Health effects of endocrine-disrupting chemicals on wildlife, with special reference to the European situation

Many wildlife species may be exposed to biologically active concentrations of endocrine-disrupting chemicals. There is strong evidence obtained from laboratory studies showing the potential of several environmental chemicals to cause endocrine disruption at environmentally realistic exposure levels. In wildlife populations, associations have been reported between reproductive and developmental effects and endocrine-disrupting chemicals. In the aquatic environment, effects have been observed in mammals, birds, reptiles, fish, and mollusks from Europe, North America, and other areas. The observed abnormalities vary from subtle changes to permanent alterations, including disturbed sex differentiation with feminized or masculinized sex organs, changed sexual behavior, and altered immune function. For most reported effects in wildlife, however, the evidence for a causal link with endocrine disruption is weak or nonexisting. Crucial in establishing causal evidence for chemical-induced wildlife effects appeared semifield or laboratory studies using the wildlife species of concern. Impaired reproduction and development causally linked to endocrine-disrupting chemicals are well documented in a number of species and have resulted in local or regional population changes. These include: Masculinization (imposex) in female marine snails by tributyltin, a biocide used in antifouling paints, is probably the clearest case of endocrine disruption caused by an environmental chemical. The dogwhelk is particularly sensitive, and imposex has resulted in decline or extinction of local populations worldwide, including coastal areas all over Europe and the open North Sea. DDE-induced egg-shell thinning in birds has caused severe population declines in a number of raptor species in Europe and North America. Endocrine-disrupting chemicals have adversely affected a variety of fish species. In the vicinity of certain sources (e.g., effluents of water treatment plants) and in the most contaminated areas is this exposure causally linked with the effects on reproductive organs that could have implications for fish populations. However, there is also a more widespread occurrence of endocrine disruption in fish in the U.K., where estrogenic effects have been demonstrated in freshwater systems, in estuaries, and in coastal areas. In mammals, the best evidence comes from the-field studies on Baltic gray and ringed seals, and from the Dutch semifield studies on harbor seals, where both reproduction and immune functions have been impaired by PCBs in the food chain. Reproduction effects resulted in population declines, whereas impaired immune function has likely contributed to the mass mortalities due to morbillivirus infections. Distorted sex organ development and function in alligators has been related to a major pesticide spill into a lake in Florida, U.S.A. The observed estrogenic/antiandrogenic effects in this reptile have been causally linked in experimental studies with alligator eggs to the DDT complex. Although most observed effects currently reported concern heavily polluted areas, endocrine disruption is a potential global problem. This is exemplified by the widespread occurrence of imposex in marine snails and the recent findings of high levels of persistent potential endocrine-disrupting chemicals in several marine mammalian species inhabiting oceanic waters.     

Heterogeneity in the ability of cytotoxic murine NK cell clones to enhance Ig secretion in vitro

We recently described a panel of cytotoxic murine NK cell clones that also enhanced Ig secretion by B cells activated in an in vitro model of T cell-independent type 2 (TI-2) responses. We employed dextran-conjugated anti-IgD (alphadelta-dex) as a model antigen. Here we study the mechanism of Ig induction by these clones. Addition of the various NK clones to sort-purified B cells stimulated with alphadelta-dex and IL-2 resulted in a markedly heterogeneous increase in Ig secretion, which varied from 3-fold, as mediated by clone PKO 56, to 15-fold, as induced by clone PKO 101. The other NK cells showed intermediate levels of Ig induction. Furthermore, while addition of as few as 0.04% of PKO 101 cells stimulated significant increases and 1% induced near maximum Ig production, a 3% addition of PKO 56 cells was required for significant enhancement of Ig secretion. Supernatant material collected from the NK clones mediated Ig production at levels that mirrored the induction by the corresponding cells. Cytokine analysis showed that while all members of the NK panel produced IFN-gamma only two secreted granulocyte macrophage colony stimulating factor and that the levels of Ig induction mediated by the NK clones correlated only with their levels of IFN-gamma secretion. Culture of B and NK cells in the presence of anti-IFN-gamma demonstrated that IFN-gamma was the critical cytokine in NK-induced Ig production. These findings establish heterogeneity in the ability of NK cells to increase Ig secretion in vitro and show that NK-produced IFN-gamma is an important factor in determining this heterogeneity.     

Sound transmission into incubators in the neonatal intensive care unit.

OBJECTIVE: To measure the attenuation of sound by modern incubators. STUDY DESIGN: LEQ, LMAX, LPEAK, and frequency distribution were measured simultaneously inside and outside two recent model incubators. RESULTS: The attenuation of sound (outside minus inside) was 15 to 18 dBA with the motor off and 4 to 8 dBA with the motor on. There was a significant difference between incubators in their attenuation of sound. Octave band analysis showed attenuation in frequency bands of > 31.5 Hz with the motor off. With the motor on, the sound level inside the incubator was higher than outside at frequency bands of < 250 Hz. CONCLUSION: Caring for infants inside modern incubators reduces "averaged" sound exposure to levels near those recommended for the neonatal intensive care unit. Lower frequency sounds are louder inside the incubator and arise from the incubator motor.     

Heparan sulphate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myeloma

The epidermal growth factor (EGF)/EGF-receptor (ErbB1-4) family is involved in the biology of multiple myeloma (MM). In particular, ErbB-specific inhibitors induce strong apoptosis of myeloma cells (MMC) in vitro. To delineate the contribution of the 10 EGF-family ligands to the pathogenesis of MM, we have assessed their expression and biological activity. Comparing Affymetrix DNA-microarray-expression-profiles of CD138-purified plasma-cells from 65 MM-patients and 7 normal individuals to those of plasmablasts and B-cells, we found 5/10 EGF-family genes to be expressed in MMC. Neuregulin-2 and neuregulin-3 were expressed by MMC only, while neuregulin-1, amphiregulin and transforming growth factor-alpha were expressed by both MMC and normal plasma-cells. Using real-time polymerase chain reaction, we found HB-EGF, amphiregulin, neuregulin-1 and epiregulin to be expressed by cells from the bone marrow-environment. Only the EGF-members able to bind heparan-sulphate proteoglycans (HSPGs) - neuregulin-1, amphiregulin, HB-EGF - promote the growth of MMC. Those ligands strongly bind MMC through HSPGs. The binding and the MMC growth activity was abrogated by heparitinase, heparin or deletion of the HS-binding domain. The number of HS-binding EGF ligand molecules bound to MMC was higher than 10(5) molecules/cell and paralleled that of syndecan-1. Syndecan-1, the main HSPG present on MM cells, likely concentrates high levels of HS-binding-EGF-ligands at the cell membrane and facilitates ErbB-activation. Altogether, our data further identify EGF-signalling as promising target for MM-therapy.     

Effect of protective filters on fire fighter respiratory health during simulated bushfire smoke exposure

BACKGROUND: Bushfire fighters are potentially subject to risks from bushfire smoke. Although many different protective masks and filters are available, it is not clear which is the most effective from a health and safety perspective. The effect of protective filters on the respiratory health of Western Australian urban career fire fighters under controlled simulated conditions is investigated. METHODS: Sixty-four healthy Fire and Emergency Services Authority of Western Australia (FESA) urban career fire fighters were subjected to controlled simulated bushfire smoke in an open smoke chamber for 15 min. The fire fighters were allocated one of the three types of protective filters: particulate only (P), particulate/organic vapor (POV), and a particulate/organic vapor/formaldehyde (POVF) filter using a double-blind randomized procedure. Personal air sampling inside the fire fighters' masks, spirometry, oximetry, and self-reported symptom data were collected at baseline and at two time intervals after the smoke exposure. RESULTS: A significant decline in oxygen saturation was seen immediately after exposure, however, the decline was small and no significant relationships could be established between this and the type of filter used. A significantly higher number of participants in the P and POV filter groups self-reported an increase in coughing, wheezing, and shortness of breath compared to the POVF group. Air sampling demonstrated a significantly higher level of formaldehyde and acrolein inside the masks fitted with P filters compared to POV and POVF filters. CONCLUSIONS: Testing the effectiveness of P, POV, and POVF filters under controlled conditions has demonstrated that the POVF filter provides statistically significant better protection for the fire fighters' airways in a simulated bushfire exposure chamber.