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Pyronaridine, 2-methoxy-7-chloro-10[3,5-bis(pyrrolidinyl-1-methyl-)4hydroxyphenyl]aminobenzyl-(b)-1,5-naphthyridine, a new Mannich base schizontocide originally developed in China and structurally related to the aminoacridine drug quinacrine, is currently undergoing clinical testing. We now show that pyronaridine targets hematin, as demonstrated by its ability to inhibit in vitro ␤-hematin formation (at a concentration equal to that of chloroquine), to form a complex with hematin with a stoichiometry of 1:2, to enhance hematin-induced red blood cell lysis (but at 1/100 of the chloroquine concentration), and to inhibit glutathionedependent degradation of hematin. Our observations that pyronaridine exerted this mechanism of action in situ, based on growth studies of Plasmodium falciparum K1 in culture showing antagonism of pyronaridine in combination with antimalarials (chloroquine, mefloquine, and quinine) that inhibit ␤-hematin formation, were equivocal.

Heymsfield SB, Chirachariyavej T, Rhyu IJ, Roongpisuthipong C, Heo M, Pietrobelli A. Differences between brain mass and body weight scaling to height: potential mechanism of reduced mass-specific resting energy expenditure of taller adults. J Appl Physiol 106: 40 -48, 2009. First published November 13, 2008 doi:10.1152/japplphysiol.91123.2008.-Adult resting energy expenditure (REE) scales as height ϳ1.5 , whereas body weight (BW) scales as height ϳ2 . Mass-specific REE (i.e., REE/BW) is thus lower in tall subjects compared with their shorter counterparts, the mechanism of which is unknown. We evaluated the hypothesis that high-metabolic-rate brain mass scales to height with a power significantly less than that of BW, a theory that if valid would provide a potential mechanism for height-related REE effects. The hypothesis was tested by measuring brain mass on a large (n ϭ 372) postmortem sample of Thai men. Since brain mass-body size relations may be influenced by age, the hypothesis was secondarily explored in Thai men age Յ45 yr (n ϭ 299) and with brain magnetic resonance imaging (MRI) studies in Korean men (n ϭ 30) age Ն20Ͻ30 yr. The scaling of large body compartments was examined in a third group of Asian men living in New York (NY, n ϭ 28) with MRI and dual-energy X-ray absorptiometry. Brain mass scaled to height with a power (mean Ϯ SEE; 0.46 Ϯ 0.13) significantly smaller (P Ͻ 0.001) than that of BW scaled to height (2.36 Ϯ 0.19) in the whole group of Thai men; brain mass/BW scaled negatively to height (Ϫ1.94 Ϯ 0.20, P Ͻ 0.001). Similar results were observed in younger Thai men, and results for brain mass/BW vs. height were directionally the same (P ϭ 0.09) in Korean men. Skeletal muscle and bone scaled to height with powers similar to that of BW (i.e., ϳ2-3) in the NY Asian men. Models developed using REE estimates in Thai men suggest that brain accounts for most of the REE/BW height dependency. Tall and short men thus differ in relative brain mass, but the proportions of BW as large compartments appear independent of height, observations that provide a potential mechanistic basis for related differences in REE and that have implications for the study of adult energy requirements. body composition; nutritional requirements ENERGY REQUIREMENTS ARE LARGELY determined by subject body weight (5b, 23). Since adult body weight increases as a function of height ϳ2 (33), taller subjects weigh more and have a greater energy requirement than their shorter counterparts (5b). The largest component of energy requirements in most adults is related to resting energy expenditure (REE), and REE scales as height ϳ1.5 (13). Accordingly, mass-specific resting energy requirements, defined as REE/body weight, decrease as height Ϫ0.5 . Tall subjects thus appear to have a smaller magnitude mass-specific REE and from the energetic perspective can be considered relatively more "efficient" at rest. Greater stature and associated body weight are thus not accompanied by a proportionally larger resting energy need.The mechanism leadin...

This report documents a rare case of carbon dioxide intoxication in a young healthy male. The deceased hid in a small plastic container, size 1.5 · 1 · 1 m, and within 5 min he was located suffering convulsions and was reported as dead within minutes. Scene investigation revealed dry ice in the container. Autopsy findings were unremarkable. The probable cause of the convulsions was carbon dioxide intoxication due to both the dry ice sublimation and the small confined space in which he was hiding. This report emphasizes the significance of scene investigation in establishing the cause of the death.