Current pharmaceutical design
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Increasingly more Americans are being diagnosed with diabetes mellitus, and the number of those using the continuous subcutaneous insulin infusion pump (CSII), commonly known as the insulin pump, is on the rise. Although evidence is lacking on how best to manage insulin pump patients perioperatively, several individual or institutional approaches have been developed. Here we propose a comprehensive algorithm for perioperative glycemic management in insulin pump patients undergoing noncardiac surgery. Where applicable, we discuss the rationale behind the algorithm.
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Central nervous system pericytes have critical and complex inductive, structural, and regulatory roles interacting with other cell types of the neurovascular unit, especially endothelial cells and astrocytes. Pericyte-endothelial interactions are particularly prominent for blood-brain barrier (BBB) maintenance, with profound effects on basement membrane and endothelial tight junction structure and function. ⋯ Stem cell characteristics of pericytes imply an important regenerative role following stroke. Pericytes thus appear to orchestrate multiple critical functions in stroke, involving blood flow, permeability, and repair of the neurovascular unit.
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Hyperglycemia is associated with increased mortality and morbidity in critically ill patients. Surgical patients commonly develop hyperglycemia related to the hypermetabolic stress response, which increases glucose production and causes insulin resistance. Although hyperglycemia is associated with worse outcomes, the treatment of hyperglycemia with insulin infusions has not provided consistent benefits. ⋯ Patients with diabetes mellitus experience chronic hyperglycemia and often require more intensive perioperative glucose management. When diabetic patients are evaluated before surgery, appropriate management of oral hypoglycemic agents is necessary as several of these agents warrant special consideration. Current recommendations for perioperative glucose management from national societies are varied, but, most suggest that tight glucose control may not be beneficial, while mild hyperglycemia appears to be well-tolerated.
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Septic shock during the perioperative period imparts significant challenges for anesthetic management. There is increasing support for standardization of care using evidence-based, international consensus guidelines, such as the Surviving Sepsis Campaign. ⋯ It will address the epidemiological data of sepsis, the diagnostic criteria, and the role of routine, goal-directed hemodynamic resuscitation. Furthermore, it will review other options for support, including antibiotics, intensive insulin therapy, and intensive care sedation in this high risk patient population.
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Pancreatic cancer is characterized by its intrinsic resistance to cytotoxic agents. But the underlying molecular mechanism is unclear. Studies demonstrate that angiogenesis, presence of highly resistant cancer stem cells (CSCs), dysregulation of cell cycle and apoptosis are main aspects of mechanisms of pancreatic cancer chemoresistance. ⋯ Conceivably, the dysregulation of Wnt/β-catenin signaling pathway is involved in pancreatic cancer chemoresistance. Though researchers have proven it in some other cancer types, however, there is no direct evidence for this reasoning in pancreatic cancer. Designing effective experiment setups to define the function and mechanism of Wnt/β-catenin signaling in pancreatic cancer chemoresistance and subsequently targeting the signaling to improve the sensitivity of chemotherapy in pancreatic cancer require a full understanding of the molecular mechanisms of Wnt/β-catenin signaling pathway in angiogenesis, maintaining of highly resistant CSCs, regulation of cell cycle and apoptosis in pancreatic cancer.