褐藻糖胶促进小鼠巨噬细胞免疫活性及机制初探

目的 探讨褐藻糖胶(Fucoidan)对小鼠巨噬细胞RAW264.7免疫活性的影响及初步探讨作用机制。方法 采用体外细胞培养方法,比色分析检测不同浓度Fucoidan(0、100、200、300、400、500 μg/mL)作用下RAW264.7吞噬中性红的能力,噻唑蓝(MTT)法检测不同浓度Fucoidan(0、50、250、500 μg/mL)作用下RAW264.7增殖,Western Blotting检测Fucoidan诱导的RAW264.7的MAPK/ERK1/2的磷酸化。结果 Fucoidan剂量依赖性地促进RAW264.7吞噬功能和增殖功能。200 μg/mL Fucoidan作用10min即使ERK1/2发生磷酸化,30min时ERK1/2磷酸化达到最大值。结论 Fucoidan可提高小鼠巨噬细胞的吞噬活性和增殖能力,其机制可能与Fucoidan直接激活RAW264.7的MAPK/ERK1/2信号转导通路有关。     

Assessment of immunotoxicity induced by chemicals in human precision-cut lung slices (PCLS)

Occupational asthma can be induced by a number of chemicals at the workplace. Risk assessment of potential sensitizers is mostly performed in animal experiments. With increasing public demand for alternative methods, human precision-cut lung slices (PCLS) have been developed as an ex vivo model.Human PCLS were exposed to increasing concentrations of 20 industrial chemicals including 4 respiratory allergens, 11 contact allergens, and 5 non-sensitizing irritants. Local respiratory irritation was characterized and expressed as 75% (EC₂₅) and 50% (EC₅₀) cell viability with respect to controls. Dose–response curves of all chemicals except for phenol were generated. Local respiratory inflammation was quantified by measuring the production of cytokines and chemokines. TNF-α and IL-1α were increased significantly in human PCLS after exposure to the respiratory sensitizers trimellitic anhydride (TMA) and ammonium hexachloroplatinate (HClPt) at subtoxic concentrations, while contact sensitizers and non-sensitizing irritants failed to induce the release of these cytokines to the same extent. Interestingly, significant increases in T_H1/T_H2 cytokines could be detected only after exposure to HClPt at a subtoxic concentration.In conclusion, allergen-induced cytokines were observed but not considered as biomarkers for the differentiation between respiratory and contact sensitizers. Our preliminary results show an ex vivo model which might be used for prediction of chemical-induced toxicity, but is due to its complex three-dimensional structure not applicable for a simple screening of functional and behavior changes of certain cell populations such as dendritic cells and T-cells in response to allergens.     

HILIC-ELSD法测定岩藻聚糖硫酸酯中岩藻糖

目的 建立一种简便、高效、准确的测定岩藻聚糖硫酸酯中岩藻糖的方法。方法 采用超声处理(300 W 100%,20 ℃,20 min);三氟乙酸(4 mol/mL)水解(110 ℃、2 h);亲水作用色谱-蒸发光检测(HILIC-ELSD)法检测,Waters XBridge^TM Amide(150 mm×4.6 mm,3.5 μm)色谱柱,流动相为乙腈-水-氨水(90:10:0.2),体积流量1 mL/min,柱温60 ℃。结果 岩藻糖的线性范围为0.100 4~1.004 mg/mL(r=0.999 4),平均加样回收率95.22%(n=6,RSD=1.16%)。结论 该方法简便、快速、准确,为岩藻聚糖硫酸酯的定量分析和质量评价研究提供了依据。     

小剂量尿激酶联合低分子肝素钙、血栓通治疗亚急性期下肢深静脉血栓临床观察

目的：探讨小剂量尿激酶联合低分子肝素钙、血栓通治疗亚急性期下肢深静脉血栓的疗效及安全性。方法51例确认为LEDVT的患者给予尿激酶20万U溶于100mL生理盐水中,应用输液泵经患肢足背静脉注射,于半小时内滴完,每天一次,连续5～7d。同时应用注射用血栓通（冻干）0.5溶于生理盐水250mL静脉滴注,每日1次。低分子肝素钙注射液4100U皮下注射,1次/12h,连续5d。第3天加用华法林钠片2.5mg,每日一次,并根据PT调整药量。结果本组51例,痊愈8例（16%）,有效34例（67%）,无效9例（17%）,总有效率为82%。治疗前后HCT、Fg都有所降低,自身对照有显著性差异（P＜0.05）。结论小剂量尿激酶延迟溶栓联合低分子肝素钙、血栓通治疗亚急性期下肢深静脉血栓是安全有效的方法。     

海藻海蒿子褐藻糖胶的分离与组成分析

目的以海藻海蒿子为原料制备褐藻糖胶，并对不同的提取、分离方法进行比较，对多糖的组成和结构进行初步分析。方法海蒿子脱脂干粉分别经水提取和酸提取以获得粗多糖，粗多糖分别经乙醇沉淀法和CaCl2沉淀法进行纯化。选取多糖组分F4用Q—Sepharose Fast Flow和Sephadex G-200凝胶柱进行分级分离，高效凝胶渗透色谱法（HPGPC）鉴定纯度及相对分子质量，气相色谱分析多糖的中性单糖组成。结果F4经分级分离得到3个级分：P1、P2和P3。P1、P2和P3均为均一组分，相对分子质量分别为：494400、61500和167600；P1由岩藻糖、木糖、甘露糖、葡萄糖和半乳糖构成，摩尔百分比43．4：33．3：6．2：4．3：12．8；P2由岩藻糖、木糖、甘露糖和半乳糖构成，摩尔百分比44．4：15．1：23．8：16．7；P3由岩藻糖、木糖和半乳糖构成，摩尔百分比68．9：3．7：27．4。结论P1、P2和P3的单糖含量均以岩藻糖为主，但其他单糖组成有较大差别。     

A systematic review of economic analyses of low-molecular-weight heparin for the treatment of venous thromboembolism

INTRODUCTION: Public concerns about the increase in health care expenditure have prompted investigators to analyze the costs and benefits of health care interventions. We conducted a systematic review of economic analyses of venous thromboembolism treatment focusing on studies evaluating low-molecular-weight heparin. MATERIALS AND METHODS: We identified studies by a MEDLINE search and a review of bibliographies of retrieved articles. From each eligible study, we extracted data on the study characteristics, the effectiveness, and the cost of managing the venous thromboembolism with respect to treatment. We critically appraised the studies according to the framework from the Users' Guides to the Medical Literature XIII: How to Use an Article on Economic Analysis of Clinical Practice. RESULTS: Six of these eight economic analyses of venous thromboembolism treatment that met the inclusion criteria for this review showed that low-molecular-weight heparin is associated with less recurrent venous thromboembolism and is less costly than treatment with unfractionated heparin. Although discrete recurrent venous thromboembolism event rates were not included in the seventh study, these investigators concluded that the cost of low-molecular-weight heparin for the treatment of venous thromboembolism treatment was offset by the savings associated with fewer hospital admissions when low-molecular-weight heparin was used. In the eighth study, although the cost of treatment with low-molecular-weight heparin was higher than treatment with unfractionated heparin, the investigators concluded that low-molecular-weight heparin is cost-effective for inpatient management. CONCLUSIONS: Low-molecular-weight heparin treatment may confer economic advantages over unfractionated heparin therapy because it does not require anticoagulant monitoring and it facilitates outpatient therapy.     

An open-label, comparative study of the efficacy and safety of once-daily dose of enoxaparin versus unfractionated heparin in the treatment of proximal lower limb deep-vein thrombosis

BACKGROUND: Treatment of deep-vein thrombosis (DVT) with a once-daily regimen of enoxaparin, rather than a continuous infusion of unfractionated heparin (UFH) is more convenient and allows for home care in some patients. This study was designed to compare the efficacy and safety of these two regimens for the treatment of patients with proximal lower limb DVT. METHODS: 201 patients with proximal lower limb DVT from 13 centers in Brazil were randomized in an open manner to receive either enoxaparin [1.5 mg/kg subcutaneous (s.c.) OD] or intravenous (i.v.) UFH (adjusted to aPTT 1.5-2.5 times control) for 5-10 days. All patients also received warfarin (INR 2-3) for at least 3 months. The primary efficacy endpoint was recurrent DVT (confirmed by venography or ultrasonography), and safety endpoints included bleeding and serious adverse events. The rate of pulmonary embolism (PE) was also collected. Hospitalization was at the physician's discretion. RESULTS: Baseline patient characteristics were comparable between groups. The duration of hospital stay was significantly shorter with enoxaparin than with UFH (3 versus 7 days). In addition, 36% of patients receiving enoxaparin did not need to be hospitalized, whereas all of the patients receiving UFH were hospitalized. The treatment duration was slightly longer with enoxaparin (8 versus 7 days). There was a nonsignificant trend toward a reduction in the rate of recurrent DVT with enoxaparin versus UFH, and similar safety. CONCLUSIONS: A once-daily regimen of enoxaparin 1.5 mg/kg subcutaneous is at least as effective and safe as conventional treatment with a continuous intravenous infusion of UFH. However, the once daily enoxaparin regimen is easier to administer (subcutaneous versus intravenous), does not require aPTT monitoring, and leads to both a reduced number of hospital admissions and an average 4-day-shorter hospital stay.     

The effect of body weight on dalteparin pharmacokinetics A preliminary study

Aim: To investigate whether there were significant differences in the volume of distribution (V) and clearance (CL) of dalteparin in obese versus normal-weight patients, and thereby determine whether dosing of dalteparin should be based on total body weight, lean body weight or an adjusted body weight in obese patients. Methods: Patients (ten obese and ten normal weight) treated with dalteparin were matched for age, gender, lean body weight and creatinine CL. Two steady-state plasma dalteparin concentrations were taken from each patient and assayed in duplicate. The pharmacokinetic values of V and CL were estimated, for each patient, using the Bayesian maximum a posteriori method with the program ABBOTTBASE. Results: The mean V in obese patients was approximately 60% larger than in normal-weight patients, but this was not statistically significant (P=0.11; two-tailed). The mean value of V (8.4 l) in the normal-weight patients was similar to that reported in the literature. The mean difference in values of CL (18% larger in obese patients) was not clinically or statistically significant. A poor correlation was seen between V and lean body weight (r ²=0.05). There was a moderate correlation between V and total body weight (r ²=0.52) and between V and adjusted body weight (r ²=0.55); adjusted body weight=[lean body weight + 0.4(total body weight – lean body weight)]. Total body weight and adjusted body weight provided a better correlation with CL (r ²=0.39, 0.32, respectively) than did lean body weight (r ²=0.01). Conclusion: These results suggest that doses of dalteparin in obese patients should be based on total body weight or an adjusted body weight, but not lean body weight. This study highlights some potential differences in the pharmacokinetics of dalteparin in individuals who are obese, and further work is necessary to quantify these differences in more detail. Received: 30 July 1999 / Accepted in revised form: 16 March 2000