A local glucose-and oxygen concentration-based insulin secretion model for pancreatic islets

<p>Abstract</p> <p>Background</p> <p>Because insulin is the main regulator of glucose homeostasis, quantitative models describing the dynamics of glucose-induced insulin secretion are of obvious interest. Here, a computational model is introduced that focuses not on organism-level concentrations, but on the quantitative modeling of local, cellular-level glucose-insulin dynamics by incorporating the detailed spatial distribution of the concentrations of interest within isolated avascular pancreatic islets.</p> <p>Methods</p> <p>All nutrient consumption and hormone release rates were assumed to follow Hill-type sigmoid dependences on local concentrations. Insulin secretion rates depend on both the glucose concentration and its time-gradient, resulting in second-and first-phase responses, respectively. Since hypoxia may also be an important limiting factor in avascular islets, oxygen and cell viability considerations were also built in by incorporating and extending our previous islet cell oxygen consumption model. A finite element method (FEM) framework is used to combine reactive rates with mass transport by convection and diffusion as well as fluid-mechanics.</p> <p>Results</p> <p>The model was calibrated using experimental results from dynamic glucose-stimulated insulin release (GSIR) perifusion studies with isolated islets. Further optimization is still needed, but calculated insulin responses to stepwise increments in the incoming glucose concentration are in good agreement with existing experimental insulin release data characterizing glucose and oxygen dependence. The model makes possible the detailed description of the intraislet spatial distributions of insulin, glucose, and oxygen levels. In agreement with recent observations, modeling also suggests that smaller islets perform better when transplanted and/or encapsulated.</p> <p>Conclusions</p> <p>An insulin secretion model was implemented by coupling local consumption and release rates to calculations of the spatial distributions of all species of interest. The resulting glucose-insulin control system fits in the general framework of a sigmoid proportional-integral-derivative controller, a generalized PID controller, more suitable for biological systems, which are always nonlinear due to the maximum response being limited. Because of the general framework of the implementation, simulations can be carried out for arbitrary geometries including cultured, perifused, transplanted, and encapsulated islets.</p

A-081:The utility of ankle-brachial index (ABI) in risk stratifying patients undergoing evaluation for coronary artery disease (CAD)

BACKGROUND: Despite its efficacy at identifying patients with CAD, stress tests still have a high incidence of inconclusive results. PAD is associated with CAD and poor outcomes. Abnormal ABI results are associated with an elevated CV risk. Research in the utility of ABI test- ing to further risk stratify patients undergoing stress tests is limited. In such patients who have undergone coronary angiograms, we studied the relationship of ABIs with the severity of CAD, as measured by the SYNTAX score, and whether an abnormal ABI can further risk stratify indeterminate stress echocardiograms. METHODS: Patients who underwent an ABI and stress echocardiogra- phy followed by a coronary angiogram between January 2010 and De- cember 2014 at Loyola University were reviewed. Among these patients, only those with diagnostic studies performed within a six year timespan were included. A retrospective analysis was conducted. Analysis included demographics, stress test parameters, ABIs and SYNTAX scores. The Student’s t-test and Fischer exact test were used with signifi- cance at p RESULTS: A total of 199 patients were studied (41% females, mean age 63). Group A (95 patients) included patients with abnormal and bor- derline ABIs (ABI ¼ 1.00 and \u3c 1.30). Baseline characteristics were sim- ilar between groups A and B, except for higher incidence of smoking and diabetes in group A. SYNTAX score was significantly higher in Group A (mean 24.3 þ/5.3) vs B (mean 11.1 þ/4.2), p CONCLUSION: PAD, as demonstrated by ABIs, is associated with an increased severity and complexity of CAD, as demonstrated by the SYNTAX score. ABIs, when combined with a stress echocardiogram, can help further risk stratify patients being evaluated for CAD. Additional study of the association of PAD with CAD to help guide di- agnosis and management of CV disease is warranted

Management of pulmonary mucormycosis after orthotopic heart transplant: A case series

Invasive pulmonary mucormycosis is a potentially fatal infection that can occur in immunosuppressed patients such as those who have undergone orthotopic heart transplant (OHT). High-dose intravenous antifungal agents, including amphotericin B, are generally accepted as the first-line medical treatment, with prompt surgical resection of lesions if feasible. The body of evidence guiding treatment decisions, however, is sparse, particularly regarding adjustment of immunosuppression during acute infection and long-term recovery. We present 2 cases of patients with pulmonary mucormycosis occurring within the first 6 months after OHT, both of whom successfully recovered after appropriate medical and surgical treatment, and we highlight differences in immunosuppression management strategies for this life-threatening condition