Perioperative hyperglycemia in critically ill surgery patients increases the risk of postoperative infection (POI), which is a common, and often costly, surgical complication. Hyperglycemia is associated with abnormal...Perioperative hyperglycemia in critically ill surgery patients increases the risk of postoperative infection (POI), which is a common, and often costly, surgical complication. Hyperglycemia is associated with abnormalities in leukocyte function, including granulocyte adherence, impaired phagocytosis, delayed chemotaxis, and depressed bactericidal capacity. These leukocyte deficiencies are the cause ofinfection and improve with tight glycemic control, which leads to fewer POIs in critically ill surgical patients. Tight glycemic control, such as intensive insulin therapy, has a risk of hypoglycemia. In addition, the optimal targeted blood glucose range to reduce POI remains unknown. Since 2006, we have investigated tight perioperative blood glucose control using a closed-loop artificial endocrine pancreas system, to reduce POI and to avoid hypoglycemia. In this Topic Highlight, we review the relationship between perioperative glycemic control and POI, including the use of the artificial pancreas.展开更多
Strict intraoperative glycemic control can significantly decrease the incidence of postoperative infection; however, anesthesiologists must carefully control blood glucose levels as well as properly manage the respira...Strict intraoperative glycemic control can significantly decrease the incidence of postoperative infection; however, anesthesiologists must carefully control blood glucose levels as well as properly manage the respiratory and cardiovascular systems. However, standard blood glucose measurement systems and insulin dosing algorithms, which are necessary for achieving strict glycemic control, have not yet been developed. An artificial pancreas (STG-22TM; Nikkiso Co., Tokyo, Japan) is considered a highly accurate blood glucose monitoring system capable of closed-loop control of blood glucose. The device has, however, many problems to be addressed since it is a large and expensive system with little versatility, and it requires a large amount of blood to be collected. Therefore, the development of less invasive and inexpensive systems with future technological progress is greatly anticipated.展开更多
The artificial endocrine pancreas is a feedback control instrument that regulates insulin delivery on a minute-by-minute basis according to measured blood glucose levels. Only one type of bedsidetype artificial endocr...The artificial endocrine pancreas is a feedback control instrument that regulates insulin delivery on a minute-by-minute basis according to measured blood glucose levels. Only one type of bedsidetype artificial endocrine pancreas is now available in Japan: STG-22 (Nikkiso Co. Ltd., Japan). In the insulin infusion algorithm, insulin is infused on the basis ofits proportional and derivative actions, to blood glucose concentrations with a constant time delay. The bedside-type artificial endocrine pancreas has been proven to be useful not only as a therapeutic tool for diabetes mellitus, but also as an elegant research tool for investigating the pathophysiology of the disease, by using the euglycemic hyperinsulinemic glucose clamp technique. The wearable type of closed-loop system has been developed recently. The breakthrough is the establishment of a needle-type glucose sensor. The development of closed-loop glycemic control systems that enable long-term physiological regulation has focused on implantable devices. Much effort has been expended to realize these devices.展开更多
To investigate the efficiency of suicide gene systems on vascular cells, HSV-tk/GCV and EC-CD/5-FC systems were established on vascular endothelial cells in vitro by retroviral transduction. Both modified cell lines w...To investigate the efficiency of suicide gene systems on vascular cells, HSV-tk/GCV and EC-CD/5-FC systems were established on vascular endothelial cells in vitro by retroviral transduction. Both modified cell lines were highly sensitive to prodrugs, the IC50 for GCV was less than 0.4 μM, and IC50 for 5-FC was less than 75 μM,while the parental endothelial cells were insensitive even at the highest concentrations of prodrugs in this experiment. Mixed cellular assay showed that significant bystander effect was exhibited in modified endothelial cells.When only 10% or 30% of the mixed cells were tk positive and exposed to 20 μM GCV for 6 days, more than 60% or 90% of the whole population was killed. Similar result was also found in CD positive cells. These results indicated that both HSV-tk/GCV and EC-CD/5-FC systems could efficiently suppress endothelial cell growth in vitro.展开更多
In this paper, we consider a nonlinear hybrid dynamic (NHD) system to describe fedbatch culture where there is no analytical solutions and no equilibrium points. Our goal is to prove the strong stability with respec...In this paper, we consider a nonlinear hybrid dynamic (NHD) system to describe fedbatch culture where there is no analytical solutions and no equilibrium points. Our goal is to prove the strong stability with respect to initial state for the NHD system. To this end, we construct corresponding linear variational system (LVS) for the solution of the NHD system, also prove the boundedness of fundamental matrix solutions for the LVS. On this basis, the strong stability is proved by such boundedness.展开更多
文摘Perioperative hyperglycemia in critically ill surgery patients increases the risk of postoperative infection (POI), which is a common, and often costly, surgical complication. Hyperglycemia is associated with abnormalities in leukocyte function, including granulocyte adherence, impaired phagocytosis, delayed chemotaxis, and depressed bactericidal capacity. These leukocyte deficiencies are the cause ofinfection and improve with tight glycemic control, which leads to fewer POIs in critically ill surgical patients. Tight glycemic control, such as intensive insulin therapy, has a risk of hypoglycemia. In addition, the optimal targeted blood glucose range to reduce POI remains unknown. Since 2006, we have investigated tight perioperative blood glucose control using a closed-loop artificial endocrine pancreas system, to reduce POI and to avoid hypoglycemia. In this Topic Highlight, we review the relationship between perioperative glycemic control and POI, including the use of the artificial pancreas.
文摘Strict intraoperative glycemic control can significantly decrease the incidence of postoperative infection; however, anesthesiologists must carefully control blood glucose levels as well as properly manage the respiratory and cardiovascular systems. However, standard blood glucose measurement systems and insulin dosing algorithms, which are necessary for achieving strict glycemic control, have not yet been developed. An artificial pancreas (STG-22TM; Nikkiso Co., Tokyo, Japan) is considered a highly accurate blood glucose monitoring system capable of closed-loop control of blood glucose. The device has, however, many problems to be addressed since it is a large and expensive system with little versatility, and it requires a large amount of blood to be collected. Therefore, the development of less invasive and inexpensive systems with future technological progress is greatly anticipated.
文摘The artificial endocrine pancreas is a feedback control instrument that regulates insulin delivery on a minute-by-minute basis according to measured blood glucose levels. Only one type of bedsidetype artificial endocrine pancreas is now available in Japan: STG-22 (Nikkiso Co. Ltd., Japan). In the insulin infusion algorithm, insulin is infused on the basis ofits proportional and derivative actions, to blood glucose concentrations with a constant time delay. The bedside-type artificial endocrine pancreas has been proven to be useful not only as a therapeutic tool for diabetes mellitus, but also as an elegant research tool for investigating the pathophysiology of the disease, by using the euglycemic hyperinsulinemic glucose clamp technique. The wearable type of closed-loop system has been developed recently. The breakthrough is the establishment of a needle-type glucose sensor. The development of closed-loop glycemic control systems that enable long-term physiological regulation has focused on implantable devices. Much effort has been expended to realize these devices.
文摘To investigate the efficiency of suicide gene systems on vascular cells, HSV-tk/GCV and EC-CD/5-FC systems were established on vascular endothelial cells in vitro by retroviral transduction. Both modified cell lines were highly sensitive to prodrugs, the IC50 for GCV was less than 0.4 μM, and IC50 for 5-FC was less than 75 μM,while the parental endothelial cells were insensitive even at the highest concentrations of prodrugs in this experiment. Mixed cellular assay showed that significant bystander effect was exhibited in modified endothelial cells.When only 10% or 30% of the mixed cells were tk positive and exposed to 20 μM GCV for 6 days, more than 60% or 90% of the whole population was killed. Similar result was also found in CD positive cells. These results indicated that both HSV-tk/GCV and EC-CD/5-FC systems could efficiently suppress endothelial cell growth in vitro.
基金This work was supported by the National Science Foundation for the Youth of China (Grant Nos. 11501574, 11401073 and 11701063), the National Natural Science Foundation of China (Grant Nos. 11771008, 61673083 and 61773086), the National Science Foundation for the Tianyuan of China (Grant No. 11626053), the Natural Science Foundation of Shandong Province in China (Grant No.: ZR2015FM014, ZR2015AL010 and ZR2017MA005), the Fundamental Research Funds for the Cen- tral Universities in China (Grant No. DUT16LK07) and the Project funded by China Postdoctoral Science Foundation (Grant No. 2016M601296).
文摘In this paper, we consider a nonlinear hybrid dynamic (NHD) system to describe fedbatch culture where there is no analytical solutions and no equilibrium points. Our goal is to prove the strong stability with respect to initial state for the NHD system. To this end, we construct corresponding linear variational system (LVS) for the solution of the NHD system, also prove the boundedness of fundamental matrix solutions for the LVS. On this basis, the strong stability is proved by such boundedness.