急性缺血再灌注肾损伤过程中Mg2+及K+协同胰岛素的对抗效应

目的:在肾移植术后可能发生急性缺血再灌注性肾损伤.作者前期实验表明在肾缺血再灌注期间注射胰岛素可减轻缺血再灌注肾损伤,在此基础上,在胰岛素溶液中加入天冬氨酸钾镁,观察Mg2 ,K 协同胰岛素对家兔急性肾缺血再灌注损伤的影响,并分析其可能机制.方法:实验于2002-02/04在泸州医学院生理实验室完成,动物实验方法符合动物伦理学要求.①实验材料及方法:选用健康成年日本大耳白兔27只,按随机数字表法分为3组(n=9),即缺血再灌注组、缺血再灌注胰岛素处理组及对照组,前两组采用钳夹肾动脉法建立急性肾缺血再灌注肾损伤模型,缺血再灌注胰岛素处理组再灌注的同时给予胰岛素溶液,含胰岛素3 U/kg,葡萄糖1.5 g/kg,K 4 mg/kg,Mg2 1.7 mg/kg.②实验评估:分别观察3组动物缺血再灌注2 h,48 h后,血清尿素氮、血糖、血清及肾组织中丙二醛含量以及肾组织超微结构变化.结果:23只动物进入结果分析.①肾缺血再灌注48 h后,缺血再灌注组血清尿素氮含量显著高于对照组(P＜0.01),缺血再灌注胰岛素处理组与对照组差异无显著性意义(P＞0.05).②缺血再灌注组血清及肾组织中丙二醛含量显著高于对照组(P＜0.05),缺血再灌注胰岛素处理组丙二醛含量显著低于缺血再灌注组(P＜0.05).③缺血再灌注2 h后,3组动物血糖均较术前增高,但以缺血再灌注组增高更为显著,与对照组比较差异具有显著性意义(P＜0.05),缺血再灌注胰岛素处理组与对照组差异无显著性意义(P＞0.05).④对照组肾组织超微结构正常,缺血再灌注组肾组织呈变性和坏死改变,缺血再灌注胰岛素处理组肾组织轻度变性.结论:Mg2 ,K 可协同胰岛素减轻家兔急性缺血再灌注性肾损伤,其作用途径可能和降低血糖、抗自由基损伤、改善能量代谢、减轻钙超载、防止低血钾等因素有关.     

Homeostatic changes of the endocannabinoid system in Parkinson's disease

Endocannabinoids (eCBs) are endogenous lipids that bind principally type‐1 and type‐2 cannabinoid (CB₁ and CB₂) receptors. N‐Arachidonoylethanolamine (AEA, anandamide) and 2‐arachidonoylglycerol (2‐AG) are the best characterized eCBs that are released from membrane phospholipid precursors through multiple biosynthetic pathways. Together with their receptors and metabolic enzymes, eCBs form the so‐called “eCB system”. The later has been involved in a wide variety of actions, including modulation of basal ganglia function. Consistently, both eCB levels and CB₁ receptor expression are high in several basal ganglia regions, and more specifically in the striatum and in its target projection areas. In these regions, the eCB system establishes a close functional interaction with dopaminergic neurotransmission, supporting a relevant role for eCBs in the control of voluntary movements. Accordingly, compelling experimental and clinical evidence suggests that a profound rearrangement of the eCB system in the basal ganglia follows dopamine depletion, as it occurs in Parkinson's disease (PD). In this article, we provide a brief survey of the evidence that the eCB system changes in both animal models of, and patients suffering from, PD. A striking convergence of findings is observed between both rodent and primate models and PD patients, indicating that the eCB system undergoes dynamic, adaptive changes, aimed at restoring an apparent homeostasis within the basal ganglia network. © 2010 Movement Disorder Society     

The ionic mechanism of gamma resonance in rat striatal fast-spiking neurons

Striatal fast-spiking (FS) cells in slices fire in the gamma frequency range and in vivo are often phase-locked to gamma oscillations in the field potential. We studied the firing patterns of these cells in slices from rats ages 16-23 days to determine the mechanism of their gamma resonance. The resonance of striatal FS cells was manifested as a minimum frequency for repetitive firing. At rheobase, cells fired a doublet of action potentials or doublets separated by pauses, with an instantaneous firing rate averaging 44 spikes/s. The minimum rate for sustained firing was also responsible for the stuttering firing pattern. Firing rate adapted during each episode of firing, and bursts were terminated when firing was reduced to the minimum sustainable rate. Resonance and stuttering continued after blockade of Kv3 current using tetraethylammonium (0.1-1 mM). Both gamma resonance and stuttering were strongly dependent on Kv1 current. Blockade of Kv1 channels with dendrotoxin-I (100 nM) completely abolished the stuttering firing pattern, greatly lowered the minimum firing rate, abolished gamma-band subthreshold oscillations, and slowed spike frequency adaptation. The loss of resonance could be accounted for by a reduction in potassium current near spike threshold and the emergence of a fixed spike threshold. Inactivation of the Kv1 channel combined with the minimum firing rate could account for the stuttering firing pattern. The resonant properties conferred by this channel were shown to be adequate to account for their phase-locking to gamma-frequency inputs as seen in vivo.     

A case report of semitendinosus tendon autograft for reconstruction of the meniscal wall supporting a collagen implant

Purpose

Describe the evolution of the reconstruction of meniscal rim with semitendinosus tendon in a patient with knee pain after a subtotal meniscectomy and absence of meniscal wall.

Method

32 years old male with a six-month history of the left knee pain after a subtotal meniscectomy. The MRI indicated a small internal meniscal remainder without posterior horn attachment. Taking this absence as a relative contraindication for implant and meniscal transplantation, the reconstruction of a new meniscal wall with semitendinosus tendon autograft was considered. A collagen meniscal implant was attached to the new wall five months later.

Results

After two years the patient referred only non specific discomfort with full pain relief in the medial compartment. The MRI revealed integration of implants without significant degenerative changes compared to previous images.

Conclusions

This staged technique was designed to restore medial meniscus-like biologic tissue in a symptomatic patient following arthroscopic subtotal meniscectomy with a significant loss of the peripheral meniscus rim. Symptomatic improvement was obtained at two years follow-up.     

同型半胱氨酸水平,MTHFR基因突变与原发性高血压的病例对照研究

从上海一个社区中随机选取１２７例３５～７５岁的原发性高血压病人和１７０例正常血压者。采用聚合酶链反应－限制性片段长度多态性分析ＭＴＨＦＲ基因多态性。使用高效液相色谱结合电化学方法检测血清中同型半胱氨酸总浓度,使用放射免疫法同时测定血甭中叶酸和Ｂ１２浓度。结果：调整年龄和性别后,病例和对照组同型半胱氨酸水平分别为１０．５６μｍｏｌ／Ｌ和１０．３４μｍｏｌ／Ｌ,差异无显著性（Ｐ＝０．６３）。在未服降压     

4-烷硫基-4-脱氧-4′-去甲表鬼臼毒素的合成和抗肿瘤活性

对4’-去甲表鬼臼毒素的C_4位进行化学修饰,合成和筛选了10个4-烷硫基-4-脱氧-4’-去甲表鬼臼毒素衍生物以进一步研究C_4位不同的原子和取代基与活性之间的关系及寻找结构简单、活性更强的抗肿瘤新药。4’-去甲表鬼臼毒素与硫醇在三氟化硼·乙醚或三氟乙酸存在下生成相应的硫醚,也可用硫醇与4β-溴-4-脱氧-4’-去甲表鬼臼毒素反应生成相应的硫醚。在体外筛选中,化合物10和12抑制L1210白血病细胞的活性与依托泊甙相当或更强,化合物9,10,12和15抑制KB细胞的活性与依托泊甙相当或更强。     

4-S-(5-酰氨基-1,3,4-噻二唑-2-基)-4-脱氧-4′-去甲基表鬼臼毒素衍生物的合成与抗肿瘤活性

基于在4′-去甲基表鬼臼毒素母核C₄位上联结含有杂原子的芳香环取代基,以此考察其结构与活性关系的设想,设计并合成了10个标题化合物。体外L₁₂₁₀白血病细胞与KB细胞生长抑制试验结果表明,这类化合物有较强的抗肿瘤活性。其中化合物SIPI-92-1772,1774,1775,1776,1777与1779的活性超过临床用药依托泊甙。其余化合物活性与依托泊甙相当或略低。