We studied how carbon monoxide (CO) is distributed within the human body through quantitation of CO concentrations in postmortem tissue samples from fatalities including possible CO exposure. Stored, frozen tissues were diced, sonicated in water, and 0.01-8.0 mg wet weight (ww) tissues were incubated with sulfosalicylic acid in CO-purged, septum-sealed vials. CO released into the headspace was quantitated by reduction gas chromatography. Mean tissue CO concentrations (pmol/mg ww) from subjects diagnosed to have no known CO exposure (control, N=14), died from fire (N=13), and CO asphyxiation (N=7), respectively, were: adipose (2;13;9), brain (3;13;65), muscle (15;97;297), heart (30;99;371), kidney (22;432;709, lung (54;690;2638), spleen (73;1366;3548), and blood (162;2238;5070). Carboxyhemoglobin concentrations were 1.4%, 25.2%, and 69.1% of total hemoglobin, respectively. We conclude that measurements of CO concentration in a variety of tissues can be used as markers for the degree of exogenous CO exposure and the identification of possible causes of death.

Abstract:The intercellular tight junctions (TJs) of endothelial cells represent the limiting structure for the permeability of the blood-brain barrier (BBB). Although the BBB has been recognized as being the interface between the bloodstream and the brain, little is known about its regulation. Zonulin and its prokaryotic analogue, zonula occludens toxin (Zot) elaborated by Vibrio cholerae, both modulate intercellular TJs by binding to a specific surface receptor with subsequent activation of an intracellular signaling pathway involving phospholipase C and protein kinase C activation and actin polymerization. Affinity column purification revealed that human brain plasma membrane preparations contain two Zot binding proteins of ϳ55 and ϳ45 kDa. Structural and kinetic studies, including saturation and competitive assays, identified the 55-kDa protein as tubulin, whereas the 45-kDa protein represents the zonulin/Zot receptor. Biochemical characterization provided evidence that this receptor is a glycoprotein containing multiple sialic acid residues. Comparison of the N-terminal sequence of the zonulin/ Zot receptor with other protein sequences by BLAST analysis revealed a striking similarity with MRP-8, a 14-kDa member of the S-100 family of calcium binding proteins. The discovery and characterization of this receptor from human brain may significantly contribute to our knowledge on the pathophysiological regulation of the BBB. Key Words: Brain-Zonulin-Zonula occludens toxin-Receptor-Tight junctions-Blood-brain barrier.

A computer-based system is described to measure objectively the geometric parameters of arteries from pairs of projection angiograms. This technique, which employs back-projection to define the vessel axes in 3-D space, was used to obtain selected parameters of coronary artery geometry from radiographic images of autopsy hearts. Results of the first 30 cases are presented, focussing on the distribution of the geometric parameters of the left anterior descending coronary artery (LAD) and its first two major branches. The derived parameters include the angle between the left circumflex artery and the LAD; the angles between the LAD and its early diagonal and septal perforator branches; distances between branch points; and tortuosity. The geometric parameters vary considerably, presumably contributing to a corresponding variability in local hemodynamic and mechanical stresses. Most parameters are uncorrelated. One exception is the angle at the origin of the second diagonal branch, which is positively correlated (p < 0.01) with the distance between the ostia of the first two diagonal vessels; this correlation could reflect the existence of "target" perfusion regions. No relation between geometric parameters and age or gender was seen. In this sample, blacks had a larger angle at the left main bifurcation than whites (p < 0.05).

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