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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 266 (1970), S. 95-100 
    ISSN: 1432-1912
    Keywords: Kidney Regeneration ; Temporary Ischaemia ; Folic Acid ; 2,4,5-Triamino 6-Styrylpyrimidine ; RNA and Protein Contents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 267 (1970), S. 297-306 
    ISSN: 1432-1912
    Keywords: Folic Acid ; 2,4,5-Triamino-6-styrylpyrimidme ; Pentose Phosphate Pathway ; Enzyme Induction ; Nuclear RNA ; PolsÄure ; 2,4,5-Triamino-6-styrylpyrimidin ; Pentose-Phosphat-Weg ; Fermentinduktion ; Kern-RNS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary After lesions of the proximal tubular cells, the administration of folic acid or 2,4,5-triamino-6-styrylpyrimidine increases the activity of both glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase during the regenerative phase. These increases are greater than those seen after temporary ischemia. Actinomycin and cycloheximide inhibit these processes. The triggering of natural regeneration processes by lesions is evidently enhanced by a chemical induction. The different enzymes are not induced equally during regenertion. This may be concluded from the deviating response of the activity of 3-phosphoglyceraldehyde dehydrogenase. The induction of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase demonstratedin vitro also seems to lead to an increased cell metabolismin vivo. After injection of14C-(U)-glucose, the specific activity of the RNA of isolated kidney cell nuclei after the administration of folic acid was 3 to 6 times that of the controls. The blockade of the oxidative part of the pentose phosphate pathway by 6-AN, which limits the biosynthesis of ribose by selective inhibition of 6-phosphogluconate dehydrogenase, reduces the specific activity of the nuclear RNA to 50% in animals treated with folic acid. The accumulation of 6-phosphogluconate in the kidney cells can lead to an inhibition of phosphoglucose isomerase.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 284 (1974), S. 383-393 
    ISSN: 1432-1912
    Keywords: Folic Acid ; Mercuric Chloride ; Ligation of the Ureter ; Ribonucleotides ; Oxidative Phosphorylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During the regeneration of the rat kidney after lesion by 500 mg folic acid/kg, the ribonucleotide concentrations (ATP, ADP, AMP, UTP, UDP, GTP, GDP) were determined. After 1, 3, and 7 days no significant changes were found, although 1 and 2 h after injection of folic acid a slight decrease in the concentrations of ATP, AMP, GTP, and UTP was measured. Mitochondria which were isolated from rat kidneys 1 and 4 days after application of folic acid showed an unchanged consumption of O2 and phosphate as compared with the controls. In mitochondria isolated 1 h after folic acid, a sharp decrease in O2-consumption and a complete inhibition of the uptake of inorganic phosphate occurred. However, the incorporation of 32P into ATP under in vivo conditions was not reduced. The unchanged synthesis of energy-rich phosphate compounds explains the rapid onset of the proliferation of the kidney. 24 h after injection of 1.5 mg HgCl2/kg, a fall of approximately 50% in the ATP-concentration was found. In the regenerative phase, only a slight increase in protein content of the kidneys was observed. Ligation of the ureter did not cause a significant drop of energy-rich adenine nucleotides. During the regenerative phase a pronounced increase in the protein content of the kidney was found. The injection of folic acid dissolved in 1 M bicarbonate produced no disturbance of kidney function. No increase of dry weight or of protein content resulted. The accumulation and precipitation of folic acid in the kidney tubules are prerequisites for the initiation of the regenerative processes.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 271 (1971), S. 206-210 
    ISSN: 1432-1912
    Keywords: Tryptophan ; Tubular Sodium Reabsorption ; Antagonism Tryptophan/6-AN
    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 271 (1971), S. 334-334 
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 48 (1970), S. 955-959 
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 51 (1973), S. 644-657 
    ISSN: 1432-1440
    Keywords: Spastic paresis ; 6-aminonicotinamide ; pentose phosphate pathway ; carbohydrate metabolism ; vulnerability of the neuroglia ; spinal gray matter ; Spastische Parese ; 6-Aminonicotinsäureamid ; Pentose-Phosphat-Weg ; Kohlenhydratstoffwechsel ; Vulnerabilität der Neuroglia ; spinale Grisea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Der Antimetabolit 6-Aminonicotinamid (6-AN) erzeugt bei Ratten eine irreversible spastische Parese Durch die mangelnde Spezifität einer Glykohydrolase des endoplasmatischen Reticulums werden aus NAD und NADP durch Austauschreaktion von 6-AN gegen Nicotinsäureamid abnorm strukturierte Nucleotide gebildet. 6-Aminonicotinsäureamid-Adenin-Dinuclcotid-Phosphat (6-ANADP) ist ein sehr wirksamer Hemmstoff der 6-Phosphogluconat-Dehydrogenase, der eine Blockade des Pentose-Phosphat-Weges mit Akkumulation von 6-Phosphogluconat bewirkt. Dies hat eine Funktionsstörung der Phosphoglucoseisomerase zur Folge, die eine Schlüsselstellung im Embden-Meyerhof-Weg einnimmt. Bei den mit 6-AN behandelten Tieren fanden sich charakteristische Abweichungen im Kohlenhydratstoffwechsel des Zentralnervensystems. Die Unterschiede gegenüber den Veränderungen nach Einwirkung einer kurzfristigen Ischämie waren eindeutig und bestätigen die celluläre Genese der experimentellen Myelopathie. Die höchsten Konzentrationen von 6-Phosphogluconat wurden in den Regionen des Zentralnervensystems festgestellt, die auch die stärksten Zellschädigungen aufwiesen. Im Rückenmark betrugen sie fast das 400fache der Norm. Elektronenmikroskopische Untersuchungen des Rückenmarks ergaben eine primäre Schädigung der Oligodendro- und Astroglia. Die Topographie der Neurogliazellen begünstigt die Aufnahme von 6-AN und erklärt die celluläre Läsion, die eine Störung der funktionellen Beziehungen zwischen Glia- und Nervenzelle in der spinalen Grisea zur Folge hat.
    Notes: Summary The antimetabolite 6-aminonicotinamide (6-AN) produces an irreversible spastic paresis in rats. By a lack of specificity of a glycohydrolase of the endoplasmic reticulum, abnormally structured nucleotides are synthesized from NAD and NADP by exchange reaction of 6-AN for nicotinamide. 6-Amino-nicotinamide-adenine-dinucleotide-phosphate (6-ANADP) is a very effective inhibitor of the 6-phosphogluconate dehydrogenase which causes a blockade of the pentose phosphate pathway with accumulation of 6-phosphogluconate. This leads to a functional disorder of the phosphoglucose isomerase which occupies a key position in the Embden-Meyerhof pathway. In the animals treated with 6-AN, characteristic deviations were found in the carbohydrate metabolism of the central nervous system. There were clear differences as compared with the changes after the effect of a temporary ischaemia which confirm the cellular genesis of the experimental myelopathy. The highest concentrations of 6-phosphogluconate were observed in those regions of the central nervous system which also exhibited the strongest cell lesions. In the spinal cord they showed to be almost 400 times the standard value. Electron microscopic studies of the spinal cord revealed a primary lesion of the oligodendroglial and astroglial cells. The topography of the neuroglial cells favours the uptake of 6-AN and explains the cellular lesion which results in a disturbance of the functional relationship between glial and nerve cells in the spinal gray matter.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 235-241 
    ISSN: 1432-1912
    Keywords: 3H-Labelled 6-Aminonicotinamide ; Spinal Cord ; 6-Phosphogluconate ; Gluconate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 271 (1971), S. 93-102 
    ISSN: 1432-1912
    Keywords: Carbohydrate Metabolism ; Kidney ; Enzymic Determination of Substrates ; 6-Aminonicotinamide ; Adrenalectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary After application of 6-aminonicotinamide (6-AN), a strong accumulation of 6-phosphogluconate was found in rat kidney. The accumulation of 6-phosphogluconate influences the activity of the phosphoglucose isomerase. The enzymic determination of the substrate concentrations of the carbohydrate metabolism after application of 6-AN revealed that fructose-6-phosphate and lactate as well as phosphoenolpyruvate are significantly increased in the kidney as compared to the controls. The increase in phosphoenolpyruvate might be caused by stimulated gluconeogenesis, as the application of 6-AN increases the release of corticosterone from the adrenal cortex. After adrenalectomy, the accumulation of 6-phosphogluconate is decreased, the ratio glucose-6-phosphate/fructose-6-phosphate is normalized, and also the values for lactate and phosphoenolpyruvate decrease. The effects of adrenaline seem to involve the passage of glucose through the pentose phosphate pathway. There is probably a relationship between the blockade of the oxidative pentose phosphate pathway and the stimulation of gluconeogenesis in the kidney, the mechanism of which is unknown. In contrast to the findings in the brain, no changes could be established in the concentrations of citrate and 2-oxoglutarate.
    Type of Medium: Electronic Resource
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