recent findings of chemical interactions with biological nucleophiles will be described. The importance of diisocyanate-adducted biomolecules will be emphasized and their potential contributions to pathogenesis discussed. It is anticipated that greater understanding of the immunopathogenesis of diisocyanate asthma, including the initial cell/diisocyanate reactions, should lead to clinically useful markers of exposure and early disease.
Assuntos
Asma/etiologia , Asma/imunologia , Tolueno 2,4-Di-Isocianato/efeitos adversos , Animais , Asma/induzido quimicamente , Asma/diagnóstico , Humanos , Fatores de RiscoRESUMO
The prevalence of asthma is increasing worldwide. The increase has been found for both sexes, for all races and age groups. The factors responsible are unclear. The short period of increase makes it unlikely that a genetic change is responsible but rather suggests that either air pollutants or a behavioral change may be involved. Behavioral changes may include decreased exercise and outdoor activity due to, for example increased usage of television and computers. What is the role of allergy in the development of asthma? In allergic sensitization, allergens initiate the inflammation and IgE antibodies are typically present. Once asthma has developed, factors such as irritants, infections and exercise may result in acute symptomatology. Infancy is a high risk period for allergic sensitization since natural defense mechanisms are not fully developed. Epidemiologic evidence suggests that microbial stimuli during early childhood can influence induction of atopic diseases. In animal studies, pre-infection with respiratory virus has resulted in enhanced response to allergens. Another factor implicated in the surge of allergic disease is airborne particulates. Evidence has been obtained for an association of environmental tobacco smoke (ETS) with development of allergic sensitization. ETS enhances IgE production as does diesel and aluminum silicate, the latter a component of fly ash. What are the mechanisms responsible for the environmental influences on development of allergy? Th2 cytokine responses, with suppression of Th1 cytokines, are prominent in children. Th1 maturation appears to be promoted by microbial exposure. Increased understanding of the complex interactions of environmental factors with the developing immune system is essential to reverse the current upward trend in allergic respiratory disease.
Assuntos
Hipersensibilidade Respiratória/epidemiologia , Poluição do Ar em Ambientes Fechados/efeitos adversos , Animais , Asma/epidemiologia , Asma/genética , Meio Ambiente , Humanos , Estilo de Vida , Hipersensibilidade Respiratória/genética , Medição de Risco , Linfócitos T/metabolismoRESUMO
Increasingly, airborne mold in home environments has been linked with asthma exacerbation and other respiratory diseases in both children and adults. This problem is particularly relevanttoday, as Hurricane Katrina has resulted in water damage and mold proliferation in numerous homes on the U.S. Gulf Coast. Policies to control indoor moisture and mold can help solve problems of mold contamination and associated adverse health effects, yet very little attention has been given to developing such policies. We address the question of howto develop effective policies by deriving lessons from successful control of other home environmental contaminants; namely, radon and lead. These two agents are being controlled by a variety of policy approaches, including federal regulations and guidelines, public education, and economic incentives among home buyers and sellers. We analyze the mold problem and identify both similarities and differences with the radon and lead situations in the United States. We recommend policy approaches for controlling mold in homes that rely on home marketing incentives, building and housing codes, and maintenance and rehabilitation regulations, as well as public education initiatives.
Assuntos
Recuperação e Remediação Ambiental/legislação & jurisprudência , Fungos , Habitação , Chumbo/análise , Política Pública , Radônio/análiseRESUMO
Nearly 9 million workers are exposed to chemical agents associated with occupational asthma, with isocyanates representing the chemical class most responsible. Isocyanate-induced asthma has been difficult to diagnose and control, in part because the biologic mechanisms responsible for the disease and the determinants of exposure have not been well defined. Isocyanate-induced asthma is characterized by airway inflammation, and we hypothesized that inflammation is a prerequisite of isocyanate-induced asthma, with tumor necrosis factor (TNF)-alpha being critical to this process. To explore this hypothesis, wild-type mice, athymic mice, TNF-alpha receptor knockout (TNFR), and anti-TNF-alpha antibody-treated mice were sensitized by subcutaneous injection (20 micro l on Day 1; 5 micro l, Days 4 and 11), and challenged 7 d later by inhalation (100 ppb; Days 20, 22, and 24) with toluene diisocyanate (TDI). Airway inflammation, goblet cell metaplasia, epithelial cell damage, and nonspecific airway reactivity to methacholine challenge, measured 24 h following the last challenge, were reduced to baseline levels in TNF-alpha null mice and athymic mice. TNF-alpha deficiency also markedly abrogated TDI-induced Th2 cytokines in airway tissues, indicating a role in the development of Th2 responses. Despite abrogation of all indicators of asthma pathology, TNF-alpha neutralization had no effect on serum IgE levels or IgG-specific TDI antibodies, suggesting the lack of importance of a humoral response in the manifestation of TDI-induced asthma. Instillation studies with fluorescein-conjugated isothiocyanate and TDI suggested that TNF-alpha deficiency also resulted in a significant reduction in the migration of airway dendritic cells to the draining lymph nodes. Taken together, these results suggest that, unlike protein antigens, TNF-alpha has multiple and central roles in TDI-induced asthma, influencing both nonspecific inflammatory processes and specific immune events.