Geographical patterns in blood lead in relation to industrial emissions and traffic in Swedish children, 1978–2007

<p>Abstract</p> <p>Background</p> <p>Blood lead concentrations (B-Pb) were measured in 3 879 Swedish school children during the period 1978–2007. The objective was to study the effect of the proximity to lead sources based on the children's home and school location.</p> <p>Methods</p> <p>The children's home address and school location were geocoded and their proximity to a lead smelter and major roads was calculated using geographical information system (GIS) software. All the statistical analyses were carried out using means of generalized log-linear modelling, with natural-logarithm-transformed B-Pb, adjusted for sex, school year, lead-exposing hobby, country of birth and, in the periods 1988–1994 and 1995–2007, parents' smoking habits.</p> <p>Results</p> <p>The GIS analysis revealed that although the emission from the smelter and children's B-Pb levels had decreased considerably since 1978, proximity to the lead smelter continued to affect levels of B-Pb, even in recent years (geometric mean: near smelter: 22.90 μg/l; far from smelter 19.75 μg/l; p = 0.001). The analysis also revealed that proximity to major roads noticeably affected the children's B-Pb levels during the period 1978–1987 (geometric mean near major roads: 44.26 μg/l; far from roads: 38.32 μg/l; p = 0.056), due to the considerable amount of lead in petrol. This effect was, however, not visible after 1987 due to prohibition of lead in petrol.</p> <p>Conclusion</p> <p>The results show that proximity to the lead smelter still has an impact on the children's B-Pb levels. This is alarming since it could imply that living or working in the vicinity of a former lead source could pose a threat years after reduction of the emission. The analysis also revealed that urban children exposed to lead from traffic were only affected during the early period, when there were considerable amounts of lead in petrol, and that the prohibition of lead in petrol in later years led to reduced levels of lead in the blood of urban children.</p

Effects of chirality on the intracellular localization of binuclear ruthenium(II) polypyridyl complexes

Interest in binuclear ruthenium(II) polypyridyl complexes as luminescent cellular imaging agents and for biomedical applications is increasing rapidly. We have investigated the cellular localization, uptake, and biomolecular interactions of the pure enantiomers of two structural isomers of [μ-bipb(phen)4Ru2]4+ (bipb is bis(imidazo[4,5-f]-1,10-phenanthrolin-2-yl)benzene and phen is 1,10-phenanthroline) using confocal laser scanning microscopy, emission spectroscopy, and linear dichroism. Both complexes display distinct enantiomeric differences in the staining pattern of fixed cells, which are concluded to arise from chiral discrimination in the binding to intracellular components. Uptake of complexes in live cells is efficient and nontoxic at 5 μM, and occurs through an energy-dependent mechanism. No differences in uptake are observed between the structural isomers or the enantiomers, suggesting that the interactions triggering uptake are rather insensitive to structural variations. Altogether, these findings show that the complexes investigated are promising for future applications as cellular imaging probes. In addition, linear dichroism shows that the complexes exhibit DNA-condensing properties, making them interesting as potential gene delivery vectors

Severity of cardiovascular disease outcomes among patients with HIV is related to markers of inflammation and coagulation

Background-In the general population, raised levels of inflammatory markers are stronger predictors of fatal than nonfatal cardiovascular disease (CVD) events. People with HIV have elevated levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and D-dimer; HIV-induced activation of inflammatory and coagulation pathways may be responsible for their greater risk of CVD. Whether the enhanced inflammation and coagulation associated with HIV is associated with more fatal CVD events has not been investigated. Methods and Results-Biomarkers were measured at baseline for 9764 patients with HIV and no history of CVD. Of these patients, we focus on the 288 that experienced either a fatal (n=74) or nonfatal (n=214) CVD event over a median of 5 years. Odds ratios (ORs) (fatal versus nonfatal CVD) (95% confidence intervals [CIs]) associated with a doubling of IL-6, D-dimer, hsCRP, and a 1-unit increase in an IL-6 and D-dimer score, measured a median of 2.6 years before the event, were 1.39 (1.07 to 1.79), 1.40 (1.10 to 1.78), 1.09 (0.93 to 1.28), and 1.51 (1.15 to 1.97), respectively. Of the 214 patients with nonfatal CVD, 23 died during follow-up. Hazard ratios (95% CI) for all-cause mortality were 1.72 (1.28 to 2.31), 1.73 (1.27 to 2.36), 1.44 (1.15 to 1.80), and 1.88 (1.39 to 2.55), respectively, for IL-6, D-dimer, hsCRP, and the IL-6 and D-dimer score. Conclusions-Higher IL-6 and D-dimer levels reflecting enhanced inflammation and coagulation associated with HIV are associated with a greater risk of fatal CVD and a greater risk of death after a nonfatal CVD even

Mechanisms of Estrogens’ Dose-Dependent Neuroprotective and Neurodamaging Effects in Experimental Models of Cerebral Ischemia

Ever since the hypothesis was put forward that estrogens could protect against cerebral ischemia, numerous studies have investigated the mechanisms of their effects. Despite initial studies showing ameliorating effects, later trials in both humans and animals have yielded contrasting results regarding the fundamental issue of whether estrogens are neuroprotective or neurodamaging. Therefore, investigations of the possible mechanisms of estrogen actions in brain ischemia have been difficult to assess. A recently published systematic review from our laboratory indicates that the dichotomy in experimental rat studies may be caused by the use of insufficiently validated estrogen administration methods resulting in serum hormone concentrations far from those intended, and that physiological estrogen concentrations are neuroprotective while supraphysiological concentrations augment the damage from cerebral ischemia. This evidence offers a new perspective on the mechanisms of estrogens’ actions in cerebral ischemia, and also has a direct bearing on the hormone replacement therapy debate. Estrogens affect their target organs by several different pathways and receptors, and the mechanisms proposed for their effects on stroke probably prevail in different concentration ranges. In the current article, previously suggested neuroprotective and neurodamaging mechanisms are reviewed in a hormone concentration perspective in an effort to provide a mechanistic framework for the dose-dependent paradoxical effects of estrogens in stroke. It is concluded that five protective mechanisms, namely decreased apoptosis, growth factor regulation, vascular modulation, indirect antioxidant properties and decreased inflammation, and the proposed damaging mechanism of increased inflammation, are currently supported by experiments performed in optimal biological settings