Changes In Tissue Microstructure Research Articles

MR properties of rat sciatic nerve following trauma.

T(1) and T(2) relaxation times, magnetization transfer (MT), and diffusion anisotropy of rat sciatic nerve were measured at different time intervals following trauma. The nerve injury was induced by either cutting (irreversible nerve degeneration) or crushing (degeneration followed by regeneration). The MR properties were measured for proximal and distal portions of the injured nerve. The portions of the nerve proximal to the induced injury exhibited MR characteristics similar to those of normal nerves, whereas the distal portions showed significant differences in all MR parameters. These differences diminished in the regenerating nerves within approximately 4 weeks post injury. In the case of irreversible nerve damage, the differences in the distal nerves were slightly larger and did not resolve even 6 weeks after induced trauma. The MR measurements were correlated with histopathology exams. Observed changes in tissue microstructure, such as demyelination, inflammation, and axonal loss, can result in a significant increase in the average T(1) and T(2) relaxation times, reduction in the MT effect, and decrease in diffusion anisotropy. MR parameters, therefore, are very good indicators of nerve damage and may be useful in monitoring therapies that assist nerve regeneration. Magn Reson Med 45:415-420, 2001.

Factors influencing the percutaneous absorption of drugs.

The skin is the most readily accessible organ of the human body; only a fraction of a millimeter separates its surface from the underlying capillary network. Yet, skin protects superbly against damage by micro- and macro-molecular entities, as well as against uncontrolled loss of vital biological substances, by virtue of its astonishingly low permeability to such substances. We have reexamined and attempted to reconcile the barrier characteristics of skin in terms not only of its composition and microstructure, but also of present understanding of membrane permeability and permselectivity. The principal barrier to percutaneous transport is localized within the stratum corneum. We have developed a mathematical model of this tissue as a two-phase protein-lipid heterogeneous membrane, which correlates the permeability of the membrane to a specific penetrant with the water solubility of the penetrant and with its lipid-protein partition coefficient. We have also found that a simplistic model of the sorption process, which invokes the coexistence of dissolved and mobile sorbed molecules in equilibrium with site-bound and immobile molecules within the membrane, accurately correlates experimental sorption data and transient transport measurements. The interstitial lipid phase of the stratum corneum is the cause of the exceedingly low, apparent diffusivity of drugs (e.g. scopolamine) and, in this regard, acts as the principal permeation barrier, whereas the drug sorbed by the stratum corneum is localized predominantly within the protein phase of the tissue. We have also found that the effects of the permeation adjuvant, dimethyl sulfoxide, on skin permeability are entirely consistent with accepted sorption-diffusion models of membrane transport, when changes in penetrant activity with changes in solvent composition and tissue microstructure induced by osmotic shock are properly allowed for.