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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 264 (1969), S. 23-31 
    ISSN: 1432-1912
    Keywords: Anaphylatoxin ; Endotoxin ; Endogenous Pyrogen ; Agar ; Cobra Venom ; Anaphylatoxin ; Endotoxin ; Endogenes Pyrogen ; Agar ; Cobragift
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two anaphylatoxin-forming agents have been investigated with respect to possible pyrogenic effects: the AT forming fraction of cobra venom and agar. The cobra venom fraction produced fever in rabbits. The pyrogenic principle is, however, not identical with the AT forming enzyme. Unlike the latter the pyrogenic principle is stable in acidic solution and destroyed by periodate. It may be a lipopolysaccharide. Rabbit plasma, incubated with agar caused fever in rabbits. Agar also induced pyrogenic activity in saline after it had been incubated in that medium. The active principle proved to be agaropectin, the water-soluble acidic fraction of agar. Agarose was inert. In contrast, anaphylatoxin formation is induced by agarose, not by agaropectin. In rabbit plasma, agaropectin induces the formation of an endogenous pyrogen. This principle can be separated from the agaropectin by DEAE cellulose chromatography. It is further distinguished from the latter by being heat-labile. Besides being activated by different agents the processes of pyrogen and AT formation differ in their requirement for cations. AT formation is blocked by EDTA but pyrogen formation is not. It is concluded that in spite of similarities and common activation by endotoxins the processes of AT and pyrogen formation are different and independent events.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 265 (1970), S. 442-454 
    ISSN: 1432-1912
    Keywords: Haemolysis ; Phospholipase A ; Direct Lytic Factor ; Polypeptides ; Toxins ; HÄmolyse ; Phospholipase A ; Direkt lytischer Faktor ; Polypeptide ; Toxine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The haemolytic action on washed guinea-pig red cells of the following substances has been studied: the direct lytic factor (DLF) of cobra venom, melittin and an apamin-containing fraction of bee venom, anaphylatoxin (AT), angiotensin, vasopressin, saponin, p-chloro-mercuribenzoate (p-CMB) and N-ethylmaleimide (NEM). Further the synergism of these substances with phospholipase A in causing haemolysis has been investigated. In regard to the lytic effects, the substances studied can be classified as follows. 1. Substances which react with SH-groups, either by means of -S-S- bonds (DLF, apamin-fraction, AT, vasopressin) or by other structures (p-CMB, NEM) produce weak or no direct haemolysis, but strongly potentiate haemolysis caused by phospholipase A. Their effect is increased by Ca++, inhibited by EDTA, and strongly dependent on temperature (as far as has been investigated). 2. Angiotensin, a peptide without disulfide groups, is not haemolytic, neither directly nor in combination with phospholipase A. Saponin, which does not react with SH-groups, also does not show potentiated haemolysis with phospholipase A in spite of being haemolytic itself. 3. Melittin, though not containing disulfide structures, does produce potentiated haemolysis with phospholipase A, even at concentrations which are not lytic when acting alone. It is concluded that more than one mechanism of potentiating phospholipase A haemolysis exists. One possibility is the reaction of potentiating agents with SH-groups of membrane constituents (enzymes?) of the red cells. This mechanism applies to p-CMB, NEM and to disulfide-containing peptides. It is independent of detergent effects. Another mechanism may be membrane changes due to a lowering of surface tension such as that produced by melittin. It seems doubtful, however, whether this is the only molecular property responsible for the potentiation, as the detergent saponin does not have such an effect. Possibly melittin, in addition to having detergent effects interferes with the same membrane properties which are altered by the SH-reactants.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 267 (1970), S. 74-79 
    ISSN: 1432-1912
    Keywords: Anaphylatoxin ; Enzymes ; Plasma ; Species Specificity ; Anaphylatoxin ; Enzyme ; Plasma ; Species-Spezifität
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma or serum of various species which do not yield directly measurable amounts of anaphylatoxin (AT) has been investigated with respect to the presence of the anaphylatoxin-forming enzyme (system), anaphylatoxinogen, and the co-factor (PI) which is necessary for the anaphylatoxin-forming enzyme of cobra venom to form anaphylatoxin. The anaphylatoxin-forming enzyme was found in plasma (serum) from man, horse, cow, sheep, pig, dog, cat, rabbit, rat, fowl, and eel. Only in frog plasma could it not be detected. Except for horse and rabbit plasma, it was regularly activated by Sephadex or zymosan. In rabbit plasma Sephadex was inactive and in horse plasma both polysaccharides often failed to activate the formation of AT. Immune precipitates caused activation in horse plasma. The substrate, anaphylatoxinogen was the limiting factor in all species mentioned. After addition of anaphylatoxinogen solutions the plasma of all species formed AT upon activation by contact. The reason for the failure of most mammalian plasmas to show AT activity after contact activation is thus lack of sufficient substrate, not inactivation of AT actually formed.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 275 (1972), S. 203-211 
    ISSN: 1432-1912
    Keywords: Glutathione Reductase ; Glutathione ; Haemolysis ; Direct Lytic Factor ; Disulphides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activity of glutathione reductase (GR) was measured in haemolysates and red cell membranes of various species. The enzyme levels were compared with the susceptibility of the respective cells to the direct lytic factor (DLF) of cobra venom. A positive correlation was found in so far as cells having high (low) GR activity were highly (little) sensitive to DLF. Further results make it likely that GR is implicated in DLF-induced lysis: 1. By enzymatic assay an interaction of membrane bound GR and DLF was found, as evident from consumption of the coenzyme NADPH. 2. Glutathione in the reduced state (GSH) as well as in the oxidized form (GSSG) inhibited haemolysis by DLF in a dose-dependent manner. A chemical interaction between DLF and glutathione was excluded. 3. NADPH showed a dual effect: it accelerated DLF-induced haemolysis at low concentrations, whereas at high concentrations inhibition was evident.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 266 (1970), S. 255-260 
    ISSN: 1432-1912
    Keywords: Anaphylatoxin ; Permeability ; Histamine Liberation ; Anaphylatoxin ; Permeabilität ; Histaminfreisetzung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of anaphylatoxin (AT) on vascular permeability has been investigated by injecting Evans-blue intravenously into guinea pigs and recording the blue spots developed at sites of intracutaneously injected AT; for quantitation the area of the spots or the amount of extracted dye was measured. The permeability increasing effect in guinea-pig skin of AT is nearly as strong as that of kallidin (w/w) and about 100 times stronger than that of histamine. Antihistamine drugs reduce the incrase in vascular permeability induced by AT, but do not block it completely. It is concluded, that the effect of AT is partly mediated by liberated histamine and partly due to a direct action.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 282 (1974), S. 255-260 
    ISSN: 1432-1912
    Keywords: Direct Lytic Factor ; Cobra Venom ; Phospholipase A ; Red Cells ; Haemolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of increasing the (colloid-)osmotic pressure in the extracellular medium on haemolysis by the direct lytic factor of cobra venom (DLF) and phospholipase A has been investigated. For comparison, N-ethyl-maleimide (NEM) and p-chloromercuribenzoate (p-CMB) were used. Dextran and sucrose abolished the haemolytic effect of NEM and p-CMB but reduced only slightly (dextran) or not (sucrose) the weak lytic activity of DLF. Haemolysis by phospholipase A in the presence of DLF, NEM or p-CMB was not significantly inhibited. Hypertonic NaCl solution considerably retarded the onset of haemolysis by DLF plus phospholipase A. The mean corpuscular volume of guinea-pig red cells increased slightly but definitely during incubation with DLF. It is concluded that the haemolytic effect of DLF has non-osmotic as well as osmotic components, and that phospholipase A causes non-osmotic haemolysis. The retardation of haemolysis by hypertonic NaCl probably indicates specific inhibition of bee venom phospholipase A2, not protection of the erythrocytes from osmotic stress.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 262 (1969), S. 399-404 
    ISSN: 1432-1912
    Keywords: Anaphylatoxin ; Histamine Liberation ; Tachyphylaxis ; Smooth Muscle ; Anaphylatoxin ; Histaminliberation ; Tachyphylaxie ; glatte Muskulatur
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Wirkung von Anaphylatoxin (AT) auf den isolierten Meerschweinchenuterus wird durch Antihistaminica nicht blockiert. Am Meerschweinchenileum haben Antihistaminica zwar einen hemmenden Effekt, aber sie verhindern auch die Wirkung von Histidylprolin, das nicht durch Histaminliberation wirkt und keine Tachyphylaxie hervorruft; d. h. sie wirken nicht spezifisch. Der histaminunempfindliche Rattendünndarm wird gleichfalls durch AT erregt. Dieser Effekt beruht nicht auf etwaiger Freisetzung von Serotonin. Die Versuche machen es unwahrscheinlich, daß die AT-Kontraktion isolierter glatter Muskulatur durch Aminliberation zustandekommt. Das Phänomen der Tachyphylaxie ist vermutlich durch Receptorblockade zu erklären, nicht durch Erschöpfung von Histaminspeichern.
    Notes: Summary The action of anaphylatoxin (AT) on the isolated guinea-pig uterus is not blocked by antihistaminics. In the guinea-pig ileum antihistaminics do inhibit AT effects, but they also antagonize the contraction induced by histidylproline, a compound which does not act by liberating histamine, i.e. they are not specific for histamine. The isolated small intestine of rats, though unresponsive to histamine, is contracted by AT. This effect is not mediated by released serotonin. The experiments render unlikely the assumption that the AT-induced contractions of isolated smooth muscle are caused by released amines. The phenomenon of AT tachyphylaxis is presumably due to a blockade of receptors by fixed AT and not by exhaustion of histamine stores.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 280 (1973), S. 201-207 
    ISSN: 1432-1912
    Keywords: Direct Lytic Factor ; Cobra Venom ; Red Cells ; Membranes ; Haemolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The binding of direct lytic factor (DLF) from cobra venom (Naja naja) to intact guinea-pig red cells and to guinea-pig ghosts was estimated quantitatively by bioassay of DLF in the supernatant. 1. DLF was not bound to intact red cells in considerable amounts, during 320 min incubation. 2. The degree of binding to ghosts was much larger than that in suspensions of intact red cells. Binding to ghosts increased with time. 3. Whereas the binding of DLF to ghosts was not much influenced by varying the incubation temperature, its haemolytic activity was completely absent at temperatures below 15°C. By an immunofluorescence technique binding of DLF to erythrocytes was studied morphologically: 1. DLF was only bound to red cell ghosts (guinea pig and rat), but not to intact red cells. This binding was not temperature dependent. 2. Pretreatment of ghosts with SH-reagents such as NEM or PCMB did not prevent binding of DLF. 3. Ghosts prepared by different methods (hypotonic shock, freezing and thawing, ultrasonication, and resealing) were all able to bind DLF to their surface. It is concluded that the binding of small amounts of DLF to intact red cells, observed by bioassay, was due to the presence of a small fraction of lysed cells, and that the binding to ghosts is not related to the lytic effect of DLF but secondary to lysis.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 274 (1972), S. 81-90 
    ISSN: 1432-1912
    Keywords: Direct Lytic Factor ; Phospholipase A ; Red Cells ; Ion Permeability ; Haemolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of the direct lytic factor (DLF) of cobra venom, bee venom phospholipase A and of combinations of these two lysins on guinea-pig red cells have been studied. DLF caused an increased permeability to Na ions, swelling of the cells and moderate haemolysis. No prelytic loss of potassium was seen. Phospholipase A produced loss of potassium, considerable gain of sodium, cell swelling, but no remarkable lysis. Combinations of the two venom constituents, more strongly haemolytic, mimicked the effect of the predominant component of the mixture. Thus prelytic loss of potassium was observed when higher concentrations of phospholipase were combined with low concentrations of DLF, but was absent when DLF predominated. The rather low critical volume and spherocytosis of haemolysing red cells exposed to DLF, and the effect of DLF on osmotic stability suggest that DLF has other effects on the cell membrane in addition to those of an osmotic haemolysin.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 305 (1978), S. 181-184 
    ISSN: 1432-1912
    Keywords: Chemotaxis ; Complement peptides ; Anaphylatoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The complement-derived peptides C3a, C3ai and C5a (= classical anaphylatoxin) were purified from hog serum and examined for chemotactic activity on rabbit and guinea-pig polymorphonuclear leukocytes (PMN) with the Boyden chamber technique (with filters of 3,0 μm pore size). When media containing albumin or serum were used all peptides induced chemotaxis of both cell species. Only C3a showed a pronounced species dependence in that it was much more active on rabbit than on guinea-pig PMN. No gross differences were found between the influence of 0.5% BSA and 10% heated (56°, 30 min) homologous serum added to the medium. In the absence of protein chemotaxis did not occur.
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