Drug-protein binding kinetics in patients with Type I diabetes

Summary Sera from 17 patients with Type I diabetes and 19 healthy volunteers have been examined to evaluate whether the kinetics of the binding of drugs to Site II of serum albumin is altered in diabetes. Stopped-flow measurements showed that the association velocity and the affinity constants of the fluorescent marker dansylsarcosine were significantly lower in diabetics (160 s^–1 and 2.0 × 10⁵ l·mol^–1) than in non-diabetics (196s^–1 and 4.0 × 10⁵ l·mol^–1). The dissociation velocity was not different [20.3 s^–1 vs. 19.4 s^–1]. Although patients with a reduced albumin concentration were excluded the diabetics had significantly lower concentrations than the healthy volunteers. There was a significant correlation between decreased glycosylation of albumin and increased association velocity. The dissociation velocity constants were correlated with the molar concentration ratio of free fatty acids/human serum albumin. Thus, the extent of glycosylation and the amount of fatty acids bound per mole albumin can both affect the kinetics of drug binding to Site II. The lower affinity in patients with Type I diabetes is due to the increased in the glycoalbumin concentration.     

Pharmacokinetics of prednisolone in children with the nephrotic syndrome

The aim of this study was to establish whether the criteria for the clinical effectiveness of steroids are correlated with the pharmacokinetics of prednisolone in children treated with prednisone during an attack of idiopathic nephrotic syndrome (INS). Thirteen patients with nephrosis were included. Prednisolone, prednisone and cortisol levels were measured using a specific high-performance liquid chromatography assay after an oral dose of 1 mg/kg body weight of prednisone taken at the onset of the disease. All the pharmacokinetic parameters, including the conversion of prednisone to prednisolone were similar to the data already published in children with INS. No correlation was found between the values of pharmacokinetic parameters and criteria of clinical effectiveness. Hypo-albuminaemia was significantly correlated with the area under the plasma-concentration curve but not with the elimination half-life of prednisolone. Moreover, the prednisolone elimination half-life correlated with the urinary exretion of 17-hydroxycorticosteroids achieved in the first 6h. The present study suggests that routine measurements of prednisolone kinetics do not help when assessing the treatment of children with INS.     

Amadori糖化白蛋白对牛视网膜血管二酯酰甘油--蛋白激酶C级联的影响

目的 :探讨Amadori糖化血清白蛋白对牛视网膜血管二酯酰甘油 (DAG)———蛋白激酶C(PKC)信号级联的影响及d-α-生育酚的干预作用。方法 :体外制备的Amadori糖化的牛血清白蛋白 (AGSA)分别在生理浓度葡萄糖 (5 .5mmol/L)和高浓度葡萄糖 (2 0mmol/L)培养液中作用于新鲜牛视网膜血管。采用薄层层析和放射自显影法测定DAG含量和PKC活性 ;并检测d -α-生育酚预处理后DAG、PKC改变。结果 :在生理葡萄糖浓度下 ,牛视网膜血管暴露于AGSA2 4h或 72h后细胞内DAG含量、PKC活性均较对照组显著增加 ,当AGSA和高葡萄糖同时作用于牛视网膜血管时 ,DAG -PKC级联显著激活 ,分别为正常葡萄糖组的 3.4 7倍和 4 .5 4倍 ;在正常血清培养液中 ,与 5 .5mmol/L的葡萄糖相比 ,2 0mmol/L高糖在 2 4h时并不刺激DAG含量增加 (P >0 .0 5 ) ,而 72h时则较对照组增加 4 5 % ,PKC活性较对照增加 5 6 % ,而d -α -生育酚可逆转上述生化改变。结论 :Amadori糖化血清白蛋白可在生理葡萄糖浓度下刺激DAG -PKC途径活化 ,从而影响血管一系列生理功能 ,而d -α-生育酚对血管生化改变有保护作用。     

Labeling efficacy of superparamagnetic iron oxide nanoparticles to human neural stem cells: comparison of ferumoxides, monocrystalline iron oxide, cross-linked iron oxide (CLIO)-NH2 and tat-CLIO.

OBJECTIVE: We wanted to compare the human neural stem cell (hNSC) labeling efficacy of different superparamagnetic iron oxide nanoparticles (SPIONs), namely, ferumoxides, monocrystalline iron oxide (MION), cross-linked iron oxide (CLIO)-NH(2) and tat-CLIO. MATERIALS AND METHODS: The hNSCs (5 x 10(5) HB1F3 cells/ml) were incubated for 24 hr in cell culture media that contained 25 microg/ml of ferumoxides, MION or CLIO-NH(2), and with or without poly-L-lysine (PLL) and tat-CLIO. The cellular iron uptake was analyzed qualitatively with using a light microscope and this was quantified via atomic absorption spectrophotometry. The visibility of the labeled cells was assessed with MR imaging. RESULTS: The incorporation of SPIONs into the hNSCs did not affect the cellular proliferations and viabilities. The hNSCs labeled with tat-CLIO showed the longest retention, up to 72 hr, and they contained 2.15+/-0.3 pg iron/cell, which are 59 fold, 430 fold and six fold more incorporated iron than that of the hNSCs labeled with ferumoxides, MION or CLIO-NH(2), respectively. However, when PLL was added, the incorporation of ferumoxides, MION or CLIO-NH(2) into the hNSCs was comparable to that of tat-CLIO. CONCLUSION: For MR imaging, hNSCs can be efficiently labeled with tat-CLIO alone or with a combination of ferumoxides, MION, CLIO-NH(2) and the transfection agent PLL.     

Preparation and evaluation of temperature sensitive liposomes containing adriamycin and cytarabine

Temperature sensitive liposomes (TSL) containing adriamycin (ADM) and cytarabine (Ara-C) were prepared. ADM and Ara-C were selected as model compounds of amphiphilic and hydrophilic drug, respectively. Encapsulation efficiency of ADM entrapped into TSL was about twice greater than that of Ara-C. It might be due to different polarity of the drugs. Lipid compositions of TSL had no effect on the encapsulation efficiency of drugs. Thermal behavior of TSL using a differential scanning calorimetry (DSC) was also investigated. Phase transition temperature (T_c) of TSL was dependent on the lipid compositions of TSL.ADM broadened thermogram of TSL but Ara-C did not. However, T_c of TSL was not changed by any drug. Release rate of drugs was highly dependent on temperature. The release profile of ADM was similar to that of Ara-C. The maximum release rate of drugs from TSL was occurred at the near T_c and observed at 39–41°C for DPPC (Dipalmitoylphosphatidylcholine) only, 52–54°C for DSPC (Distearoylphosphatidylcholine) only, 41–43°C for DPPC and DSPC (3∶1), and 43–45°C for DPPC and DSPC (1∶1), respectively. Effect of human serum albumin (HSA) on the release rate of ADM was investigated. HSA had no significant effect on the release of ADM below T_c. However, ADM release from TSL was increased at the near and above T_c. The HSA-induced leakage of drug may result from the interaction of liposomal constituents with HSA structure at the near T_c. From the fact that the release profiles of ADM from freshly prepared TSL and stored TSL for 1 week at 4°C was not changed, the TSL was considered to be stable for at least 1 week at 4°C. Based on these findings, TSL may be useful to deliver drugs to preheated target sites due to its thermal behaviors.     

血清腹水白蛋白梯度与门脉高压性腹水的关系研究

目的研究血清腹水白蛋白梯度(SAAG)与门脉高压性腹水的关系.方法研究47例肝硬化腹水患者(均有门脉高压),比较不同Child分级的患者其血清腹水白蛋白梯度(SAAG)有无差异,比较不同食管静脉曲张程度的患者其SAAG有无差异,研究SAAG与门脉压力升高程度的关系.结果三组不同Child分级的患者其血清腹水白蛋白梯度(SAAG)无差异(P＞0.05).SAAG与血清白蛋白相关(r=0.478,P=0.001),SAAG与血清总胆红素及凝血酶原时间无关(均P＞0.05).三组不同食管静脉曲张程度的患者其SAAG无差异(P＞0.05).SAAG与门脉压力升高的程度无关(r=-0.140,P=0.649).结论SAAG并不能完全反映食管静脉曲张程度及门脉压力升高的程度,SAAG与肝功能受损程度无关.     

中老年普外非急诊入院患者营养状况调查(附169例分析)

本文报道了169例中、老年普外科非急诊入院患者营养状况调查,多参数指标包括人体测量和实验室检查。结果显示40％患者有不同程度的营养不良。120例(71％)患者在8项调查指标中,有2～6项异常。按消化道和非消化道疾病进行比较,体重身高指数(WT/HT)、上臂周径(AMC)在中年组有显著差异(P<0.05)。     

磁处理酒对大鼠糖脂蛋白质代谢的影响

12只大白鼠空腹灌注大剂量磁处理酒(实验组1、2); 另外18只大白鼠同等条件下灌注非磁处理酒(对照组1、2)及自来水(空白组),对比研究表明,血清胆固醇及清蛋白含量变化无显著差异(P>0.05),而血清葡萄糖含量实验组低于对照组,差异显著(P<0.05),提示,大剂量非磁处理酒可使血糖升高,而磁处理酒对血糖含量无显著影响.     

顺铂白蛋白微球肝动脉栓塞后在体内的分布

用生物降解材料牛血清白蛋白制得顺铂微球，采用肝动脉插管术对新西兰兔实施肝动脉栓塞，以常规注射剂为照，研究药物体内分布。结果：肝组织顺铂量在不同时间均显著高于注射剂对照组（Ｐ＜０．０１），栓塞１４ｄ肝中顺铂量仍为对照组的３．５倍；肾脏、脾、肺、心、脑等组织的药物量均低于对照组。提示顺铂微球肝动脉栓塞能显著提高靶区的药物浓度，同时减少在其他组织中的分布，并可降低药物的肾毒性及神经毒性反应。     

青中年人群微量白蛋白尿患病率与心血管疾病危险因素的关系

目的　探讨微量白蛋白尿患病率与心血管疾病危险因素的关系。方法　选择 775例 (男 32 6例 ,女 4 4 9例 )年龄 2 0～ 5 0岁的社区人群 ,测定其体重指数 (BMI)、血压、空腹血糖、血脂谱 ;收集晨尿检测尿白蛋白、尿肌酐浓度 ,并计算尿白蛋白 /尿肌酐的比率。根据有无高血糖、高血压或高三酰甘油 /低高密度脂蛋白胆固醇 (高TG/低HDL C)血症分为 4组 ,即正常组 (A组 )、1种代谢紊乱组 (B组 )、2种代谢紊乱组 (C组 )及代谢综合征组 (D组 ) ,评价微量白蛋白尿与代谢紊乱的关系。结果　①糖尿病患者微量白蛋白尿的患病率为 2 2 .2 % ,显著高于正常血糖者 (5 .2 % ,P =0 .0 0 2 ) ;高TG/低HDL C血症者微量白蛋白尿的患病率为 8.3% ,显著高于正常血脂者 (4.0 % ,P =0 .0 12 ) ;高血压患者与正常血压者的差异无显著性。②随代谢紊乱加重 ,尿白蛋白浓度显著升高 (协方差分析 ,P <0 .0 1) ,微量白蛋白尿患病率升高 (趋势分析 ,P =0 .0 0 3)。③ 4组间尿肌酐浓度、尿白蛋白 /尿肌酐的差异无显著性。结论　①糖尿病、高TG/低HDL血症人群的微量白蛋白尿的发病率显著升高。②随代谢紊乱加重 ,微量白蛋白尿患病率亦升高