Synaptic metaplasticity through NMDA receptor lateral diffusion

Lateral diffusion of glutamate receptors was proposed as a mechanism for regulating receptor numbers at synapses and affecting synaptic functions, especially the efficiency of synaptic transmission. However, a direct link between receptor lateral diffusion and change in synaptic function has not yet been established. In the present study, we demonstratedNMDAreceptor(NMDAR) lateral diffusion in CA1 neurons in hippocampal slices by detecting considerable recovery of spontaneous or evoked EPSCs from the block of (+)-MK-801[(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine maleate], an irreversible NMDAR open-channel blocker. We observed changes on both the number and the composition of synaptic NMDAR on recovery. More importantly, after the recovery, long-term potentiation(LTP)-producing protocol induced only LTD(long-term depression) instead of LTP. In contrast, a complete recovery from competitive NMDAR blocker D,L-AP-5 was observed without subsequent changes on synaptic plasticity. Our data suggest a revised model of NMDAR trafficking wherein extrasynaptic NMDARs, mostly NR1/NR2B receptors, move laterally into synaptic sites, resulting in altered rule of synaptic modification. Thus, CA1 synapses exhibit a novel form of metaplasticity in which the direction of synaptic modification can be reverted through subtype-specific lateral diffusion of NMDA receptors.     

Aldosterone acts via an ATP autocrine/paracrine system: the Edelman ATP hypothesis revisited

Aldosterone, the most important sodium-retaining hormone, was first characterized >50 years ago. However, despite numerous studies including the classical work of Isidore S. "Izzy" Edelman showing that aldosterone action depended on ATP production, the mechanism by which it activates sodium reabsorption via the epithelial sodium channel remains unclear. Here, we report experiments that suggest that one of the key steps in aldosterone action is via an autocrine/paracrine system. The hormone stimulates ATP release from the basolateral side of the target kidney cell. Prevention of ATP accumulation or its removal blocks aldosterone action. ATP then acts via a purinergic mechanism to produce contraction of small groups of adjacent epithelial cells. Patch clamping demonstrates that it is these contracted cells that have channel activity. With progressive recruitment of contracting cells, there is then a parallel increase in transepithelial electrical conductance. In common with other stimuli of sodium transport, this pathway involves phosphatidylinositol 3-kinase. Inhibition of phosphatidylinositol 3-kinase blocks both cell contraction and conductance. We put forward the hypothesis that redistribution of the cell volume caused by the lateral contraction results in apical swelling and that this change, in turn, disrupts the epithelial sodium channel interaction with the F-actin cytoskeleton, opening the channel and hence increasing sodium transport.     

Complement takes its Toll: an inflammatory crosstalk between Toll-like receptors and the receptors for the complement anaphylatoxin C5a

The innate immune system is responsible for a rapid inflammatory response to pathogens that is essential for the clearance of infections. Although this response is vital, it is nonetheless potentially harmful, and dysregulated inflammation is a feature of many disease states. Thus, the mechanisms that regulate the release of soluble mediators of inflammation are an active focus of investigation. The activation by infections of two key components of the innate immune system, the Toll-like receptors (TLRs) and complement, leading to the release of soluble mediators of inflammation, is critical to microbial killing and clearance. Both TLRs and complement are independently capable of triggering pro-inflammatory responses, but their synergistic interaction resulting from a substantial crosstalk markedly amplifies those responses and may contribute to the pathophysiology of diseases such as sepsis.     

精子库电脑管理系统的开发与应用

从１９９０年起我实验室起开始筹建上海市第一家人类精子库，并同时开展供者精液人工受精和丈夫精液人工受精的临床和科研工作，鉴于我国对人工受精尚无明确的法律和法规，对可能出现的一系列社会和伦理问题有待解决为此我科设计建立一套精子库电脑管理系统。     

雄激素替代治疗Klinefelter综合征

本文报道经临床及染色体分析证实的４７例Ｋｌｉｎｅｆｅｌｔｅｒ综合征患者，其中３６例连续使用睾酮治疗１年以上，青春发育顺序以阴毛生长最快，其次为腋毛和胡须，最后为喉节。阴茎长度从５．２６ｃｍ增长到８．２３ｃｍ，睾丸容积右侧从３．１ｍｌ增大到４．８ｍｌ，左侧从３．０９ｍｌ到４．７０ｍｌ，精液量从０．５～１ｍｌ增多到１．５～４．４ｍｌ，说明睾丸酮有促发附属性腺分泌功能。但患者仍不育。睾丸酮治疗３月后患者性功能即有明显改善。     

彩色多普勒血流显像检测阴茎血流的价值

目的研究临床疑阳萎患者阴茎血流变化。方法应用彩色多普勒血流显像于注射前列腺素Ｅ１前及注药后１５分钟内连续检测拟阳萎患者阴茎血流８６例。结果①注药后勃起正常５６例,不良３０例,两组峰值血流速度、阻力指数、动脉伸展性及反应性充血率差异显著。②勃起不良诊断效率以收缩期峰值流速（＜３５ｃｍ／ｓ）和反应性充血率（＜７５％）最佳。③中老年组动脉伸展性、反应性充血率及阻力指数低于青年组,多普勒频谱形态圆钝,彩色血流束走行迂曲、粗糙,呈串珠样。④阴茎深静脉显示２０例,９例为青年组,６例血管造影证实存在静脉瘘,３例自幼无勃起,１１例并动脉伸展性、反应性充血率降低。结论彩色多普勒显像可客观、准确反映阴茎动静脉血流     

4,5,7-三羟基异黄酮对肝纤维化大鼠肝窦内皮细胞窗孔、增殖及合成一氧化氮的影响

目的 探讨酪氨酸蛋白激酶抑制剂4、5、7-三羟基异黄酮(genistein)对肝窦内皮细胞(sinusoidalendothelial cell, SEC)窗孔、增殖及合成一氧化氮(nitric oxide, NO)的影响。方法 用胶原酶原位灌注,Percoll不连续密度梯度离心法分离正常及CCl_4实验性肝纤维化大鼠的SEC并进行体外培养。采用扫描电镜技术,MTT法及硝酸还原酶法,分别观察genistein对SEC细胞窗孔、增殖及合成NO的影响。结果 Genistein对肝纤维化各级 SEC的窗孔数目及大小均无明显的影响。经不同浓度的genistein作用24h后,肝纤维化各级大鼠SEC的生长均受抑制,以100 μmol/L浓度的genistein对肝纤维化Ⅰ级大鼠SEC的作用最为明显[细胞增殖率为-(15.38±6.26)% vs(4.91±2.16)%,t=13.7. P＜0.05]。100 μmol/L浓度的genistein作用24h,可明显促进肝纤维化Ⅰ级大鼠SEC NO的合成[NO合成为(25.4±3.8)μmol/L vs(16.6±3.3)μmol/L,t=6.79,P＜0.05];但对肝纤维化Ⅱ级、Ⅲ级大鼠SEC的NO合成的影响却不明显。结论 体外实验中genistein可以抑制肝纤维化Ⅰ级SEC增殖,促进SEC细胞NO的合成;对肝纤维化SEC细胞的功能有一定的调节作用。     

YIGSR五肽及RGD三肽对肝窦内皮细胞窗孔的调节作用

目的　探讨酪氨酸 -异亮氨酸 -甘氨酸 -丝氨酸 -精氨酸 (Tyr- Ile- Gly- Ser- Arg,YIGSR)五肽及精氨酸 -甘氨酸 -天门冬氨酸 (Arg- Gly- Asp,RGD)三肽对肝窦内皮细胞 (SEC)窗孔的影响。方法　用胶原酶原位灌注、Percoll不连续密度梯度离心法分离大鼠的 SEC,并加入包被有 型胶原或层粘连蛋白 (lam inin,L N)基质的盖玻片上培养。采用扫描电镜技术及放免方法 ,分别观察 YIGSR五肽及 RGD三肽对 SEC窗孔数目、大小 ,以及 SEC分泌 型胶原能力的影响。结果　生长在包被 L N的盖玻片上 48小时的 SEC,其窗孔数目及大小均比生长在 型胶原上的 SEC明显降低 (P<0 .0 5 ) ;但同时加入 YIGSR五肽 (5 0 μg/ ml)及 RGD三肽 (5 0 μg/ m l)作用 48小时后 ,SEC窗孔数目及大小均有明显增加 (P<0 .0 5 ) ,同样地 ,经 YIGSR五肽及 RGD三肽作用后 ,生长在 L N上的 SEC分泌 型胶原的能力亦明显下降 (P<0 .0 5 )。结论　 YIGSR五肽及 RGD三肽对 SEC的形态 (如窗孔 )及功能 (如分泌 型胶原 )均有一定调节作用