An ultrasmall superparamagnetic iron oxide (USPIO) preparation was developed that is small enough to migrate across the capillary wall, a prerequisite in the design of targetable particulate pharmaceuticals. Seventy percent of particles were smaller than 10 nm; 26%, smaller than 5 nm. The blood half-life of USPIO in rats was 81 minutes, considerably longer than that of larger superparamagnetic iron oxide preparations such as AMI-25 (6 minutes). Electron microscopy demonstrated that USPIO particles transmigrate the capillary wall by means of vesicular transport and through interendothelial junctions. Twenty-four hours after intravenous administration, 3.6% of the injected dose per gram of tissue was found in lymph nodes, 2.9% per gram in bone marrow, 6.3% per gram in liver, and 7.1% per gram in spleen. The major potential applications for USPIO are as (a) an intravenous contrast agent for the lymphatic system, (b) a bone marrow contrast agent, (c) a long-half-life perfusion agent for brain and heart, and (d) the magnetic moiety in organ-targeted superparamagnetic contrast agents for magnetic resonance imaging.

On solid substrates MDCK, a cell line derived from normal dog kidney, forms a confluent monolayer that is studded with "blisters". Previous studies with this cell line suggest that these hemicysts develop as a result of active fluid accumulation between cell sheet and substratum. One factor that may determine when and how hemicysts appear only in localized sites is the interruption of occluding junctions in nonhemicyst areas. To study this possibility, we compared the permeability characteristics of the occluding junctions in hemicysts and in an uninterrupted monolayer of MDCK grown on a permeable support of collagen-coated nucleopore filter. The spontaneous electrical potential differences were small, without statistical differences between them. Relative ionic permeability coefficients were evaluated from the voltage deflections to imposed salt gradients or to a single ion substitution across both structures. The results showed that the relative permeability ratios for Na+, K+, choline+, and Cl- were the same in hemicysts and the uninterrupted monolayer. These and other results indicate that the junctional complex encircling the apical surface of a sheet of MDCK cells can provide an effective permeability barrier constituting a true occluding junction with the same properties in hemicyst and nonhemicyst areas.

A Na+-dependent hexose transport system with similar characteristics that observed in the kidney is retained in a cultured epithelial cell line from pig kidney (LLC-PK1). The active transport of oc methyl-D-glucoside (oc MGP), a nonmetabolizable sugar, which shares the glucose-galactose transport system in kidney cells is mediated through a Na+-dependent, substrate-saturable process. The kinetic analysis of the effect of Na+ on the uptake of ocMGP indicated that the Na+-sugar cotransport system is an affinity type system in which the binding of either sugar or Na+ carrier increases the affinity for the other ligand without affecting the Vmax. The sequence of selectivity for different sugars studied by the inhibition produced in the uptake of ocMGP is very similar to that reported in rat kidney, rabbit kidney cortex slices, and rabbit renal brush border membrane vesicles. Phlorizin, even at very low concentration, almost completely inhibits ocMGP uptake. Conversely, phloretin at the same low concentration stimulated the sugar accumulation by inhibition of efflux, probably at the level of the basolateral membrane. Sulfhydryl group inhibitors also blocked the ocMGP uptake, suggesting that these groups were required for normal functioning of the sugar carrier system. This sugar transport system is an important functional marker to study the molecular events associated with the development of polarization in epithelial cells.

among the public, as people often choose not to heed any recommendations until consensus is achieved.A limitation of this study includes selection bias, as dermatologists who have stronger beliefs about sun protection may have been more likely to respond. In addition, social desirability bias may have been a factor, leading the dermatologists to provide more positive than negative answers.As debate continues about optimizing the use of sunscreen, it is important to assess and understand dermatologists' views as well as the recommendations they provide to patients. This study provides insights into these issues and has identified potential knowledge gaps and corresponding educational opportunities where existing recommendations can be reviewed to better align with actual dermatologic practices.