Undernutrition combined with dietary mineral oil hastens depuration of stored dioxin and polychlorinated biphenyls in ewes. 2. Tissue distribution, mass balance and body burden.

Food safety crises involving persistent organic pollutants (POPs) lead to systematic slaughter of livestock to prevent contaminants from entering the food chain. Therefore, there is a need to develop strategies to depurate livestock moderately contaminated with POPs to reduce economic and social damage. This study aimed to test undernutrition (37% of energy requirements) combined with mineral oil (10% in total dry matter intake) in nine non-lactating ewes contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) 126 and 153 as a strategy to enhance the depuration of POPs through faecal excretion. To better understand the underlying mechanisms of the depuration process, lipophilic POPs and lipid fluxes were co-monitored in various body and excretion compartments. Body compartments (adipose tissues, muscle, liver and blood) and the total empty body were analyzed for lipids and POPs concentrations and burdens at slaughter, as well as excretion compartments (faeces and wool) collected during the depuration period. Decreases in empty body total and lipid weights were 6-fold higher in underfed and supplemented ewes compared to control ewes. In addition, over the depuration period undernutrition and supplementation treatment increased faecal TCDD, PCBs 126 and 153 excretions by 1.4- to 2.1-fold but tended to decrease wool PCB 153 excretion by 1.4-fold. This induced 2- to 3-fold higher decreases in the empty body POPs burdens for underfed and supplemented ewes. Nonetheless, when expressed relative to the calculated initial empty body burdens, burdens at slaughter decreased only slightly from 97%, 103% and 98% for control ewes to 92%, 97% and 94% for underfed and supplemented ones, for TCDD, PCBs 126 and 153, respectively. Fine descriptions at once of POPs kinetic (companion paper 1) and mass balance (companion paper 2), and of body lipid dynamics were very useful in improving our understanding of the fate of POPs in the ruminants.

Effects of synthetic biomacromolecule addition on the flow behavior of concentrated mesenchymal cell suspensions.

In the fields of tissue engineering and regenerative medicine, many researchers and companies alike are investigating the utility of concentrated mesenchymal stem cell suspensions as therapeutic injectables, with the hope of regenerating the damaged tissue site. These cells are seldom used alone, being instead combined with synthetic biomacromolecules, such as branched poly(ethylene glycol) (PEG) polymers, in order to form cross-linked hydrogels postinjection. In this article, we present the results of a detailed experimental and analytical investigation into the impacts of a range of eight-arm PEG polymers, each presenting functional end groups, on the rheological properties of concentrated living cells of mesenchymal origin. Using two-photon confocal microscopy, we confirmed that the aggregates formed by the cells are fractal structures, the dimension of which changed with PEG polymer type addition. From these results and the observed substantial variation in rheological footprint with increasing volume fraction and different PEG polymer type, we propose a number of mechanisms driving such structural changes. Lastly, we derived a modified Krieger-Dougherty model to produce a master curve for the relative viscosity as a function of volume fraction over the range of conditions investigated (including shear stress and PEG polymer type), from which we extract the adhesion force between individual cells within these concentrated suspensions. The outcomes of this study provide new insights into the complex interactions occurring in concentrated mesenchymal cell suspensions when combined with synthetic biomacromolecules commonly used as precursors in tissue engineering hydrogels, highlighting their substantial impacts on the resultant rheological footprint.

Effects of cell density and biomacromolecule addition on the flow behavior of concentrated mesenchymal cell suspensions.

With the rapidly growing interest in the use of mesenchymal stromal cells (MSCs) for cell therapy and regenerative medicine applications, either alone as an injected suspension, or dispersed within injectable hydrogel delivery systems, greater understanding of the structure-function-property characteristics of suspensions of adhesion-dependent mesenchymal cells is required. In this paper, we present the results of an experimental study into the flow behavior of concentrated suspensions of living cells of mesenchymal origin (fibroblasts) over a wide range of cell concentrations, with and without the addition of hyaluronic acid (HA), a commonly utilized biomolecule in injectable hydrogel formulations. We characterize the change in the shear viscosity as a function of shear stress and shear rate for cell volume fractions varying from 20 to 60%. We show that high volume fraction suspensions of living mesenchymal cells, known to be capable of homotypic interactions, exhibit highly complex but reproducible rheological footprints, including yield stress, shear thinning and shear-induced fracture behaviors. We show that with the addition of HA, we can significantly modify and tailor the rheology of these cell suspensions at all volume fractions. Using FACS and confocal imaging, we show that the observed effect of HA addition is due to a significantly modulation in the formation of cellular aggregates in these suspensions, and thus the resultant volume spanning network. Considering the aggregates as fractal structures, we show that by taking into account the changes in volume fractions with shear, we are able to plot a master curve for the range of conditions investigated and extract from it the average adhesion force between individual cells, across a population of millions of cells. The outcomes of this study not only provide new insight into the complexity of the flow behaviors of concentrated, adhesive mesenchymal cell suspensions, and their sensitivity to associative biomacromolecule addition, but also a novel, rapid method by which to measure the average adhesion force between individual cells, and the impacts of biomacromolecules on this important parameter.

Feasibility, accuracy and safety of chorionic villus sampling: a report of 10741 cases.

OBJECTIVES: To evaluate the feasibility, accuracy and safety of chorionic villus sampling (CVS). METHODS: Ten thousand seven hundred and forty one singleton pregnancies at risk of chromosome abnormalities (96.3%) and gene disorders (2.8%) were referred from 1990 to 1999 to the fetal medicine unit of a teaching hospital. CVS was performed transabdominally after 11 weeks, using a modified freehand ultrasonographically guided technique by 5 operators. Fetal karyotyping was obtained using a direct method before 1995 and was completed by cell culture after 1996. Failed results, feto-placental discrepancy and fetal loss were assessed. RESULTS: Villi were sampled using extra-amniotic puncture (89.4%) and one sampling-device insertion (92.3%). The mean weight of the specimen was 15.2 +/- 6.0 mg. All attempts at sampling were successful, except eight (0.07%). The number of failed results following direct preparation, cell culture and both methods was 20 (0.19%), 23 (0.21%) and 2 (0.02%), respectively. Light maternal cell contamination occurred in less than 1% of the samplings after microscopic selection of the villi, and never interfered with the assessment of karyotyping. All 3 false-negative results (0.03%) were recorded after direct preparation and 2 were corrected by culture. The rate of chromosomal abnormalities confined to the placenta decreased from 1.08% before 1995 to 0.73% after 1996. True fetal mosaicisms were recorded in 7 cases (0.06%). The rate of fetal loss at <28 weeks was 1.64% in all pregnancies and 1.92% when CVS was performed before 13 weeks. Advanced maternal age was the single factor significantly associated with fetal loss. CONCLUSIONS: CVS was feasible, accurate and safe in our institution, as a result of the increasing experience of the operators and the cytogeneticists.