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Biomedical subjects

K L March

Publications and source records attributed to K L March.

6 recordsLinked to original sources
PubMed1991

Direct intraarterial wall injection of microparticles via a catheter: a potential drug delivery strategy following angioplasty.

Local delivery into the arterial wall of medications at high concentrations may evolve as a method to reduce postangioplasty restenosis. However, since the atherosclerotic artery has increased vasa vasorum, medications injected in a fluid state may diffuse out of the arterial wall too quickly to have a therapeutic effect. Thus we evaluated whether microparticles as a model for a particulate microcarrier drug delivery system, injected via a porous balloon catheter, could be retained within the atherosclerotic rabbit femoral arterial wall. Arteries were injected with a 5 microns microparticle suspension for 45 seconds at either 3 or 5 atm of infusion pressure immediately following balloon angioplasty. Arteries were obtained immediately following the procedure or at 1, 3, 7, or 14 days after infusion to evaluate for the presence of retained microparticles. Of 34 arteries, 30 contained retained microparticles, with 21 exhibiting microparticles in the neointimia, 12 in the media, and 25 in the adventitia. Microparticles were retained for as long as 14 days, and there was no difference between the distribution or quantity of microparticles at 3 or 5 atm of infusion pressure. The mode of microparticle distribution probably involved deposition within dissection planes, although evidence for vasa vasorum transport was observed. We hypothesize that biodegradable microparticles could serve as a vehicle for intramural drug delivery in the treatment of restenosis.

Angioplasty, Balloon↗
PubMed1989

Current concepts of left ventricular pseudoaneurysm: pathophysiology, therapy, and diagnostic imaging methods.

Left ventricular pseudoaneurysm represents a cardiac rupture which is temporarily confined by pericardium and is amenable to curative surgical treatment. The case described illustrates several atypical features of its presentation and diagnosis, highlighting the importance of maintaining a sufficient clinical index of suspicion for this relatively uncommon, but potentially lethal entity. The use of various diagnostic imaging methods is described, including the first description of magnetic resonance imaging of ventricular pseudoaneurysm. The prospect of medical therapies directed toward the prevention of cardiac rupture, and thus pseudoaneurysm, is discussed in the context of its pathophysiology which involves alterations in the cardiac fibroskeletal support.

Aged↗
PubMed1989

Molecular cardiology: new avenues for the diagnosis and treatment of cardiovascular disease.

This review summarizes some of the major advances in the investigation of molecular mechanisms underlying both normal and abnormal cardiovascular function. Four major areas are highlighted including cardiac muscle, the blood vessel, atherosclerosis and thrombosis/thrombolysis. The remarkable strides in understanding multifactorial diseases such as atherosclerosis, and the development of innovative new therapies such as the use of thrombolytic agents produced by recombinant deoxyribonucleic acid (DNA) technology, are noted. Moreover, it is concluded that the past decade of basic research has provided a solid framework for improvements in the diagnosis and therapy of other forms of cardiovascular disease as well. An evaluation of current trends in basic cardiovascular research suggests that diagnostic and therapeutic approaches to disease will increasingly target specific molecular processes underlying the pathophysiologic state.

Animals↗
PubMed1985

Electrostatic interactions in sperm whale myoglobin. Site specificity, roles in structural elements, and external electrostatic potential distributions.

The electrostatic free energy contribution to the stability of sperm whale ferrimyoglobin was evaluated according to the static accessibility modified Tanford-Kirkwood model. The electrostatic free energy contribution of each distinct structural element was divided into one term arising from interactions between it and other elements (interelemental) and another from interactions within the particular element itself (intraelemental). At pH 7 the majority of the terms were found to be stabilizing. The interelemental terms are the dominant ones for most structural elements. The small interelemental terms of the C and D helices are compensated by large intraelemental interactions which stabilize these short helices. Perturbations in pH can be accommodated by the structural elements through a redistribution of stabilizing and destabilizing interactions. The electrostatic potentials calculated at the surface of the protein indicate that the internal compensation of local potentials achieved during folding results in a generally neutral protein-solvent interface save for two distinct areas of nonzero potential. The accessibility of each charged atom to solvent was analyzed in terms of the surface area lost to charged, polar and nonpolar atoms separately. The net solvent accessibility lost parallels closely that lost to nonpolar atoms alone, indicating a specific role for nonpolar atoms in defining dielectric shielding of charged atoms, aside from their participation in the well-known hydrophobic interactions.

Amino Acids↗
PubMed1985

pH-dependent processes in proteins.

Recent improvements in the understanding of electrostatic interactions in proteins serve as a focus for the general topic of pH-dependent processes in proteins. The general importance of pH-dependent processes is first set out in terms of hydrogen ion equilibria, stability, ligand interactions, assembly, dynamics, and events in related molecular systems. The development of various theoretical treatments includes various formalisms in addition to the solvent interface model developed by Shire et al. as an extension of the Tanford-Kirkwood treatment. A number of detailed applications of the model are presented and future potentialities are sketched.

Animals↗