Sources of hepatic glycogen synthesis during an oral glucose tolerance test: Effect of transaldolase exchange on flux estimates

Sources of hepatic glycogen synthesis during an oral glucose tolerance test were evaluated in six healthy subjects by enrichment of a 75‐g glucose load with 6.67% [U‐¹³C]glucose and 3.33% [U‐²H₇]glucose and analysis of plasma glucose and hepatic uridine diphosphate–glucose enrichments (sampled as urinary menthol glucuronide) by ²H and ¹³C nuclear magnetic resonance. The direct pathway contribution, as estimated from the dilution of [U‐¹³C]glucose between plasma glucose and glucuronide, was unexpectedly low (36 ± 5%). With [U‐²H₇]glucose, direct pathway estimates based on the dilution of position 3 ²H‐enrichment between plasma glucose and glucuronide were significantly higher (51 ± 6%, P = 0.05). These differences reflect the exchange of the carbon 4, 5, and 6 moiety of fructose‐6‐phosphate and glyceraldehyde‐3‐phosphate catalyzed by transaldolase. As further evidence of this exchange, ²H‐enrichments in glucuronide positions 4 and 5 were inferior to those of position 3. From the difference in glucuronide positions 5 and 3 enrichments, the fraction of direct pathway carbons that experienced transaldolase exchange was estimated at 21 ± 4%. In conclusion, the direct pathway contributes only half of hepatic glycogen synthesis during an oral glucose tolerance test. Glucose tracers labeled in positions 4, 5, or 6 will give significant underestimates of direct pathway activity because of transaldolase exchange. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Quantitation of erythrocyte pentose pathway flux with [2-13C]glucose and 1H NMR analysis of the lactate methyl signal.

A simple and sensitive NMR method for quantifying excess (13)C-enrichment in positions 2 and 3 of lactate by (1)H NMR spectroscopy of the lactate methyl signal is described. The measurement requires neither signal calibrations nor the addition of a standard and accounts for natural abundance (13)C-contributions. As a demonstration, the measurement was applied to approximately 3 micromol of lactate generated by erythrocyte preparations incubated with [2-(13)C]glucose to determine the fraction of glucose metabolized by the pentose phosphate pathway (PP). PP fluxes were estimated from the ratio of excess (13)C-enrichment in lactate carbon 3 relative to carbon 2 in accordance with established metabolic models. Under baseline conditions, PP flux accounted for 7 +/- 2% of glucose consumption while in the presence of methylene blue, a classical activator of PP activity, its contribution increased to 27 +/- 10% of total glucose consumption (P < 0.01).     

PI3K/Akt信号通路与肝星状细胞活化的关系及其在放射性肝纤维化中的作用

目的 探讨磷脂酰肌醇3激酶-蛋白激酶B(PI3K/Akt)信号通路与肝星状细胞(HSC)活化的关系及其在放射性肝纤维化中的作用。方法 6 MV X射线照射,联合PI3K/Akt信号通路特异性抑制剂处理HSC,分为空白对照组、抑制剂组、10 Gy照射组、10 Gy+抑制剂组、20 Gy照射组和20 Gy+抑制剂组。检测各组的细胞凋亡率、细胞上清液转化生长因子β1(TGF-β1)浓度、平滑肌肌动蛋白(α-SMA)的mRNA表达量和磷酸化蛋白激酶B(p-Akt)的表达量。结果 与空白对照组相比,10 和20 Gy照射组细胞的凋亡率随照射剂量的增加而增加(t=8.43、11.63,P<0.05);与10 和20 Gy照射组比较,分别加抑制剂后细胞的凋亡率降低(t=8.09、4.88,P<0.05)。与10 Gy照射组比较,20 Gy照射组TGF-β1、α-SMA、p-Akt的量增加(t=6.91、7.80、9.28,P<0.05),10 Gy+抑制剂组TGF-β1、α-SMA、p-Akt的量降低(t=6.17、15.11、10.34,P<0.05)。与20 Gy照射组比较,20 Gy+抑制剂组TGF-β1、α-SMA、p-Akt的量同样降低(t=10.04、6.85、23.84,P<0.05)。结论 X射线通过激活PI3K/Akt信号通路使HSC活化,导致放射性肝纤维化的发生。     

Quantification of the effect of water exchange in dynamic contrast MRI perfusion measurements in the brain and heart.

Measurement of myocardial and brain perfusion when using exogenous contrast agents (CAs) such as gadolinium-DTPA (Gd-DTPA) and MRI is affected by the diffusion of water between compartments. This water exchange may have an impact on signal enhancement, or, equivalently, on the longitudinal relaxation rate, and could therefore cause a systematic error in the calculation of perfusion (F) or the perfusion-related parameter, the unidirectional influx constant over the capillary membranes (K(i)). The aim of this study was to quantify the effect of water exchange on estimated perfusion (F or K(i)) by using a realistic simulation. These results were verified by in vivo studies of the heart and brain in humans. The conclusion is that water exchange between the vascular and extravascular extracellular space has no effect on K(i) estimation in the myocardium when a normal dose of Gd-DTPA is used. Water exchange can have a significant effect on perfusion estimation (F) in the brain when using Gd-DTPA, where it acts as an intravascular contrast agent.     

The effects of physical activity and exercise on brain‐derived neurotrophic factor in healthy humans: A review

The purpose of this study was to summarize the effects of physical activity and exercise on peripheral brain‐derived neurotrophic factor (BDNF) in healthy humans. Experimental and observational studies were identified from PubMed, Web of Knowledge, Scopus, and SPORT Discus. A total of 32 articles met the inclusion criteria. Evidence from experimental studies suggested that peripheral BDNF concentrations were elevated by acute and chronic aerobic exercise. The majority of the studies suggested that strength training had no influence on peripheral BDNF. The results from most observational studies suggested an inverse relationship between the peripheral BDNF level and habitual physical activity or cardiorespiratory fitness. More research is needed to confirm the findings from the observational studies.     

高强度聚焦超声对中晚期肝癌患者机体免疫细胞及其活性的影响

目的 观察高强度聚焦超声(HIFU)对中晚期肝癌患者的机体免疫细胞及其活性的影响.方法 HCC患者30例,经全身麻醉、超声肿瘤定位进行HIFU治疗,采用流式细胞仪及双抗体夹心法检测治疗前、后外周血T细胞亚群(CD3+、CD4+、CD8+)、NK细胞的百分率及sIL-2R的变化.采用LDH释放法检测NK细胞的杀伤活性.结果 HIFU治疗后CD3+、NK细胞的百分率明显升高(P＜0.05),NK细胞杀伤活性也升高(P＜0.05),而CD8+细胞的百分率及sIL-2R的水平明显降低(P＜0.05).结论 HIFU具有激活机体免疫细胞活性作用,可使机体的免疫功能得到一定程度的改善.     

Assessment of T1 and T2* effects in vivo and ex vivo using iron oxide nanoparticles in steady state--dependence on blood volume and water exchange.

Accurate knowledge of the relationship between contrast agent concentration and tissue relaxation is a critical requirement for quantitative assessment of tissue perfusion using contrast-enhanced MRI. In the present study, using a pig model, the relationship between steady-state blood concentration levels of an iron oxide nanoparticle with a hydrated diameter of 12 nm (NC100150 Injection) and changes in the transverse and longitudinal relaxation rates (1/T2* and 1/T1, respectively) in blood, muscle, and renal cortex was investigated at 1.5 T. Ex vivo measurements of 1/T2* and 1/T1 were additionally performed in whole pig blood spiked with different concentrations of the iron oxide nanoparticle. In renal cortex and muscle, 1/T2* increased linearly with contrast agent concentration with slopes of 101 +/-22 s(-1)mM(-1) and 6.5 +/-0.9 s(-1)mM(-1) (mean +/- SD), respectively. In blood, 1/T2* increased as a quadratic function of contrast agent concentration, with different quadratic terms in the ex vivo vs. the in vivo experiments. In vivo, 1/T1 in blood increased linearly with contrast agent concentration, with a slope (T1-relaxivity) of 13.9 +/- 0.9 s(-1)mM(-1). The achievable increase in 1/T1 in renal cortex and muscle was limited by the rate of water exchange between the intra- and extravascular compartments and the 1/T1-curves were well described by a two-compartment water exchange limited relaxation model.