We have employed the fluorescent dye nile red to distinguish between normal cells and cells containing lysosomal accumulations of phospholipids. When fibroblasts from an individual with a genetic deficiency in lysosomal sphingomyelinase activity (Niemann-Pick disease) were stained with nile red and visualized by fluorescence microscopy, orange-colored inclusions were observed throughout the cytoplasm. The orange fluorescent bodies could be distinguished from the neutral lipid droplets that fluoresce a brilliant yellow-gold in the presence of nile red. These inclusions were also observed in alveolar macrophages obtained from rats treated with amiodarone, an antiarrhythmic agent known to produce lysosomal phospholipidosis. Flow cytofluorometric analysis revealed that staining of these phospholipid-rich macrophages with nile red can distinguish them from control alveolar macrophages. These results demonstrate that nile red can be employed for the rapid staining of cellular phospholipid inclusions.

SUMMARYAccumulating evidence suggests interactions between bone and energy metabolism, which may affect the risk of cardiovascular disease. Recent animal studies indicate that osteocalcin (OC) plays a key role in the coordinated regulation of glucose and insulin metabolism while insulin receptors on osteoblasts may regulate bone turnover and circulating OC levels. Association studies, weight loss interventions, and observational data lend some support to the existence and relevance of these mechanisms in humans. However, corroborating evidence from pharmacologic interventions in either bone or glucose metabolism is limited by the number, design, and complex pharmacological effects of the drugs used. Furthermore, such clinical trials are complicated by the alteration of metabolic feedback mechanisms in the insulin resistant state. Purpose-designed studies are needed to further establish the existence and significance of the role of OC and its subfractions in human insulin metabolism. In this review we summarize existing animal evidence regarding the role of OC and its subfractions in bone and energy metabolism and assess current clinical trial evidence relating to the significance and consequences of this relationship in humans.

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Neither pharmacological nor molecular genetic manipulations of galanin altered depression-related profiles in the TST. Possible functional alterations in hippocampal 5-HT neurotransmission may have contributed to these negative results. These preliminary findings provide evidence against the hypothesis that galanin plays a central role in mouse depression-related behaviors. It remains possible that galanin modulates depression-related responses in other experimental paradigms and species.

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