山莨菪碱对中性粒细胞糖皮质激素受体的影响

以~3H地塞米松(Dex)为特异性配基,以一点分析法测得大白鼠腹腔中性粒细胞(PMNs)的糖皮质激素受体(GCR)位点数为5270±216/个PMN(n=18,X±SE下同);体外实验,PMNs直接与山莨菪碱(654-23×10~(-5)M)温育,对GCR无明显影响,测得位点数为4896±360/个PMNs(n=20,P>0.4);体内实验表明,给大鼠肌肉注射654-2(10mg/kg)每日两次共二天,则GCR位点数降至2740±101/个PMNs(n=18,P<0.001)。此时还测得血浆皮质酮含量明显增高(P<0.01)。提示654-2对GCR的影响可能与增加皮质激素所致的“降调节”有关。     

丹参提取物对氧自由基引起的化学发光的抑制作用

观察了经调理的酵母多糖（ＯＺ）、Ｎ－ｆｏｒｍｙｌｍｅｔｈｉｏｎｙｌ－Ｌｅｕｃｙｌ－ｐｈｅｎｙｌａｌａｎｉｎｅ（ｆＭＬＰ）Ｃａｌｃｉｕｍ ｉｎｏｐｈｏｒｅ（Ａ２３１８７），等几种白细胞激动剂引起的大鼠腹腔中性粒细胞（ＰＭＮｓ）的化学发光和次黄嘌呤－黄嘌呤氧化酶系统（ＨＯ－ＸＯ）产生的化学发光。观察到了具有抗炎作用的中药单体７６４－３对ＰＭＮ吞噬ＯＺ引起的化学发光及ＨＯ－ＸＯ系统产生的化学发光具有明显     

白细胞进入腹腔是引起蛋白质经腹腔丢失的关键

目的为了研究细菌性腹膜炎时经腹腔蛋白质丢失的机制,阐明白细胞移行与蛋白质丢失的关系。方法给兔腹腔内注射大肠杆菌(E.coil)4×106CFU+生理盐水(35ml/kg),做成急性腹膜炎动物模型。通过测定实验6或8h期间腹透液中白细胞总数(WBC)及中性粒细胞(PMNs)计数情况以及腹膜对蛋白质的通透性(蛋白质D/P比值)。设立了两个系列的实验系列一,应用氮介(mustine),1.2mg/kg,实验前3天静脉注射,以耗尽循环血中的白细胞;系列二,用单克隆抗体(mAb)60.32mg/kg,实验前5min静脉注射,以阻滞PMNs上的粘附分子CD18,从而抑制PMNs向腹腔移行。同时设立了阳性对照组(即腹膜炎组)及阴性对照组(无腹膜炎组)。结果系列一中mustine降低87%循环血中白细胞及93%循环血中PMNs,此时即使腹腔内注射细菌,白细胞向腹腔的移行及腹腔蛋白质的渗出均较未注射mustine的腹膜炎组明显降低,而与无腹膜炎的正常对照组结果相似。系列二,静脉注射mAb60.3同样也明显降低白细胞及PMNs向腹腔的移行及经腹腔蛋白质的丢失。结论急性细菌性腹膜炎时白细胞向腹腔移行导致了经腹腔蛋白质的丢失。     

Antioxidant effects and anti-elastase activity of the calcium antagonist nicardipine on activated human and rabbit neutrophils--a potential antiatherosclerotic property of calcium antagonists?

Activated neutrophils which produce certain proteases, such as elastase and reactive oxygen species (ROS) are involved in oxidative stress and inflammation. In the present study, we have shown that nicardipine, a calcium channel blocker, affects the release of elastase and superoxide anion radicals (O₂ ^–) in vitro during human and rabbit neutrophil respiratory bursts. The drug inhibited the release of elastase and O₂ ^– by fMLP (N-formyl-methionylleucin-phenylalaninin), calcium ionophore (A23187) and PMA (phorbol-myristate-acetate)-stimulated human and rabbit neutrophils. Besides the release of elastase, strongly inhibited in the fMLP and A23187 stimulated systems, nicardipine affected elastase and O₂ ^– in a dose-dependent manner. The corresponding 50% inhibitory concentration (IC₅₀) of nicardipine for elastase, released in PMA-stimulated human and rabbit neutrophils, was 15.95 ± 0.17 M and 18.06 ± 0.08 M, respectively, whereas for O₂ ^–, the IC₅₀ of nicardipine in PMA, fMLP and A23187-stimulated human and rabbit neutrophils was 55.41 ± 0.09 M and 58.43 ± 0.03 M, 45.21 ± 0.13 M and 37.19 ± 0.53 M, 33.54 ± 0.09 M and 30.54 ± 0.29, respectively. The mechanisms underlying the inhibition of elastase and superoxide anion radicals by nicardipine appear related to an inhibiting effect on the mobilisation of cytosolic calcium and on activation of protein kinase C (PKC). These antioxidant and anti-elastasic activities contribute to the properties of nicardipine, as positive side effects of its antihypertensive activity and may be useful to prevent inflammatory disorders (tissue damage, oxidative injury) involved in the pathogenesis of hypertension.     

Enhancing global vaccine pharmacovigilance: Proof-of-concept study on aseptic meningitis and immune thrombocytopenic purpura following measles-mumps containing vaccination

New vaccines designed to prevent diseases endemic in low and middle-income countries (LMICs) are now being introduced without prior record of utilization in countries with robust pharmacovigilance systems. To address this deficit, our objective was to demonstrate feasibility of an international hospital-based network for the assessment of potential epidemiological associations between serious and rare adverse events and vaccines in any setting. This was done through a proof-of-concept evaluation of the risk of immune thrombocytopenic purpura (ITP) and aseptic meningitis (AM) following administration of the first dose of measles-mumps-containing vaccines using the self-controlled risk interval method in the primary analysis. The World Health Organization (WHO) selected 26 sentinel sites (49 hospitals) distributed in 16 countries of the six WHO regions. Incidence rate ratios (IRR) of 5.0 (95% CI: 2.5–9.7) for ITP following first dose of measles-containing vaccinations, and of 10.9 (95% CI: 4.2–27.8) for AM following mumps-containing vaccinations were found. The strain-specific analyses showed significantly elevated ITP risk for measles vaccines containing Schwarz (IRR: 20.7; 95% CI: 2.7–157.6), Edmonston-Zagreb (IRR: 11.1; 95% CI: 1.4–90.3), and Enders’Edmonston (IRR: 8.5; 95% CI: 1.9–38.1) strains. A significantly elevated AM risk for vaccines containing the Leningrad-Zagreb mumps strain (IRR: 10.8; 95% CI: 1.3–87.4) was also found. This proof-of-concept study has shown, for the first time, that an international hospital-based network for the investigation of rare vaccine adverse events, using common standardized procedures and with high participation of LMICs, is feasible, can produce reliable results, and has the potential to characterize differences in risk between vaccine strains. The completion of this network by adding large reference hospitals, particularly from tropical countries, and the systematic WHO-led implementation of this approach, should permit the rapid post-marketing evaluation of safety signals for serious and rare adverse events for new and existing vaccines in all settings, including LMICs.     

高频水针疗法对颈椎病神经根性痛患者外周血TNF-α含量 及中性粒细胞百分率影响的初步研究

目的:研究TNF-α、中性粒细胞(PMNs)与神经根型颈椎病(CRS)根性痛的相关性及高频水针疗法对该病患者血清TNF-α含量、PMNs百分率的影响。方法:收集20例符合条件的CRS患者,按门诊就诊顺序随机分为观察组和对照组,各10例,观察组用高频水针疗法,对照组用水针疗法。同时与20例正常人作对照。于治疗前和1个疗程后清晨空腹抽取静脉血,ELISA法检测血清TNF-α含量及行血常规检查。结果:TNF-α含量升高且与根性痛程度成正相关(r=0.830,P<0.01),PMNs百分率虽然升高,但与根性痛程度无相关性(r=0.210,P>0.05)。高频水针组和水针组均能改善患者的TNF-α含量、PMNs百分率,但前者对TNF-α含量、PMNs百分率的改善情况好于后者(P<0.01)。结论:TNF-α与神经根型颈椎病根性痛程度成正相关。高频水针疗法能降低或抑制炎性细胞因子的释放,具有明显的抗炎、镇痛作用,对神经根性痛有明显的干预作用。     

Inhibitory effects of phenolic compounds from Artocarpus styracifolius on respiratory burst of rat neutrophils

Context: Searching for polymorphonuclear neutrophils (PMNs) respiratory burst inhibitors is an important topic in the treatment of human diseases associated with inflammation.

Objective: To investigate the inhibitory effects of phenolics isolated from Artocarpus styracifolius Pierre (Moraceae) on respiratory burst induced by phorbol myristate acetate (PMA).

Materials and methods: The anti-respiratory burst activities of eight phenolics (20?µM) were assessed by determining luminol-dependent chemiluminiscence in rat PMNs. Cytotoxicity of active compounds (1–1000?µM) was assayed by Trypan blue dye exclusion method. Cell-free models were employed to evaluate scavenging capacity of active compounds (20?µM) against reactive oxygen species.

Results: The PMA-induced respiratory burst was significantly inhibited (p?1–6) at the concentration of 20?µM (below the toxic concentration) with the inhibition rate ranging from 25.0 to 99.6%. The inhibitory potency estimated by IC₅₀ was in the order of AS1 (3.1?µM) >AS6 (5.9?µM) >AS2 (9.1?µM) >AS3 (10.0?µM) >AS5 (29.7?µM) >AS4 (57.7?µM). AS1–4, four isoprenylated flavones, potently quenched superoxide anion, hydroxyl radical, and hydrogen peroxide at the concentration of 20?µM with their scavenging rates in the range of 30.1–78.1%, 35.4–69.7%, and 65.5–86.3%, respectively. In contrast, AS5–6, two isoprenylated 2-arylbenzofurans, showed less effect than that exhibited by AS1–4.

Conclusion and discussion: The isoprenylated phenolics from A. styracifolius can potently inhibit PMA-induced respiratory burst in rat neutrophils without showing cytotoxicity. The inhibitory effects of these isoprenylated phenolics on the respiratory burst might depend on their different types of structure.     

虎杖晶4号对人血PMNs呼吸暴发和氧自由基的作用

应用化学发光法测定①人血PMNs受PMA刺激产生的化学发光;②黄嘌呤—黄嘌呤氧化酶体系产生O_2;③VitC—CU~(2+)—酵母多糖产主·OH;④H_2O_2的释放。观察虎杖晶4号对上述体系产生自由基的影响。结果提示.虎杖晶4号对PMN呼吸暴发的早期(1～6 min)有明显的抑制作用,呈剂量依赖性;而在12min时发光强度均高于空白对照.表明因虎杖晶4号而使呼吸暴发滞后。其对O_2.·OH.H_2O_2均有清除作用.且呈剂量依赖性.IC_(50)分别为14.6.29.6和13.0μmol·L~(-1).     

CAPD腹膜炎的中性粒细胞移行导致蛋白质渗出

目的 :通过CAPD腹膜炎动物模型 ,研究中性粒细胞 (PMNs)移行与蛋白质渗出的关系。方法 :给兔腹腔内注射大肠杆菌 (E .coli) 4× 10 6CFU ,做成急性腹膜炎动物模型。实验前 3d静脉注射氮介 (mustine) ,耗尽循环血中的PMNs(系列一 ) ,或实验前 5min静脉注射单克隆抗体 (mAb 6 0 .3) ,该抗体能与粘附分子CD18结合阻滞PMNs粘附 ,从而抑制PMNs向腹腔移行 (系列二 )。测定两个系列实验中腹透液PMNs计数及蛋白质渗出情况。结果 :系列一 ,mustine将循环血中PMNs降低了 (93 9) % (mean±s) ,此时即使腹腔内注射细菌 ,PMNs向腹腔的移行及腹腔蛋白质的渗出均较未注射mustine的腹膜炎组明显降低 ,而与无腹膜炎的正常对照组结果相近。系列二 ,静脉注射mAb6 0 .3同样也明显降低PMNs向腹腔的移行及腹腔蛋白质渗出。结论 :CAPD中的急性细菌性腹膜炎时PMNs向腹腔移行导致了蛋白质的渗出。