Signal transduction of a G protein-coupled receptor in caveolae: colocalization of endothelin and its receptor with caveolin.

Caveolae are small invaginations of the plasma membrane 50-100 nm in diameter. Since calcium channels, inositol 1,4,5-trisphosphate receptors, and heterotrimeric GTP-binding proteins (G proteins) are localized in caveolae, they may participate in signal transduction by G protein-coupled receptors. Here we show that the G protein-coupled endothelin receptor subtype A (ETA) and its bound endothelin ligand are found in plasma membrane caveolae. ETA and its bound ligand coimmunoprecipitate with caveolin, a structural component of caveolae, in extracts of cells expressing transfected ETA receptors. Confocal fluorescence microscopy shows colocalization of ETA receptors and caveolin in micropatches at or near the plasma membrane, in the absence of endothelin ligands. These observations demonstrate a functional role for plasma membrane caveolae in signal transduction by this G protein-coupled receptor.     

青蒿琥酯分别与诺氟沙星、甲硝唑伍用的体内、外抗恶性疟作用

目的　了解青蒿琥酯分别与诺氟沙星、甲硝唑伍用的体内、外抗疟作用。　方法　采用青蒿琥酯与诺氟沙星 (A组 )或甲硝唑 (B组 )联用 3d疗法治疗无并发症的恶性疟。体外测定采用 Rieckmann体外微量法测定恶性疟原虫对 3种药物单一用药及青蒿琥酯分别与诺氟沙星或甲硝唑联用的敏感性。　结果　体内观察法共收治 70例病人 ,其中 A组 5 5例 ,B组 15例。平均退热时间分别为 (2 6 .5± 16 .5 ) h(8h～ 93h)、(19.2± 11.0 ) h(4h～ 4 1h) ;平均原虫无性体转阴时间分别为 (37.4± 15 .3) h(13h～ 93h)和 (42 .8± 14 .7) h(2 5 h～ 72 h) ;2 8d复燃率分别为 4 7.4 %和 75 .0 %。体外微量法测得青蒿琥酯与诺氟沙星伍用的 ID50 分别为单用组的 5 .9%和 0 .3% ;青蒿琥酯与甲硝唑伍用的 ID50 分别为单用组的38.8%和 5 .6 %。　结论　青蒿琥酯分别与诺氟沙星、甲硝唑伍用在体外对抗青蒿琥酯恶性疟原虫有明显增效作用 ,但在临床治疗中未能提高治愈率     

Comparison of Helicobacter pylori eradication rate according to different PPI-based triple therapy--omeprazole, rabeprazole, esomeprazole and lansoprazole--]

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) is an important cause of various gastrointestinal diseases. H. pylori eradication is essential for the cure and prevention of associated diseases. Nowdays, proton pump inhibitor (PPI)-based triple therapy is the standard eradication regimen. The aims of this study were to compare the H. pylori eradication rate of different PPI-based triple therapies and to find out the factors influencing the eradication rate. METHODS: From May 2002 through February 2004, H. pylori infected patients were treated with the eradication regimen based on one of the four PPIs (omeprazole, rabeprazole, esomeprazole and lansoprazole) for 1 or 2 weeks. After two weeks, drug compliance, adverse effects, and smoking history during the eradication therapy were obtained. The follow-up H. pylori test was performed 4 weeks after the completion of therapy. The data were analyzed by Chi-square test and multiple logistic regression analysis. RESULTS: Overall eradication rate was 83.5%. There was no significant difference in eradication rate among four PPIs (p=0.379). Odds ratio (OR) for omeprazole and rabeprazole was 1.15 (95% CI 0.50-2.68); for omeprazole and esomeprazole, OR 1.63 (95% CI 0.68-3.89); and for omeprazole and lansoprazole, OR 1.13 (95% CI 0.50-2.56). Smoking habit, site of ulcer, and the duration of therapy affected the eradication rate significantly. CONCLUSIONS: The efficacy of four different PPIs for H. pylori eradication is similar to each other. Smoking, site of ulcer, and the duration of treatment have significant effects on eradication rates.     

Biomechanics of cartilage articulation: effects of lubrication and degeneration on shear deformation

OBJECTIVE: To characterize cartilage shear strain during articulation, and the effects of lubrication and degeneration. METHODS: Human osteochondral cores from lateral femoral condyles, characterized as normal or mildly degenerated based on surface structure, were selected. Under video microscopy, pairs of osteochondral blocks from each core were apposed, compressed 15%, and subjected to relative lateral motion with synovial fluid (SF) or phosphate buffered saline (PBS) as lubricant. When cartilage surfaces began to slide steadily, shear strain (Exz) and modulus (G) overall in the full tissue thickness and also as a function of depth from the surface were determined. RESULTS: In normal tissue with SF as lubricant, Exz was highest (0.056) near the articular surface and diminished monotonically with depth, with an overall average Exz of 0.028. In degenerated cartilage with SF as lubricant, Exz near the surface (0.28) was 5-fold that of normal cartilage and localized there, with an overall E(xz) of 0.041. With PBS as lubricant, Exz values near the articular surface were approximately 50% higher than those observed with SF, and overall Exz was 0.045 and 0.062 in normal and degenerated tissue, respectively. Near the articular surface, G was lower with degeneration (0.06 MPa, versus 0.18 MPa in normal cartilage). In both normal and degenerated cartilage, G increased with tissue depth to 3-4 MPa, with an overall G of 0.26-0.32 MPa. CONCLUSION: During articulation, peak cartilage shear is highest near the articular surface and decreases markedly with depth. With degeneration and diminished lubrication, the markedly increased cartilage shear near the articular surface may contribute to progressive cartilage deterioration and osteoarthritis.     

Soluble Fms-like tyrosine kinase associated with preeclampsia in pregnancy in systemic lupus erythematosus

OBJECTIVE: Placental synthesis of soluble Fms-like tyrosine kinase (sFlt-1) is responsible for the increased level of serum sFlt-1 in preeclampsia. sFlt-1 binds to the receptor-binding domain of placental growth factor (PlGF) and vascular endothelial growth factor (VEGF), acting as an endogenous inhibitor of VEGF and PlGF signaling in endothelial cells. It has been hypothesized that increased circulating sFlt-1 contributes to the endothelial dysfunction, hypertension, and proteinuria of preeclampsia. We examined the association of sFlt-1 and preeclampsia in pregnancies in patients with systemic lupus erythematosus (SLE). METHODS: A case-control study was performed using stored serum samples. Cases were SLE pregnancies with later preeclampsia and controls were SLE pregnancies without later preeclampsia. RESULTS: The 52 SLE pregnancies occurred from 1998 to 2001. Nine (17%) pregnancies met the definition of preeclampsia and an additional 9 (17%) met the definition of superimposed preeclampsia. sFlt-1 concentration was significantly higher in SLE pregnancies with preeclampsia (1768 +/- 196 pg/ml) than in those without (1177 +/- 143 pg/ml) (p = 0.0185). CONCLUSION: Our study shows for the first time that sFlt-1 is associated with preeclampsia in patients with SLE, as previously shown in the general pregnancy population. This suggests that SLE pregnancies at risk for preeclampsia can be identified early in the pregnancy by sFlt-1, thus identifying them for high-risk obstetric referral and appropriate monitoring.     

低剂量口服避孕药、高血压及其联合作用对女性脑卒中发病危险性的影响

目的探讨低剂量口服避孕药、高血压及其联合作用对女性脑卒中发病危险l生的影响。方法应用病例对照研究方法,共收集了453例脑卒中病例,按照年龄与地区等分布特征1：2匹配919例对照。通过问卷调查收集基本资料,并采集了静脉血用于脂代谢测定。结果多因素Logistic回归分析显示：不同类型脑卒中的主要风险因素不同,出血型脑卒中的风险因素有高血压、复方口服避孕药（combinedoralcontraceptives,COC）使用和脑卒中家族史;而梗塞型脑卒中的风险因素则包括：高血压、高脂血症及脑卒中家族史。联合作用分析结果显示：COC使用与高血压的联合作用使女性出血型脑卒中的风险增加18．51倍（OR=19．51,95％C／：9．70～39．23）,梗塞型脑卒中的风险增加14．49倍（OR=15．49,95％C／：8．87～27．67）。结论COC使用与高血压的联合作用可以显著升高女性出血型及梗塞型脑卒中的发病危险。     

氟哌噻吨美利曲辛联合奥美拉唑与莫沙比利治疗功能性消化不良的疗效观察

目的：探讨氟哌噻吨美利曲辛联合奥美拉唑与枸橼酸莫沙比利治疗功能性消化不良的疗效。方法：选择本院门诊治疗的190例功能性消化不良患者,随机分为观察组和对照组各95例,观察组给予氟哌噻吨美利曲辛片1片/d,晨服,睡眠不佳者中午加服1片,奥美拉唑20 mg,2次/d,枸橼酸莫沙比利5 mg,3次/d,治疗4周;对照组给予奥美拉唑20 mg,2次/d,枸橼酸莫沙比利5 mg,3次/d,治疗4周。观察两组患者治疗前及治疗4周后的临床症状改善情况,并对临床疗效及不良反应进行评价。结果：两组患者治疗4周后症状均明显减轻（P〈0.01）,观察组治疗后的症状平均总评分、显效率和总有效率明显高于对照组,两组比较差异有统计学意义（P〈0.05）;两组不良反应发生率比较差异无统计学意义（P〉0.05）。结论：抗抑郁药联合PPI与促动力药治疗功能性消化不良优于PPI加用促动力药,可提高功能性消化不良的治疗效果。氟哌噻吨美利曲辛联合奥美拉唑与枸橼酸莫沙比利治疗功能性消化不良疗效高,不良反应发生率低。