SLE患者抗ENA抗体及抗DNA抗体的检测分析

为探讨系统性红斑狼疮 ( SLE)患者血清中抗 ENA抗体与抗 DNA抗体的关系及意义 ,对 88例 SL E患者分别测定血清中抗 ss-DNA抗体、抗 ds-DNA抗体及 7种抗 ENA抗体。结果显示 ,88例 SLE患者中有 65例 ( 73 .5 % )检测到至少一种抗 ENA抗体 ,以抗 Sm、抗 U1 RNP和抗 SSA为主 ,分别占 45 .5 %、5 2 .3 %及 40 .9% ,其次为抗 SSB及抗 Rib,分别占 2 5 .0 %及 15 .9%。 88例SLE患者的 7种自身抗体与抗 ds-DNA抗体总的阳性符合率为 75 .2 % ,与抗 ss-DNA抗体总的阳性符合率为 60 .2 %。因此 ,抗 ENA抗体与抗 DNA抗体同时检测有助于提高 SLE的诊断阳性率。     

钙通道阻滞剂在心血管系统的临床应用

本文对钙通道阻滞剂在抗高血压，抗心绞痛、抗心律失常及抗心衰和改善左室功能等方面的临床应用机理及疗效作了评述。     

抗自身抗体与系统性红斑狼疮疾病活动性及狼疮肾炎关系的探讨

目的研究抗C1q抗体、抗核小体抗体(AnuA)、抗dsDNA抗体及抗中性粒细胞胞质抗体(AN-CA)等自身抗体与系统性红斑狼疮(SLE)疾病活动性及肾损害。方法测定93例初诊SLE患者血清抗Clq、Anu-A、抗核抗体(ANA)、抗dsDNA、ANCA、抗Sm。结果狼疮肾炎(LN)患者血清抗C1q抗体浓度及阳性率显著高于无肾炎表现的狼疮对照组。无论患者有无肾损害,狼疮疾病活动患者抗C1q抗体浓度及阳性率显著高于疾病稳定的狼疮对照组。而AnuA和抗dsDNA抗体只在伴有狼疮肾损害的疾病活动组即活动LN的阳性率显著高于非活动LN对照组。进一步分析,在活动性LN组血清抗C1q抗体和AnuA双阳性的概率为63.6%,而无一例抗C1q抗体和AnuA同时阴性。相反,在非活动LN的SLE对照组患者无抗C1q抗体和AnuA双阳性。LN组抗C1q、AnuA、抗dsDNA抗体和抗Sm抗体阳性率显著高于非LN组。SLE疾病活动组抗Clq抗体、AnuA、抗dsDNA阳性率显著高于疾病稳定组。活动LN抗Clq抗体、AnuA、抗dsDNA抗体阳性率显著高于非活动LN。活动LN组抗C1q抗体、AnuA、抗dsDNA抗体及ANCA阳性率显著高于其他SLE组。结论抗C1q抗体、抗核小体抗体、抗dsDNA抗体都是狼疮疾病活动的指标,均与LN有关,可以相互补充,联合检测可以提高LN及疾病活动检出率。     

橙皮苷及橙皮素对心血管系统保护作用及机制的研究进展

心血管疾病是全球发病率和致死率最高的疾病.大量实验表明橙皮苷及橙皮素在抗氧化、抗炎、抗心肌重构、血脂调控、抗动脉粥样硬化、抗心肌缺血、抗栓、降血压及抗心律失常等心血管保护作用方面均有较好的效果.文章对近年来橙皮苷及橙皮素在心血管系统保护作用及其机制方面的研究进行综述.     

泽泻的药理研究概况

查阅近年来的相关文献,对泽泻的药理作用研究进行综述。泽泻具有利尿、降血糖血脂及抗动脉粥样硬化、抗肾结石形成、抗肾炎活性、抗脂肪肝、对心血管系统及’免疫调节的作用。     

体力劳动者抗感冒药社会用药风险评价

目的：促进重视体力劳动者抗感冒药社会使用风险。方法根据体力劳动者生活及抗感冒药使用特性,评估体力劳动者抗感冒药社会使用风险。结果资料显示抗感冒药用药安全性与其不良及不合理使用方式极其相关,而体力劳动者经济收入及受教育总体水平较低的特性及生活方式等因素,加之看病难花费高等因素,使得该群体感冒的自我治疗不良及不合理用药方式,潜藏着巨大的抗感冒药社会用药风险。结论有针对性地对体力劳动者群体开展患者用药教育,降低抗感冒药社会用药风险刻不容缓。     

检测抗核抗体谱在系统性红斑狼疮诊治中的意义

目的探讨抗核抗体谱(ANAs)检测在系统性红斑狼疮(SLE)诊治中的应用价值。方法对102例SLE(SLE组)、32例其他风湿性疾病(疾病对照组)及30名健康体检者(正常对照组),分别采用间接免疫荧光法、免疫印记法测定血清中抗核抗体(ANA)和ANAs中15种抗体的水平。结果 SLE组ANA和ANAs中抗nRNP/Sm抗体、抗Sm抗体、抗双链DNA抗体、抗核小体抗体、抗组蛋白抗体及抗核糖体P蛋白抗体阳性率与疾病对照组和正常对照组比较差异有统计学意义(P<0.01)。SLE组2项及以上抗体阳性者占93.1%。ANA、抗Sm抗体、抗双链DNA抗体及抗核小体抗体同时阳性且资料完整的20例SLE住院患者治疗后上述抗体均有不同程度的转阴和(或)滴度下降。结论联合检测动态观察ANAs对SLE的诊断及治疗具有重要意义。     

我院2011~2013年抗精神病药用药分析

目的调查我院2011~2013年抗精神病药的应用情况及趋势。方法采用限定日剂量为指标,对我院2011~2013年使用的抗精神病药的品种、用量、销售金额、用药频度(DDDs)及限定日费用(DDC)进行统计分析。结果我院抗精神病药的销售总金额及总用药频度均逐年增高,而典型抗精神病药销售金额出现负增长。结论我院抗精神病药用药合理,非典型抗精神病药有逐步取代典型抗精神病药的趋势。     

抗-E及抗-Fyb引起交叉配血不合原因分析

血清中抗-E及抗-Fy^b大多由免疫产生，而抗-Fy^b的发生率极小，二者均可致新生儿溶血病及溶血性输血反应,还可影响配血实验。笔者在给一位反复输血的患者配血时发现，在盐水介质中相合，而在凝聚胺（Polybrene）及抗人球蛋白介质中主侧出现1＋-2＋，疑有ABO以外抗体。经检查发现患者血清中含有免疫性抗-E及抗-Fy^b抗体，现报告如下。     

临床标本抗核抗体4188份检测结果回顾性分析

目的探讨抗核抗体（ANA）常见类型在四川地区自身免疫性疾病（AID）患者中的分布趋势及临床价值。方法采用免疫印迹法对2011年1月至2013年9月4 188份疑似AID患者的临床标本进行ANA常见15种类型（抗NRNP、抗SM、抗SS-A、抗RO-52、抗SS-B、抗SCL-70、抗PM-SCL、抗JO-1、抗CENP、抗PCNA、抗ds-DNA、抗组蛋白、抗核小体、抗核糖体P蛋白及抗AMAM2）的检测,统计其分布情况,并对性别、年龄及季节进行分组,采用χ2检验进行统计学分析。结果 （1）在4 188份标本中,ANA阳性率为28.8%,AID阳性率为7.2%。在确诊的303例AID患者中,干燥综合征（SS）患者抗SS-A阳性率（75.4%）最高,依次为抗RO-52（61.5%）及抗SS-B（20.5%）;系统性红斑狼疮（SLE）患者抗SS-A阳性率（76.8%）最高,依次为抗RO-52（64.2%）及抗ds-DNA（41.1%）;混合性结缔组织（MCTD）患者抗RO-52阳性率（42.5%）最高,其次为抗SS-A（41.1%）及抗NRNP（26.0%）;类风湿性关节炎（RA）患者抗SM阳性率（65.4%）最高,其次为抗SS-A（38.5%）。SS是四川地区最常见的AID,依次为SLE、MCTD及RA等。（2）在4 188例疑似AID患者中,女性AID阳性率（11.0%）显著高于男性（1.5%）,差异有统计学意义（χ^2=136.44,P〈0.05）;年龄组中18～45岁组阳性率最高（8.4%）,〈18岁组最低（2.1%）,差异有统计学意义（χ2=8.92,P〈0.05）;季度组中第4季度阳性率最高（8.6%）,第1季度最低（6.2%）,差异有统计学意义（χ^2=3.47,P〈0.05）。结论四川地区AID患者ANA常见类型分布可能与年龄、季节及性别相关,这在AID的诊断方面有重要价值。     

Investigations on plasma activity of low molecular weight heparin after intravenous and oral administrations.

This study investigated the absorption of low molecular weight heparin (LMWH) after oral administration in man. Six healthy subjects received 5,000 anti-Xa units of LMWH (Kabi 2165) by both i.v. and oral administration. The oral formulations were prepared in pH 4.0 and pH 7.0 buffered solutions. Multiple blood samples were collected after each dose for measurements of anti-Xa, anti-IIa and APTT plasma heparin activities. Pharmacokinetic parameters based on the anti-Xa activity measurements after the i.v. dose were as follows (mean +/- s.d.): t1/2, 1.82 +/- 0.23 h; V, 4.34 +/- 0.651; and CL, 28.0 +/- 6.2 ml min-1. Half-life values based on the anti-IIa and APTT activities were 1.63 +/- 0.43 and 1.09 +/- 0.51 h, respectively. Considerable prolongations in APTT were observed, with APTT at 30 min averaging 55.7 +/- 4.1 s (1.84 +/- 0.27 times baseline values). After oral administration, no measurable plasma heparin activities were observed with either LMWH preparation. The results of this investigation indicate that LMWH does not have detectable plasma activity after oral administration, and that after i.v. administration it has significant anti-IIa and APTT activities in addition to its anti-Xa activity.     

Studies on the intestinal absorption of low molecular weight heparin using saturated fatty acids and their derivatives as an absorption enhancer in rats

Intestinal absorption of low molecular weight heparin (LMWH) as well as unfractionated heparin (UFH) is limited due to its large molecular size and extensive negative charge. Development of its oral formulations would allow outpatient treatment with LMWH and UFH, and contribute a reduction in hospital expenses. The present study was aimed at evaluating the absorption enhancers Labrasol and Gelucire 44/14, which mainly consist of glycerides and fatty acids esters, to improve the intestinal absorption of LMWH. The absorption effects of saturated fatty acids with several carbon chain lengths (C6-C14) were also investigated. LMWH formulated with or without absorption enhancer was administered to the duodenum of fasted rats. The doses of LMWH and absorption enhancer were 20 mg/kg and 30 mg/kg, respectively. Plasma anti-Xa activity was measured as a marker of the LMWH absorption. By administration of the LMWH formulation with Labrasol but not with Gelucire 44/14, the plasma anti-Xa activity was increased to a level above 0.2 IU/ml which is the critical level for elucidation of its anticoagulant activity. Saturated fatty acids also enhanced the intestinal absorption of LMWH, and the order of absorption-enhancing effect was C10=C12>C14>C16>C8> or =C6. These results suggest that the intestinal absorption of LMWH varies with carbon chain lengths of the saturated fatty acids.     

In situ intestinal absorption studies on low molecular weight heparin in rats using labrasol as absorption enhancer

Oral absorption of low molecular weight heparin (LMWH) is limited by its molecular size and negative charge. Development of its oral formulations would allow outpatient treatment with LMWH and decrease the hospital expenses. Studies were aimed at evaluating Labrasol for improving intestinal absorption of LMWH. Formulations containing LMWH and Labrasol were administered to duodenum, jejunum, and ileum of the fasted rats. The doses of LMWH and Labrasol were 200 IU/kg and 50 mg/kg, respectively. Reversibility of absorption enhancing effect of Labrasol was assessed by administering LMWH to jejunum after 0.5 and 1 h of administration of Labrasol. The effect of different doses of Labrasol on LMWH absorption was studied by administering Labrasol at 50, 100, and 200 mg/kg doses. Administration of LMWH formulation tojejunum resulted in the highest plasma anti-Xa activity (0.50+/-0.03 IU/ml) compared to duodenum (0.19+/-0.03 IU/ml), and ileum (0.29 +/-0.06 IU/ml) and the anti-Xa levels were maintained above the therapeutic level for about 160 min. The absorption of LMWH was negligible when LMWH was administered at 0.5 and 1 h post-Labrasol administration. Increasing the dose of Labrasol has decreased the absorption of LMWH from jejunum. Labrasol increased the intestinal absorption of LMWH, and jejunum was found to be the best site of absorption. Intestinal membrane permeability changes induced by Labrasol were transient and reversible. Maintaining high drug concentration gradient across intestinal wall is important to obtain increased intestinal LMWH absorption.     

Evaluation of self-dissolving needles containing low molecular weight heparin (LMWH) in rats

Feasibility study of self-dissolving needles containing polysaccharide was performed. Low molecular weight heparin (LMWH) was used as a representative polysaccharide. Using chondroitin, dextran and dextrin as the base, self-dissolving needles (SDN) were prepared. The obtained SDNs were evaluated in rat absorption experiment, where pharmacological availability (PA) was calculated by comparing the plasma anti-Xa activity vs. time curves between SDNs and i.v. solution. After the insertion of SDNs to rats skin where the doses of LMWH were 25, 50 and 100 IU/kg, plasma samples were collected for 6h and anti-Xa activity was measured as the pharmacological index of LMWH. The anti-Xa level was maintained above 0.2 IU/ml, the therapeutic level, for about 2h at a dose of 100 IU/kg. Almost the same PAs of LMWH were obtained with dextran and dextrin SDNs, 97.7% and 102.3%, though lower PA was obtained with chondroitin SDN, 81.5%. In vitro dissolution experiment showed that LMWH was released from dextran, dextrin and chondroitin SDNs within 10 min. The T(50%)s were 0.84+/-0.06 min for dextran SDN, 1.07+/-0.12 min for chondroitin SDN and 2.11+/-0.31 min for dextrin SDN, respectively. Plasma anti-Xa activity vs. time profiles showed good dose-dependency in the 25-100 IU/kg range and high PAs were obtained, 90.0% for 25 IU/kg, 95.4% for 50 IU/kg and 97.7% for 100 IU/kg from dextran SDNs. Stability experiment was performed with dextran SDNs for 3 months. Above 97% of LMWH were remained in SDNs under three different conditions, -80, 4 and 40 degrees C. These results suggest the usefulness of SDN to polysaccharide drug.     

Effect of sesame oil emulsion on nitroglycerin pharmacokinetics

When nitroglycerin (3.5 mg/kg) was administered orally in a 20% sesame oil emulsion to rats, peak plasma concentrations were decreased but bioavauability was unaffected when compared to those observed using an aqueous solution vehicle. Pre-dosing with drug-free emulsion for 3 days, however, caused significant increases in nitroglycerin biovailability (2.5X) and peak plasma concentrations (5X) compared to controls. This increase appeared to be reversible when emulsion dosing was withdrawn. The apparent increase in bioavailability was not due to a change in nitroglycerin distribution or elimination kinetics from drug-free emulsion administration nor could it be attributed to the surfactant used. There was no change in in vitro liver organic nitrate reductase activity or reduced glutathione concentration with emulsion pretreatment. The results suggested that, when using emulsion as a dosage form, repeated dosing of the vehicle could have an effect on the drug absorption process that was not predicted from single dose administration.     

Preparation and evaluation of oral solid heparin using emulsifier and adsorbent for in vitro and in vivo studies

Oral anticoagulant therapy with heparin has been challenged by formulating heparin in oral solid preparation. As heparin, low molecular weight heparin (LMWH) was used. LMWH was dispersed with a surfactant used for the self-microemulsifying drug delivery system (SMEDDS), PEG-8 caprylic/capric glycerides (Labrasol), and the mixture was solidified with three kinds of adsorbents, microporous calcium silicate (Florite RE), magnesium alminometa silicate (Neusilin US(2)) and silicon dioxide (Sylysia 320). The in vitro release study showed that the T50%s were 3.2+/-0.1min for Sylysia 320, 4.6+/-0.2min for Florite RE, 13.7+/-0.1min for Neusilin US(2). The in vivo rat absorption study showed that Florite RE system had the highest C(max), 0.42+/-0.01IU/mL and AUC, 0.59+/-0.06IUh/mL, where plasma LMWH levels were measured as anti-Xa activity. Other preparations had the C(max) and AUC, 0.12+/-0.01IU/mL and 0.15+/-0.02IUh/mL for Neusilin US(2) and 0.25+/-0.02IU/mL and 0.40+/-0.03IUh/mL for Sylysia 320, respectively. The bioavailability (BA) of LMWH from the microporous calcium silicate preparation, Florite RE, was 18.8% in rats by comparing the AUC obtained after i.v. injection of LMWH, 40IU/kg to another group of rats. Florite RE system was evaluated in dogs after oral administration in an enteric capsule made of Eudragit S100 at the LMWH dose of 200IU/kg. High plasma anti-Xa activity levels were obtained, i.e., the C(max) was 0.48+/-0.11IU/mL and AUC was 1.64+/-0.32IUh/mL. These results suggest that adsorbent system is useful as an oral solid delivery system of poorly absorbable drugs such as LMWH.     

Effects of administration route on pharmacokinetics of aspirin in the rabbit

The absorption of aspirin used in the form of lysine acetylsalicylate was studied in the rabbit. Each animal received the drug by three routes: intravenous, gastric and duodenal. Plasma concentrations of acetylsalicylic acid (ASA) and salicylic acid (SA) were compared. ASA plasma concentrations obtained after gastric or duodenal administration were low compared to those after intravenous injection. Concentrations were 2 to 5 times higher after gastric than duodenal administration. SA plasma concentrations were lower at the beginning of the experiment for gastric than for duodenal administration; after 90 min the concentrations were similar. A better absorption of aspirin (as lysine acetylsalicylate) after administration occurred in the stomach than in the duodenum, but the amount of ASA which reached the central compartment was quite poor.     

Effects of administration route on pharmacokinetics of viloxazine in the rabbit.

The absorption of viloxazine chlorhydrate was investigated in ten rabbits. Each animal received the drug (15 mg/kg) by three routes: intravenous, gastric and duodenal. Viloxazine plasma concentrations were low when administered by gastric and duodenal routes compared to those after intravenous injection. Concentrations to peak were 1-2 times higher after duodenal than gastric administration. Times to peak were 23.0 +/- 4.7 min after gastric administration and 9.5 +/- 5.4 min after duodenal administration. A better absorption of viloxazine after administration occurred in the duodenum than in the stomach; these results agree with viloxazine pKa = 8.13. The other pharmacokinetic parameters such as half-life, clearance and volume of distribution where the same irregardless of the administration route.     

Evaluation of the pharmacokinetics of dalteparin in patients with renal insufficiency

The pharmacokinetics of the low-molecular weight heparin (LMWH), dalteparin, was evaluated after a single intravenous bolus injection of 50 IU anti-Xa/kg in 8 healthy volunteers, 8 patients with moderate/severe renal failure (Cl(crea) 13.1-56.5 ml/min) and 8 hemodialysis patients. Venous blood samples were taken over a 1-day period to determine anti-Xa activity, anti-IIa activity and plasma levels of free tissue factor pathway inhibitor (free TFPI). Plasma anti-Xa and anti-IIa activities were measured using chromogenic assays and free TFPI levels using an ELISA technique. The anti-Xa clearance was significantly decreased (p < 0.05) in both groups with renal insufficiency when compared with healthy volunteers. There was a positive correlation between creatinine clearance and anti-Xa clearance in the healthy volunteers and patients with moderate/severe renal failure. The anti-Ila activity was characterized by 3- to 4-fold lower plasma concentrations and faster elimination compared with the anti-Xa activity. In patients with moderate/severe renal failure the elimination of anti-lla was only slightly decreased, whereas in hemodialysis patients anti-Ila clearance was significantly decreased (p < 0.01). There was no correlation between creatinine clearance and anti-IIa clearance. The baseline mean free TFPI plasma levels in the two groups with renal insufficiency were significantly higher (p < 0.01) than in healthy volunteers. Dalteparin administration induced a transient, 6.0- to 8.1-fold increase in the free TFPI values in the three study groups. Dalteparin induced an increase in C(max) and AUC(0 - infinity) values of free TFPI in the two groups with renal insufficiency that was higher than in healthy volunteers. No bleeding complications occurred during the study. In conclusion, this is the first report showing retarded elimination of dalteparin and enhanced free TFPI plasma levels induced by a LMWH in patients with renal insufficiency.     

Excretion of low molecular weight heparin in human milk

AIMS: The excretion of low molecular weight heparin (LMWH) in breast milk was investigated in 15 lactating mothers after Caesarean section. METHODS: Blood and milk samples were collected before and 3-4 h after once daily routine subcutaneous injection of 2500 IU dalteparin. Anti-Xa activity was measured by an assay utilizing prolonged clotting times in plasma or breast milk as an index of LMWH activity. RESULTS: Plasma anti-Xa activities ranged from 0.074 to 0.308 IU ml(-1) of plasma. Anti-Xa activities in breast milk ranged from < 0.005-0.037 IU ml(-1) of milk. This is equivalent to a milk/plasma ratio of < 0.025-0.224. CONCLUSIONS: Therefore, it appears highly unlikely that puerperal thromboprophylaxis with LMWH has any clinically relevant effect on the nursing infant.