幽门螺杆菌cagⅡ对胃上皮细胞IL-8基因转录的影响及机制

目的探讨HpcagⅡ对胃上皮细胞IL-8基因转录的影响及信号传导机制。方法构建 cagⅡ基因位点缺失Hp突变株及带有IL-8报告基因的人胃癌细胞系L5F11,用液体闪烁计数仪测定荧光素酶(IL8转录)活性,用ELISA法测定IL8蛋白浓度。结果所有Hp突变株诱导荧光素酶活性与IL8蛋白浓度较亲代菌株26695均降低[(0．13±0．01)×cpm比(0．59±0．05)×(P<0．01);(0．73±0．13)ng／ml比(2．22±0．65)ng／ml,(P<0．05)]。PTK抑制剂herbimycinA不仅抑制Hp诱导的荧光素酶活性[(0．71±0．18)×cpm比(1．51±0．23)×cpm,(P<0．05)],而且抑制IL-8蛋白表达[(0．83±0．41)ng／ml比(3．22±0．59)ng／ml,(P<0．05)],但herbimycinA对TNFα诱导的荧光素酶活性及IL8蛋白表达均无影响(P均>0．05);PKA抑制剂H7抑制TNFα诱导的荧光素酶活性[(0．74±0．16)×cpm比(2．62±0．26)×cpm,(P<0．001)]及IL8蛋白表达[(1．45±0．38)ng／ml比(4．12±0．43)ng／ml,(P<0．01)],而对Hp诱导的荧光素酶活性无影响(P>0．05)。结论HpcagⅡ中的多基因能够调节胃上皮细胞IL-8基因转录,且这一作用主要经蛋白酪氨酸激酶途径。     

Decreased intracellular degradation and increased secretion of apo B-100 in Hep G2 cells after inhibition of cholesteryl ester synthesis

Control of apolipoprotein B (apo B) secretion in hepatocytes occurs partly at the post-translational level. The key step in this process appears to be intracellular degradation of newly synthesized apo B. The aim of this paper was to investigate the mechanisms that regulate apo B secretion by Hep G2 cells, in response to the inhibition of Acyl-CoA Acyltransferase (ACAT) by the compound Sandoz 58035 (S-58035). S-58035 (20 μM) reduced cholesteryl ester synthesis from [¹⁴C]oleate by 95%, and increased significantly, in a dose-dependent manner, (2–100 μM) apo B secretion, either in control conditions (from 78±4.3 to 126±6.1 ng apo B-100/mg cell protein/4 h) or upon stimulation of apo B secretion by oleate (from 134±4.23 to 177±4.3 ng apo B/mg cell protein/4 h). This increased secretion of newly synthesized apo B-100 was confirmed by pulse experiments and by gradient ultracentrifugation of the media. Moreover pulse-chase experiments showed that the addition of S-58035 reduced intracellular degradation of apo B-100, both in control conditions and in the presence of oleate. S-58035 (20 μM) did not affect total cellular cholesterol content, but free cholesterol increased with a concomitant decrease of cholesteryl ester (−20%). S-58035 increased cellular triglyceride mass, which was observed in basal conditions (from 12.8±1.09 to 22.7±2.7 μg TG/mg cellular protein) and also in presence of oleate (from 48±0.53 to 59±6.3 μg TG/mg cellular protein). This effect is due to a stimulation of triglyceride synthesis, as determined by incorporation of [³H]glycerol into cellular triglycerides. From these data we conclude that, under our experimental conditions, triglyceride synthesis and/or availability is likely to control intracellular degradation of apo B.     

Serum blood urea nitrogen and long-term mortality in acute ST-elevation myocardial infarction

Older age is an independent predictor of mortality after percutaneous coronary intervention (PCI) in patients with Non-ST elevation Acute Coronary Syndrome (ACS). GPIIb/IIIa inhibitors are proved to improve outcome in high risk patients, but conflicting data are available about the effects of these inhibitors in elderly. Accordingly, we studied a consecutive population of elderly patients undergoing PCI for Non-ST elevation ACS. A total of 500 patients were divided in: GPI group (247 pts; mean age 77 ± 1.9 years) treated by stenting plus abciximab and, no GPI group (253 pts; mean age 77 ± 2.4 years) treated by stenting alone. Propensity analysis was used to account for the nonrandomized use of GPIIb/IIIa inhibitors. During hospitalization, incidence of death was similar among groups (3.2% vs 4.6%) without difference regarding incidence of major (1.6% vs 1.1%) and minor bleedings (4% vs 3%). At long-term follow-up the rate of death was significantly lower in GPI group (4.5% vs 12.3%; p = 0.002) as well as the rate of acute myocardial infarction (2.8% vs 11.1%; p = 0.0001), and pre-PCI (5.7% vs 13.4%; p = 0.003). Cox regression analysis identified abciximab use as an independent predictor of lower long-term major adverse cardiac event (MACE) after adjustment for propensity score (Exp (B) 0.620, 95%CI 0.394–0.976, p = 0.039). Our results suggest that addition of abciximab to stenting improves outcome in elderly patients with Non-ST elevation ACS, leading to an absolute benefit for reduction of death and MACE, with an acceptable rate of major and minor bleedings.     

Case Reports on Emergency Treatment of Cardiovascular Syndromes Through Heparin‐Mediated Low‐Density Lipoprotein/Fibrinogen Precipitation: A New Approach to Augment Cerebral and Myocardial Salvage

Abstract: We report the first experiences with HELP apheresis as an emergency treatment for acute cardiovascular syndromes; two patients who were not eligible for lysis therapy and catheter intervention were treated with HELP apheresis instead. Both patients had a most severe, generalized atherosclerosis and reached the hospital too late for conventional measures. In both cases, the use of the apheresis dramatically improved the clinical situation to such an extent that the possibilities of this apheresis system urge further investigation.     

西洛他唑与缺血性卒中

西洛他唑通过抑制环核苷酸磷酸二酯酶-3提高细胞内环磷酸腺苷(cyclic adenosine monophosphate,cAMP)水平.其主要作用由cAMP所介导,包括抑制血小板聚集、抗血栓形成、血管扩张和抗内皮细胞增殖等.最近的实验研究表明,西洛他唑在干预急性脑缺血和慢性脑灌注不足方面显示出希望;临床试验亦证明其有效.文章总结了西洛他唑的药理学作用和机制,及其在缺血性卒中时的保护作用.     

瑞舒伐他汀和阿托伐他汀对氯吡格雷抗血小板活性的影响

目的观察瑞舒伐他汀和阿托伐他汀对氯吡格雷抗血小板活性的影响。方法选择60例冠心病患者接受阿司匹林100mg/d、氯吡格雷75 mg/d及低分子肝素5000 U/12 h治疗,5 d后随机分为阿托伐他汀20mg/d(阿托伐他汀组,30例)和瑞舒伐他汀10 mg/d(瑞舒伐他汀组,30例)。在服用氯吡格雷之前(基线值)、加用他汀类药物之前及服用他汀类药物3d后,用全血阻抗法分别测定不同浓度二磷酸腺苷(5、10、20μmol/L)诱导的血小板聚集率。结果与基线值比较,服用氯吡格雷5 d后和加服他汀类药物治疗3 d后,2组患者血小板聚集率明显降低,差异有统计学意义(P<0.05);与治疗前比较,阿托伐他汀组患者血小板聚集率有所升高,而瑞舒伐他汀组患者血小板聚集率有所下降,但差异无统计学意义(P>0.05)。结论经细胞色素3A4途径代谢的阿托伐他汀及不经细胞色素3A4代谢的瑞舒伐他汀,短期内对氯吡格雷抗血小板活性无影响。     

颈部动脉支架置入术后双联抗血小板治疗:多久合适?

目的 观察颈部动脉支架置入术后双联抗血小板治疗不同时间的效果,探讨合理的双联抗血小板治疗时间.方法 66例颈部动脉有症状狭窄＞50%或无症状狭窄＞70%的患者在局麻下行支架置入术,术后随机分为双联抗血小板治疗(阿司匹林+氯吡格雷)1个月组和3个月组,然后长期服用阿司匹林.前瞻性观察并发症、血管事件以及再狭窄发生率.结果 术后6～36个月,两组均无血管事件和死亡,并发症和再狭窄(9%对6%)发生率无显著差异(P=0.642).结论 颈部动脉支架置入术后阿司匹林+氯吡格雷联合治疗1个月与3个月的疗效并无显著差异,1个月的双联抗血小板治疗可能比较合适,但还需大规模随机对照试验证实.

Abstract：

Objective To observe the effects of dual antiplatelet therapy at different time after cervical artery stenting and to investigate the reasonable time for dual antiplatelet therapy. Methods Sixty-six patients with symptomatic cervical artery artery stenosis ＞50% or asymptomatic stenosis ＞70% performed stenting under local anesthesia. They were randomly allocated into dual antiplatelet therapy (aspirin + clopidogrel) for 1 month and for 3-month groups after procedure, and then they began to take aspirin for a long time. The complications, vascular events, and the incidence of restenosis were observed respectively. Results There were no vascular events and death in both groups from 6 to 36 months after procedure. There was no significant difference in the incidence of complication and restenosis (9% vs. 6%, P = 0. 642). Conclusions There was no significant difference in the efficacy of aspirin + clopidogrel treatment after cervical artery stenting between 1 month and 3 months. One month dual antiplatelet therapy may be appropriate, but large-scale randomized controlled trials are needed to confirm it.     

非对称性二甲基精氨酸和胱氨酸蛋白酶抑制剂C与冠心病

目的 探讨冠状动脉疾病中血浆非对称性二甲基精氨酸(ADMA)与胱氨酸蛋白酶抑制剂C(Cystatin C)之间的关系.方法 选取冠心病患者87例(其中急性心肌梗死39例,不稳定性心绞痛48例),健康对照组51例;同时,依据Cystatin C水平将冠心病患者分为Cystatin C升高组(51例)与无Cystatin C升高组(36例),采用高效液相色谱法测定血浆中ADMA、对称性二甲基精氨酸(SDMA)、左旋精氨酸(L-Arg)的含量,采用德国BNProSpec全自动速率散色比浊仪测定血浆Cystatin C的含量.结果 冠心病患者血浆ADMA[(0.47±0.15)μmol/L比(0.37±0.15)μmol/L]、SDMA[(0.39±0.19)μmol/L比(0.28±0.12)μmol/L]和Cystatin C浓度[(1.16±0.32)mg/L比(0.73±0.16)mg/L]均高于正常对照组(P均<0.05),L-Arg浓度低于正常对照组[(59.4±19.4)μmol/L比(83.7±19.6)μmol/L,P<0.05];对冠心病组的亚组分析显示血浆ADMA、L-Arg和Cystatin C浓度在心肌梗死组较心绞痛组差异无统计学意义.在Cystatin C<1 mg/L的冠心病患者中血浆ADMA与正常对照组比较,差异无统计学意义;而在Cystatin C>1 mg/L的冠心病患者血浆ADMA高于正常对照组[(0.50±0.17)μmol/L比(0.39±0.15)μmol/L,P<0.05].结论 只有在血浆Cystatin C水平升高的冠心病患者血浆ADMA水平才明显升高,提示冠心病患者血浆ADMA水平的升高并不与冠心病直接相关,可能与冠心病患者伴随轻微肾损害有关.     

Secretion of respiratory syncytial virus inhibitors and antibody in human milk throughout lactation

Neutralising inhibitors to respiratory syncytial (RS) virus have been demonstrated in the whey of most samples of human milk tested. Although high titres were secreted in colostra of some mothers (1/10–1/2,560; median 1/40) inhibitor levels in milk collected after the first week of lactation were uniformly low (median 1/10). High neutralising titres correlated with high colostral levels of specific antiviral IgA but, unlike neutralising activity, IgA antiviral antibody persisted in the milk of only four of 18 mothers. Similarly, antiviral IgG and IgM antibodies were not generally detected after the first postpartum week. Differences in antibody secretion among mothers did not correlate with differences in total protein or total immunoglobulin secretion, and appeared to reflect maternal immune status. In one mother a marked rise in specific antiviral IgA and IgG secretions during the second and third months of lactation suggested a response to virus infection. The relevance of maternal immunity and colostral and milk antiviral antibody to protection of breast-fed babies from RS-virus bronchiolitis is discussed.