大孔吸附树脂法分离7—氨基头孢烷酸和头孢菌素C的条件探索

在静态吸附条件下，测定了５种大孔吸附树脂在３种ｐＨ缓冲液中对７－氨基头孢烷酸（７－ＡＣＡ）和头孢菌素Ｃ（ＣＰＣ）的吸附量，筛选出对７－ＡＣＡ和ＣＰＣ吸附差异较大的ＨＰ２０，进一步测定其在动态吸附条件下对７－ＡＣＡ和ＣＰＣ吸附的泄漏曲线、吸附等温线及最大吸附量，以探索在动态吸附条件下吸附树脂对７－ＡＣＡ和ＣＰＣ混合物的吸附及解吸最佳条件，７－ＡＣＡ及ＣＰＣ的纯度及回收率均达到９０％以上。     

利用固定在不同载体上的双酶系统一步转化头孢菌素C成为7-氨墓头孢烯酸

利用Ｄ－氨基酸氧化酶（ＤＡＯ）和戊二酰－７－氨基头孢烯酸（ＧＬ－７－ＡＣＡ）脱酰酶酶促转化头孢菌素 Ｃ（ＣＰＣ）为７－氨基头孢烯酸（７－ＡＣＡ）时，为了最大限度提高催化活性和稳定性，将这两种酶分别固定在不同载体上。反应是同时利用这两种酶以类似一步方式进行。ＤＡＯ制剂中的过氧化氢酶杂质的影响可通过外加过氧化氢解决。在最适条件下，ＣＰＣ转化为７－ＡＣＡ的转化率高于９０％，副产物形成率低于４％。这种固定化酶混合物可反复循环使用，具有显著的操作稳定性。     

利用固定在不同载体上的双酶系统一步转化头孢菌素C成为7—氨？…

利用Ｄ－氨基酸氧化酶（ＤＡＯ）和戊二酰－７－氨基头孢烯酸（ＧＬ－７－ＡＣＡ）脱酰酶酶促转化头孢菌素Ｃ（ＣＰＣ）为７－氨基头孢烯酸（７－ＡＣＡ）时,为了最大限度提高催化活性和稳定性,将这两种酶分别固定在不同载体上。反应是同时利用这两种酶以类似一步方式进行。ＤＡＯ制剂中的过氧化氢酶杂质的影响可通过外加过氧化氢解决。在最适条件下,ＣＰＣ转化为７－ＡＣＡ的转化率高于９０％,副产物形成率低于４％。这种固定化     

单克隆抗体与多克隆抗体荧光偏振免疫分析法测定环孢素A…

本文用单克隆抗荧光偏振免疫分析法（ＭＡｂ－ＦＰＬＡ）与多克隆ＦＰＬＡ法（ＰＣ－ＦＰＩＡ）测定肾移植病环孢素（ＣｓＡ）的全血浓度并进行了比较。４９例肾移植术后病人口服不同剂量ＣｓＡ期间，共监测ＣｓＡ全血谷浓度６５例次。结果表明：表ＭＡｂ－ＦＰＩＡ法观察浓度４０～６００ｎｇ／ｍｌ的范围内，ＰＣ－ＦＰＩＡ法的测定结果为１１０～１７００ｎｇ／ｍｌ，是ＭＡｂ－ＦＰＩＡ法的１．７～３．９倍。两种方法之间有良好     

大孔吸附树脂提取泰乐星的研究

用几种典型的大孔吸附树脂对发酵过渡液中泰乐星吸附,筛选出Ｈ－３型树脂为吸附剂。静态实验表明,Ｈ－３型大孔吸附树脂对泰乐星吸附量达１５５。．９ｍｇ／ｇ干树脂,最佳吸附ＰＨ在７．５～８．０,吸附剂投入放量７％～８％（ｗ／Ｖ）,吸附时间６为最适宜吸附条件。其吸附等温线服从Ｆｒｅｕｎｄｌｉｃｈ吸曙式。以甲醇－柠檬酸缓冲液体系做洗脱剂,解吸率达８４．６％。选出以Ｄ２９０大孔碱性树脂为脱色剂。动态实验确定吸附     

7-ACA的质量对头孢噻肟钠(HR-756)色泽影响的探讨

用紫外分光光度法测定７－氨基头孢烷酸（７－ＡＣＡ）的质量，并探讨了７－ＡＣＡ的紫外吸收系数对头孢噻肟钠（ＨＲ－７５６）成品色泽的影响，结果证明７－ＡＣＡ紫外吸收系数的变化对ＨＲ－７５６成品色泽有较大的影响。通过对７－ＡＣＡ强化处理，解决了ＨＲ－７５６成品色泽问题。     

冷凝集试验和聚合酶链式反应在支原体肺炎检测中的应用

对５１例临床疑似支原体肺炎的住院患儿分别采用冷凝集试验（ｃｏｌｄａｇｇｌｕｔｉｎａｔｉｏｎｔｅｓｔＣＡ）和聚合酶链式反应（ＰｏｌｙｍｅｒａｓｅＣｈａｉｎＲｅａｃｔｉｏｎＰＣＲ）进行检测，，并对检测结果与入院时的病程之间的关系加以探讨。１６例确诊为支原体肺炎，其中２例病程小于１周，ＰＣＲ（＋）、ＣＡ（－），复查后ＣＡ（＋）；１２例病程在１周～４周，ＰＣＲ（＋）、ＣＡ（＋）或ＰＣＲ（＋）、ＣＡ（－）；２例病程大于４周，ＰＣＲ（－）、ＣＡ（＋）。表明两种实验结果与病程密切相关，两者联合应用有利于支原体肺炎诊断水平的提高。     

垂体腺苷酸环化酶激活肽诱导PC12细胞突起生长的作用

目的　研究垂体腺苷酸环化酶激活肽（ＰＡＣＡＰ） ３８与ＰＡＣＡＰ２７ 在ＰＣ１２ 细胞突起生长中的作用，并探讨介导其作用的受体和细胞内第二信使机制。方法　采用ＰＣ１２细胞分散培养法，观察接种７２ ｈ 时ＰＣ１２ 细胞突起生长阳性细胞的百分比。结果　当ＰＡＣＡＰ３８ 和ＰＡＣＡＰ２７ 的浓度为１ ×１０－ ７ ～１ ×１０－ １１ ｍｏｌ·Ｌ－１ 之间时，均能诱导ＰＣ１２细胞突起生长，其中以１×１０ －９ ｍｏｌ·Ｌ－ １ 的浓度作用最明显，量效曲线呈“钟”形。ＰＡＣＡＰ Ⅰ型受体拮抗剂ＰＡＣＡＰ６～３８和ｃＡＭＰ依赖的蛋白激酶抑制剂ＲｐｃＡＭＰＳ 能显著地抑制ＰＡＣＡＰ诱导ＰＣ１２ 细胞突起生长的作用，而蛋白激酶Ｃ 抑制剂Ｈ７ 却没有这个作用。结论　ＰＡＣＡＰ３８ 和ＰＡＣＡＰ２７均能诱导ＰＣ１２ 细胞突起生长，该作用是由ＰＡＣＡＰ Ⅰ型受体介导的，是通过细胞内ｃＡＭＰ 依赖的蛋白激酶系统实现的     

冷凝集试验和聚合酶链式反应在支原体肺炎检测中的应用

对５１例临床疑似支原体肺炎的住院患儿分别采用冷凝集试验（ｃｏｌｄａｇｇｌｕｔｉｎａｔｉｏｎｔｅｓｔＣＡ）和聚合酶链式反应（Ｐｏｌｙｍｅｒａｓｅ－Ｃｈａｉｎ－ＲｅａｃｔｉｏｎＰＣＲ）进行检测，并对检测结果与入院时的病程之间的关系加以探讨，１６例确诊为支原体肺炎，其中２例病程小于１周，ＰＣＲ（＋），ＣＡ（－）复查后ＣＡ（＋），１２例病程在１周～４周，ＰＣＲ（＋），ＣＡ（＋）或ＰＣＲ（＋），ＣＡ（－）；     

细胞色素P4501A1基因mRNA的化学诱导及在人肝中的基础表达

利用Ｎｏｒｔｈｅｒｎ印迹杂交及逆转录聚合酶链式反应（ＲＴ－ＰＣＲ）技术研究了几种传代培养细胞和成人肝组织及人胚胎肝组织细胞色素Ｐ４５０１Ａ１（１Ａ１）基础表达水平并观察了几种化学诱导剂对人羊膜细胞ＦＬ系和原代胚肝细胞该基因ｍＲＮＡ水平的诱导．结果显示：３－甲基胆蒽，苯巴比妥，β－萘黄酮在不同程度上能高诱导ＦＬ细胞１Ａ１ｍＲＮＡ表达．ＲＴ－ＰＣＲ结果显示ＣＨＬ细胞及Ｖ７９细胞存在基础表达，但Ｎｏｒｔｈｅｒｎ杂交结果提示其表达量极低．成人肝脏中１Ａ１亦存在极低的表达水平，而人胚胎肝脏不能用高灵敏度的ＲＴ－ＰＣＲ检测到痕迹表达，提示胚胎发育时期１Ａ１基因处于完全关闭状态．     

实例（7）

某作者于 1996年 4月～ 2 0 0 0年 6月采用中西医结合治疗方法 ,对痛风性关节炎进行疗效观察。作者在骨伤科门诊共收集到痛风性关节炎 82例 ,随机分为两组。中西医结合组 (治疗组 )5 0例 ,其中男性 35例 ,女性 15例 ;年龄 4 2～ 6 7岁 ;病程 2天～17年 ,平均 4 .4年。中医诊断 :湿热蕴结型 18例 ,瘀热阻滞型 9例 ,痰浊阻滞型 11例 ,肝肾阴虚型 12例。西药组 (对照组 ) 32例 ,其中男性 2 3例 ,女性 9例 ;年龄 4 1～ 6 9岁 ,平均 5 1.5岁 ;病程 3天～ 15年 ,平均 4 .2年。中医诊断 :湿热蕴结型 10例 ,瘀热组滞型 8例 ,痰浊阻滞型 4例 ,肝肾阴…     

Serotonin(7) receptors (5-HT(7)Rs) and their ligands

Serotonin (5-HT) is involved in various physiological and pathological processes by interaction with 14 distinct receptor subtypes, grouped in seven classes of receptors (5-HT(1-7)) on the basis of amino acid sequence, pharmacology, and signal transduction pathways. The 5-HT(7)R is a G-protein coupled receptor with seven transmembrane domains. It was found by the application of molecular cloning and has been identified in rat, mouse, human, pig, and guinea pig. Although the biological functions of the 5-HT(7)Rs are poorly understood, preliminary evidence suggests that it may be involved in depression, control of circadian rhythms, and relaxation of vascular smooth muscles. For these reasons, the 5-HT(7)R has become a target for the development of novel drugs. This review will give a brief introduction of the pharmacology of 5-HT(7)R (molecular structure, distribution of 5-HT(7)R mRNA, localization of the 5-HT(7)R protein, functional correlates, and therapeutic potential) and a detailed survey of the 5-HT(7)R ligands, which have appeared in the literature in both papers and patents. Structure-activity relationships (SAR) of these ligands will also be described.     

X-RAY STUDY ON HOMO-OLIGOPEPTIDES t-BOC-(d-Ala)7-OMe AND HCI·H(d-Ala)7-OMe

Observations of extended peptide chains, whose direction is perpendicular to the fiber axis (cross-β-structures) have hitherto been confined to fibrous proteins and to some synthetic polydisperse polypeptides of rather low molecular weight. This structure has now been found in some monodisperse linear homooligopeptides with aliphatic hydrocarbon side chains. X-ray diffraction photographs of t-Boc-(d -Ala)₇-OMe and HCl·H(d -Ala)₇-OMe show characteristic reflections for this form. In addition, the good orientation of suitably prepared specimens has enabled a fairly complete determination of the unit cell of the heptapeptides to be made. t-Boc-(d -Ala)₇-OMe and HCl·H(d -Ala)₇-OMe molecules are packed in a monoclinic lattice with a = 4.80, b = 34.5, c = 5.82 Å, β = 65.6° and a = 4.80, b = 29.5, c = 5.82 Å, β = 65.6°, respectively. It has not been possible to establish whether the arrangement of the chains within the sheets is parallel or antiparallel.     

NS-7 (Nippon Shinyaku)

Nippon Shinyaku is developing NS-7, a sodium and calcium channel blocker, as a neuroprotectant for use following cerebral infarction [249336]. It entered phase I trials for the treatment of acute stage cerebrovascular disorders in 1997 [271963]. As of November 1999, Nippon Shinyaku was preparing to start phase II studies in Japan [347972]. In November 1999, Nippon Shinyaku granted Schering exclusive developing and marketing rights to NS-7. Schering will conduct clinical trials in Europe and the US [347972].     

(7) The risk society

In previous articles in this series, we have discussed classical and modern sociological theories. This article addresses risk: a field of sociological research that is the subject of current debate. One commentator has described it as “one of the most lively areas of theoretical debate in social and cultural theory in recent times”.¹     

Neural KCNQ (Kv7) channels

KCNQ genes encode five Kv7 K⁺ channel subunits (Kv7.1–Kv7.5). Four of these (Kv7.2–Kv7.5) are expressed in the nervous system. Kv7.2 and Kv7.3 are the principal molecular components of the slow voltage-gated M-channel, which widely regulates neuronal excitability, although other subunits may contribute to M-like currents in some locations. M-channels are closed by receptors coupled to Gq such as M1 and M3 muscarinic receptors; this increases neuronal excitability and underlies some forms of cholinergic excitation. Muscarinic closure results from activation of phospholipase C and consequent hydrolysis and depletion of membrane phosphatidylinositol-4,5-bisphosphate, which is required for channel opening. Some effects of M-channel closure, determined from transmitter action, selective blocking drugs (linopirdine and XE991) and KCNQ2 gene disruption or manipulation, are as follows: (i) in sympathetic neurons: facilitation of repetitive discharges and conversion from phasic to tonic firing; (ii) in sensory nociceptive systems: facilitation of A-delta peripheral sensory fibre responses to noxious heat; and (iii) in hippocampal pyramidal neurons: facilitation of repetitive discharges, enhanced after-depolarization and burst-firing, and induction of spontaneous firing through a reduction of action potential threshold at the axon initial segment. Several drugs including flupirtine and retigabine enhance neural Kv7/M-channel activity, principally through a hyperpolarizing shift in their voltage gating. In consequence they reduce neural excitability and can inhibit nociceptive stimulation and transmission. Flupirtine is in use as a central analgesic; retigabine is under clinical trial as a broad-spectrum anticonvulsant and is an effective analgesic in animal models of chronic inflammatory and neuropathic pain.     

Avertin-(Tribrommethanol-) Vergiftungen. (7 Fälle)

Ohne Zusammenfassung     

Inhibition of acetylcholine muscarinic M(1) receptor function by the M(1)-selective ligand muscarinic toxin 7 (MT-7)

MT-7 (1 - 30 nM), a peptide toxin isolated from the venom of the green mamba Dendroaspis angusticeps and previously found to bind selectively to the muscarinic M(1) receptor, inhibited the acetylcholine (ACh)-stimulated [(35)S]-guanosine-5'-O-(3-thio)triphosphate ([(35)S]-GTPgammaS) binding to membranes of Chinese hamster ovary (CHO) cells stably expressing the cloned human muscarinic M(1) receptor subtype. MT-7 failed to affect the ACh-stimulated [(35)S]-GTPgammaS binding in membranes of CHO cells expressing either the M(2), M(3) or M(4) receptor subtype. In N1E-115 neuroblastoma cells endogenously expressing the M(1) and M(4) receptor subtypes, MT-7 (0.3 - 3.0 nM) inhibited the carbachol (CCh)-stimulated inositol phosphates accumulation, but failed to affect the CCh-induced inhibition of pituitary adenylate cyclase activating polypeptide (PACAP) 38-stimulated cyclic AMP accumulation. In both CHO/M(1) and N1E-115 cells the MT-7 inhibition consisted in a decrease of the maximal agonist effect with minimal changes in the agonist EC(50) value. In CHO/M(1) cell membranes, MT-7 (0.05 - 25 nM) reduced the specific binding of 0.05, 1.0 and 15 nM [(3)H]-N-methylscopolamine ([(3)H]-NMS) in a concentration-dependent manner, but failed to cause a complete displacement of the radioligand. Moreover, MT-7 (3 nM) decreased the dissociation rate of [(3)H]-NMS by about 5 fold. CHO/M(1) cell membranes preincubated with MT-7 (10 nM) and washed by centrifugation and resuspension did not recover control [(3)H]-NMS binding for at least 8 h at 30 degrees C. It is concluded that MT-7 acts as a selective noncompetitive antagonist of the muscarinic M(1) receptors by binding stably to an allosteric site.