The metabolic and hormonal response to acute normoglycaemia in type 1 (insulin-dependent) diabetes: Studies with a glucose controlled insulin infusion system (artificial endocrine pancreas)

Summary Twelve insulin deficient Type 1 (insulin-dependent) diabetic subjects were studied over an 11 1/2 h period during both subcutaneous insulin therapy and closed loop insulin delivery, using a glucose controlled insulin infusion system (Biostator) programmed to maintain normoglycaemia. Results were compared with those from 21 age and weight-matched normal subjects. Using the Biostator, normoglycaemia was achieved in all diabetic subjects within 3.5 h and normal profiles maintained thereafter. Blood metabolite and hormone values were evaluated during the subsequent 8 h normoglycaemic period. Subcutaneous therapy resulted in abnormal glucose levels throughout the study period (mean 8 h value 8.3±0.7 compared with 5.6±0.3 mmol/l on feedback control and 5.5.±0.1 mmol/l in normal subjects). The mean value of lactate and pyruvate over the final 8 h period was 25% higher in diabetic patients than in normal subjects with no difference between the two insulin treatments (blood lactate: 0.94±0.04 on subcutaneous insulin, 0.91±0.04 on feedback control and 0.74±0.03 mmol/l in control subjects). The pre-prandial peaks of blood glycerol and plasma non-esterified fatty acids were significantly decreased or absent during both feedback control and subcutaneous therapy in comparison with the normal subjects, whereas after the midday and evening meals, total ketone body levels were significantly higher in the diabetic patients. Peripheral serum free insulin levels were two-to fourfold greater in the diabetic than in the normal subjects. There were no significant differences between levels in diabetic patients receiving subcutaneous insulin or on the Biostator. Glucose turnover (1600–1800 h) was normal on feedback control (1.41±0.20 versus 1.55±0.18 mg · kg^-1 · min^-1 in the normal subjects) but was significantly decreased during subcutaneous insulin (1.04±0.09 mg · kg^-1 · min^-1). There was, in addition, a decrease in glucose recycling during both subcutaneous insulin therapy and feedback control in the diabetic subjects. These data suggest that although fine control of glucose metabolism both in terms of circulating concentrations and rates of production can be achieved by feedback-control, insulin infusion by the peripheral route is associated with significant metabolic abnormalities, at least in the short term. Longer term studies and examination of portal insulin delivery seem warranted.     

Use of the molecular adsorbent recycling system in the treatment of postoperative hepatic failure and septic multiple organ dysfunction--preliminary results.

PURPOSE OF THE STUDY: Molecular adsorbent recycling system (MARS) has been applied successfully in patients with a variety of liver diseases. However, preliminary results in patients with multiple organ failure (MOF) and sepsis were disappointing, possibly because the number of applied MARS cycles was too low. To determine potential effects of prolonged MARS treatment in patients with postsurgical MOF we evaluated five postoperative patients with acute liver failure and septic multiple organ dysfunction in a retrospective observational study. METHODS: MARS cycles (13.4+/-1.9) were applied during an average time period of 17.2+/-5.2 days. Fresh frozen plasma, thrombocyte units and blood units were transfused to maintain pre-MARS Quick values and thrombocyte counts, and to keep the hemoglobin concentration above 8 g/dl. MAIN FINDINGS: Plasma bilirubin concentrations declined significantly during treatment. In contrast, ammonia concentration remained constant, and parameters of the clotting system (Quick value) did not get better or even worsened (partial thromboplastin time) despite significantly increasing the substitution frequency of coagulatory factors. Due to poor clotting, we observed significant bleeding complications during MARS therapy causing a simultaneous rise in the number of transfused blood units. All patients demonstrated persistent, severe abdominal infection during MARS therapy. After discontinuing MARS treatment because of insufficient efficiency, all patients died of progressive septic organ malfunction. CONCLUSION: Our preliminary findings do not support use of MARS in patients with postoperative hepatic failure and progressive septic multiple organ dysfunction, particularly if the septic focus cannot be eliminated. If MARS is still applied, special attention should be paid to simultaneous clotting disorders and bleeding complications.     

ROTUNDA3 function in plant development by phosphatase 2A-mediated regulation of auxin transporter recycling

The shaping of organs in plants depends on the intercellular flow of the phytohormone auxin, of which the directional signaling is determined by the polar subcellular localization of PIN-FORMED (PIN) auxin transport proteins. Phosphorylation dynamics of PIN proteins are affected by the protein phosphatase 2A (PP2A) and the PINOID kinase, which act antagonistically to mediate their apical–basal polar delivery. Here, we identified the ROTUNDA3 (RON3) protein as a regulator of the PP2A phosphatase activity in Arabidopsis thaliana. The RON3 gene was map-based cloned starting from the ron3-1 leaf mutant and found to be a unique, plant-specific gene coding for a protein with high and dispersed proline content. The ron3-1 and ron3-2 mutant phenotypes [i.e., reduced apical dominance, primary root length, lateral root emergence, and growth; increased ectopic stages II, IV, and V lateral root primordia; decreased auxin maxima in indole-3-acetic acid (IAA)-treated root apical meristems; hypergravitropic root growth and response; increased IAA levels in shoot apices; and reduced auxin accumulation in root meristems] support a role for RON3 in auxin biology. The affinity-purified PP2A complex with RON3 as bait suggested that RON3 might act in PIN transporter trafficking. Indeed, pharmacological interference with vesicle trafficking processes revealed that single ron3-2 and double ron3-2 rcn1 mutants have altered PIN polarity and endocytosis in specific cells. Our data indicate that RON3 contributes to auxin-mediated development by playing a role in PIN recycling and polarity establishment through regulation of the PP2A complex activity.Organ growth is determined by cell numbers produced by meristems and by cell expansion to reach final volume. Plant hormones steer the extent and timing of growth and mediate signals of various types that are transmitted within the cell, between cells, or at a long distance within the plant. The phytohormone auxin is a major regulator of cell division and expansion during plant growth and development. The molecular mechanisms by which auxin controls these essential cellular responses are roughly understood thanks to the recent progress in the identification of auxin receptors and components of auxin signaling, transport, and metabolism (1). Auxin gradients between the cells are generated and maintained by intercellular auxin transport mediated by efflux carriers from the PIN-FORMED (PIN) family (2). PIN proteins contain transmembrane domains and continuously cycle between the basal (rootward) and apical (shootward) plasma membranes and endosomes, allowing rapid and dynamic changes in the PIN localization (3). The sorting of PIN proteins into the apical or basal trafficking pathway depends on the PIN phosphorylation status, which is controlled by the PINOID (PID) protein kinase and phosphatase 2A (PP2A) (4, 5), a heterotrimeric complex consisting of a C-catalytic subunit together with A- and B-regulatory subunits. One of the A-subunit isoforms, ROOTS CURL IN NAPHTHYLPHTHALAMIC ACID1 (RCN1), acts as a key positive regulator of the PP2A activity in seedlings. The rcn1 mutant that lost part of the PP2A activity displays abnormalities related to defective auxin transport, such as altered gravity response and lateral root growth (6, 7).In an ethyl methanesulfonate-induced collection of Arabidopsis thaliana leaf mutants (8), we identified ROTUNDA3 (RON3) as a proline-rich, plant-specific single-copy gene with a function in auxin-related processes in all organs throughout the plant’s lifecycle. Affinity purification of the PP2A complex with RON3 as bait, and genetic and cell biology analyses support the hypothesis that RON3 affects the cellular dynamics of PIN proteins through interference with the PP2A activity.     

中药资源化学研究与资源循环利用途径及目标任务

中药资源化学研究目的是促进中药及天然药物资源的有效生产、合理利用和产业的提质增效。中医药事业的发展有赖于中药资源的高效利用和可持续发展,有赖于药用生物资源可利用物质、潜在利用价值的发现技术和手段,有赖于中药资源类群中资源性化学成分的多途径、多层次、精细化利用和产业链的有效延伸,从而实现其循环利用的资源化学研究和资源产业健康发展的目的。该文基于中药资源化学的研究思路,将围绕5个方面对中药资源化学与中药资源循环利用途径及目标任务进行论述:立足于资源稀缺性原则,寻找发现或人工生产可替代性资源,保护珍稀濒危物种及自然资源;立足于资源多宜性原则,通过系统性和精细化开发利用,实现资源价值增值和价值补偿,提升资源利用效率;立足于资源节约和环境友好原则,减少资源消耗,促进循环利用,降低资源成本,提升资源利用效益;基于化害为利的资源化策略,研究揭示外来入侵生物资源的药用及多途径利用价值并加以有效利用,转化和丰富我国药物资源体系;基于化学成分结构修饰策略,发掘和提升中药资源性化学物质的利用价值和潜在利用价值。以期为提升中药资源利用效率,推进中药资源循环经济产业发展,从根本上转变中药农业和中药工业的经济增长方式提供参考和借鉴。     

某电子废弃物处理区居民健康状况调查

[目的]了解电子废弃物处理区主要处理工艺类型与污染状况,探讨电子废弃物拆解产生的污染对拆解区居民及拆解从业者可能的健康损害。[方法]采用普查方法,选择浙江省某镇3个集中从事电子废弃物回收处理的自然村作为电子废弃物拆解A区,另选择1个从事电子废弃物拆解较少、经济状况可比的自然村作为B区,对756户共1432人进行健康问卷调查。[结果]A区电子废弃物处理厂主要采取手工拆解工艺,对电路板、电线电缆等废弃物进行处理。A区与B区比较,15岁以上人群的疾病患病状况差异无统计学意义,而A区15岁以下儿童的贫血患病率明显较高。与无拆解史人群比较,有拆解工作史人群的高血压和冠心病患病率明显较高;而呼吸系统、神经系统和皮肤类疾病以及其他慢性疾病患病差异无统计学意义。[结论]电子废弃物污染对当地儿童健康有较大影响,对成人居民与从业者健康可能存在潜在危害。     

考虑再生单元水质约束的多杂质再生循环水系统优化

废水分类分级处理的再生模式是废水再生的方向,建立和完善该模式的多杂质再生循环水系统的模型具有重要意义。本文从工业实际情况出发,在现有数学模型的基础上,考虑了再生单元进口质量浓度的上下限约束,使得数学模型更加完善。通过实例研究,显示了增加该约束的必要性,并分析了该约束对水网络结构和系统新鲜水目标值的影响。     

Leaching and VOC Emission Tests of Polymer Composites Produced from Post-Consumer Waste in Terms of Application in the Construction Sector

One of the existing priorities of the European Union is to search for rational waste management and to keep such waste in the economic cycle, while meeting the highest safety requirements. The paper presents the results of environmental tests of composites based on the polyethylene (rPE) and polypropylene (rPP) matrix and reinforced with cellulose fibres (newsprint, NP). Raw materials were obtained by recycling post-consumer waste such as beverage bottles and newsprint. The composites were tested for their potential use as materials in cladding panels and acoustic barriers. Given that normative documents for these products do not define specific environmental requirements, the composites were tested for the release of dangerous substances, such as anions of inorganic compounds, heavy metals, volatile organic compounds (VOCs), and their impact on the environment. A detailed in-depth analysis of the mechanisms of release of substances (diffusion, dissolution, surface leaching and depletion) from the rPP/NP composite into surface water, groundwater and soil was carried out. In turn, emission of VOCs from the rPE (low-density:high-density (LD:HD)—50:50) and rPE (LD:HD—30:70) composites into indoor air was also carried out. Raw materials in the form of granulates and loose cellulose fibres, used to produce the composites, were also tested for their environmental impact.     

Analysis and Assessment of the Usefulness of Recycled Plastic Materials for the Production of Airfield Geocell

The load-bearing capacity of natural airfield pavement has a direct impact on the safety of air operations. Unfortunately, the field tests often indicate that the load-bearing capacity of natural airfield pavements is not sufficient. In this case, it is necessary to reinforce them in order to meet the requirements set out in international documents. It is important that the method of reinforcing the subsoil is fast and as noninvasively as possible. There are many methods of reinforcing the subsoil, however, they are expensive and time-demanding, which involves turning off the airport for a long time. Airfield geocells made of recycled plastics discussed in the article seem to be the optimal solution due to the quick implementation of their application by pressing into the existing natural pavement. The article presents the results of laboratory tests demonstrating that material in question is load-resistant and chemical-resistant, while field studies have confirmed that the airfield geocell made of the plastic in question improves the load carrying capacity of natural airfield pavement.     

AMPA receptor pHluorin-GluA2 reports NMDA receptor-induced intracellular acidification in hippocampal neurons

NMDA receptor activation promotes endocytosis of AMPA receptors, which is an important mechanism underlying long-term synaptic depression. The pH-sensitive GFP variant pHluorin fused to the N terminus of GluA2 (pH-GluA2) has been used to assay NMDA-mediated AMPA receptor endocytosis and recycling. Here, we demonstrate that in somatic and dendritic regions of hippocampal neurons a large fraction of the fluorescent signal originates from intracellular pH-GluA2, and that the decline in fluorescence in response to NMDA and AMPA primarily describes an intracellular acidification, which quenches the pHluorin signal from intracellular receptor pools. Neurons expressing an endoplasmic reticulum-retained mutant of GluA2 (pH-GluA2 ΔC49) displayed a larger response to NMDA than neurons expressing wild-type pH-GluA2. A similar NMDA-elicited decline in pHluorin signal was observed by expressing cytosolic pHluorin alone without fusion to GluA2 (cyto-pHluorin). Intracellular acidification in response to NMDA was further confirmed by using the ratiometric pH indicator carboxy-SNARF-1. The NMDA-induced decline was followed by rapid recovery of the fluorescent signal from both cyto-pHluorin and pH-GluA2. The recovery was sodium-dependent and sensitive to Na⁺/H⁺-exchanger (NHE) inhibitors. Moreover, recovery was more rapid after shRNA-mediated knockdown of the GluA2 binding PDZ domain-containing protein interacting with C kinase 1 (PICK1). Interestingly, the accelerating effect of PICK1 knockdown on the fluorescence recovery was eliminated in the presence of the NHE1 inhibitor zoniporide. Our results indicate that the pH-GluA2 recycling assay is an unreliable assay for studying AMPA receptor trafficking and also suggest a role for PICK1 in regulating intracellular pH via modulation of NHE activity.     

利用苯乙烯染料揭示突触囊泡循环过程的研究进展

苯乙烯类染料 (Styryldyes) ,如FM 1 4 3和FM 2 10等是近年来发展和广泛应用于突触囊泡循环及突触传递研究领域的一类工具药。这类化合物特异性地标记突触囊泡 ,发出荧光 ,而又不影响囊泡的活性和运转。因此在突触事件中依照荧光强度的变化就可以推断相应的神经胞吞及胞吐的程度 ,跟踪囊泡循环过程。一些突触事件的具体环节 ,在应用了苯乙烯类染料之后 ,得到了进一步的阐明。本文简要介绍苯乙烯类染料的性质和近年来在突触事件研究中的一些主要应用及进展。