类风湿性关节炎与几种炎性指标血清水平分析

[目的]探讨血清超敏C反应蛋白(hs-CRP)、血小板活化因子(PAF)及抗环瓜氨酸肽(CCP)抗体等对类风湿性关节炎(RA)活动期中的水平变化及临床意义.[方法]采用酶联免疫吸附法检测68例活动RA患者(A组)血清PAF含量及抗-CCP抗体,采用速率散射比浊法检测血清hs-CRP水平,并与70例非活动期RA患者(B组)、45例健康体检者(C组)比较.[结果]活动期RA患者血清PAF含量为(117.26±23.52)pg/ml,hs-CRP为(14.12±1 1.37)mg/L,明显高于健康对照组；与非活动期组RA患者比较,CCP抗体阳性率明显较高,血清PAF水平差异有极显著性(Jp＜0.01),但hs-CRP水平差异无显著性(P＞0.05).[结论]活动期RA患者血清PAF、hs-CRP及CCP抗体水平明显升高,可作为反映RA患者风湿活动的评估指标,但hs-CRP对评估活动期RA与非活动期RA效果不明显,无明显鉴别诊断意义.     

阵发性房颤的初步诊断及血流动力学研究

目的 探讨阵发性房颤(PAF)发生前后的血流动力学变化及早期诊断。方法 利用多普勒超声仪对21例PAF患者窦律及房颤时LAD、LVEF、S-LAmax、V-LAmax、LAEF进行检测,并与20例正常人及18例慢性房颤(CAF)患者进行对比。结果 (1)PAF患者窦律时左心房较正常人扩大,左心房功能降低,E/A比值降低且<1。(2)PAF发生前后左心房、左心室功能明显降低,而左心房大小无明显变化。(3)CAF比PAF患者,左心房进一步扩大,左心房功能进一步降低,左心室功能也降低,但无统计学意义。结论 (1)PAF患者的血流动力学有显著性改变。(2)超声心动图有助于评价PAF发生前后的血流动力学,对预防和治疗均有指导作用。(3)动态心电图是临床筛选PAF的重要方法。     

血小板激活因子拮抗剂

血小板激活因子(platelet activatingfactor,PAF)为乙酰甘油醚磷酰胆碱(1-O-十六烷基/十八烷基-2-乙酰基-sn-甘油-3-磷酰胆碱)。特异性PAF拮抗剂有助于研究PAF的病理生理学作用。本文评论PAF拮抗剂的进展和讨论PAF的潜在作用。 PAF的药理学已证明PAF与血清病有关,它是炎症的自体有效递质,主要作用是增加血管的通透性。     

山药新木脂素成分的研究

自胡椒科(Piperaceae)植物山蒟(Piper hancei Maxim)的藤茎分离到三种木脂素类化合物,根据光谱(UV,IR,NMR和MS)及X-射线单晶衍射分析,化合物Ⅲ确定为新结构,(7S,8R,3′S)-1′-烯丙基-3′-甲氧基-7-(3,4-次甲二氧基苯基)-7,8,3′,6′-四氢-6′-氧苯并呋喃,命名为山蒟素(hancinone);化合物Ⅰ为海风藤酮(kadsurenone);化合物Ⅱ为denudatin B。后两种化合物首次从本植物中分离。山蒟民间草药,治疗风湿和关节炎。以血小板活化因子(PAF)受体结合实验及PAF血小板聚集实验测定,化合物Ⅰ的抑制作用最强,化合物Ⅱ明显减弱,而化合物Ⅲ无活性。     

阵发性心房颤动的生物标记物

阵发性心房颤动(PAF)约占所有心房颤动(AF)的50％,PAF作为一种过渡性心律失常显著增加血栓栓塞事件风险,但并未引起足够重视.目前,PAF不再被视为良性病变实体,早期发现或预测PAF具有重要的临床意义.本文从电生理、分子及形态学三方面阐述PAF的生物标记物,以期对PAF的早期诊断和预测提供帮助.     

银杏内酯B抑制中性粒细胞活化的研究

目的 研究银杏内酯B(GB,抗血小板聚集)抑制血小板活化因子(PAF)介导的中性粒细胞活化.方法 将银杏内酯B加入抗凝全血中,阻断PAF对中性粒细胞活化;用PAF及二磷酸腺苷(ADP)活化下述各组的中性粒细胞,包括对照组、PAF组、PAF+GB组、ADP组和ADP+GB组,用流式细胞术检测中性粒细胞整和素(CD11b)平均荧光强度.结果 PAF及ADP均可明显增加中性粒细胞CD11b的平均荧光强度,银杏内酯B可明显抑制PAF及ADP诱导的CD11b的平均荧光浓度.结论 银杏内酯B可明显抑制PAF介导的中性粒细胞活化.     

心电图P波最大时限与P波离散度对阵发性房颤的预测价值

目的 了解体表心电图的P波最大时限(P_(max))及P波离散度(P_(disp))对阵发性心房颤动(PAF)的预测价值。 方法 测量了32例PAF病人的体表心电图的P_(max)及P_(disp),并与30例无PAF者进行了比较。结果P_(max)和P_(disp)在PAF病人中明显延长,P_(max)>110ms和P_(disp)≥40ms可区分开PAF病人和对照组,其敏感度均为97％,特异性分别为76％和73％。结论 体表心电图的P_(max)及P_(disp)是一种预测PAF简便实用的方法。     

银杏叶提取物制剂、阿司匹林及氯吡格雷抗血小板聚集作用比较及对血小板活化因子含量的影响

目的:观察银杏叶提取物(EGB)制剂、阿司匹林及氯吡格雷对家兔血小板聚集率及血小板活化因子(PAF)含量的影响。方法:采用体内实验,观察EGB制剂、阿司匹林及氯吡格雷对由花生四烯酸(AA)、二磷酸腺苷(ADP)和PAF诱导的家兔血小板聚集作用的影响,以及对给药前后家兔PAF含量的影响。结果:与生理盐水组比较,EGB制剂抑制AA、ADP、PAF诱导的家兔血小板聚集有统计学差异(P<0.05,P<0.01),并能够降低血清中PAF的含量(P<0.05),阿司匹林对AA诱导的血小板聚集有统计学差异(P<0.01),氯吡格雷对ADP诱导的血小板聚集有统计学差异(P<0.01),而阿司匹林和氯吡格雷对PAF的含量没有显著影响。结论:EGB制剂具有抗血小板聚集作用,抗PAF诱导的血小板聚集作用最强,并能显著降低PAF含量。     

新生儿缺氧缺血性脑病治疗过程中血小板活化因子监测的临床价值

目的：分析新生儿缺氧缺血性脑病(HIE)治疗过程中血小板活化因子(PAF)的监测价值。方法将2012年3月~2014年3月于本院接受治疗的100例HIE新生儿作为研究对象，选取同期10例正常健康新生儿作为对照组，采用放射免疫法测定患儿急性期与恢复期外周PAF及超氧化物歧化酶(SOD)水平，并将70例中重度HIE患儿分为A(中度，n=35)、B(重度，n=35)两组，比较两组患儿治疗后PAF的变化情况。结果恢复期，A组血清PAF水平低于B组，血清SOD水平高于B组(P<0.05)；恢复期，A组神经行为评分明显高于B组(P<0.05)；HIE组血清PAF水平明显高于对照组，且随病情严重程度提升，血清PAF水平越高，且急性期PAF水平高于恢复期(P<0.05)。结论 HIE患儿血清PAF水平与疾病严重程度呈明显正相关，与SOD呈负相关，采取银杏叶片治疗，可抑制患儿血清PAF的释放，减轻患儿炎症反应，改善症状表现，优化患儿的预后水平，值得推广。     

心电图P波最大时限与P波离散度对阵发性房颤的预测价值

目的了解体表心电图的P波最大时限(Pmax)及P波离散度(Pdisp)对阵发性心房颤动(PAF)的预测价值.方法测量了32例PAF病人的体表心电图的Pmax及Pdisp,并与30例无PAF者进行了比较.结果Pmax和Pdisp在PAF病人中明显延长,Pmax＞110 ms和Pdisp≥40 ms可区分开PAF病人和对照组,其敏感度均为97%,特异性分别为76%和73%.结论体表心电图的Pmax及Pdisp是一种预测PAF简便实用的方法.     

Arachidonic acid inhibits Na⁺-K⁺-ATPase via cytochrome P-450, lipoxygenase and protein kinase C-dependent pathways in sheep pulmonary artery

The purpose of the study was to examine whether arachidonic acid inhibits vascular Na(+)-K(+)-ATPase in pulmonary vasculature and if so, what are the mechanisms involved. Functional Na(+)-K(+)-ATPase activity was studied in terms of K(+)-induced relaxation in sheep pulmonary arterial rings contracted with K(+)-free solution and 5-HT. Arachidonic acid (10-100 μM) caused concentration-dependent inhibition of KCl-induced relaxations and also increased basal arterial tone. Cytochrome P-450 inhibitor, 17-octadecynoic acid (17-ODYA) completely reversed the arachidonic acid (30 μM)-induced inhibition of KCl relaxation. Further, in the presence of HET0016, a selective blocker of 20-hydroxyeicosatetraenoic acid (20-HETE), arachidonic acid-induced inhibition of KCl relaxation was not evident. Accordingly, 20-HETE, a cytochrome P-450 metabolite of arachidonic acid, also significantly attenuated KCl-induced relaxations. Norhydihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, however, partially restored the relaxation to K(+), impaired in the presence of arachidonic acid (30 μM). On the other hand, cyclooxygenase inhibitor indomethacin failed to reverse the inhibitory effect of arachidonic acid on KCl-induced relaxation. Staurosporin, a protein kinase C inhibitor, completely reversed the inhibitory effect of arachidonic acid and 20-HETE on K(+)-induced relaxation. In conclusion, the results suggest that 20-HETE, a cytochrome P-450 metabolite of arachidonic acid has a predominant role in the inhibition of functional Na(+)-K(+)-ATPase activity in the sheep pulmonary artery, while the lipooxygenase pathway has a secondary role. It is also evident that protein kinase C is involved in the inhibition of Na(+)-K(+)-ATPase by arachidonic acid/20-HETE in sheep pulmonary artery.     

R-(+)-硫代四氢呋喃-2-甲酸的制备

目的制备R-(+)-硫代四氢呋喃-2-甲酸。方法以四氢呋喃-2-甲酸为原料,经拆分、氯代、取代3步反应得到R-(+)-硫代四氢呋喃-2-甲酸。结果反应总收率为29%,产物结构经1H-NMR和MS确证。结论通过实验摸索了一条制备光学纯度的R-(+)-硫代四氢呋喃-2-甲酸的路线,该方法简单、易于操作。     

A metabonomic characterization of (+)-usnic acid-induced liver injury by gas chromatography-mass spectrometry-based metabolic profiling of the plasma and liver in rat

Three doses of (+)-usnic acid (100, 200, and 240 mg/kg per d) were administered orally to Wistar rats for 8 days, and metabonomic characterization of (+)-usnic acid-induced liver injury based on gas chromatography-mass spectrometry metabolic profiles was evaluated. Serum biochemical analysis and histopathological examinations were simultaneously performed. The liver/body weight ratio was significantly increased in (+)-usnic acid-treated groups, whereas serum alanine aminotransferase and total bilirubin were significantly elevated. In liver sections of 200 and 240 mg/kg dosage groups, widespread hydropic degeneration of hepatocytes was observed. Clusters in partial least squares discriminant analysis score plots showed control and (+)-usnic acid-treated groups had an obvious separation. (+)-Usnic acid exposure can lead to disturbances in energy metabolism, amino acid metabolism, lipid metabolism, and nucleotide metabolism, which may be attributable to (+)-usnic acid toxicological effects on the liver through oxidative stress. The significant changes in 22 metabolites in liver might be adopted as potential biomarkers.     

A comparison of prodrug esters of nipecotic acid

The relative ability of the enantiomers of the ethyl and m-nitrophenyl esters of nipecotic acid to block convulsions induced by bicuculline and pentylenetetrazol, as well as to block the uptake of GABA into whole brain mini-slices, was studied in mice. Neither (+)ethyl nipecotate hydrogen tartrate [(+)E.Tartrate], which is hydrolyzed to (-)nipecotic acid, nor (-)ethyl nipecotate hydrogen tartrate [(-)E.Tartrate], which is hydrolyzed to (+)nipecotic acid, provided protection against challenge with bicuculline. Both (+)E.Tartrate and (-)ethyl nipecotate hydrochloride [(-)E.HCl], which are hydrolyzed to (-)nipecotic acid, blocked seizures induced by pentylenetetrazol. However, neither (-)E.Tartrate nor (+)ethyl nipecotate hydrochloride [(+)E.HCl], which are hydrolyzed to (+)nipecotic acid, provided significant protection against challenge with pentylenetetrazol. These results agree with the relative ability of these compounds to inhibit the uptake of GABA, where (-)nipecotic acid was more potent than (+)nipecotic acid and (+)E.Tartrate was more potent than (-)E.Tartrate. The enantiomers of m-nitrophenyl-3-piperidinecarboxylate hydrochloride, (+)MNPC.HCl and (-)MNPC.HCl, were almost equi-effective in preventing seizures induced by bicuculline. This lack of significant difference in anticonvulsant activity is in contrast with the ability to inhibit the uptake of GABA, where (-)MNPC.HCl was significantly more potent than (+)MNPC.HCl. Changing the route of administration from subcutaneous to intraperitoneal injection reduced the onset of time of the peak effect and the anticonvulsant potency of (+/-)MNPC.HCl. Cholinergic effects were observed with the administration of (+)E.Tartrate and (-)E.HCl, but not with (-)E.Tartrate, (+)E.HCl, (+)MNPC.HCl or (-)MNPC.HCl.(ABSTRACT TRUNCATED AT 250 WORDS)     

Behavioral effects of salbutamol and/or L-(+)-ascorbic acid in the mouse after single and multiple dosing

The acute and chronic effects of salbutamol alone and L-(+)-ascorbic acid alone and in combination were evaluated on "open-field" test in mice. Administered singly and acutely (30 min before the test), both salbutamol (0.003 mmol/kg i.p.) and L-(+)-ascorbic acid (0.35-0.71 and 1.42 mmol/kg i.p.) significantly reduced ambulation scores. This decrease was higher in L-(+)-ascorbic acid - than in salbutamol-treated mice. Rearing behavior was significantly increased only in salbutamol-treated animals. In animals treated chronically (once a day for 15 days) the depression of salbutamol-induced ambulation was more marked than in mice treated acutely. This decrease was partially reversed by L-(+)-ascorbic acid treatment. With respect to rearing scores, a significant increase was found after salbutamol and L-(+)-ascorbic acid administered alone or in combination. In conclusion, these experiments show that salbutamol induces a direct effect on behavior, that is to reduce motor activity, being the reduction more marked after chronic treatment. The association of the beta 2-agonist with L-(+)-ascorbic acid can attenuate some of the depressant effects of chronic salbutamol administration on behavior.     

Altered regulation of renal Acid base transporters in response to ammonium chloride loading in rats

The role of the kidney in combating metabolic acidosis has been a subject of considerable interest for many years. The present study was aimed to determine whether there is an altered regulation of renal acid base transporters in acute and chronic acid loading. Male Sprague-Dawley rats were used. Metabolic acidosis was induced by administration of NH(4)Cl for 2 days (acute) and for 7days (chronic). The serum and urinary pH and bicarbonate were measured. The protein expression of renal acid base transporters [type 3 Na(+)/H(+) exchanger (NHE3), type 1 Na(+)/HCO(3) (-) cotransporter (NBC1), Na-K(+) ATPase, H(+)-ATPase, anion exchanger-1 (AE-1)] was measured by semiquantitative immunoblotting. Serum bicarbonate and pH were decreased in acute acid loading rats compared with controls. Accordingly, urinary pH decreased. The protein expression of NHE3, H(+)-ATPase, AE-1 and NBC1 was not changed. In chronic acid loading rats, serum bicarbonate and pH were not changed, while urinary pH was decreased compared with controls. The protein expression of NHE3, H(+)-ATPase was increased in the renal cortex of chronic acid loading rats. These results suggest that unaltered expression of acid transporters combined with acute acid loading may contribute to the development of acidosis. The subsequent increased expression of NHE3, H(+)-ATPase in the kidney may play a role in promoting acid excretion in the later stage of acid loading, which counteract the development of metabolic acidosis.     

Inhibition of sodium-dependent L-leucine uptake in rat brain synaptosomes

Synaptosomes isolated from adult rat cerebral cortices were used for studying the uptake of L-leucine by the Na(+)-dependent route. Three non-metabolizable amino acid analogues, which had been used previously to discriminate the Na(+)-dependent A-type uptake system of animal cells, were employed in this study. It was found that Na(+)-dependent uptake of leucine was insensitive to inhibition by 2-aminoisobutyric acid (AIB) and N-methylaminoisobutyric acid (MeAIB) whereas N-methylalanine (NMA) was markedly inhibitory. Inhibition by NMA was stereospecific--only the L-isomer had a pronounced effect. Na(+)-dependent uptake of leucine as well as its inhibition by L-NMA were rather insensitive to changes in pH from 6 to 9. Kinetic analysis of inhibition by L-NMA of Na(+)-dependent uptake revealed a non-competitive type of inhibition with a Ki value of approximately 0.5 mM.     

Inhibition of gastric H+, K(+)-ATPase and acid secretion by ellagic acid.

The effects of ellagic acid on gastric H+, K(+)-ATPase, acid secretion, and the occurrence of gastric ulcers were studied. Ellagic acid inhibited hog gastric H+, K(+)-ATPase activity with a 50% inhibition at 2.1 x 10(-6)M; kinetic studies showed that the inhibition of H+, K(+)-ATPase by ellagic acid is competitive with respect to ATP and is noncompetitive with respect to K+. The effect on gastric ulcers was investigated by using a stress ulcer model. Intraperitoneal administration of ellagic acid at above 5 mg/kg markedly reduced the occurrence of gastric lesion. Ellagic acid significantly reduced acid secretion at the same doses. These results suggest that ellagic acid has a marked inhibitory effect on acid secretion and the occurrence of stress-induced gastric lesions, and these effects may be attributed to the inhibition of H+, K(+)-ATPase activity.     

假麻黄碱转变为麻黄碱(Ⅰ)

L(+)-ψ-麻黄鹼經下列步驟轉变为L(-)-盐酸麻黄鹼:将L(+)-ψ-麻黄鹼乙酰化得N-乙酰化合物,然后在冰醋酸中使成5%溶液,不加任何物質廻流1.5小时立即回收醋酸后,用10%氫氧化鈉进行水解,再变为盐酸盐即得、以L(+)-N-乙酰-ψ-麻黄鹼为基础計算收得率約为81-85%.L(-)-麻黄鹼在同样情况下只有約24%轉化为盐酸-ψ-麻黄鹼.     

山莨菪碱四个光学异构体的合成和分离

以6-(甲氧)亚甲氧基托品酮(Ⅰ)为原料,与(+)L-酒石酸或(-)D-酒石酸成盐,可分离得到右旋的6-(甲氧)亚甲氧基托品酮[(+)Ⅰ]和左旋的6-(甲氧)亚甲氧基托品酮[(-)Ⅰ].(+)Ⅰ和(-)Ⅰ氢化还原后,分别与α-甲酰基苯乙酸甲酯进行酯交换,硼氢化钠还原侧链上醛基,水解脱去羟基保护基得到左旋山良菪碱(-)Ⅳ和右旋山莨菪碱(+)Ⅳ.(-)Ⅳ和(+)Ⅳ分別与(-)二苯甲酰酒石酸和(+)二苯甲酰酒石酸成盐,可用分步结晶法拆分到山崀菪碱的四个光学异构体。