Die analyse von aluminium im serum und urin zur überwachung emonierter personen

Zusammenfassung Die Einführnung der flammenlosen Atomabsorptionsspektrometrie in die chemische Analytik ermöglicht eine einfache quantitative Bestimmung des Aluminiums im biologischen Material. Die verwendeten Analysen-methoden und deren Zuverlässigkeitskriterien wurden beschrieben. Entsprechend der heute üblichen Verfahren zur Überwachung schwermetallexponierter Personen wurden von uns bei verschiedenen Kollektiven Aluminiumbestimmungen im Blut und Urin durchgeführt. Untersucht wurde ein Kollektiv von 110 Arbeitern eines Korund-herstellenden und -verarbeitenden Werkes. 82 dieser Arbeiter waren durch staubförmigen Korund exponiert, während 28 Personen an den Öfen zusätzlich noch Metalldämpfen ausgesetzt waxen. Die Expositionsdauer betrug im Mittel 6,9 Jahre. Als Vergleichskollektiv dienten 40 männliche nicht aluminiumexponierte Probanden. Zusädtzlich wurden 33 Dialyse-Patienten, die mit Aluminiumhydroxid (Aludrox) therapiert wurden, in die Studie einbezogen.Für die Aluminiumausscheidung im Urin errechnete sich bei den Normalpersonen eine obere Normgrenze von 30 g/l. Die Ausscheidungswerte der aluminiumexponierten Personen lagen mit einem Median von 39 g Al/l signifikant höher als das Normalkollektiv. Erwartungsgemä zeigten die dampfförmig belasteten Personen einen statistisch signifikant höheren Al-Spiegel im Urin als die staubförmig belastete Gruppe.Die Serumanalysen ergaben keine Hinweise für einen signifikanten Unterschied gegenüber Normalpersonen. Aus den Untersuchungen der Seren von nicht aluminiumexponierten Probanden errechnete sich ein oberer Grenzwert von 35 g/l. Der Serum-Aluminium-Spiegel der exponierten Personen war von der Art und Dauer der Exposition nicht beeinflut. Dagegen lagen die Aluminium-Spiegel im Serum der Dialyse-Patienten im Bereich von 6 – 254 g/l. Bei dieser Patientengruppe mit erhöhten Serum-Aluminiumwerten wurden keine klinischen Zeichen einer manifesten Toxicität gefunden. Damit kommt den Aluminiumkonzentrationen im biologischen Material der aluminiumexponierten Arbeiter keine gesundheitsgefahrdende Relevanz zu.Bei der inhalativen Aufnahme von Aluminium scheint die Menge des resorbierten und in die Blutbahn übergehenden Aluminiums gering zu sein. Hinweise für eine Akkumulation des Metalls im Organismus wurde bei Versuchen mit D-Penicillamin nicht gefunden.Aluminiumbestimmungen im Serum oder Harn sind für die Überwachung von Korund-herstellenden und -verarbeitenden Personen nach diesen Ergebnissen nicht notwendig. Bei Substanzen, wie dem Aluminium, mit geringer Resorptions-quote und groer Toleranzbreite für den menschlichen Organismus sowie ohne manifeste signifikante Gesundheitsschäden erscheint ein Biological Monitoring nicht indiziert.D 29     

Scorpion alpha and alpha-like toxins differentially interact with sodium channels in mammalian CNS and periphery

Scorpion alpha-toxins from Leiurus quinquestriatus hebraeus, LqhII and LqhIII, are similarly toxic to mice when administered by a subcutaneous route, but in mouse brain LqhII is 25-fold more toxic. Examination of the two toxins effects in central nervous system (CNS), peripheral preparations and expressed sodium channels revealed the basis for their differential toxicity. In rat brain synaptosomes, LqhII binds with high affinity, whereas LqhIII competes only at high concentration for LqhII-binding sites in a voltage-dependent manner. LqhII strongly inhibits sodium current inactivation of brain rBII subtype expressed in HEK293 cells, whereas LqhIII is weakly active at 2 microM, suggesting that LqhIII affects sodium channel subtypes other than rBII in the brain. In the periphery, both toxins inhibit tetrodotoxin-sensitive sodium current inactivation in dorsal root ganglion neurons, and are strongly active directly on the muscle and on expressed muI channels. Only LqhII, however, induced repetitive end-plate potentials in mouse phrenic nerve-hemidiaphragm muscle preparation by direct effect on the motor nerve. Thus, rBII and sodium channel subtypes expressed in peripheral nervous system (PNS) serve as the main targets for LqhII but are mostly not sensitive to LqhIII. Toxicity of both toxins in periphery may be attributed to the direct effect on muscle. Our data elucidate, for the first time, how different toxins affect mammalian central and peripheral excitable cells, and reveal unexpected subtype specificity of toxins that interact with receptor site 3.     

Specific activation of the mu opioid receptor (MOR) by endomorphin 1 and endomorphin 2

The recently discovered endomorphin 1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin 2 (Tyr-Pro-Phe-Phe-NH2) were investigated with respect to their direct receptor-binding properties, and to their ability to activate G proteins and to inhibit adenylyl cyclase in both cellular and animal models. Both tetrapeptides activated G proteins and inhibited adenylyl cyclase activity in membrane preparations from cells stably expressing the mu opioid receptor, an effect reversed by the mu receptor antagonist CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2), but they had no influence on cells stably expressing the delta opioid receptor. To further establish the selectivity of these peptides for the mu opioid receptor, brain preparations of mice lacking the mu opioid receptor gene were used to study their binding and signalling properties. Endomorphin 2, tritiated by a dehalotritiation method resulting in a specific radioactivity of 1.98 TBq/mmol (53.4 Ci/mmol), labelled the brain membranes of wild-type mice with a Kd value of 1.77 nM and a Bmax of 63.33 fmol/mg protein. In membranes of mice lacking the mu receptor gene, no binding was observed, and both endomorphins failed to stimulate [35S]guanosine-5'-O-(3-thio)triphosphate ([35S]GTPgammaS) binding and to inhibit adenylyl cyclase. These data show that endomorphins are capable of activating G proteins and inhibiting adenylyl cyclase activity, and all these effects are mediated by the mu opioid receptors.     

Mapping of c-fos gene expression in the brain during morphine dependence and precipitated withdrawal, and phenotypic identification of the striatal neurons involved

The c-fos gene is expressed in the central nervous system in response to various neuronal stimuli. Using in situ hybridization, we examined the effects of chronic morphine treatment and withdrawal on c-fos mRNA in the rat brain, and particularly within identified striatal neurons. Morphine dependence was induced by subcutaneous implantation of two pellets of morphine for 6 days and withdrawal was precipitated by administration of naltrexone. Placebo animals and morphine-dependent rats showed a very weak c-fos mRNA expression in all the structures studied. Our study emphasized the spatial variations in c-fos mRNA expression, and also revealed a peak expression of c-fos mRNA at 1 h after naltrexone-precipitated withdrawal in the projection areas of dopaminergic neurons, noradrenergic neurons and in several regions expressing opiate receptors. Interestingly, morphine withdrawal induces c-fos mRNA expression in the two efferent populations of the striatum (i.e. striatonigral and striatopallidal neurons) both in the caudate putamen and nucleus accumbens. Moreover, the proportions of activated neurons during morphine withdrawal are different in the caudate putamen (mostly in striatopallidal neurons) and in the shell and core parts of the nucleus accumbens (mostly in striatonigral neurons). The activation of striatopallidal neurons suggests a predominant dopaminergic regulation on c-fos gene expression in the striatum during withdrawal. On the contrary, c-fos induction in striatonigral neurons during withdrawal seems to involve a more complex regulation like opioid-dopamine interactions via the mu opioid receptor and the D1 dopamine receptor coexpressed on this neuronal population or the implication of other neurotransmitter systems.     

Norepinephrine regulation of growth hormone release from goldfish pituitary cells. II. Intracellular sites of action

Previous results suggest that norepinephrine decreases growth hormone (GH) release in goldfish by means of alpha-2 adrenoceptor activation. The intracellular mechanisms by which norepinephrine inhibits GH release were examined in the present study using dispersed goldfish pituitary cells. In 2-h static incubation experiments, norepinephrine and the alpha-2 agonist clonidine decreased basal GH release and the GH responses to stimulation by the dopamine D1 agonist SKF38393 and two native gonadotropin-releasing hormones (GnRH). Norepinephrine also reduced GH responses to the adenylate cyclase activator forskolin, two protein kinase C (PKC) activators (phorbol ester and synthetic diacylglycerol), and two Ca2+ ionophores (ionomycin and A23187). Similarly, norepinephrine applied as a 1-h pulse in cell column perifusion experiments reduced basal GH release and abolished the GH response to a 5-min pulse of arachidonic acid. In goldfish, D1-stimulated GH release is mediated by AC-, arachidonic acid-and Ca2+-dependent pathways, whereas GnRH action is coupled to PKC-and Ca2+-dependent mechanisms. These results suggest that norepinephrine activation of alpha-2 receptors inhibits ligand-induced GH secretion by actions subsequent to activation of these second messenger cascades. To further characterize norepinephrine mechanisms of action on unstimulated hormone release, the ability of norepinephrine and an alpha-2 agonist to affect activation of two second messenger cascades under basal conditions was also investigated. Static incubation with clonidine reduced cAMP production in a time-and dose-dependent manner, suggesting that norepinephrine inhibitory action can also be expressed at the level of cAMP production. Resting intracellular free calcium levels in single, identified goldfish somatotropes was unaffected by norepinephrine. However, the inhibitory effects of norepinephrine on basal GH secretion was not observed in the presence of a voltage-sensitive Ca2+ channel agonist. Whether these channels are targets for norepinephrine action on unstimulated GH release requires further investigation.     

血清化学的研究现状与展望

阐述了有关血清化学的由来，国内外研究状况及其前景展望。长期以来，中药的体外试验不能准确的反应药物的体内活性，体内的药物成分性质与体外试验对照存在诸多不一致现象。忽视中药特点的体外实验方法不能完成药物体内的作用成分的有效检测，经过国内外专家不懈的努力，一种全新可行的方法——血清化学逐渐被认可，尽管值得探讨和操作的问题还很多，但它已展现了在中药研究试验运用中的光明前景。若紧密配合中药化学、血清药理学、药代动力学、免疫学、分子生物学及微生物学的研究，其必将为加速中药现代化进程，可望在中药质控、药物作用靶位、开发新药和中药现代化方面做出独特贡献。     

γ-闪烁扫描法确定替硝唑结肠释放片人体内释药部位的研究

 目的确定替硝唑结肠释放片在人体内释药部位。方法以氧化钐为标记物，利用γ-闪烁扫描技术对替硝唑结肠释放片在人体内的释药部位进行跟踪监测。结果替硝唑结肠释放片在2名志愿者胃肠道内的崩解部位均为升结肠,药片崩解时间为7～8 h。结论替硝唑结肠释放片在人体胃肠道内具有结肠定位释药效果,达到了预期的设计目的。     

肱骨外髁的生物力学实验研究及其临床应用

目的 :从生物力学角度探讨肱骨外髁骨折的发生机制和固定方法。方法 :通过电测实验法、三维光弹实验法 ,空间有限元分析法 ,研究肱骨外髁在各种体位下的受力情况和复位固定方法 ,三种实验方法互为验证 ,并应用于临床。结果 :66例肱骨外髁翻转骨折病人 ,经治疗优良率达 90 .9%。结论 :肱骨外髁骨折好发于肘关节半屈曲位跌倒 ,和肘关节伸直内翻位跌倒。骨折复位后固定在屈肘 60°～ 90°前臂旋后位最为稳定。本实验结论具有推广应用价值。