中性pH值、低葡萄糖降解产物腹膜透析液的生物相容性

传统腹膜透析(PD)液的高浓度葡萄糖、高葡萄糖降解产物、高糖基化终产物、低pH值等生物不相容性是影响PD疗效、导致PD技术失败的主要原因.因此研制生物相容性更好的透析液,已成为改进PD质量的重要内容.使用中性pH值、低葡萄糖降解产物(neutral pH、low-GDP,NpHLGDP)的透析液可延长腹膜寿命、提高疗效.本文主要针对NpHLGDP透析液的生物相容性、评价生物相容性的生物标志物及可能的临床预后作一简述.     

超滤腹膜透析抢救慢性肾衰并严重肺水肿二例报告

我院最近采用超滤腹膜透析抢救2例慢性肾衰并发严重肺水肿患者,取得较好疗效。现告如下: 用上海长征制药厂生产的腹膜透析液(内含2%葡萄精)1000ml,加入50%葡萄糖60ml,组成5和葡萄糖腹膜透析液。每次灌注透析液1000ml,10分钟内灌注毕,透析液在腹腔内留置30分钟,排液时间20分钟。每次连续交换8～10次,以后据病情及超滤液体量的多少,调整透析液内葡萄糖浓度。     

如何合理选用腹膜透析液

腹膜透析（PD）是肾脏替代治疗（CRRT）中的重要组成部分，而腹腹透析液则是PD中的核心环节。在过去的20多年中，PD虽然在慢性肾衰的治疗中发挥了十分重要的作用，但从人体生理学角度看，目前常规使用的透析液仍突出存在以下问题：（1）透析液以葡萄糖为主要渗透剂，因其能被腹膜吸收，故其渗透作用维持时间很短，难以达到理想的液体及溶质清除；（2）透析液中某些成分（葡萄糖及碱基等）可以活化炎性细胞因子（生长因子、一氧化氮合成酶），长期使用可以引起腹膜慢性炎性改变，促进腹膜纤维化及增厚；（3）透析液中的葡萄糖在体内被分解后，可以产生大量的糖基化终未产物（AGEs），后者可广泛在体内沉积，尤其在血管壁及腹膜间质沉积后可引起间质增厚，导致超滤功能下降；     

腹膜透析液肌酐浓度测定的校正

腹膜透析液肌酐浓度测定的校正李勇俞雨生韩国锋马柏坤关键词腹膜透析液葡萄糖肌酐中图法分类号Ｒ４５９５腹膜透析是治疗尿毒症的重要手段。在测定透析液中肌酐浓度时，常常发现葡萄糖对肌酐测定有一定的干扰，从而影响了检测的准确性［１～３］。本研究观察透析液...     

营养不良对腹膜透析预后影响及处理对策

蛋白质-能量营养不良(PEM)是腹膜透析(PD)患者常见的并发症,并随着透析时间的延长而升高,严重地影响着患者的生活质量、住院率及生存率。PEM可分为原发性(Ⅰ型)和继发性(Ⅱ型)两大类。导致PEM的主要因素有炎症、糖尿病、腹膜高转运及腹膜透析患者的年龄等。防止腹膜透析患者出现PEM的主要对策包括营养支持、使用氨基酸腹膜透析液、改善微炎症状态、充分透析、控制容量负荷、纠正代谢性酸中毒、保护残余肾功能等。另外自动化腹膜透析(APD)具有透析剂量大、交换次数多、腹内透析液存留时间短等特点,因而可以较好防治腹膜透析患者的PEM。     

无需卧床的持续性腹膜透析理论与实践

1976年Popovich等提出无需卧床的持续性腹膜透析(简称CAPD)用于慢性肾衰治疗。CAPD即透析液持续保留在腹腔间歇引出液体,再灌入新鲜透析液,形成持续性的体内透析系统。为将尿素氮(BUN)控制在70mg%,用1.5%或偶用4.25%葡萄糖溶液作为透析液,每次灌入2 L,保留3.5～4小     

腹膜透析的解剖基础和原理

自1976年Popovich实施第1例持续性非卧床腹膜透析以来[1],腹膜透析作为肾脏替代治疗的主要方法之一,得到了很大的发展.目前在全球接受腹膜透析的患者约占总透析人群的11％[2-3].腹膜透析是利用腹膜的半透膜特性,通过弥散和渗透原理,规律、定时地向腹腔内注入透析液,借助腹膜两侧的毛细血管内血浆及腹膜腔内透析液中的溶质浓度梯度和渗透梯度,以清除机体代谢废物和潴留过多的水分.因此,腹膜结构和功能的完整性是腹膜透析能否成功以及腹膜透析能否长期进行的关键因素.     

用腹膜腔CT评价持续不卧床腹膜透析的非感染性并发症

在持续不卧床腹膜透析（CAPD）患者，可因腹膜渗漏、透析液回流不良或透析液腹膜腔内积聚而引起腹壁水肿和生殖器水肿。CT用以评价腹内液体的分布和特征，对诊断各种腹膜透析并发症很有帮助。本研究报道20例腹膜透析患者使用腹膜腔CT，特别加用腹膜内对比剂，可有助于对透析液渗漏作出定位，评价腹膜腔内透析液分布以及发现导管在液体腔中的位置。病N和方法研究对象20例，女8、男12例，平均年龄46（23－70）岁，CAPD治疗平均持续16（2－26）个月。用卷曲腹膜透析导管在正中旁线植人，研究开始前连续透析14－ZI天。腹膜CT用于有不同主…     

高浓度葡萄糖对人腹膜间皮细胞生长和基质合成的影响

持续性不卧床腹膜透析（ＣＡＰＤ）时腹膜间皮层直接浸泡于含葡萄糖１．５０％～４．２５％的透析液中，为了探讨高浓度葡萄糖对腹膜间皮细胞生长和基质合成的影响，我们建立了人腹膜间皮细胞（ＨＭＣ）培养体系。ＨＭＣ在含葡萄糖浓度≥１．００％的培养基中生长时，￣３Ｈ－ＴｄＲ掺入量较在０．１０％或不加葡萄糖的培养基中生长时明显降低。当介质中葡萄糖浓度≥０．５０％时ＨＭＣ培养上清的纤维连接蛋白（ＦＮ）水平明显增高。葡萄糖引起的细胞增殖抑制和ＦＮ分泌增加均呈时间与剂量依赖关系。用甘露醇代替葡萄糖进行试验得到相似结果，但其抑制细胞增殖的作用明显弱于相同渗量的葡萄搪。上述结果表明，周围介质中高浓度的葡萄糖对ＨＭＣ生长和基质合成具有直接影响。反复或长期使用高糖透析液引起的ＨＭＣ修复和代谢障碍可能参与了ＣＡＰＤ相关性腹膜硬化的发生。     

高渗腹膜透析治疗心力衰竭并严重肺水肿6例报告

我们用高渗腹膜透析法抢救6例经药物治疗无效的心力衰竭(下称心衰)并严重肺水肿患者,疗效满意。现举3例报告如下。一、方法透析液系上海长征制药厂袋装成品。若无此成品,可按下方配制:即5%葡萄糖盐水500毫升 5%葡萄糖液250毫升 生理盐水250毫升 5%碳酸氢钠60毫升,此即为2%的透析液。在此透析液内再加入50%葡萄糖40毫升、80毫升、120毫升,则可使其     

The effects of glucose on myocardial substrate utilization in acute myocardial infarction or angina pectoris

Infusion of glucose-insulin-potassium during acute myocardial infarction has favorable clinical and hemodynamic effects, presumably as a result of decreased myocardial utilization of free fatty acids. In 14 patients with coronary artery disease, hypertonic glucose (a bolus of 10 g followed by infusion of a 30% glucose solution at a constant rate of 10 mg/kg/min) was infused and arterial and coronary sinus levels of glucose, lactate and free fatty acids were measured before and after 15 and 30 minutes of infusion. Arterial glucose and lactate levels increased significantly after glucose infusion, whereas free fatty acid levels decreased significantly. Modest but significant correlations also existed between glucose arterial levels and the arterial-coronary sinus glucose difference (r = 0.53, p less than 0.001); arterial lactate and the arterial-coronary sinus lactate difference (r = 0.35, p less than 0.01); arterial free fatty acids; and the arterial-coronary sinus free fatty acid difference (r = 0.62, p less than 0.001). These results with a hypertonic glucose infusion are similar to those reported after infusion of glucose-insulin-potassium without the potential for harmful adverse effects from infusions of insulin or potassium. Therefore, infusion of hypertonic glucose may be beneficial in patients with coronary artery disease. Further work is necessary to study its effects in different subgroups of patients with coronary artery disease.     

Dual carbon-labeled isotope experiments using D-[6-14C] glucose and L-[1,2,3-13C3] lactate: a new approach for investigating human myocardial metabolism during ischemia

Simultaneous lactate production and extraction have been previously demonstrated in the myocardium in patients with coronary artery disease. To quantitate this lactate production and determine its source, dual carbon-labeled isotope experiments were performed. L-[1,2,3-13C3] lactate and D-[6-14C] glucose were infused in 10 patients with significant coronary artery disease. Metabolic samples were obtained at rest and during atrial pacing. Despite net chemical myocardial lactate extraction in the 10 patients at rest and no evidence of clinical ischemia, the L-[1,2,3-13C3] lactate analysis demonstrated that lactate was being released by the myocardium. During atrial pacing, seven patients did not develop clinical symptoms of ischemia, and the chemical lactate analysis showed net lactate extraction. However, tracer analysis demonstrated that there was a significant increase in the lactate released during atrial pacing (from 6.9 +/- 2.3 to 16.2 +/- 10.1 mumol/min) (p less than 0.05). In these seven patients, circulating glucose was the source of 23 +/- 15% of the lactate released at rest, and there was no significant change during pacing. The remaining three patients had mild chest pain and net chemical lactate production during pacing. Lactate release detected by the tracer increased from 5.7 +/- 3.0 mumol/min at rest to 50.9 +/- 16.8 mumol/min during pacing (p less than 0.01). In these patients, the contribution of glucose to lactate production increased significantly during pacing-induced clinical ischemia from 25 +/- 22 to 67 +/- 14% (p less than 0.005). Thus, dual carbon-labeled isotopic experiments are powerful tools for investigating myocardial metabolic pathways.(ABSTRACT TRUNCATED AT 250 WORDS)     

Volume control in peritoneal dialysis patients: role of new dialysis solutions

This paper reviews the most recent clinical data on the volume status of long-term peritoneal dialysis (PD) patients. It appears that many PD patients are volume overloaded, associated with a high prevalence of hypertension and left ventricular hypertrophy. In the presence of the poor results in patients with peritoneal ultrafiltration, the introduction of the polyglucose solution, icodextrin, has ameliorated volume control in some of these patients. In a second part of the review, some of the structural and functional alterations in the peritoneal membrane and the role of glucose degradation products (GDP) in the commonly used dialysates as well as the resulting formation of advanced glycation end products are described. The introduction of low GDP-containing solutions at normal pH has at least in experimental models of PD attenuated the hemodynamic changes observed with the classical solutions. The solutions at normal pH containing either bicarbonate or a mixture of bicarbonate/lactate were clinically associated with less inflow pain.     

Ischemic preconditioning prior to intermittent Pringle maneuver in liver resections

Background/Purpose

Continuous inflow vascular occlusion during liver resections causes less severe ischemia and reperfusion injury (IRI) if it is preceded by ischemic preconditioning (IP) or if intermittent inflow occlusion is used during the resection. No previous clinical trial has studied the effects of adding IP to intermittent inflow occlusion.

Methods

Consecutive patients (n?=?32) with suspicion of malignant liver disease had liver resections (minimum 2 segments) performed with inflow occlusion (intermittent clamping in a manner of 15?min of ischemia and 5?min of reperfusion repetitively; 15/5). Half of the patients were randomized to receive IP (10?min of ischemia and 10?min of reperfusion before parenchymal transection; 10/10). The patients were stratified according to volume of resection and none had chronic liver disease. The patients were followed for 5?days with microdialysis (??D).

Results

All patients completed the study and there were no deaths. No differences were seen between the groups regarding demographics or perioperative parameters (bleeding, duration of ischemia, resection volume, complications, and serum laboratory tests). There were no differences in alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, or prothrombin time (PT)-INR levels, but ??D revealed lower levels of lactate, pyruvate, and glucose in the IP group having major liver resections (analysis of variance; ANOVA). Nitrite and nitrate levels in ??D decreased postoperatively, but no differences were seen between the groups. In one patient an elevated ??D?Cglycerol curve was seen before the diagnosis of a stroke was made.

Conclusions

IP before intermittent vascular occlusion does not reduce the serum parameters used to assess IRI. IP seems to improve aerobic glucose metabolism, as the levels of glucose, pyruvate, and lactate locally in the liver were reduced, compared to controls, in patients having >3 segments resected. ??D may be used to monitor metabolism locally.     

Physiologic hyperinsulinemia stimulates lactate extraction by heart muscle in the conscious dog

The effect of physiologic hyperinsulinemia on the net balance of lactate, glucose, and free fatty acids across the heart was studied in eight normal postabsorptive conscious dogs. After obtaining basal measurements of myocardial substrate balance, arterial plasma insulin was increased from 8 +/- 1 to 68 +/- 14 microU/mL while blood glucose was maintained constant (64 +/- 1 mg/dL) using the hyperinsulinemic euglycemic clamp. Myocardial lactate uptake increased nearly fourfold, from 5.8 +/- 1.8 to 22.4 +/- 2.9 mumol/min (P less than .005). Despite a small increase in arterial lactate concentration from 0.46 +/- 0.08 to 0.79 +/- 0.11 mmol/L (P less than .02), the lactate extraction fraction increased from 23% +/- 7% to 54% +/- 2% (P less than .001) indicating an increased efficiency of lactate extraction. Euglycemic hyperinsulinemia led to a comparable increase in myocardial glucose uptake (6.7 +/- 2.3 to 18.2 +/- 3.7 mumol/min, P less than .05). Arterial free fatty acid concentrations fell from 1.06 +/- 0.13 to 0.35 +/- 0.06 mmol/L (P less than .001) with a concomitant decline in the myocardial uptake of free fatty acids from 18.5 +/- 5.3 to 5.8 +/- 2.9 mumol/min (P less than .05). These results indicate that physiologic hyperinsulinemia increases lactate as well as glucose uptake in normal heart muscle.     

A wire-based dual-analyte sensor for glucose and lactate: in vitro and in vivo evaluation

Continuous measurement of lactate is potentially useful for detecting physical exhaustion and for monitoring critical care conditions characterized by hypoperfusion, such as heart failure. In some conditions, it may be desirable to monitor more than one metabolic parameter concurrently. For this reason, we designed and fabricated twisted wire-based microelectrodes that can measure both lactate and glucose. These dual-analyte sensors were characterized in vitro by measuring their response to the analyte of interest and to assess whether they were susceptible to interference from the other analyte. When measured in stirred aqueous buffer, lactate sensors detected a very small amount of crosstalk from glucose in vitro, although this signal was less than 3% of the response to lactate. Glucose sensors did not detect crosstalk from lactate. Sensors were implanted subcutaneously in rats and tested during infusions of lactate and glucose. Each sensing electrode responded rapidly to changes in its analyte concentration, and there was no evidence of in vivo crosstalk. This study constitutes proof of the concept that oxidase-based, amperometric wire microsensors can detect changes in glucose and lactate during subcutaneous implantation in rats.     

Lactate generation following glucose ingestion: relation to obesity, carbohydrate tolerance and insulin sensitivity

To examine early metabolic abnormalities in obesity prior to the development of carbohydrate intolerance, we studied 14 lean and 37 obese subjects with normal glucose tolerance. All subjects underwent a standard 75 g oral glucose tolerance test (OGTT) with the addition of lactate measurement. As expected, there was a positive relationship between basal insulin and body mass index (BMI kg/m2;r=0.64, P less than 0.0001). In addition, even though the subjects had normal glucose tolerance, both basal glucose and sum of glucose during OGTT showed significant positive associations with obesity. Basal lactate correlated significantly and positively with obesity (r = 0.29, P = 0.04). When incremental areas during OGTT were examined, glucose area during OGTT was positively associated with BMI and insulin area was positively associated with both BMI and sum of glucose. Conversely, the incremental area of lactate decreased as BMI increased (r = -0.41, P = 0.003), despite the increasing glucose area. The results indicate that even prior to frank carbohydrate intolerance, progressive changes in basal levels of glucose, insulin, and lactate, as well as sum of glucose, accompany the expansion of adipose mass in obesity. Two different aspects of lactate metabolism have been examined in obesity. First, the association of increased basal lactate levels with increased obesity may reflect increased lactate production from enlarged adipocytes and an increased fat mass. Secondly, the inverse association between acute lactate generation following glucose ingestion and obesity, despite the increased sum of glucose in obese subjects, may reflect a decreased ability of adipose and/or extra-adipose tissues to convert glucose to lactate due to insulin resistance.     

Epinephrine-induced increase in glucose turnover is diminished during sepsis

The responsiveness of septic rats to epinephrine-induced alterations in carbohydrate metabolism was studied. Nonlethal sepsis was produced by subcutaneous injections of live Escherichia coli over 18 hours in conscious catheterized rats. Glucose kinetics were assessed by IV infusion of [6-3H]-glucose. After two hours of tracer infusion, blood samples were taken for basal values. Thereafter, epinephrine was infused at 0, 0.05, 0.2, or 1.0 microgram/min/kg for an additional four hours. Compared with nonseptic rats, septic animals had increased basal values for glucose rate of appearance (Ra, 63%), glucose clearance (86%), and plasma lactate concentration (133%). Infusion of epinephrine resulted in dose-dependent increases in glucose Ra, as well as plasma glucose and lactate concentrations, and decreases in glucose clearance and muscle glycogen content. At each dose of epinephrine, the increases in response from basal of plasma glucose and glucose Ra in septic rats were 50% or less of that observed in nonseptic animals. There were no differences between septic and nonseptic rats in plasma lactate and glucose clearance responses from basal or in circulating levels of catecholamines achieved during the epinephrine infusion. The present results indicate that septic rats are less responsive than control animals to epinephrine-induced increases in glucose turnover.     

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??Abstract??Type 2 Diabetes Mellitus (T2DM) is exacting a high level of patient suffering and social cost worldwide.The past several decades witnessed intensive investigations on new lines of therapeutics regimen for T2DM.Among them??there is a new class of oral anti-hyperglycemic agent called dipeptidyl peptidase-4 inhibitor which includes Sitagliptin??Saxagliptin??Vildagliptin??Alogliptin and Linagliptin.In the current review??we are endeavored to provide a comprehensive overview on clinical and translational evidence of DPP-4 inhibitor action and the safety profile.Particularly??we are interested in reviewing evidence on the underlying mechanism for blood glucose control??micro and macro vascular benefits??clinical data which involves Sitagliptin as monotherapy and combined therapy and beneficial effects beyond blood glucose control.The data currently available strongly suggest DPP-4 inhibitor is an effective oral anti-hyperglycemic agent with optimal safety profile.Thus??it has been recommended by numerous high-impact guidelines as a major second-line (ADA??CDS) or even optional first-line for elderly T2DM patients (IDF).     

Skeletal muscle is a major site of lactate uptake and release during hyperinsulinemia.

During conditions of increased glucose disposal, plasma lactate concentrations increase due to an increase in plasma lactate appearance. The tissue sites of the elevated lactate production are controversial. Although skeletal muscle would be a logical source of this lactate, studies using the limb net balance technique have failed to demonstrate a major change in net lactate output when plasma glucose disposal is increased. Because the limb balance technique underestimates production of a substrate when the limb not only produces but also consumes that substrate, we infused 3-14C-lactate basally and during a hyperinsulinemic euglycemic clamp in seven normal volunteers to determine plasma lactate appearance, forearm lactate fractional extraction, and forearm lactate uptake and release. After 3 hours of hyperinsulinemia, glucose and lactate turnovers increased from basal values of 11.8 +/- 0.13 and 12.2 +/- 0.59 to 32.6 +/- 3.4 and 16.5 +/- 1.07 mumol/(min.kg), accompanied by an increase in plasma lactate from 0.88 +/- 0.07 to 1.16 +/- 0.09 mmol/L (P less than .05). Forearm lactate extraction increased from 27% +/- 2% to 38% +/- 2% (P less than .001), resulting in an increase in forearm lactate uptake from 0.65 +/- 0.09 to 1.18 +/- 0.08 mumol/(min.100 mL tissue) (P less than .001). Although forearm lactate net output decreased during hyperinsulinemia, forearm lactate production increased from 1.04 +/- 0.12 basally to 1.69 +/- 0.13 mumol/(min.100 mL). When forearm data was extrapolated to whole body, muscle could account for 41% +/- 4% of systemic lactate appearance basally and 45% +/- 4% during hyperinsulinemia.(ABSTRACT TRUNCATED AT 250 WORDS)