The effects of higenamine on LPS-induced experimental disseminated intravascular coagulation (DIC) in rats

The effect of higenamine, a benzyl-tetrahydroisoquinoline alkaloid of the roots of Aconitum spp. (Ranunculaceae), on disseminated intravascular coagulation (DIC), was investigated using an experimental DIC rat model. The oral administration of higenamine (10 mg/kg or 50 mg/kg), significantly ameliorated the decrease of fibrinogen level in plasma, the increase of fibrinogen/fibrin degradation product (FDP) level, and the prolongation of prothrombin time (PT) induced by the i. v. infusion of lipopolysaccharide (LPS). The prolongation of activated partial thrombin time (aPTT) and the decrease of platelet count were suppressed. The increase in serum aspartate aminotransferase (AST) and blood urea nitrogen (BUN) were also significantly prevented with higenamine. The above results are suggestive that higenamine has therapeutic potential for DIC and/or accompanying multiple organ failure (MOF).     

The effects of FUT-175 (nafamostat mesilate) on blood coagulation and experimental disseminated intravascular coagulation (DIC)

FUT-175 is a newly synthesized serine protease inhibitor. In the present study, we investigated the effects of FUT-175 on blood coagulation and experimental DIC. The effects on coagulation were examined in vitro by measuring the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) of rat plasma in the presence of FUT-175. FUT-175 exhibited remarkable anticoagulative effects to prolong APTT at a plasma concentration of 3 x 10(-7) M, PT at 1 x 10(-5) M and TT at 3 x 10(-5) M. The anticoagulative effect of FUT-175 at 1 x 10(-6) M on APTT was almost similar to that of heparin at 0.3 U/ml or that of gabexate mesilate at 1 x 10(-3) M. Experimental DIC was induced by a four-hr sustained intravenous infusion of endotoxin. FUT-175 was administered intraperitoneally prior to the injection of endotoxin or infused intravenously with endotoxin. As a result, the prolongation of APTT and PT, the decreases of fibrinogen level, platelet counts and complement level, and the increase of FDP were remarkably improved by FUT-175. Furthermore, glomerular fibrin deposits were reduced by the infusion of FUT-175. These results indicate that FUT-175, having a potent inhibitory effect on blood coagulation, is clinically applicable to therapy for DIC.     

Tanshinone IIA protects rabbits against LPS-induced disseminated intravascular coagulation (DIC)

Aim:

To evaluate the effects of tanshinone IIA (Tan IIA), a lipophilic diterpene from the Chinese herb Salvia miltiorrhiza, on lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) in rabbits.

Methods:

LPS-induced DIC model was made in adult male New Zealand rabbits by continuous intravenous infusion of LPS (0.5 mg/kg) via marginal ear vein for 6 h. The animals were simultaneously administered with Tan IIA (1, 3 and 10 mg/kg) or heparin (500 000 IU/kg) through continuous infusion via the contralateral marginal ear vein for 6 h. Before and 2 and 6 h after the start of LPS infusion, blood samples were taken for biochemical analyses.

Results:

Continuous infusion of LPS into the rabbits gradually impaired the hemostatic parameters, damaged renal and liver functions, increased the plasma TNF-α level, and led to a high mortality rate (80%). Treatment of the rabbits with Tan IIA dose-dependently attenuated the increase in activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrin-fibrinogen degradation products (FDP); ameliorated the decrease in plasma levels of fibrinogen and platelets; and reversed the decline in activity of protein C and antithrombin III. Meanwhile, the treatment significantly suppressed the increase in the plasma levels of aminotransferase, creatinine and TNF-α, and led to much lower mortality (46.7% and 26.7% for the medium- and high-dose groups). Treatment of the rabbits with the high dose of heparin also effectively improved the hemostatic parameters, ameliorated liver and renal injuries, and reduced the plasma level of TNF-α, and significantly reduced the mortality (33.3%).

Conclusion:

Tan IIA exerts a protective effect against DIC in rabbits.     

Effect of urinastatin on disseminated intravascular coagulation

Effect of urinary enzyme inhibitor urinastatin (MTI) on disseminated intravascular coagulation (DIC) was investigated. The prolongation of PTT and increase in FDP in endotoxin-induced DIC in rats were restored by the intravenous infusion of MTI. The reduction in platelet counts, decrease in fibrinogen level and prolongation of PT were partially suppressed by the drug. Furthermore, in vitro addition of MTI prevented the decrease in r and k values and increase in ma and m epsilon values in the thromboelastogram of whole blood in endotoxin-induced DIC in rabbits. It is suggested that MTI might prevent DIC in vivo and in vitro through the inhibition of Factor XII activity and through the prevention of thromboplastin release caused by endotoxin.     

Discovery of Novel 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole Derivatives as Potential Anti‐Inflammatory Agents

A novel 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole derivative 5 with good anti‐inflammatory activity was identified from our in‐house library. Based on hit compound 5 , two series of 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole derivative 6a – g and 7a – h were designed and synthesized as novel anti‐inflammatory agents. Most of synthesized compounds exhibited good inhibitory activity on NO and TNF‐α production in LPS‐stimulated RAW 264.7 macrophages, in which the compound 6e showed most potent inhibitory activity on NO (IC₅₀ = 0.86 μm ) and TNF‐α (IC₅₀ = 1.87 μm ) production. Further evaluation revealed that compound 6e displayed more potent in vivo anti‐inflammatory activity than ibuprofen did on xylene‐induced ear oedema in mice. Additionally, Western blot analysis revealed that compound 6e could restore phosphorylation level of IκBα and protein expression of p65 NF‐κB in LPS‐stimulated RAW 264.7 macrophages.     

Effects of two tetrahydroisoquinolines (YS-49 and YS-51) on experimental disseminated intravascular coagulation induced by lipopolysaccharide in rats

Disseminated intravascular coagulation (DIC) is a pathological syndrome, which occurs following the uncontrolled widespread activation of blood coagulation, resulting in the intravascular formation of fibrin, which may lead to thrombotic occlusion of small and midsize vessels. The effects of 1-(alpha-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (YS-49, CAS 132836-42-1) and 1-(beta-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetra-hydroisoquinoline (YS-51, CAS 213179-96-5) on the experimental DIC induced by lipopolysaccharide (LPS) in rats, were investigated. The oral administration of YS-49 and YS-51 (10 or 50 mg/kg) attenuated the dramatic increase of serum fibrinogen/fibrin degradation product (FDP) level, the decrease of plasma fibrinogen concentration and the number of platelets in blood and the prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) induced by LPS. The liver and kidney function parameters, aspartate amino-transferase (AST) and blood urea nitrogen (BUN), were also improved with YS-49 and YS-51. The above results suggest that YS-49 and YS-51 have therapeutic potential for DIC and/or accompanying multiple organ failure.     

妊娠期高血压疾病母亲所娩新生儿凝血功能变化及临床意义

目的:探讨母亲妊娠期高血压疾病(HDCP)与新生儿凝血功能的关系。方法:选择2014年2月至2017年10月宜宾市第一人民医院新生儿科NICU收治的HDCP母亲分娩的新生儿280例为研究对象。所有新生儿分为A、B、C三组:A组(n=80例)母亲为重度子痫前期、B 组(n=92例)母亲为轻度子痫前期、C 组(n =108 例)母亲为HDCP;根据胎龄将纳入的新生儿分为中期早产儿(n =90 例)、晚期早产儿(n =112 例)和足月儿(n =78 例)。于出生后2 h 内检测纳入新生儿的各项凝血功能指标[凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、纤维蛋白原降解产物(FDP)、D-二聚体(D-D)、血小板计数 (PLT)]水平,并进行组间比较。应用Spearman 秩相关分析HDCP 孕母分娩的新生儿凝血指标水平与HDCP 严重程度的相关性。结果:A、B、C 组PLT、PT、APTT、FIB、D-D、FDP 水平组间比较差异有统计学意义(P<0.05);不同严重程度HDCP 孕母分娩的中期早产儿、晚期早产儿和足月儿PLT、PT、APTT、FIB、D-D、FDP 水平组间比较差异有统计学意义(P<0.05);经Spearman 秩相关性分析显示,HDCP 孕母分娩的新生儿PT、APTT、D-D、FDP 水平与HDCP 的严重程度呈正相关(P<0.05);HDCP 孕母分娩的新生儿FIB、PLT 水平与HDCP 严重程度呈负相关(P<0.05)。结论:HDCP 孕母分娩的新生儿血液处于低凝和继发性纤溶亢进的状态,母亲HDCP 越严重,新生儿越易出现凝血功能障碍。     

A novel fibrinogenase from Agkistrodon acutus venom protects against DIC via direct degradation of thrombosis and activation of protein C

The incidence of disseminated intravascular coagulation (DIC), which leads to multiple organ dysfunction and high mortality, has remained constant in recent years. At present, treatments of DIC have focused on preventing cytokine induction, inhibiting coagulation processes and promoting fibrinolysis. Recent clinical trials have supported the use of antithrombin and activated protein C supplementation in DIC. To better understand the mechanism of treatment on DIC, we here report a novel fibrinogenase from Agkistrodon acutus (FIIa) that effectively protected against LPS-induced DIC in a rabbit model, and detected the tissue factors expression in HUVE cells after using FIIa. In vivo, administration of FIIa reduced hepatic and renal damage, increased the concentration of fibrinogen, the activities of protein C, the platelet count, APTT, PT, FDP, the level of AT-III and t-PA, decreased the level of PAI-1, and increased survival rate in LPS-induced DIC rabbits. In vitro experiments, we further confirmed that FIIa up-regulated the expression of t-PA and u-PA, down-regulated the expression of PAI-1, and directly activated protein C. Our findings suggest that FIIa could effectively protect against DIC via direct degradation of microthrombi and activation of protein C as well as provide a novel strategy to develop a single proteinase molecule for targeting the main pathological processes of this disease.     

1,6-二磷酸果糖对脓毒症大鼠凝血功能和血糖的影响

目的：观察1,6-二磷酸果糖（FDP）对脓毒症大鼠凝血功能、血小板聚集率以及血糖水平的影响。方法：盲肠结扎穿孔术建立Wistar大鼠的脓毒症模型,大鼠共分为4组：对照组,假手术组,脓毒症组和FDP组。对照组不给予任何处理,假手术组行开关腹手术,脓毒症组建立脓毒症模型,FDP组在建立脓毒症模型的基础上股静脉给予1,6-二磷酸果糖（FDG）,比较4组大鼠的凝血酶原时间（PT）、活化部分凝血酶时间（APTT）、纤维蛋白原（FIB）、凝血时间（TT）,D-二聚体（D-D）、抗凝血酶Ⅲ（ATⅢ）、血小板聚集率以及血糖水平。结果：脓毒症组的PT、APTT、TT、D-D明显高于对照组和假手术组,4组大鼠FIB无显著性差异。FDP组的PT、APTT、TT、D-D明显低于脓毒症组,PT、APTT、TT稍高于对照组,FIB、D-D和ATⅢ和对照组无显著性差异。脓毒症组血小板聚集率明显高于对照组和假手术组,FDP组血小板聚集率明显低于脓毒症组,但高于对照组和假手术组。第1,3,7天时脓毒症组和FDP组血糖水平均明显高于对照组和假手术组。FDP组第1,3,7天时血糖水平明显低于脓毒症组。结论：FDP能改善脓毒症大鼠的凝血功能,控制应激性的血糖升高。     

Urinary protein C inhibitor as a therapeutic agent to disseminated intravascular coagulation (DIC): a comparison with low molecular weight heparin in rats with lipopolysaccharide-induced DIC

We compared urinary protein C inhibitor (uPCI) with low molecular weight heparin (LMWH) in terms of the effect on the pathophysiology of disseminated intravascular coagulation (DIC), such as hypercoagulation, induction of secondary fibrinolysis and organ failure, using lipopolysaccharide (LPS)-induced DIC in rats. The uPCI (0.5 and 1.0 mg/kg) administration significantly inhibited both the decrease in fibrinogen level and the increase in fibrin/fibrinogen degradation products (FDP) level, and the effects compared favorably with those of LMWH (100 and 200 IU/kg). Both uPCI (0.5 and 1.0 mg/kg) and a low dose of LMWH also inhibited the increases in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), thrombin, and plasma kallikrein equally, but a high dose of LMWH did not inhibit the changes in those parameters. Furthermore, uPCI dose-dependently prevented the prolongation of activated partial thromboplastin time (APTT), while LMWH excessively prolonged APTT at a high dose. These results suggest that the preventive effect of uPCI on the pathophysiology of DIC compares favorably with that of LMWH, including the lack of a hemorrhagic reaction in contrast to LMWH.     

Synthesis and Anti‐Inflammatory Evaluation of Novel C66 Analogs for the Treatment of LPS‐Induced Acute Lung Injury

We previously reported a symmetric monocarbonyl analog of curcumin (MACs), C66, which demonstrated potential anti‐inflammatory activity and low toxicity. In continuation of our ongoing research, we designed and synthesized 34 asymmetric MACs based on C66 as a lead molecule. A majority of the C66 analogs effectively inhibited LPS induction of TNF‐α and IL‐6 expression. Additionally, a preliminary SAR was conducted. Furthermore, active compounds 4a11 and 4a16 were found to effectively reduce the W/D ratio in the lungs and the protein concentration in the bronchoalveolar lavage fluid (BALF). Meanwhile, a histopathological examination indicated that these two analogs significantly attenuate tissue injury in the lungs with LPS‐induced ALI rats. 4a11 and 4a16 also inhibited mRNA expression of several inflammatory cytokines, including TNF‐α, IL‐6, IL‐1β, COX‐2, ICAM‐1 and VCAM‐1, in the Beas‐2B cells after LPS challenge. Altogether, the data exhibit a series of new C66 analogs as promising anti‐inflammatory agents for the treatment of LPS‐induced ALI.     

Murrayanine Attenuates Lipopolysaccharide‐induced Inflammation and Protects Mice from Sepsis‐associated Organ Failure

Murrayanine (MK) is the main compound isolated from Murraya koenigii, an aromatic plant belonging to the Rutaceae family, also known as curry leaf tree. Murrayanine was reported to possess potential antioxidant, antimycobacterial and antifungal effects. However, its effect in sepsis remains unclear. This study was designed to investigate the anti‐inflammatory effect of MK using both in vitro and in vivo assay. Results of this study indicated that MK decreased NO, TNF‐α and IL‐6 production in both lipopolysaccharide (LPS)‐stimulated RAW 264.7 cells and murine peritoneal macrophages. Moreover, iNOS and COX‐2 protein expression as well as their downstream product, PGE2, was also decreased effectively in RAW 264.7 cells. Furthermore, MK decreased the phosphorylation of IKB and repressed NF‐kB activity in LPS‐activated RAW 264.7 cells. Additionally, we evaluated MK efficacy in vivo using LPS‐induced sepsis, a systemic inflammation model in mice. Administration of MK inhibits pro‐inflammatory cytokines (TNF‐α and IL‐6) secretion; decreases AST, ALT, BUN and CRE level in mouse sera; mitigates lung, liver and kidney injuries; and also increases LPS‐challenged mice survival rate. Collectively, our results suggest that MK exerts potential as a new anti‐inflammatory and immunosuppressive drug in sepsis treatment.     

益气活血风静胶囊对大鼠及家兔血液流变学的影响

目的：研究益气活血风静胶囊对大鼠及家兔的血液流变学的影响。方法：采用SD大鼠及家兔分别灌胃给药14 d及10 d,检测SD大鼠及家兔血浆凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）、纤维蛋白原（FIB）及血小板聚集率。另采用SD大鼠,大脑中动脉阻塞（MCAO）大鼠造模后灌胃给药5 d,检测MCAO大鼠PT、APTT、TT、FIB及脑组织含水量。结果：与空白组比较,益气活血风静胶囊高、中剂量组及阳性对照组,能显著延长大鼠血浆的PT、TT、APTT （P<0.05）,并能显著降低FIB的含量（P<0.05或P<0.01）,显著降低以二磷酸腺苷（ADP）诱导的大鼠血小板聚集率（P<0.05）。与空白组比较,益气活血风静胶囊高、中、低剂量组及阳性对照组能显著延长家兔血浆的PT、TT、APTT （P<0.05或P<0.01）,并能显著降低FIB的含量（P<0.01）,显著降低以ADP诱导的大鼠血小板聚集率（P<0.05或P<0.01）。MACO大鼠模型组给药后,与假手术组比较,模型组大鼠PT、APTT、TT明显缩短（P<0.05）,FIB含量升高（P<0.05）,脑组织含水量明显增加（P<0.01）;与模型组比较,益气活血风静组和人参有效部位组能延长大鼠血浆PT、APTT、TT时间（P<0.05或P<0.01）,降低纤维蛋白原的含量（P<0.01）,显著降低模型大鼠脑组织含水量（P<0.05）,牡丹皮有效部位组大鼠TT延长（P<0.05）,降低纤维蛋白原的含量（P<0.01）,显著降低模型大鼠脑组织含水量（P<0.05）。结论：益气活血风静胶囊具有显著的抗凝血以及抑制以ADP诱导的血小板聚集的作用,并对MCAO大鼠有较好的活血作用。     

细胞外信号调节激酶1/2抑制剂PD98059对弥散性血管内凝血大鼠多器官损伤的保护作用

目的:研究细胞外信号调节激酶1/2(ERK1/2)抑制剂PD98059对大鼠内毒素弥散性血管内凝血(DIC)多器官损伤的保护作用。方法:Sprague-Dawley(SD)大鼠随机分为对照组、DIC组及抑制剂组。DIC组通过腹腔注射6mg/kg脂多糖(LPS)建立内毒素DIC模型,抑制剂组腹腔注射6mg/kg LPS和10mg/kg PD98059。5h后取血,利用全自动血凝仪及生化仪检测活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、乳酸脱氢酶(LDH)、碱性磷酸酶(ALP)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、尿素(BUN)及肌酐(Cr)等指标;并留取心肝肾组织,光镜下观察其形态学变化。结果:与对照组相比:DIC组APTT、LDH、ALP、ALT、AST、BUN及Cr均延长或升高(P<0.01),FIB较对照组降低(P<0.01),心、肝、肾组织病理学检查均有明显的血管扩张充血;PD98059预防性用药后,除Cr外各指标均有明显改善(P<0.01),心、肝、肾组织血管充血减轻。结论:ERK1/2抑制剂PD98059能够减轻内毒素DIC时的多器官损伤,其机制与ERK1/2信号通路的抑制有关。     

注射用血塞通(冻干)对家兔下腔静脉血栓的抑制作用研究

目的 观察注射用血塞通（冻干）对电刺激所致家兔下腔静脉血栓形成的影响,并对其作用机制进行探讨。方法 使用电刺激伴狭窄法制备家兔下腔静脉血栓模型,造模1 h后,连续5天iv给予5、10、20 mg/kg的注射用血塞通（冻干）、sc给予100 U/kg的低分子肝素钠注射液,最后一次给药1 h后测定家兔出血时间和出血量,颈动脉取血分离血浆,试剂盒法检测活化部分凝血活酶时间（APTT）、凝血酶原时间（PT）、凝血酶时间（TT）以及纤维蛋白原（FIa）水平,ELISA试剂盒法检测血浆内凝血因子FIIa、FXa、FXIa、抗凝血酶III（ATIII）、凝血因子TAT、活化蛋白C（APC）、组织性纤维溶酶激活剂（t-PA）、纤溶酶原（PLG）、尿激酶原（PROUK）、胰蛋白酶（Trypsin）、6-酮前列腺素F1a（6-keto-PGF1a）和血栓素B₂（TXB₂）水平;取血栓,测定血栓湿质量、干质量以及基质量。在血小板聚集实验中,制备家兔贫、富血小板血浆,分别以胶原（CG）、二磷酸腺苷二钠盐（ADP）和花生四烯酸钠（AA）为诱导剂,比浊法测定不同浓度血塞通对血小板聚集的影响。结果 家兔iv注射用血塞通（冻干）后,与模型组比较,血栓湿质量、干质量及基质量均显著降低,并具有一定的剂量依赖性;出血时间和出血量未出现明显增加,APTT、PT和TT也未出现明显变化;血浆内t-PA和6-keto-PGF1a水平显著增加,TXB₂水平显著降低,其他指标没有明显变化。在血小板聚集实验中,血塞通可以剂量依赖性地抑制由AA诱导的血小板聚集。结论 注射用血塞通（冻干）具有良好的抑制下腔静脉血栓作用,且无明显出血副作用,作用机制与增强纤溶活性、抑制血小板聚集和血管收缩有关。     

Suppression of tumour necrosis factor‐α by Schizonepeta tenuifolia water extract via inhibition of IκBα degradation and Jun N‐terminal kinase/stress‐activated protein kinase activation

Objectives The anti‐inflammatory effects of an aqueous extract of Schizonepeta tenuifolia on lipopolysaccharide (LPS)‐induced tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) in vivo and in vitro have been investigated. Methods C57BL/6 mice were orally administered phosphate‐buffered saline (control) or S. tenuifolia water extract (50, 200, 500 or 1000 mg/kg) for 10 days before intraperitoneal administration of LPS (1.3 mg/kg). Blood samples were obtained 1 h after LPS challenge, followed by determination of TNF‐α and IL‐6 levels. Peritoneal macrophages from thioglycollate‐injected mice were obtained and stimulated with LPS and S. tenuifolia water extract for viability assay, cytokine analysis, real‐time RT PCR and Western blotting. Key findings Oral administration of S. tenuifolia water extract to mice significantly reduced LPS‐induced serum levels of TNF‐α, but not IL‐6. When peritoneal macrophages were treated in vitro with S. tenuifolia water extract, the inhibition of LPS‐induced TNF‐α was more pronounced than that of IL‐6 at the level of secreted protein and mRNA. S. tenuifolia water extract reduced the degradation of IκBα and the nuclear relocation of p65 NF‐κB, but the phosphorylation of IκBα was not affected. Inhibition of c‐Jun N‐terminal kinase/stress‐activated protein kinase (JNK/SAPK) by S. tenuifolia water extract led secondarily to the inhibition of phospho‐c‐Jun and phospho‐ATF‐2. Conclusions These results indicated that the downregulation of TNF‐α by S. tenuifolia water extract may have involved the inhibition of both IκBα degradation and activation of c‐Jun and ATF‐2 involving suppression of JNK/SAPK.     

不同病因急性弥漫性血管内凝血临床特点及指标观察

目的探讨感染、急性白血病、病理产科3种不同病因急性弥漫性血管内凝血(DIC)临床特点及血小板(PLT)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(Fg)、凝血酶时间(TT)、硫酸鱼精蛋白副凝(3P)试验、D-二聚体(D-D)阳性率在不同病因DIC中有无差异。方法回顾性分析青岛市第八人民医院2006年11月至2010年11月收治住院的71例以感染、急性白血病、病理产科为基础病的DIC患者的临床资料,对比3种不同病因DIC患者临床出血程度、休克、重要器官损害、微血管溶血表现及PLT、PT、APTT、Fg、TT、3P试验、D-二聚体阳性率。结果 3组患者在出血程度、休克发生率、重要器官损害发生率、疗效、病死率、APTT阳性率方面比较,差异有统计学意义(P<0.05),在PLT、PT、Fg、TT、3P试验、D-二聚体阳性率方面,3组比较差异无统计学意义(P>0.05)。组间两两比较结果显示,感染组与急性白血病组、病理产科组在出血程度、重要器官损害发生率、疗效、病死率方面比较有统计学意义(P<0.05);急性白血病组与感染组、病理产科组在休克发生率方面比较有统计学意义(P<0.01);急性白血病组和感染组在APTT阳性率方面比较,差异有统计学意义(P<0.01)。结论病理产科相关DIC和急性白血病相关DIC临床出血重,器官损害较少,预后较好。感染相关DIC出现休克、器官损害多见,疗效、预后差、病死率高。     

多发伤患者出现DIC的早期诊断和治疗

目的观察52例多发伤患者弥散性血管内凝血的早期诊断及早期给予血小板、冷沉淀、凝血酶原复合物、血浆、肝素治疗的临床效果。方法对多发伤患者早期进行血小板计数、凝血功能、D-二聚体检查,对合并DIC的52例患者根据其血小板计数、凝血功能给予血小板、冷沉淀、凝血酶原复合物、血浆、肝素治疗并观察治疗后1天患者的血小板计数、凝血功能。结果治愈46例,死亡6例,治愈率88．5％。52例患者输注血小板、冷沉淀、凝血酶原复合物、血浆、肝素治疗后1天与输注前相比,患者的血小板计数明显增加,凝血酶原时间（PT）明显缩短,纤维蛋白原（Fbg）含量增加。结论对多发伤并发DIC患者早期输注血小板、冷沉淀、凝血酶原复合物、血浆、肝素等综合治疗可有效阻止DIC的继续发展,重建凝血机制,恢复机体功能。     

Evaluation and in vivo efficacy study of pyrano[3,2‐c]quinoline analogues as TNF‐α inhibitors

A series of pyrano[3,2 c]quinoline was evaluated for its in vivo efficacy as TNF‐α inhibitor using LPS, phosphodiesterase (PDE)‐4, and CIA assays in different mice/rat models. The synthesis was performed using one‐pot multicomponent condensation between 2,4‐dihydroxy‐1‐methylquinoline, malononitrile, and diverse un(substituted) aromatic aldehydes. In vivo efficacy of the title compounds was evaluated using LPS assay in BALB/c mice, PDE4 inhibition in ketamine–xylazine‐induced anesthetize SD rats, and CIA assay was performed in DBA/1J mice as per the standard literature protocols. The outcome of the study revealed that compound 4v was found to be most promising candidate of the series. It was efficacious with 48.8 ± 13.0% inhibition of TNF‐α release at 100 mg/kg p.o., in the LPS assay in Balb/c mice model. It was effective in PDE4 assay in ketamine–xylazine‐induced anesthetize SD rats with duration of 38.3 ± 4.5 min for reversal of anesthetic effect and also showed significant inhibition of PDE4 in salbutamol treated U937 cell assay. It was also abolished TNF‐α induced phosphorylation and degradation of IκBα. Ultimately, its effect on CIA‐related bone and cartilage damage was found statistically similar to Enbrel.     

实验性兔羊水栓塞血浆凝血指标的含量变化

目的　观察兔羊水栓塞 ( AFE)后血浆凝血指标的动态变化。方法　采用怀孕家兔制作羊水栓塞动物模型 ,将不同性质的自身羊水注入兔血循环 ,分别在羊水注入前、注入后 5、45 m in从兔心脏取血 ,用血凝仪检测血浆中各项凝血指标包括纤维蛋白原定量 ( FIB)、血浆凝血酶原时间 ( PT)、凝血酶凝固时间 ( TT)、活化部分凝血活酶时间 ( APTT)的动态变化。结果　注入羊水后 PT、TT、APTT时间显著延长 ( P<0 .0 1) ,FIB则显著降低 ( P<0 .0 1) ,而对照组无显著变化 ( P>0 .0 5 )。结论　凝血指标的动态变化表明羊水栓塞早期有发生弥漫性血管内凝血 ( DIC)的趋势 ,胎盘提取液中的某些成分可能加重了 DIC的严重程度