Biomedical subjects

Timothy W Secomb

Publications and source records attributed to Timothy W Secomb.

23 records · Page 2Linked to original sources

PubMed2002

Information transfer in microvascular networks.

The adequate and efficient functioning of the circulatory system requires coordination of vessel diameters and of vascular responses to local and remote stimuli. Such coordination implies transfer of information about functional status and demands to all parts of the vascular system. In the peripheral circulation, blood flow must be controlled locally to accommodate spatial variations in demand. This requires information transfer from peripheral vessels to the more proximal vessels that feed and drain them. Principal mechanisms available for this information transfer are hemodynamic coupling, diffusive and convective transport of metabolites, and responses conducted along vessel walls. Current knowledge of these mechanisms is reviewed here. Theoretical models provide a framework for examining how information transfer mechanisms and vascular responses are integrated, so as to provide short-term regulation of blood flow and long-term structural adaptation of microvascular networks.

Adaptation, Physiological↗

PubMed2002

Effect of the glial envelope on extracellular K(+) diffusion in olfactory glomeruli.

In many species, including vertebrates and invertebrates, first-order olfactory neuropils are organized into spherical glomeruli, partially enveloped by glial borders. The effect of this characteristic organization on olfactory information processing is poorly understood. The extracellular concentration of potassium ions ([K(+)]) must rise around olfactory receptor axons in specific glomeruli following odor-induced activation. To explore the time course and magnitude of K(+) accumulation and possible effects of such accumulation on neural activity within and among glomeruli, we developed a theoretical model to simulate the diffusion of K(+) in extracellular spaces of the glomeruli of the moth Manduca sexta. K(+) released by activated axons was assumed to diffuse through the extracellular spaces in glomeruli and the glial borders that surround them. The time-dependent diffusion equations were solved in spherical coordinates using a finite-difference method. The results indicate that the glial envelope forms a significant barrier to the spread of K(+) between neighboring glomeruli, thus reducing the likelihood of cross-talk between glomeruli, and may cause elevation of extracellular [K(+)] to levels that influence neural activity within the activated glomerulus for many seconds. Such effects could enhance olfactory discrimination and sensitivity, respectively.

Animals↗

PubMed2002

Angioadaptation: keeping the vascular system in shape.

The development and maintenance of the vascular system requires not only the formation of new vessels (vasculogenesis, angiogenesis) but also the continuous adjustment of vessel and network structures in response to functional needs. This "angioadaptation" depends on the interplay of vascular responses to growth factors, to the metabolic status of the tissue, and to hemodynamic forces exerted by the flowing blood.

Adaptation, Physiological↗

PubMedDate not supplied

A mathematical model for cisplatin cellular pharmacodynamics.

A simple theoretical model for the cellular pharmacodynamics of cisplatin is presented. The model, which takes into account the kinetics of cisplatin uptake by cells and the intracellular binding of the drug, can be used to predict the dependence of survival (relative to controls) on the time course of extracellular exposure. Cellular pharmacokinetic parameters are derived from uptake data for human ovarian and head and neck cancer cell lines. Survival relative to controls is assumed to depend on the peak concentration of DNA-bound intracellular platinum. Model predictions agree well with published data on cisplatin cytotoxicity for three different cancer cell lines, over a wide range of exposure times. In comparison with previously published mathematical models for anticancer drug pharmacodynamics, the present model provides a better fit to experimental data sets including long exposure times (approximately 100 hours). The model provides a possible explanation for the fact that cell kill correlates well with area under the extracellular concentration-time curve in some data sets, but not in others. The model may be useful for optimizing delivery schedules and for the dosing of cisplatin for cancer therapy.

Antineoplastic Agents↗

PubMedDate not supplied

A theoretical model for intraperitoneal delivery of cisplatin and the effect of hyperthermia on drug penetration distance.

A theoretical model for the intraperitoneal (i.p.) delivery of cisplatin and heat to tumor metastases in tissues adjacent to the peritoneal cavity is presented. The penetration distance (the depth to which drug diffuses directly from the cavity into tissues) is predicted to be on the order of 0.5 mm. The model shows that exchange with the microvasculature has more effect than cellular uptake in limiting the penetration distance. Possible effects of hyperthermia are simulated, including increased cell uptake of drug, increased cell kill at a given level of intracellular drug, and decreased microvascular density. The model suggests that the experimental finding of elevated intracellular platinum levels up to a depth of 3 to 5 mm when drug is delivered i.p. by a heated infusion solution is due to penetration of heat to this distance, causing increased cell uptake of drug. Beyond a depth of about 0.5 mm, the drug is delivered mainly through the circulation. Use of sodium thiosulfate to deactivate systemic cisplatin may therefore be counterproductive when heat is delivered locally. The model suggests that i.p. delivery of heat, combined with systemic delivery of drug, may be as effective as i.p. delivery of heat and drug.

Animals↗