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Biomedical subjects

Deborah Cooper

Publications and source records attributed to Deborah Cooper.

9 recordsLinked to original sources
PubMed2004

Ponicidin and oridonin are responsible for the antiangiogenic activity of Rabdosia rubescens, a constituent of the herbal supplement PC SPES.

Antiangiogenic activity has been identified in an aqueous EtOH extract of Rabdosia rubescens, a component of the dietary supplement PC SPES. Bioassay-guided fractionation using a novel in vitro human endothelial cell-based assay for angiogenesis afforded the diterpenoids ponicidin (1) and oridonin (2), with significant antiangiogenic activity at subcytotoxic concentrations, suggesting that these constituents may strongly contribute to the demonstrated clinical efficacy of PC SPES as a treatment for advanced prostate cancer.

Angiogenesis Inhibitors↗
PubMed2004

Peritoneal mesothelial cells produce cytokines in a murine model of peritonitis.

BACKGROUND: Many of the effector mechanisms that characterize peritonitis are generated by neutrophils and macrophages. However, it is now appreciated that peritoneal mesothelial cells can also produce mediators of inflammation when grown in culture. This study tested the hypothesis that peritoneal mesothelial cells produce inflammation-related cytokines in a murine model of peritonitis. METHODS: Fifty Wistar rats were randomized to either a control group or a peritonitis group. Groups of five animals were sacrificed at 4, 18, 24, 48, and 96 h after the induction of peritonitis, which was induced by the administration of 5 mg zymosan intra-peritoneally. Control animals received an equal volume of phosphate-buffered saline. Monolayers of peritoneal mesothelial cells were obtained using an imprint technique. The expression and production of TNFalpha, IL-1beta, IL-10, and ICAM-I were determined using semi-quantitative reverse transcription- polymerase chain reaction, immunocytochemistry, and Western blotting. RESULTS: The mesothelial cells significantly expressed TNFalpha, IL-1beta, IL-10, and ICAM-I in a time-dependent manner. We were able to demonstrate increased production for each of these cytokines, and this coincided with the initial shedding of mesothelial cells and their regeneration within 96 h. CONCLUSIONS: Peritoneal mesothelial cells play a role in peritonitis by producing inflammation- associated cytokines. This implies that they may be suitable targets for molecular interventions aimed at modulating the effects of peritonitis.

Analysis of Variance↗
PubMed2004

Zymosan induces nitric oxide production by peritoneal mesothelial cells.

INTRODUCTION: The production of nitric oxide is an important peritoneal defense mechanism. We have evaluated the effect of various putative stimulants on nitric oxide production by peritoneal mesothelial cells. METHODS: Wistar rats were randomized to either a control group or a peritonitis group (5 mg zymosan intraperitoneally). Groups of five animals were sacrificed at 4, 18, 24, 48 and 96 h after the induction of peritonitis and their peritoneal fluid was harvested for assay. Cultures of peritoneal mesothelial cells were stimulated with lipopolysaccharide, myeloperoxidase, TNFalpha, zymosan, peritoneal fluid from a control animal and peritoneal fluid from a peritonitis animal. Supernatants were collected after incubation for 4, 24 and 48 h for assay. The assay for nitric oxide was based upon the nitrite content of the samples. RESULTS: The intraperitoneal administration of zymosan was associated with an increased production of nitric oxide (NO) when compared with control animals (P < 0.01). In cultures of peritoneal mesothelial cells, zymosan, but not the other putative stimulants, was associated with a marked output of nitric oxide (P < 0.001). CONCLUSION: Zymosan has a direct effect on peritoneal mesothelial cells, which are able to generate nitric oxide in the absence of co-stimulatory molecules. This suggests that it may be possible to use some form of external stimulation to up-regulate the NO response by peritoneal mesothelial cells.

Animals↗
PubMed2003

Putting the Q into quality of life; the identification of subjective constructions of health-related quality of life using Q methodology.

Health related quality of life (HRQOL) is presented as a largely subjective construct of increasing importance in health discourse and practice. Key difficulties with the assessment and measurement of quality of life (QOL) are discussed. A Q methodological investigation of subjective constructions of health-related QOL is then reported using importance items derived from studies of the WHOQOL. Eight factors emerged from a factor analysis of the Q sorts of 90 healthy participants, each corresponding to a distinct construction of the meaning and relevance of QOL. The factors are interpreted and discussed under the following headings: 'Happy families, 'Stand on my own two feet', 'Emotional independence', 'Just do it!', 'Life as a positive challenge', 'In God we trust', 'Staying healthy enough to bring home the bacon' and 'You can't choose your family'. This diversity of views has implications for QOL testing.

Adult↗
PubMed2003

Myeloperoxidase response to peritonitis in an experimental model.

INTRODUCTION: Patients with peritonitis often exhibit systemic manifestations of sepsis, especially in the lungs. The aim of the present study was to evaluate the local and systemic effects of the neutrophil response to peritonitis in a rat model. METHODS: Fifty Wistar rats were randomized to either a control group or a peritonitis group (5 mg zymosan intraperitoneal). Groups of five animals were killed at 4, 18, 24, 48 and 96 h for evaluation of the morphology of the peritoneum (mesothelial imprint), the number and phenotype of cells within peritoneal fluid (flow cytometry), and myeloperoxidase activity within the peritoneal fluid and distant organs (enzyme assay). RESULTS: Zymosan produced macroscopic evidence of peritonitis and on microscopy there was disruption of peritoneal mesothelial cells. This was accompanied by an influx of neutrophils between 4 and 48 h (P < 0.001) and macrophages between 48 and 96 h (P < 0.001). There was also an increase in myeloperoxidase activity within peritoneal fluid between 4 and 48 h (P < 0.05), the lung at 4 h (P < 0.01) and the liver at 48 h (P < 0.001). CONCLUSION: The present study has confirmed the validity of using zymosan to create a low-morbidity model of peritonitis. Besides the anticipated peritoneal response, there were distant effects of neutrophil activation within the lungs and liver. In the future, strategies that modulate neutrophil activation within these organs might play a useful adjunctive role in the management of patients with peritonitis.

Animals↗
PubMed2002

A low-morbidity murine model of peritonitis.

PURPOSE: Peritonitis continues to be a major source of mortality and morbidity in patients undergoing abdominal surgery. The aim of this study was to develop a nonfatal model of bacterial peritonitis in mice so that we could study aspects of the pathobiology and treatment of peritonitis in an in vivo model. METHODS: Mice were inoculated via a midline laparotomy with 0.5 mg of zymosan in 0.1 ml of saline into the subomental space. At 24, 48, and 96 hours after treatment, animals were killed, and analysis was performed to determine the degree of peritoneal inflammation. End points included intraperitoneal cellular influx, tumor necrosis factor-alpha concentrations, and myeloperoxidase activity. In addition, peritoneal lavage fluid was plated onto blood agar for analysis of bacterial colony-forming units. There were 40 mice in each group. RESULTS: There were no deaths in either group. Facultative Gram-negative bacteria were cultured from the peritoneal cavities of zymosan-treated animals at 24 and 48 hours after insult (colony-forming unit counts of 92+/-11 vs. 0 in control animals). In the zymosan-treated animals, there were significantly increased numbers of inflammatory cells (especially neutrophils) in the peritoneal cavity at 24 and 48 hours after treatment; these numbers returned to control levels by 96 hours. Myeloperoxidase activity was also elevated both in the peritoneal fluid (2.4 X 10(-4) units/ml compared with 1.6 x 10(-4) units/ml, P < 0.05) and in remote organs (i.e., lung, P < 0.05; liver, P < 0.001; and kidney, P < 0.05) at 24 hours after treatment. There was no significant difference in tumor necrosis factor-alpha levels between zymosan-treated and control mice in either serum or peritoneal fluid at any time point investigated. There was no mortality in either the zymosan-treated or control animals. CONCLUSION: In this model of bacterial peritonitis in mice, we have demonstrated how the peritoneal cavity can resolve a relatively localized inflammatory insult within 96 hours of induction. This response is characterized by a cellular influx of predominantly neutrophils and macrophages and by pronounced oxidative activity. We will use this in vivo model to characterize aspects of the pathobiology and treatment of peritonitis.

Animals↗
PubMed2000

The omentum.

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Journal Article↗
PubMedDate not supplied

Pharmacy benefit forecast for a new interferon Beta-1a for the treatment of multiple sclerosis: development of a first-line decision tool for pharmacy-budget planning using administrative claims data.

OBJECTIVE: To estimate the incremental change in pharmacy per-member-permonth (PMPM) costs, according to various formulary designs, for a new interferon beta-1a product (IB1a2) using administrative claims data. METHODS: Cross-sectional sex- and age-specific disease prevalence and treatment rates for relapsing, remitting multiple sclerosis (RRMS) patients were measured using integrated medical and pharmacy claims data from a 500,000- member employer group in the southern United States. Migration to IB1a2 from other drugs in the class was based on market-share data for new and existing RRMS patients. Duration of therapy was estimated by analyzing claims for current RRMS therapies. Daily therapy cost was provided by the manufacturer of IB1a2, adjusted for migration from other therapies, and multiplied by estimated volume to predict incremental and total PMPM cost impact. Market-share estimates were used to develop a PMPM cost forecast for the next 2 years. PMPM cost estimates were calculated for preferred (copayment tier 2) and nonpreferred (copayment tier 3) formulary designs with and without prior authorization (PA). One-way sensitivity analysis was performed to assess the influence of product pricing, duration of therapy, and other market factors. RESULTS: Annual incremental PMPM change was $0.047 for the scenario of third copayment tier with PA. The incremental change was greatest for those aged 55 to 65 years ($0.056 PMPM) and did not vary greatly by benefit design. Duration of therapy had the greatest impact on the PMPM estimate across benefit designs. CONCLUSION: IB1a2 will not cause a significant change in managed care pharmacy budgets under a variety of formulary conditions, according to this crosssectional analysis of current care-seeking behavior by RRMS patients. Economic impact may differ if IB1a2 expands RRMS patients. treatment-seeking behavior.

Adjuvants, Immunologic↗