In order to discover marine bioactive compounds, we investigated the chemical constituents from the organic extracts of soft coral Klyxum molle. Repeated column chromatography on the ethyl acetate extract of soft coral Klyxum molle, resulted in the isolation of nine new eunicellin-type diterpenoids, klymollins V¡ÐZ (1¡Ð5) and klyxumollins A¡ÐD (6¡Ð9), and four known compounds (10¡Ð13). The structures of new compounds were determined on the basis of extensive spectroscopic data (IR, MS, 1D and 2D NMR) and by comparison of the spectral data with those of the related known compounds. The cytotoxicity of compounds 1¡Ð13 was evaluated against five tumor cell lines including CCRF-CEM (human T cell lymphoblast-like cell line), K562 (human erythromyeloblastoid leukemia cell line), Molt 4 (human acute lymphoblastic leukemia cell line), T47D (human ductal breast epithelial tumor cell line) and DLD-1 (human colorectal adenocarcinoma cell line). Compound 2 exhibited weak cytotoxicity toward three cancer cells (CCRF-CEM, Molt 4 and T47D) and compounds 4 and 9 showed weak cytotoxicity against CCRF-CEM cancer cells. Compound 11 was found to exhibit stronger cytotoxicity toward CCRF-CEM cancer cells (ED50 values of 4.2 £gg/mL). On the other hand, compound 3 showed weak activity against the accumulation of the pre-inflammatory cytokine IL-6 in LPS-induced macrophages, at a concentration of 25 £gM.

Soft corals belonging to the genus Nephthea have been found to be a rich source of terpenoids and steroids. Chromatographic separation of acetone and CH2Cl2/MeOH extracts of Formosan soft coral Nephthea chabrolii resulted in the isolation of thirteen new steroids, including nine 4£\-methylated steroids (1−6, 8−10), three 19-oxygenated steroids (11−13), and a novel skeleton 19-norsteroid (7). The structures of these metabolites were elucidated by extensive spectral analyses and anti-inflammatory activities were measured in vitro. Compounds 1−2, 4−5, 7−11 and 13 at a concentration of 10 £gM significantly reduce the levels of iNOS (inducible nitric oxide synthase ). Compounds 2, 4, 6−7 and 10−11 at a concentration of 10 £gM also significantly reduce the levels of COX-2 (cyclooxygenase-2). Compounds 2, 4, 7, 10 and 11 can reduce the levels of both iNOS and COX-2. All compounds at a concentration of 10 £gM did not affect the housekeeping £]-actin protein expression.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently prescribed classes of drugs worldwide. Due to their excellent effects for analgesic, anti-inflammatory and antipyretic, most elder population used frequently for osteoarthritis. Gastrointestinal symptoms and ulceration associated with NSAIDs are common. Such ulcers may cause pain, bleeding, or perforation. It leads to other medical problems. The aim of this study was to examine the utilizations of medical resources associated with inpatients with NSAID related peptic ulcer disease and compared to non-NSAID related peptic ulcer disease. The study used the database from a teaching hospital in southern Taiwan. Inpatients who were identified ICD-9 CM codes as peptic ulcer diseases from January 1st of 2008 to December 31 of 2008 were included in this study. We also examined the indications for usage of NSAIDs, the date of prescription before the index date. The results showed 17.6% of inpatients with peptic ulcer disease related to NSAIDs. Inpatients with NSAIDs related peptic ulcer disease compared with inpatients with non-NSAIDs related peptic ulcer disease had significant difference in age and comorbidity. Although rapid urease test positive rate for Helicobacter pylori was higher in group of non-NSAID related peptic ulcer disease, it seemed underestimate because of the test number of patients was low. The average total direct medical cost of inpatients with NSAID related peptic ulcer was NT$ 36,491 and non-NSAID related peptic ulcer was NT$ 37,266.1. There were no significant difference in medical costs of standard care , intensive care , blood products,endoscopy, endoscopic hemostasis, surgery, CT scan , ultrasound, laboratory tests,medications, doctor¡¦s service between the two groups. Diagnostic and therapeutic procedures were no statistically significant difference, including blood transfusion,CT scan, endoscopic hemostasis, surgery, symptoms presentations, and intensive care. In this study, the duration for using NSAID was within 30 days for inpatients associated with NSAID related peptic ulcer, which had a substantial excess numbers of ulcer hospitalization. Since the common disease for using NSAID is osteoarthritis,which is very popular in elderly, therefore, we suggested that the policy makers of the National Health Insurance should be aware that preventive usage of proton pump inhibitors for the elder population who need frequent use of NSAIDs might decrease NSAID related ulcer complications.

Thesis (MChD(Chir. Max. Fac.-Med.))--Universiteit van Pretoria, 2000. / Also available online.

Thesis (Ph.D.)--University of Alberta, 2010. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Department of Chemical and Materials Engineering, Medical Sciences - Biomedical Engineering. Title from pdf file main screen (viewed on January 30, 2010). Includes bibliographical references.

Thesis (Ph. D.)--Rutgers University, 2008. / "Graduate Program in Medicinal Chemistry." Includes bibliographical references.

Ph.d.

Obesity is a known risk factor for postmenopausal breast cancer, and is associated with worse disease prognosis in pre- and postmenopausal women. Adjuvant hormonal therapies improve disease prognosis in obese women, but many still recur. Given that obesity induces inflammation and increases levels of cyclooxygenase-2 (COX-2) enzyme, resulting in tumor proliferation, this retrospective study investigated if women on anti-inflammatory drugs would have improved disease outcomes by reduced production of prostaglandins by COX-2 pathway. Four hundred and forty women treated for invasive breast cancer in San Antonio clinics were included. Cases were classified as NSAID users if notes included daily use of aspirin, ibuprofen, celecoxib or another COX-2 inhibitor; patients were categorized as NSAID nonusers if they were not taking any NSAIDs, or if they used COX-2 drugs for pain as needed rather than daily. Patients on NSAIDs were more likely to be older, be slightly more obese and postmenopausal. NSAID and NSAID nonusers did not statistically significantly differ in regards to BMI categories, tumor stage, hormone receptor status, type of invasive tumor, ethnicity/race and type of surgery. NSAID users had significantly less recurrence rates compared to nonusers (p=0.05). Further, time to disease progression was delayed by almost 28 months in patients who were NSAIDs users. Although this trend was non-significant statistically due to low number of total recurrences, it is promising in the clinical setting. In a logistic regression model using NSAID use, BMI categories and hormonal therapy drug as independent variables to predict recurrence, use of NSAID was only statistically significant in the univariate model. Overweight women were more likely to develop recurrence than normal weight when holding NSAID use and endocrine therapy constant. Obese women had increase recurrence risk, but the trend was not statistically significant. Females using aromatase inhibitors were less likely to recur than those on tamoxifen. The results of this exploratory study had limited power to determine multiple modulating factors, but because they suggest a major clinical benefit, further analyses in a larger sample size are needed to confirm these findings. / text

Neural electrodes are an important part of brain-machine interface devices that can restore functionality to patients with sensory and movement impairments including spinal cord injury and limb loss. Currently, chronically implanted neural electrodes induce an unfavorable tissue response which includes inflammation, scar formation, and neuronal cell death, eventually causing loss of electrode functionality in the long term. The objective of this research was to develop a coating to improve the tissue response to implanted neural electrodes. The hypothesis was that coating the surface of neural electrodes with a non-fouling, anti-inflammatory coating would cause reduced inflammation and a better tissue response to the implanted electrode. We developed a polymer coating with non-fouling characteristics, incorporated an anti-inflammatory agent, and engineered a stimulus-responsive degradable portion for on-demand release of the anti-inflammatory agent in response to inflammatory stimuli. We characterized the coating using XPS and ellipsometry, and analyzed cell adhesion, cell spreading, and cytokine release in vitro. We analyzed the in vivo tissue response using immunohistochemistry and microarray qRT-PCR. Although no differences were observed among the samples for inflammatory cell markers, lower IgG penetration into the tissue around PEG + IL-1Ra coated electrodes suggests an improvement in BBB integrity. Gene expression analysis showed higher expression of IL-6 and MMP-2 around PEG + IL-1Ra samples, as well as an increase in CNTF expression, an important marker for neuronal survival. An important finding from this research is the increased neuronal survival around coated electrodes compared to uncoated controls, which is a significant finding as neuronal survival near the implant interface is an essential part of maintaining electrode functionality.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences