Pancreatic neuroendocrine tumors (PNETs), also known as islet cell tumors, are mostly indolent neoplasms that probably arise from a network of endocrine cells that includes islet cells and pluripotent precursors in the pancreatic ductal epithelium. The incidence and prevalence of PNETs continue to rise in recent years because of more sensitive detection. The molecular pathogenesis, early detection, molecular predictors of tumor behavior, and targeted drug therapy of PNETs are not well understood and require additional basic and translational research. The rarity and indolent nature of these tumors, difficulty of access to appropriate patient tissue samples, and varying histopathology and secreted hormones pose particular challenges to PNET researchers. Animal models and cell lines are indispensable tools for investigating the pathogenesis, pathophysiology, mechanisms for tumor invasion and metastasis, and therapeutics of PNETs. This review summarizes currently available animal models and cell lines of PNETs, which have provided valuable insights into the pathogenesis and natural history of human PNETs. In the future, animal models and cell lines of PNETs should also be used to study early tumor detection and molecular predictors of tumor behavior and to test the responses to, and mechanisms for, novel targeted drug therapies.
Objectives: Hyperglycemia is a well-known marker of poor clinical outcomes in acute myocardial infarction and critical illness; however, its effect in congestive heart failure (CHF) is controversial. We hypothesized that persistent hyperglycemia is associated with increased length of stay (LOS) and increased total cost in patients admitted with CHF. Methods: We studied 203 consecutive patients admitted with a primary diagnosis of CHF. Patient characteristics, admission glucose, mean blood glucose (MBG) during the entire hospital stay, length of stay, total cost, and readmission rates were assessed. Persistent hyperglycemia was defined as a MBG level ≥140 mg/dl. Results:Patients with persistent hyperglycemia had longer mean LOS (8.1 vs 5.2 days, p = 0.001) and higher total hospital costs (median $8940 vs $6892, p = 0.01) independent of diabetes status. Similarly, prolonged hospital stay >7 days (38% vs 21%; p = 0.01) and total cost >$10,000/patient (46% vs 29%; p = 0.01) were seen more commonly in patients with poor glucometrics. Neither admission glucose >140 mg/ dL or diabetes status was predictive of total costs or LOS. In multivariate linear regression, only MBG ≥ 140 mg/dl was associated with increased LOS and total cost. Patients with persistent hyperglycemia also had higher 6 months all-cause readmission rates (51% vs 37%; p = 0.03). Conclusion: Persistent hyperglycemia (MBG > 140 mg/dL), but not admission glucose, was associated with increased LOS, total cost and readmission rates independent of diabetes status. Our study emphasizes the need to further examine the role of glycemic control in patients admitted with CHF.
Our current investigation comprises the synthesis and pharmacological impact of bromelain copper nanoparticles (BrCuNP) against diabetes mellitus (DM) and associated ischemia/reperfusion (I/R) – induced myocardial infarction. Bromelain is a proteolytic enzyme obtained from Ananas comosus L. Merr., which has blood platelet aggregation inhibiting and arterial thrombolytic potential. Moreover, copper is well-known to facilitate glucose metabolism and strengthen cardiac muscle and antioxidant activity; although, chronic or long-term exposure to high doses of copper may lead to copperiedus. To restrict these potential hazards, we synthesized herbal nano-formulation which convincingly indicated the improved primordial therapeutic potential of copper by reformulating the treatment carrier with bromelain, resulting in facile synthesis of BrCuNP. DM was induced by administration of double cycle repetitive dose of low dose streptozotocin (20 mg/kg, i.p.) in high-fat diet- fed animals. DM and associated myocardial I/R injury were estimated by increased serum levels of total cholesterol, low-density lipoprotein, very low-density lipoprotein, lactate dehydrogenase, creatine kinase myocardial band, cardiac troponin, thiobarbituric acid reactive substances, tumor necrosis factor α, interleukin 6, and reduced serum level of high-density lipoprotein and nitrite/nitrate concentration. However, treatment with BrCuNP ameliorates various serum biomarkers by approving cardioprotective potential against DM- and I/R-associated injury. Furthermore, upturn of histopathological changes were observed in cardiac tissue of BrCuNP-treated rats in comparison to disease models.
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