Thesis (M.S.)--Florida State University, 2004. / Advisors: Dr. Wei-Chun Chin and Dr. George Bates, Florida State University, College of Arts and Sciences, Dept. of Biological Science. Title and description from dissertation home page (viewed Sept. 23, 2004). Includes bibliographical references.

Thesis (Ph. D.)--Florida State University, 2006. / Advisor: Wei-Chun Chin, Florida State University, College of Engineering, Dept. of Chemical and Biomedical Engineering. Title and description from dissertation home page (viewed July 5, 2006). Document formatted into pages; contains xiii, 118 pages. Includes bibliographical references.

Cartas al editor

Objectives Concurrent diabetic ketoacidosis (DKA) is highly prevalent in patients with hypertriglyceridemia-induced pancreatitis (HP). Diabetic ketoacidosis could potentially complicate the diagnosis, management, and prognosis of HP. This study aimed to directly compare the clinical course of HP with and without DKA and assess the outcomes of frequently used severity-prediction scores in such population. Methods We retrospectively analyzed 140 patients with HP; 37 patients (26.4%) had concurrent DKA. We compared epidemiologic characteristics, initial laboratory values, and clinical courses between the DKA and non-DKA groups. Bedside Index for Severity in Acute Pancreatitis score, Sequential Organ Failure Assessment score, Ranson criteria, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Marshall score were calculated and compared between groups. Results We observed more acute kidney injury in the DKA group. Patients with DKA more likely required intensive care unit admission, received intravenous insulin, and were discharged on subcutaneous insulin. Ranson criteria and APACHE II score were significantly higher with DKA. Conclusions Concurrent DKA does not affect length of stay, in-hospital mortality, and readmission rate in patients with HP. Higher Ranson criteria and APACHE II score likely reflected derangement of clinical parameters secondary to DKA rather than true severity of pancreatitis in such population.

Thesis (Doctoral)--Departments of Surgical Pathophysiology and Anaesthesiology, University of Lund, University Hospital MAS. / Added t.p. with thesis statement inserted. Summary in Swedish. Includes bibliographical references.

Thesis (Doctoral)--Departments of Surgical Pathophysiology and Anaesthesiology, University of Lund, University Hospital MAS. / Added t.p. with thesis statement inserted. Summary in Swedish. Includes bibliographical references.

Introduction: Impairment of cytosolic calcium ([Ca2+]i) signaling and in particular calcium overload has emerged as a possible unifying mechanism for precipitating acute pancreatitis (AP.) In the L-arginine (L-arg) experimental model of AP, nitric oxide (NO) has been implicated however the disease progression is largely unaffected by nitric oxide synthase (NOS) inhibitors (8). Additionally, L-ornithine (L-orn), a NOS-independent metabolite of L-arg, has been shown to be potent at inducing AP (28). Both L-arg and L-orn activate calcium-sensing like receptors (CaSR) (31) such as the GPRC6a which may be responsible for initiating the [Ca2+]i overload. The aim of this study is to investigate the effects of L-arg and L-orn on pancreatic acinar cells that maybe linked to the pathophysiology of AP. Furthermore to provide an alternative theory to the NO mediated ones, in particular that L-arg induces toxic changes in [Ca2+]i via a GPRC6a like receptor. Methods: Whole pancreata were harvested from male Sprague Dawley rats. Pancreatic acinar cells were isolated by collagenase digestion. [Ca2+]i was measured using fura-2 imaging, and cell viability assessed using physiological CCK. Oxidative stress was measured using dichlorofluorescein (DCF) and cell death was quantified using trypan blue exclusion. Results: L-arg and L-orn (100mM) induced spike-like, reversible increases in [Ca2+]i in 46% and 74% of cells and Ca2+ overload in 11% and 26% respectively. At 500 mM both induced Ca2+ overload in all cells however this was also seen with the osmotic control, mannitol. Isosmotic L-arg and L-orn (100mM) induced only reversible increases in [Ca2+]i. Neither L-arg nor L-orn had significant effects on CCK-evoked [Ca2+]i oscillations. Both L-arg and L-orn induced significant oxidative stress responses (22% and 37% of a maximum response seen with 3mM H202, respectively). Both L-arg and L-orn caused cell death in 76% +/- 4 and 89% +/- 7 at 3 hours respectively, compared to 35% +/- 4 and 40% +/- 3 with controls (Hepes, Glycine). Conclusion: The data suggests that the L-arg and L-orn causes significant increase in oxidative stress and cell death. The data suggests that although changes in [Ca2+]i were induced by both L-arg and L-orn the large concentrations used experimentally are likely to induce significant osmotic effects.

published_or_final_version / Medicine / Master / Doctor of Medicine

Multiple lines of experimental evidence demonstrate that chronic alcoholconsumption causes mitochondrial injury, as well as acinar cell oxidative and metabolicstress. Alcoholics are more susceptible to acute and chronic pancreatitis. Despite alcoholrelatedacinar cell injury, apoptosis, or programmed cell death, appears to be reduced inacinar cells rather than increased, as is seen in the liver.This work describes the possible mechanisms through which alcohol affects theacinar cell apoptosis pathways in the rat pancreas. Two apoptotic pathways wereinvestigated: (1) receptor-mediated apoptosis via Fas/FasL and caspase-8, and (2)mitochondrial-mediated apoptosis via Bcl-2/Bax and caspase-9. Both pathways canactivate the final apoptosis executer caspase-3. Using the Lieber-DeCarli alcohol/controldiet, rats fed alcohol for 14 weeks had a significant decrease of key mediators of theFas/Fas ligand receptor-mediated pathway, while the mitochondria-associated apoptoticpathway is inappropriately deactivated. In addition, this study describes the mRNAexpression of inflammatory cytokines, such as IL-1??, IL-6, TNF??, IL-18 and TGF??,which are reported to influence inflammation and apoptosis. The anti-inflammatoryeffects of alcohol were confirmed with decreased expression of regulatory cytokinesincluding IL-1??, IL-18, TGF?? and IL-6 in alcohol-fed rats.Alcohol appears to block apoptosis in the pancreas through multiple mechanisms.Activity of the Fas/Fas ligand receptor-mediated pathway appears to be suppressed at thelevel of caspase-8, with further inhibition by down-regulation of caspase-3. Despiteknown acinar cell stress and mitochondria injury, the mitochondria-mediated apoptoticpathway was not activated. This data suggest that alcohol consumption suppresses theremoval of mitochondria injured acinar cells, promoting apoptosis resistance, and mayincrease the susceptibility to pancreatitis. The increased susceptibility to pancreatic injurywas further investigated by using lipopolysaccharide (LPS). Alcohol exacerbates LPSinducedpancreatoxicity by enhanced pancreatic apoptosis. The attenuation of apoptosisby ethanol increased the threshold of apoptosis in response to LPS and acceleratesapoptosis. Here it is hypothesized that alcoholics are more susceptible to endotoxinmediatedacute pancreatitis and the response is more severe than in non-alcoholics.

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