BACKGROUND & AIMS: UNLABELLED:The objective of the present study was to investigate whether the endogenous opioids are involved in the control of endothelin-1 release from the pituitary gland. To test this hypothesis we have measured the peripheral plasma concentration of ET-1 as well as the content of immunoreactive ET-1 (irET-1) in the pituitary in response to opioid receptors blockade in euhydrated and 24 h water-deprived Wistar-Kyoto rats. Placebo or naltrexone (50 micrograms/kg body wt.) were given i.v. in both groups. Trunk blood was collected to determine hematocrit, plasma sodium and ET-1 levels (RIA). Immunostaining of ET-1 in the whole pituitary glands was performed by colloidal gold labeling. The quantitative analysis of irET-1 was carried out under a light microscope using a computerized image analyzer (MultiScan). RESULTS:(1) Twenty-four-hour dehydration resulted in marked increase of peripheral concentration of ET-1. Naltrexone injection induced a significant elevation of ET-1 plasma concentration in both, dehydrated and control animals. (2) The content of irET-1 in anterior and intermediate lobes of the pituitary in dehydrated rats was markedly higher than in control group. (3) Naltrexone injection caused a rapid and significant reduction irET-1 within the anterior, intermediate and posterior lobes in dehydrated and control animals. CONCLUSIONS:(1) An elevation of irET-1 in the pituitary gland and peripheral circulation in dehydrated animals may play a role in maintaining of water-electrolyte balance. (2) The mu-opioid system appears to control the ET-1 release from the pituitary in normal and dehydrated animals.

背景与目标： 未标记：本研究的目的是调查内源性阿片类药物是否参与垂体中内皮素-1的释放。为了检验这一假设，我们测量了在无水和缺水24小时的Wistar-Kyoto中阿片受体阻滞后垂体中ET-1的外周血浆浓度以及免疫反应性ET-1（irET-1）的含量大鼠。静脉注射安慰剂或纳曲酮（50微克/千克体重）。在两组中。收集躯干血液以确定血细胞比容，血浆钠和ET-1水平（RIA）。 ET-1在整个垂体中的免疫染色是通过胶体金标记进行的。使用计算机图像分析仪（MultiScan）在光学显微镜下对irET-1进行定量分析。
结果：（1）脱水24小时导致ET-1的外周血浓度明显升高。纳曲酮注射液在脱水和对照动物中均引起ET-1血浆浓度的显着升高。 （2）脱水大鼠垂体前叶和中间叶中irET-1的含量明显高于对照组。 （3）纳曲酮注射液导致脱水和对照动物的前叶，中叶和后叶内的irET-1迅速大量降低。
结论：（1）脱水动物垂体中irET-1的升高和外周循环可能在维持水电解质平衡中发挥了作用。 （2）在正常和脱水动物中，μ阿片样物质系统似乎可以控制ET-1从垂体的释放。

BACKGROUND & AIMS: :Neuronal death associated with cerebral ischemia and hypoglycemia is related to increased release of excitatory amino acids (EAA) and energy failure. The intrahippocampal administration of the glycolysis inhibitor, iodoacetate (IOA), induces the accumulation of EAA and neuronal death. We have investigated by microdialysis the role of exocytosis, glutamate transporters and volume-sensitive organic anion channel (VSOAC) on IOA-induced EAA release. Results show that the early component of EAA release is inhibited by riluzole, a voltage-dependent sodium channel blocker, and by the VSOAC blocker, tamoxifen, while the early and late components are blocked by the glutamate transport inhibitors, L-trans-pyrrolidine 2,4-dicarboxylate (PDC) and DL-threo-beta-benzyloxyaspartate (DL-TBOA); and by the VSOAC blocker 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS). Riluzole, DL-TBOA and tamoxifen did not prevent IOA-induced neuronal death, while PDC and DNDS did. The VSOAC blockers 5-nitro-2-(3-phenylpropyl-amino) benzoic acid (NPPB) and phloretin had no effect either on EAA efflux or neuronal damage. Results suggest that acute inhibition of glycolytic metabolism promotes the accumulation of EAA by exocytosis, impairment or reverse action of glutamate transporters and activation of a DNDS-sensitive mechanism. The latest is substantially involved in the triggering of neuronal death. To our knowledge, this is the first study to show protection of neuronal death by DNDS in an in vivo model of neuronal damage, associated with deficient energy metabolism and EAA release, two conditions involved in some pathological states such as ischemia and hypoglycemia.

背景与目标： ：与脑缺血和低血糖有关的神经元死亡与兴奋性氨基酸（EAA）释放增加和能量衰竭有关。海马内糖酵解抑制剂碘乙酸盐（IOA）的给药可诱导EAA积累和神经元死亡。我们已经通过微透析研究了胞吐作用，谷氨酸转运蛋白和体积敏感性有机阴离子通道（VSOAC）对IOA诱导的EAA释放的作用。结果表明，EAA释放的早期组分被电压依赖性钠通道阻滞剂利鲁唑和VSOAC阻断剂他莫昔芬抑制，而谷氨酸转运抑制剂L-反式吡咯烷2则阻断了早期和晚期组分。 ，4-二羧酸盐（PDC）和DL-苏-β-苄氧基天冬氨酸（DL-TBOA）;通过VSOAC阻滞剂4,4'-二硝基二苯乙烯-2,2'-二磺酸（DNDS）。利鲁唑，DL-TBOA和他莫昔芬不能预防IOA诱导的神经元死亡，而PDC和DNDS可以预防。 VSOAC阻滞剂5-硝基-2-（3-苯基丙基-氨基）苯甲酸（NPPB）和荧光素对EAA流出或神经元损伤均无影响。结果表明，糖酵解代谢的急性抑制可通过胞吐作用，谷氨酸转运蛋白的损伤或逆作用以及DNDS敏感机制的激活来促进EAA的积累。最新消息实质上涉及神经元死亡的触发。据我们所知，这是第一个在体内神经元损伤模型中由DNDS保护神经元死亡的研究，该模型与能量代谢不足和EAA释放有关，这是某些病理状态（例如局部缺血和低血糖）的两个条件。

BACKGROUND & AIMS: :Rat basophilic leukemia (RBL 2H3) cells were passively sensitized by exposure to monoclonal anti-trinitrophenol mouse immunoglobulin E (anti-trinitrophenol IgE) (0.5 microgram/ml) and triggered by exposure to a sub-optimal concentration of trinitrophenol ovalbumin conjugate (5 ng/ml). At this concentration, trinitrophenol-ovalbumin increased histamine release from a basal rate of 4.8 +/- 0.5 to 28.5 +/- 4.6% and peptidoleukotrienes from less than 0.1 to 4.2 +/- 1.3 ng/10(6) cells in the activated cells. Ro 19-3704 and Ro 19-1400, platelet activating factor (PAF) antagonists which are structural analogs of PAF, potently inhibited both the IgE-dependent release of histamine (IC50 values of 3.0 and 3.6 microM, respectively) and LT release (IC50 values of 5.0 microM for both compounds) from the cells. These effects appeared to be independent to the ability of the compounds to act as PAF antagonists since PAF on its own had no effect on mediator release, and WEB 2086 and BN 52021, structurally distinct PAF antagonists, were relatively ineffective as inhibitors of mediator release. Ro 19-3704 and Ro 19-1400 were observed to be potent inhibitors of the soluble phospholipase A2 activity in synovial fluid from rheumatoid arthritic patients (IC50 values of 6.5 and 8.4 microM, respectively). In contrast, WEB 2086 and BN 52021 had no effect on this phospholipase A2. Ro 19-3704 significantly inhibited the IgE-dependent formation of inositol phosphates in RBL 2H3 cells (IC50 value of 7.0 microM). These data suggest that the mediator release inhibitory action of these compounds may be related to the ability of these compounds to inhibit phospholipase A2 and/or phospholipase C.

背景与目标： ：暴露于单克隆抗三硝基苯酚小鼠免疫球蛋白E（抗三硝基苯酚IgE）（0.5微克/毫升）可以被动致敏大鼠嗜碱性粒细胞白血病（RBL 2H3）细胞，并通过暴露于次适量浓度的三硝基苯酚卵白蛋白缀合物（5 ng / ml）。在此浓度下，三硝基苯酚-卵清蛋白将组胺释放从基础速率的4.8 /-0.5增加到28.5 /-4.6％，而肽白三烯从少于0.1到4.2 /-1.3 ng / 10（6）细胞增加。 Ro 19-3704和Ro 19-1400，血小板活化因子（PAF）拮抗剂，是PAF的结构类似物，可有效抑制IgE依赖的组胺释放（IC50分别为3.0和3.6 microM）和LT释放（IC50）。两种化合物的浓度值均为5.0 microM）。这些作用似乎与化合物充当PAF拮抗剂的能力无关，因为PAF本身对介质释放没有影响，并且结构不同的PAF拮抗剂WEB 2086和BN 52021作为介质释放抑制剂相对无效。观察到Ro 19-3704和Ro 19-1400是类风湿关节炎患者滑液中可溶性磷脂酶A2活性的有效抑制剂（IC50值分别为6.5和8.4 microM）。相反，WEB 2086和BN 52021对这种磷脂酶A2没有影响。 Ro 19-3704显着抑制RBL 2H3细胞中IgE依赖性肌醇磷酸的形成（IC50值为7.0 microM）。这些数据表明这些化合物的介质释放抑制作用可能与这些化合物抑制磷脂酶A2和/或磷脂酶C的能力有关。

BACKGROUND & AIMS: :The fumigant insecticide phosphine (PH3) is known to inhibit cytochrome c oxidase in vitro. Inhibition of the respiratory chain at this site has been shown to stimulate the generation of superoxide radicals (O2-), which dismutate to form hydrogen peroxide (H2O2). This study was performed in order to investigate the production of H2O2 by mitochondria isolated from granary weevil (Sitophilus granarius) and mouse liver on exposure to PH3. Other respiratory inhibitors, antimycin, myxothiazol, and rotenone were used with insect mitochondria. Hydrogen peroxide was measured spectrophotometrically using yeast cytochrome c peroxidase as an indicator. Insect and mouse liver mitochondria, utilizing endogenous substrate, both produced H2O2 after inhibition by PH3. Insect organelles released threefold more H2O2 than did mouse organelles, when exposed to PH3. Production of H2O2 by PH3-treated insect mitochondria was increased significantly on addition of the substrate alpha-glycerophosphate. Succinate did not enhance H2O2 production, however, indicating that the H2O2 did not result from the autoxidation of ubiquinone. NAD(+)-linked substrates, malate and pyruvate also had no effect on H2O2 production, suggesting that NADH-dehydrogenase was not the source of H2O2. Data obtained using antimycin and myxothiazol, both of which stimulated the release of H2O2 from insect mitochondria, lead to the conclusion that glycerophosphate dehydrogenase is a source of H2O2. The effect of combining PH3, antimycin, and myxothiazol on cytochrome spectra in insect mitochondria was also recorded. It was observed that PH3 reduces cytochrome c oxidase but none of the other cytochromes in the electron transport chain. There was no movement of electrons to cytochrome b when insect mitochondria are inhibited with PH3. The spectral data show that the inhibitors interact with the respiratory chain in a way that would allow the production of H2O2 from the sites proposed previously.

背景与目标： ：已知熏蒸杀虫剂膦（PH3）在体外可抑制细胞色素C氧化酶。已显示出在该部位抑制呼吸链会刺激超氧化物自由基（O2-）的生成，这些自由基会歧化形成过氧化氢（H2O2）。进行这项研究是为了研究暴露于PH3时从粮象鼻虫（Sitophilus granarius）和小鼠肝脏分离的线粒体产生H2O2。其他呼吸抑制剂，抗霉素，甲噻唑和鱼藤酮与昆虫线粒体一起使用。使用酵母细胞色素c过氧化物酶作为指示剂，通过分光光度法测量过氧化氢。昆虫和小鼠肝线粒体利用内源性底物，在被PH3抑制后均产生H2O2。当暴露于PH3时，昆虫细胞器释放的H2O2比小鼠细胞器释放的三倍。加入底物α-甘油磷酸后，PH3处理的昆虫线粒体产生的H2O2显着增加。琥珀酸酯并没有增加H2O2的产生，但是，这表明H2O2不是由泛醌的自氧化作用产生的。 NAD（）连接的底物，苹果酸和丙酮酸也对H2O2的产生没有影响，这表明NADH脱氢酶不是H2O2的来源。使用抗霉素和甲噻唑获得的数据均刺激了昆虫线粒体释放H2O2，得出的结论是甘油磷酸脱氢酶是H2O2的来源。还记录了PH3，抗霉素和Mythothiazol组合对昆虫线粒体中细胞色素光谱的影响。观察到PH3会还原细胞色素c氧化酶，但在电子传输链中没有其他细胞色素。当昆虫线粒体被PH3抑制时，电子不会移动到细​​胞色素b。光谱数据表明，抑制剂与呼吸链相互作用的方式可以使先前提出的位点产生H2O2。

BACKGROUND & AIMS: :The objective of this study was to prepare a 72 h-release formulation of silybin (72 h-SLB) using a combination of solid dispersion, gel matrix and porous silica nanoparticles (PSNs) and to investigate the in vitro/in vivo correlations (IVIVCs). The results of scanning electron microscopy and N(2) adsorption demonstrated that empty PSNs possessed a spherical shape, a highly porous structure, a large specific surface area (385.89 ± 1.12 m(2)/g) and a small pore size (2.74 nm on average). The in vitro dissolution profiles of both 72 h-SLB and silybin-loaded PSNs in different concentrations (0.01, 0.06 and 0.08M) of Na(2)CO(3) solutions revealed that 0.06 M Na(2)CO(3) solution was the optimal medium in which silybin could be released from 72 h-SLB with first-order release kinetics and from PSNs with Higuchi kinetics. Furthermore, the IVIVCs of 72 h-SLB and silybin-loaded PSNs in beagle dogs were also established. Using 0.06 M Na(2)CO(3) solution as the in vitro dissolution medium, a good linear relationship could be achieved for both 72 h-SLB and silybin-loaded PSNs. The findings support the fact that the 72 h-SLB (consisting of solid dispersion, regular gel matrix and PSNs) together with Na(2)CO(3) solution as an in vitro dissolution medium can be developed into a promising formulation for poorly soluble drugs, which enjoys a good IVIVC.

背景与目标： ：这项研究的目的是使用固体分散体，凝胶基质和多孔二氧化硅纳米粒子（PSN）的组合制备水飞蓟宾（72 h-SLB）的72 h释放制剂，并研究体内/体外相关性（ IVIVC）。扫描电子显微镜和N（2）吸附的结果表明，空的PSN具有球形，高度多孔的结构，较大的比表面积（385.89±1.12 m（2）/ g）和较小的孔径（2.74 nm）一般）。 Nah（2）CO（3）解决方案中不同浓度（0.01、0.06和0.08M）的72 h-SLB和水飞蓟宾加载的PSNs的体外溶出曲线显示0.06 M Na（2）CO（3）解决方案是最佳的培养基，其中水飞蓟宾可以从72 h-SLB中以一级释放动力学释放，而从PSN中以Higuchi动力学释放。此外，还建立了比格犬中72 h-SLB和水飞蓟宾的PSN的IVIVC。使用0.06 M Na（2）CO（3）解决方案作为体外溶出介质，可以为72 h-SLB和水飞蓟宾加载的PSNs都实现良好的线性关系。这些发现支持以下事实：72 h-SLB（由固体分散体，规则的凝胶基质和PSN组成）与Na（2）CO（3）解决方案一起作为体外溶出介质，可以开发为溶解性较差的有前途的制剂药物，享有良好的IVIVC。

BACKGROUND & AIMS: :A novel type of N-acetyltransferase, clearly different from the nuclear and cytosolic polyamine N-acetyltransferases of mammals, was recently found in the intestinal nematode Ascaris suum. The occurrence of this putrescine N-acetylating enzyme has also been noted in the filarial parasite Onchocerca volvulus. The enzyme was partially purified from adults of O. volvulus and A. suum by chromatography on DEAE-cellulose and cadaverine-Sepharose. Substrate specificities of the filarial enzyme resemble those of the N-acetyltransferase from A. suum, with respect to its preference for putrescine and other diamines above polyamines and histones. Additionally, both nematode enzymes acetylated histamine, whereas dopamine and serotonin were not accepted as substrates. The activities of the N-acetyltransferase from O. volvulus and A. suum were potently inhibited by the drug berenil; the type of inhibition was competitive with respect to putrescine. The inhibition constants for berenil were determined as 4.2 and 1.2 microM for the enzymes of O. volvulus and A. suum, the Km values for putrescine were found to be 330 microM and 250 microM, respectively. Putrescine N-acetyltransferase is discussed as a regulatory step in the degradation of excessive polyamines via polyamine oxidase to putrescine. At this branching point, putrescine is retained in the cell for de novo synthesis of spermidine and spermine, catabolized via diamine oxidase or acetylated to a suitable transport product for excretion.

背景与目标： ：最近在肠道线虫A虫中发现了一种新型的N-乙酰基转移酶，其明显不同于哺乳动物的核和胞质多胺N-乙酰基转移酶。还已经在丝状寄生虫Onchocerca volvulus中发现了这种腐胺N-乙酰化酶的存在。通过在DEAE-纤维素和尸胺-Sepharose上进行色谱分离，从食蟹曲霉和成虫曲霉的成虫中部分纯化该酶。就其对腐胺和其他多胺（高于多胺和组蛋白）的偏爱而言，丝状酶的底物特异性类似于来自A. suum的N-乙酰基转移酶。另外，两种线虫酶均使组胺乙酰化，而多巴胺和5-羟色胺不被接受为底物。苯丙胺类药物有效地抑制了来自贪食弧菌和su。suum的N-乙酰基转移酶的活性。抑制类型相对于腐胺具有竞争性。测定肠旋螺旋杆菌和猪链霉菌的酶的苯胺的抑制常数为4.2和1.2μM，发现腐胺的Km值分别为330μM和250μM。讨论了腐胺N-乙酰基转移酶，作为通过聚胺氧化酶将过量的聚胺降解为腐胺的调控步骤。在该分支点，腐胺保留在细胞中，用于从头合成亚精胺和亚精胺，通过二胺氧化酶分解代谢或乙酰化为合适的转运产物以排泄。

BACKGROUND & AIMS: :To date, several studies have demonstrated that phospholipase C-coupled receptors stimulate the production of endocannabinoids, particularly 2-arachidonoylglycerol. There is now evidence that endocannabinoids are involved in phospholipase C-coupled serotonin 5-HT(2A) receptor-mediated behavioral effects in both rats and mice. The main objective of this study was to determine whether activation of the 5-HT(2A) receptor leads to the production and release of the endocannabinoid 2-arachidonoylglycerol. NIH3T3 cells stably expressing the rat 5-HT(2A) receptor were first incubated with [(3)H]-arachidonic acid for 24 h. Following stimulation with 10 mum serotonin, lipids were extracted from the assay medium, separated by thin layer chromatography, and analyzed by liquid scintillation counting. Our results indicate that 5-HT(2A) receptor activation stimulates the formation and release of 2-arachidonoylglycerol. The 5-HT(2A) receptor-dependent release of 2-arachidonoylglycerol was partially dependent on phosphatidylinositol-specific phospholipase C activation. Diacylglycerol produced downstream of 5-HT(2A) receptor-mediated phospholipase D or phosphatidylcholine-specific phospholipase C activation did not appear to contribute to 2-arachidonoylglycerol formation in NIH3T3-5HT(2A) cells. In conclusion, our results support a functional model where neuromodulatory neurotransmitters such as serotonin may act as regulators of endocannabinoid tone at excitatory synapses through the activation of phospholipase C-coupled G-protein coupled receptors.

背景与目标： 迄今为止，数项研究表明磷脂酶C偶联受体刺激内源性大麻素，特别是2-花生四烯酸甘油酯的产生。现在有证据表明，内源性大麻素与磷脂酶C偶联的5-羟色胺5-HT（2A）受体介导的大鼠和小鼠行为影响有关。这项研究的主要目的是确定5-HT（2A）受体的激活是否导致内源性大麻素2-花生四烯酸甘油酯的产生和释放。首先将稳定表达大鼠5-HT（2A）受体的NIH3T3细胞与[（3）H]-花生四烯酸孵育24小时。用10毫升血清素刺激后，从测定培养基中提取脂质，通过薄层色谱分离，并通过液体闪烁计数进行分析。我们的结果表明5-HT（2A）受体激活刺激2-花生四烯酸甘油酯的形成和释放。 5-花生四烯酸甘油酯的5-HT（2A）受体依赖性释放部分取决于磷脂酰肌醇特异性磷脂酶C的活化。在5-HT（2A）受体介导的磷脂酶D或磷脂酰胆碱特定的磷脂酶C激活的下游产生的二酰基甘油似乎没有促进NIH3T3-5HT（2A）细胞中2-花生四烯酰基甘油的形成。总之，我们的研究结果支持了一种功能模型，其中神经调节性神经递质（如5-羟色胺）可能通过磷脂酶C偶联的G蛋白偶联受体的激活在兴奋性突触中充当内源性大麻素的调节剂。

BACKGROUND & AIMS: Using a melt-pressing technique, we produced a small solid cylinder containing cisplatin (CDDP) embedded in poly-d, l-lactic acid (CDDP-PLA). The in vitro release of CDDP from the polymer was examined in an immersion system. CDDP was released continuously for more than four weeks with no initial burst. Drug distribution for CDDP-PLA was compared with CDDP solution (CDDP-SOL) by subcutaneous administration into the back of rats. In the CDDP-PLA group, a high concentration of CDDP was maintained in the subcutaneous tissues near the implants for 20 days. However, in the CDDP-SOL group, the concentration of CDDP was low by 10 days after drug administration. CDDP-PLA may become a useful tool in locoregional chemotherapy as a solid type of drug delivery system with longlasting release.

背景与目标： 使用熔融压制技术，我们生产了一个小的固态圆柱体，其中含有嵌入聚-d-L-乳酸（CDDP-PLA）中的顺铂（CDDP）。在浸没系统中检查了CDDP从聚合物中的体外释放。 CDDP连续释放了四个多星期，没有最初的爆发。通过向大鼠背部皮下给药，将CDDP-PLA的药物分布与CDDP溶液（CDDP-SOL）进行比较。在CDDP-PLA组中，在植入物附近的皮下组织中维持高浓度的CDDP达20天。但是，在CDDP-SOL组中，给药后10天CDDP的浓度低。 CDDP-PLA作为局部释放持久释放的固体药物传递系统，可能成为局部化疗的有用工具。

BACKGROUND & AIMS: Extended-spectrum beta-lactamases (ESBLs) are found in numerous Enterobacteriaceae, mainly in Klebsiella pneumoniae. We investigated the pharmacodynamics of two new extended-spectrum cephalosporins, cefepime and cefpirome, alone and combined with either amikacin or gentamicin or ciprofloxacin by means of time-kill curves against ESBL-producing, aminoglycoside-resistant K. pneumoniae. When used alone, cefepime (8 and 16 mg/l) resulted in a 2 and 3 log decrease at 6 h, respectively, but at 24 h regrowth occurred. The combination of cefepime (8 mg/l) with amikacin (4 mg/l) resulted in a 4 log decrease at 6 h, but there were no surviving bacteria at 6 h when combined with amikacin (8 mg/l). The combination of cefepime (16 mg/l) with gentamicin (4 mg/l) resulted in a 4 log decrease in 24 h. The antimicrobial combination of cefepime (32 mg/l) with ciprofloxacin (2 mg/l) resulted in a 4 log decrease in 24 h. Cefpirome (8 mg/l) induced a 2 log decrease at 4 h; 32 mg/l cefpirome resulted in a 3 log decrease followed by regrowth at 24 h. The regrowth observed in the late phase with cefpirome alone disappeared when combined with aminoglycoside. When cefpirome (32 mg/l) was used in combination with ciprofloxacin (1 mg/l), it resulted in a 4 log decrease in 24 h.

背景与目标： 在许多肠杆菌科中发现了广谱β-内酰胺酶（ESBLs），主要存在于肺炎克雷伯菌中。我们研究了两种新的广谱头孢菌素（头孢吡肟和头孢吡肟）的药效学，它们分别通过抗ESBL产生，对氨基糖苷类耐药的肺炎克雷伯菌的时间杀灭曲线与阿米卡星或庆大霉素或环丙沙星合用。单独使用时，头孢吡肟（8和16 mg / l）分别在6 h减少2和3 log，但在24 h发生再生长。头孢吡肟（8 mg / l）与丁胺卡那霉素（4 mg / l）的组合在6 h时降低了4 log，但与丁胺卡那霉素（8 mg / l）组合时在6 h没有存活细菌。头孢吡肟（16毫克/升）与庆大霉素（4毫克/升）的组合在24小时内降低了4 log。头孢吡肟（32 mg / l）与环丙沙星（2 mg / l）的抗菌组合导致24小时内下降4 log。头孢哌酮（8 mg / l）在4 h导致2 log下降； 32 mg / l头孢哌酮导致3 log下降，然后在24 h再生长。与氨基糖苷类药物合用时，仅在头孢哌酮的晚期观察到的再生长消失了。当头孢哌酮（32 mg / l）与环丙沙星（1 mg / l）组合使用时，导致24小时内减少4 log。

BACKGROUND & AIMS: :The mechanism underlying dopamine D1 receptor-mediated attenuation of glutamatergic synaptic input to nucleus accumbens (NAcc) neurons was investigated in slices of rat forebrain, using whole-cell patch-clamp recording. The depression by dopamine of EPSCs evoked by single-shock cortical stimulation was stimulus-dependent. Synaptic activation of NMDA-type glutamate receptors was critical for this effect, because dopamine-induced EPSC depressions were blocked by the competitive NMDA receptor antagonist D/L-2-amino-5-phosphonopentanoate (AP5). Application of NMDA also depressed the EPSC, and both this effect and the dopamine depressions were blocked by the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), implicating adenosine release in the EPSC depression. A1 receptor agonists also depressed EPSCs by a presynaptic action, causing increased paired-pulse facilitation, but this was insensitive to AP5. Activation of D1 receptors enhanced both postsynaptic inward currents evoked by NMDA application and the isolated NMDA receptor-mediated component of synaptic transmission. The biochemical processes underlying the dopamine-induced EPSC depression did not involve either protein kinase A or the production of cAMP and its metabolites, because this effect was resistant to the protein kinase inhibitors H89 and H7 and the cAMP-specific phosphodiesterase inhibitor rolipram. We conclude that activation of postsynaptic D1 receptors enhances the synaptic activation of NMDA receptors in nucleus accumbens neurons, thereby promoting a transsynaptic feedback inhibition of glutamatergic synaptic transmission via release of adenosine. Unusually for D1 receptors, this phenomenon occurs independently of adenylyl cyclase stimulation. This process may contribute to the locomotor stimulant action of dopaminergic agents in the NAcc.

背景与目标： ：使用全细胞膜片钳记录技术，在大鼠前脑切片中研究了多巴胺D1受体介导的伏谷核（NAcc）神经元的谷氨酸能突触输入衰减的机制。单电刺激皮层刺激引起的EPSCs的多巴胺抑制与刺激有关。 NMDA型谷氨酸受体的突触激活对此效应至关重要，因为多巴胺诱导的EPSC抑制被竞争性NMDA受体拮抗剂D / L-2-氨基-5-膦基戊酸酯（AP5）阻止。 NMDA的应用也抑制了EPSC，这种作用和多巴胺抑制均被A1受体拮抗剂8-环戊基-1,3-二丙基黄嘌呤（DPCPX）阻断，这暗示了EPSC抑制中腺苷的释放。 A1受体激动剂也通过突触前作用抑制EPSC，导致成对脉冲促进作用增强，但这对AP5不敏感。 D1受体的激活增强了由NMDA引起的突触后内向电流和分离的NMDA受体介导的突触传递成分。多巴胺引起的EPSC抑郁症的生化过程既不涉及蛋白激酶A，也不涉及cAMP及其代谢产物的产生，因为这种作用对蛋白激酶抑制剂H89和H7以及cAMP特异性磷酸二酯酶抑制剂咯利普兰具有抵抗力。我们得出的结论是，突触后D1受体的激活增强伏隔核神经元中NMDA受体的突触激活，从而通过释放腺苷促进谷氨酸能突触传递的突触反馈抑制。对于D1受体，这种现象通常与腺苷酸环化酶的刺激无关地发生。该过程可能有助于NAcc中多巴胺能药物的运动刺激作用。

BACKGROUND & AIMS: :The minimal cardiopulmonary bypass (mini-CPB) circuit, a closed system with neither cardiotomy suction nor an open venous reservoir and thus no air-blood interface, reportedly reduces blood loss and inflammatory reactions associated with coronary bypass surgery. We evaluated the inflammatory reactions in patients in whom coronary bypass operations were performed with conventional CPB or mini-CPB (n=15 each). Interleukin (IL)-6, IL-8, and neutrophil elastase levels; the neutrophil count; and the C-reactive protein value were measured before and immediately after surgery and on postoperative days 1 and 2. In addition, intraoperative blood loss and the transfusion volume were evaluated in these groups. Neutrophil elastase levels were lower in the mini-CPB group than in the conventional group on postoperative days 1 (127 +/- 52 vs. 240 +/- 100 microg/l, P=0.013) and 2 (107 +/- 17 vs. 170 +/- 45 micro/l, P=0.0001), as was the IL-8 level on postoperative day 1 (8.3 +/- 6.4 vs. 19 +/- 11 pg/ml, P=0.016). The intraoperative blood loss and transfusion volumes were significantly lower in the mini-CPB group than in the conventional group (510 +/- 244 vs. 1046 +/- 966 ml, P=0.012, and 691 +/- 427 vs. 1416 +/- 918 ml, P=0.0033). Thus, mini-CPB appears to attenuate neutrophil activation and cytokine release after coronary bypass surgery and, in addition, has some beneficial effects on blood conservation.

背景与目标： ：据报道，最小的体外循环（mini-CPB）回路是一个既没有心脏切开术也没有开放的静脉储液器的封闭系统，因此没有气血界面，据报道可减少失血和与冠状动脉搭桥手术相关的炎症反应。我们评估了使用常规CPB或mini-CPB（每组n = 15）进行冠状动脉搭桥手术的患者的炎症反应。白介素（IL）-6，IL-8和中性粒细胞弹性蛋白酶水平；中性粒细胞计数；在术前和术后以及术后第1和2天测量C和C反应蛋白值。此外，评估这些组的术中失血量和输血量。术后1天（127 /-52 vs. 240 /-100 microg / l，P = 0.013）和2（107 /-17 vs. 170 / -45 micro / l，P = 0.0001），术后第1天的IL-8水平也是如此（8.3 /-6.4 vs. 19 /-11 pg / ml，P = 0.016）。 mini-CPB组的术中失血量和输血量显着低于常规组（510 /-244 vs. 1046 /-966 ml，P = 0.012和691 /-427 vs. 1416 /-918 ml ，P ＝ 0.0033）。因此，mini-CPB似乎减弱了冠状动脉搭桥手术后中性粒细胞的活化和细胞因子的释放，此外，对血液保存也有一些有益的作用。

BACKGROUND & AIMS: :Cefpodoxime proxetil is a third generation cephalosporin antibiotic demonstrates pH dependent solubility and is highly soluble only in acidic pH. The purpose of this investigation was to design and develop immediate release tablets of cefpodoxime proxetil by direct compression method and determine the effect of different solid buffers (organic acids) such as fumaric acid (formulations F1-F4), maleic acid (formulations M1-M4) and citric acid (formulations C1-C4) by using cefpodoxime and acid in the ratios of 4:1, 2:1, 1:1 and 1:2 to achieve pH-independent release of the drug. Physical parameters and assay were found to be within the acceptable range as prescribed in USP 36 / NF 31. In vitro dissolution studies of each formulation were performed in distilled water, USP dissolution medium, HCl buffer solution of pH 1.2, phosphate buffer solutions of pH 4.5 and 6.8 to observe the drug release. The formulations F3, F4, M4 were selected for film coating on the basis of better drug release profile, to protect the drug from chemical degradation through hydrolysis. Film coated formulation F3, F4 and M4 showed a remarkable in vitro release of the drug (72.88±0.43 to 92.67±0.71%) within 30min of observation in all dissolution media and further evaluated by model independent and model dependent approaches. The drug release was found to be best fit to Weibull model as highest r2adjusted (0.924-0.998) and lowest AIC (18.416-54.710) values were obtained in all dissolution media. R Gui® applied for stability studies of F3 and F4 formulations, showing shelf lives of 28 & 27months at ambient and 33 months at accelerated temperatures. Formulation F4 was chosen as best formulation on the basis of physical properties, highest dissolution rate and stability studies.

背景与目标： ：头孢泊肟酯是第三代头孢菌素抗生素，显示出pH依赖性溶解度，仅在酸性pH值下高度可溶。这项研究的目的是通过直接压缩方法设计和开发头孢泊肟肟酯的速释片，并确定不同的固体缓冲剂（有机酸）如富马酸（配方F1-F4），马来酸（配方M1-M4）的作用。 ）和柠檬酸（配方C1-C4），使用头孢泊肟和酸的比例为4：1、2：1、1：1和1：2，以实现不依赖pH值的药物释放。发现物理参数和测定均在USP 36 / NF 31规定的可接受范围内。每种制剂的体外溶出度研究是在蒸馏水，USP溶出介质，pH 1.2的HCl缓冲溶液，pH 1.2的磷酸盐缓冲溶液中进行的。 4.5和6.8观察药物释放情况。基于更好的药物释放曲线，选择制剂F3，F4，M4进行薄膜包衣，以保护药物免受水解的化学降解。薄膜包衣的制剂F3，F4和M4在观察到的30分钟内在所有溶出介质中均显示出显着的药物体外释放（72.88±0.43至92.67±0.71％），并通过模型独立和模型依赖的方法进行了进一步评估。发现在所有溶出介质中均获得了最高的r2调整值（0.924-0.998）和最低的AIC值（18.416-54.710），从而使药物释放最适合于Weibull模型。 RGui®应用于F3和F4配方的稳定性研究，在环境温度下的货架期为28和27个月，在加速温度下的货架期为33个月。根据物理性能，最高的溶出速率和稳定性研究，选择配方F4作为最佳配方。

BACKGROUND & AIMS: :Closing the gap between adverse health effects of aluminum and its mechanisms of action still represents a huge challenge. Cholinergic dysfunction has been implicated in neuronal injury induced by aluminum. Previously reported data also indicate that in vivo and in vitro exposure to aluminum inhibits the mammalian (Na(+)/K(+))ATPase, an ubiquitous plasma membrane pump. This study was undertaken with the specific aim of determining whether in vitro exposure to AlCl(3) and ouabain, the foremost utilized selective inhibitor of (Na(+)/K(+))ATPase, induce similar functional modifications of cholinergic presynaptic nerve terminals, by comparing their effects on choline uptake, acetylcholine release and (Na(+)/K(+))ATPase activity, on subcellular fractions enriched in synaptic nerve endings isolated from rat brain, cuttlefish optic lobe and torpedo electric organ. Results obtained show that choline uptake by rat synaptosomes was inhibited by submillimolar AlCl(3), whereas the amount of choline taken up by synaptosomes isolated from cuttlefish and torpedo remained unchanged. Conversely, choline uptake was reduced by ouabain to a large extent in all synaptosomal preparations analyzed. In contrast to ouabain, which modified the K(+) depolarization evoked release of acetylcholine by rat, cuttlefish and torpedo synaptosomal fractions, AlCl(3) induced reduction of stimulated acetylcholine release was only observed when rat synaptosomes were challenged. Finally, it was observed that the aluminum effect on cuttlefish and torpedo synaptosomal (Na(+)/K(+))ATPase activity was slight when compared to its inhibitory action on mammalian (Na(+)/K(+))ATPase. In conclusion, inhibition of (Na(+)/K(+))ATPase by AlCl(3) and ouabain jeopardized the high-affinity (Na(+)-dependent, hemicholinium-3 sensitive) uptake of choline and the Ca(2+)-dependent, K(+) depolarization evoked release of acetylcholine by rat, cuttlefish and torpedo synaptosomal fractions. The effects of submillimolar AlCl(3) on choline uptake and acetylcholine release only resembled those of ouabain when rat synaptosomes were assayed. Therefore, important differences were found between the species regarding the cholinotoxic action of aluminum. The variability of (Na(+)/K(+))ATPase sensitivity to aluminum of cholinergic neurons might contribute to their differential susceptibility to this neurotoxic agent.

背景与目标： ：缩小铝的不良健康影响与其作用机制之间的差距仍然是巨大的挑战。胆碱能功能障碍与铝诱导的神经元损伤有关。先前报道的数据还表明，体内和体外暴露于铝会抑制普遍存在的质膜泵哺乳动物（Na（）/ K（））ATPase。进行这项研究的特定目的是确定体外暴露于AlCl（3）和ouabain（最主要利用的（Na（）/ K（））ATPase的选择性抑制剂）是否诱导胆碱能突触前神经末梢的类似功能修饰。比较它们对胆碱摄取，乙酰胆碱释放和（Na（）/ K（））ATPase活性的影响，对富集自大鼠脑，墨鱼视神经叶和鱼雷电器官的突触神经末梢富集的亚细胞级分。获得的结果表明，大鼠毫微摩尔的AlCl（3）抑制了大鼠突触小体对胆碱的摄取，而从墨鱼和鱼雷分离的突触小体对胆碱的吸收量却保持不变。相反，在所有分析的突触体制剂中，哇巴因在很大程度上降低了胆碱的摄取。相比于哇巴因，它修饰了大鼠，乌贼和鱼雷突触小体部分的K（）去极化引起乙酰胆碱的释放，仅当挑战大鼠突触体时才观察到AlCl（3）诱导的乙酰胆碱释放减少。最后，观察到铝对墨鱼和鱼雷突触体（Na（）/ K（））ATPase活性的抑制作用与其对哺乳动物（Na（）/ K（））ATPase的抑制作用相比是轻微的。总之，AlCl（3）和哇巴因对（Na（）/ K（））ATPase的抑制作用损害了胆碱和Ca（2）依赖的高亲和性（Na（依赖），hemicholinium-3敏感）的摄取。 ，K（）去极化引起大鼠，墨鱼和鱼雷突触体级分释放乙酰胆碱。当测定大鼠突触小体时，亚毫摩尔AlCl（3）对胆碱摄取和乙酰胆碱释放的影响仅类似于哇巴因。因此，在物种之间发现了关于铝的胆碱毒性作用的重要差异。 （Na（）/ K（））ATPase对胆碱能神经元铝的敏感性的变异性可能有助于它们对这种神经毒性剂的敏感性不同。

BACKGROUND & AIMS: BACKGROUND:Conservative treatment for plantar fasciitis usually provides improvement, but some patients progress to surgery. Open release is most commonly performed but is associated with prolonged recovery and complications. Endoscopic plantar fascia release (EPFR) has become popular recently. We present our results. METHODS:Twenty patients (23 feet) had EPFR. Sixteen patients (19 feet) were available for followup after at least 1 year. Ten were women and 6 were men, with an average age of 44.7 (range 28 to 70) years. The average followup was 47 months. The American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale and Maryland Foot Score were used for evaluation. Gender, obesity, severity, length of preoperative symptoms, and workers compensation (WC) status were studied. RESULTS:The average AOFAS and Maryland scores improved postoperatively (66 to 88, p<0.05; 62 to 83, p<0.05, respectively). Women improved 25 (AOFAS) and 23 points (Maryland) points. Men improved 16 (AOFAS) and 17 points (Maryland) points. Obese patients improved 38 and 28 points, respectively. Normal weight patients improved 16 and 19 points, respectively. Postoperative scores for patients with high preoperative severity improved from 58 to 81 (AOFAS) and from 52 to 73 (Maryland). Patients with moderate preoperative severity achieved scores from 72 to 93 and from 70 to 91. Patients who had symptoms longer than 2 years before EPFR had lower postoperative scores. Non-WC patients improved 25 (AOFAS) and 24 (Maryland) points. WC patients improved 18 and 16 points, respectively. CONCLUSIONS:EPFR provides significantly improved patient outcomes. Patients with more severe symptoms before EPFR and those with symptoms for longer than 2 years had worse results. Obesity had no negative effect on outcome. WC patients had inferior results compared to non-WC patients. Women achieved better results than men. This finding may be biased because most WC patients were men.

背景与目标： 背景：足底筋膜炎的保守治疗通常可以改善病情，但有些患者可以接受手术治疗。公开释放最常执行，但与恢复时间延长和并发症相关。内窥镜足底筋膜释放术（EPFR）最近变得很流行。我们介绍我们的结果。
方法：20名患者（23英尺）患有EPFR。至少1年后可对16例患者（19英尺）进行随访。女性10名，男性6名，平均年龄为44.7岁（28至70岁）。平均随访47个月。使用美国骨科足踝协会（AOFAS）的踝部-足部评分表和马里兰州的足部评分进行评估。研究者对性别，肥胖，严重程度，术前症状持续时间和工人补偿（WC）状况进行了研究。
结果：术后AOFAS和马里兰州的平均评分有所改善（分别为66至88，p <0.05； 62至83，p <0.05）。妇女提高了25分（AOFAS）和23分（马里兰）。男子提高16（AOFAS）和17点（马里兰）。肥胖患者分别改善了38点和28点。体重正常的患者分别改善了16点和19点。术前严重程度高的患者的术后评分从58分（81）（AOFAS）和52分（73）（马里兰州）提高。术前轻度中度的患者得分分别为72分至93分和70分至70分。症状出现时间超过EPFR前2年的患者术后得分较低。非WC患者提高了25（AOFAS）和24（Maryland）点。 WC患者分别改善了18点和16点。
结论：EPFR可显着改善患者预后。 EPFR前症状较重的患者和症状超过2年的患者的病情较差。肥胖对结局没有负面影响。与非WC患者相比，WC患者的结果较差。妇女取得了比男子更好的结果。由于大多数WC患者是男性，因此该发现可能有偏见。

BACKGROUND & AIMS: :Extended-spectrum β-lactamase (ESBL)-producing-Enterobacteriaceae strains were detected in 12% (6 out of 50) of fecal samples collected from the inpatients of a Japanese pediatric hospital. All the ESBLs belonged to the CTX-M-1 group. The proportion of carriage of ESBL producers was higher among patients who had received antibiotics within the past 3 months and among those who had cardiologic diseases.

背景与目标： ：从日本儿科医院住院患者收集的粪便样本中，有12％（50个中有6个）检测到产生超广谱β-内酰胺酶（ESBL）的肠杆菌科菌株。所有ESBL都属于CTX-M-1组。在过去3个月内接受过抗生素治疗的患者和患有心脏病的患者中，携带ESBL生产者的比例更高。