Organ targeted prenatal gene therapy—how far are we?

Prenatal gene therapy aims to deliver genes to cells and tissues early in prenatal life, allowing correction of a genetic defect, before long-term tissue damage has occurred. In contrast to postnatal gene therapy, prenatal application can target genes to a large population of dividing stem cells, and the smaller fetal size allows a higher vector-to-target cell ratio to be achieved. Early-gestation delivery may allow the development of immune tolerance to the transgenic protein which would facilitate postnatal repeat vector administration if needed. Targeting particular organs will depend on manipulating the vector to achieve selective tropism and on choosing the most appropriate gestational age and injection method for fetal delivery. Intra-amniotic injection reaches the skin, and other organs that are bathed in the fluid however since gene transfer to the lung and gut is usually poor more direct injection methods will be needed. Delivery to the liver and blood can be achieved by systemic delivery via the umbilical vein or peritoneal cavity. Gene transfer to the central nervous system in the fetus is difficult but newer vectors are available that transduce neuronal tissue even after systemic delivery. Copyright © 2011 John Wiley & Sons, Ltd.     

Elemental concentrations in aerosols at the Belgian coast versus seasons and air mass trajectories

Marine aerosols have extensively been monitored in the framework of a research project to investigate the inorganic and organic nutrient fluxes of the atmospheric nitrogen input into the North Sea. As a part of this project bulk analysis was also performed by energy dispersive X-ray fluorescence (EDXRF) on a total of 366 samples in order to provide detailed elemental composition. Samples have been clustered per campaign and differences were related to backward trajectories. Elements as Cl, Si, and S appeared to be the best tracers for coastal aerosols. Therefore they have been chosen to represent each campaign and to map the seasonal variations. It is clear that Cl is an excellent tracer for oceanic trajectories, while a less clear correlation between the soil dust components and the air mass trajectories is found.     

Chemical stability of geopolymers containing municipal solid waste incinerator fly ash

Municipal solid waste incinerators every year produce tons of fly ashes which, differently from coal fly ashes, contain large amounts of toxic substances (heavy metals, dioxins, furans). The stabilization/solidification (S/S) technology known as geopolymerization is proposed with the purpose to bond physically and chemically incinerator fly ashes (IFA) in a solid matrix, in order to reduce pollutant mobility. The chemical stability of geopolymers with Si/Al ratio of 1.8–1.9 and Na/Al ratio of 1.0, synthesized by alkali activation of metakaolin and the addition of 20 wt% of two different kinds of IFA, is presented. The concentration of the alkaline solution, water to solid ratio and curing process have been optimized. The room temperature consolidation of IFA containing geopolymers has been tested for leachability in water for 1 day, accordingly to EN 12457 regulation and extended to 7 days to increase the water attack on solid granules. Leachable metals in the test solution, determined by ICP_AES, fall within limit values set by regulation for non-dangerous waste landfill disposal. Geopolymeric matrix evolution with leaching time has been also evaluated in terms of pH and electrical conductivity increase in solution.     

Combined application of Triton X-100 and Sinorhizobium sp. Pb002 inoculum for the improvement of lead phytoextraction by Brassica juncea in EDTA amended soil

The process of EDTA-assisted lead phytoextraction from the Bovisa (Milan, Italy) brownfield soil was optimized in microcosms vegetated with Brassica juncea. An autochthonous plant growth-promoting rhizobacterium (PGPR), Sinorhizobium sp. Pb002, was isolated from the rhizosphere of B. juncea grown on the Pb-contaminated soil in presence of 2 mM EDTA. The strain was augmented (10(8) CFU g(-1) soil) in vegetated microcosms to stimulate B. juncea biomass production and, hence, its phytoextraction potential. Triton X-100 was also added to microcosms at 5 and 10 times the critical micelle concentration (cmc) to increase the permeability of root barriers to the EDTA-Pb complexes. Triton X-100 amendment determined an increase in Pb concentration within plant tissues. However it contextually exerted a phytotoxic effect. Sinorhizobium sp. Pb002 augmentation was crucial to plant survival in presence of both bioavailable lead and Triton X-100. The combination of the two treatments produced up to 56% increase in the efficiency of lead phytoextraction by B. juncea. The effects of these treatments on the structure of the soil bacterial community were evaluated by 16S rDNA denaturing gradient gel electrophoresis (DGGE).     

Increased levels of polychlorobiphenyls in Italian women with endometriosis

Endometriosis has been hypothesised to be linked to persistent and toxic organochlorinated chemicals. Dioxins and dioxin-like compounds have in particular been associated with the disease, mainly on the basis of experimental studies. Data in women are conflicting. A case-control study on 80 Italian nulliparous women of reproductive age was carried out to assess whether there is a correlation between the presence of endometriosis and blood levels of polychlorobiphenyls (PCBs), a family of ubiquitary environmental pollutants which comprises congeners with dioxin-like activity. Higher levels of PCBs were found in women with endometriosis. A mean cumulative value of 410 ng g(-1), lipid base, was found in cases versus the value of 250 ng g(-1) observed in the control group (odds ratio for upper tertile 4.0, CI 95% 1.3-13; p = 0.0003). PCB increase involved both dioxin-like (PCBs 105, 118, 156, and 167) and non-dioxin-like congeners (PCBs 101, 138, 153, 170, 180).     

Tetrodotoxin prevents copper-induced bradycardia in gastropod limpets

Acute exposure to waterborne copper is followed by a reduction in heart rate in gastropod limpets. In order to understand the mechanism of this effect, exposure to copper (0.25 or 0.5 mg l(-1); for 3 and 6 h) was combined with an injection of tetrodotoxin (TTX, 20 microl, 0.5 or 1 microM), a natural toxin that inhibits the propagation and transmission of impulses in excitable tissues. Experiments were performed on the Mediterranean limpet Patella caerulea, using a non-invasive method for the recording of cardiac activity. TTX did not affect the bradycardic effect of the cholinergic agonist carbachol. However, this toxin significantly antagonized the bradycardia induced by 0.25 and 0.5mg l(-1) of copper exposure and prevented the acardia observed in some limpets exposed to 0.5mg l(-1) of copper for 6h. These results are consistent with the hypothesis that the inhibitory action of copper on limpet cardiac activity involves an extrinsic, cholinergic neuronal control.     

A spatially-evaluated methodology for assessing risk to a population from contaminated land

A methodology is proposed which combines quantitative probabilistic human health risk assessment and spatial statistical methods (geostatistics) to produce an assessment of risks to human health from exposure to contaminated land, in a manner which preserves the spatial distribution of risks and provides a measure of uncertainty in the assessment. Maps of soil contaminant levels, which incorporate uncertainty, are produced from sparse sample data using sequential indicator simulation. A real, age-stratified population is mapped across the contaminated area, and intake of soil contaminants by individuals is calculated probabilistically using an adaptation of the Contaminated Land Exposure Assessment (CLEA) model. An abundance of information is contained in results which can be interrogated at the population and individual level, and mapped to provide a powerful visual tool for risk managers, enabling efficient targeting of risk reduction measures to different locations.