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  • 1
    Electronic Resource
    Electronic Resource
    Pentyl-4-yn-valproic acid enhances both spatial and avoidance learning and attenuates age-related NCAM-mediated neuroplastic decline within the rat medial temporal lobe (2001)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 78 (2001), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 2-N-Pentyl-4-pentynoic acid [pentyl-4-yn-valproic acid (VPA)] is an analogue of valproic acid that induces neuritogenesis and increases neural cell adhesion molecule (NCAM) prevalence in cultured neural cells. As memory consolidation involves synapse growth, aided by cell adhesion molecule function, we determined whether or not pentyl-4-yn-VPA had cognition-enhancing properties. Pentyl-4-yn-VPA (16–85 mg/kg) significantly improved water maze learning and task retention when given prior to each training session. Acute administration of pentyl-4-yn-VPA also influenced memory consolidation processes as, when given at 3 h post-passive avoidance training, the amnesia induced by scopolamine given 6 h post-training was prevented in a dose-dependent manner. Chronic administration of pentyl-4-yn-VPA (16.8 or 50.4 mg/kg) also significantly reduced escape latencies in the water maze task, 24 h following the last drug administration. This improved spatial learning was accompanied by enhanced neuroplasticity as the expression of NCAM polysialylated neurons in the infragranular zone of the dentate gyrus and in layer II of the perirhinal and piriform cortex was increased significantly following chronic drug treatment. The cognition-enhancing qualities of pentyl-4-yn-VPA, combined with its ability to attenuate the age-related loss of the NCAM polysialylation state, suggest that it may effectively slow the onset of cognitive decline.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2001.00411.x
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  • 2
    Electronic Resource
    Electronic Resource
    Gas chromatography-mass spectrometry for probing the structure and mechanism of action of enzyme active sites. Role of Glu-270 in carboxypeptidase A (1975)
    s.l. : American Chemical Society
    Biochemistry 14 (1975), S. 5285-5294 
    Details
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/bi00695a009
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  • 3
    Electronic Resource
    Electronic Resource
    Intramedullary pilocytic astrocytomas — a clinical and morphological study after combined surgical and photon or neutron therapy (1989)
    Springer
    Neurosurgical review 12 (1989), S. 309-313 
    Details
    ISSN: 1437-2320
    Keywords: Astrocytoma ; autopsy findings ; complications ; intramedullary neoplasm ; long-term results ; neutron therapy ; pilocytic astrocytoma ; spinal tumors ; surgical tumor therapy ; vertebral column
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ten patients suffering from intramedullary pilocytic astrocytomas (WHO-classification: astrocytoma grade I) were investigated catamnesticly. Combined surgery and radiotherapy was performed. Seven patients received neutron irradiation postoperatively. In four cases the neurological symptoms were improved after follow-up periods ranging from 33 to 89 months. The three other patients died after 6 to 21 months. The autopsy findings of a 14 year old child are presented. Our results are compared with reports in the literature. In addition, long-term problems of the spinal column are discussed. It seems that the combined surgical and neutron therapy improves the prognosis of pencil gliomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01780847
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  • 4
    Electronic Resource
    Electronic Resource
    Neuropathological findings in lesions of the optic nerve of different etiologies (1988)
    Springer
    Neurosurgical review 11 (1988), S. 225-230 
    Details
    ISSN: 1437-2320
    Keywords: Demyelinating disease ; intracranial pressure ; optic nerve ; trauma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cases of optic nerve lesions of various origins are described. These were seen in a systematic study of 59 autopsy cases with underlying neurological or neurosurgical diseases. The characteristic morphological signs of direct and indirect as well as primary and secondary lesions are discussed. Circulatory complications in cases with increased intracranial pressure are stressed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01741413
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  • 5
    Electronic Resource
    Electronic Resource
    Operative treatment and prognosis of syringomyelia (1994)
    Springer
    Neurosurgical review 17 (1994), S. 37-41 
    Details
    ISSN: 1437-2320
    Keywords: Syringomyelia ; syringo-pleural shunt ; syringo-subarachnoid shunt
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Twenty-two patients suffering from syringomyelia were treated operatively. Different shunt procedures were performed. Most often syringo-subarachnoid shunt (seven cases) and syringopleural shunt (eight cases) were used. Operative findings and complications were discussed. Postoperative improvement was observed in five patients, twelve were stable-unchanged, four showed further deterioration and one died. Operative treatment should be performed before gross neurological deficit is established.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00309984
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  • 6
    Electronic Resource
    Electronic Resource
    Biological effects and metabolism of 9-cis-retinoic acid and its metabolite 9,13-di-cis-retinoic acid in HaCaT keratinocytes in vitro: comparison with all-trans-retinoic acid (2000)
    Springer
    Archives of dermatological research 292 (2000), S. 612-620 
    Details
    ISSN: 1432-069X
    Keywords: Keywords all-trans-Retinoic acid ; 9-cis-Retinoic acid ; 9 ; 13-di-cis-Retinoic acid ; HaCaT keratinocytes ; Intracellular metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 9-cis-Retinoic acid (9cRA), a geometric isomer of all-trans-retinoic acid (atRA), is an endogenous high-affinity ligand for retinoid X receptors and retinoic acid receptors activating them with high potency. 9,13-di-cis-Retinoic acid (9,13dcRA) has been described as a major plasma metabolite of 9cRA. In this study, the biological activity and the metabolism of 9cRA and 9,13dcRA were investigated and compared with those of atRA in a retinol-free culture system of HaCaT keratinocytes. 9cRA exhibited a slightly weaker activity overall than atRA in inhibiting cell proliferation, inducing cellular retinoic acid binding protein II (CRABP II) mRNA levels and upregulating cytokeratin 19 expression. 9,13dcRA regulated HaCaT keratinocyte activity only at the highest concentration tested (10–6 M). In cultures of HaCaT keratinocytes with atRA and 9cRA, rapid intracellular accumulation of atRA was observed within 2 h, and atRA levels were higher with atRA treatment than with 9cRA treatment. 9,13dcRA remained relatively stable in the medium with intracellular 9,13dcRA levels below the level of detection. Taken together, 9cRA seems to be slightly less potent than atRA in regulating the biological activity of HaCaT keratinocytes, while its metabolite 9,13dcRA is effectively inactive at biologically relevant concentrations. Our data suggest a prodrug/drug relationship between 9cRA and atRA in human keratinocytes. 9,13dcRA seems to be a weaker prodrug of atRA or an inactive metabolic derivative.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030000189
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  • 7
    Electronic Resource
    Electronic Resource
    Weak acids may act as teratogens by accumulating in the basic milieu of the early mammalian embryo (1986)
    [s.l.] : Nature Publishing Group
    Nature 323 (1986), S. 276-278 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The intracellular pH of 9-day-old GDI mouse embryos (vaginal plug = day 0) was determined by maternal intra-peritoneal (i.p.) injection of 100 jxCi kg"1 of 14C-dimethadione (5,5'-dimethyloxazolidine-2,4-dione, or DMO, the demethylated metabolite of trimethadione; specific activity SOmCimmor1) to ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/323276a0
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  • 8
    Electronic Resource
    Electronic Resource
    Placental transfer of thiamphenicol in the rat (1981)
    Springer
    Archives of toxicology 48 (1981), S. 1-9 
    Details
    ISSN: 1432-0738
    Keywords: Placental transfer ; Organogenesis ; Rat ; Embryotoxicity ; Toxicokinetics ; Thiamphenicol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Measurement of thiamphenicol transfer to the rat embryo during organogenesis was performed as one step of the determination of possible drug embryotoxicity in man. Extrapolation of data on animal embryotoxicity to man will only become possible when data on the toxicokinetic properties of the substance under investigation are available for both animal and man. 1) Thiamphenicol, given between day 11.5 and 14 of rat gestation, rapidly reached the embryo; 4–6 h after single i.v. or s.c. injection, embryonic and maternal thiamphenicol levels became equal and decreased from that time on at the same rate. 2) No evidence was found for development of a placental barrier with increasing placental function. The same dose applied at different developmental stages yielded the same embryonic drug concentrations. 3) Elimination via kidney (unchanged) or bile (glucuronide), may become rate-limiting for thiamphenicol excretion. Doses exceeding 50 mg/kg (i.v.) or approx. 100 mg/kg (s.c.) yielded thiamphenicol levels higher than those expected from linear dose-concentration relationships. 4) Drug concentrations (〉 3–5 μg/g wet weight) obtained with dosing regimens (〉 100 mg/kg/day) used for experimental induction of embryolethality in rats are equal to those necessary for inhibition of mitochondrial protein synthesis in vitro and to those necessary for treatment of bacterial infections in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00297070
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  • 9
    Electronic Resource
    Electronic Resource
    Pharmacokinetic aspects of drug effects in vitro: effects of serum protein binding on concentration and teratogenicity of valproic acid and 2-en-valproic acid in whole embryos in culture (1986)
    Springer
    Archives of toxicology 58 (1986), S. 239-242 
    Details
    ISSN: 1432-0738
    Keywords: Valproic acid ; Whole-embryo culture ; Teratogenicity ; Embryo drug concentrations ; Bovine serum culture medium ; Valproic acid metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pharmacokinetic studies were performed in connection with culture experiments. Using the technique of cultivating whole rat embryos of the early postimplantation stage, we measured the concentration of valproic acid (VPA) and 2-en-VPA in the culture medium (free and protein-bound form) and in embryonic tissue. The following results were obtained: 1. The concentrations of VPA and 2-en-VPA reached in the embryos were lower than corresponding total concentrations added to the culture medium, but exceeded the free concentrations in the medium. 2. The concentrations of 2-en-VPA found in the embryo were lower than the comparable VPA total levels because of the more extensive protein binding of 2-en-VPA in the culture serum. 3. The percentage of binding to serum proteins decreased with increasing total drug concentratrations in the medium; the concentration of the free drug in the medium increased overproportionally with increasing total drug concentrations. Therefore, the free drug concentrations in the medium were not proportional to the dose of the drug dissolved in the medium (for a drug bound to plasma proteins). 4. The concentrations of VPA and 2-en-VPA found in the embryos after incubation in vitro were not proportional to the drug concentrations dissolved in the medium. This result has to be taken into account when dose-response relationships are evaluated. 5. VPA concentrations of 40 μg/g wet weight and above in the embryos clearly induced abnormal development in about 30% of the embryos, while 2-en-VPA concentrations as high as 200 μg/g embryo (wet weight) were inactive. Thus, differences in the embryotoxic potencies — in vivo and in vitro — were not due to pharmacokinetic differences. 6. The results of these investigations show for the first time that pharmacokinetic studies are essential for the interpretation of in vitro experiments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00297113
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  • 10
    Electronic Resource
    Electronic Resource
    Effects of all-trans-retinoyl-β-d-glucuronide and all-trans-retinoic acid on chondrogenesis and retinoid metabolism in mouse limb bud mesenchymal cells in vitro (1997)
    Springer
    Archives of toxicology 71 (1997), S. 142-150 
    Details
    ISSN: 1432-0738
    Keywords: Key words Chondrogenesis ; Limb bud ; Retinoic acid ; Retinoyl glucuronide ; Retinol metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Retinoids, derivatives of vitamin A, are essential for many vertebrate functions. Furthermore, several drugs of this class of compounds are valuable in the treatment of certain forms of skin disorders and cancer. However, the therapeutic application of retinoids is limited by their teratogenic potency. The limbs are important sites of retinoid-induced malformations in rodents. Therefore, organoid cultures of limb bud mesenchymal cells have been established for screening of the teratogenic potency of retinoids. We have now applied this system to compare the effects of all-trans-retinoyl-β-d-glucuronide (all-trans-RAG) with those of all-trans-retinoic acid (all-trans-RA) on chondrogenesis, as assessed by the Alcian blue binding assay and by electron microscopic evaluation including quantitative morphometric analysis. First data of retinoid toxicokinetics in the culture media as well as retinoid concentrations in the cultured mesenchymal limb bud cells were established. While all-trans-RA inhibited chondrogenesis at 10−7 M by ca. 50%, tenfold higher concentrations of all-trans-RAG were necessary to obtain the same effect. This difference reflects the ratio of RA isomers which were found in the medium after incubation with either all-trans-RAG or all-trans-RA. A pulse experiment (10−5 M all-trans-RAG or all-trans-RA for the first 2 h of a 6-day incubation period) demonstrated inhibition of chondrogenesis with all-trans-RA, but not with all-trans-RAG. The data indicate that RAG inhibits chondrogenesis upon hydrolysis to RA. Surprisingly, the rather polar RAG isoforms were extensively accumulated in the limb bud mesenchymal cells when compared to the medium. Both all-trans-RAG and all-trans-RA also induced a large increase of retinyl ester concentrations in the chondrocytes compared to vehicle-treated cells. This finding further supports a recent suggestion that RA regulates retinol metabolism via feedback inhibition of retinol oxidation and stimulation of the esterification of retinol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050368
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