急性肺损伤/急性呼吸窘迫综合征的药物治疗

急性肺损伤(acute lung injury,ALI)/急性呼吸窘迫综合征(acute respiratory dysfunction syndrome,ARDS)是危重病医学的重要课题,死亡率很高。尽管一些药物治疗包括肺表面活性物质、一氧化氮、糖皮质激素以及利索茶碱已经在ALI/ARDS患者中应用,但是没有一种药物可降低死亡率。本文综述了ALI/ARDS治疗药物的临床试验结果及其目前推荐应用的等级,同时也就一些有望在未来临床应用的药物,如β2-受体激动剂、角质化细胞生长因子以及活化蛋白-C进行讨论。

P48-Triggered transmembrane signaling transduction of human monocytes:mobilization of calcium ion and activation of protein kinase C(PKC)

P48 is a cytokine which induces monocyte differentia-tion and the induction of cytotoxic activity. In this study,the signal transduction events involved in the stimulation of monocytes with the membrane form of P48 (mP48) were investigated. Monocyte stimulation with mP48 was found to involve the mobilization of intracellular calcium (Ca2+)and the activation and translocation of PKC from the cy-tosol to the membrane. Membane P48 induced a rapid rise of intracellular Ca2+ in a dose dependent maner. Simi-larly the stimulation of monocytes with P48 was found to involve the activation and translocation of PKC. The translocation of PKC was rapid (within 0-5 min) yet tran-sient with PKC activity returning to control levels by 8 min. The functional role of protein kineses in P48 induced TNF secretion was studied using various kinese inhibitors. The PKC inhibitors, H-7 and sphingosine, were found to inhibit P48 induced TNF secretion with 50% inhibition at 5μM HA1004, which inhibts cyclic nucleotide-dependent kinase (PKA, Ki 1.2μM), did not inhibit TNF secretion. H-8 (PKA inhibitor) was found to be an effective inhibitor of TNF secretion only at high concentrations(30μp. The Calmodulin-dependent kinase inhibitor, W7 (Ki 12μM)was found to be effective at concentration above 5μM.These findings suggest that P48-triggered TNF secretion involves transmembrane Ca2+ signaling and the subse-quent activation of at least two protein kineses, PKC and CaMK.

Factor V Leiden mutation in one family of Chinese origin

目的 研究中国人FVLeiden基因突变引起的抗活化蛋白C现象 (APCR)。方法 采用APTT±APC方法、多聚酶链反应 (PCR)、MnLI限制性内切酶分析 ,序列特异性引物 (PCR SSP)和DNA测序方法 ,对中国汉族 30例“正常”无关个体和 2 0例血栓性疾病患者进行APCR测定和FVLeiden基因突变分析。结果 发现一例正常人抗APC敏感值比值 (APC SR)明显减低 (0 8) ,并确诊为FVLeiden基因 (Arg50 6 Gln)突变杂合子 ,其叔祖父、父亲、弟弟和儿子同样确定为FVLeiden基因杂合子 ;有 3例血栓性疾病患者APC SR低于正常 ,但均无FVLeiden基因突变。结论 这是在国内发现的首例四代FVLeiden突变所致的APCR现象的家系。中国人血栓症中APCR的产生是否导致其它未知的基因缺陷 ,尚待进一步研究。