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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 3 (1973), S. 20-23 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of single doses of colchicine on the acute arthritis elicited by the injection of microcrystalline sodium urate, calcium pyrophosphate or talcum into one intertarsal joint of chickens was functionally assessed. Colchicine was significantly active against the urate challenge. The arthritic inflammation induced by calcium pyrophosphate or talcum was reduced to a lesser degree. Colchicine may thus particularly affect inflammatory processes related to urate.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 43 (1994), S. 218-220 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A pharmacokinetic interpretation of the effects and side-effects of acidic non-steroid anti-inflammatory drugs is presented. It is based on the general principles of drug action and leads to the conclusion that aspirin-like drugs should specifically accumulate and exert pharmacological activity in inflammed tissue, stomach and kidney. Therefore the common effects and side-effects of these drugs may result from unspecific effects in these compartments and might not necessarily be due to specific, i.e., receptor mediated action(s).
    Type of Medium: Electronic Resource
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  • 3
    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 urate crystals (UC) into the intertarsal joint. From the resulting inflammation two parameters were recorded simultaneously: temperature-rise in the inflamed tissue and nociception, a correlate of pain. The effects of sodium salicylate, acetaminophen and colchicine on both parameters were investigated. All reduced nociception when administered at appropriate times and in suitable doses. However, only colchicine prevented temperature-rise in the inflamed area. After the injection of sodium salicylate an increase in temperature was also seen in non-inflamed control tissue. Acetaminophen did not produce this effect. From these results it is concluded that colchicine acts peripherally at the site of inflammation whilst acetaminophen acts primarily on nociception leaving local events at the site of inflammation unimpaired. For sodium salicylate a neripheral effect cannot be ruled out. The temperature effect of this drug appears to be of interest for the understanding of its antipyretic action.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 4 (1974), S. 95-100 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An attempt was made to find a suitable parameter for the cellular events taking place at the site of inflammation of the avian microcrystal arthritis. For that purpose, the arthritis elicited by injections of urate crystals (UC) in pigeons was adopted for chicken. In the larger animals it was possible to obtain sufficient joint fluid for histological and biochemical investigation. In order to find a parameter specific for the UC arthritis, the histological and biochemical findings were compared with the time-course of nociception and temperature-rise of the inflammed joints and with results from animals having received intra-articular injections of Latex particles (LP). It was found that UC-injections cause an inflammation in intertarsal joints of chicken. Nociception and temperaturerise as parameters of this inflammation show similar time-courses as described for pigeons [4]. LP-injections also caused moderate signs of inflammation. They appeared later and only in some animals. However, the time-course of appearance of polymorphonuclear leukocytes (PMN) and lysozyme in the joint fluid was the same in UC-and LP-treated animals. Only beta-glucuronidase-activity was found to reflect the other two parameters of inflammation. From the results it is concluded that the beta-glucuronidase activity in the joint fluids might be used as an enzymatic parameter of this inflammation. In addition, doubts are raised against the proposed mediator function of PMN.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 10 (1980), S. 491-492 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract On investigating the release of PGE2 from mouse peritoneal macrophages in tissue culture it was found that the spontaneous release of PGE2 was dependent on the culture conditions employed. The type of buffering of the medium was especially important. Using CO2-sodium bicarbonate buffers we observed little, if any, spontaneous release of prostaglandins (PGs) from macrophages, whereas in the presence ofN-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid (HEPES) buffer in some cases a dramatic increase in PG release was observed.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 26 (1973), S. 110-126 
    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
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  • 7
    ISSN: 1432-0738
    Keywords: Non-steroidal anti-inflammatory drugs ; Pharmacokinetics ; Biodistribution ; Absorption ; Gastric mucosal damage ; Proquazone ; BW755C ; MDL 035 ; Flufenamic acid ; Fenclofenac ; Salicyclic acid ; Diflunisal ; Azapropazone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Evidence has accumulated during the last decade to support the view that the pharmacokinetic behaviour of non-steroidal anti-inflammatory drugs (NSAIDs) contributes not only decisively to their therapeutic effects but also to the type and incidence of their side effects. It has been shown that NSAIDs reach particularly high concentrations in those compartments in which they cause effects and side effects. Specifically, the data reviewed herein indicate that the accumulation of NSAID within gastric mucosal cells a priori is a principal factor associated with the intervention of intracellular biochemical events and resultant gastric mucosal damage. To a large extent this behaviour is according to the precepts of classical absorption theory; in this respect the limitations of such theory are examined. Our survey further indicates that the failure of certain NSAIDs to significantly reduce gastric mucosal levels of prostaglandins (PG) in vivo may reflect pharmacokinetic differences between NSAIDs rather than tissuespecific differences in their potency as inhibitors of cyclooxygenase.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 64 (1990), S. 1-6 
    ISSN: 1432-0738
    Keywords: Non-steroidal anti-inflammatory drugs ; Pharmacokinetics ; Biodistribution ; Absorption ; Gastric mucosal damage ; Azapropazone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Since most non-steroidal anti-inflammatory drugs (NSAIDs) contain only one obvious ionisable group at physiological pH levels then they may be easily identified as having either acidic or basic character. Basic NSAIDs are simply non-acidic NSAIDs capable of accepting a proton within the physiological pH range. Within this range, however, a few NSAIDs contain two obvious ionisable groups, one acidic and the other basic. Such compounds should be described as amphiprotic, and include NSAIDs such as 4- and 5-amino substituted salicylic acids, niflumic acid, amfenac, WY 18251, and azapropazone. The aqueous ionisation equilibrium of such compounds is complex and is described by two macroscopic ionisation constants. Evidence has accumulated during the last decade to support the view that the pharmacokinetic behaviour of NSAIDs contributes not only decisively to their therapeutic effects but also to the type and incidence of their side-effects.A priori, using a physico-chemical argument, certain amphiprotic NSAIDs should be better tolerated by the gastric mucosa than the classical acidic compound. Of those NSAIDs commercially available in the United Kingdom azapropazone remains the only one for which amphiprotic behaviour has been described. Following our examination of available data for azapropazone we conclude that the use of amphiprotic compounds represents a logical approach towards solving the problem of NSAID-induced gastric mucosal damage.
    Type of Medium: Electronic Resource
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  • 9
    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
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  • 10
    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
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