Stereoselectivity of actions of the calcium sensitizer [+]-EMD 60263 and its enantiomer [-]-EMD 60264

The thiadiazinone derivative [+]-EMD 60263 ((+)-5-(1-(α-ethylimino-3,4-dimethoxybenzyl)-1,2,3,4- tetrahydroquinoline-6-yl)-6-methyl-3,6-dihydro-2H-1,3,4 -thiadiazine-2-on) is a Ca²⁺-sensitizing agent with only minor phosphodiesterase inhibitory activity. Our aim was to characterize the inotropic and electrophysiological effects of [+]-EMD 60263 and its enantiomer [-]-EMD 60264 in several cardiac muscle preparations. The Ca²⁺-sensitizing activity resided in the [+]-enantiomer only. [+]-EMD 60263 (3 μM) shifted the EC₅₀ of Ca²⁺ for contractile activation of skinned fibers of pig heart from 2.41 μM to 0.73 μM, whereas [-]-EMD 60264 (30 μM) was ineffective. In Langendorff-perfused guinea pig hearts, [+]-EMD 60263 and [-]-EMD 60264 induced concentration-dependent positive and negative inotropic effects, respectively; both enantiomers reduced spontaneous heart rate but did not influence perfusion pressure. The maximum increase in force of human atrial trabeculae was 35 % of pre-drug control with [+]-EMD 60263 in comparison to 113 % with forskolin. In guinea-pig papillary muscles, [+]-EMD 60263 and [-]-EMD 60264 had opposite inotropic responses, however, both agents similarly prolonged action potential duration. Both enantiomers concentration-dependently blocked the rapidly activating component I_Kr of the delayed rectifier in guinea-pig myocytes. The block saturated at potentials positive to +30 mV, closely resembling the effects of the antiarrhythmic agent E-4031 which had been originally used to define I_Kr. It is concluded, that the positive inotropic action of [+]-EMD 60263 can be explained by prevalence of the Ca²⁺-sensitizing effect. The accompanying prolongation in action potential duration is caused by block of the I_Kr component of the delayed rectifier. While the inotropic effects are stereoselective, most of the electrophysiological actions are clearly independent of sterical configuration. The combination of Ca²⁺-sensitizing with class-III antiarrhythmic action may provide an interesting pharmacological profile of potential therapeutic use. Received: 7 January 1997 / Accepted: 25 February 1997     

艾司洛尔预注射对预防颈丛阻滞后心血管副反应的观察

颈丛阻滞常可引起心率增快 ,血压增高 ,被认为是颈动脉窦及迷走神经被阻滞 ,交感神经活性增强所致 [1 ]。我们采用艾司洛尔预注射的方法 ,抑制颈丛阻滞后的心血管副反应 ,取得了良好的效果 ,现介绍如下。1　临床资料和方法1.1　一般资料　选择 ASA I～ 级 ,择期行甲状腺瘤或囊     

颈丛阻滞、硬膜外阻滞下甲状腺手术应激反应的比较

目的 :比较颈丛阻滞、硬膜外阻滞下甲状腺手术应激反应的大小。方法 :选择ASAⅠ～Ⅱ级 ,女性 ,甲状腺手术患者 30例 ,年龄 2 2～ 5 5岁 ,术前无呼吸、循环和内分泌疾病 ,随机分为颈丛阻滞组 (颈丛组 ) 15例 ,硬膜外阻滞组(硬膜外组 ) 15例 ;颈丛阻滞选用 0 .8%利多卡因和 0 .2 5 %布比卡因混合液 ,以C4一点法行双侧深浅丛阻滞 ;硬膜外阻滞选用 1.3%利多卡因和 0 .15 %丁卡因混合液 ,穿刺点选择C4～ 5或C5～ 6间隙 ,采用侧卧位直入法 ,并向头置管 3cm ;分别测定并记录麻醉前、麻醉后 2 0min、切皮、分上极、切腺体和术毕共六个时点的血糖、血压和心率的变化。结果 :两组病例各时点血糖均逐步上升 ,于分上极、切腺体和术毕血糖值与麻醉前比较有显著性差异 (P <0 .0 1) ;硬膜外组只在分上极时SBP与麻醉前比较有差异外 (P <0 .0 5 ) ,而颈丛组在分上极、切腺体时DBP与麻醉前比较有差异 (P <0 .0 5 ) ,SBP、MAP与麻醉前比较有显著性差异 (P <0 .0 1)。结论 :本研究表明颈丛阻滞、硬膜外阻滞均不能完全抑制甲状腺手术的应激反应 ,在稳定甲状腺手术循环功能方面硬膜外阻滞优于颈丛阻滞     

完全性左束支传导阻滞伴快速心房纤颤并急性左心衰竭的抢救

目的总结完全性左束支传导阻滞伴快速心房纤颤并急性左心衰竭的治疗经验,以提高抢救成功率.方法对经抢救治疗的完全性左束支传导阻滞伴快速心房纤颤并急性左心衰竭9例(16次)患者进行治疗方面的回顾分析.结果9例(16次)患者14次抢救成功,成功率87.0%,但复发率较高,预后较差,有5例患者在抢救时或出院后1～2年内猝死.结论该组患者经传统"强心、利尿、扩血管",控制心房纤颤、心室率等治疗是远远不够的.应在未发生肺泡性肺水肿及心源性休克之前,尽早尽快地应用血管扩张剂及联合应用小剂量非洋地黄类正性肌力药物,并维持治疗24～72 h.其中以酚妥拉明加多巴胺和(或)多巴酚丁胺效果可能较佳,血管扩张剂硝酸酯类不及α-受体阻滞剂酚妥拉明疗效明显.     

胸廓矢状面倾斜度的测定及其对放疗的意义

目的了解人体前胸矢状面倾斜度的大小及对放疗剂量分布的影响。方法选择126例患者行胸部CT扫描并予正中矢状面重建。分别测定上中下胸廓层面前后体表中线至脊髓距离及各层上下间距,计算出前胸倾斜度。查TMR表得出中平面深度及脊髓深度处上中胸及中下胸层面剂量误差。结果前野各层面至脊髓距离变化较大,后野变化较小。人体前胸倾斜度范围为25~56°。上中胸段组的上下缘剂量误差较大,躯体中平面平均相差8%,脊髓17%。中下胸段组剂量误差较小,躯体中平面4%,脊髓7%。误差随倾斜角度增加而增加。根据倾斜度得出合适的楔形板修正角度大约为10~35°。结论人体前胸矢状面存在自然倾斜度,这种倾斜影响前野剂量分布,应予以个体化修正。建议根据角度的大小选择合适的头足向楔形板优化。     

臂丛神经阻滞加用地塞米松和小剂量吗啡用于术后镇痛的效果观察

目的 观察臂丛神经阻滞的局麻药液中加入地塞米松和小剂量吗啡用于术后镇痛的效果和副作用。方法 80例患者随机分为A、B、C、D四组。全部用肌间沟法臂丛神经阻滞，A组（n=20)注入0.5%布比卡因、2%利多卡因等量混合液25ml；B组（n=20)注入A组用药加地塞米松10mg(2ml)；C组（n=20)注入A组用药加吗啡2mg(0.2ml)；D组（n=20)注入A组用药加地塞米松10mg(2ml)、吗啡2mg(0.2ml)。结果 B、C、D组与A组相比起效时间显著缩短、镇痛时间显著延长，差异非常显著（P＜0.01)；而D组和B、C组相比镇痛时间又明显延长，差异非常显著（P＜0.01)；C组中有1例（5％）因发生恶心呕吐，其余多组无并发症发生。结论 臂丛神经阻滞的局麻药液中加入地塞米松和小剂量吗啡用于术后镇痛，镇痛时间长，效果可靠，副作用少，操作方便，经济实用。     

无水酒精阻滞大鼠腹腔神经丛后脊髓、孤束核C-FOS和NOS-1的表达

目的:通过免疫组化的方法研究无水酒精阻滞大鼠腹腔神经丛后脊髓和延髓孤束核内CFOS和NOS1的表达。材料和方法:对70只Wistar大鼠实施手术,建立实验动物模型。分5组于术后不同时间取得脊髓和延髓样本,并用标准方法对其进行CFOS和NOS1免疫组化染色,观察脊髓和延髓孤束核CFOS和NOS1的表达。结果:无水酒精阻滞后脊髓后角、延髓孤束核神经元细胞内均有CFOS和NOS1表达。结论:无水酒精阻滞腹腔神经丛后,短时间内脊髓后角和延髓孤束核内CFOS和NOS1表达阳性,表明FOS和NOS1与内脏信息在脊髓水平的传导有关。CFOS和NOS1参与了内脏信息在孤束核内的传导。     

Safety and reliability of external fixation for basicervical and intertrochanteric fractures in high-risk elderly patients

Forty elderly patients with basicervical and pertrochanteric fractures were managed with uniplanar AO external fixator under regional anaesthetic block of the femoral nerve and lateral cutaneous nerve of the thigh from April 2003 to March 2006. The mean age of the patients was 67.9 ± 5.5 years. External fixator application was performed under radiological control after closed reduction had been obtained. Comorbid factors, duration of surgery, duration of hospitalisation, complications, walking ability, time to union and mortality rate were recorded. Patients were followed up for a mean period of 12 ± 4.5 months. Superficial pin tract infection occurred in 13 patients, healing in varus >10° and with shortening >2 cm occurred in six patients, and one patient suffered a spontaneous ipsilateral femoral neck fracture after removal of the fixator. The mean time for union was 10.4 ± 1.2 weeks. Rapid union rate and minor complications obtained in the present study are comparable to those obtained with standard internal fixation techniques. Minimal intraoperative blood loss, short operative time and early patient mobilisation are advantages signifying uniplanar external fixator application under regional anaesthetic block to be a viable option in treatment of basicervical and pertrochanteric fractures in high-risk elderly patients.     

Priming with a very low dose of DNA complexed with cationic block copolymers followed by protein boost elicits broad and long-lasting antigen-specific humoral and cellular responses in mice

Cationic block copolymers spontaneously assemble via electrostatic interactions with DNA molecules in aqueous solution giving rise to micellar structures that protect the DNA from enzymatic degradation both in vitro and in vivo. In addition, we have previously shown that they are safe, not immunogenic and greatly increased antigen-specific CTL responses following six intramuscular inoculations of a very low dose (1 μg) of the vaccine DNA as compared to naked DNA. Nevertheless, they failed to elicit detectable humoral responses against the antigen. To gain further insight in the potential application of this technology, here we show that a shorter immunization protocol based on two DNA intramuscular inoculations of 1 μg of DNA delivered by these copolymers and a protein boost elicits in mice broad (both humoral and cellular) and long-lasting responses and increases the antigen-specific Th1-type T cell responses and CTLs as compared to priming with naked DNA. These results indicate that cationic block copolymers represent a promising adjuvant and delivery technology for DNA vaccination strategies aimed at combating intracellular pathogens.     

平面导板在深覆(牙合)矫治中的临床应用研究

目的：探讨平面导板矫治重度深覆[牙合]患者的作用机制及临床作用要点。方法：对18名生长发育期的重度深覆[牙合]患者,用平面导板来打开咬合,并对咬合打开前后的硬软组织变化进行分析。结果：①上下后牙及牙槽高度均增加,下后牙及牙槽高度的增加值大于上后牙及牙槽高度的增加值,而对前牙及牙槽高度的影响无统计学差异;②上下颌骨在水平方向上无改变,但下颌平面角与下面高/全面高治疗后较治疗前增大,后面高/前面高治疗后较治疗前减小;③覆[牙合]减小,Spee氏曲线得到整平;④松弛的下唇肌肉得到紧张,从而改善了侧貌外形。结论：平面导板使覆[牙合]减小主要是后牙及后牙齿槽突高度增加的结果,对生长发育期的低角重度深覆[牙合]患者治疗效果较好。