UMD Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/3
New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a given thesis/dissertation in DRUM.
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Item Blood Coagulation Inducing Synthetic Polymer Hydrogel(2010) Casey, Brendan John; Kofinas, Peter; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Uncontrolled hemorrhaging, or blood loss, accounts for upwards of 3 million deaths each year and is the leading cause of preventable deaths after hospital admission around the world. Biological-based hemostatics are quite effective at controlling blood loss, but prohibitively expensive for people in developing countries where over 90 % of these deaths are occurring. Synthetic-based hemostatics are less expensive, yet not nearly as effective as their biological counterparts. A better understanding of how synthetic materials interact with and affect the body's natural clotting response is vital to the development of future hemostatic material technology which will help millions around the world. Initial in vitro experimentation focused on investigating the key chemical and structural material properties which affect Factor VII (FVII) activation in citrated human plasma. Enzyme-linked assays were utilized to confirm the ability of specifically formulated charged hydrogels to induce FVII activation and provided insight into the critical material parameters involved in this activation. Dynamic mechanical analysis was used to establish a correlation between polymeric microstructure and FVII activation. Experiments utilizing coagulation factor depleted and inhibited plasmas indicated that FVII, FX, FII, and FI are all vital to the process outlining the general mechanism of fibrin formation from the onset of FVII activation. The ability of the polymer to induce fibrin formation in "artificial plasma" explicitly lacking calcium, TF, and platelets suggested that a specifically designed material surface has the capability to substitute for these vital cofactors. Clinical diagnostic experimentation using sheep blood indicated that hydrogels containing higher amounts of electrostatic positive charge and lower cross-link density were able to induce faster, more robust clot formation in the presence of a coagulation cascade activator. Subsequent in vivo animal experimentation clearly demonstrated the ability of such hydrogels to aggregate platelets and erythrocytes promoting the formation of an effective hemostatic seal at the wound site. Moreover, in vivo testing confirmed the viability of such a charged polymer hydrogel to effectively control blood loss in a clinically relevant model.Item DEFINING THE HEMOSTATIC RESPONSE TO AN ORAL FAT LOAD BEFORE AND AFTER EXERCISE TRAINING.(2005-07-21) Paton, Chad Michael; Hagberg, Jim; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)INTRODUCTION: Chronic hypertryglyceridemia is thought to be atherogenic and is associated with an elevated thrombotic potential. Aerobic exercise training is known to reduce plasma triglyceride (TG) levels and the purpose of this study was to determine the effect of a single, high-fat meal on markers of inflammation, coagulation, and fibrinolysis before and after exercise training. MATERIALS and METHODS: Eight subjects were tested for aerobic capacity, body composition, and postprandial lipemia (PPL), followed by 6-months of exercise training and final testing. Blood samples were obtained every 30-minutes following the lipemic challenge for measurement of free fatty acid (FFA), TG, insulin (Ins), and glucose (Glu). Hemostatic variables including factor VII activity (FVIIa), tissue factor pathway inhibitor-factor Xa complex (TFPI/Xa), and plasminogen activator inhibitor-1 (PAI-1) antigen / activity were assessed at 0, 2, and 4 hours postprandial, as well as leukocyte interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and PAI-1 gene expression among 4 subjects during the lipemic challenge. RESULTS: The exercise training was of sufficient intensity to increase aerobic capacity (p < 0.0001) and improve body composition (p = 0.04). There were no differences between tests among PPL responses of FFA, TG, Ins, or Glu, however the main effect mean TG response averaged across all time-points was lower at final testing (139 ± 19 mgdl-1) versus baseline (154 ± 24 mgdl-1) (p = 0.02). Furthermore, the 4-hour averages for total fat oxidation rate increased by 68% (p = 0.01) and total carbohydrate oxidation rate decreased by 29% (p = 0.009) from baseline to final testing. IL-6 and PAI-1 gene expression were undetectable in the Paxgene® blood samples, however PAI-1 antigen / activity, FVIIa, TFPI/Xa, and TNF-α gene expression were all improved following exercise training after adjusting for confounders. CONCLUSION: Aerobic exercise training reduces the potential for coagulation, improves fibrinolytic potential, and reduces leukocyte TNF-α gene expression following the ingestion of a high fat meal.