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  • 1
    Electronic Resource
    Electronic Resource
    Inhibition of Noxious Stimulus-Induced Spinal Prostaglandin E2 Release by Flurbiprofen Enantiomers (2000)
    Oxford UK : Blackwell Science Ltd.
    Journal of neurochemistry 74 (2000), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Peripheral noxious stimuli have been shown to induce prostaglandin (PG) E2 release at the site of inflammation and in the spinal cord. The antiinflammatory and antinociceptive effects of cyclooxygenase-inhibiting drugs are thought to depend on the inhibition of PG synthesis. R-Flurbiprofen, however, does not inhibit cyclooxygenase activity in vitro but still produces antinociceptive effects. To find out whether R-flurbiprofen acts via inhibition of spinal PG release, concentrations of PGE2 and flurbiprofen in spinal cord tissue were assessed by microdialysis. The catheter was transversally implanted through the dorsal horns of the spinal cord at level L4. R- and S-flurbiprofen (9 and 27 mg kg-1, respectively) were administered intravenously 10-15 min before subcutaneous injection of formalin into the dorsal surface of one hindpaw. Flurbiprofen was rapidly distributed into the spinal cord with maximal concentrations after 30-45 min. Baseline PGE2 dialysate concentrations were 100.6 ± 6.4 pg ml-1 (mean ± SEM). After formalin injection they rose about threefold with a maximum of 299.4 ± 68.4 pg ml-1 at 7.5 min. After ∼ 1 h PGE2 levels returned to baseline. Both flurbiprofen enantiomers completely prevented the formalin-induced increase of spinal PGE2 release and reduced PGE2 concentrations below basal levels. S- and R-flurbiprofen at 9 mg kg-1 produced a minimum of 15.8 ± 5.2 and 27.7 ± 14.9 pg ml-1, respectively, and 27 mg kg-1S- and R-flurbiprofen resulted in 11.7 ± 1.7 and 9.3 ± 4.7 pg ml-1, respectively. PGE2 levels remained at the minimum up to the end of the observation period at 5 h. When 27 mg kg-1R-flurbiprofen was injected intravenously without subsequent formalin challenge, baseline immunoreactive PGE2 concentrations were not affected. S-Flurbiprofen (27 mg kg-1), however, led to a moderate reduction (∼40%). The data suggest that antinociception produced by R-flurbiprofen is mediated at least in part by inhibition of stimulated spinal PGE2 release and support the current view that increased spinal PGE2 release significantly contributes to nociceptive processing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2000.0742094.x
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  • 2
    Electronic Resource
    Electronic Resource
    Normal sensitivity to acute pain, but increased inflammatory hyperalgesia in mice lacking the nociceptin precursor polypeptide or the nociceptin receptor (2003)
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 17 (2003), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Nociceptin/orphanin FQ (N/OFQ) is the endogenous agonist of the N/OFQ peptide receptor (NOP receptor). It is released from a larger precursor polypeptide, called prepro-nociceptin (ppN/OFQ) from which, in addition to N/OFQ, other biologically active neuropeptides may be derived. Increasing evidence indicates that exogenous application of N/OFQ to the central nervous system of mice and rats induces pro- and antinociceptive effects depending on the dose and site of administration. Much less is known about a potential contribution of endogenous N/OFQ to pain control. Here, we have used a genetic approach to address this topic. Mice deficient in either the NOP receptor (NOP-R−/− mice) or the N/OFQ precursor polypeptide (ppN/OFQ−/− mice) or both (double knockout mice) were compared with wild-type littermates in animal models of acute and tonic pain. Nociceptive responses to acute noxious heat of all three types of mutant mice were indistinguishable from those of wild-type mice. Accordingly, nociceptive behaviour was very similar in the early phase of the formalin test. However, NOP-R−/−, ppN/OFQ−/− and double knockout mice showed markedly stronger nociceptive responses during prolonged nociceptive stimulation in the second phase of the formalin test and significantly lower thermal pain thresholds in inflamed tissue after zymosan A injection. These results indicate that N/OFQ contributes significantly to endogenous pain control during prolonged nociceptive stimulation but does not affect acute pain sensitivity. Among the three types of mutant mice nociceptive behaviour was nearly identical, indicating that the lack of other potential ppN/OFQ products in the ppN/OFQ−/− mice was apparently without effect on the nociceptive phenotype.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.2003.02676.x
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  • 3
    Electronic Resource
    Electronic Resource
    Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts (2006)
    [s.l.] : Nature Publishing Group
    Nature medicine 12 (2006), S. 452-458 
    Details
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The concept of regenerating diseased myocardium by implantation of tissue-engineered heart muscle is intriguing, but convincing evidence is lacking that heart tissues can be generated at a size and with contractile properties that would lend considerable support to failing hearts. Here we created ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nm1394
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  • 4
    Electronic Resource
    Electronic Resource
    Opioid activity and distribution of fentanyl metabolites (1986)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 334 (1986), S. 267-274 
    Details
    ISSN: 1432-1912
    Keywords: Anesthetics ; Biodistribution ; Fentanyl ; Fentanyl rebound ; Fentanyl metabolites ; Neuroleptanalgesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fentanyl, a short-term analgesic frequently used in neuroleptanalgesia, has in a number of cases been reported to cause unexpected, severe postanesthetic respiratory depression which can successfully be treated with naloxone. Several explanations for this rebound effect produced by fentanyl (in combination with other drugs) have been proposed, though so far none has proved completely satisfactory. The possibility that this effect may be due to a secondary accumulation of fentanyl or fentanyl metabolites with opioid activity in the brain has led us to investigate the relative opioid potency of several known or proposed metabolites by measuring their inhibitory action on the contraction of guinea-pig ileum in comparison with that of morphine, pethidine, and fentanyl itself. Two proposed metabolites containing the phenethyl sidechain were found to possess an opioid activity lying between that of morphine and pethidine, whereas metabolites without the side-chain were generally less active than pethidine. Using thin-layer chromatography, it was possible to detect one of these proposed active metabolites in vivo in rats. This result may have some relevance for the understanding of the fentanyl rebound. However, the possibility that multiple doses of fentanyl, such as may be given during neuroleptanalgesia, or interactions with other drugs, e.g. tranquilizers and general anesthetics, may be the cause of fentanyl robound, remains open.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00508781
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  • 5
    Electronic Resource
    Electronic Resource
    Hühnergranulozyten: Ein Modell für die antimikrobielle Funktion peroxidasefreier menschlicher Granulozyten (1973)
    Springer
    Annals of hematology 26 (1973), S. 110-126 
    Details
    ISSN: 1432-0584
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Human subjects exhibiting the anomaly described byAlius andGrignaschi lack myeloperoxidase in their neutrophil polymorphonuclear leukocytes (PMN). Chicken heterophile granulocytes naturally lack myeloperoxidase as well. Therefore they must be incapable for killing ingested microorganisms by aid of H2O2, an oxidizable cofactor and myeloperoxidase, a mechanism proposed for human PMN. To get closer insight into alternative bactericidal mechanisms we chose chicken PMN as a model. We checked the antimicrobial potencies of these cells in vitro, isolated their different classes of granules, determined their enzyme content and localized an antimicrobial mechanism within these granules. The following results could be established: 1. Vital chicken PMN are not inferior to human PMN in respect to their antimicrobial potencies against four strains of microorganisms. 2. An antibacterial mechanism was located in the large granules of chicken heterophile PMN. 3. Evidently this antibacterial mechanism consists of five or more basic proteins. One of these is lysozyme. Up to now the other proteins could not be shown to be enzymes. These results prove that there exists an alternative antimicrobial mechanism within PMN. Basic proteins appear to be of central importance for this mechanism. Our results might shed some light upon the controversial observations concerning the antimicrobial potencies of patients exhibiting the anomaly ofAlius andGrignaschi.
    Notes: Zusammenfassung Granulozyten von Hühnern besitzen natürlicherweise keine Myeloperoxidase. Sie gleichen darin den bei derAlius-Grignaschi-Anomalie gefundenen menschlichen Granulozyten. Sie können daher phagozytierte Mikroorganismen nicht mit Hilfe von Myeloperoxidase und einem oxidierbaren Kofaktor zerstören, wie es für normale menschliche Granulozyten postuliert wird. Um Einblicke in alternative antimikrobielle Mechanismen von Granulozyten zu erhalten, untersuchten wir die antimikrobiellen Potenzen intakter Hühnergranulozyten in vitro, isolierten ihre Granula, bestimmten den Enzymgehalt dieser Granula und lokalisierten einen antimikrobiellen Mechanismus in diesen Granula. Es zeigte sich: 1. Intakte Hühnergranulozyten sind wie menschliche Granulozyten in vitro in der Lage, vier verschiedene Stämme von Mikroorganismen zu phagozytieren und abzutöten. 2. Ein antimikrobieller Mechanismus von Hühnergranulozyten konnte in den großen Granula lokalisiert werden. 3. Dieser antimikrobielle Mechanismus besteht wahrscheinlich aus 5 basischen Proteinen. Eines dieser basischen Proteine ist Lysozym. Die anderen konnten bisher nicht als Enzyme definiert werden. Die erhobenen Befunde zeigen, daß neben dem obengenannten antimikrobiellen Mechanismus von Granulozyten alternative Mechanismen bestehen. Bei diesen Alternativmechanismen spielen basische Proteine eine zentrale Rolle. In wieweit diese Befunde zum Verständnis der widersprüchlichen klinischen Beobachtungen an Patienten mit granulozytären Anomalien beitragen können, wird diskutiert.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01635760
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  • 6
    Electronic Resource
    Electronic Resource
    Homöopathikum ist Diclofenac ebenbürtig?! (2000)
    Springer
    Der Orthopäde 29 (2000), S. 271-272 
    Details
    ISSN: 1433-0431
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Nachdem vor einiger Zeit behauptet wurde, das “Homöopatikum” Zeel® comp. (i.a.) sei der Hyaluronsäure (i.a.) ebenbürtig und daher therapeutisch wirksam [2], wird nunmehr in verschiedenen Zeitschriften über wirkungsbeweisende Untersuchungen mit dem “Homöopathikum” Zeel® comp. (p.o.) berichtet. Zum Beweis wird aus einer randomisierten, verblindeten (?) Untersuchung zitiert. In dieser Studie wird Diclofenac (25 mg, dreimal täglich, p.o.) mit Zeel® comp. (p.o.) [3] verglichen. Obwohl die Originaldaten bisher nicht vorliegen, muss vor einer erheblichen Irreführung von Ärzten, Apothekern und Laien gewarnt werden. Es ist erstaunlich, dass in sogenannten wissenschaftlichen Zeitschriften bereits vor Vorliegen einer endgültigen Publikation Begeisterungsstürme ausbrechen [3], obwohl aufgrund der vorliegenden Daten größte Zweifel an der Validität und Dignität dieser Studie geltend gemacht werden müssen. Gleiches gilt übrigens für die Vergleichsstudie mit Hyaluronsäure. Um nur einige zu nennen:
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001320050445
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  • 7
    Electronic Resource
    Electronic Resource
    Correlation between Antimicrobial Activity and Peroxidase Content of Leukocytes (1973)
    [s.l.] : Nature Publishing Group
    Nature 245 (1973), S. 209-210 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Fig. 1 Blood smears stained for peroxidase (black in photograph) by the method of Graham-Knoll, a, PMN filled with MPO-positive granules from a normal human; b, PMN of pig showing only few MPO-positive granules; c, PMN of chicken completely lacking MPO. We have developed a simple and ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/245209a0
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  • 8
    Electronic Resource
    Electronic Resource
    Workshop session summary: Prostaglandins: immunoregulatorsin vivo? (1984)
    Springer
    Inflammation research 15 (1984), S. 66-66 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01966971
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  • 9
    Electronic Resource
    Electronic Resource
    Pharmacological control of leukotriene and prostaglandin production from mouse peritoneal macrophages (1984)
    Springer
    Inflammation research 14 (1984), S. 729-734 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Leukotriene and prostaglandin production by mouse peritoneal macrophages was investigated. It could be shown that the tumour promoter 12-O-tetradecanoylphorbol-13-acetate initiated the release of prostaglandin E2 but had little effect on the release of leukotriene C4-like immunoreactivity. The divalent cation ionophore A 23187 at concentrations between 10−6 and 10−8 mol/l initiated prostaglandin as well as leukotriene release. This prostaglandin and leukotriene release could be modulated by drugs. Non-steroidal anti-inflammatory drugs including benoxaprofen inhibited prostaglandin release but simultaneously enhanced leukotriene production. The analgesics paracetamol and 4-methylaminoantipyrine had similar effects at high concentrations. The experimental compound BW 755 c inhibited prostaglandin and leukotriene production while the antithrombotic compound nafazatrom inhibited the production of leukotriene C4-like immunoreactivity but enhanced prostaglandin E2 production. Nordihydroguaiaretic acid inhibited prostaglandin and leukotriene production. The results show that the metabolism of arachidonic acid in macrophages via the cyclooxygenase or the lipoxygenase pathway is dependent on the stimulus applied. Both pathways can be inhibited conjointly or selectively by drugs. Our results do not provide evidence that differences in anti-inflammatory activity claimed for some of the drugs tested can be explained by differential inhibition of either pathway. The experimental system described may be used for assessing the potency of drugs to inhibit the lipoxygenase and the cyclooxygenase pathway of arachidonic acid metabolism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01978916
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  • 10
    Electronic Resource
    Electronic Resource
    The avian microcrystal arthritis I. Simultaneous recording of nociception and temperature effect in the inflamed joint (1974)
    Springer
    Inflammation research 4 (1974), S. 21-26 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An acute inflammation was elicited in pigeons by the injection of a suspension of urate crystals (UC) into the intertarsal joint. Two parameters of the resulting inflammation were recorded simultaneously: (1) the standing behaviour, reflecting nociception, (2) the temperature in the inflamed joint as compared to the control. The time-course of both parameters was recorded and the influence of volume and UC concentration of the suspension was established. Thus, appropriate conditions for the use of this experimental model for pharmacological experiments could be defined.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01965488
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