Biomedical subjects

Stephen C Armstead

Publications and source records attributed to Stephen C Armstead.

4 recordsLinked to original sources

PubMed2006

A guest molecule-host cavity fitting algorithm to mine PDB for small molecule targets.

Inhaled anesthetic molecule occupancy of a protein internal cavity depends in part on the volumes of the guest molecule and the host site. Current algorithms to determine volume and surface area of cavities in proteins whose structures have been determined and cataloged make no allowance for shape or small degrees of shape adjustment to accommodate a guest. We developed an algorithm to determine spheroid dimensions matching cavity volume and surface area and applied it to screen the cavities of 6,658 nonredundant structures stored in the Protein Data Bank (PDB) for potential targets of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane). Our algorithm determined sizes of prolate and oblate spheroids matching dimensions of each cavity found. If those spheroids could accommodate halothane (radius 2.91 A) as a guest, we determined the packing coefficient. 394,766 total cavities were identified. Of 58,681 cavities satisfying the fit criteria for halothane, 11,902 cavities had packing coefficients in the range of 0.46-0.64. This represents 20.3% of cavities large enough to hold halothane, 3.0% of all cavities processed, and found in 2,432 protein structures. Our algorithm incorporates shape dependence to screen guest-host relationships for potential small molecule occupancy of protein cavities. Proteins with large numbers of such cavities are more likely to be functionally altered by halothane.

Algorithms↗

PubMed2006

Influence of endothelial glycocalyx degradation and surfactants on air embolism adhesion.

BACKGROUND: Microbubble adherence to endothelial cells is enhanced after damage to the glycocalyx. The authors tested the hypothesis that exogenous surfactants delivered intravascularly have differential effects on the rate of restoration of blood flow after heparinase-induced degradation of the endothelial glycocalyx. METHODS: Air microbubbles were injected into the rat cremaster microcirculation after perfusion with heparinase or saline and intravascular administration of either saline or one of two surfactants. The surfactants were Pluronic F-127 (Molecular Probes, Eugene, OR) and Perftoran (OJSC SPC Perftoran, Moscow, Russia). Embolism dimensions and dynamics were observed using intravital microscopy. RESULTS: Significant results were that bubbles embolized the largest diameter vessels after glycocalyx degradation. Bubbles embolized smaller vessels in the surfactant treatment groups. The incidence of bubble dislodgement and the magnitude of distal displacement were smallest after glycocalyx degradation alone and largest after surfactant alone. The time to bubble clearance and restoration of blood flow was longest with heparinase alone and shortest with Pluronic F-127 alone. CONCLUSIONS: Degradation of the glycocalyx causes air bubbles to adhere to the endothelium more proximally in the arteriolar microcirculation. Surfactants added after glycocalyx degradation and before gas embolization promotes bubble lodging in the distal microcirculation. Surfactants may have a clinical role in reducing embolism bubble adhesion to endothelial cells undergoing glycocalyx disruption.

Animals↗

PubMed2005

Surfactants reduce platelet-bubble and platelet-platelet binding induced by in vitro air embolism.

BACKGROUND: The effect of gas bubbles on platelet behavior is poorly characterized. The authors assessed platelet-bubble and platelet-platelet binding in platelet-rich plasma in the presence and absence of bubbles and three surface-active compounds. METHODS: Platelet-rich plasma was prepared from blood drawn from 16 volunteers. Experimental groups were surfactant alone, sparging (microbubble embolization) alone, sparging with surfactant, and neither sparging nor surfactant. The surfactants were Pluronic F-127 (Molecular Probes, Eugene, OR), Perftoran (OJSC SPC Perftoran, Moscow, Russia), and Dow Corning Antifoam 1510US (Dow Corning, Midland, MI). Videomicroscopy images of specimens drawn through rectangular glass microcapillaries on an inverted microscope and Coulter counter measurements were used to assess platelet-bubble and platelet-platelet binding, respectively, in calcium-free and recalcified samples. Histamine-induced and adenosine diphosphate-induced platelet-platelet binding were measured in unsparged samples. Differences between groups were considered significant for P < 0.05 using analysis of variance and the Bonferroni correction. RESULTS: Sixty to 100 platelets adhered to bubbles in sparged, surfactant-free samples. With sparging and surfactant, few platelets adhered to bubbles. Numbers of platelet singlets and multimers not adherent to bubbles were different (P < 0.05) compared both with unsparged samples and sparged samples without surfactant. No significant platelet-platelet binding occurred in uncalcified, sparged samples, although 20-30 platelets adhered to bubbles. Without sparging, histamine and adenosine diphosphate provoked platelet-platelet binding with and without surfactants present. CONCLUSIONS: Sparging causes platelets to bind to air bubbles and each other. Surfactants added before sparging attenuate platelet-bubble and platelet-platelet binding. Surfactants may have a clinical role in attenuating gas embolism-induced platelet-bubble and platelet-platelet binding.

Adenosine Diphosphate↗

PubMed2004

Surfactant reduction in embolism bubble adhesion and endothelial damage.

BACKGROUND: Surfactants may reduce the adhesion force holding bubbles to the vessel wall in gas embolism. The authors measured bubble adhesion force using excised microvessels. They assessed endothelial damage by measuring vessel reactivity and with microscopy. METHODS: Microbubbles injected into arterioles resided for 5, 10, or 30 min, with intact or damaged endothelium. Perfusion was with rat serum alone (control) or with 1% Perftoran (OJSC SPC Perftoran, Moscow, Russia) or 1% Pluronic F-127 (Molecular Probes, Eugene, OR) added. Pressure across the bubble, bubble length, and bubble diameter were measured, and adhesion force per unit surface area, K = deltaPD/4 l, was calculated. Vessel reactivity was assessed using topical application of phenylephrine and acetylcholine. RESULTS: With the endothelium intact, K was higher in controls than with Perftoran at 10 and 30 min or Pluronic F-127 at 10 min (P < 0.05). With surfactant added after air perfusion to damage the endothelium, K was lower (P < 0.05) at all times for both Perftoran and Pluronic F-127. With surfactant in the perfusate before air perfusion, K was lower at 10 and 30 min for Perftoran and at 10 min for Pluronic F-127 than for controls (P < 0.05). Phenylephrine-induced vasoconstriction was identical among groups. Acetylcholine-induced vasodilatation was the same among groups with an intact endothelium but was found to be lower in controls after air perfusion that followed surfactant exposure than in either surfactant group (P < 0.05). CONCLUSIONS: Surfactants reduced bubble adhesion force and preserved basic endothelial structure and vasodilatory function despite attempts to damage the endothelium. Surfactants seem to protect the endothelium from mechanically induced injury in addition to decreasing bubble adhesion forces.

Adhesiveness↗