Modeling the glucose regulatory system in extreme preterm infants

Background

Premature infants represent a significant proportion of the neonatal intensive care population. Blood glucose homeostasis in this group is often disturbed by immaturity of endogenous regulatory systems and the stress of their condition. Hypo- and hyperglycemia are frequently reported in very low birth weight infants, and more mature infants often experience low levels of glycemia. A model capturing the unique fundamental dynamics of the neonatal glucose regulatory system could be used to develop better blood glucose control methods.

Methods

A metabolic system model is adapted from adult critical care to the unique physiological case of the neonate. Integral-based fitting methods were used to identify time-varying insulin sensitivity and non-insulin mediated glucose uptake profiles. The clinically important predictive ability of the model was assessed by assuming insulin sensitivity was constant over prediction intervals of 1, 2 and 4 h forward and comparing model-simulated versus actual clinical glucose values for all recorded interventions. The clinical data included 1091 glucose measurements over 3567 total patient hours, along with all associated insulin and nutritional infusion data, for N = 25 total cases. Ethics approval was obtained from the Upper South A Regional Ethics Committee for this study.

Results

The identified model had a median absolute percentage error of 2.4% [IQR: 0.9-4.8%] between model-fitted and clinical glucose values. Median absolute prediction errors at 1-, 2- and 4-h intervals were 5.2% [IQR: 2.5-10.3%], 9.4% [IQR: 4.5-18.4%] and 13.6% [IQR: 6.3-27.6%] respectively.

Conclusions

The model accurately captures and predicts the fundamental dynamic behaviors of the neonatal metabolism well enough for effective clinical decision support in glycemic control. The adaptation from adult to a neonatal case is based on the data from the literature. Low prediction errors and very low fitting errors indicate that the fundamental dynamics of glucose metabolism in both premature neonates and critical care adults can be described by similar mathematical models.     

荔枝保鲜的研究

在低温下 ,对不同时期的贮藏荔枝的酸度和含糖量进行了测定 ,对比了不同贮藏方法下 ,荔枝内部发生的变化     

Effect of heparin on high glucose induced proliferation and expression of matrix metalloproteinases in normal human mesangial cells

Background The pathogenesis of diabetic nephropathy (DN) is a complex pathophysiological process. Its precise mechanism is not fully known. In recent years it has been recognized that synthesis of various extracelluar matrix (ECM) components may increase, and that degradation of ECM may decrease in DN. It was reported heparin could inhibit mesangial cells proliferation in vitro. The main aim of this study is to explore whether heparin inhibits proliferation of mesangial cells grown in high glucose concentration and to measure the effect of heparin on matrix metalloproteinases (MMPs) expression in mesangial cells. Methods The medium contained either low glucose (5 mmol/L) or high glucose (25 mmol/L). The concentrations of heparin in the culture medium were 0, 25, 50, 100, 200 or 400 μg/mL. A metabolic (WST-1) assay was used to measure mesangial cell proliferation and Western blot analysis was used to measure MMPs expression of mesangial cells. Results Normal human mesangial cell (NHMC) proliferation was higher in high glucose (HG) medium than in low glucose (LG) medium. They showed a 1.93 fold expansion after 72 h in high glucose in contrast to a 1.63 fold expansion in low glucose. In the presence of heparin, mesangial cells proliferation was inhibited, which was more obvious at high glucose concentrations than at low glucose concentrations. In high glucose, with heparin concentration of 50, 100, 200 and 400 μg/mL, the mesangial cells showed a 0.61 fold, 0.52 fold, 0.52 fold and 0.41 fold reductions in cell number compared to cells grown without heparin. In low glucose, only concentrations of 200 μg/mL and 400 μg/mL showed reduction in cell number, namely 0.54 fold and 0.45 fold, when compared to cells grown without heparin. In Western blot analysis, MMP₁, MMP₂, MMP₃ and MMP₉ was expressed by mesangial cells expressed in both high and low glucose concentrations, which was more prominent in high glucose medium. Incubation of heparin further increased expression of MMP₁, MMP₂, MMP₃ and MMP₉. Conclusions This study suggests that glucose can accelerate mesangial cell proliferation while heparin can reduce proliferation, being more obvious at high glucose concentrations. Higher glucose concentrations led to increased MMP expression, which may take part in the regulation of mesangial matrix synthesis and degradation. Addition of heparin resulted in a corresponding increase in MMP expression, most notably at high glucose concentrations, indicating a potentially renoprotective role in DN. Foundation item: Project (30370663) supported by the National Natural Science Foundation of China     

纳米金与二茂铁在葡萄糖传感器中的相互作用

针对纳米金颗粒修饰的葡萄糖生物传感器对葡萄糖的响应电流随着工作电压的下降快速下降的问题,进一步利用电子媒介体二茂铁对其进行修饰,并选用丝网印刷电极研究了纳米金颗粒和二茂铁之间的相互作用。实验结果表明:二茂铁有效地降低了纳米金颗粒修饰的葡萄糖生物传感器响应电流的下降值,纳米金颗粒降低了电子媒介体二茂铁的氧化还原反应电位,并且,纳米金颗粒与电子媒介体二茂铁在葡萄糖生物传感器中表现协同增效效应。     

医用微型全量分析系统中的酶生物传感器研究

酶生物传感器由于其对被分析物具有高度的选择性,成为解决μTAS(微型全量分析系统)中,复杂体系下的多种组分同时测定问题一个有效方法.以基于葡萄糖氧化酶的葡萄糖传感器为例,研究了酶生物传感器对被分析物的选择特性,实验证明,酶生物传感器完全适用于μTAS 中多种组分同时测定的用途.     

磁场对大鼠血清营养相关生化指标的影响

报道了旋转恒定磁场对大鼠血液生化指标的影响.在强度为0 4T,旋转速率为8Hz的磁场条件下,鼠龄3周的大鼠,磁场每天处理2h,共持续10周,导致血清葡萄糖水平显著下降;鼠龄为10周的大鼠,每天磁场处理2h,共持续4周,则引起血清甘油三酯水平的显著降低,血清高密度脂蛋白水平则显著上升.     

Effects of monensin on glucose metabolism in transition dairy cows

Eight multiparous periparturient Holstein cows fitted with ruminal cannula were used in a split plot design to evaluate the effects of monensin on plasma glucose metabolism. Diets were top-dressed daily with 0 mg/cow of monensin (control) or 300 mg/cow of monensin (MON) both pre- and postpartum. Plasma glucose kinetic parameters on d ?13 ± 2.0 and 19 ± 1.6 relative to parturition were determined by using stable isotopes. Na-1-¹³C₃-Propionate (labeled propionate) was infused into the rumen to measure glucose synthesis originating from ruminal propionate, and U-¹³C-glucose (labeled glucose) was injected into the jugular vein to determine total glucose kinetics. A sampling period of 480 min following labeled glucose injection was implemented. A compartmental analysis was employed to determine steady state glucose kinetic parameters. To develop a steady state glucose model, the Windows version of SAAM software (WinSAAM) was used. A 4-compartment model was adequate to comprehensively describe plasma glucose metabolism. The main model compartments consisted of propionate and plasma glucose. The time frame of the 480-min sampling period post-tracer glucose infusion allowed accurate quantification of glucose metabolism. The model estimated that glucose input from sources other than ruminal propionate decreased with MON, from 2.26 to 1.09 g/min postpartum. Gluconeogenesis, expressed as the propionate contribution to the plasma glucose pool, increased in cows fed MON (22 vs. 31%), whereas glucose oxidation, expressed as the glucose disposal rate, significantly decreased (1.67 vs. 0.92 g/min). In conclusion, MON may improve the energy status of transition cows by (1) improving the efficiency of propionate to produce glucose and (2) decreasing glucose oxidation in body tissues.     

Pheromone responsiveness is regulated by components of the Gpr1p‐mediated glucose sensing pathway in Saccharomyces cerevisiae

Many fungi have evolved mechanisms to assess environmental nutrient availability prior to the energy‐intensive process of mating. In this study, we examined one such system in Saccharomyces cerevisiae, involving a glucose‐sensing pathway mediated by Gpr1p and the pheromone‐induced mating pathway. Initially we observed that the mating pathway in MATa cells is sensitive to environmental glucose depletion. This phenomenon can be partially reversed with a high glucose spike, but not with the addition of low levels of glucose. Deletion of the low‐affinity glucose receptor, Gpr1p, eliminated this glucose‐induced recovery of pheromone responsiveness. We then determined the impact of GPR1 deletion on the mating pathway and observed that, in all end points studied, the mating pathway response to pheromone is reduced in the absence of Gpr1p. Similarly, elimination of the Gα for Gpr1p, Gpa2p, resulted in reduction in pheromone sensitivity in all assays studied. The negative effect of removing Gpr1p on mating pathway activation could be recovered by overexpressing the mating receptor, Ste2p. Furthermore, Ste2p levels are reduced in the absence of glucose and GPR1. These data suggest that activity of the GPCR‐mediated mating pathway in S. cerevisiae is modulated by extracellular glucose concentrations through the only other GPCR in MATa cells, Gpr1p. Copyright © 2014 John Wiley & Sons, Ltd.     

Conversion efficiency of glucose/xylose mixtures for ethanol production using Saccharomyces cerevisiae ITV01 and Pichia stipitis NRRL Y‐7124

BACKGROUND: Efficient conversion of glucose/xylose mixtures from lignocellulose is necessary for commercially viable ethanol production. Oxygen and carbon sources are of paramount importance for ethanol yield. The aim of this work was to evaluate different glucose/xylose mixtures for ethanol production using S. cerevisiae ITV‐01 (wild type yeast) and P. stipitis NRRL Y‐7124 and the effect of supplying oxygen in separate and co‐culture processes. RESULTS: The complete conversion of a glucose/xylose mixture (75/30 g L^?1) was obtained using P. stipitis NRRL Y‐7124 under aerobic conditions (0.6 vvm), the highest yield production being Y_p/s = 0.46 g g^?1, volumetric ethanol productivity Q_pmax = 0.24 g L^?1 h^?1 and maximum ethanol concentration P_max = 34.5 g L^?1. In the co‐culture process and under aerobic conditions, incomplete conversion of glucose/xylose mixture was observed (20.4% residual xylose), with a maximum ethanol production of 30.3 g L^?1, ethanol yield of 0.4 g g^?1 and Q_pmax = 1.26 g L^?1 h^?1. CONCLUSIONS: The oxygen present in the glucose/xylose mixture promotes complete sugar consumption by P. stipitis NRRL Y‐7124 resulting in ethanol production. However, in co‐culture with S. cerevisiae ITV‐01 under aerobic conditions, incomplete fermentation occurs that could be caused by oxygen limitation and ethanol inhibition by P. stipitis NRRL Y‐7124; nevertheless the volumetric ethanol productivity increases fivefold compared with separate culture. Copyright © 2011 Society of Chemical Industry