Ex Vivo Evaluation in Normal Dogs of Insulin Released by a Bioartificial Pancreas Containing Isolated Rat Islets of Langerhans

In bioartificial pancreatic systems, isolated islets of Langerhans are protected against immune rejection by an artificial membrane, permeable to glucose and insulin, but not to immunoglobulins and lymphocytes. Some of these devices, referred to as vascular systems, are set up to be connected to a vascular site in the recipient, with blood circulating in contact with one side of the membrane, and the islets on the other side. Such a bioartificial pancreas, containing isolated rat islets of Langerhans, was connected to an arteriovenous shunt of a normal anesthetized dog. The aim of this experiment was to investigate the kinetics of the insulin secretory response of the system to a glucose load. Glucose was infused upstream of the system, increasing the glucose concentration inside the bioartificial pancreas from 7 to 14 mmol/l, without altering the blood glucose concentration of the dog. Insulin concentration was determined simultaneously upstream and downstream of the bioartificial pancreas. Insulin production was calculated by multiplying the difference between these values by the blood flow rate. Blood flow rate (Q) was estimated from the change in the glucose concentration produced by the glucose infusion using a mass transfer analysis derived from Fick's principle. Insulin production increased from 20 +/- 8 to 59 +/- 15 microU/100 islets/min within 15 min following the beginning of the stimulation (n = 6, p less than 0.05). Five min after the end of the stimulation, insulin production decreased from 75 +/- 13 to 50 +/- 9 microU/100 islets/min (p less than 0.05) to reach the basal level (21 +/- 3 microU/100 islets/min) 30 min after the end of the glucose stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Why study transport of peptides and proteins at the neurovascular interface

The blood–brain barrier (BBB) is an immense neurovascular interface. In neurodegenerative, ischemic, and traumatic disorders of the central nervous system (CNS), the BBB may hinder the delivery of many therapeutic peptides and proteins to the brain and spinal cord. Fortunately, the mistaken dogma that peptides and proteins do not cross the BBB has been corrected during the past two decades by the accumulating evidence that peptides and proteins in the periphery exert potent effects in the CNS. Not only can peptides and proteins serve as carriers for selective therapeutic agents, but they themselves may directly cross the BBB after delivery into the bloodstream. Their passage may be mediated by simple diffusion or specific transport, both of which can be affected by interactions in the blood compartment (outside the BBB) and within the endothelial cells (at the BBB level). Although the majority of current delivery strategies focuses on modification of the molecule to be delivered, understanding the mechanisms of transport will eventually facilitate regulation of the BBB directly. We review the different aspects of interactions and discuss recent advances in the cell biology of peptide/protein transport across the BBB. Better understanding of the nature and regulation of the transport systems at the BBB will provide a new direction to enhance the interactions of peripheral peptides and proteins with the CNS.     

高脂血症患者血小板体积及有关参数的研究

本文报道242例高脂血症患者血小板(PLT)、平均血小板数(MPLT)及平均血小板体积(MPV)等参数的测定结果,其中高胆固醇并高甘油三酯患者,PLT、MPLT及巨大血小板比例(Macro-PLT)高于正常,MPV正常;而单纯高胆固醇或高甘油三酯患者,上述指标与正常人无显著性差异。提示高胆固醇并高甘油三酯患者,存在血小板生成动力学异常,其血小板的破坏增加,生成率加速、但处于一种高水平的动态平衡之中。这可能是高脂血症出现高凝状态的原因之一。同时表明此类患者使用抗血小板疗法具有一定的合理性和必要性。     

对数期继代对南方红豆杉细胞培养动力学的影响

目的 解决南方红豆杉细胞生长缓慢及代谢水平低下的问题。方法 对对数期(20d)和静止期(30d)的红豆杉细胞分别进行继代，在整个生长周期中测定了培养基中的碳源、氮源、磷酸盐的变化并分析了红豆杉细胞生长及紫杉醇的合成情况。结果 对数期继代细胞吸收碳源和硝态氮早于静止期继代的细胞，且前者的比生长速度是后者的1．5倍，紫杉醇含量提高了近4倍。结论 对数期继代有利于生物量的积累及紫杉醇的合成。     

Lack of effect of cimetidine on cigarette smoking

Summary The efficacy of cimetidine as a treatment that could reduce smoking in heavily dependent smokers has been determined. In a randomised, double-blind, double-crossover experiment, 43 heavy smokers were divided into two groups, one receiving cimetidine 400 mg orally three times a day, and the other receiving placebo for two weeks followed by the alternative treatment (placebo or cimetidine).No significant difference in the mean alveolar carbon monoxide, nicotine or cotinine levels was found between the two treatment groups compared to baseline. Since the alveolar carbon monoxide level reflects the intensity of smoking behaviour, the results suggest that no change in smoking behaviour occurred in the subjects.Contrary to our previous findings that cimetidine decreased the total body clearance of nicotine by 30% in a population of non-smokers, in the heavily dependent smokers, cimetidine did not appear to alter nicotine elimination. One possible explanation for the discrepancy is that tobacco smoking is known to induce nicotine metabolism and the induction might have offset any effect of cimetidine on nicotine elimination.Cimetidine does not appear to be a useful treatment leading to a reduction or cessation of cigarette smoking.     

Effects of glucagon-like peptide 1 (7–36 amide) on whole-body protein metabolism in healthy man

The incretin glucagon-like peptide 1 (GLP-1) shows glucose-dependent insulinotropic activity and may exert anabolic effects. Whole-body protein metabolism was assessed by measuring [1-¹³C]-leucine kinetics in 13 healthy volunteers during hyperglycaemic clamping with or without pancreatic clamping (somatostatin infusion) in order to differentiate between insulin-mediated and direct GLP-1 effects. During intact pancreatic secretion leucine flux and leucine oxidation rate as parameters of whole-body protein breakdown decreased markedly after 180 min of synthetic GLP-1 infusion (GLP-1 vs. placebo: P  < 0.003). Indirect calorimetry showed an increase in energy expenditure and CO₂ production during GLP-1 administration ( P  < 0.0005). Plasma insulin increased after 3 h of GLP-1 infusion to 1486 ± 145 pmol L⁻¹ vs. 185 ± 12 pmol L⁻¹ for saline ( P  < 0.0001). When plasma insulin levels were kept constant (GLP-1 vs. saline, NS) during pancreatic clamping, GLP-1 effects on both protein metabolism and energy expenditure were abolished. Thus, GLP-1 infusion in man exerts protein anticatabolic and thermic effects, which are mediated by GLP-1-induced stimulation of insulin secretion.     

Population kinetics of gentamicin in neonates

A population kinetic analysis was carried out on sparse plasma gentamicin (GE) concentration data from 469 neonates obtained as part of a routine therapeutic drug monitoring (TDM) programme in the hospital neonatology unit.The best predictors of the kinetic parameters of the monoexponential model, volume of distribution (Vd) and clearance (CL), were the weight (WT) and gestational age (GA). Vd of the neonates was only related to WT, whereas the half-life was only related to the GA.     

Expression and kinetic characteristics of muscle type acetylcholine receptors in Xenopus oocytes

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Adsorption of Salmon Calcitonin to PLGA Microspheres

Purpose. The interaction of salmon calcitonin (sCT) and poly (d,l-lactide-co-glycolide) was detected during preparation and evaluation of microspheres. The purpose of this study was to quantitate the extent and nature of the interaction. Methods. Blank microspheres were prepared by an aqueous emulsification solvent extraction technique. Adsorption studies were carried out at six concentrations of sCT and three concentrations of microspheres. Adsorption isotherms were constructed using the Langmuir and Freundlich treatments. Results. Adsorption at 1 mg/ml sCT concentration resulted in almost complete depletion of the peptide from the adsorption medium with the time to reach maximum adsorption decreasing with increasing microsphere concentration. At sCT concentrations below 100 µg/ml, a true equilibrium occurred in 1 hour or less while at higher concentrations (up to 350 µg/ml), a transient equilibrium was reached in 1 to 2 hours, followed by further adsorption of the peptide. The adsorption followed the Langmuir isotherm at concentrations below 200 µg/ml, indicating formation of a monolayer. Multilayer interaction, described by the Freundlich isotherm, occurred at higher concentrations and resulted in complete depletion of sCT from the adsorption medium. The affinity constant during monolayer formation was 0.09 and the plateau surface concentration was 5.1 µg/mg. The multilayer peptide-peptide adsorption showed a lower affinity (0.025) but higher capacity (24 µg/mg) than the monolayer peptide-polymer adsorption. Conclusions. The results show that poly (d,l-lactide-co-glycolide) microspheres have a high adsorption capacity for sCT which must be considered in formulating a controlled delivery product of this peptide.     

HMME在不同溶液中光漂白反应动力学规律

目的 分析国产光敏剂血卟啉单甲醚（HMME）在不同溶液中光漂白反应动力学规律，加深对光漂白反应复杂反应过程的理解，并为HMME-PDT治疗微血管病变的数学建模研究提供实验依据和参数。 方法 根据光化学反应动力学原理，从理论上推导出在单纯溶液和复杂溶液（含可被光氧化的底物）中，单态氧介导的光漂白反应动力学方程，通过对实验测定的漂白数据（不同时间点的HMME浓度）进行拟合，进一步验证理论推导出光漂白反应动力学方程。 结果 HMME在单一溶液体系（PBS、DMSO）中的光漂白符合1级反应动力学过程，在含底物的复杂体系（白蛋白缓冲液、细胞悬液）中符合2级反应动力学过程。 结论 HMME在不同溶液体系中的光漂白遵循不同的反应动力学规律。根据化学反应动力学原理进行光漂白等复杂光化学反应过程的数学模拟是可行的，并有利于对复杂光化学反应过程的深入理解。