Nancy Zikri

Black raspberry components inhibit proliferation, induce apoptosis, and modulate gene expression in rat esophageal epithelial cells.

We have shown that a diet containing freeze-dried black raspberries (BRB) inhibits the development of chemically induced cancer in the rat esophagus. To provide insights into possible mechanisms by which BRB inhibit esophageal carcinogenesis, we evaluated an ethanol (EtOH) extract of BRB, and two component anthocyanins (cyanidin-3-O-glucoside and cyanidin-3-O−rutinoside) in BRB, for their effects on growth, apoptosis, and gene expression in rat esophageal epithelial cell lines. The EtOH extract and both anthocyanins selectively caused significant growth inhibition and induction of apoptosis in a highly tumorigenic cell line (RE-149 DHD) but not in a weakly tumorigenic line (RE-149). The uptake of anthocyanins from the EtOH extract into RE-149 DHD cells far exceeded their uptake into RE-149 cells, which may have accounted for the selective effects of the extract on growth and apoptosis of RE-149 DHD cells. The growth inhibitory and proapoptotic effects were enhanced by the daily addition of the EtOH extract and the anthocyanins to the medium. Interestingly, the EtOH extract did not alter cyclooxygenase-2 (COX-2) and nitric oxide synthase (i-NOS) expression in RE-149 DHD cells, whereas both anthocyanins downregulated the expressions of these genes. This differential effect may have been related to the relative amounts of anthocyanins in the extract vs. when they were added individually to the medium. We conclude that the selective effects of the EtOH extract on growth and apoptosis of highly tumorigenic rat esophageal epithelial cells in vitro may be due to preferential uptake and retention of its component anthocyanins, and this may also be responsible for the greater inhibitory effects of freeze-dried whole berries on tumor cells in vivo.

Beyond the bundle - journey of a tertiary care medical intensive care unit to zero central line-associated bloodstream infections

IntroductionWe set a goal to reduce the incidence rate of catheter-related bloodstreaminfections to rate of <1 per 1,000 central line days in a two-year period.MethodsThis is an observational cohort study with historical controls in a 25-bedintensive care unit at a tertiary academic hospital. All patients admitted to theunit from January 2008 to December 2011 (31,931 patient days) were included. Amultidisciplinary team consisting of hospital epidemiologist/infectious diseasesphysician, infection preventionist, unit physician and nursing leadership wasconvened. Interventions included: central line insertion checklist, demonstrationof competencies for line maintenance and access, daily line necessity checklist,and quality rounds by nursing leadership, heightened staff accountability,follow-up surveillance by epidemiology with timely unit feedback and case reviews,and identification of noncompliance with evidence-based guidelines. Molecularepidemiologic investigation of a cluster of vancomycin-resistant Enterococcusfaecium (VRE) was undertaken resulting in staff education forproper acquisition of blood cultures, environmental decontamination and dailychlorhexidine gluconate (CHG) bathing for patients.ResultsCenter for Disease Control/National Health Safety Network (CDC/NHSN) definitionwas used to measure central line-associated bloodstream infection (CLA-BSI) ratesduring the following time periods: baseline (January 2008 to December 2009),intervention year (IY) 1 (January to December 2010), and IY 2 (January to December2011). Infection rates were as follows: baseline: 2.65 infections per 1,000catheter days; IY1: 1.97 per 1,000 catheter days; the incidence rate ratio (IRR)was 0.74 (95% CI = 0.37 to 1.65, P = 0.398); residual seven CLA-BSIsduring IY1 were VRE faecium blood cultures positive from central linealone in the setting of findings explicable by noninfectious conditions. Followingstaff education, environmental decontamination and CHG bathing (IY2): 0.53 per1,000 catheter days; the IRR was 0.20 (95% CI = 0.06 to 0.65, P = 0.008)with 80% reduction compared to the baseline. Over the two-year interventionperiod, the overall rate decreased by 53% to 1.24 per 1,000 catheter-days (IRR of0.47 (95% CI = 0.25 to 0.88, P = 0.019) with zero CLA-BSI for a total of15 months.ConclusionsResidual CLA-BSIs, despite strict adherence to central line bundle, may be relatedto blood culture contamination categorized as CLA-BSIs per CDC/NHSN definition.Efforts to reduce residual CLA-BSIs require a strategic multidisciplinary teamapproach focused on epidemiologic investigations of practitioner- or unit-specificetiologies.

Cancer Prevention with Berries: Role of Anthocyanins

1. Berries have been part of the human diet for many centuries. They are a rich source of known chemopreventive agents including provitamin A carotenoids, C, E, and folate, calcium and selenium, simple and complex phenols, and phytosterols.

Induction of CD4+CD25+ T Regulatory Cells with CD103 Depletion

BACKGROUND M290SAP, a murine CD103 antibody conjugated with the immunotoxin saporin, has been found to induce the indefinite acceptance of transplanted pancreatic islets in mice. We sought to understand the underlying mechanism of this alloacceptance, particularly with respect to the CD4 CD25 T regulatory phenotype. METHODS In this study, we established the kinetics of M290SAP and evaluated the requirement of alloantigen for the induction and maintenance of CD4 CD25 T regulatory cells (Tregs). Naive C57BL/6 mice were treated with several doses of M290SAP with and without donor-specific blood or splenocytes. Blood and spleens were collected at specific time points and underwent FACS analysis. RESULTS M290SAP significantly depleted CD103 cells and induced the up-regulation of CD4 CD25 T regulatory population in spleen cell preparations. The combination of alloantigen in the form of donor-specific blood or splenocytes, with M290SAP, further induced the up-regulation of CD4 CD25 Tregs in the spleen compared with either M290SAP alone or alloantigen alone. The generation of CD4 CD25 cells and the depletion of CD103 cells reached a maximum at 7 d and by 3 wk CD103 and CD4 CD25 T regulatory cell populations returned to baseline. When multiple antigenic challenges were administered, the splenic CD4 CD25 cell population was again up-regulated and persisted for 3 wk. CONCLUSION Our data confirm that M290SAP induces the generation of the CD4 CD25 T regulatory phenotype in spleens of naïve mice. Alloantigen further enhances and rejuvenates the CD4 CD25 cell population in mice treated with M290SAP.