Baclofen-induced disinhibition in area CA1 of rat hippocampus is resistant to extracellular Ba

The mechanism of disinhibition produced by (±)-baclofen was studied using intracellular recording in area CA1 of rat hippocampal slices. Baclofen reversibly depressed monosynaptic IPSPs evoked by direct activation of interneurons in the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) andd,l-2amino-5-phosphonovalerate (APV). Ba²⁺ prevented baclofen-induced hyperpolarization of pyramidal neurons but not depression of monosynaptic IPSPs by baclofen. Baclofen reversibly depressed monosynaptic IPSPs when applied close to the recording site, but was ineffective when applied close to the stimulating site in stratum radiatum. These results suggest that baclofen disinhibits pyramidal neurons in area CA1 of the rat hippocampus by activating receptors on the terminals of inhibitory neurons that are coupled to a Ba²⁺-insensitive effector mechanism.     

子宫腺肌症病变中雌激素、孕激素、癌基因、凋亡抑制基因的表达研究

目的 研究雌激素（ER）、孕激素（PR）及癌基因（cerbB-2）、凋亡抑制基因（Bcl-2）在子宫腺肌症病变中的表达和子宫腺肌症发病的相关性。方法 用免疫组化方法检测40例子宫腺肌症病变组织中ER及其他生物学指标的表达。结果 ER、PR与CerbB．2、Bcl-2在子宫腺肌症病变中均有不同程度的阳性表达，子宫肌层异位内膜ER阳性表达率97．5％，PR阳性率97．5％，cerbB-2阳性率82．5％，Bcl-2阳性率62．5％。在位内膜和异位内膜ER、PR均呈阳性，阳性率比较差异无统计学意义（P〉0．05）。异位内膜cerbB-2的强阳性率高于在位内膜，差异有统计学意义（P〈0．05）。ER、PR与cerbB-2、Bcl-2阳性率相比具有相关性（P〈0．05）。结论 ER、PR与cerbB．2、Bcl-2在异位内膜高表达，提示这些生物学指标在子宫腺肌症发生发展中发挥作用。     

Severe hypoglycaemia in a person with insulin autoimmune syndrome accompanied by insulin receptor anomaly type B.

AIMS: A rare case of the insulin autoimmune syndrome (IAS) accompanied by insulin receptor anomaly is reported. METHODS: Antibodies to insulin and insulin receptor were determined in the patient with severe hypoglycaemia before and after the treatment with prednisolone. RESULTS: Titers of antibody to insulin and insulin receptors were 73.0% and 41.5%, respectively. Drug-induced lymphocyte stimulation tests were all negative for the suspicious drugs. Her HLA-DR was DRB1*0403/04051. Following steroid therapy, the formation of antibodies was suppressed and alleviated her symptoms. Scatchard analysis yielded findings specific to polyclonal antibodies. CONCLUSIONS: The changes in autoantibodies resulted in alleviation of the hypoglycemic symptoms as a result of steroid therapy.     

Activation of 5-HT3 receptor by 1-phenylbiguanide increases dopamine release in the rat nucleus accumbens

The serotonin-3 (5-HT₃) agonist 1-phenylbuguanide (0.1–1.0 mM in perfusate) caused a robust, dose-dependent enhancement of extracellular dopamine content in nucleus accumbens as measured by in vivo microdialysis. This action was antagonized by co-perfusion of the 5-HT₃ antagonists zacopride and GR38032F (1 mM in perfusate). Similar effects were observed in 5-HT-denervated rats. These findings suggest that there is a potent modulation of dopamine (DA) release in the nucleus accumbens mediated via 5-HT₃ receptors, which appear to be located presynaptically on DA terminals of the mesolimbic DA pathway.     

Bacterial ghosts (BGs)—Advanced antigen and drug delivery system

Bacterial ghosts (BGs) are empty bacterial envelopes of Gram-negative bacteria produced by controlled expression of cloned gene E, forming a lysis tunnel structure within the envelope of the living bacteria. BGs are devoid of cytoplasmic content and possess all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat. BGs are ideally suited as an advanced drug delivery system (ADDS) for toxic substances in tumor therapy. The inner space of BGs can be loaded with either single components or combinations of peptides, drugs or DNA which provides an opportunity to design new types of (polyvalent) drug delivery vehicles. Uptake of BGs loaded with Doxorubicin (Dox) by CaCo2 cells led to effective Dox release from endo-lysosomal compartments and accumulation in the nucleus. Viability and proliferative capacity of the cells were significantly decreased (2–3 orders of magnitude) after internalization of Dox loaded BGs as compared to cells incubated with free Dox. The same effect was observed with leukemia cells. Melanoma cells also revealed a high capability to internalize BGs. These results indicate that BGs are able to target a range of types of cancer. BGs have also been investigated as DNA delivery vectors. Studies show DNA loaded BGs are efficiently phagocytosed and internalized by both professional APCs and tumor cells with up to 82% of cells expressing the plasmid-encoded reporter gene. Our studies with BGs as an ADDS system contribute (i) to optimize drug delivery for the treatment of cancer; (ii) define specific conditions for selection and preparation of BG formulations; (iii) and provide a background for the clinical application of BGs in cancer therapy.     

多发性骨髓瘤患者血浆尿激酶型纤溶酶原激活物及其可溶性受体的检测与临床意义

目的 :研究多发性骨髓瘤 ( MM)患者血浆尿激酶型纤溶酶原激活物 ( u- PA )及其可溶性受体 ( su PAR )的水平变化 ,并探讨其临床意义。方法 :用 ELISA法检测 34例 MM患者血浆 u- PA及 su PA R的浓度 ,同时观察其中6例 MM患者化疗前后血浆 u- PA及 su PAR的浓度变化。结果 :MM患者血浆 u- PA及 su PA R水平均明显高于正常对照组 ,其中进展期 MM患者血浆 u- PA及 su PAR水平明显高于正常对照组和稳定期 MM患者 ( P <0 .0 1) ,而稳定期 MM患者血浆 u- PA及 su PA R水平与正常对照组无显著性差异 ( P>0 .0 5)。 6例 MM患者化疗后血浆 u- PA及 su PA R水平 ,明显低于化疗前血浆 u- PA及 su PAR水平 ( P<0 .0 5)。骨髓涂片瘤细胞比例 >2 0 %的 MM患者血浆 u- PA及 su PA R水平 ,明显高于瘤细胞比例≤ 2 0 % M M患者 ( P<0 .0 5;P<0 .0 1)。M M患者血浆 u- PA及su PA R水平均与骨髓瘤细胞百分比及血清球蛋白呈正相关 ,而与血清白蛋白呈负相关。结论 :血浆 u- PA及 su PA R水平升高可能与多发性骨髓瘤的发生、发展有密切关系 ;其水平可作为临床分期、判断疗效、了解疾病进展情况及预后的一个重要指标。     

瘦素受体在条件性厌味大鼠脑的表达

目的 :观察瘦素受体 (LR)在条件性厌味 (CTA)大鼠脑的表达 .方法 :采用高度特异的抗瘦素受体血清 ,用免疫组化ABC法观察LR在CTA和对照大鼠脑的分布与表达 .结果 :与对照组大鼠相比 ,CTA大鼠皮层Ⅲ层、视交叉上核、弓状核、杏仁基底外侧核、海马CA3、下丘脑外侧区等核团瘦素受体表达增加 (14 6vs 12 0 ,138vs 92 ,118vs 78,10 7vs70 ,85vs 38cells·mm-2 ,P <0 .0 5 ) ,而下丘脑前区、脑桥臂旁核、杏仁中央核瘦素受体表达减弱 (13vs2 6 ,70vs5 5 ,12 2vs 16 2cells·mm-2 ,P <0 .0 5 ) ,孤束核瘦素受体的表达与对照大鼠无显著性差异 (5 0vs 5 7cells·mm-2 ,P >0 .0 5 ) .结论 :瘦素可能通过杏仁核、臂旁核、海马、皮层的瘦素受体参与CTA的形成与维持