Multivariate analysis using total IEQ and IEQ/g as outcome variables indicated that age older than 2, being male and moderate distension by Liberase injection are major determinants influencing successful islet isolation.
Prediction of islet yield and posttransplant outcome is essential for clinical porcine islet xenotransplantation. Although several histomorphometric parameters of biopsied porcine pancreases are predictive of islet yield, their role in the prediction of in vivo islet potency is unknown. We investigated which histomorphometrical parameter best predicts islet yield and function, and determined whether it enhanced the predictive value of in vitro islet function tests for the prediction of posttransplant outcome. We analyzed the histomorphometry of pancreases from which 60 adult pig islet isolations were obtained. Islet function was assessed using the β-cell viability index based on flow cytometry analysis, oxygen consumption rate, ADP/ATP ratio, and/or concurrent transplantation into NOD/SCID mice. Receiver operating characteristic (ROC) analysis revealed that only islet equivalent (IEQ)/cm 2 and the number of islets >200 µm in diameter significantly predicted an islet yield of >2000 IEQ/g ( p < 0.001 for both) and in vivo islet potency ( p = 0.024 and p = 0.019, respectively). Although not predictive of islet yield, a high proportion of large islets (>100 µm in diameter) best predicted diabetes reversal ( p = 0.001). Multiple regression analysis revealed that the β-cell viability index ( p = 0.003) and the proportion of islets >100 µm in diameter ( p = 0.048) independently predicted mean posttransplant blood glucose level (BGL). When BGL was estimated using both these parameters [area under the ROC curve (AUC), 0.868; 95% confidence interval (CI), 0.730-1.006], it predicted posttransplant outcome more accurately than the β-cell viability index alone (AUC, 0.742; 95% CI, 0.544-0.939). In conclusion, we identified the best histomorphometric predictors of islet yield and posttransplant outcome. This further enhanced the predictive value of the flow cytometry analysis. These parameters should be useful for predicting islet yield and in vivo potency before clinical adult porcine islet xenotransplantation.
Use of the newer bovine nervous tissue-free enzymes including a GMP-grade enzyme resulted in better islet quality than that of islet isolated using Liberase PI. To obtain high-quality islet from DPF pigs, the donor should be male pig and histomorphometrical parameters from donor pancreas should be considered.
Intraductal administration of a c-Jun NH(2)-terminal kinase (JNK) inhibitor enhances islet viability. However, its role in reducing the inflammatory response in islets is unknown. It is also unknown whether a JNK inhibitor could act in synergy with statins. We examined if the sequential combination of a JNK inhibitor and simvastatin would reduce islet inflammation and improve islet viability. We performed porcine islet isolation with or without intraductal administration of SP600125, a JNK inhibitor. This was followed by culture medium supplementation with either nicotinamide alone or nicotinamide plus simvastatin. We assessed the viability of islets by flow cytometry, islet loss during overnight culture, graft function in NOD/SCID mice, and expression of inflammation-related genes in islets. The sequential combination of a JNK inhibitor and simvastatin increased the β-cell viability index of porcine islets cultured overnight (p = 0.015) as well as islet viability as assessed by a DNA binding dye staining (p = 0.011). The combination of a JNK inhibitor and simvastatin significantly increased the islet survival rate (p = 0.027) when the histomorphometry of donor pancreas indicated a large islet proportion of greater than 50.55%. When we transplanted the same islet mass per recipient for each group, there was no difference in overall islet graft function. Intraductal administration of JNK inhibitor significantly suppressed mRNA expression levels of interleukin-1β (IL-1β), interferon-γ, tumor necrosis factor-α, IL-6, IL-8, and macrophage chemoattractant protein-1. It also decreased the concentration of IL-1β (p = 0.040) and IL-8 (p = 0.023) in the culture supernatant. In conclusion, the sequential combination of a JNK inhibitor and simvastatin protected porcine islets from peritransplant apoptosis. Inhibition of JNK reduced the inflammatory response and could be considered an alternative target for suppression of porcine islet inflammation.
Fiber Reinforced Plastic (FRP) sheets have been widely used to retrofit and rehabilitate RC structures, while in case of retrofitting steel structures, there are no codes and researches. It stems from configuration of member and characteristics of bonding behavior. This study focused on the static behavior of steel beams reinforcement by AFRP sheets. The main objective of the experimental programme was the evaluation of the force transfer mechanism, the increment of the beam load carrying capacity and the bending stiffness. A bending test was conducted on a H-shaped steel beam, with aramid FRP sheets bonded to its flanges. The mid-span deflection and the strain from three points along AFRP sheets were recorded Test results exhibit that the increment of the load-carrying capacity with reference to a mid-span deflection level of 15 mm(1/125mm of the clear span) was equal to 9.4% and for the two layers case, an elastic stiffness increment is slightly higher than one layer case.
Fatigue damage increases with applied load cycles in a cumulative manner. Cumulative fatigue damage analysis plays a key role in life prediction of structures subjected to field load histories. Steel structures of substations are subjected to a large number of repetitive loading of different magnitudes caused mainly by mechanical equipment such as gas insulated switchgear (GIS). In this paper, a method is presented to predict the fatigue damage of the steel structures of a 153kV substation using dynamic characteristics. Through the field measurements and the fatigue analysis, it was observed that the accumulated fatigue damage was very small after a year of operation and the amount of accumulated fatigue damage will be smaller than 0.2 until the end of the working life. The structural safety of the 153kV substation can be guaranteed by the normal inspection.
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