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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 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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  • 4
    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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  • 5
    ISSN: 1432-1912
    Keywords: Histamine ; Prostaglandin ; Mast Cells ; Cobra Venom ; Phospholipase A ; Direct Lytic Factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of Direct Lytic Factor (DLF) and phospholipase A (ph-ase A) from cobra venom, alone and in combination, on mast cell degranulation, histamine release and formation of prostaglandin-like activity (SRS-C) was studied in perfused guinea-pig lungs and in mast cell-containing rat peritoneal cell suspensions. For comparison, the effect of equivalent doses of whole cobra venom was investigated. 1. Cobra venom caused mast cell degranulation, histamine release and SRS-C formation in both systems. For comparable effects much higher doses had to be used in guinea-pig lungs than in rat peritoneal cell suspensions. 2. Ph-ase A showed little degranulation of mast cells in both systems, a limited histamine release in rat peritoneal cell suspensions and none in perfused guinea-pig lungs. It caused a considerable SRS-C formation in both, lung tissue and peritoneal cell suspensions. 3. DLF caused histamine release, SRS-C formation and mast cell degranulation in both systems; in rat peritoneal cell suspensions it acted almost as strong as equivalent doses of cobra venom, in guinea pig lungs it was much less active. 4. In rat peritoneal cell suspensions the effects of DLF and ph-ase A in combination did not exceed the sum of their single effects. In guinea-pig lungs these two substances interacted in a potentiating synergism. It is concluded that DLF is the main cytotoxic principle of cobra venom, whereas ph-ase A alone is not cytotoxic. The difference in the synergism of DLF and ph-ase A between rat peritoneal cells and guinea-pig lungs may be due to two different actions of DLF and species differences as regards sensitivity against these actions.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 262 (1969), S. 124-134 
    ISSN: 1432-1912
    Keywords: Prostaglandins ; Guinea-Pig Lung ; Phospholipase A ; Cobra Venom ; Biosynthesis ; Prostaglandine ; Meerschweinchenlunge ; Phospholipase A ; Kobragift ; Biosynthese
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung SRS-C tritt in Perfusaten von Meerschweinchenlungen auf, wenn Phospholipase A-haltige Gifte einwirken. Sie wurde aus den Perfusaten angereichert. Die Wirkung von SRS-C beruht im wesentlichen auf Prostaglandinen, z.T. auf Peroxyden. Beide stammen von mehrfach ungesättigten Fettsäuren ab. Die freigesetzten Prostaglandine sind nur z. T. im Gewebe vorgebildet, der größere Teil entsteht neu nach Abspaltung der als Vorstufen dienenden Fettsäuren aus Phosphatiden. In den Lungenphosphatiden selbst wurde Prostaglandin als Bestandteil nicht gefunden.
    Notes: Summary SRS-C appears in perfusates of guinea-pig lungs when the lungs are treated with phospholipase A or venoms containing this enzyme. SRS-C has been concentrated and purified from such perfusates. The biological activity of SRS-C depends mainly on the presence of prostaglandins and to a minor degree also on peroxides. Both compounds originate from unsaturated fatty acids. The liberated prostaglandins are only partially preformed. The bulk of them is formed after cleavage of the precursor acids from tissue phosphatides. Prostaglandins have not been detected as constituents of lung phosphatides.
    Type of Medium: Electronic Resource
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  • 7
    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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  • 8
    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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  • 9
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Journal of High Resolution Chromatography 3 (1980), S. 85-86 
    ISSN: 0935-6304
    Keywords: Liquid chromatography, HPLC ; Ion-pair reversed-phase ; Free porphyrin carboxylic acids in urine, complete separation ; Quantitation within 4.4-5.4% precision ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    New York : Wiley-Blackwell
    Die Makromolekulare Chemie 163 (1973), S. 111-134 
    ISSN: 0025-116X
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: The transesterification of diethyl phosphite with diols of type HO-(CH2)x-OH (x = 2 to 6 and 8) was investigated. A balance of the reaction showed that besides the desired transesterification ether structures are formed to a more or less extent. This reaction, not yet described in this connection, proceeds very probably as a direct alkylation of the alcoholic OH-groups by the phosphite ester because it does not need a catalyst. In the course of this reaction, the ester groups change to acidic P-OH-groups which are not able to condense with diols under the applied conditions. The ratio of undesired ether formation and polycondensation depends on the number of CH2-groups in the diol. Polyesters of considerably higher molecular weights are obtained only if x ≥ 6. With 1.5-pentanediol and 1.4-butanediol the cyclic ethers tetrahydropyran and tetrahydrofuran are the main products. With 1.3-propanediol the cyclic ester 2-hydro-2-oxo-1.3.2-dioxaphosphorinane is formed, besides small amounts of ether structures and of low molecular oligomers. Ethylene glycol leads to a complex mixture of oligomers of the desired structure and of oligoethylene glycols. All the reaction phenomena obey the following rule: The main products of reactions between diethyl phosphite and diols are always obtained via 5- or 6-membered transition states. Polycondensation is a slow process, which is observed only if reactions with such cyclic transition states are impossible.
    Notes: Die Umesterungsreaktion von Diäthylphosphit mit linearen Diolen HO-(CH2)x-OH (x = 2-6 und 8) wurde untersucht. Ihre Bilanz zeigte, daß neben der angestrebten Umesterungsreaktion in teilweise sehr erheblichem Umfang auch Ätherstrukturen gebildet werden. Diese bis jetzt in diesem Zusammenhang noch nicht beschriebene Reaktion verläuft sehr wahrscheinlich im Sinn einer direkten Alkylierung der alkoholischen OH-Gruppen durch die Phosphitestergruppen, denn sie erfordert keinen Katalysator. Die Estergruppen gehen dabei in saure P-OH-Gruppen über, die unter den angewendeten Bedingungen nicht mehr ohne weiteres zur Kondensation mit den Diolen befähigt sind. Das Verhältnis von unerwünschter Ätherbildung zur Polykondensation hängt von der Anzahl der Methylengruppen im jeweils verwendeten Diol ab. Höhermolekulare Polyester werden nur bei ≥ 6 erhalten. Die Reaktion mit 1.5-Pentandiol und 1.4-Butandiol liefert dagegen die cyclischen Äther Tetrahydropyran und Tetrahydrofuran als Hauptprodukte. Bei der Reaktion mit 1.3-Propandiol tritt die Ätherbildung ganz zurück; es entsteht jedoch kein Polymeres, sondern der bekannte cyclische Phosphorigsäureester des Propandiols, das 2-Hydro-2-oxo-1.3.2-dioxaphosphorinan. Mit Äthylenglykol erhält man ein kompliziertes Gemisch, in dem neben Oligomeren der gewünschten Polyesterstruktur auch ein großer Anteil von linearen Oligomeren des Äthylenglykols enthalten ist. Für das ganze Reaktionsgeschehen läßt sich folgende Regel aufstellen: Es entstehen immer diejenigen Substanzen als Hauptprodukte, die über 5- oder 6-gliedrige Übergangszustände gebildet werden können. Nur wenn solche cyclischen Übergangszustände nicht möglich sind (bei ≥ 6), kommt die offenbar nur langsam verlaufende Kondensation zum Polyester zum Zuge.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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