Inhibition of collagen-induced platelet activation by 5'-p- fluorosulfonylbenzoyl adenosine: evidence for an adenosine diphosphate requirement and synergistic influence of prostaglandin endoperoxides

The relative roles of platelet autacoids such as adenosine diphosphate (ADP), prostaglandin endoperoxides, and thromboxane A2 (TXA2) in collagen-induced platelet activation are not fully understood. We reexamined this relationship using the ADP affinity analogue, 5'-p- fluorosulfonylbenzoyl adenosine (FSBA), which covalently modifies a receptor for ADP on the platelet surface, thereby inhibiting ADP- induced platelet activation. Collagen-induced shape change, aggregation, and fibrinogen binding were each fully inhibited under conditions in which FSBA is covalently incorporated and could not be overcome by raising the collagen used to supramaximal concentrations. In contrast, TXA2 synthesis stimulated by collagen under conditions that produced maximum aggregation was only minimally inhibited by FSBA. Since covalent incorporation of FSBA has been previously shown to specifically inhibit ADP-induced activation of platelets, the present study supports the contention that ADP is required for collagen-induced platelet activation. Under similar conditions, indomethacin, an inhibitor of cyclooxygenase, inhibited collagen-induced shape change, indicating that endoperoxides and/or TXA2 also play a role in this response. Shape change induced by low concentrations (10 nmol/L) of the stable prostaglandin endoperoxide, azo-PGH2, was also inhibited by FSBA. These observations indicate a role for ADP in responses elicited by low concentrations of endoperoxides. However, at higher concentrations of azo-PGH2 (100 nmol/L), inhibition by FSBA could be overcome. Thus, the effect of collagen apparently has an absolute requirement for ADP for aggregation and fibrinogen binding and for both ADP and prostaglandins for shape change. Aggregation and fibrinogen binding induced by prostaglandin endoperoxides also required ADP as a mediator, but ADP is not absolutely required at high endoperoxide concentration to induce shape change.     

A randomized study comparing the efficacy and safety of nadroparin 2850 IU (0.3 mL) vs. enoxaparin 4000 IU (40 mg) in the prevention of venous thromboembolism after colorectal surgery for cancer

BACKGROUND: The optimal thromboprophylactic dosage regimen of low-molecular-weight heparins in high-risk general surgery remains debatable. OBJECTIVES: We performed a randomized, double-blind study to compare the efficacy and safety of nadroparin 2850 IU (0.3 mL) and enoxaparin 4000 IU (40 mg) in the prevention of venous thromboembolism (VTE) after colorectal surgery for cancer. Patients and methods: Patients undergoing resection of colorectal adenocarcinoma were randomized to receive once daily either 2850 IU nadroparin or 4000 IU enoxaparin s.c. for 9 +/- 2 days. The primary efficacy outcome was the composite of deep vein thrombosis (DVT) detected by bilateral venography or documented symptomatic DVT or pulmonary embolism up to day 12. The main safety outcome was major bleeding. A blinded independent committee adjudicated all outcomes. RESULTS: Out of 1288 patients analyzed, efficacy was evaluable in 950 (73.8%) patients. The VTE rate was 15.9% (74/464) in nadroparin-treated patients and 12.6% (61/486) in enoxaparin-treated patients, a relative risk of 1.27 (95% confidence interval; CI: 0.93-1.74) that did not met the criterion for non-inferiority of nadroparin. The rate of proximal DVT was comparable in the two groups (3.2% vs. 2.9%, respectively), but that of symptomatic VTE was lower in nadroparin-treated patients (0.2% vs. 1.4%). There was significantly (P = 0.012) less major bleeding in nadroparin- than in enoxaparin-treated patients (7.3% vs. 11.5%, respectively). CONCLUSION: Compared with those receiving enoxaparin 4000 IU, patients treated with nadroparin 2850 IU showed a higher incidence of asymptomatic distal DVT, but a lower incidence of symptomatic VTE. Nadroparin treatment was safer in terms of bleeding risk.     

运动状态下CT扫描后靶区三维重建的形变规律

目的:观察呼吸运动对肺部靶区三维重建的影响。方法:用步进电机、步进电机驱动器、导轮、有机玻璃球、低密度度泡沫等设计能模拟肿瘤随呼吸运动的体模;取不同螺距(0.875,1.675,0.625mm)、不同层厚(8mm×1.25mm或8mm×2.50mm)和运动周期组成6个不同的扫描序列在GE LightSpeed16CT上扫描,然后采用体绘制技术对所获得CT图像进行三维重建,用三维工具软件测量不同扫描条件下各靶体积大小,计算动态与静态扫描靶区重建体积的相对偏差。结果:静态模型同一靶区在层厚与螺距不同时,扫描后三维重建的靶区外形无明显变化,重建靶区的体积差异可忽略;在不同运动状态下扫描,同一靶区重建图像的外形差异明显,重建靶体积的相对偏差最大值为54.1%;同一运动状态下,各靶区重建体积变化随靶而异;外形较小的靶区重建体积相对偏差变化范围为-39.8%～54.1%,外形较大的靶区重建体积相对偏差变化范围是-18.4%～8.7%。结论:呼吸运动对靶区重建的响影极大,三维放疗计划设计所依赖的CT图像,必须是肿瘤靶区处于相对静止状态下扫描的图像,否则,适形射野和剂量体积直方图将严重失真。     

钛网结合表面植骨修复先天性脊椎裂

目的:应用钛网结合表面植骨技术修复先天性脊椎裂骨缺损,随访观察其远期骨修复效果。方法:选择2003-04/2006-04承德北方医院脊柱外科收治的脊椎裂患者36例,其中显性脊椎裂12例,隐性脊椎裂24例,均采用脊柱后正中入路、显露病变两侧的椎板,显性者要先还纳脊膜脊髓结扎囊颈;隐性者分离硬膜与周围软组织的粘连带。选相适宜的钛网(天津市康利民医疗器械有限公司生产)塑形后敷盖骨缺损表面,两侧给予固定,将人工骨或自体骨剪成细小颗粒状植入表面。结果:36例均完成治疗进入结果分析。①随访远期效应:36例术后随访≥12个月。24例隐性突出者术后腰痛症状即消失,2个月后恢复工作,均未再出现腰痛;12例显性脊椎裂患者中,8例脊膜膨出者术后无任何神经系统症状,尿便正常,下肢肌力正常,3例合并有马尾神经部分突出者,术后遗尿症消失,均无下肢功能障碍,切口及周围未再有包块形成,只有1例马尾神经整体膨出着尿便功能障碍及部分下肢功能障碍无明显改善。②植骨区骨愈合情况:植骨区形成紧密的骨性愈合,未出现不愈合、假关节形成和并发症。③宿主反应和材料反应:3例术后出现低热,对症治疗后好转;钛网与宿主骨紧密结合,无排斥和电解反应。结论:钛网表面植骨修复脊椎裂排斥反应小,植入后能与宿主骨形成紧密的骨性结合,能起到近期支撑、远期融合的效果,适用于显性和隐性脊椎裂患者。     

脑损伤大鼠皮质神经细胞凋亡过程中细胞外调节激酶通路的作用

目的:细胞外调节激酶通路在凋亡信号转导中具有重要作用,观察细胞外调节激酶信号转导通路在颅脑损伤中的作用。方法:实验于2004-09/2006-01在华北煤炭医学院中心实验室完成。选用SD大鼠70只,按随机数字表法分为2组,即对照组(n=28)和模型组(n=42),每组又分为伤后10min,30min,3h,6h,24h,48h和72h7个时相点,对照组每个时相点4只大鼠,模型组每个时相点6只大鼠。按照Mamarou方法建立大鼠重型弥漫性颅脑损伤模型,在不同时相点采用免疫组化、Western-blot法分别检测两组大鼠颅脑损伤后皮质细胞外调节激酶的表达情况,另外分别应用原位杂交方法、原位末端标记法检测半胱氨酸天冬氨酸酶3及凋亡细胞,并进行比较。结果:70只大鼠全部进入结果分析,无脱失。①模型组大鼠皮质p-细胞外调节激酶1/2蛋白在伤后10min时已较对照组明显升高(P<0.05),逐渐增强,伤后6h达高峰,24h仍有大量表达,明显高于对照组(P<0.01),至伤后48h降至对照组水平(P>0.05)。②模型组大鼠皮质半胱氨酸天冬氨酸酶3mRNA杂交阳性信号表达在伤后3h开始升高,48h达高峰,72h仍明显高于对照组(P<0.01)。③模型组大鼠皮质伤后3h偶见原位末端标记阳性细胞,6h开始增加,明显高于对照组(P<0.01),48h达高峰。④p-细胞外调节激酶1/2蛋白与半胱氨酸天冬氨酸酶3mRNA及原位末端标记阳性细胞均主要分布于损伤中心区及其周围,在分布区域上呈现很大的相似性。结论:脑损伤时p-细胞外调节激酶1/2蛋白表达呈一种过度激活状态,而且与半胱氨酸天冬氨酸酶3mRNA及原位末端标记阳性细胞在分布区域上呈现很大的相似性,推测大鼠脑损伤后细胞外调节激酶通路的过度激活是导致神经细胞凋亡的作用途径之一。     

新型牙种植体及圆柱状种植体与颌骨结合力的比较

目的:为适应牙槽骨吸收严重,高度和宽度不足的病例,设计一种一段式新型牙种植体,通过动物体内种植体种植实验观察其与颌骨的结合力,并与圆柱状种植体进行对照。方法:实验于2006-08/2007-05在四川大学华西口腔动物中心完成。①材料:新型牙种植体由直径为3.6 mm的3个圆柱体并排,长14.8 mm,高6 mm,表面积为406.93 mm2,有效抗压面积为134.60 mm2;圆柱状种植体直径为3.6 mm,长为9 mm,基桩高度2 mm,表面积为117.06 mm2,抗压面积为10.174 mm2。2种种植体均由纯钛制成,由成都力威特数控设备有限公司提供。②实验方法:选健康成年雄性狼狗6只,随机分为1,2,3个月组3组,每组2只,分别拔除其双侧下颌全部前磨牙,3个月后每侧拔牙窝内种植新型种植体2颗,同时种植2颗圆柱状种植体为对照。于术后1,2,3个月各处死2只犬,拍摄X射线片观察种植体-骨界面愈合情况及骨密度变化,并利用万能力学实验机通过推出实验测试种植体-骨结合力。结果:狼狗6只均进入结果分析。①种植体-骨界面愈合情况:2种种植体和骨界面的一般观察、牙周检测和X射线表现均相似,均无骨质破坏。②种植体-骨结合力:新型种植体在植入后1个月,骨结合力已达承受正常力的水平;时间变化曲线表明2种种植体的骨结合力随时间均逐渐增加,但新型种植体的骨结合力明显大于圆柱状种植体(P<0.001)。结论:新型种植体因为其特殊的设计体部形态、圆盘状结构增加了支持骨组织的承载面积,较圆柱状种植体有更大的骨结合力。     

Differential and Converging Molecular Mechanisms of Antidepressants' Action in the Hippocampal Dentate Gyrus

Major depression is a highly prevalent, multidimensional disorder. Although several classes of antidepressants (ADs) are currently available, treatment efficacy is limited, and relapse rates are high; thus, there is a need to find better therapeutic strategies. Neuroplastic changes in brain regions such as the hippocampal dentate gyrus (DG) accompany depression and its amelioration with ADs. In this study, the unpredictable chronic mild stress (uCMS) rat model of depression was used to determine the molecular mediators of chronic stress and the targets of four ADs with different pharmacological profiles (fluoxetine, imipramine, tianeptine, and agomelatine) in the hippocampal DG. All ADs, except agomelatine, reversed the depression-like behavior and neuroplastic changes produced by uCMS. Chronic stress induced significant molecular changes that were generally reversed by fluoxetine, imipramine, and tianeptine. Fluoxetine primarily acted on neurons to reduce the expression of pro-inflammatory response genes and increased a set of genes involved in cell metabolism. Similarities were found between the molecular actions and targets of imipramine and tianeptine that activated pathways related to cellular protection. Agomelatine presented a unique profile, with pronounced effects on genes related to Rho-GTPase-related pathways in oligodendrocytes and neurons. These differential molecular signatures of ADs studied contribute to our understanding of the processes implicated in the onset and treatment of depression-like symptoms.     

Endoureteropyelotomy: percutaneous treatment of ureteropelvic junction obstruction

A total of 47 percutaneous operations (endoureteropyelotomy) was performed for treatment of 41 congenital and 6 secondary cases of ureteropelvic junction obstruction between September 1983 and April 1988. Evaluation was available in 39 cases with a followup of 4 to 56 months (mean 16 months). Good results were obtained in 28 of 39 cases (72 per cent) and there were 3 failures (8 per cent). Eight patients (20 per cent) were symptomatically improved but they had residual obstruction on a diuretic study. Only 1 multioperated patient with a good early postoperative result has shown radiological deterioration at 1 year. Complications were managed conservatively, except for 1 case of intravascular coagulopathy. Endoureteropyelotomy is an effective alternative treatment for ureteropelvic junction obstruction but further evaluation definitely is warranted to define better its indications and risk factors.