Synaptic potentials and effects of amino acid antagonists in the auditory cortex

Neurons of in vitro guinea pig and rat auditory cortex receive a complex synaptic pattern of afferent information. As many as four synaptic responses to a single-stimulus pulse to the gray or white matter can occur; an early-EPSP followed, sequentially, by an early-IPSP, late-EPSP, and late-IPSP. Paired pulse stimulation and pharmacological studies show that the early-IPSP can modify information transmission that occurs by way of the early-EPSP. Each of these four synaptic responses differed in estimated reversal potential, and each was differentially sensitive to antagonism by pharmacological agents. DNQX (6,7-dinitroquinoxaline-2,3-dione), a quisqualate/kainate receptor antagonist, blocked the early-EPSP, and the late-EPSP was blocked by the NMDA receptor antagonist APV (D-2-amino-5-phosphonovalerate). The early-IPSP was blocked by the GABA-a receptor antagonist bicuculline, and the late-IPSP by the GABA-b receptor antagonists 2-OH saclofen or phaclofen. Presentation of stimulus trains, even at relatively low intensities, could produce a long-lasting APV-sensitive membrane depolarization. Also discussed is the possible role of these synaptic potentials in auditory cortical function and plasticity.     

S-100 beta and insulin-like growth factor-II differentially regulate growth of developing serotonin and dopamine neurons in vitro.

To study the phenotypic specificity of S-100 beta and insulin-like growth factor II (IGF-II) for developing monoamine neurons, serotonin (5-HT) neurons from the embryonic day 14 (E14) rostral raphe or dopamine (TH) neurons from the substantia nigra/ventral tegmental area were cultured for 3 days in vitro (3 DIV) in the presence of these factors. Neuronotrophic effects were analyzed by computer-assisted morphometry of 5-HT and TH-immunoreactive neurons. S-100 beta and IGF-II differentially regulated the growth of 5-HT and TH neurons but did not affect their survival. S-100 beta significantly increased several parameters of neurite outgrowth by 5-HT neurons but inhibited the spatial extent (field area) of TH neurites. IGF-II promoted growth of cell bodies of both phenotype, but only stimulated neurite outgrowth by TH neurons. S-100 beta and IGF-II differentially affected the number of GFAP immunoreactive cells from raphe and substantia nigra, but these effects did not correlate with the specificity of neuronotrophic effects. S-100 beta and IGF-II immunoreactivities were expressed in glial cultures derived from the same brain regions, raising the possibility that these factors have autocrine effects on glia as well as paracrine actions on neurons. The results of this study suggest that specificity of neurotrophic factors for particular embryonic neurons may be correlated with their neurotransmitter phenotype.     

Acute selective serotonin reuptake inhibitors increase conditioned fear expression: blockade with a 5-HT(2C) receptor antagonist.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) effectively treat various anxiety disorders, although symptoms of anxiety are often exacerbated during early stages of treatment. We previously reported that acute treatment with the SSRI citalopram enhances the acquisition of auditory fear conditioning, which is consistent with the initial anxiogenic effects reported clinically. Here, we extend our findings by assessing the effects of acute SSRI treatment on the expression of previously acquired conditioned fear. METHODS: Rats underwent fear conditioning drug-free. Tone-evoked fear responses were tested after drug treatment the following day. This protocol more closely resembles the clinical setting than pre-conditioning treatment, because it evaluates effects of treatment on a pre-existing fear rather than on the formation of a new fear memory. RESULTS: A single pre-testing injection of the SSRIs citalopram or fluoxetine significantly increased fear expression. There was no effect of the antidepressant tianeptine or the norepinephrine reuptake inhibitor tomoxetine, indicating that this effect is specific to SSRIs. The SSRI-induced enhancement in fear expression was not blocked by tropisetron, a 5-HT(3) receptor antagonist, but was blocked by SB 242084, a specific 5-HT(2C) receptor antagonist. CONCLUSIONS: Enhanced activation of 5-HT(2C) receptors might be a mechanism for the anxiogenic effects of SSRIs observed initially during treatment.     

血清1,5-脱水葡糖醇的测定及在糖尿病诊断中的应用

目的:应用血清1,5-脱水葡糖醇(1,5AG)的酶动力学法,探讨其在糖尿病诊断中的应用价值。方法:应用全自动生化分析仪,采用全酶法测定健康人和糖尿病患者血清1,5AG的含量。结果:该法测定血清1,5AG精密度好,高、低值混合血清的CV分别为1.47％和1.70％;回收率分别为98.28％、101.32％和97.64％、103.36％,平均回收率为100.15％;在1,5-AG浓度为360μmol/L内呈良好的线性;60例糖尿患者血清1,5AG(5.38-59.54μmol/L)明显低于健康人(60.89～269.79μmol/L),P<0.01。结论:该方法重复性好,准确度高,工作试剂在2 d内稳定,适合常规实验室开展;血清1,5AG测定有助于糖尿病的诊断和治疗过程的监控。     

肝动脉化疗栓塞对肝癌细胞黏附分子CD44v6和ICAM-1表达的影响

目的:研究肝细胞癌(hepatocellular carcinoma,HCC)经导管肝动脉化疗栓塞(transcatheter arterial chemoemboli-zation,TACE)后残癌组织细胞黏附分子CD44v6和ICAM-1(intercelluar adhesion molecule-1,ICAM-1)的表达情况。方法:经病理证实的HCC 50例,包括单纯手术切除30例(对照组),TACE术后行Ⅱ期手术切除20例(TACE组)。TACE组患者术前接受1~2次不等的TACE治疗,均按统一规范标准给予化疗药物灌注+栓塞治疗。对标本行免疫组织化学PV-9000染色,其中TACE组取病灶边缘残存肿瘤部分,检测肿瘤组织CD44v6和ICAM-1的表达,将两组结果进行对照分析。结果:对照组和TACE组CD44v6和ICAM-1均有不同程度的表达。对照组CD44v6表达阳性22例(22/30,73.33%),TACE组CD44v6表达阳性13例(13/20,65%),两者间无显著性差异(P>0.05);对照组ICAM-1表达阳性19例(19/30,63.33%),TACE组ICAM-1表达阳性12例(12/20,60%),两者间亦无显著性差异(P>0.05)。对照组和TACE组中CD44v6和ICAM-1表达间均呈正相关(P<0.05)。结论:TACE术后残癌组织CD44v6和ICAM-1仍有较高的表达,TACE并不能有效降低肝癌组织CD44v6和ICAM-1的表达;两者表达呈正相关。     

小肠吸收胆固醇的分子生物学研究进展

胆固醇通过分布于十二指肠和近段空肠黏膜上皮细胞刷状缘膜的Niemann—Pick C1样蛋白1摄取，ATP结合盒G5、G8抑制小肠对胆固醇的摄取过程。进入上皮细胞的胆固醇大多数被乙酰辅酶A，胆固醇转乙酰基酶2酯化，随后通过组装形成乳糜微粒，经淋巴管进入血循环；另一部分胆固醇则以未酯化形式直接进入血循环形成高密度脂蛋白颗粒。这些过程受核受体——肝脏X受体的调控。年龄、性别、黏膜屏障和小肠传输速度也影响胆固醇的吸收。     

Airway hyper-responsiveness to adenosine 5''-monophosphate in preschool-age children with asthma

Airway hyper-responsiveness (AHR) to adenosine 5'-monophosphate (AMP) is closely associated with airway inflammation; however, not all asthmatic patients are responsive to it. This study was planned to investigate the predictive factors of AHR to AMP in asthmatic children aged between 3 and 6 yr. We performed a retrospective analysis of data from 63 asthmatic preschool-age children who were challenged by AMP in our department. All children were characterized by skin-prick tests, serum immunoglobulin E (IgE) levels, peripheral blood eosinophil percentage and bronchial challenge with methacholine (MCH) and AMP. Potential determinants for AHR to AMP were assessed within the group. AHR to AMP was found in 46% of preschool-age children with asthma, while that of MCH was 93.7%. All children responsive to AMP were also responsive to MCH. The geometric mean provocative concentration of MCH and AMP causing a 15% fall in transcutaneous oxygen tension (PC(15)PtcO(2)MCH and AMP) were 0.55 mg/ml (0.004-9.19) and 10.53 mg/ml (0.59-342.89), respectively. AMP-responsive children did not differ from non-responsive ones with respect to demographic factors, geometric mean PC(15)PtcO(2)MCH and atopic status. The median serum IgE level was significantly higher in AMP-responsive group than the non-responsive ones (p = 0.011). The peripheral blood eosinophilia was more frequent among responsive children (p = 0.019), and it was found as the only predictive factor for AMP responsiveness in preschool-age children with asthma in logistic regression model (odds ratio: 5.14; 95% CI: 1.23-21.47; p = 0.025). AMP responsiveness may be predicted by peripheral blood eosinophilia but not with atopy markers in young children with asthma.