The Bispectral Index (BIS) is an empirically calibrated number derived from adult electroencephalograph data that correlates with the depth of sedation in adults. We tested the hypothesis that the BIS score is a valid measure of the depth of pediatric sedation in a study designed to avoid limitations of a previously published report. BIS values from 96 healthy ASA physical status I-II children aged 1-12 yr undergoing sedation were continually recorded and electronically transferred to a computer. Two independent observers blinded as to BIS score evaluated sedation using the Observer's Assessment of Alertness/Sedation (OAA/S) and the University of Michigan Sedation Scale (UMSS) at 3-5 min intervals. There was a significant correlation between BIS and UMSS and between BIS and OAA/S by both the Spearman's rank correlation test and by prediction probability (P < 0.001). In children <6 yr, there was a significant correlation between BIS and the clinical sedation scores for subgroups undergoing invasive and noninvasive procedures (P < 0.001). There was also good agreement between the 2 independent observers who assessed clinical sedation scores (kappa = 0.51, P < 0.001). We conclude that the BIS monitor is a quantitative, nondisruptive and easy to use depth of sedation monitor in children.

Human IBD, including UC and Crohn's disease, is characterized by a chronic, relapsing, and remitting condition that exhibits various features of immunological inflammation and affects at least one/1000 people in Western countries. Polyphenol extracts from a variety of plants have been shown to have immunomodulatory and anti-inflammatory effects. In this study, treatment with APP was investigated to ameliorate chemically induced colitis. Oral but not peritoneal administration of APP during colitis induction significantly protected C57BL/6 mice against disease, as evidenced by the lack of weight loss, colonic inflammation, and shortening of the colon. APP administration dampened the mRNA expression of IL-1β, TNF-α, IL-6, IL-17, IL-22, CXCL9, CXCL10, CXCL11, and IFN-γ in the colons of mice with colitis. APP-mediated protection requires T cells, as protection was abated in Rag-1(-/-) or TCRα(-/-) mice but not in IL-10(-/-), IRF-1(-/-), μMT, or TCRδ(-/-) mice. Administration of APP during colitis to TCRα(-/-) mice actually enhanced proinflammatory cytokine expression, further demonstrating a requirement for TCRαβ cells in APP-mediated protection. APP treatment also inhibited CXCR3 expression by TCRαβ cells, but not B or NK cells, in the colons of mice with colitis; however, depletion of CD4(+) or CD8(+) T cells alone did not abolish APP-mediated protection. Collectively, these results show that oral administration of APP protects against experimental colitis and diminishes proinflammatory cytokine expression via T cells.

The anti-tumor effects of polyphenols have received considerable attention in recent years. The majority of research in this area has focused on the direct effect of these compounds on tumor cells, as well as their antioxidant activities. However, few studies have focused on the effect of these compounds on leukocyte responses involved in anti-tumor immunity. Two polyphenol extracts, which have been shown to have immunomodulatory and antitumor properties, are apple peel polyphenols (APP) and oenothein B (OB), a compound isolated from the Epilobium angustifolium plant. We have previously shown that these compounds are capable of stimulating innate lymphocytes, such as NK cells and γδ T cells. Since these innate lymphocytes play an important role in anti-tumor responses through several mechanisms, the effects of these polyphenol extracts on these cells was investigated further. We found that both APP and OB can modulate the expression of certain surface proteins and cytokines involved in tumor cell recognition and killing by innate lymphocytes, such as NKG2D and IFNγ. The effect of these polyphenols on the anti-tumor activity of innate lymphocytes and their importance is currently under investigation in both human cells and mouse models. Funded by NIH NCCAM PO1 AT004986.

We recently characterized the capacity of procyanidins and polysaccharides found in common dietary supplements to stimulate innate immunity. Our studies focused on γδ T cells, innate lymphocytes found in mucosal epithelium and well positioned to encounter and respond to agonists found in dietary supplements. Higher order oligomeric procyanidins, such as those found in unripe apple peel (APP) and polysaccharides from plant bark (Yamoa(tm)) primed γδ T cells. Priming of γδ T cells results in rapid increases in innate cytokine expression and enhanced responses to secondary stimuli. Intraperitoneal injection of either procyanidin or polysaccharide agonists induced rapid peritonitis in mice. Feeding Yamoa(tm) extract to calves altered peripheral blood leukocyte responses. Although both procyanidins and polysaccharides primed γδ T cells, they acted via different mechanisms. Whereas procyanidins directly primed γδ T cells, polysaccharides required accessory cells such as monocytes for optimal priming. Procyanidins induced GM‐CSF and IL‐8 production and mRNA stabilization. Our ongoing studies suggest that the responses of γδ T cells may be responsible, to some degree, for the innate immune benefit provided by these dietary supplements. These studies were supported by a PO1 grant from NIH‐NCCAM and an NIH‐NIAID Contract.