Hepatic Disposition Characteristics of Electrically Charged Macromolecules in Rat in Vivo and in the Perfused Liver

The effect of electric charge on the hepatic disposition of macromolecules was studied in the rat. Charged derivatives of dextran (T-70) and bovine serum albumin (BSA), mitomycin C–dextran conjugates (MMC-D), and lactosaminated BSA (Lac-BSA) were employed as model macromolecules. After intravenous injection, cationic macromolecules were rapidly eliminated from plasma because of their extensive hepatic uptake, while anionic and neutral macromolecules were slowly eliminated. Cationic macromolecules were recovered from parenchymal and nonparenchymal hepatic cells at a cellular uptake (per unit cell number) ratio of 1.4–3.2, while that of Lac-BSA was 14. During liver perfusion using a single-pass constant infusion mode, cationic macromolecules were continuously extracted by the liver, with extraction ratios at steady-state (E _ss) ranging between 0.03 and 0.54, whereas anionic and neutral macromolecules were almost completely recovered in the outflow at steady state. The E _ss for cationized BSA (Cat-BSA) and cationic MMC-Dcat were concentration dependent and decreased at low temperatures and in the presence of colchicine and cytochalasin B. The possible participation of the internalization process in the uptake of cationic macromolecules by hepatocytes was suggested.     

诺氟沙星的吸附伏安法研究

在ｐＨ＝７．４９氨－氯化铵缓冲液中，诺氟沙星在滴汞电极上产生一灵敏的还原峰，峰电位为－１．５２Ｖ（ｖｓ．ＳＣＥ）。在１．９８×１０（－７）～４．８８×１０（－６）ｍｏｌ／Ｌ之间有良好的线性关系。本文对其极谱性质和电极过程进行了研究，用于诺氟沙星的测定，方法简便，结果准确、可靠。     

Adhesion dependent release of hepatocyte growth factor and interleukin-1 receptor antagonist from human blood granulocytes and monocytes: Evidence for the involvement of plasma IgG,complement C3 and β2 integrin

Objective:Evolving evidence of anti-inflammatory effects is observed in patients with rheumatoid arthritis or ulcerative colitis following periodic adsorptive granulocyte and monocyte (GM) apheresis with a column containing cellulose acetate (CA) beads as apheresis carriers. This study was undertaken to obtain insights into mechanisms of anti-inflammatory actions of adsorptive GM apheresis with CA beads. Methods:In a series of in-vitro experiments, we investigated the effects of plasma proteins and the leucocytes 2 integrin (CD18) on granulocyte adsorption to CA beads. Results:Granulocyte adsorption to CA beads required plasma IgG, the complement C3 and was inhibited by an antibody to leucocytes CD18. Further, hepatocyte growth factor (HGF) and interleukin-1 receptor antagonist (IL-1ra) which have strong anti-inflammatory actions were released by granulocytes that adhered to CA beads. Conclusions:Plasma IgG, C3 derived complement activation fragments and leucocytes CD18 are involved in granulocyte adhesion to CA beads and hence the release of HGF and IL-1ra.Received 27 October 2003; returned for revision 16 December 2003; accepted by M. J. Parnham 8 January 2004     

活性氧化铝除氟剂的除氟性能研究

目的通过对经特殊工艺处理的不同粒径的活性氧化铝的除氟性能进行研究．开发实用的除氟剂。方法模拟A（粒径2．0～3．0mm）、B（粒件3．5～5．5mm）样除氟剂对氟含量为10mg／L的原水进行处理试验，研究除氟性能。结果A、B样除氟剂当流速分别为80ml／min及以下和20ml／min及以下时，其终端流出水中的氟含量均小于1mg／L；A、B样除氟剂的绝对饱和吸附最分别为1．67mg／g和1.30mg／g，相对饱和吸附量分别为1．57mg／g和0.17mg／g。结论除氟剂粒径小、比表面积较大时，有利于除氟性能的提高。     

Evaluation of Double Filtration Plasmapheresis, Thermofiltration, and Low–Density Lipoprotein Adsorptive Methods by Crossover Test in the Treatment of Familial Hypercholesterolemia Patients

Abstract: A comparative assessment has been made regarding efficacy and safety of the double filtration plasmapheresis (DFPP), thermofiltration (TFPP), and low–density lipoprotein (LDL) adsorptive (PA) methods by making a crossover test on heterozygous familial hypercholesterolemia patients. Treatments by DFPP, TFPP (secondary membrane Evalux 5A), and PA (Liposorber LA–40) were carried out 5 times each, with a 2–week interval, in 5 patients with heterozygous familial hypercholesterolemia. The same plasma separator (Plasmacure PS–60, polysulfone) was used in all cases, and the volume of plasma processed was set at 4 L. High removal rates were obtained of total cholesterol, LDL cholesterol, triglycerides TG, and apolipoprotein B (apoB) by all three methods, and no differences were observed. Lipoprotein (a), apoA–2, apoC–3, fibrinogen, and immunoglobulin M (IgM) showed significantly high removal rates by the DFPP and TFPP methods compared with the PA method.
The sieving coefficient of albumin and high–density lipoprotein (HDL) cholesterol at 2 and 4 L of plasma processed exhibited high permeabilities using all three methods. Supplementing albumin was not necessary. An increase of the transmembrane pressure was observed in 1 case treated by DFPP but was not observed when using the TFPP or PA method. No changes were observed in serum interleukin 1β (IL–lβ) or tumor necrosis factor–a (TNF–α) before and after treatment by any of the three methods. No remarkable side effects were observed using either the DFPP or TFPP method. The DFPP and TFPP methods showed efficacy and safety that was not inferior to the PA method in conventional LDL apheresis, and the dead–end method of the filter operation without the discarding of plasma was shown to be possible.     

大孔吸附树脂对红花多糖脱色工艺的影响研究

目的:探讨大孔吸附树脂对红花多糖脱色工艺的影响。方法:采用单因素试验,以脱色率和多糖保留率作为评价指标,比较AB-8、HPD-400A、HPD-100、HPD-750、D101、ADS-17等6种不同型号大孔吸附树脂在温度、多糖浓度、pH值、吸附流速、洗脱剂5个方面对红花多糖脱色效果的影响。结果:HPD-100大孔吸附树脂对红花多糖的脱色率和保留率较为理想。最佳工艺为40℃,多糖浓度为5 mg·mL-1,pH值为4,流速为1 ml·min-1,洗脱剂为pH 4的蒸馏水。在该条件下色素的吸附率可达86.71%,多糖保留率为72.10%。结论:HPD-100大孔树脂对红花多糖可以获得较高的脱色率和保留率。     

植物生长调节剂对盾叶薯蓣产量及薯蓣皂苷元含量的影响

目的大田条件下,研究几种植物生长调节剂对盾叶薯蓣根茎中薯蓣皂苷元含量及根茎产量的影响。方法采用单因素施肥方法,结果采用SPSS17．0统计软件包进行分析。结果发现施用萘乙酸、多效唑、烯效唑和2,4-D均可大大提高盾叶薯蓣根茎产量,但对于薯蓣皂苷元含量的影响较小。对薯蓣皂苷元含量的影响,2,4-D〉膨大素〉NAA〉稀效唑〉多效唑：对盾叶薯蓣根茎产量的影响,2,4-D〉NAA〉多效唑〉稀效唑〉膨大素。结论喷施一定浓度的2,4-D,对优质、高产盾叶薯蓣的栽培,具有重要的实践意义。     

Characterization of LLC-PK1 Kidney Epithelial Cells as an in Vitro Model for Studying Renal Tubular Reabsorption of Protein Drugs

Purpose. The purpose of this study was to assess whether LLC-PK₁ renal epithelial cells could serve as an in vitro model for studying the renal tubular reabsorption of protein drugs. Methods. The association of ¹¹¹In-labeled model protein drugs, bovine serum albumin (BSA), superoxide dismutase (SOD), soybean trypsin inhibitor (STI), and [Asu^1,7]-eel calcitonin (Asu-ECT), with the monolayers of LLC-PK₁ renal epithelial cells was characterized under various conditions. Results. The cellular association of these proteins was temperature-dependent and varied according to the protein. Saturation kinetics were observed for STI association, with the apparent Km and Vmax values determined to be 66.3 µg/ml and 250 ng/mg protein/min, respectively. The association of STI decreased with increases in medium pH from 5.4 to 8.4 and was inhibited significantly by 2,4-dinitrophenol, sodium azide, cytochalasin B, and colchicine, suggesting that the cellular association involved endocytosis. Mutual inhibition was observed in competitive binding experiments with the four protein drugs, suggesting that they shared a common binding site on the luminal membrane of LLC-PK₁ cells. Taken together, these findings show that a variety of protein drugs bind to LLC-PK₁ cells in a non-specific manner and possibly undergo endocytosis, a phenomenon that is similar to in vivo proximal tubular reabsorption. Conclusions. LLC-PK₁ renal epithelial cells would be a suitable model system for the study of the renal proximal tubular reabsorption of protein drugs.     

Immunomodulatory effects of granulocyte and monocyte adsorption apheresis as a treatment for patients with ulcerative colitis

Our aim was to understand the mechanism of immunological changes associated with the use of an adsorptive-type extracorporeal device (Adacolumn) that has been developed for selective adsorption of granulocytes and monocytes/macrophages from peripheral blood of patients with active ulcerative colitis. The column is filled with carriers (G-1 beads) that have a diameter of 2 mm and are made of cellulose diacetate. In peripheral blood treated with the G-1 beads or peripheral blood from patients with active ulcerative colitis following granulocyte and monocyte adsorption apheresis, a significant suppression of proinflammatory cytokines (tissue necrosis factor-, interleukin-1, interleukin-6, and interleukin-8) production by leukocytes, neutrophil chemotaxis, down-regulation of leukocyte adhesion molecule (L-selectin) and neutrophil adhesion to interleukin-1-activated endothelial cells were observed. Furthermore, after granulocyte adsorption therapy, the number of CD10-negative premature granulocytes increased, indicating increased turnover of these cells in the circulation. Our observations suggest that selective granulocyte and monocyte adsorption is associated with modified peripheral blood leukocyte function favorable to patients with ulcerative colitis and possibly other autoimmune disorders which reflect leukocyte hyperactivity.