Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:BIOD00035 (CSF)
 30,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Superoxide dismutase (SOD) activity in CSF of patients was determined by electron spin resonance spectrometry using the spin trap method. Variation in SOD activity was found among patients. SOD activity in CSF of subjects increased with age and this was identified as Cu,Zn-SOD activity by electrophoresis. In addition, animal experiments showed that SOD activities were higher in mitochondrial and cytosol fractions of aged rats than in those of adult rats. This finding on aged rat brain validates the increase of SOD activity in aged human CSF.
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PMID:Increased superoxide dismutase activity in aged human cerebrospinal fluid and rat brain determined by electron spin resonance spectrometry using the spin trap method. 131 Jul 21

To evaluate the regulation of endothelial cell Cu,Zn-SOD, we have exposed bovine pulmonary artery endothelial cells in culture to hyperoxia and hypoxia, second messengers or related agonists, hormones, free radical generating systems, endotoxin, and cytokines and have measured Cu,Zn-SOD protein of these cells by an ELISA developed in our laboratory. Control preconfluent and confluent cells in room air contained 196 +/- 18 ng Cu,Zn-SOD/10(6) cells. A23187 (0.33 microM), forskolin (10 microM), isobutylmethylxanthine (0.1 mM), dexamethasone (1 microM), triiodothyronine (1 microM) and retinoic acid (1 microM) failed to alter this level of Cu,Zn-SOD. Exposure to anoxia and hyperoxia both elevated the level approximately 1.5-2.0-fold over 20% oxygen-exposed controls at 48-72 hr. Similarly, exposures to glucose oxidase (0.0075 units/ml), menadione (12.5 microM), xanthine-xanthine oxidase (10 microM, 0.03 units/ml) and H2O2 (0.0005%) increased the level up to two-threefold over controls at 24-48 hr. Lipopolysaccharide, TGF beta 1, TNF alpha, and Il-1 also increased levels of cellular Cu,Zn-SOD, but only in proliferating cells. Il-2, Il-4, interferon-gamma, and GM-CSF had no effect on Cu,Zn-SOD. All treatments that elevated SOD resulted in inhibition of cellular growth, but decreased growth of cells at confluence alone was not associated with increased Cu,Zn-SOD. We propose from these studies that Cu,Zn-SOD of endothelial cells is not under conventional second messenger or hormonal regulation, but that up-regulation of the enzyme is associated with (and perhaps stimulated by) free-radical or oxidant production that also may be influenced by availability of certain cytokines under replicating conditions.
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PMID:Regulation of Cu,Zn-superoxide dismutase in bovine pulmonary artery endothelial cells. 133 80

Clinical evidence suggests that deprenyl may slow progression of Parkinson's disease, although mechanisms underlying this putative neuroprotective action remain poorly understood. To address this issue, we studied deprenyl in 12 parkinsonian patients using a single-blind, placebo-controlled, crossover design. After 1 month, deprenyl (10 mg/d) decreased the optimal levodopa requirement by 24% (oral) and 16% (intravenous). Levodopa-induced dyskinesias were prolonged by 430%, and antiparkinsonian action by 44%. Mood improved by 47%. One month after withdrawing deprenyl, effects on dyskinesias and mood had yet to return to baseline. There was no change in activities of circulating glutathione peroxidase, glutathione reductase, glutathione transferase, superoxide dismutase, and catalase, nor in levels of lipid peroxide and vitamin E. Deprenyl also failed to modify CSF levels of total glutathione and activities of glutathione peroxidase or superoxide dismutase. These effects on levodopa pharmacodynamics and mood complicate the interpretation of available investigations of deprenyl's neuroprotective action and increase the risk of adverse effects of levodopa.
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PMID:Deprenyl effects on levodopa pharmacodynamics, mood, and free radical scavenging. 154 14

In this experiment, LPO increased and SOD reduced as the time pass when erythrocytes (RBC) and CSF were mixed and incubated. There was a negative relationship between LPO and SOD. LPO in RBC of arterial blood was higher than that of venous blood after incubation for 3 days (P less than 0.01). When arterial RBCs were incubated together with various scavengers of free radical (SOD catalase and histidine and mannitol), the production of LPO was less than that of arterial RBC incubation singly (P less than 0.01). The change of LPO was not reduced when sodium nitrite and arterial RBC incubated. The results demonstrated that the scavengers of free radicals could be eliminated free radical but failed with sodium nitrite.
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PMID:[Changes in lipid peroxides and superoxide dismutase as incubation of in vitro erythrocytes with cerebrospinal fluids and the action of various scavengers of free radicals]. 186 Mar 79

An avirulent and a virulent strain of Mycobacterium avium were selected on the basis of their growth patterns in human monocyte-derived macrophages. The virulent 7497 M. avium grew progressively in untreated macrophages, whereas the avirulent LR/149 M. avium was killed to a moderate extent by untreated human macrophages (50% of the original infectious inoculum killed 7 days after infection). We set out to investigate the possibility of modulating these growth patterns by cytokine treatment. Application of tumor necrosis factor (TNF) (100 U/ml) led to macrophages restricting significantly the growth of virulent M. avium 7497 (tenfold decrease at 7 days). TNF was also effective at modulating positively the interaction between avirulent LR/149 M. avium and macrophages inasmuch as TNF-treated cells killed 99% of infecting mycobacteria at 7 days. Granulocyte macrophage-colony stimulating factor (GM-CSF) (100-10,000 U/ml) treatment led to macrophages being as mycobacteriostatic for virulent 7497 M. avium as TNF-alpha-treated cells (i.e., tenfold reduction in growth). Treatment of macrophages with both GM-CSF and TNF-alpha was shown to have additive effects on bacteriostatic activity on M. avium. The mechanism of killing of avirulent M. avium by TNF-alpha was shown to be dependent on the generation of reactive nitrogen intermediates, as seen by inhibition of effector mechanisms by NG-monomethyl-arginine and arginase. Moreover, there was a correlation between NO2- generation and mycobactericidal activity of macrophages. Addition of superoxide dismutase reversed the killing of avirulent M. avium by untreated or TNF-treated macrophages. This abrogation was also apparent in chronic granulomatous disease (CGD) macrophages, which were inefficient at generating reactive oxygen intermediates. Moreover, macrophages from CGD patients killed avirulent M. avium as efficiently as cells from normal individuals. We conclude from these results that 1) GM-CSF and TNF-alpha, alone or in combination, increase effector functions of macrophages against virulent and avirulent strains of M. avium; 2) reactive nitrogen intermediates seem to be involved in this effector mechanism; and 3) superoxide dismutase protected M. avium against macrophage effector function, seemingly by protecting the bacteria against endogenous superoxide anion. The implications of these findings for host resistance to atypical mycobacteria are discussed.
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PMID:Tumor necrosis factor and granulocyte macrophage-colony stimulating factor stimulate human macrophages to restrict growth of virulent Mycobacterium avium and to kill avirulent M. avium: killing effector mechanism depends on the generation of reactive nitrogen intermediates. 190 May 22

Twenty five isolates of S. typhimurium from clinical specimens were studied for markers of virulence. Three of five isolates from blood, both isolates from CSF and urine and only two of fifteen isolates from faeces were positive for fluid accumulation in rabbit ileal loop. All these strains produced an enterotoxic principle, antigenically related to cholera coli family of enterotoxins, as detected by latex agglutination and immuno-dot-blot tests. Polymyxin-B treated 6 h cultures yielded the best toxin. All 5 blood isolates, both CSF isolates and one of the two urine isolates showed low LD50 indicating high virulence. The study thus revealed that some strains of S. typhimurium are more virulent and produce more enterotoxins. These strains invade the intestinal mucosa potently and lead to extra-intestinal manifestations. The low virulent strains, on the other hand, are confined to the intestine and cause mild/moderate gastroenteritis. Enzyme assays were done in 5 representative strains of good, moderate and low toxin producers. Catalase and superoxide dismutase assays did not show any correlation with toxin production, thus suggesting that the enzyme production is unlikely to be a reliable indicator of the virulence for S. typhimurium.
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PMID:Enterotoxin production & mouse virulence of clinical isolates of Salmonella typhimurium strains. 193 94

The ability of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to augment the fungicidal activity of human monocytes for Candida albicans was evaluated. Purified human monocytes cultured with [3H]leucine-labeled C. albicans caused a dose-dependent release of the [3H]leucine. The amount of [3H]leucine released correlated with a decrease in the number of viable yeast colonies. Monocyte cytotoxicity for C. albicans was reduced by superoxide dismutase and catalase and by inhibitors of myeloperoxidase and scavengers of hydroxyl radical and single oxygen, consistent with monocyte candidacidal activity being partly dependent upon products of oxidative metabolism. Monocytes incubated with rhGM-CSF produced more superoxide anion (O2-) spontaneously and after stimulation than control monocytes (P less than .05). Enhanced O2- production was dose-dependent and specific for rhGM-CSF and could be inhibited by antibody to rhGM-CSF. In association with rhGM-CSF-induced production of O2-, the cytokine enhanced cytotoxic activity for C. albicans. These findings indicate that rhGM-CSF stimulates human monocyte fungicidal activity for C. albicans.
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PMID:Granulocyte-macrophage colony-stimulating factor augments human monocyte fungicidal activity for Candida albicans. 215 74

Supernatants of human mononuclear cells cultured in the presence of LPS (LPS-MNC-SN) directly induced production of superoxide by isolated polymorphonuclear leukocytes, measured as superoxide dismutase--inhibitable cytochrome c reduction or, more sensitively, Lucigenin-enhanced chemiluminescence. Of recombinant human cytokines, only TNF and to a lesser degree also LT, but not GM-CSF, showed this activity. Neutralising antibody to TNF reduced the activity of LPS-MNC-SN to activate an oxidative burst in polymorphonuclear leukocytes by 30-50%. In contrast, killing of TNF-sensitive mouse L 929 cells by LPS-MNC-SN was completely inhibited by anti-TNF, while the L929 killing assay was at least as sensitive for TNF as the granulocyte chemiluminescence assay. Material with granulocyte chemiluminescence inducing (GCI) activity but devoid of TNF was obtained by sequential chromatography of LPS-MNC-SN on Mono Q anion exchange and phenyl sepharose hydrophobic interaction chromatography. The time course of GCI-induced superoxide generation was prolonged with a tmax of approximately 60 minutes. Subsequent separation of this GCI-active material on Superose gel filtration yielded two overlapping activity peaks with apparent molecular weights of approximately 40-50 and 200 kDa. Further, two distinct GCI activity peaks were found when Mono Q--and phenyl-sepharose--separated material was subjected to reversed phase chromatography. Thus, in addition to TNF, LPS-triggered mononuclear cells produce also other granulocyte chemiluminescence inducing mediators which appear distinct from presently known cytokines.
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PMID:Long-lasting polymorphonuclear leukocyte oxidative burst activation by products of lipopolysaccharide-treated mononuclear cells is only partially due to tumor necrosis factor. 216 31

Over the last few years, several studies showing that production of superoxide by neutrophils in response to chemotactic factors such as FMLP is enhanced after preincubation of the cells with granulocyte-macrophage (GM)-CSF or TNF-alpha have been published. Subsequent reports have indicated that this effect of the cytokines may be mediated by modulation of the number and/or affinity of surface receptors for FMLP. In the present study we have investigated the effect of preincubation with GM-CSF and TNF-alpha on the oxidative burst induced by sodium fluoride and guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S)-agents which directly activate guanine-nucleotide binding proteins in neutrophils. Pretreatment of neutrophils with either GM-CSF or TNF-alpha dose-dependently enhanced the production of superoxide induced by NaF, as determined by the superoxide dismutase-inhibitable reduction of ferricytochrome c. Furthermore, preincubation of neutrophils with these cytokines enhanced the production of hydrogen peroxide induced by GTP gamma S in electroporated neutrophils. Because both NaF and GTP gamma S directly activate G proteins independently of external receptor-G protein interaction, these results imply that both GM-CSF and TNF-alpha alter the neutrophil signal transduction pathway in response to subsequent agonists independently of a modulation in the expression of the cell surface receptors for such agonists.
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PMID:Priming of the human neutrophil respiratory burst by granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha involves regulation at a post-cell surface receptor level. Enhancement of the effect of agents which directly activate G proteins. 217 May 31

As shown previously monocytes upon stimulation with bacterial lipopolysaccharides (LPS) release granulocyte-activating mediator(s) (M-GRAM) which induced a long-lasting chemiluminescence (CL) response in human granulocytes. M-GRAM could be separated from interleukin-1 alpha and beta, interleukin-2, interferon alpha and gamma, granulocyte colony stimulating factor (G-CSF) and macrophage colony stimulating factor (M-CSF), since these cytokines are shown to be unable to induce a significant CL response. In contrast, granulocyte macrophage colony stimulating factor (GM-CSF) and particularly tumor necrosis factor (TNF) are important triggers of the oxidative burst and they are capable of inducing a CL response. TNF activity but not lymphotoxin (LT) activity could be demonstrated in M-GRAM samples. A polyclonal rabbit IgG as well as a monoclonal antibody to recombinant human TNF which neutralized the TNF activity in M-GRAM preparations did not substantially block the CL signal. Furthermore, M-GRAM-induced CL response was not significantly inhibited by a polyclonal calf antiserum to human recombinant GM-CSF. For further functional characterization of M-GRAM-induced granulocyte activation different assays were performed in order to compare GM-CSF and TNF: (a) SOD-inhibitable cytochrome C-reduction (.O2-); (b) horseradish peroxidase-mediated oxidation of phenol red (H2O2); (c) the release of peroxidase; (d) ultrastructural detection of hydrogen peroxide production; and (e) scanning and transmission electron microscopy (SEM and TEM). Significant release of .O2- was induced by M-GRAM, TNF, and GM-CSF, whereas H2O2 production was significantly stimulated only by M-GRAM and TNF, as shown by functional and ultrastructural assays.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Granulocyte-activating mediators (GRAM): III. Further functional characterization of monocyte-derived GRAM. 284 61


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