c-Fos expression in the auditory pathways related to the significance of acoustic signals in rats performing a sensory-motor task

Neuronal activity was established in the auditory pathways in relation to behavioural response and cognitive information processing during a sensory-motor acoustic learning. Rats were trained in three consecutive phases. The first phase was an association between an auditory stimulus and a food reward; the second phase a simple discrimination between two sounds of different frequency components, and the third phase a more complex discrimination involving both spectral and spatial sound dimensions. Auditory stimuli were bursts of complex sounds lasting 500 ms. Neuronal activity related to the behaviourally relevant stimuli was established in 20 "learning" rats undergoing this protocol, which were progressively sacrificed at the beginning, middle and end of each phase. For comparison, activity was also established in four "control" rats exposed to the same stimuli delivered pseudo-randomly, thus carrying no behavioural meaning. Neuronal activity was assessed immunocytochemically using the functional marker Fos. To establish a baseline, two rats were unexposed to controlled acoustic stimulation ("unstimulated" rats). In the superior olivary complex (SOC), inferior colliculus (IC) and medial geniculate body (MGB), the number of Fos-like immunopositive cells was comparable in "learning" and "control" animals, but higher than in the "unstimulated" rats. In the auditory cortex (AC), most prominently in the secondary area Te2, the number of Fos-like positive cells differed between "learning" and "control" rats, suggesting that the auditory cortical areas may be involved in the encoding of the behavioural significance of the acoustic stimuli.     

Defensive reactions are counteracted by midazolam and muscimol and elicited by activation of glutamate receptors in the inferior colliculus of rats

 The inferior colliculus is involved in conveying auditory information of an aversive nature to higher cortical structures. Gradual increases in the electrical stimulation of this structure produce progressive aversive responses from vigilance, through freezing, until escape. Recently, we have shown that microinjections of NMDA into the inferior colliculus mimic these aversive effects and that the neural substrates responsible for learned escape behavior in the inferior colliculus are regulated by GABA−benzodiazepine mechanisms. In the present study, we extend these observations showing that unlearned aversive responses are also depressed by muscimol and midazolam, both GABA-benzodiazepine agonists, and that microinjection of glutamate, an excitatory amino acid, into the inferior colliculus can trigger freezing responses. Electrical stimulation of the inferior colliculus of rats placed inside an open field allowed the determination of thresholds for the aversive responses, alertness, freezing and escape. Systemic administration (3 and 5.6 mg/kg) as well as microinjections into the inferior colliculus of the anxiolytic compound midazolam (10, 20 and 40 nmol) caused increases in threshold for these aversive responses. Similar results were obtained following microinjections of the GABA-A agonist muscimol (0.1, 1 and 5 nmol) into this brainstem structure. Microinjections of low doses of glutamate (5 nmol), presumed to activate mainly AMPA/kainate receptors, into the ventrolateral division of the central nucleus of the inferior colliculus of rats placed inside a circular arena induced aversive reactions, characterized by freezing responses. However, higher doses of glutamate caused no apparent effects. GDEE, an AMPA/kainate receptor antagonist, inhibited, whereas AP7, a NMDA receptor antagonist, did not influence these responses. It is suggested that GABA-benzodiazepine processes modulate the expression of defensive reactions in the inferior colliculus and that activation of fast-acting excitatory amino acid receptors in this midbrain region can trigger the initial steps of the defense reaction without eliciting the motor explosive behavior usually seen following the activation of NMDA receptors. Received: 13 May 1998 / Final version: 12 August 1998     

36种注射剂中不溶性微粒的研究

目的：研究36种注射剂中的不溶性微粒现状及解决方法。方法：将36种注射剂按治疗剂量(其中24种溶配于0．9％氯化钠注射液或5％葡萄糖注射液中，12种输液直接测试)，用HIAC Royco8000A仪计数该液中直径≥1，2，3，5，8，10，20，25μm的微粒数；对微粒进行理化性质和显微鉴别；考察精密药液过滤器流速、流量、吸附性和截留作用。结果：11种新药静脉注射剂超过《美国药典》(25版)标准，占实验总数30．56％。不溶性微粒有玻璃碴、活性炭、橡胶屑、毛屑索条和药物残渣；精密药液过滤器的流速、流量符合临床要求，截留率为91．01％～99．97％，未见其有吸附作用。结论：精密药液过滤器可截留注射剂中的有害微粒。     

青霉素过滤工艺改进

目的：为了进一步解决青霉素生产过过程中的过滤问题和进一步扩大产量，克服原设备的缺陷。方法：我们采用了目前国内制药企业广泛使用的鼓式过滤机过滤技术及利用热交换器进行热量交换以达到生产工艺的要求同时改进相应工艺。结果：达到降低生产成本、扩大生产产量、加快生产速度，提高生产产率的结果。结论：通过实际生产证明完全符合实际生产的需要。本文就目前青霉素过滤过程中的几个关键环节作简要讨论。     

UV filters with antagonistic action at androgen receptors in the MDA-kb2 cell transcriptional-activation assay.

The fact that certain ultraviolet (UV) filters used in cosmetics display estrogenic activity prompted us to study potential actions on androgen receptors (AR) in the human breast carcinoma cell line MDA-kb2, which expresses functional endogenous AR and glucocorticoid receptors (GR) and is stably transfected with a luciferase reporter plasmid. Dihydrotestosterone (DHT), methyltrienolone (R1881), methyltestosterone, danazol, and androstenedione increased luciferase activity, with EC50 values between 0.11 nM (R1881), 0.14 nM (DHT), and 73.5 nM (androstenedione). DHT-induced luciferase gene expression was inhibited by nonsteroidal antiandrogens, hydroxyflutamide, flutamide, bicalutamide, and vinclozolin. In contrast, the steroidal AR agonist/antagonist cyproterone actetate showed agonistic activity in the absence and presence of DHT, which was not blocked by hydroxyflutamide and thus seems not to be mediated by AR. GR-mediated activation of luciferase by dexamethasone was 100 times less potent than DHT and was not antagonized by hydroxyflutamide. The cell line was used for screening of UV filters, benzophenone-3 (Bp-3), benzophenone-4, 3-benzylidene camphor, 4-methylbenzylidene camphor, butyl-methoxy-dibenzoylmethane, homosalate (HMS), octyl-dimethyl-PABA, and octyl-methoxycinnamate. Two of these, Bp-3 and HMS, antagonized DHT-induced AR activation below cytotoxic concentrations, with IC50 of 5.57 10-6 M (HMS) and 4.98 10-6 M (Bp-3). None of the eight UV filters displayed agonistic activity when tested alone, but high concentrations of Bp-3 induced an increase of luciferase activity in the presence of dexamethasone, which was not blocked by hydroxyflutamide or the estrogen antagonist, ICI 182,780. These data indicate that the UV filters Bp-3 and HMS possess antiandrogenic activity in vitro in addition to estrogenic activity.     

In vivo efficacy of a novel double liposome as an oral dosage form of salmon calcitonin

A simple method for the preparation of the inner liposomes for double liposomes (DL) was developed. The encapsulation efficiency of erythrosine in liposomes prepared by this new method is superior to that of the previous method because of the concentration of the drug in the lipid membrane. To evaluate the usefulness of DL prepared by the glass‐filter method modified in this study as an oral dosage form of salmon calcitonin (SCT), a suspension of liposomes containing SCT was administered to rats at a dose of 10 μg SCT/kg. Each type of DL showed better efficacy than its inner liposomes alone. The decrease in plasma calcium level was dependent on the electrical charge and particle size of the inner liposomes. The hypocalcemic efficacy of DL encapsulating SCT‐loading cationic liposomes relative to that after subcutaneous administration of SCT at a dose of 1 μg/kg was 6.47%, which was the largest value obtained. These results indicated that not only the particle size but also the electrical charge of inner liposomes affect intestinal absorption. This study verified that the efficacy was increased because of the decrease in diameter of the inner liposomes and the use of lipid with a positive charge. These findings concluded that DL might be useful as an oral dosage form of SCT. Drug Dev. Res. 58:253–257, 2003. © 2003 Wiley‐Liss, Inc.     

包括腔静脉旁部的肝右尾叶及全尾叶切除

目的 探讨并总结包括腔静脉旁部肝尾叶切除的方法和经验。方法 分别采用右后途径和左侧途径行右尾叶和全尾叶切除；前者附加部分右后叶切除，后者可为单独全尾叶切除或附加左外叶或左半肝切除。结果 成功施行包括腔静脉旁部的肝尾叶切除13例，其中右尾叶切除7例，全尾叶切除6例；全组无手术死亡，术中、术后均无严重病发症发生；术后平均失血量为896.15ml，平均肝门阻断时间为25.40min，术后平均住院12.38天。结论 虽然解剖关系复杂，切除包括腔静脉旁部的肝尾叶安全可行。     

耳蜗急性纯音损伤后下丘及耳蜗核快速功能重组

实验比较高强度纯音损伤耳蜗局部区域前后，耳蜗背核及下丘接近损伤区边缘的神经元反应特性的改变。致损纯音的频率高于神经元的特征频率，且位于其兴奋区以外，所以不影响其兴奋性输入。结果发现此种纯音损伤在逾半数的神经元产生不同程度的去抑制效应，提示皮层的功能重组可能部分地起源于低位中枢的功能改变，下丘和耳蜗背核的抑制性神经网络具有相当程度的侧抑制组分。     

瞬态诱发耳声发射信号数字滤波及相关函数分析

用数字滤波及相关函数处理技术对１０名（２０耳）学龄前儿童短声诱发的ＴＥＯＡＥ信号进行二次处理。结果表明：通过数字滤波及相关处理后的ＴＥＯＡＥ信号比原始记录的ＴＥＯＡＥ信号波形更加清晰，易于辨认，有效地提高了ＴＥＯＡＥ信号的信噪比及识别率。     

冬虫夏草及其伪劣商品的鉴别

冬虫夏草为名贵滋补药。明代即出口日本，现畅销国际市场，是中国传统的出口商品，享有极高的声誉。近年来国内外市场需求增大，而产量小，价格上扬，伪品、掺杂品增多。本文提出实用鉴别方法，以利保证冬虫夏草的质量。