Nicotine

Cholinergic input plays a critical role in brain development, and nicotine, a cholinergic agonist, can disrupt this normal development (Roy et al. 2002). Interference with this input (excessive or inappropriately timed) can have broad-ranging results both in the brain and the peripheral nervous system. Activation of cholinergic input by nicotine is suspected to cause many of the adverse effects of maternal smoking. This is particularly important since the fetus accumulates relatively high...

Effects of ETS on Respiratory Health

There exists a significant body of research on the potential effects on respiratory health from exposure to environmental (passive) tobacco smoke (ETS) (reviewed in National Academy of Sciences 2000). Many components of ETS are known lung irritants. There have been direct associations shown between exposure to tobacco smoke and the development of lung cancer, obstructive airway disease, chronic bronchitis, ear infections, and asthma. It is small wonder that ETS is associated with so many...

Heavy Metals

The immunotoxic effects of heavy metals, such as lead, arsenic, and mercury exposure are well recognized (Bernier et al. 1995 Schuppe et al. 1998). In comparison to most environmental toxicants, the mechanism of metal immunotoxicity is well studied (reviewed in Schuppe et al. 1998). It is currently believed that metals initially elicit a cell-mediated immune response by binding to MHC class II molecules or MHC-bound self-peptides. The metal-MHC complex is then recognized by CD4+ T cells....

Polycyclic Aromatic Hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs) are a group of unsaturated cyclic hydrocarbons containing two or more rings, derived from the incomplete burning of organic materials. They are common environmental contaminants produced by diverse industrial (Ball and Dawson 1969 Ball et al. 1966 Gricuite 1979) and domestic (Huhti 1981 Aggarwal et al. 1982 Grimmer and Pott 1983) processes. Contamination and exposure to PAHs can occur in industrial, rural, and urban settings, as PAHs can be found in...

Common Effects of TCDD and CsA on T Cell Development

The developing immune system has been demonstrated to have a high sensitivity to TCDD. This, coupled with evidence that increased autoimmune disease may result following TCDD exposure in adult animals, has raised questions regarding possible relationships between prenatal exposure to TCDD and increased postnatal autoim-munity. Low-level maternal TCDD exposure results in atrophy of the developing thymus as well as inhibition of thymocyte differentiation (Table 13.2). T-progenitor cells from the...

Manipulators Of The Developing Immune System

The immune system matures according to developmental pathways but also in response to the environment. Four manipulators impact many facets of the immune system and deserve attention. First and foremost, nutrition plays a vital role in the ability of the body to defend against pathogens (Bardare et al. 1993 Devereux et al. 2002). The majority of immunocompromised individuals in the world simply lack nourishment (Janeway Jr. et al. 1997a). Studies implicate maternal diet in development of atopic...

Pyrethroid Insecticides Cypermethrin

Cypermethrin is a widely used synthetic type II pyrethroid insecticide due to its high insect toxicity, low mammalian toxicity, and rapid metabolism (Crawford et al. 1981 Rhodes et al. 1984). Cypermethrin is primarily considered to be a sodium channel toxin. At high concentrations, pyrethroids induce a long-lasting depolarization and block nerve conduction. However, other secondary mechanisms of action are also involved in their toxicity, including antagonism of GABA inhibitory action,...

Signaling Pathways and Transcription Factors Involved in Asthma Pathogenesis

Soluble mediators may play important roles in the sensitization and triggering of asthmatic responses, but they only do so by acting through specific receptors. Binding to a specific receptor by any cognate ligand normally transduces a signal to the nucleus to transcribe, or block the transcription of, a gene or genes via one or more intracellular biochemical pathways. Steps along a pathway are referred to as pathway intermediates, and those intermediates directly responsible for binding to DNA...

Asthmatic Inflammation

Eotaxin Tnf

Asthma is a chronic inflammatory disease of the airways. Asthmatic inflammation involves complex interactions between the cytokines and signaling pathways of many cell types. In adults and children, T cells are known to be integrally involved in this process (Azzawi et al. 1990 Corrigan and Kay 1990 Wardlaw et al. 1988). The maintenance of airway inflammation is attributed, in adults, to chronically activated memory T cells sensitized against a variety of allergens (Corrigan and Kay 1990) and,...

Therapeutic Immunosuppressant Levels In Mammary Gland Secretions

Many of the immunosuppressive drugs used during pregnancy are also found in breast milk. Currently, the American Academy of Pediatrics AAP provides guidelines for breastfeeding based on the excretion rate and potential teratogenic effects of each drug Tendron et al. 2002 . For example, limited concentrations lt 10 of prednisone and prednisolone have been measured in breast milk, levels perceived by the AAP as nonthreatening to the breastfed infant Coulam et al. 1982 Ost et al. 1985 . Thus,...

Diazepam Valium

Diazepam DZP is a benzodiazepine BDZ with central nervous system CNS -depressant properties. It has anxiolytic, sedative hypnotic, muscle relaxant, and anticonvulsant effects. DZP is used in humans for the short-term relief of symptoms related to anxiety disorders the treatment of agitation, tremors, delirium, seizures, and hallucinations as a result of alcohol withdrawal the relief of muscle spasms in certain neurological diseases and the control of active seizures Costa and Guidotti 1979 ....

Proposed Content Of A Developmental Immunotoxicity Study

Although the need for developmental immunotoxicity testing has long been recognized by the scientific and regulatory communities NRC 1993b USEPA 1999, 2002b , there is currently no formal EPA testing guideline protocol for this study. Studies have, however, been conducted in numerous laboratories to assess the developmental immunotoxic potential for a myriad of pharmaceuticals, pesticides, and environmental pollutants. Additionally, the National Toxicology Program NTP has devised an...