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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 25 (1974), S. 159-167 
    ISSN: 0027-5107
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 255 (1966), S. 87-88 
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 256 (1967), S. 333-347 
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 1. In Erythrocytensuspensionen von Schweinen, Rindern und Schafen wurde über 2 Std der Glucoseverbrauch, die Lactat-, Pyruvat- und CO2-Bildung in Gegenwart von 2 · 10−5 M Phenylhydroxylamin und unter Kontrollbedingungen bestimmt. Außerdem wurden O2-Verbrauch, Methämoglobinbildung und GSH-Konzentration gemessen. Die Summen der Endprodukte aus Lactat, Pyruvat und CO2 stimmen unter Kontrollbedingungen und während der Hämoglobinoxydation mit dem gefundenen Glucoseverbrauch überein. 2. 2 · 10−5 M Phenylhydroxylamin beeinflußt in Erythrocyten aller drei Tierarten die GSH-Konzentration nicht. Es bewirkt gesteigerten Glucoseverbrauch, verminderte Lactatbildung bei erhöhter Bildung von Pyruvat und CO2. Der Sauerstoffverbrauch wird bis auf das 40 fache erhöht. Die Stimulierung des Pentosephosphatcyclus, über den in Schaferythrocyten während der Methämoglobinbildung sämtliche Glucose abgebaut wird, geht mit verminderter Recyclisierung einher. 3. Unter Kontrollbedingungen wird in Erythrocyten die aus dem Glucoseabbau gewonnene Energie zu 80% auf ATP und zu 20% auf reduzierte Pyridinnucleotide übertragen. Durch Phenylhydroxylamin wird der Energieumsatz bei fast gleicher ATP-Bildung erheblich gesteigert. Dabei treten 80% der Energie in Form reduzierter Pyridinnucleotide auf, und auf ATP entfallen nur noch 20%.
    Notes: Summary 1. The utilization of glucose, the formation of lactic, pyruvic, and carbonic acid were determined in the presence of phenylhydroxylamine (2 × 10−5M) in suspensions of the red blood cells of pigs, cows and sheep. In addition, the consumption of oxygen, the formation of methaemoglobin, and the concentration of reduced glutathione were determined. In controls and during the formation of methaemoglobin, the sum of the end products (lactic, pyruvic, and carbonic acid) at the end of the reaction agrees with the utilization of glucose. 2. Phenylhydroxylamine did not influence the concentration of reduced glutathione in the red blood cells of those animals, but increased the utilization of glucose and diminished the formation of lactic acid with simultaneous enhancement of pyruvic and carbonic acid. The consumption of oxygen is increased up to 40 times. The stimulation of pentose phosphate pathway is coupled with diminished recyclisation. In the red blood cells of sheep, the total of glucose during the formation of methaemoglobin is metabolized by this way. 3. Under control conditions 80% of the energy from glucose metabolism is converted to ATP. In the presence of phenylhydroxylamine, the formation of ATP is not decreased, but the transfer of energy to reduced pyridinnucleotides is increased in such a manner that only 20% appears in the form of ATP.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 257 (1967), S. 75-75 
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 259 (1967), S. 66-90 
    ISSN: 1432-1912
    Keywords: Enzyme Induction ; Liver Weight ; Microsomal Proteins ; Microsomal Specific Activity ; Drug Metabolism ; Enzyminduktion ; Lebergewicht ; Mikrosomenprotein ; Spezifische Mikrosomenaktivität ; Arzneimittel-Stoffwechsel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Female rats (Wistar, 50 g) were injected intraperitoneally, prior to sacrifice, with phenobarbital (Ph) 50 mg/kg, 18 h, and 42 h; methylcholanthrene (Mc) 20 mg/kg, 18 h and chlorophenothane (DDT) 160 mg/kg, 5 days. Relative liver weights increased after Ph 20%, Mc 14% and DDT 31% compared to controls. Combined stimulation resulted in a nearly additive increase of liver weight after injections of Ph + Mc and Ph + DDT. Mc + DDT revealed no addition. Prepared isolated liver microsomes (mg microsomal protein prepared from 1 g of liver) increased after stimulation: Ph 43%, Mc 27%, DDT 54%. Ph + Mc and Mc + DDT were not found to act additively, but Ph + DDT did. Specific microsomal oxidation capacity was followed by estimating the metabolites formed during the following reactions: p-C-hydroxylation of N-butylaniline, O-dealkylation of o-nitroanisol, N-hydroxylation of p-chloroaniline, N-dealkylation of N-methylaniline and N-hydroxylation of N-methylaniline. The specific microsomal hydroxylation activity (mμmoles of metabolite pro mg microsomal protein formed in a given time period) for C-hydroxylation was increased most by DDT. Among single stimulations Ph accellerated O-dealkylation to the greatest extent, Ph + Mc operated in an additive manner, but Ph + Mc + DDT stimulated even more. N-hydroxylation was influenced greatest by Mc (43%). DDT did not change the velocity of N-hydroxylation. N-Dealkylation was stimulated optimally by DDT; Ph + DDT gave additive effects. The N-oxidation of N-methylaniline decreased to 50% after giving all 3 substances. This picture of multiform changes in specific activities after stimulation with different compounds, single and in combinations, differs in other animal species and can hardly be explained by varying levels of specific enzymes.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 264 (1969), S. 434-461 
    ISSN: 1432-1912
    Keywords: N-Hydroxylation ; p-Phenetidine and Phenacetin ; Microsomes ; Liver and Kidney ; Phenobarbital-Stimulation ; N-Hydroxylierung ; p-Phenetidin und Phenacetin ; Mikrosomen ; Leber und Niere ; Phenobarbital-Stimulierung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Reactive metabolites are considered to be responsible for toxic effects of phenacetin or p-phenetidine. The velocity of ferri-haemoglobin formation in dogs fed 13.7 mg (0.1 mmole)/kg p-phenetidine was increased by about 100% after phenobarbital (Phb) pretreatment (6×40 mg/kg). N-oxidation metabolites, estimated as the nitroso derivative, reached blood levels of 0.3 fig/ml in control dogs and about 1 μg/ml in phenobarbital pretreated dogs. Nitrosophenetol extracted into CCl4 from the blood of Phb treated dogs dosed with 0.5 mmoles/kg p-phenetidine was identified by thin layer chromatography, chemical reactions and UV-absorption. In dogs, the urinary excretion in 8 h of N-oxidation metabolites of p-phenetidine (160–280 μg, estimated in the form of p-nitrosophenetol) increased by 80–100% after Phb treatment. The half life in blood of intraveneously injected p-phenetidine was decreased from 90 to 40 min by Phb pretreatment. Rats given 0.5 mmoles/kg p-phenetidine orally, excreted in 10h, only about 0.1% of the dose in the form of N-oxidation products. The excretion of N-oxidation products in the urine of dogs fed 1 mmole/kg phenacetin was very low. In the urines of dogs pretreated with Phb 50–120 μg of N-oxidation products appeared during 8 h. Isolated microsomal fractions of rabbit liver and kidney catalysed the N-hydroxylation of p-phenetidine in vitro in the presence of O2 and NADPH2.10–20% of the substrate (1 μmole/ml) was N-hydroxylated in 10 min by liver microsomes of rabbits pretreated with Phb. Kidney microsomes of the same animals, on the other hand, N-hydroxylated only 3–6/o of the substrate in 10 min. N-hydroxylation products formed in the incubation mixtures were extracted in the form of p-nitrosophenetol into CCl4 after addition of 3mM K3[Fe(CN)6]. The nitroso compound was isolated in crystalline form and fully characterized. In vitro, the formation of ferri-haemoglobin in suspensions of bovine erythrocytes by p-nitrosophenetol is considerably increased by addition of washed microsomes + NADPH2. Therefore, the formation of ferri-haemoglobin in a system of microsomes, p-phenetidine, NADPH2 and erythrocytes cannot be used for a quantitative evaluation of oxidizing metabolites of p-phenetidine.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 278 (1973), S. 55-68 
    ISSN: 1432-1912
    Keywords: Dapsone ; N-Hydroxylation ; Methaemoglobin Formation ; Liver Microsomes ; Urinary Excretion in Dogs and Humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. During the incubation of Dapsone1 with rabbit liver microsomes, NADPH and bovine erythrocytes, rapid haemoglobin oxidation was observed. The velocity increased 2–3 times with liver microsomes of rabbits pretreated with phenobarbital. 2. Liver microsomes of rabbits catalyzed the N-hydroxylation of DDS in the presence of O2 and NADPH. The oxidation was dependent upon microsomal protein, DDS concentration, NADPH concentration and pH. The velocity of N-hydroxylation in incubates with microsomes from rabbits pretreated with phenobarbital was 2–3 times greater than the velocity with microsomes from control animals. Carbon monoxide and metyrapone inhibited the microsomal N-hydroxylation of DDS. The reaction must be included in the cytochrome P-450 dependent N-hydroxylations of primary arylamines. 3. In dogs, very low amounts of free DDS-NOH were found in the urine. 7–10% of an oral dose of 50 mg/kg DDS was excreted in the urine in the form of conjugated DDS-NOH liberated by acid hydrolysis (1 N HCl at 20°C). 4. Human volunteers receiving 200 mg DDS in capsules excreted 0.9–3.4% of the dose as free DDS-NOH and 6–20% as conjugated, acid labile DDS-NOH within 24h. After 72 h 5–7% of the dose was excreted as free DDS-NOH and 25–33% as conjugated, acid labile DDS-NOH. 80–90% of the DDS-NOH conjugates were liberated by treatment with 1 N HCl at 20°C. The total amount of conjugates in the urine was split by glusulase treatment under anaerobic condition. N-Hydroxy metabolites of DDS in the urine can reach 50% of the dose. Dapsone metabolism in humans is the first example in which N-hydroxylation is the principal metabolic pathway.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 279 (1973), S. 39-52 
    ISSN: 1432-1912
    Keywords: Halothane ; Carbon Tetrachloride ; Microsomal Metabolism ; Cytochrome P-450 ; Covalent Protein Binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. In suspensions of rabbit liver microsomes reduced by dithionite or NADPH, halothane produces a difference absorption spectrum with a maximum at 473 nm and a minimum at 408 nm. The “optical affinity” (K s) was in the region of 3–6×10−6 M for dithionite reduced microsomes. The maximal absorption with dithionite reduced microsomes for halothane (473–550 nm) was 0.017–0.019 and for CCl4 (454–500 nm) 0.04–0.05 per nmol of cytochrome P-450. The appearance of the difference absorption with halothane is faster than that with CCl4. 2. During anaerobic incubation with NADPH-reduced liver microsomes from phenobarbital pretreated rabbits, 14C-labelled halothane (1 mM) was covalently bound to microsomal proteins at a rate of 2 nmol/mg protein in 30 min (CCl4: 11 nmol/mg protein in 30 min). Reduction by dithionite was ineffective. The binding of halothane was 60% inhibited in a gas phase of air, 75% by CO, 55% in the presence of 1 mM metyrapone, 50% by CCl4, but only 20% by red. glutathione. The binding of the radioactivity from labelled halothane and CCl4 to proteins of isolated rabbit lung and kidney microsomes was approximately proportional to the concentrations of cytochrome P-450 in the organ fractions. 3. Like CCl4, halothane (1 mM) inhibited several microsomal drug oxidation reactions. 4. Irreversible binding of halothane or its metabolite(s) to endoplasmic proteins might be connected with halothane liver damage.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naturwissenschaften 44 (1957), S. 377-378 
    ISSN: 1432-1904
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Mutation Research/Environmental Mutagenesis and Related Subjects 38 (1976), S. 114 
    ISSN: 0165-1161
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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