蓝斑核、中缝大核和迷走神经背核在胃运动调节中的关系

目的：探讨蓝斑（LC）、中缝大核（NRM）和迷走神经背核（DMV）,及其相关递质和受体对胃运动的调节途径及机制,阐明它们在调节胃运动中的相互关系。方法：实验采用了核团定位电刺激、损毁和核团微量注射等实验方法,以记录胃内压,统计胃收缩幅度作为胃运动变化的指标。结果：①刺激LC显著降低胃收缩幅度（P〈0.01）,损毁DMV可以减弱此效应,而阻断DMV上的肾上腺素能α受体,可以反转此抑胃效应。②刺激NRM显著降低胃收缩幅度（P〈0.01）,损毁DMV后此效应被消除;阻断DMV上的5-HT2A受体使胃收缩幅度大幅度降低（P〈0.01）,此时再刺激NRM不能进一步的抑制胃运动;而损毁LC后刺激NRM,可消除NRM的抑胃效应,在LC注射5-HT2A受体阻断剂也可以消除该效应。结论：①LC可能通过DMV的5-HT2A受体和α受体对生理条件下正常胃的运动起着重要的双向调节作用;②NRM通过LC上的5-HT2A受体而发挥其对胃运动的抑制效应。     

大鼠眶额叶GABA及其B型受体在应激性抑郁行为发生中的作用及其影响机制

为了探讨眶额叶(orbital frontal cortex,OFC)GABA及其B型受体在应激性抑郁行为发生中的作用及其影响机制,实验采用强迫游泳方法建立急性应激抑郁模型。在OFC区微量注射γ-氨基丁酸(γ-aminobutyric acid,GABA)及其B型受体阻断剂,通过开场实验、强迫游泳方式检测动物行为学表现,用免疫组织化学染色和Western blotting方法检测OFC区Kalirin表达,用高尔基染色法观察锥体细胞树突和树突棘。结果显示:强迫游泳应激引起动物抑郁样行为表现,同时,OFC区Kalirin阳性颗粒数及表达量显著减少,且锥体细胞树突棘密度下降;OFC区微量注射GABA具有抗抑郁效应,使OFC区Kalirin表达显著升高,锥体细胞树突棘密度增加;GABA-B型受体阻断剂CGP35348可以抑制GABA的这种效应。由此可见,通过强迫游泳应激诱发的抑郁样的行为变化与OFC区Kalirin表达减少和神经元树突棘密度降低有关,GABA可能通过GABA-B型受体增加OFC区Kalirin表达,以防止神经元退行性变化而产生抗抑郁作用。     

Orexin-A通路对胃运动的调控研究

目的:探讨下丘脑外侧核(LHA)-伏隔核(NAcc)orexin-A神经和功能通路构成及该通路对胃运动的影响及潜在机制。方法:将健康成年雄性Wistar大鼠随机分为逆行追踪组和胃运动组:逆行追踪组大鼠采用逆行追踪技术结合免疫荧光组织化学染色法,观察下丘脑外侧核-伏隔核间是否存在orexin-A神经通路;胃运动组大鼠通过在体胃运动研究,观察伏隔核内微量注射不同浓度orexin-A对大鼠胃运动幅度和频率的影响,以及电刺激下丘脑外侧核后,大鼠胃运动的变化及机制。结果:荧光逆行追踪结合荧光免疫组织化学染色结果显示:下丘脑外侧核内有荧光金和orexin-A双重标记的神经元。胃运动研究结果显示:伏隔核内微量注射orexin-A,大鼠胃运动幅度和频率显著增加,并呈现显著剂量依赖关系(P0.05),伏隔核预先微量注射SB-334867,可反转该效应(P0.05)。电刺激下丘脑外侧核,大鼠胃运动幅度和频率显著增强(P0.05)。同样,伏隔核内微量注射SB-334867,再电刺激下丘脑外侧核,电刺激导致的胃运动增强效应显著减弱(P0.05)。结论:下丘脑外侧核-伏隔核存在orexin-A神经和功能通路,该通路可能通过orexin-A受体介导参与胃动力和能量代谢调控。     

Orexin-A对大鼠胃功能的影响

目的:探讨Orexin-A对大鼠胃功能的影响。方法:通过大鼠迷走神经复合体微量注射Orexin-A后,观察大鼠胃运动、胃液和胃酸分泌的变化。结果:DVC微量注射Orexin-A后,大鼠胃收缩幅度以及收缩频率明显升高,且呈明显剂量依赖关系(P0.05),SB334867可显著阻断Orexin-A对促胃运动效应(P0.05)。DVC微量注射orexin-A后,大鼠胃液及胃酸分泌且呈剂量依赖性增加(P0.05)。结论:迷走神经复合体微量注射Orexin-A能影响胃的运动以及胃内体液的分泌。     

眶额叶区5-HT与Glu、NO在急性强迫游泳应激抑郁症模型中的关系

目的：探讨眶额叶区5-羟色胺（5-HT）与谷氨酸（Glu）、一氧化氮（N0）在急性强迫游泳应激抑郁症模型中的相互作用。方法：雄性SD大鼠随机分为对照组及各种药物注射组,强迫游泳制造大鼠应激性抑郁模型,眶额叶区微量注射各组药物,敞箱实验及游泳测试观察大鼠的抑郁样行为表现。结果：①与对照组比,注射Glu使大鼠强迫游泳不动时间显著增加;注射NMDA受体拮抗剂（MK-801）使大鼠强迫游泳不动时间减少;与Glu组比,MK-801预注射后Glu注射使大鼠强迫游泳不动时间减少;②与5-HT组比,MK-801预注射后5-HT注射使大鼠强迫游泳不动时间增加;③与对照组比,注射L-精氨酸（L-Ars）使大鼠强迫游泳不动时间显著增加;注射NOS抑制剂（L-NAME）（10μg/μl）使大鼠强迫游泳不动时间减少;L-NAME（20μg／μl）注射使大鼠强迫游泳不动时间增加;L-NAME（40μg/μl）注射使大鼠强迫游泳不动时间增加;④与L-NAME（10μg/μl）组比较,5-HT1A受体拮抗剂spipemne预注射后LNAME（10μg／μl）注射使大鼠强迫游泳不动时间增加。结论：眶额叶（OFC）区Glu含量的增加能够诱发抑郁,其作用可能主要是通过NMDA受体实现的,Glu经NMDA受体引发抑郁的同时还可能通过调节突触后膜上5-HT1A受体减弱5-HT的抗抑郁作用;OFC区NO可通过调节5-HT神经元进而参与抑郁的发生。     

大豆甙元磺酸钠对胃运动的影响及其机制

目的:研究大豆甙元磺酸钠对胃运动的影响及其作用机制。方法:采用SD大鼠腹腔和侧脑室给药,记录胃运动收缩的幅度和频率。结果:①腹腔注射不同剂量的大豆甙元磺酸钠,均引起胃收缩幅度下降,但未呈现剂量效应关系;胃收缩频率无明显变化。②腹腔注射纳洛酮可反转大豆甙元磺酸钠的作用。③腹腔注射心得安,可使大豆甙元磺酸钠抑制胃运动的作用增强,注射酚妥拉明可反转大豆甙元磺酸钠的作用。④腹腔注射阿托品对大豆甙元磺酸钠的作用无明显的影响。⑤侧脑室注射不同剂量的大豆甙元磺酸钠,其中小剂量组出现胃收缩幅度下降,但胃收缩频率亦无明显变化。结论:腹腔和侧脑室注射大豆甙元磺酸钠对胃运动均有抑制作用,且腹腔注射大豆甙元磺酸钠的效应至少部分是与内源性阿片肽及其受体和去甲肾上腺素能神经元及其α受体有关,肾上腺素能神经元及β肾上腺素能受体也参与了大豆甙元磺酸钠抑制胃运动的作用。     

5,6-DHT损毁大鼠蓝斑内5-HT能神经末梢对电针镇痛的影响

在大鼠蓝斑注射5.6-DHT 以破坏其5-HT 末梢,然后观察电针镇痛效应的变化。动物分注药组和对照组,注药组在注射5.6-DHT 后7天,针刺镇痛效应比注药前显著下降。与此同时,蓝斑内的5-HT 末梢发生变性,产生逆行性荧光积累,从荧光积累的末梢走向来看,蓝斑内被5.6-DHT 损毁的5-HT 末梢主要来源于中缝背核。随着蓝斑内5-HT 末梢的变性,脑桥区5-HT 含量下降,下降率达27%P<0.01。对照组动物,蓝斑内5-HT 末梢保持正常,其镇痛效应与注药前相比也无明显改变。鉴于一般认为蓝斑核的活动削弱针刺镇痛效应,以上结果提示,在电针镇痛过程中,支配蓝斑的5-HT 神经末梢,对该核 NA 能神经元可能有抑制性影响。     

尾核P物质对胃运动的抑制效应系通过黑质,迷走背核经迷走神经所介导

本工作观察损毁下丘脑外侧区,黑质,迷走背核及其传出神经对尾核微量注射Ｐ物质引起的胃肌电快波和胃运动抑制效应的影响。实验结果：该抑制效应不依赖于下丘脑外侧区的完整但可被损毁黑质,迷走背核或迷走上所消除。用利血平耗竭交感神经递质则不影响该效应。这些结果表明：尾核ＳＰ的抑胃效应系通过黑质、迷走背核经迷走神经所传出。     

谷氨酸钠兴奋室旁核引起的升压效应及其与蓝斑-升压反应和A_1-降压反应间的关系

将L-谷氨酸钠(Glu)注入乌拉坦麻醉、箭毒化、人工呼吸大鼠的室旁核(NPV)或蓝斑内引起升压反应。蓝斑升压反应可被双侧室旁核内预先注射酚妥拉明或心得安明显衰减;双侧室旁核内预先注射酚妥拉明或荷包牡丹碱还可使Glu兴奋延髓A_1区引起的降压反应减小,但注射心得安对A_1-降压反应无明显影响。以上结果提示蓝斑-升压反应和A_1-降压反应均部分通过NPV实现,A_1降压过程中可能有NPV内GABA能抑制性中间神经元参与。     

猫中缝大核与蓝斑复合核区:两个不同的调制血管反射活动的结构

在无麻醉的麻痹猫,电刺激内脏大神经或腓总神经、阻断颈总动脉血流所引起的加压反射和皮肤电阻下降,在损毁双侧蓝斑复合核区后均明显减弱,而在损毁延髓中缝大核区后则大为增强。这两种效应在去大脑动物仍可出现。若先损毁中缝大核,则损毁蓝斑复合核的效应难以出现。上述脑损毁本身均不影响血压水平。以弱电流刺激蓝斑复合核通常强化这些反射,而刺激中缝大核有时可压抑它们。在胸8水平切断双侧背外侧索的背部,不影响窦加压反射,但有时增强内脏大神经加压反射;在颈2水平切断则使这两种加压反射不同程度地增强。本结果提示:中缝大核对主管血管反射活动的延髓-脊髓回路起着紧张性抑制作用,而蓝斑复同核则起着兴奋性作用。     

Structure and function of S-adenosylhomocysteine hydrolase

In mammals, S-adenosylhomocysteine hydrolase (AdoHcyase) is the only known enzyme to catalyze the breakdown of S-adenosylhomocysteine (AdoHcy) to homocysteine and adenosine. AdoHcy is the product of all adenosylmethionine (AdoMet)-dependent biological transmethylations. These reactions have a wide range of products, and are common in all facets of biometabolism. As a product inhibitor, elevated levels of AdoHcy suppress AdoMet-dependent transmethylations. Thus, AdoHcyase is a regulator of biological transmethylation in general. The three-dimensional structure of AdoHcyase complexed with reduced nicotinamide adenine dinucleotide phosphate (NADH) and the inhibitor (1′R, 2′S, 3′R)-9-(2′,3′-dihyroxycyclopenten-1-yl)adenine (DHCeA) was solved by a combination of the crystallographic direct methods program, SnB, to determine the selenium atom substructure and by treating the multiwavelength anomalous diffraction data as a special case of multiple isomorphous replacement. The enzyme architecture resembles that observed for NAD-dependent dehydrogenases, with the catalytic domain and the cofactor binding domain each containing a modified Rossmann fold. The two domains form a deep active site cleft containing the cofactor and bound inhibitor molecule. A comparison of the inhibitor complex of the human enzyme and the structure of the rat enzyme, solved without inhibitor, suggests that a 17° rigid body movement of the catalytic domain occurs upon inhibitor/substrate binding.     

Land,livestock, and livelihoods: Changing dynamics of gender,caste, and ethnicity in a Nepalese Village

Over the past 10 years, Ghusel VDC, Lalitpur District has moved from primarily subsistence agriculture into the wider cash economy aided by the Small Farmers' Development Program (SFDP), which provides credit to farmers mainly for the purchase of buffalo for milk production, and by the National Dairy Corporation, which supports local dairy cooperatives. Analysis reveals that buffalo-keeping and milk sales are increasing the well-being of many households, while at the same time creating new inequalities in gender roles and responsibilities, greater inequities between Brahmin and Tamang residents in Ghusel, and placing pressures on the ecosystem for increased supplies of fodder and fuelwood. Evidence suggests that there is critical, need for attention to the social, and particularly gender-based, implications of maintaining livestock for milk sales and to the ecological underpinnings of this livelihood system.     

Tuning of electronic properties of one-dimensional cyano-bridged Cu-Ni, Cu-Pd, and Cu-Pt bimetallic assemblies by stereochemistry of ligands

Preparations, XPS and electronic spectroscopy, and magnetism of seven new one-dimensional cyano-bridged coordination polymers, chiral [Cu(RR-chxn)₂][Pd(CN)₄] · 2H₂O (1), [Cu(trans-chxn)₂][M(CN)₄] · 2H₂O (2, 4, and 6 for M = Pd, Ni, and Pt), and [Cu(cis-chxn)₂][M(CN)₄] · 2H₂O (3, 5, and 7 for M = Pd, Ni, and Pt) (RR-chxn = cyclohexane-(1R,2R)-diamine, trans-chxn = racemic trans-cyclohexane-(1,2)-diamine, and cis-chxn = racemic cis-cyclohexane-(1,2)-diamine) have been reported in view of tuning of their electronic properties by stereochemistry of chxn ligands and metal-substitution. Comparison of Cu 2p_1/2 and 2p_3/2 peaks of XPS and broad d-d bands around 18 000 cm⁻¹ of electronic spectra are described systematically for 1-7. Variable-temperature magnetic measurement shows that complexes 1-7 indicate weak antiferromagnetic interactions via cyano-bridges. Because of semi-coordination coupled with pseudo Jahn-Teller elongation and electrostatic interaction for 1, the axial Cu-N coordination bond distances of 2.330(7) and 3.092(8) Å are considerably longer than those of equatorial ones in the range from 2.016(6) to 2.030(6) Å. The former bond distances of 1 are intermediate values among the related Ni (2.324(6) and 3.120(8) Å) and Pt (2.34(1) and 3.09(1) Å) complexes.     

Influence of Fluoride on Rat Kidney Antioxidant System: Effects of Methionine and Vitamin E

The aim of the study has been to determine and compare the influence upon the kidney antioxidative system, exercised by administration of vitamin E, and vitamin E in combination with methionine, under conditions of oxidative stress induced by sodium fluoride. The experiment was carried out on Wistar FL rats (adult males) that, for 35 days, were administered water, NaF, NaF with vitamin E, or vitamin E with methionine (doses: 10 mg NaF/kg of body mass/24 h, 3 mg vitamin E per 10 μl per rat for 24 h, 2 mg methionine per rat for 24 h). The influence of administered sodium fluoride and antioxidants upon the antioxidative system in kidney was examined by analyzing the concentration of malondialdehyde (MDA) and the activity of the most important antioxidative enzymes (SOD, total and both its isoenzymes, GPX, GST, GR, and CAT). The studies carried out confirmed the disadvantageous effect of the administered dose of NaF upon the antixodiative system in rats (increase in the concentration MDA, decrease activity of all antioxidative enzymes). The administration of vitamin E increased the activity of studied enzymes with the exception of glutathione reductase GR; it also reduced the procesess of lipid peroxidation. It has been found that combined doses of vitamin E and methionine were most effective in inhibiting lipid peroxidation processes. The results confirmed the antioxidative properties of methionine.     

Gamma-glutamylcysteine protects ergothioneine-deficient Mycobacterium tuberculosis mutants against oxidative and nitrosative stress

Mycobacterium tuberculosis (M.tb.), the causative agent of tuberculosis (TB), cannot synthesize GSH, but synthesizes two major low molecular weight thiols namely mycothiol (MSH) and ergothioneine (ERG). Gamma-glutamylcysteine (GGC), an intermediate in GSH synthesis, has been implicated in the protection of lactic acid bacteria from oxidative stress in the absence of GSH. In mycobacteria, GGC is an intermediate in ERG biosynthesis, and its formation is catalysed by EgtA (GshA). GGC is subsequently used by EgtB in the formation of hercynine-sulphoxide-GGC. In this study, M.tb. mutants harbouring unmarked, in-frame deletions in each of the fives genes involved in ERG biosynthesis (egtA, egtB, egtC, egtD and egtE) or a marked deletion of the mshA gene (required for MSH biosynthesis) were generated. Liquid chromatography tandem mass spectrometry analyses (LC-MS) revealed that the production of GGC was elevated in the MSH-deficient and the ERG-deficient mutants. The ERG-deficient ΔegtB mutant which accumulated GGC was more resistant to oxidative and nitrosative stress than the ERG-deficient, GGC-deficient ΔegtA mutant. This implicates GGC in the detoxification of reactive oxygen and nitrogen species in M.tb.     

Reorientation of Microfibrils and Microtubules at the Outer Epidermal Wall of Maize Coleoptiles During Auxin-Mediated Growth

Auxin-mediated elongation growth of isolated subapical coleoptile segments of maize (Zea mays L.) is controlled by the extensibility of the outer cell wall of the outer epidermis (Kutschera et al., 1987). Here we investigate the hypothesis that auxin controls the extensibility of this wall by changing the orientation of newly deposited microfibrils through a corresponding change in the orientation of cortical microtubules. On the basis of electron micrographs it is shown that cessation of growth after removal of the endogenous source of auxin is correlated with a relative increase of longitudinally orientated microfibrils and microtubules at the inner wall surface. Conversely, reinduction of growth by exogenous auxin is correlated with a relative increase of transversely orientated microfibrils and microtubules at the inner wall surface. These changes can be detected 30–60 min after the removal and addition of auxin, respectively. The functional significance of directional changes of newly desposited wall microfibrils for the control of elongation growth is discussed.     

Highly flexible O,O′,N ligands and their Fe, Ni, Cu and Zn complexes

Three new chiral ligands bearing an O,O′,N donor set (O_methoxyO_hydroxyN_pyridine) were synthesised and coordinated to Fe^III, Fe^II, Ni^II, Cu^II and Zn^II to yield complexes with the general formula [M(OON)Cl_x]_y. While the pyridine N and the hydroxy O atoms coordinate strongly to all applied metal ions, the methoxy donor seems not to be involved in coordination, although some evidence for a weak interaction between O_Me and the Zn^II were found in NMR spectra. In the bidentate O′,N coordination mode the new ligands exhibit several coordination geometries as analysed in the solid compounds by XRD, EXAFS and EPR and in solution by UV-Vis absorption, cyclic voltammetry, EXAFS, EPR or NMR spectroscopy.     

Expression of mRNA for PACAP and its receptors in intra- and extra-adrenal human pheochromocytomas and their relationship to catecholamine synthesis

Purpose: Pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the secretin/glucagons/vasoactive intestinal peptide family, induces the expression of catecholamine-synthesizing enzymes in adrenal medullary cells. In addition, PACAP and its receptor have been detected in human pheochromocytoma tissues, though it is not yet known whether PACAP enhances the expression of genes encoding catecholamine-synthesizing enzymes. To address this question, we analyzed PACAP, PACAP receptor, and tyrosine hydroxylase (TH) and phenylethanolamine-N-methyltransferase (PNMT) mRNAs in pheochromocytomas. Methods: The levels of the mRNA for PACAP and vasoactive intestinal peptide (VIP), and their receptors, and for TH and PNMT were measured by RT-PCR or real-time PCR analysis, and the concentrations of catecholamines were measured by HPLC in 24 intra-adrenal and six extra-adrenal pheochromocytomas. Results: mRNA expression of PACAP and its receptor VPAC1R were detected in many pheochromocytomas (24/30 and 29/30, respectively), but mRNA expression of the PAC1R and VPAC2R receptor subtypes were detected in only one of six extra-adrenal pheochromocytomas. PACAP mRNA expression correlated with TH (p=0.0018) and PNMT (p=0.05) mRNA expression, as well as epinephrine (p=0.0342) levels in 16 intra-adrenal pheochromocytomas. Conclusion: Our findings support a possible role for PACAP in the regulation of expression of genes encoding catecholamine-synthesizing enzymes in intra-adrenal pheochromocytomas.     

邻苯二甲酸二丁酯对翡翠贻贝抗氧化酶及脂质过氧化水平的影响

实验室条件下,研究了不同浓度邻苯二甲酸二丁酯(DBP)长期胁迫(15 d)对翡翠贻贝内脏团和外套膜抗氧化酶(超氧化物歧化酶SOD、过氧化氢酶CAT)及脂质过氧化(LPO)水平(以MDA含量表示)的影响,以及受胁迫翡翠贻贝在清洁海水中恢复阶段上述生化指标的变化特征.结果表明:胁迫阶段,0.5和2.5 mg.L-1DBP下翡翠贻贝内脏团SOD活性表现为先抑制后逐渐恢复,12.5和62.5 mg.L-1下则持续受到显著抑制;不同浓度组CAT活性均明显被抑制.LPO水平明显升高.外套膜中,2.5 mg.L-1下SOD活性受到持续诱导,其他浓度组则先被抑制,后随曝露时间延长逐渐被诱导;各浓度组CAT的变化波动较大,没有明显规律;而LPO水平明显升高.净化恢复阶段,12.5和62.5 mg.L-1DBP胁迫下的内脏团SOD和CAT活性恢复较慢,其LPO水平随时间延长逐渐恢复至对照组水平;外套膜中SOD活性呈持续升高趋势,CAT活性和LPO水平则随时间延长恢复到对照组水平.