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  • Articles  (137)
  • liver
  • Springer  (137)
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  • 1995-1999  (88)
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  • Articles  (137)
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  • 1
    Electronic Resource
    Electronic Resource
    Vitamin E content of different animal products: Influence of animal nutrition (1997)
    Springer
    European journal of nutrition 36 (1997), S. 23-27 
    Details
    ISSN: 1436-6215
    Keywords: Vitamin E ; Fleisch ; Fettgewebe ; Leber ; Eigelb ; Vitamin E ; meat ; adipose tissue ; liver ; egg yolk
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary The α-tocopherol content of different meat cuts was examined. Chicken thigh had the highest vitamin E content, followed by chicken breast and pork shoulder (p〈0.05). The lowest concentrations were found in longissimus dorsi muscle from pork, beef, veal and in beef shoulder. Considering the average daily lean meat consumption (105 g) in Switzerland, recommendation for daily vitamin E intake was met to 3 %. Supplementation of 200 mg α-tocopherol acetate/kg feed to pigs and laying hens significantly increased the α-tocopherol content in all examined products. The α-tocopherol accumulation differed according to the following ranking: egg yolk 〉 liver 〉 adipose tissue 〉 musculus longissimus dorsi. The α-tocopherol:energy ratios were 28.8, 7.3, 0.9 and 1.2 mg/MJ for egg yolk, liver, adipose tissue and longissimus dorsi muscle of the vitamin E supplemented groups, respectively. The results showed that meat, with the exception of chicken thigh, is not an important supplier of vitamin E, not even from animals fed a vitamin E enriched diet. Egg yolk became a good source of vitamin E for human nutrition by dietary modification.
    Notes: Zusammenfassung In der vorliegenden Studie wurde der α-Tocopherolgehalt verschiedener Fleischstücke untersucht. Hähnchenschenkel hatte den höchsten α-Tocopherolgehalt, gefolgt von Hähnchenbrust und Schweineschulter (p〈0.05). Die niedrigsten Konzentrationen wurden im Musculus longissimus dorsi vom Schwein, Rind, Kalb und in der Rindsschulter nachgewiesen. Mit dem durchschnittlichen, täglichen Verzehr an magerem Fleisch (105 g) in der Schweiz wurden die Empfehlungen für die tägliche Vitamin E-Zufuhr zu 3 % gedeckt. Die Supplementierung des Schweine- und Legehennenfutters mit 200 mg α-Tocopherolacetat/kg führte zu einem signifikanten Anstieg des α-Tocopherolgehaltes in allen untersuchten Produkten. Die α-Tocopherolakkumulierung unterschied sich gemäß folgender Rangordnung: Eigelb 〉 Leber 〉 Fettgewebe 〉Musculus longissimus dorsi. Die Nährstoffdichten betrugen 28.8, 7.3, 0.9 und 1.2 mg α-Tocopherol/MJ für Eigelb, Leber, Fettgewebe und Musculus longissimus dorsi der jeweiligen mit Vitamin E supplementierten Gruppe. Diese Ergebnisse zeigen, daß Fleisch, mit Ausnahme des Hähnchenschenkels, von Tieren mit supplementierten Diäten kein bedeutender Vitamin E-Lieferant ist. Hingegen wurde Eigelb durch fütterungsbedingte Modifikation zu einer guten Vitamin E-Quelle.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01618896
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  • 2
    Electronic Resource
    Electronic Resource
    Analysis of magnetic material in the human heart, spleen and liver (1997)
    Springer
    BioMetals 10 (1997), S. 351-355 
    Details
    ISSN: 1572-8773
    Keywords: heart ; liver ; maghemite ; magnetite ; spleen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Isothermal remanent magnetization (IRM) acquisition and alternating field (A.F.) demagnetization analyses were performed on human heart, spleen and liver samples resected from cadavers. The magnetic properties of the samples were measured both at 77K and at 273K. A.F. demagnetization was performed at 273K. Results from the analyses of the tissue indicate the presence of ferromagnetic, fine-grained, magnetically interacting particles which, due primarily to magnetic properties, are thought to be magnetite and/or maghemite. The presence of superparamagnetic particles can be inferred from the increase in saturation IRM values when measured at 77K compared with measurements at 273K and the decay of remanent magnetization upon warming from 77K. The concentration of magnetic material (assuming it is magnetite or maghemite) in the samples varies from 13.7 ng g-1 to 343 ng g-1, with the heart tissue generally having the highest concentration. The presence of magnetic material in these organs may have implications for the function of biogenic magnetite in the human body.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018340920329
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  • 3
    Electronic Resource
    Electronic Resource
    Determination of copper, manganese and zinc in human liver (1998)
    Springer
    BioMetals 11 (1998), S. 49-53 
    Details
    ISSN: 1572-8773
    Keywords: copper ; liver ; manganese ; metals ; zinc
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Autopsied liver tissue samples collected from 42 males and 31 females were analyzed for copper, manganese and zinc using atomic absorption spectrometry (AAS). With the exception of two liver samples for which the copper levels were determined to be 74.8 and 104.0 μg/g (dry weight), hepatic copper concentrations were found to range from 1.7 to 32.4 μg/g with a mean concentration of 14.2 μg/g and standard deviation of 7.0 μg/g. Manganese concentrations (with the exception of one sample having 12.9 μg/g) ranged from 0.22 to 4.6 μg/g with a mean of 2.26 ± 1.00 μg/g. Hepatic zinc levels averaged 118.3 ± 44.4 μg/g and ranged from 38.5 to 231.3 μg/g. There were no apparent trends for the levels of any metals versus age nor were there any differences in average hepatic metal concentrations for males and females. © Rapid Science 1998.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009209408034
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  • 4
    Electronic Resource
    Electronic Resource
    X-ray fluorescence in the assessment of inter-elemental interactions in rat liver following lead treatment (1995)
    Springer
    BioMetals 8 (1995), S. 105-110 
    Details
    ISSN: 1572-8773
    Keywords: energy dispersive X-ray fluorescence ; liver ; lead toxicity ; inter-elemental effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Energy dispersive X-ray fluorescence technique was employed to study the interactions of lead (50 and 100 mg/kg body wt) with K, Fe, Cu, Zn, Br and Rb in rat liver. Lead was administered orally to rats daily for dosage periods of 1 and 4 months (short and long terms). Hepatic Fe levels were found to increase significantly with the supplementation of low and high doses of lead for both the treatment periods, although the increase was more pronounced following long-term treatment. The levels of hepatic K, Cu and Br were seen to decrease significantly over both time intervals. Moreover, hepatic Rb contents were lowered with the short-term supplementation of low doses of lead. In contrast, Rb and Zn levels were increased when lead was administered for the longer period at both dose levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00142008
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  • 5
    Electronic Resource
    Electronic Resource
    Hepatic iron deposition in human disease and animal models (1996)
    Springer
    BioMetals 9 (1996), S. 205-209 
    Details
    ISSN: 1572-8773
    Keywords: iron ; liver ; human ; animal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Iron deposition occurs in parenchymal cells of the liver in two major defects in human subjects (i) in primary iron overload (genetic haemochromatosis) and (ii) secondary to anaemias in which erythropolesis is increased (thalassaemia). Transfusional iron overload results in excessive storage primarily in cells of the reticule endothelial system. The storage patterns in these situations are quite characteristic. Excessive iron storage, particularly in parenchymal cells eventually results in fibrosis and cirrhosis. There is no animal model or iron overload which completely mimics genetics haemochromatosis but dietary iron loading with carbonyl iron or ferrocene does produce excessive parenchymal iron stores in the rat. Such models have been used to study iron toxicity and the action of iron chelators in the effective removal of excessive iron stores.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00144626
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  • 6
    Electronic Resource
    Electronic Resource
    Differences in membrane ion transport between hepatocytes from the periportal and the pericentral areas of the liver lobule (1996)
    Springer
    Cellular and molecular life sciences 52 (1996), S. 554-557 
    Details
    ISSN: 1420-9071
    Keywords: Ion transport ; hepatocytes ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We studied the Na+/K+ pump, Na+/K+ ATPase activity, and oxygen consumption (QO2) in hepatocytes isolated from the periportal (PH) and pericentral (CH) regions of the liver lobule, to provide an insight into the functional properties of these cells. Na+/K+ pump activity was determined using86Rb+ (a functional analog of K+) and ouabain, a specific inhibitor of this transport system. Our results indicate the the Na+/K+, pump and Na+/K+ ATPase activity are significantly lower in CH than in PH, although basal ouabain-sensitive (OS) QO2 was negligible in both of these cell preparations. However, OSQO2 was significantly lower in CH than in PH when the Na+/K+ pump was activated using the ionophore nystatin in a Na+-containing medium. These results indicate that the differences in membrane ion transport exist between hepatocytes from different locations of the liver lobule.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01969727
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  • 7
    Electronic Resource
    Electronic Resource
    Effects of female sex hormones on polyamine-oxidizing enzyme activities and polyamine concentrations in immature rat uterus and liver (1996)
    Springer
    Cellular and molecular life sciences 52 (1996), S. 795-798 
    Details
    ISSN: 1420-9071
    Keywords: Estradiol ; progesterone ; polyamine oxidase ; diamine oxidase ; polyamines ; uterus ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract 17β-estradiol (E2) and progesterone (P) treatment of immature female rats (10 μg/100 g body weight) respectively resulted in 1.38-fold (p〈0.02) and 1.42-fold (p〈0.02) increase in the uterine polyamine oxidase activity, and 2.45-fold (p〈0.001) and 1.43-fold (p〈0.02) increase in the uterine diamine oxidase activity, as compared to the controls. E2 caused a 5-fold (p〈0.05) and a 1.36-fold (p〈0.05) increase in putrescine and spermidine concentration respectively in rat uterus. Increases of 1.7-fold (p〈0.02) and 1.6-fold (p〈0.05) in putrescine and spermine concentration were determined in the P-treated uterus, as compared to the controls. The spermidine/spermine ratio, which is regarded as an index of growth rate, was higher in the E2-treated uterus and lower in the P-treated uterus than in the control uterus. No statistically significant hormonal effects were estimated in the immature liver. The data reported suggest the possibility of an involvement of polyamine-oxidizing enzymes in the modulation of polyamine concentrations in rat uterus by the female sex hormones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01923991
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  • 8
    Electronic Resource
    Electronic Resource
    Transferrin response in normal and iron-deficient mice heterozygotic for hypotransferrinemia; effects on iron and manganese accumulation (1998)
    Springer
    BioMetals 11 (1998), S. 265-276 
    Details
    ISSN: 1572-8773
    Keywords: brain ; ferritin ; liver ; plasma ; TIBCAbbreviations: Fe (iron) ; Mn (manganese) ; Tf (transferrin) ; TIBC (total iron binding capacity) ; +/+ (wild-typeBALB/cJ mice) ; +/hpx (mice heterozygotic for the hypotransferrinemiamutation)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Hypotransferrinemia is a genetic defect in mice resultingin 1% of normal plasma transferrin (Tf) concen-trations;heterozygotes for thismutation (+/hpx) have low circulating Tf concentrations. These mice providea unique opportunity toexamine the developmental pattern and response of Tf to iron-deficient diets, andfurthermore,to address the controversial role of Tf in Mn transport. Twenty-three weanling +/hpx miceandforty-five wild-type BALB/cJ mice were either killed at weaning or fed diets containing either13 or 72 mgkg Fe, and killed after four or eight weeks. Plasma Tfconcentrations were lower in +/hpx mice, plasmaTf nearly doubled and liver Tf was only 50% of normalin response to iron deficiency. Brain iron concen-trationdid not correlate significantlywith either plasma Tf or TIBC. However, iron accumulation into braincontinued with irondeficiency whereas most other organs had less iron. These results imply that eitherthereis a selected targeting of iron to the brain by plasma Tf or there is an alternative irondelivery system tothe brain. Furthermore, we observed no differences in tissuedistribution of Mn despite the differences incirculating Tf concentrationsand body iron stores; this suggests that there are non-Tf dependent mecha-nismsfor Mntransport.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009280922387
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  • 9
    Electronic Resource
    Electronic Resource
    Subcellular distribution of metallothionein and cadmium in the liver and kidneys of bank voles (Clethrionomys glareolus) exposed to dietary cadmium (1999)
    Springer
    BioMetals 12 (1999), S. 173-179 
    Details
    ISSN: 1572-8773
    Keywords: cadmium ; kidneys ; liver ; metallothionein ; tissue injury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Metallothionein (MT) and cadmium (Cd) contents were determined in the subcellular fractions of the liver and kidneys of bank voles exposed for 6 weeks to elevated levels of dietary Cd-40 and 80 μg g-1 dry weight. Hepatic and renal MT was detected exclusively in the cytosol, while Cd was found in the cytosol (73–79% of the total content), nuclei (14–18%) and particulates (4–9%). The concentration of MT in the cytosol as well as Cd content in the particular subcellular fractions appeared to be a dose-dependent. The absence of MT in the nuclear and particulate fractions implied that Cd present in these compartments was not bound to the protein that is considered to provide protection against the toxic metal. Therefore, it is assumed that this component of intracellular Cd could be responsible for the histopathological changes that occurred in the liver (granuloma and focal hepatocyte swelling) and kidneys (focal degeneration of proximal tubules) of bank voles exposed to the higher level of dietary Cd.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009285820760
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  • 10
    Electronic Resource
    Electronic Resource
    The effect of graded ascorbic acid intake on the activity of GSH-Px in the liver of female guinea pigs (1995)
    Springer
    European journal of nutrition 34 (1995), S. 220-223 
    Details
    ISSN: 1436-6215
    Keywords: Ascorbic acid ; glutathioneperoxidase ; lipid peroxides ; liver ; Ascorbinsäure ; Glutathion-Peroxidase ; Lipidperoxiden ; Leber
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Verschiedene Werte an antioxidativem Potential, erzeugt mit Hilfe verschiedener Konzentrationsstufen an Ascorbinsäure (1, 10, 100 mg/Tier/Tag) führten zu Veränderungen in der GSH-Px Aktivität und der Menge den Lipidperoxiden in der Leber von Meerschweinchen. Die Gruppe mit der kleinsten Dosierung (1 mg) von Ascorbinsäure hatte die niedrigste GSH-Px Aktivität und den höchsten Anteil an Lipidperoxiden. Die zwei anderen Gruppen zeigten eine Erhöhung der GSH-Px Aktivität und Senkung von Lipidperoxiden auf. Es bestand kein Unterschied zwischen den Gruppen mit der Dosis von 10 und 100 mg Ascorbinsäure.
    Notes: Summary Differing antioxidant potentials created by graded ascorbic acid supplementation (1, 10, 100 mg per animal daily) evoked changes in the level of glutathione peroxidase activity and lipid peroxides in the liver of female guinea pigs. The group with the lowest ascorbic acid intake (1 mg) had the lowest activity of glutathione peroxidase and the highest level of lipid peroxides. The two other groups (10 and 100 mg) showed enhancement of glutathione peroxidase activity and decline in lipid peroxides. There was no difference between the groups with 10 and 100 mg ascorbic acid intake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01623161
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  • 11
    Electronic Resource
    Electronic Resource
    Untersuchungen zum Einfluß einer unterschiedlichen Riboflavinversorgung während der Laktation auf den Riboflavingehalt von Milch, Leber und Restkörper laktierender Ratten (1997)
    Springer
    European journal of nutrition 36 (1997), S. 176-181 
    Details
    ISSN: 1436-6215
    Keywords: Riboflavin ; Milch ; Leber ; Restkörper ; Laktation ; Ratte ; Riboflavin ; milk ; liver ; carcass ; lactation ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary The present study investigated the effect of various dietary riboflavin supplementations (0 to 4 000 mg/kg) during lactation on riboflavin concentrations of liver, carcass (bled body without intestine and liver), and milk in the rat. The experiment was conducted until the 14th day of lactation; milk samples were drawn on the 7th and 13th day of lactation. Riboflavin concentrations of milk raised continuously with increasing riboflavin supplementation; in the range between 0 and 10 mg/kg riboflavin supplementation, there was a linear relationship, and in the range between 12 and 4 000 mg/kg there was a logarithmic relationship between riboflavin supplementation and riboflavin concentration in the milk. Maximum riboflavin concentration of milk obtained by supplementation with 4 000 mg/kg was twelve-fold higher than without riboflavin supplementation. For riboflavin supplementation up to 12 mg/kg, riboflavin concentrations in milk on the 7th day of lactation and that on the 13th day of lactation were not different. In contrast, in rats fed diets with higher riboflavin supplementation, riboflavin concentrations were higher by 25 % in average in milk on the 13th day of lactation than in milk on the 7th day of lactation. Contrary to the milk, riboflavin concentrations in liver and carcass exhibited a saturation, which was achieved at a supplementation of 6 mg/kg (liver) and 10 mg/kg (carcass), respectively. Maximum riboflavin concentrations obtained at a supplementation of 4 000 mg/kg were 1.9- and 2.3-fold higher for liver and carcass, respectively, than concentrations obtained without riboflavin supplementation. The dose-response relationship using riboflavin concentrations of liver and carcass as response factors indicates a riboflavin requirement of 8 to 9 mg/kg for lactating rats fed a semisynthetic diet with 17.4 MJ ME/kg dry matter and 20.8 % protein in dry matter.
    Notes: Zusammenfassung In der vorliegenden Arbeit wurde der Einfluß unterschiedlicher Riboflavinzulagen zum Futter (0 bis 4 000 mg/kg) während der Laktation auf die Riboflavinkonzentrationen in Leber, Restkörper (ausgebluteter Gesamtkörper ohne Magen-Darm-Trakt und Leber) und Milch von Ratten untersucht. Der Versuch dauerte bis zum 14. Laktationstag; Milchproben wurden am 7. und am 13. Laktationstag gewonnen. Die Riboflavinkonzentration der Milch erhöhte sich mit steigender Zulage stetig, wobei im Bereich zwischen 0 und 10 mg Riboflavinzulage/kg Futter eine lineare und im Bereich zwischen 12 und 4 000 mg/kg eine logarithmische Funktion vorlag. Die maximale Riboflavinkonzentration in der Milch bei einer Zulage von 4 000 mg/kg war dabei etwa zwölfmal so hoch wie bei fehlender Zulage. Bei Riboflavinzulagen bis 12 mg/kg unterschieden sich die Riboflavinkonzentrationen der Milch am 7. und 13. Laktationstag nicht. Bei den höheren Zulagen waren die Konzentrationen der Milch am 13. Laktationstag im Mittel um 25 % höher als am 7. Laktationstag. Im Gegensatz zur Milch zeigte sich in Leber und Restkörper eine Sättigung der Riboflavinkonzentrationen, die bei einer Riboflavinzulage von 6 mg/kg (Leber) bzw. 10 mg/kg (Restkörper) erreicht war. Die maximalen Riboflavinkonzentrationen bei Zulagen von 4 000 mg/kg waren dabei 1,9 (Leber) bzw. 2,3 (Restkörper) mal so hoch wie bei fehlender Riboflavinzulage. Diese Befunde sprechen für eine ausgeprägte homöostatische Kontrolle der Riboflavinkonzentrationen im Organismus. Anhand von Dosis-Wirkungsbeziehungen mit den Riboflavinkonzentrationen in Leber und Restkörper als Wirkungskriterien leitete sich bei Verwendung des halbsynthetischen Futters (17,4 MJ ME/kg Trockenmasse (T), 20,8 % Rohprotein in T) ein Riboflavinbedarf von 8 bis 9 mg/kg Futter für die laktierende Ratte ab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01611397
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  • 12
    Electronic Resource
    Electronic Resource
    Influence of environmental temperature on in vivo energy expenditure and in vitro ouabain-sensitive respiration in duodenal mucosa and liver in rats fed different levels of dietary fibre or protein (1997)
    Springer
    European journal of nutrition 36 (1997), S. 278-284 
    Details
    ISSN: 1436-6215
    Keywords: Environmental temperature ; energy expenditure ; ouabain-sensitive respiration ; duodenal mucosa ; liver ; rats ; Umgebungstemperatur ; Energieumsatz ; Quabain-sensitive Respiration ; Duodenalmukosa ; Leber ; Ratten
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Die Wirkung der Umgebungstemperatur (18°C oder 28°C) und des Fasergehalts in der Diät (g je kg Trockensubstanz (TS) niedrig - 68, mittel - 110, hoch - 157) oder des Proteingehalts (g je kg TS niedrig - 91, mittel- 171, hoch - 262) auf den Verdauungstrakt, die Darmmasse, den Energieumsatz und auf die mit der Na+, K+-ATPase-Aktivität zusammenhängenden Respiration von Duodenalmukosa und Leber wurde bei 72 Wistar-Ratten in wiederholten Experimenten untersucht. Der Gesamte und Quabain-sensitive (ein Maß der Na+, K+-ATPase Aktivität) O2-Verbrauch der Gewebe wurde in vitro polarographisch ermittelt (YSI-biologische Sauerstoff-Erfassung nach dem Clark-Meßprinzip). Die Wärmeproduktion (WP) intakter Tiere wurde über Respirationskammern mit offenem Gasaustausch erfaßt. Die bei 18°C gehaltenen Ratten wiesen im Vergleich zu 28°C eine höhere Darmmasse auf. Die Masse an leerem Dünndarm, Caecum und Colon stieg mit ansteigendem Fasergehalt in der Diät (P〈0.05). Die WP als Korrelat der umsetzbaren Energie war nur im 1. Experiment höher (P〈0.05) bei 18°C als bei 28°C. Bei niedriger Proteinstufe war die WP signifikant höher (P 0.05) als bei den anderen Stufen. Verglichen mit 28°C erzeugte 18°C einen ansteigenden Gesamt- und Quabain-sensitiven O2-Verbrauch in der Duodenalmukosa. Die Leber reagierte nicht auf Temperaturunterschiede. Jedoch war ihr Quabain-sensitiver O2-Verbrauch bei niedrigem Proteingehalt in der Nahrung höher (P〈0.05) als bei den anderen Varianten. Bei niedrigem Fasergehalt war der gesamte und Quabain-sensitive O2-Verbrauch der Duodenalmukosa höher als bei den anderen Fasergehaltsvarianten. Die In-vitro-Ergebnisse stimmten mit der WP und dem O2-Verbrauch intakter Tiere überein.
    Notes: Summary Seventy two Wistar rats were used in two repeat studies to investigate the effect of environmental temperature (18°C or 28°C) and increasing levels of dietary fibre (low, 68 g/kg DM; medium 110 g/kg DM; high, 157 g/kg DM) or protein (low, 91 g/kg DM; medium, 171 g/kg DM; high, 262 g/kg DM) on digestive tract, visceral organ size, energy metabolism, and respiration attributable to Na+,K+-ATPase activity in duodenal mucosa and liver. Total and ouabain-sensitive (a measure of Na+,K+-ATPase activity) O2 consumptionin vitro of tissues were measured polarographically using a Clark-style YSI biological O2 monitor. Whole body heat production (in vivo) was measured using open-circuit respiration chambers. The weight of the visceral organs was higher in rats housed at 18°C than at 28°C. The empty weight of the small intestine, caecum, and colon increased as the level of dietary fibre increased (P 0.05). Heat production as a proportion of metabolizable energy was higher (P〈0.05) at 18°C than at 28°C in the first experiment but this difference was not significant in the second experiment. Rats fed the low protein diet had significantly higher (P〉0.05) heat production than those fed medium or high protein diets. Compared to 28°C, environmental temperature of 18°C caused an increased total and ouabain-sensitive O2 consumption in duodenal mucosa. There was no significant effect of environmental temperature on total and ouabain-sensitive O2 consumption in the liver. However, ouabain-sensitive O2 consumption in liver was significantly higher (P 0.05) when rats were fed a low protein diet compared to the medium or high protein diet. Total and ouabain-sensitive O2 consumption increased in duodenal mucosa of rats fed low level of dietary fibre compared to the medium or high dietary fibre diets. Thein vitro results corresponded with the whole animal energy expenditure and O2 consumptionin vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01617798
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  • 13
    Electronic Resource
    Electronic Resource
    Resuscitation of cadaveric livers from non-heart-beating donors after warm ischemic insult: a novel technique tested in the rat (1996)
    Springer
    Cellular and molecular life sciences 52 (1996), S. 661-663 
    Details
    ISSN: 1420-9071
    Keywords: Non-heart-beating donor ; liver ; oxygen ; persufflation ; aerobic ischemia ; transplantation ; preservation ; resuscitation ; viability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Clinical liver transplantation has become the therapy of choice in end-stage liver disease, but the limited availability of suitable donor organs still impedes its widespread application. In order to increase the availability of donor organs for liver transplantation, it would be advantageous if ischemically damaged livers could be resuscitated from cadavers in which the heart has stopped beating. A method for doing this has been developed in a rat model. Compared to livers excised from rats in which the heart is still beating, severe deteriorations of tissue integrity and functional performance were evident in predamaged livers after cold preservation without supplementary treatment. A treatment of those livers which included an antioxidant rinse with superoxide dismutase, and venous vascular insufflation of gaseous oxygen during preservation, completely prevented tissue alterations upon reperfusion, and promoted a functional recovery of the livers, making them comparable to organs harvested from heart-beating donors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01925569
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  • 14
    Electronic Resource
    Electronic Resource
    Oyster mushroom (Pleurotus ostreatus) reduces the activity of 3-hydroxy-3-methylglutaryl CoA reductase in rat liver microsomes (1995)
    Springer
    Cellular and molecular life sciences 51 (1995), S. 589-591 
    Details
    ISSN: 1420-9071
    Keywords: Oyster mushroom (Pleurotus ostreatus) ; cholesterol ; serum ; lipoproteins ; liver ; HMG-CoA reductase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The effect of dried oyster mushroom (Pleurotus ostreatus) on cholesterol (C) content in serum, in lipoproteins and in liver, and on the activity of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase in liver microsomes, was studied in male rats (strain Wistar, initial body weight 75 g) fed on low-cholesterol (9 mg/100 g) and high-cholesterol (0.3%) diets. Addition of 5% oyster mushroom to both diets reduced significantly the C-content in serum (by 30%), in very-low- and low-density lipoproteins (in a 1∶1 ratio to the decrease of total serum C) and in liver (by 50%), as well as the activity of HMG-CoA reductase (by more than 30%).
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    URL: http://dx.doi.org/10.1007/BF02128749
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    Plasma and hepatic antioxidant control and vitamin A nutritional status (1996)
    Springer
    Cellular and molecular life sciences 52 (1996), S. 687-690 
    Details
    ISSN: 1420-9071
    Keywords: Vitamin A ; diet ; rats ; plasma ; liver ; scavengers ; antioxidant enzymes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Twenty-seven rats were divided into three groups and fed on diets containing 0.3, 6 or 60 RE (retinol equivalent) retinyl palmitate/g food. After 7 weeks, hepatic vitamin A uptake was found to be more efficient in vitamin A-deficient rats than in rats given adequate vitamin A. We showed that during the metabolic adaptation of the animals to the level of vitamin A in the diet, extensive modifications occur in the antioxidant defences of the organism. In parallel with the increase in the level of vitamin A, the decrease in the level of α-tocopherol in the plasma can bring about a greater susceptibility of the lipoproteins to oxidative stress. Similarly, the decrease in the hepatic α-tocopherol level and in glutathione peroxidase activity leads to the weakening of the liver's antioxidant defences.
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    URL: http://dx.doi.org/10.1007/BF01925575
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  • 16
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    Interindividual variation in the enzymatic 15-keto-reduction of 13,14-dihydro-15-keto-prostaglandin E1 in human liver and in human erythrocytes (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 147-153 
    Details
    ISSN: 1432-1041
    Keywords: Key wordsProstaglandin E1 ; Carbonyl reductase; 13 ; 14-dihydro-15-keto-PGE1 ; 13 ; 14-dihydro-PGE1 ; human ; liver ; erythrocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The therapeutic response to PGE1 is highly variable, and a contribution by variable formation of its active tertiary metabolite PGE0 is in question. Hence, the objective of this study was to assess the person-to-person variation of the reduction of the inactive intermediate metabolite 15-KD PGE1 by human liver and human erythrocytes in forming the active metabolite PGE0. Methods: Source of enzyme was lysed erythrocytes from 29 donors, and a bank of 37 donor livers including specimens from 15 children. Tritium-labelled 13,14-dihydro-15-keto-prostaglandin E1 (15-KD PGE1) was used at low nanomolar concentrations and found to be converted almost exclusively to the more polar compound 13,14-dihydro-prostaglandin E1 (PGE0) by an NADPH-dependent carbonyl reductase. The identity of the product PGE0 was established by comparison of its chromatographic and mass spectral characteristics with authentic PGE0. Results: Lysed erythrocytes had readily measurable enzymatic activity; differences between the preparations from 29 subjects were very small with only a twofold range of variation. In contrast to lysed erythrocytes, intact erythrocytes did not catalyse the reaction so that the erythrocyte activity should be medically immaterial. 15-KD PGE1 15-ketoreductase activity of liver cytosol averaged 61.1 fmol · min−1 · mg−1 protein in preparations from 37 human livers. Individual activities varied over an almost tenfold range, with indications of a non-normal distribution. Kinetic studies of selected specimens showed substantially different Vmax values but indistinguishable k M values, suggesting that the individual variation in 15-KD PGE1 15-ketoreduction is the result of differences in enzyme concentration rather than of structural enzyme variations. The activity in 15 livers from children was significantly lower than in those from adults. Inhibition data suggest that both the liver and the erythrocyte enzymes belong to the class of carbonyl reductases. Conclusions: The variations in hepatic enzyme activity may be expected to affect the transformation of 15-KD PGE1 to the active metabolite PGE0 in vivo. The clinical significance remains to be explored.
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    Variability in the rate of 6-mercaptopurine methylation in the erythrocytes, liver and kidney in an Italian population (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 23-29 
    Details
    ISSN: 1432-1041
    Keywords: Key words 6-Mercaptopurine ; Thiopurine methyltransferase ; Polymorphism; erythrocytes ; liver ; kidney ; newborns ; adults
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective. The polymorphism of erythrocyte thiopurine methyltransferase (TPMT) is genetically regulated as an autosomal codominant trait, and so should be congenital. Results. We tested this hypothesis by measuring TPMT activity in erythrocyte preparations from adults and newborns and observed polymorphic distribution of TPMT activity in the adult and newborn erythrocytes. The activity of TPMT was higher in red cells from the newborns than adults. The frequency distribution of TPMT activity was also investigated in the liver and kidney. In the kidney, TPMT activity fell into two subgroups, whereas in the liver the distribution pattern was more complex. The activity of TPMT in erythrocytes and liver from the same subject was correlated, but the values of only half the cases fell within the 95% confidence limits, suggesting that the control of hepatic and/or erythrocyte TPMT is multifactorial.
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    URL: http://dx.doi.org/10.1007/s002280050155
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  • 18
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    Comparative study of DNA adducts levels in white sucker fish (Catostomus commersoni) from the basin of the St. Lawrence River (Canada) (1995)
    Springer
    Molecular and cellular biochemistry 148 (1995), S. 133-138 
    Details
    ISSN: 1573-4919
    Keywords: DNA adducts ; liver ; fish ; 32P-postlabelling ; polycyclic aromatic hydrocarbons ; genotoxic biomarker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The levels of DNA adducts in the hepatic tissue of the white sucker fish speciesCatostomus commersoni were determined by32P-postlabelling. The fish were caught at four sites: two sites near the city of Windsor (Québec, Canada) on the St. François River, a downstream tributary of the St. Lawrence River, and two sites in the St. Lawrence River itself, near the city of Montréal (Québec, Canada). The latter sites are known to be contaminated by many pollutants including polycyclic aromatic hydrocarbons. Total adduct levels in all fish ranged from 25.1–178.0 adducts per 109 nucleotides. White sucker from the selected sites of the St. Lawrence River had a significantly higher mean level of DNA adducts than those of the St. François River (129.4 vs 56.8, respectively). These results suggest that the effluents of many heavy industries (e.g. from a Soderberg aluminium plant) flowing in the St. Lawrence River are more likely to produce genotoxic damage to fish than those released in one of its tributary, and mainly associated to the activities of a small town and a nearby pulp and paper mill.
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    URL: http://dx.doi.org/10.1007/BF00928150
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  • 19
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    The Ca2+ threshold for the mitochondrial permeability transition and the content of proteins related to Bcl-2 in rat liver and Zajdela hepatoma mitochondria (1999)
    Springer
    Molecular and cellular biochemistry 194 (1999), S. 251-256 
    Details
    ISSN: 1573-4919
    Keywords: Bcl-2 ; Ca2+ ; hepatoma ; liver ; mitochondrial permeability transition ; tumor cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Zajdela hepatoma mitochondria were able to accumulate two to five times more Ca2+ than rat liver mitochondria before the permeability transition was induced. Pulses of Ca2+ were given in series to determine the Ca2+ threshold by recording changes in [Ca2+] and membrane potential, the permeability transition causing the release of accumulated Ca2+ and collapse of the membrane potential. Hepatoma mitochondria had lower Ca2+ efflux rates, higher net Ca2+ uptake rates and lower phosphorylation rates than liver mitochondria. Since the differences in regard to induction of the permeability transition might be due to higher expression of the Bcl-2 protein in hepatoma cells than in hepatocytes, the transcription of Bcl-2 and the proteins reacting with a Bcl-2 polyclonal antiserum were estimated by Northern and Western blotting, respectively. Hepatoma cells had two Bcl-2 specific mRNA bands of 7 and 2.4 kb, and substantial amounts of the Bcl-2 protein, whereas in liver cells and mitochondria these were not detected. Both cell lines had a reactive band at 19-20 kDa, and hepatocytes a small band at 31-32 kDa. Bcl-2 antibodies stimulated the permeability transition potently in hepatoma mitochondria.
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    URL: http://dx.doi.org/10.1023/A:1006913526643
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  • 20
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    Genetics of aryl hydrocarbon hydroxylase induction in mice: Response of the lung to cigarette smoke and 3-methylcholanthrene (1977)
    Springer
    Biochemical genetics 15 (1977), S. 723-740 
    Details
    ISSN: 1573-4927
    Keywords: aryl hydrocarbon hydroxylase, gene loci controlling ; cigarette smoke ; mice ; lung ; liver ; 3-methylcholanthrene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract When mice from different inbred strains are injected intraperitoneally with 3-methylcholanthrene (MC), the activity of aryl hydrocarbon hydroxylase (AHH) rapidly increases in livers of some strains but not others. AHH plays a role in the metabolism of polycyclic hydrocarbons. Alleles at a small number of loci account for most of the variation in inducibility of hepatic AHH among mice, when MC is used as the inducing agent. Cigarette smoke is a common source of carcinogenic polycyclic hydrocarbons in the environment. Since some of the hydrocarbons in cigarette smoke are metabolized by AHH, the activity of AHH in tissues may affect the carcinogenicity of smoke in those tissues. The purpose of these experiments was to see whether induction of AHH in lung in response to cigarette smoke is regulated by the same genes that regulate induction of AHH in liver in response to MC. Mouse strains AKR/J and C57L/J and six recombinant inbred (RI) lines derived from them were tested for the response of AHH in lung and liver to parenteral MC or inhalation of cigarette smoke. Inducibility (the ratio of MC-induced AHH activities to basal AHH activities) in liver from MC-treated RI lines is bimodal and compatible with Mendelian segregation of genes at a small number of loci. Increased activities of AHH in MC-treated liver are associated with increased ability to metabolize BP and whole smoke condensates to mutagens detected by Salmonella typhimurium TA1538. Inducibility of AHH in lung in response to MC is not bimodal, and no definite conclusion about the number of loci can be made. When actual levels of AHH activity are considered, following the administration of MC as inducing agent, there is a correlation (r=0.89, p〈0.01) between AHH levels in liver and lung, suggesting that some genes affecting liver also affect lung. Basal and MC-induced AHH levels in lung are also correlated (r=0.86, p〈0.01). Mice with high basal activities have two to threefold higher levels of AHH after MC treatment than do mice with low basal activities. Induction of AHH in pulmonary tissues occurs in all mice after either parenteral MC or smoke inhalation. In contrast to MC treatment, AHH activities in lungs following smoke inhalation are not correlated with AHH levels in liver after MC (r=0.49) and are only weakly correlated with basal (r=0.66, 0.05〈p〈0.10) pulmonary levels. The correlation between MC-induced and smoke-induced AHH activities in lung is weak (r=0.63, 0.05〈p〈0.10). We conclude that the genetic regulation of AHH activity in lung is not as simple as the genetic regulation of AHH activity in liver, especially when complex inducing agents such as cigarette smoke are used.
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    URL: http://dx.doi.org/10.1007/BF00484100
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    In vivo modulation of N-myristoyltransferase activity by orthovanadate (1995)
    Springer
    Molecular and cellular biochemistry 153 (1995), S. 151-155 
    Details
    ISSN: 1573-4919
    Keywords: sodium orthovanadate ; diabetes ; N-myristoyltransferase ; liver ; membrane-associated ; vanadate ; obese Zucker rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract N-Myristoyltransferase (NMT) catalyses the transfer of myristate from myristoyl-CoA to the NH2-terminal glycine residue of several proteins and are important in signal transduction. STZ-induced diabetes (an animal model for insulin-dependent diabetes mellitus, IDDM) resulted in a 2-fold increase in rat liver NMT activity as compared with control animals. In obese Zucker (fa/fa) rats (an animal model for non-insulin dependent diabetes mellitus, NIDDM) there was a∼4.7-fold lower liver particulate NMT activity as compared with the control lean rat livers. Administration of sodium orthovanadate to the diabetic rats normalised liver NMT activity. These results would indicate that the rat liver particulate N-myristoyltransferase activity appears to be inversely proportional to the level of plasma insulin, implicating insulin in the control of N-myristoylation.
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    URL: http://dx.doi.org/10.1007/BF01075931
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    On the regulation of cellular energetics in health and disease (1996)
    Springer
    Molecular and cellular biochemistry 160-161 (1996), S. 195-208 
    Details
    ISSN: 1573-4919
    Keywords: respiration ; ADP diffusion ; heart ; skeletal muscle ; liver ; brain ; in vivo regulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Very recent experimental data, obtained by using the permeabilized cell technique or tissue homogenates for investigation of the mechanisms of regulation of respiration in the cells in vivo, are shortly summarized. In these studies, surprisingly high values of apparent Km for ADP, exceeding that for isolated mitochondria in vitro by more than order of magnitude, were recorded for heart, slow twitch skeletal muscle, hepatocytes, brain tissue homogenates but not for fast twitch skeletal muscle. Mitochondrial swelling in the hypo-osmotic medium resulted in the sharp decrease of the value of Km for ADP in correlation with the degree of rupture of mitochondrial outer membrane, as determined by the cytochrome c test. Very similar effect was observed when trypsin was used for treatment of skinned fibers, permeabilized cells or homogenates. It is concluded that, in many but not all types of cells, the permeability of the mitochondrial outer membrane for ADP is controlled by some cytoplasmic protein factor(s). Since colchicine and taxol were not found to change high values of the apparent Km for ADP, the participation of microtubular system seems to be excluded in this kind of control of respiration but studies of the roles of other cytoskeletal structures seem to be of high interest. In acute ischemia we observed rapid increase of the permeability of the mitochondrial outer membrane for ADP due to mitochondrial swelling and concomitant loss of creatine control of respiration as a result of dissociation of creatine kinase from the inner mitochondrial membrane. The extent of these damages was decreased by use of proper procedures of myocardial protection showing that outer mitochondrial membrane permeability and creatine control of respiration are valuable indices of myocardial preservation. In contrast to acute ischemia, chronic hypoxia seems to improve the cardiac cell energetics as seen from better postischemic recovery of phosphocreatine, and phosphocreatine overshoot after inotropic stimulation. In general, adaptational possibilities and pathophysiological changes in the mitochondrial outer membrane system point to the central role such a system may play in regulation of cellular energetics in vivo.
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    URL: http://dx.doi.org/10.1007/BF00240050
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    Effect of cadmium, mercury and copper on partially purified hepatic flavokinase of rat (1997)
    Springer
    Molecular and cellular biochemistry 167 (1997), S. 73-80 
    Details
    ISSN: 1573-4919
    Keywords: cadmium ; zinc ; liver ; flavokinase ; thiol group
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of cadmium (Cd2+), mercury (Hg2+) and copper (Cu2+) was studied with partially purified flavokinase (ATP:riboflavin 5′-phosphotransferase EC 2.7.1.26) from rat liver. All the divalent heavy metal cations inhibited flavokinase activity in a concentration-dependent manner. The inhibitory effect of cadmium on the enzyme was completely reversed by increasing concentration, of Zinc (Zn2+) indicating a competition between Zn2+ and Cd2+ for binding with the enzyme. A competition between riboflavin and Cd2+ is also evident from the present investigation. These observations hint at the possibility that Zn2+ and Cd2+ probably compete for the same site on the enzyme where riboflavin binds. However, inhibition of flavokinase by Hg2+ could not be reversed by Zn2+. Our studies further reveal that hepatic flavokinase appears to contain an essential, accessible and functional thiol group(s) which is evident from a concentration dependent inhibition of activity by sulfhydryl reagent s like parachloromercuribenzoate (PCMB), 5,5′-dithiobis (2-nitrobenzoic acid)(DTNB), and N-ethylmaleimide (NEM). Inhibition of flavokinase by sulfhydryl reagents were protected, except in case of NEM inhibition, when the enzyme was incubated with thiol protectors like glutathione (GSH) and dithiothreitol (DTT). Furthermore, the enzyme could also be protected from the inhibitory effect of Cd2+ and Hg2+ by GSH and DTT suggesting that Cd2+ probably interacts with a reactive thiol group at or near the active site of enzyme in bringing about its inhibitory effect. (Mol Cell Biochem 167: 73-80, 1997)
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    URL: http://dx.doi.org/10.1023/A:1006815504302
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    Studies on hepatic injury and antioxidant enzyme activities in rat subcellular organelles following in vivo ischemia and reperfusion (1997)
    Springer
    Molecular and cellular biochemistry 176 (1997), S. 337-347 
    Details
    ISSN: 1573-4919
    Keywords: antioxidant enzymes ; sub-cellular organelles ; liver ; ischemia-reperfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The activities of rat hepatic subcellular antioxidant enzymes were studied during hepatic ischemia/reperfusion. Ischemia was induced for 30 min (reversible ischemia) or 60 min (irreversible ischemia). Ischemia was followed by 2 or 24 h of reperfusion. Hepatocyte peroxisomal catalase enzyme activity decreased during 60 min of ischemia and declined further during reperfusion. Peroxisomes of normal density (d = 1.225 gram/ml) were observed in control tissues. However, 60 min of ischemia also produced a second peak of catalase specific activity in subcellular fractions corresponding to newly formed low density immature peroxisomes (d = 1.12 gram/ml). The second peak was also detectable after 30 min of ischemia followed by reperfusion for 2 or 24 h. Mitochondrial and microsomal fractions responded differently. MnSOD activity in mitochondria and microsomal fractions increased significantly (p 〈 0.05) after 30 min of ischemia, but decreased below control values following 60 min of ischemia and remained lower during reperfusion at 2 and 24 h in both organelle fractions. Conversely, mitochondrial and microsomal glutathione peroxidase (GPx) activity increased significantly (p 〈 0.001) after 60 min of ischemia and was sustained during 24 h of reperfusion. In the cytosolic fraction, a significant increase in CuZnSOD activity was noted following reperfusion in animals subjected to 30 min of ischemia, but 60 min of ischemia and 24 h of reperfusion resulted in decreased CuZnSOD activity. These studies suggest that the antioxidant enzymes of various subcellular compartments respond to ischemia/reperfusion in an organelle or compartment specific manner and that the regulation of antioxidant enzyme activity in peroxisomes may differ from that in mitochondria and microsomes. The compartmentalized changes in hepatic antioxidant enzyme activity may be crucial determinant of cell survival and function during ischemia/reperfusion. Finally, a progressive decline in the level of hepatic reduced glutathione (GSH) and concomitant increase in serum glutamate pyruvate transaminase (SGPT) activity also suggest that greater tissue damage and impairment of intracellular antioxidant activity occur with longer ischemia periods, and during reperfusion.
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    URL: http://dx.doi.org/10.1023/A:1006829902442
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    Differential time course of liver and kidney glucose-6 phosphatase activity during long-term fasting in rat correlates with differential time course of messenger RNA level (1996)
    Springer
    Molecular and cellular biochemistry 155 (1996), S. 37-41 
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    ISSN: 1573-4919
    Keywords: glucose-6 phosphatase ; messenger RNA ; liver ; kidney ; fasting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract We have studied the role of Glc6Pase mRNA abundance in the time course of Glc6Pase activity in liver and kidney during long-term fasting in rat. Refered to the mRNA level in the fed state, Glc6Pase mRNA abundance was increased by 3.5 ± 0.5 and 3.7 ± 0.5 times (mean ± S.E.M., n = 5) in the 24 h and 48 h-fasted liver, respectively. Then, the liver Glc6Pase mRNA was decreased to the level of the fed liver after 72 and 96 h of fasting (1.0 ± 0.3 and 1.4 ± 0.3). In the kidney, Glc6Pase mRNA abundance was increased by 2.7 ± 1.0 and 5 ± 1.2 times at 24 and 48 h of fasting, respectively. Then, it plateaued at the level of the 48 h fasted kidney after 72 h and 96 h of fasting (4.5 ± 1.0 and 4.3 ± 1.0). After 24 and 48 h-refeeding, the abundance of Glc6Pase mRNA in 48 h-fasted rats was decreased to the level found in the liver and kidney of fed rats. The time course of the activity of Glc6Pase catalytic subunit during fasting and refeeding was strikingly parallel to the time course of Glc6Pase mRNA level in respective tissues. These data strongly suggest that the differential expression of Glc6Pase activity in liver and kidney in the course of fasting may be accounted for by the respective time course of mRNA abundance in both organs.
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    URL: http://dx.doi.org/10.1007/BF00714331
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    Alterations in isoforms of glutathione S-transferase in liver and kidney of cadmium exposed rhesus monkeys: Purification and kinetic characterization (1997)
    Springer
    Molecular and cellular biochemistry 166 (1997), S. 55-63 
    Details
    ISSN: 1573-4919
    Keywords: cadmium ; glutathione S-transferase ; liver ; kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Exposure of animals to cadmium (Cd) (25 mg kg-1 body wt day-1) for 10 weeks resulted in preferential accumulation of the metal in liver and kidney. Cd accumulation concomitantly increased zinc (Zn) concentration in both the organs. However, significant decrease in copper level was observed in liver, whereas kidney showed increase in copper (Cu) level. Cd exposure resulted in decreased total GST activity in liver (63%) and kidney (41%) as compared to control group monkeys on normal diet (group I). On isoelectric focusing (IFP) control liver GST segregated into thirteen isoenzymes, while in Cd-treated experimental animals (group II) liver GST resolved into nine isoenzymes. Similarly kidney GST from control animals separated into seven isoenzymes as compared to four isoenzymes from Cd-treated animals. Kinetic analysis showed that Cd exposure did not alter the affinity constant (Km) of GST for GSH and CDNB whereas maximal velocity (Vmax) for these substrates decreased as compared to controls in both the organs, indicating inhibition in GST synthesis by Cd. Cd resulted in a noncompetitive type of inhibition with respect to GSH in vitro. On isoelectric focussing GST of liver and kidney in group II resolved into nine and four isoenzymes as compared to thirteen and seven in group I, showing loss of four basic isoenzymes in case of liver and three isoenzymes in case of kidney. Monkey liver and kidney expressed all the three classes of GST isoenzymes i.e. α, µ and π, which were serologically identical to human α, µ and π GSTs. (Mol Cell Biochem 166: 55-63, 1997)
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    Retinol uptake and metabolism, and cellular retinol binding protein expression in an in vitro model of hepatic stellate cells (1998)
    Springer
    Molecular and cellular biochemistry 187 (1998), S. 11-21 
    Details
    ISSN: 1573-4919
    Keywords: vitamin-A ; cellular retinol-binding protein ; liver ; hepatic stellate cells ; lipocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Liver is a major site of retinoid metabolism and storage, and more than 80% of the liver retinoids are stored in hepatic stellate cells. These cells represent less than 1% of the total liver protein, reaching a very high relative intracellular retinoid concentration. The plasma level of retinol is maintained close to 2 μM, and hepatic stellate cells have to be able both to uptake or to release retinol depending upon the extracellular retinol status. In view of their paucity in the liver tissue, stellate cells have been studied in primary cultures, in which they loose rapidly the stored lipids and retinol, and convert spontaneously into the activated myofibroblast phenotype, turning a long-term study of their retinol metabolism impossible. We have analyzed the retinol metabolism in the established GRX cell line, representative of stellate cells. We showed that this cell line behaves very similarly, with respect the retinol uptake and release, to primary cultures of hepatic stellate cells. Moreover, we showed that the cellular retinol binding protein (CRBP-I) expression in these cells, relevant for both uptake and esterification of retinol, responds to the extracellular retinol status, and is correlated to the retinol binding capacity of the cytosol. Its expression is not associated with the overall induction of the lipocyte phenotype by other agents. We conclude that the GRX cell line represents an in vitro model of hepatic stellate cells, and responds very efficiently to wide variations of the extracellular retinol status by autonomous controls of its uptake, storage or release.
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    URL: http://dx.doi.org/10.1023/A:1006886308490
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    Gene gun-mediated in vivo analysis of tissue-specific repression of gene transcription driven by the chicken ovalbumin promoter in the liver and oviduct of laying Hens (1998)
    Springer
    Molecular and cellular biochemistry 185 (1998), S. 27-32 
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    ISSN: 1573-4919
    Keywords: chicken ; oviduct ; liver ; tissue-specific repression ; in vivo gene transfer ; gene gun
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract In order to search tissue-specific elements in the 5′-upstream promoter region, gene gun was used to transfect in vivo plasmid DNAs with varying lengths of truncated ovalbumin promoter fused to the CAT reporter gene to the oviduct and liver of laying hens. The results indicated that in the oviduct, consistently high reporter gene expression was observed irrespective of the length of the truncated ovalbumin gene promoters, whereas in the liver the ovalbumin promoter extending from -3200 to +8 bp suppressed substantially the reporter gene expression compared with consistently high gene expression obtained by the ovalbumin promoters from -2800 to +8 bp or shorter length. It was concluded, therefore, that a tissue-specific silencer-like element might reside most likely in the ovalbumin gene promoter region between -3200 and -2800 bp which represses the ovalbumin gene transcription in the liver, but not in the oviduct of laying hens.
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    URL: http://dx.doi.org/10.1023/A:1016507900718
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    In vitro desaturation or elongation of monotrans isomers of linoleic acid by rat liver microsomes (1998)
    Springer
    Molecular and cellular biochemistry 185 (1998), S. 17-25 
    Details
    ISSN: 1573-4919
    Keywords: trans polyunsaturated fatty acid ; linoleic acid ; desaturation elongation ; microsomes ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Several nutritional studies have shown the in vivo conversion of the 9c,12t-18:2 and 9t,12c-18:2 into long chain polyunsaturated fatty acids (PUFA) containing 20 carbons (geometrical isomers of eicosadienoic and eicosatetraenoic acids). In the present work, some in vitro studies were carried out in order to have precise information on the conversion of these two isomers. In a first set of experiments, studies were focused on the in vitro Δ6 desaturation, the first regulatory step of the biosynthesis of n-6 long chain PUFA, from 9c,12c-18:2. Rat liver microsomes were prepared and incubated under desaturation conditions with [1-14C]-9c,12c-18:2 in presence of unlabelled 9c,12t-, 9t,12c- or 9t,12t-18:2. The data show that each trans isomer induced a decrease of the Δ6 desaturation of the [1-14C]-9c,12c-18:2, but the 9c,12t-18:2 was the most potent inhibitor (up to 63%). Rat liver microsomes were also incubated with [1-14C]-9c,12c-18:2, [1-14C]-9c,12t-18:2 or [1-14C]-9t,12c-18:2 under desaturation conditions. The results indicated that 18:2 Δ9c,12t is a much better substrate for desaturase than 9t,12c-18:2. Moreover, the conversion levels of [1-14C]-9c,12t-18:2 was similar to what was observed for its all cis homologue, at low substrate concentration only. In a second set of experiments, in vitro elongation studies of each mono-trans 18:2 isomers and 9c,12c-18:2 were carried out. For that purpose, rat liver microsomes were incubated with [1-14C]-9c,12c-18:2, [1-14C]-9c,12t-18:2 or [1-14C]-9t,12c-18:2 under elongation conditions. The data show that [1-14C]-9t,12c-18:2 is better elongated than 9c,12c-18:2 while the amount of product formed from [1-14C]-9c,12t-18:2 was lower than was produced from the 9c,12c-18:2. Thus, the desaturation enzymes presented a higher affinity for the 9c,12t-18:2 whereas the elongation enzyme presented a higher affinity for the 9t,12c-18:2.
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    Selective changes in the protein-turnover rates and nature of growth induced in trout liver by long-term starvation followed by re-feeding (1999)
    Springer
    Molecular and cellular biochemistry 201 (1999), S. 1-10 
    Details
    ISSN: 1573-4919
    Keywords: hyperplasia ; hypertrophy ; liver ; nucleic-acid concentration ; protein-growth rate ; protein-turnover rate ; rainbow trout (Oncorhynchus mykiss) ; starvation/re-feeding cycle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract We report upon the effects of a cycle of long-term starvation followed by re-feeding on the liver-protein turnover rates and nature of protein growth in the rainbow trout (Oncorhynchus mykiss). We determined the protein-turnover rate and its relationship with the nucleic-acid concentrations in the livers of juvenile trout starved for 70 days and then re-fed for 9 days. During starvation the total hepatic-protein and RNA contents decreased significantly and the absolute protein-synthesis rate (AS) also fell, whilst the fractional protein-synthesis rate (KS) remained unchanged and the fractional protein-degradation rate (KD) increased significantly. Total DNA content, an indicator of hyperplasia, and the protein:DNA ratio, an indicator of hypertrophy, both fell considerably. After re-feeding for 9 days the protein-accumulation rates (KG, AG) rose sharply, as did KS, AS, KD, protein-synthesis efficiency (KRNA) and the protein-synthesis rate/DNA unit (KDNA). The total hepatic protein and RNA contents increased but still remained below the control values. The protein:DNA and RNA:DNA ratios increased significantly compared to starved fish. These changes demonstrate the high response capacity of the protein-turnover rates in trout liver upon re-feeding after long-term starvation. Upon re-feeding hypertrophic growth increased considerably whilst hyperplasia remained at starvation levels.
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    URL: http://dx.doi.org/10.1023/A:1006953917697
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    In vivo effects of vanadate on hepatic glycogen metabolizing and lipogenic enzymes in insulin-dependent and insulin-resistant diabetic animals (1995)
    Springer
    Molecular and cellular biochemistry 153 (1995), S. 87-94 
    Details
    ISSN: 1573-4919
    Keywords: vanadate ; diabetes ; glycogen synthase ; phosphorylase ; lipogenic enzymes ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The insulin-mimetic action of vanadate is well established but the exact mechanism by which it exerts this effect is still not clearly understood. The role of insulin in the regulation of hepatic glycogen metabolizing and lipogenic enzymes is well known. In our study, we have, therefore, examined the effects of vanadate on these hepatic enzymes using four different models of diabetic and insulin-resistant animals. Vanadate normalized the blood glucose levels in all animal models. In streptozotocin-induced diabetic rats, the amount of liver glycogen and the activities of the active-form of glycogen synthase, both active and inactive-forms of phosphorylase, and lipogenic enzymes like glucose 6-phosphate dehydrogenase and malic enzyme were decreased and vanadate treatment normalized all of these to near normal levels. The other three animal models (db/db mouse, sucrose-fed rats and fa/fa obese Zucker rats) were characterized by hyperinsulinemia, hypertriglyceridemia, increases in activities of lipogenic enzymes, and marginal changes in glycogen metabolizing enzymes. Vanadate treatment brought all of these values towards normal levels. It should be noted that vanadate shows differential effects in the modulation of lipogenic enzymes activities in type I and type II diabetic animals. It increases the activities of lipogenic enzymes in streptozotocin-induced diabetic animals and prevents the elevation of activities of these enzymes in hyperinsulinemic animals. The insulin-stimulated phosphorylation of insulin receptor β subunit and its tyrosine kinase activity was increased in streptozotocin-induced diabetic rats after treatment with vanadate. Our results support the view that insulin receptor is one of the sites involved in the insulin-mimetic actions of vanadate.
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    URL: http://dx.doi.org/10.1007/BF01075922
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    Liver and intestinal fatty acid binding proteins in control and TGFβ1 gene targeted deficient mice (1996)
    Springer
    Molecular and cellular biochemistry 159 (1996), S. 149-153 
    Details
    ISSN: 1573-4919
    Keywords: fatty acid binding protein ; liver ; intestine ; growth factor ; TGFβ1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of transforming growth factor beta-1 (TGFβ1) expression on fatty acid binding proteins was examined in control and two strains of gene targeted TGFβ1-deficient mice. Homozygous TGFβ1-deficient 129 × CF-1, expressing multifocal inflammatory syndrome, had 25% less liver fatty acid binding protein (L-FABP) when compared to control mice. The decrease in L-FABP expression was not due to multifocal inflammatory syndrome since homozygous TGFβ1-deficient/immunodeficient C3H mice on a SLID background had 36% lower liver L-FABP than controls. This effect was developmentally related and specific to liver, but not the proximal intestine, where L-FABP is also expressed. Finally, the proximal intestine also expresses intestinal-FABP (1-FABP) which decreased 3-fold in the TGFβ1-deficient/immunodeficient C3H mice only. Thus, TGFβ1 appears to regulate the expression of L-FABP and I-FABP in the liver and the proximal intestine, respectively.
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    URL: http://dx.doi.org/10.1007/BF00420917
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    The effect of dexamethasone treatment on the expression of the regulatory genes of ketogenesis in intestine and liver of suckling rats (1998)
    Springer
    Molecular and cellular biochemistry 178 (1998), S. 325-333 
    Details
    ISSN: 1573-4919
    Keywords: carnitine palmitoyl transferase I ; mitochondrial HMG-CoA synthase ; dexamethasone ; suckling rats ; ketogenesis ; intestine ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The influence of the injection of dexamethasone on ketogenesis in 12 day old suckling rats was studied in intestine and liver by determining mRNA levels and enzyme activity of the two genes responsible for regulation of ketogenesis: carnitine palmitoyl transferase I (CPT 1) and mitochondrial HMG-CoA synthase. Dexamethasone produced a 2 fold increase in mRNA and activity of CPT I in intestine, but led to a decrease in mitt HMG-CoA synthase. In liver the mRNA levels and activity of both CPT I and mitt HMG-CoA synthase decreased. Comparison of these values with the ketogenic rate of both tissues following dexamethasone treatment suggests that mitt HMG-CoA synthase could be the main gene responsible for the regulation of ketogenesis in suckling rats. The changes produced in serum ketone bodies by dexamethasone, with a profile that is more similar to the ketogenic rate in the liver than that in the intestine, indicate that liver contributes more to ketone body synthesis in suckling rats. Two day treatment with dexamethasone produced no change in mRNA or activity levels for CPT I in liver or intestine. While mRNA levels for mitt HMG-CoA synthase changed little, the enzyme activity is decreased in both tissues.
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    Genetic variation in alkaline phosphatase of the house mouse (Mus musculus) with emphasis on a manganese-requiring isozyme (1979)
    Springer
    Biochemical genetics 17 (1979), S. 1093-1107 
    Details
    ISSN: 1573-4927
    Keywords: Mus musculus ; alkaline phosphatase ; intestine ; kidney ; liver ; blood plasma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Genetic variation among inbred strains is described for electrophoretic migration of alkaline phosphatase from intestine, kidney, blood plasma, and three isozymes of liver. A manganese-requiring isozyme of liver and kidney unaffected by neuraminidase is described, and the locus controlling variation in this isozyme is designated Akp-1. Data from recombinant inbred strains place the locus on chromosome 1 at a distance of 3.6±2.9 cM from the Mls locus on the side distal to the centromere. Test-cross data show the following gene order and recombination percentages: $${\text{Dip - 1 }}19.0 \pm 3.8\% {\text{Lp }}7.4 \pm 2.2\% {\text{Akp - 1}}$$
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    Alcohol dehydrogenase (ADH) isozymes in the AdhN/AdhN strain ofPeromyscus maniculatus (ADH− deermouse) and a possible role of class III ADH in alcohol metabolism (1995)
    Springer
    Biochemical genetics 33 (1995), S. 349-363 
    Details
    ISSN: 1573-4927
    Keywords: alcohol dehydrogenase (ADH) ; liver ; stomach ; ADH− and ADH+ deermouse ; Class I, II, III, and IV ADH ; alcohol metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Although the AdhN/AdhN strain ofPeromyscus maniculatus (so-called ADH− deermouse) has been previously considered to be deficient in ADH, we found ADH isozymes of Classes II and III but not Class I in the liver of this strain. On the other hand, the AdhF/AdhF strain (so-called ADH+ deermouse), which has liver ADH activity, had Class I and III but not Class II ADH in the liver. In the stomach, Class III and IV ADHs were detected in both deermouse strains, as well as in the ddY mouse, which has the normal mammalian ADH system with four classes of ADH. These ADH isozymes were identified as electrophoretic phenotypes on the basis of their substrate specificity, pyrazole sensitivity, and immunoreactivity. Liver ADH activity of the ADH− strain was barely detectable in a conventional ADH assay using 15 mM ethanol as substrate; however, it increased markedly with high concentrations of ethanol (up to 3M) or hexenol (7 mM). Furthermore, in a hydrophobic reaction medium containing 1.0M t-butanol, liver ADH activity of this strain at low concentrations of ethanol (〈100 mM) greatly increased (about sevenfold), to more than 50% that of ADH+ deermouse. These results were attributable to the presence of Class III ADH and the absence of Class I ADH in the liver of ADH− deermouse. It was also found that even the ADH+ strain has low liver ADH activity (〈40% that of the ddY mouse) with 15 mM ethanol as substrate, probably due to low activity in Class I ADH. Consequently, liver ADH activity of this strain was lower than its stomach ADH activity, in contrast with the ddY mouse, whose ADH activity was much higher in the liver than in the stomach, as well as other mammals. Thus, the ADH systems in both ADH− and ADH+ deermouse were different not only from each other but also from that in the ddY mouse; the ADH− strain was deficient in only Class I ADH, and the ADH+ strain was deficient in Class II ADH and down-regulated in Class I ADH activity. Therefore, Class III ADH, which was found in both strains and activated allosterically, may participate in alcohol metabolism in deermouse, especially in the ADH− strain.
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    Alcohol dehydrogenase (ADH) isozymes in the AdhN/AdhN strain ofPeromyscus maniculatus (ADH− deermouse) and a possible role of class III ADH in alcohol metabolism (1995)
    Springer
    Biochemical genetics 33 (1995), S. 349-363 
    Details
    ISSN: 1573-4927
    Keywords: alcohol dehydrogenase (ADH) ; liver ; stomach ; ADH− and ADH+ deermouse ; Class I, II, III, and IV ADH ; alcohol metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Although the AdhN/AdhN strain ofPeromyscus maniculatus (so-called ADH− deermouse) has been previously considered to be deficient in ADH, we found ADH isozymes of Classes II and III but not Class I in the liver of this strain. On the other hand, the AdhF/AdhF strain (so-called ADH+ deermouse), which has liver ADH activity, had Class I and III but not Class II ADH in the liver. In the stomach, Class III and IV ADHs were detected in both deermouse strains, as well as in the ddY mouse, which has the normal mammalian ADH system with four classes of ADH. These ADH isozymes were identified as electrophoretic phenotypes on the basis of their substrate specificity, pyrazole sensitivity, and immunoreactivity. Liver ADH activity of the ADH− strain was barely detectable in a conventional ADH assay using 15 mM ethanol as substrate; however, it increased markedly with high concentrations of ethanol (up to 3M) or hexenol (7 mM). Furthermore, in a hydrophobic reaction medium containing 1.0M t-butanol, liver ADH activity of this strain at low concentrations of ethanol (〈100 mM) greatly increased (about sevenfold), to more than 50% that of ADH+ deermouse. These results were attributable to the presence of Class III ADH and the absence of Class I ADH in the liver of ADH− deermouse. It was also found that even the ADH+ strain has low liver ADH activity (〈40% that of the ddY mouse) with 15 mM ethanol as substrate, probably due to low activity in Class I ADH. Consequently, liver ADH activity of this strain was lower than its stomach ADH activity, in contrast with the ddY mouse, whose ADH activity was much higher in the liver than in the stomach, as well as other mammals. Thus, the ADH systems in both ADH− and ADH+ deermouse were different not only from each other but also from that in the ddY mouse; the ADH− strain was deficient in only Class I ADH, and the ADH+ strain was deficient in Class II ADH and down-regulated in Class I ADH activity. Therefore, Class III ADH, which was found in both strains and activated allosterically, may participate in alcohol metabolism in deermouse, especially in the ADH− strain.
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    Effect of streptozotocin diabetes on polysomal aggregation and protein synthesis rate in the liver of pregnant rats and their offspring (1995)
    Springer
    Bioscience reports 15 (1995), S. 15-20 
    Details
    ISSN: 1573-4935
    Keywords: diabetes ; liver ; polysome ; pregnancy ; protein synthesis ; streptozotocin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract To study the effect of diabetes on hepatic protein synthesis and polysomal aggregation in pregnant rats, female rats were treated with streptozotocin prior to conception. Some animals were mated, and studied at day 20 of pregnancy, whereas, others were studied in parallel under non pregnant conditions. The protein synthesis rate measured with an “in vitro” cell-free system was higher in pregnant than in virgin control rats. It decreased with diabetes in both groups, although values remained higher in diabetic pregnant rats than in the virgin animals. The fetuses of diabetic rats had a lower protein synthesis rate than those from controls, although they showed a higher protein synthesis rate than either their respective mothers or virgin rats. Liver RNA concentration was higher in control and diabetic, pregnant rats than in virgin rats, and the effect of diabetes decreasing this parameter was only significant for pregnant rats. Liver RNA concentration in fetuses was lower than in their mothers, and did not differ between control and diabetic animals. The decreased protein synthesis found in diabetic animals was accompanied by disaggregation of heavy polysomes into lighter species, indicating an impairment in peptide-chain initiation.
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    URL: http://dx.doi.org/10.1007/BF01200211
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    Purification and properties of pig liver and muscle enolases (1995)
    Springer
    The protein journal 14 (1995), S. 487-497 
    Details
    ISSN: 1573-4943
    Keywords: Enolase ; isozymic structure ; pig ; purification ; properties ; liver ; muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Enolases (2-phospho-d-glycerate hydrolase, EC 4.2.1.11) were purified from both pig liver and muscle. Graphs of InC vs.r 2 from sedimentation equilibrium experiments are linear, which suggests homogeneous preparations of liver and muscle enolases. From these data the molecular weight of liver enolase is calculated to be approximately 92,000 D and that of muscle enolase to be approximately 85,000 D. SDS-PAGE experiments give a molecular weight value of 46,000 D for liver enolase and a value of 44,000 D for muscle enolase. These molecular weight values for liver and muscle enzymes are within the range for other enolases and show that both of these pig enolases are dimers. Amino acid composition data support the sedimentation equilibrium data and also give a smaller molecule weight (84,968 D) for muscle enolase compared to that of the liver enzyme (89,021 D). The two enzymes differ in their content of lysine [liver enolase (L)=94 residues, muscle enolase (M)=68 residues], histidine (L=13, M=21), serine (L=53, M=36), proline (L=52, M=34), and cysteine (L=4, M=21). Partial specific volumes of 0.737 ml/g for liver enolase and 0.735 ml/g for muscle enolase were calculated from the amino acid composition data. Pig liver and muscle enolases differ radically in their isoelectric points (pI=6.4–6.5 for liver enolase, and pI=8.8–9.0 for muscle enolase), and in their degree of inactivation by 750 mM LiCI (liver enolase is inactivated to a greater degree than the muscle enolase). Despite these physical and chemical differences, the kinetic constantsK M values for Mg2+, 2-phosphoglyceric acid, and phospho(enol)pyruvate appear not to be significantly different for these two forms of enolase. The physical, chemical, and kinetic data for pig liver and muscle enolases are compared to similar data for pig kidney enolase.
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    Sialyl Lewisx epitopes do not occur on acute phase proteins in mice: relationship to the absence of α3-fucosyltransferase in the liver (1998)
    Springer
    Glycoconjugate journal 15 (1998), S. 389-395 
    Details
    ISSN: 1573-4986
    Keywords: α1-acid glycoprotein ; orosomucoid ; mouse ; fucosyltransferase ; liver ; blood serum ; sialyl lewisx ; AAL, Aleuria aurantia lectin ; AGP, α1-acid glycoprotein ; PI, α1-protease inhibitor ; CAIE, crossed affino-immunoelectrophoresis ; LPS, lipopolysaccharide ; FucT, fucosyltransferase ; LacNAc, Galβ1→4GlcNAc ; H-type 2, Fucα1→2Galβ1→4GlcNAc ; H-type 1, Fucα1→2Galβ1→3GlcNAc ; ag-GP-F2, asialo/agalacto-diantennary glycopeptide from human fibrinogen. sLex, sialyl Lewis x.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Mice are frequently used in models for the study of immunological processes related to inflammation. Since it is known that the degree of fucosylation of human acute phase proteins (APPs) is altered as a consequence of an inflammatory response, we have undertaken this study to gain more insight into the fucosylation of acute phase proteins as it occurs in mouse liver. Mice carrying the cluster of the three genes encoding human α1-acid glycoprotein (AGP), one of the well known APPs, were used and the fucosylation of AGP was assessed. A complete absence of fucosylation on the transgenic human AGP was found, which is in sharp contrast to AGP in human serum, of which a major proportion is normally α3-fucosylated. Remarkably, a large proportion of mouse AGP did contain fucose residues. Fucosylation was also detected on another APP, mouse protease inhibitor (PI). α3-Fucosylation of the transgenic human AGP can be achieved in vitro, using an α3/4-fucosyltransferase (α3/4-FucT) isolated from human milk, showing that the glycoprotein is not intrinsically resistant to fucosylation. Upon subsequent measurement of the activities of the possible fucosyltransferases present in liver membranes of parent and transgenic mice, only an N-linked-core α6-FucT and no α2-, α3- or α4-FucT activity was detected. This indicates that fucose residues found on the mouse serum proteins AGP and PI, which are synthesized in the liver, are most probably in α6-linkage to the core chitobiosyl unit. Interestingly, both α6- and α3-FucT activity was detectable in human liver membranes. None of the above mentioned findings were influenced by the induction of an acute phase response by administration of bacterial lipopolysaccharide. This study shows that: (a) α6-FucT is probably a protein specific-glycosyltransferase, since mouse AGP, but not human AGP, may be used as an acceptor; (b) in contrast to human liver, mouse liver does not express any α3-FucT-activity, thereby making the mouse incapable of producing the Sialyl Lewisx epitope on APPs, which is an important part of the inflammatory reaction in humans. This last finding indicates that the mouse is not suitable as a model for the study of those phenomena related to inflammation in humans, in which glycosylation of acute phase proteins could play a significant role. © 1998 Rapid Science Ltd
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    Chemiluminescence of mouse liver after administration of a carcinogen (1976)
    Springer
    Bulletin of experimental biology and medicine 82 (1976), S. 1556-1557 
    Details
    ISSN: 1573-8221
    Keywords: liver ; chemiluminescence ; carcinogens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Changes in the intensity of chemiluminescence of the liver were observed at different times after injection of 9,10-dimethyl-1,2-benzanthracene into mice. The possible connection between the observed phenomena and the formation and accumulation of the endogenous carcinogen in the liver is examined.
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    Changes in the structure of chromatin in hepatocyte nuclei of rats adapted to hypoxia (1976)
    Springer
    Bulletin of experimental biology and medicine 81 (1976), S. 445-448 
    Details
    ISSN: 1573-8221
    Keywords: hypoxia ; liver ; structure of hepatocyte chromatin ; Acridine Orange ; microfluorometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The structure of chromatin in the nuclei of isolated surviving hepatocytes and of isolated hepatocyte nuclei was studied by fluorochroming with Acridine Orange and microfluorometry of the luminescence of chromatin-bound dye at 530 and 590 nm in intact rats and rats adapted to hypoxia in a pressure chamber for 60 days. Hepatocyte nuclei of intact rats were shown to be distributed on the basis of their fluorescence at 530 nm into three classes, with a ratio between intensities of 1∶2∶4, whereas hepatocyte nuclei of rats adapted to hypoxia formed only one class, corresponding to the second class in the control. The ratio between the intensities of luminescence at 590 nm and 530 nm (the coefficient α) forms a normal distribution in intact rats, but in adapted rats it formed a bimodal distribution with a shaft of the maxima toward both sides of the control. During hypoxia repression of some genes and depression of others is considered to take place in the chromatin of liver nuclei.
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    Effect of carbon tetrachloride on RNA metabolism in the rat liver (1976)
    Springer
    Bulletin of experimental biology and medicine 81 (1976), S. 677-680 
    Details
    ISSN: 1573-8221
    Keywords: carbon tetrachloride ; liver ; total, nuclear, and cytoplasmic RNA ; RNA turnover
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The effect of systematic administration of carbon tetrachloride (CCl4) to rats on the RNA content in the liver and the intensity of incorporation of the labeled precursor (uridine-H3) into it was investigated. Comparison of the results of morphological and biochemical studies revealed two consecutive stages of the toxic process, terminating in the formation of septal fibrosis. The sharpest changes in rapid RNA turnover in the rat liver were observed during the first 3 months of action of the toxic agent. The disturbance of metabolism also was reflected in a lowered RNA level and changes in the nucleo-cytoplasmic ratio in the tissue of the affected liver.
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    Effect of disturbance of the innervation of the liver and loss of bile on biliary and hepatic enzyme activity (1976)
    Springer
    Bulletin of experimental biology and medicine 81 (1976), S. 847-849 
    Details
    ISSN: 1573-8221
    Keywords: enzymes ; liver ; disturbance of innervation ; loss of bile
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Continuous loss of bile from rats with a bile reservoir connected to the common bile duct led to an increase in specific activity of malate, lactate, glutamate, and glucose-6-phosphate dehydrogenases, alkaline and acid phosphatases, urokinase, and histidase in liver homogenates by the seventh day. By the tenth day their specific activity had fallen. After disturbance of the innervation of the rats' livers the ATP concentration fell sharply and the specific activity of the above-mentioned enzymes in the liver was considerably inhibited. During continuous loss of bile, fluctuating changes took place in the specific activity of these enzymes and also of sorbitol dehydrogenase in the bile, starting from the first and continuing until the tenth day of the experiment. Support for the view that these fluctuations were under the control of the nervous system was given by the considerable changes in their character following disturbance of the hepatic innervation.
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    Content of adenyl mononucleotides and respiratory phosphorylation in mitochondria of rats with transplantable tumors (1976)
    Springer
    Bulletin of experimental biology and medicine 81 (1976), S. 903-905 
    Details
    ISSN: 1573-8221
    Keywords: tumor growth ; oxidative phosphorylation ; ATPase ; adenyl mononucleotides ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The content of adenyl mononucleotides, the process of oxidative phosphorylation, and the ATPase activity of the liver mitochondria of rats with transplantable sarcoma 45 and Walker's carcinosarcoma were investigated at different stages of tumor growth. The fall in the ATP level observed in the liver mitochondria of the rats with tumors was due, first, to inhibition of its formation as a result of the partial uncoupling of oxidative phosphorylation and, second, to an increased rate of its breakdown as a result of increased ATPase activity.
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    Effect of contrycal on activity of dehydrogenases and their isozymes in muscles and organs of animals with developing granulation tissue (1976)
    Springer
    Bulletin of experimental biology and medicine 82 (1976), S. 1001-1003 
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    ISSN: 1573-8221
    Keywords: lactate dehydrogenase ; malate dehydrogenase ; isozymes ; protease inhibitor, contrycal ; muscles ; liver ; kidneys ; heart
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The effect of contrycal on the state of the enzyme systems of the muscles, liver, kidneys, and heart was investigated in rats with developing granulation tissue. This protease inhibitor was found to stimulated lactate and malate dehydrogenase activity and also the isozyme spectrum of these enzymes. The action of the inhibitor was manifested as a change in the state of the enzyme systems both at the site of injury (granulations and underlying tissue) and in certain internal organs (liver and kidneys).
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    Effect of bilateral subdiaphragmatic vagotomy on the activity of some enzymes of energy metabolism in the liver (1976)
    Springer
    Bulletin of experimental biology and medicine 82 (1976), S. 1010-1011 
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    ISSN: 1573-8221
    Keywords: vagotomy ; liver ; enzymes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Bilateral subdiaphragmatic vagotomy leads to a marked decrease in hexokinase, glucokinase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and lactate dehydrogenase activity in the soluble fraction of rat liver. The blood sugar level was unchanged at all times after the operation. These changes in enzyme activity evidently take place on account of the absence of parasympathetic impulses to the liver cell.
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    Effect of benzo(a)pyrene on monolayer cultures of normal and malignant mouse liver cells (1977)
    Springer
    Bulletin of experimental biology and medicine 84 (1977), S. 1331-1334 
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    ISSN: 1573-8221
    Keywords: benzo(a)pyrene ; liver ; hepatoma ; tissue culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Cells of a monolayer culture of embryonic mouse liver, like cells of a culture of highly malignant hepatoma 22A, maintained by transplantation for 20 years, actively metabolized the carcinogenic hydrocarbon benzo(a)pyrene and are highly sensitive to its toxic action. Considering that liver tissue in vivo is resistant to carcinogenic hydrocarbons, the authors suggest that this resistance is due to factors acting at the organ or organism level but not at the cell level. The problem of the mechanism of preservation of the sensitivity of hepatoma 22A to the toxic action of benzo(a)pyrene also is discussed.
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    Effect of enteral oxygen therapy on liver function in acute degeneration (1977)
    Springer
    Bulletin of experimental biology and medicine 84 (1977), S. 1413-1415 
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    ISSN: 1573-8221
    Keywords: carbon tetrachloride ; oxygen ; liver ; bile acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The effect of enteral oxygen therapy was studied in rats with acute degeneration of the liver caused by CCl4. Intragastric injection of oxygen foam reduced the severity of poisoning and led to more rapid and complete recovery of the intensity of bile secretion, synthesis of primary bile acids, and their conjugation with amino acids, and improved the stabilizing properties of the bile.
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    Bile secretory function of the liver in birds of different ages with experimental atherosclerosis (1976)
    Springer
    Bulletin of experimental biology and medicine 82 (1976), S. 1298-1301 
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    ISSN: 1573-8221
    Keywords: experimental atherosclerosis ; age ; bile acids ; cholesterol ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The bile-secretory function of the liver under normal conditions and in experimental atherosclerosis produced by administration of cholesterol was studied in experiments on young (3–4 months old) and adult (30–36 months old) hens of the Russian White breed. During natural aging a decrease in the total and free cholesterol concentrations in the blood serum and in the bile-secretory function of the liver was observed These indices were raised during administration of cholesterol and atherosclerotic changes developed in the aorta. The severity of these changes compared with normal was greater in the adult than in the young experimental birds.
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    Effect of alcohol on hepatocyte mitochondria (1977)
    Springer
    Bulletin of experimental biology and medicine 84 (1977), S. 1783-1784 
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    ISSN: 1573-8221
    Keywords: mitochondria ; liver ; alcohol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Ultrastructural changes in the hepatocytes under the influence of alcohol were studied. The greatest changes were found in the mitochondria. Physical exertion and a low protein diet have a marked effect on the degree of alcohol poisoning. The first factor reduces whereas the second aggravates the harmful action of alcohol.
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    Method of combined histological staining of the liver with alcian blue and carbol fuchsin (1978)
    Springer
    Bulletin of experimental biology and medicine 85 (1978), S. 254-256 
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    ISSN: 1573-8221
    Keywords: liver ; hepatocytes ; alcian blue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A modification of Novelli's combined histological staining method whereby the functional state of hepatocytes can be determined is suggested.
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    Some features of growth of an organ culture of the liver from mice infected with coxsackie A13 virus (1978)
    Springer
    Bulletin of experimental biology and medicine 85 (1978), S. 477-479 
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    ISSN: 1573-8221
    Keywords: Coxsackie A13 virus ; organ culture ; proliferation ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Features of growth and proliferation of organ cultures of the liver from noninbred albino mice infected with a single dose of Coxsackie A13 virus were investigated. A marked zone of growth mainly of epithelial cells was found early in explants of the liver of the experimental group of mice, whereas growth of cells around the liver explants of the control mice either was absent or was very weak. Moreover, many lymphocytes uniformly distributed in the zone of growth of the liver cells were found in preparations of the liver of the experimental mice. In some explants the picture of adhesion of lymphocytes to the hepatocytes of the culture was seen, and in places where lymphocytes accumulated death of the liver cells and marked thinning of the cellular layer were observed on the 21st and 28th days of growth of the culture.
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    Localization of albumin, transferrin, andα-fetoprotein in normal and regenerating mouse liver (1978)
    Springer
    Bulletin of experimental biology and medicine 85 (1978), S. 689-693 
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    ISSN: 1573-8221
    Keywords: α-fetoprotein ; albumin ; transferrin ; immunofluorescence ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A technique of tissue fixation with a mixture of acetone and formalin followed by embedding in paraffin wax, enabling good detection of antigens, including serum proteins, is described. By means of this method the distribution of albumin, transferrin, andα-fetoprotein was described in normal and regenerating mouse liver. Both under normal conditions and during regeneration albumin and transferrin are contained by strictly the same hepatocytes.α-Fetoprotein is found in the regenerating liver independently of the other two proteins, although it is found in the same zones. Albumin and transferrin are found only in the perinecrotic zone in each cell containingα-fetoprotein.
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    Immunohistochemical study of cardiolipin and phosphatidylinositol in mouse liver (1978)
    Springer
    Bulletin of experimental biology and medicine 86 (1978), S. 1206-1209 
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    ISSN: 1573-8221
    Keywords: immunofluorescence ; cardiolipin ; phosphatidylinositol ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The localization of phospholipid haptens (cardiolipin and phosphatidylinositol) in frozen and paraffin sections of mouse liver fixed in acetone and in an acetone-buffer-formalin mixture was studied by the indirect fluorescent antibodies method. Antiphospholipid sera specifically stained the plasma membranes of the hepatocytes, especially the region of the membrane facing the blood sinus. Detection of phospholipid haptens in liver sections with the aid of antiphospholipid sera depends on the method of obtaining and fixing the sections. Depending on the method of immunization, two types of antiphospholipid sera are obtained; they differ in their stability, in the possibility of isolating antibodies on lipid immunosorbents from them, and in their ability to stain liver sections.
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    Effect of cytidine and uridine on regeneration of the liver in rats poisoned with carbon tetrachloride (1979)
    Springer
    Bulletin of experimental biology and medicine 88 (1979), S. 1480-1483 
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    ISSN: 1573-8221
    Keywords: liver ; regeneration ; cytidine ; uridine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The effect of uridine and cytidine on the course of repair processes in the liver of rats with experimental hepatitis due to CCl4 was studied. Injection of uridine or cytidine simultaneously with CCl4 over a period of 7 days did not prevent damage to the liver by the poison. Further treatment with the nucleosides (up to 15 and 20 days) accelerated, although to different degrees, the course of repair processes after discontinuation of CCl4. Cytidine, for instance, caused marked hypertrophy of regenerating hepatocytes, combined with proliferation of mesenchymal cells, which, however, was not accompanied by restoration of the conjugating and excretory functions of the liver. Unlike cytidine, uridine led to more rapid normalization of the abovementioned functions, although restoration of the structure of the organ in this case was less complete.
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    Diurnal changes in the number of mitoses and of DNA-synthesizing cells in tissues of young rats (1976)
    Springer
    Bulletin of experimental biology and medicine 82 (1976), S. 1712-1714 
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    ISSN: 1573-8221
    Keywords: Mitotic index (MI) ; index of labeled nuclei (ILN) ; diurnal changes in MI and ILN ; liver ; epidermis ; pancreas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Regular diurnal changes in the number of mitoses (MI) and the number of DNA-synthesizing cells (ILN) were demonstrated in the liver, epidermis, and exogenous part of the pancreas of rats aged 7 days. The character of these changes differed in the various tissues. No regular correlation was found between diurnal changes in MI or ILN.
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    Changes in rat liver mitochondria after bilateral subdiaphragmatic vagotomy (1977)
    Springer
    Bulletin of experimental biology and medicine 83 (1977), S. 487-490 
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    ISSN: 1573-8221
    Keywords: mitochondrion ; liver ; vagotomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Changes in the liver mitochondria of rats after bilateral subdiaphragmatic vagotomy were studied. Two stages were distinguished in the dynamics of the response of the mitochondrial system to denervation. During the first stage (0.5–3 days after vagotomy) reversible functional disturbances due to postoperative stress took place in the mitochondria. The second stage (7–60 days after denervation) is characterized by more marked structural and functional changes with some common features with those observed in hypoxia and resulting from vagotomy itself.
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    Effect of absence of polyploid hepatocytes on regeneration in the liver (1977)
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    Bulletin of experimental biology and medicine 84 (1977), S. 1183-1186 
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    ISSN: 1573-8221
    Keywords: liver ; polyploidy ; mitotic index ; index of labeled nuclei ; guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract An autoradiographic study with [3H]thymidine showed that the hepatocytes of young sexually mature guinea pigs commence the phase of DNA synthesis 25 h after partial hepatectomy. Peaks of the number of labeled nuclei were found 30, 45, and 60 h after the operation. Two waves of mitoses were found by counting mitotic figures in squash preparations: 40 and 55 h after hepatectomy. A cytophotometric study of the DNA content showed that practically all the mononuclear and binuclear hepatocytes contained diploid nuclei 3 and 5 days after the operation. By the end of the 7th day of regeneration there were 6% of mononuclear tetraploid cells. The number of binuclear cells fell during the period of regeneration studied from 16 to 8%. It is concluded that the principal cytological mechanism of liver regeneration in guinea pigs is normal mitosis terminating in separation of the cells.
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    Effect of gnotobiotic conditions on the histophysiology of liver and spleen tissues (1978)
    Springer
    Bulletin of experimental biology and medicine 85 (1978), S. 95-98 
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    ISSN: 1573-8221
    Keywords: germfree animals ; liver ; spleen ; histochemical changes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The liver and spleen of gnotobiotic Wistar rats were studied by histochemical methods and the liver electron-microscopically. Under germfree conditions of existence of the animal the succinate dehydrogenase and nonspecific esterase activity in the liver decreased, fatty infiltration of the cytoplasm of the hepatocytes and Kupffer cells increased, and some of the cells developed fatty degeneration. Meanwhile acid phosphatase activity and the number of lysosomes increased in the biliary poles of the hepatocytes, whereas in the spleen destruction of erythrocytes and the liberation of free iron and pigments, which stimulate the excretion of bile in germfree animals, were increased.
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    Effect of o,p-dichlorodiphenyldichloroethane and perthane in vitro on glutathione reductase activity in the adrenals of dogs and guinea pigs (1978)
    Springer
    Bulletin of experimental biology and medicine 85 (1978), S. 152-154 
    Details
    ISSN: 1573-8221
    Keywords: glutathione reductase ; o,p′-dichlorodiphenyldichloroethane ; p,p′-diethyldiphenyldi-chloroethane (Perthane) ; adrenals ; liver ; kidneys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract o,p′-Dichlorodiphenyldichloroethane (o,p′-DDD) and Perthane, when added in a concentration of 312 μM to homogenate and cytoplasmic fraction of dog adrenals, activate glutathione reductase. In a concentration of 156 μM, o,p′-DDD and Perthane do not affect glutathione reductase activity of the dog adrenals. When given in vitro, o,p′-DDD and Perthane activate glutathione reductase of the guinea pig adrenals. o,p′-DDD has no effect on glutathione reductase activity of the cytoplasmic fraction of dog liver and kidney, thus confirming the high specificity of its effect on the adrenal cortex.
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    Effect of chronic carbon tetrachloride poisoning on the turnover of RNA fractions in rat liver tissue (1977)
    Springer
    Bulletin of experimental biology and medicine 83 (1977), S. 490-494 
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    ISSN: 1573-8221
    Keywords: carbon tetrachloride ; liver ; RNA metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Changes in the content and incorporation of 5-3H-uridine after brief exposure to its labeled precursor were studied in the individual liver RNA fractions of rats during administration of carbon tetrachloride for 24 weeks. These fractions were obtained by preparative electrophoresis in 2.5% polyacrylamide gel from previously isolated nuclear and cytoplasmic RNA. Administration of CCl4 to rats was shown to reduce the quantity of transfer and ribosomal RNA in the liver tissue. Chronic CCl4 poisoning also disturbs the synchronization of the turnover of the individual components of fast-labeled RNA.
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    Design for Cell-Specific Targeting of Proteins Utilizing Sugar-Recognition Mechanism: Effect of Molecular Weight of Proteins on Targeting Efficiency (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 209-214 
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    ISSN: 1573-904X
    Keywords: protein targeting ; sugar recognition ; pharmacokinetics ; molecular weight ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Hepatic targeting of proteins utilizing the sugar-recognition mechanism was investigated in mice after intravenous injection. Five proteins with different molecular weights, i.e., bovine γ-globulins (IgG), bovine serum albumin (BSA), recombinant human superoxide dismutase (SOD), soybean trypsin inhibitor (STI), and chicken egg white lysozyme (LZM), were modified with 2-imino-2-methoxyethyl 1-thiogalactoside to obtain galactosylated proteins (Gal-IgG, Gal-BSA, Gal-SOD, Gal-STI, and Gal-LZM). The numbers of galactose residues were 38, 20, 11, 6, and 5 for Gal-IgG, Gal-BSA, Gal-SOD, Gal-STI, and Gal-LZM, respectively. All galactosylated proteins were dose-dependently taken up by the liver and the relative amount accumulated in the liver was decreased with an increase of the administered dose. At low doses (0.05 and 0.1 mg/kg), Gal-IgG, Gal-BSA, and Gal-SOD could be taken up by the liver up to more than 70–80% of dose within 10 min after intravenous injection, but the maximum amounts accumulated in the liver were approximately 40 and 30% of the dose for Gal-STI and Gal-LZM, respectively. Pharmacokinetic analysis revealed that the hepatic uptake clearance (CLliver) was quite different around the molecular weight of 32 kDa and correlated with the amount delivered to the liver; Gal-IgG, Gal-BSA, and Gal-SOD has a large CLliver that is close to the hepatic plasma flow rate (85 ml/hr), whereas those of Gal-STI and Gal-LZM were approximately 10 ml/hr at low doses. As for the total amount accumulated in the liver, high glomerular filtration rate of Gal-STI and Gal-LZM was also shown to cause insufficient delivery to the liver apart from being caused by their low CLliver.
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    Cellular Pharmacokinetics: Effects of Cytoplasmic Diffusion and Binding on Organ Transit Time Distribution (1999)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 233-256 
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    ISSN: 1573-8744
    Keywords: pharmacokinetic model ; multiple indicator dilution ; binding kinetics ; liver ; tissue distribution ; cytoplasmic diffusion coefficient ; membrane permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Distribution between well-stirred compartments is the classical paradigm in pharmacokinetics. Also in capillary–issue exchange modeling a barrier-limited approach is mostly adopted. As a consequence of tissue binding, however, drug distribution cannot be regarded as instantaneous even at the cellular level and the distribution process consists of at least two components: transmembrane exchange and cytoplasmic transport. Two concepts have been proposed for the cytoplasmic distribution process of hydrophobic or amphipathic molecules, (i) slowing of diffusion due to instantaneous binding to immobile cellular structures and (ii) slow binding after instantaneous distribution throughout the cytosol. The purpose of this study was to develop a general approach for comparing both models using a stochastic model of intra- and extravascular drug distribution. Criteria for model discrimination are developed using the first three central moments (mean, variance, and skewness) of the cellular residence time and organ transit time distribution, respectively. After matching the models for the relative dispersion the remaining differences in relative skewness are predicted, discussing the relative roles of membrane permeability, cellular binding and cytoplasmic transport. It is shown under which conditions the models are indistinguishable on the basis of venous organ outflow concentration–time curves. The relative dispersion of cellular residence times is introduced as a model-independent measure of cytoplasmic equilibration kinetics, which indicates whether diffusion through the cytoplasm is rate limiting. If differences in outflow curve shapes (their relative skewness) cannot be detected, independent information on binding and/or diffusion kinetics is necessary to avoid model misspecification. The method is applied to previously published hepatic outflow data of enalaprilat, triiodothyronine, and diclofenac. It provides a general framework for the modeling of cellular pharmacokinetics.
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    One Step Isolation of Bovine Asialoglycoprotein Receptor and Its Characterization by Sequence Analysis and MALDI Mass Spectrometry (1999)
    Springer
    Bioscience reports 19 (1999), S. 115-124 
    Details
    ISSN: 1573-4935
    Keywords: Carbohydrate binding proteins ; liver ; plasma membrane ; MALDI-TOF mass spectrometry ; sequence analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The asialoglycoprotein receptor (ASGP-R), which is responsible for the uptake of partially deglycosylated serum glycoproteins was isolated from bovine liver. The receptor was purified in one step from solubilized plasma membranes by affinity chromatography on 6-(β-D-lactosyl)-n-hexylamine coupled to N-hydroxysuccinimide activated Sepharose with a coupling degree of 7.6 μmol/ml gel. The preparation yielded two distinct polypeptides with apparent molecular weights of 48 and 43 kDa as determined by sodium dodecyl sulfatepolyacrylamide gel electrophoresis. A polyclonal antibody raised against the human ASGP-R recognized the bovine 43 kDa protein in Western blot analysis. The 48 and 43 kDa polypeptides were digested by trypsin and the digests were subsequently analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Sequence analysis of four tryptic fragments, two each of the 48 kDa and of the 43 kDa polypeptides revealed that these were highly homologous to ASGP-R subunits from man, mouse and rat.
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    Lack of presystemic metabolism of nifedipine in the rabbit (1995)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 23 (1995), S. 567-580 
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    ISSN: 1573-8744
    Keywords: nifedipine ; first-pass metabolism ; intestinal ; liver ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract In humans, oral bioavailability of nifedipine has been reported to be around 60%, although the organ(s) contributing to its first-pass metabolism have not been determined. The aim of this study was to determinein vivo, in anesthetized and conscious rabbits the role of the intestine, liver, and lungs in the first-pass metabolism of nifedipine. To assess the extraction of nifedipine by the intestine, liver, and lungs, nifedipine was administered before and after each organ, and serial blood samples were withdrawn from an artery. In conscious rabbits, the systemic clearance of nifedipine injected into a lateral vein of an ear was 14.6±1.6 ml/min per kg, a value that was slightly decreased by anesthesia. In anesthetized rabbits, compared to the clearance estimated when nifedipine was administered into the thoracic aorta, the administration of nifedipine into a jugular vein, into the portal vein, or into the duodenum did not increase the value of the systemic clearance. In conscious rabbits, the clearance of nifedipine estimated when the drug was administered into the duodenum, the peritoneum, the portal vein, or into the jugular vein was identical to the clearance calculated when the drug was injected into the thoracic aorta.In vitro, nifedipine was metabolized in liver and intestinal epithelial cells homogenates but not in lungs or kidneys. We concluded that in the rabbit, oral nifedipine is not subjected to a first-pass metabolism, even though the intestine and the liver may contribute to nifedipine systemic clearance.
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    An expanded model of bilirubin kinetics: Effect of feeding, fasting, and phenobarbital in Gilbert's syndrome (1976)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 4 (1976), S. 115-155 
    Details
    ISSN: 1573-8744
    Keywords: bilirubin kinetics ; Gilbert's syndrome ; compartmentation ; liver ; heme ; multicompartmental model ; 14C-bilirubin ; 3H-bilirubin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract In a patient with classical Gilbert's syndrome, tracer 14C-bilirubin was infused intravenously at constant rate for 20–32 hr. Total bilirubin production (TBrP) and bilirubin production as estimated from plasma data only (PBrP) were calculated from the specific activity of bilirubin in hepatic bile and in plasma. Pulse labeling with 3 H -δ-aminolevulinic acid permitted estimation of bilirubin fractions synthesized in the liver and excreted directly into bile or returned to plasma. Neither fasting nor phenobarbital (PB) affected TBrP or PBrP; the rise in plasma bilirubin on fasting and fall on PB were entirely accounted for by changes in hepatic pigment clearance. A multicompartmental model, formulated to fit the data obtained in all three experimental conditions, suggested that bilirubin produced in hepatocytes is characterized by three discrete, noncommunicating compartments which differ kinetically and in the manner of pigment transport into plasma, bile, or both. The size and kinetics of each hepatic compartment resembled those of known hepatic heme or hemoprotein fractions. Transfer of bilirubin from plasma to bile occurs by separate hepatic channels which do not communicate in the liver with compartments of endogenously formed pigment. Fasting and PB produced minor modifications in mass and turnover of individual hepatic compartments but did not significantly alter the total rate of bilirubin synthesized in the liver and delivered either to plasma or directly into bile. These findings suggest that production and transport of bilirubin in the liver are highly compartmentized processes.
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    Contribution of Parenchymal and Non-Parenchymal Liver Cells to the Clearance of Hepatocyte Growth Factor From the Circulation in Rats (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 1737-1740 
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    ISSN: 1573-904X
    Keywords: hepatocyte growth factor ; receptor-mediated endocytosis ; pharmacokinetics ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The distribution of 125I-hepatocyte growth factor (HGF) to either liver parenchymal cells (PC) or non-parenchymal cells (NPC) was investigated in rats. Methods. After injection of a trace amount of 125I-HGF, the distribution of radioactivity determined by microautoradiography closely resembled that of 125I-epidermal growth factor which distributes mainly to PC. Results. The uptake clearance of 125I-HGF estimated by determining the radioactivity of isolated liver cells was three times higher for PC than for NPC. This suggests that HGF distributes mainly to PC at relatively low doses. On the other hand, the uptake clearance by PC fell on coadministering an excess (80 µg/kg) of unlabeled HGF, while no change was observed for NPC, indicating that a saturable process for the hepatic handling of HGF exists only in PC where the HGF receptor is expressed. Conclusions. At such a dose the uptake clearance was comparable for both PC and NPC showing that HGF distributes to both cell types although NPC have few HGF receptors. Since the distribution to NPC was relatively non-specific and heparin-sensitive, it may be that heparin-like substances, which are believed to exist on PC and/ or the extracellular matrix, also exist on NPC.
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    URL: http://dx.doi.org/10.1023/A:1016273907749
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    Comparison of the Disposition of Hepatically-Generated Morphine-3-glucuronide and Morphine-6-glucuronide in Isolated Perfused Liver from the Guinea Pig (1997)
    Springer
    Pharmaceutical research 14 (1997), S. 1014-1018 
    Details
    ISSN: 1573-904X
    Keywords: morphine ; morphine-3-glucuronide ; morphine-6-glucuronide ; liver ; membrane transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Humans and guinea pigs metabolise morphine extensively, forming the isomers morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in relatively similar ratios. Both metabolites are formed in the liver, and their greater polarity relative to the parent aglycone may limit their permeability across hepatic membranes. This study compared the disposition of hepatically-generated M3G and M6G in perfused livers isolated from guinea pigs. Methods. Livers were perfused at 30 ml/min in a non-recirculating manner with Krebs bicarbonate buffer containing morphine (6 to 7 μM). Perfusing medium, venous perfusate and bile were collected at regular intervals and concentrations of morphine, M3G and M6G determined by reversed-phase HPLC. Results. Concentrations of morphine, M3G and M6G in perfusate and the rates of biliary excretion of M3G and M6G were consistent between 20 and 50 min of perfusion. The mean (±s.d.) ratio for the rate of formation of M3G relative to M6G was 3.7 ± 1.5. A mean 33 ± 3% of morphine extracted by the liver was recovered as summed M3G and M6G. Of the M3G and M6G formed during a single passage, 19 ± 11% and 9 ± 9%, respectively, was excreted into bile; the values were significantly different (P = 0.002). Conclusions. A greater fraction of hepatically-generated M3G excreted into bile compared to that for M6G reflects differences in their relative transport across sinusoidal and canalicular membranes of hepatocytes, possibly via carrier-mediated systems.
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    URL: http://dx.doi.org/10.1023/A:1012145126847
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    Targeting of Drug to the Hepatocytes by Fatty Acids. Influence of the Carrier (Albumin or Galactosylated Albumin) on the Fate of the Fatty Acids and Their Analogs (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 27-31 
    Details
    ISSN: 1573-904X
    Keywords: liver ; fatty acid ; asialoglycoprotein ; albumin ; selective ; drug delivery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of this study was to evaluate the potential of fatty acids as shuttles to deliver xenobiotic inside the hepatocytes as well as to study the mechanism of incorporation into isolated hepatocytes when bound to native albumin or galactosylated albumin. Theoretically, they can enter into the hepatocytes after recognition of the Fatty Acid Binding Protein (FABPPM), or remain bound to galactosylated proteins and enter into these cells by a process known as receptor mediated endocytosis after selective recognition of the asialoglycoprotein receptor (ASGPR). Methods. We synthesized a 3H-benzoyl adduct of lauric acid (BLA) (benzoyl adduct choosen to mimick any low molecular weight drug or contrast agent), and compared the behavior of BLA with oleic acid for their binding properties to carrier-proteins and the uptake mechanism by isolated hepatocytes. Results. No significant difference was found in the binding properties of BLA for albumin and galactosylated albumin. The incorporation into the hepatocytes was found essentially depending on the FABPPM transport system whenever BLA was bound to albumin or to galactosylated albumin in the incubation medium: indeed, the transport was inhibited by phloretin (inhibitor of sodium dependent transport), increased when the free part of BLA was higher, and BLA was recovered in the cytosolic fraction of the hepatocytes. Conclusions. This study showed the convenience in using fatty acids as drug carriers possessing tropism for the hepatocytes.
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    URL: http://dx.doi.org/10.1023/A:1016012913664
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    First-Pass Metabolism of Diltiazem in Anesthetized Rabbits: Role of Extrahepatic Organs (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 124-128 
    Details
    ISSN: 1573-904X
    Keywords: diltiazem ; first-pass metabolism ; intestine ; liver ; lungs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of this study was to assess in vivo which organs contribute to the first-pass metabolism of diltiazem. Methods. Anaesthetized rabbits received diltiazem into the thoracic aorta (TA) (1 mg/kg), jugular vein (JV) (2 mg/kg), portal vein (PV) (4 mg/kg) or small intestine (SI) (5 mg/kg). Serial blood samples were withdrawn from the abdominal aorta to assay diltiazem, N-demethyl-diltiazem (MA) and deacetyldiltiazem (M1). Results. The area under diltiazem plasma concentration curve/time (AUC0−∞) normalized by the dose was AUCTA ≈ AUCJV 〉 AUCPV 〉 AUCSI. Intestinal and hepatic diltiazem availability was 43 and 33%, respectively. The systemic availability of oral diltiazem was 12%. Diltiazem given into the SI and PV generated primarily MA, and injected into the JV and TA produced mainly Ml. Conclusions. In rabbits, the intestine and the liver contribute to the first-pass metabolism of diltiazem, and the amount and species of metabolites generated depend upon the route of administration of diltiazem.
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    URL: http://dx.doi.org/10.1023/A:1016097805003
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    Metabolism of Diltiazem in Hepatic and Extrahepatic Tissues of Rabbits: In Vitro Studies (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 609-614 
    Details
    ISSN: 1573-904X
    Keywords: diltiazem ; metabolism ; liver ; extrahepatic tissues
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Diltiazem (DTZ) is a calcium channel blocker widely used in the treatment of angina and hypertension. DTZ undergoes extensive metabolism yielding several metabolites, some of which are active like N-desmethyldiltiazem (MA), desacetyldiltiazem (M1) and N-desmethyl,desacetyldiltiazem (M2). Due to the nature of its biotransformation, several organs should have the ability to metabolize DTZ, however it is still assumed that the liver is the only organ implicated in its elimination. In this study, the fate of DTZ, MA and M1 was assessed in several organs that could contribute to their biotransformation. To this purpose, DTZ (48.2 µM) was incubated in the 10,000 × g supernatant of homogenates of rabbit tissues for 60 min at 37°C. Multiple samples were withdrawn, and DTZ and its metabolites were assayed by HPLC. The elimination rate constant of DTZ in 10,000 × g supernatants varied between the organs: liver 334 ± 45, proximal small intestine 69 ± 11, distal small intestine 25 ± 3, lungs 15 ± 6 and kidneys 8 ± 6 (10−4 min−1). The metabolism of DTZ in the liver generated large amounts of MA but no M1, and in the small intestine, modest amounts of both metabolites. When MA (50.0 µM) or M1 (53.7 µM) were incubated in liver homogenates, the estimated elimination rate constant were 166 ± 23 and 468 ± 53 (10−4 min−1), respectively. The rate of degradation of the metabolites in the small intestine was much slower. These results demonstrate that, in vitro, DTZ is metabolized by several organs, the liver accounting for 75% of the total activity, and that MA is the major metabolite generated.
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    URL: http://dx.doi.org/10.1023/A:1016226601988
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    The Role of Liver and Kidney on the Pharmacokinetics of a Recombinant Amino Terminal Fragment of Bactericidal/Permeability-Increasing Protein in Rats (1997)
    Springer
    Pharmaceutical research 14 (1997), S. 224-229 
    Details
    ISSN: 1573-904X
    Keywords: bactericidal/permeability-increasing protein ; pharmacokinetics ; liver ; kidney ; heparin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The pharmacokinetics of rBPI23, a recombinant amino terminal fragment of bactericidal/permeability-increasing protein that binds to and neutralizes endotoxin, was investigated. Methods. rBPI23 was administered to rats at doses 0.01−10 mg/kg and plasma rBPI23 levels were measured by ELISA. rBPI23 was also administered to bilaterally nephrectomized rats. In addition, rBPI23 was administered intra-hepatically via the pyloric vein to determine the first-pass effect by the liver. rBPI23 concentrations were also simultaneously measured in the right atrium and aorta to determine the removal of rBPI23 by the lungs. Results. The concentration-time profile of rBPI23 was described by a 3-compartmental model with parallel first order and Michaelis-Menten (saturable) elimination. The clearance of rBPI23 was not altered by bilateral nephrectomy. Clearance of intra-hepatically administered rBPI23 was 4.5 fold lower than intra-femorally administered rBPI23. The concentration difference of rBPI23 between aortic and right atrial blood was no greater than 11%. Clearance of rBPI23 in rats could be reduced up to 10 fold by co-administration of heparin. Uptake by liver of intra-hepatically administered rBPI23 was prevented by co-administration of heparin. Conclusions. rBPI23 is not significantly cleared by the kidneys, and no more than 11% of the rBPI23 was removed by the lungs with each pass. The liver could remove 78% of the rBPI23 from the hepatic circulation. Studies with heparin suggest rBPI23 is cleared by binding to heparan sulfate sites in the liver.
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    URL: http://dx.doi.org/10.1023/A:1012013113759
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    A Model with Separate Hepato-Portal Compartment ("First-Pass" Model): Fitting to Plasma Concentration-Time Profiles in Humans (1997)
    Springer
    Pharmaceutical research 14 (1997), S. 230-237 
    Details
    ISSN: 1573-904X
    Keywords: compartmental pharmacokinetic models ; "first pass" effect ; distribution ; liver ; intestine ; sensitivity analysis ; parameter estimability ; NONMEM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To demonstrate the value of "first-pass" pharmacokinetic models (FPMs) in which the hepato-portal (HP) system is kinetically separated from the central compartment in fitting pharmacokinetic data obtained after intravenous (IV) and oral administration. Methods. Plasma concentration-time profiles of an investigational drug obtained in six healthy subjects each received 4 mg as an intravenous (IV) bolus dose and 10 mg as an oral solution served as a real data example. The common three- and four-compartment models with the first-order absorption and lag time (3CM and 4CM, respectively) in which HP system is assumed to be part of the central compartment were used as alternative models. We tested also: (i) the sensitivity of the output of FPM to variations in its parameters assuming IV and oral administration; (ii) practical estimability of the FPM parameters by fitting it to 20 simulated noisy data sets; (iii) distinguishability of FPM, 3CM and 4CM by fitting them to the simulated data sets. Results. FPM was shown to give the best fit as compared to 3CM or 4CM in 5 subjects of 6. The sensitivity of FPM was sufficient for the sake of parameter estimation. The "individual" means of parameter estimates obtained after fitting simulated data did not differ significantly from the preselected values. The variance in "individual" estimates was dependent on the sampling frequency. FPM was demonstrated to be distinguishable among relevant models. Conclusions. FPM is preferable as compared to standard compartmen-tal models for drugs extensively taken up by the intestine and/or the liver, and may have a broad spectrum of applications.
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    URL: http://dx.doi.org/10.1023/A:1012065130597
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    Content and binding characteristics of the mitochondrial ATPase inhibitor, IF1 in the tissues of several slow and fast heart-rate homeothermic species and in two poikilotherms (1995)
    Springer
    Journal of bioenergetics and biomembranes 27 (1995), S. 117-125 
    Details
    ISSN: 1573-6881
    Keywords: Mitochondrial ATPase ; ATPase inhibitor protein ; IF1 ; myocardial ischemia ; effects of ionic strength ; higher and lower affinity IF1 ; homeothermic and poikilothermic species ; tissue distribution of If1 ; cardiac muscle ; skeletal muscle ; liver ; brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract We determined the IF1 contents of pig, rabbit, rat, mouse, guinea pig, pigeon, turtle, and frog heart mitochondria and the effects of varying ionic strength upon the IF1-mediated inhibition of the ATPase activity of IF1-depleted rabbit heart mitochondrial particles (RHMP) by IF1-containing extracts from these same eight species. The IF1 binding experiments were run at both species-endogenous IF1 levels and at an IF1 level normalized to that present in rabbit heart mitochondria. When species-endogenous levels of rabbit heart IF1 or either speciesendogenous or normalized levels of pig heart IF1 were incubated with RHMP over a range of KCl concentrations, increasing the [KCl] to 150 mM had relatively little effect on IF1-mediated ATPase inhibition. When either species-endogenous or normalized levels of guinea pig, pigeon, turtle, or frog heart IF1 were incubated with RHMP under the same conditions, increasing [KCl] to 150 mM nearly completely blocked IF1-mediated ATPase inhibition. While species-endogenous levels of rat and mouse heart IF1 inhibited the ATPase activity of RHMP virtually not at all at any [KCl] examined, normalized levels of rat and mouse IF1 inhibited the ATPase activity of RHMP to the same extents as species-endogenous levels of pig and rabbit heart IF1, respectively, in the presence of increasing [KCl]. These experiments suggest that, while pig and rabbit heart mitochondria contain a full complement of higher-affinity IF1, pigeon, guinea pig, turtle, and frog heart mitochondria cell contain essentially a full complement of a lower-affinity form of IF1. In contrast, rat and mouse heart mitochondria contain only low levels of IF1 which exhibit binding characteristics similar to those of the pig and rabbit heart inhibitor. The guinea pig is the only mammal thus far examined that contains a loweraffinity form of IF1. In the present study we also determined the IF1 contents and IF1-to-F1 ATPase activity ratios of cardiac muscle, skeletal muscle, liver, and brain mitochondria of rabbit, pigeon, and rat, species representative of the three homeothermic regulatory classes.
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    URL: http://dx.doi.org/10.1007/BF02110339
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    Mitochondrial Biogenesis in the Liver during Development and Oncogenesis (1997)
    Springer
    Journal of bioenergetics and biomembranes 29 (1997), S. 365-377 
    Details
    ISSN: 1573-6881
    Keywords: Mitochondrial biogenesis ; differentiation of mitochondria ; proliferation of mitochondria ; liver ; oxidative phosphorylation genes ; regulation gene expression ; development ; oncogenesis ; mitochondrial DNA ; mRNA localization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract The analysis of the expression of oxidative phosphorylation genes in the liver during development reveals the existence of two biological programs involved in the biogenesis of mitochondria. Differentiation is a short-term program of biogenesis that is controlled at post-transcriptional levels of gene expression and is responsible for the rapid changes in the bioenergetic phenotype of mitochondria. In contrast, proliferation is a long-term program controlled both at the transcriptional and post-transcriptional levels of gene expression and is responsible for the increase in mitochondrial mass in the hepatocyte. Recently, a specific subcellular structure involved in the localization and control of the translation of the mRNA encoding the β-catalytic subunit of the H+-ATP synthase (β-mRNA) has been identified. It is suggested that this structure plays a prominent role in the control of mitochondrial biogenesis at post-transcriptional levels. The fetal liver has many phenotypic manifestations in common with highly glycolytic tumor cells. In addition, both have a low mitochondrial content despite a paradoxical increase in the cellular representation of oxidative phosphorylation transcripts. Based on the paradigm provided by the fetal liver we hypothesize that the aberrant mitochondrial phenotype of fast-growing hepatomas represents a reversion to a fetal program of expression of oxidative phosphorylation genes by the activation, or increased expression, of an inhibitor of β-mRNA translation.
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    URL: http://dx.doi.org/10.1023/A:1022450831360
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    Liver cell hydration (1997)
    Springer
    Cell biology and toxicology 13 (1997), S. 275-287 
    Details
    ISSN: 1573-6822
    Keywords: hydration ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Liver cells possess potent mechanisms to maintain their volume, i.e., their hydration state. These volume-regulatory mechanisms, however, are apparently not designed to maintain absolute cell volume constancy; they rather act as dampeners to prevent excessive cell volume deviations, which would otherwise result from cumulative substrate uptake or anisotonic stress. Furthermore, these volume-regulatory mechanisms can even be activated in the resting state by hormones and other stimuli, and by that means cell volume changes are affected secondarily. Thus, liver cell hydration can change within minutes under the influence of aniso-osmolarity, hormones, nutrients, and oxidative stress. Such short-term modulation of cell volume within a narrow range acts as an independent and potent signal which modifies hepatocellular metabolism and gene expression. Accordingly, cell volume homeostasis involves the integration of events that allow cell hydration to play a physiologic role as a regulator of cell function.
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    URL: http://dx.doi.org/10.1023/A:1007483324138
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    Liver cell culture methods for measuring DNA alterations produced by chemicals and radiation (1997)
    Springer
    Cell biology and toxicology 13 (1997), S. 317-321 
    Details
    ISSN: 1573-6822
    Keywords: DNA ; hepatocytes ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Liver culture systems, both primary cultures of hepatocytes and replicating cell lines, can be used in a variety of ways to study the DNA-damaging effects of chemicals and radiation. The present report describes some of the available methods and their interpretation.
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    URL: http://dx.doi.org/10.1023/A:1007439509117
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    Apoptosis in the liver and its role in hepatocarcinogenesis (1997)
    Springer
    Cell biology and toxicology 13 (1997), S. 339-348 
    Details
    ISSN: 1573-6822
    Keywords: apoptosis ; hepatocarcinogenesis ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Apoptosis seems to be the predominant type of active cell death in the liver (type I), while in other tissues cells may die via biochemically and morphologically different pathways (type II, type III). Active cell death is under the control of growth factors and death signals. In the liver, endogenous factors, such as transforming growth factor β1 (TGF-β1), activin A, CD95 ligand, and tumor necrosis factor (TNF) may be involved in induction of apoptosis. Release and action of these death factors seems to be triggered by exogenous signals such as withdrawal of hepato-mitogens, food restriction, etc. During stages of hepatocarcinogenesis, not only DNA synthesis but also apoptosis gradually increase from normal to preneoplastic to adenoma and carcinoma tissue. Also, in human carcinomas, birth and death rates of cells are several times higher than in surrounding liver. (Pre)neoplastic liver cells are more susceptible than normal hepatocytes to stimulation of cell replication and of cell death. Consequently, tumor promoters may act as survival factors, i.e., inhibit apoptosis preferentially in preneoplastic and even in malignant liver cells, thereby stimulating selective growth of (pre)neoplastic lesions. On the other hand, regimens favoring apoptosis and lowering cell replication may result in selective elimination of (pre)neoplastic cell clones from the liver. Finally, we have studied the first stage of carcinogenesis, namely the appearance of putatively initiated cells after a single dose of the genotoxic carcinogen N-nitrosomorpholine (NNM). Most of these cells were found to be eliminated by apoptosis, suggesting that initiation, at the organ level, can be reversed at least partially by preferential elimination of initiated cells. These events may be regulated by autocrine or paracrine actions of survival factors.
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    URL: http://dx.doi.org/10.1023/A:1007495626864
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    Liver cell culture methods to measure DNA alterations produced by chemicals and radiation (1997)
    Springer
    Cell biology and toxicology 13 (1997), S. 399-403 
    Details
    ISSN: 1573-6822
    Keywords: DNA ; hepatocytes ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Liver culture systems, both primary cultures of hepatocytes and replicating cell lines, can be used in a variety of ways to study the DNA-damaging effects of chemicals and radiation. The present report describes some of the available methods and their interpretation.
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    URL: http://dx.doi.org/10.1023/A:1007415609796
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    DNA ploidy and autophagic protein degradation as determinants of hepatocellular growth and survival (1997)
    Springer
    Cell biology and toxicology 13 (1997), S. 301-315 
    Details
    ISSN: 1573-6822
    Keywords: autophagy ; carcinogenesis ; hepatocyte ; liver ; ploidy ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Hepatocytes have the ability to go through specialized cell cycles, which, during normal developmental liver growth, result in the formation of binuclear and polyploid cells. In the adult rat liver, the majority of the hepatocytes (about 70%) are tetraploid, 15-20% are octoploid, and only 10-15% are diploid (about 50% in humans). One-third of the hepatocytes in either rats or humans are binuclear (with two diploid or two tetraploid nuclei). Among cultured rat hepatocytes stimulated with growth factors (EGF and insulin), one-half of the mitoses are of the binucleating type (suggesting a "quantal" mechanism), causing one-third of the postmitotic cells to become binuclear. In contrast, regenerative liver growth, induced by partial hepatectomy, is predominantly nonbinucleating. During rat liver carcinogenesis, the early populations of phenotypically altered cells (foci) are predominantly diploid, as are the later neoplastic nodules and carcinomas, which can be shown to have a regeneration-like, largely nonbinucleating growth pattern. A negative correlation between growth capacity and ploidy can be demonstrated in cultured hepatocytes, regenerating livers, neoplastic nodules, and hepatocellular carcinomas, suggesting that suppression of binucleation and polyploidization may carry a growth advantage, in addition to helping to maintain a large population of diploid, potential stem cells. Since a diploid genome is less protected against mutagenic change than a polyploid genome, diploid tumor cells may, furthermore, be more prone than polyploid cells to undergo mutation-based progression toward increasing malignancy. The ability of liver tumor promoters like 2-acetylaminofluorene, cyproterone acetate, α-hexachlorocyclohexane and methylclofenapate to induce nonbinucleating hepatocyte growth may, therefore, cooperate with the selective growth stimulation of cancer cells and cancer cell precursors to promote liver carcinogenesis. Autophagy, a mechanism for the bulk degradation of cytoplasm, contributes to intracellular protein turnover and serves to restrict cellular growth. Rat liver carcinogenesis is accompanied by a progressive reduction of autophagic capacity, preneoplastic livers having 50% and hepatocellular carcinoma cells only 20% as much autophagy as normal hepatocytes. The ascites hepatoma cell line AH-130 has virtually no autophagy during logarithmic growth, but some autophagy is turned on when the cells become growth-arrested at high cell density. Ascitic fluid from AH-130 cells is able to completely inhibit autophagy in normal hepatocytes, suggesting that the cancer cells may improve their growth ability through an autocrine, autophagy-suppressive mechanism. Hepatocytes from preneoplastic livers similarly maintain a low autophagic activity under restrictive culture conditions, thereby surviving much better than normal hepatocytes, which switch on their autophagy. In the presence of an autophagy inhibitor (3-methyladenine), normal and preneoplastic hepatocytes survive equally well, testifying to the importance of autophagy as a determinant of cell survival and growth.
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    URL: http://dx.doi.org/10.1023/A:1007487425047
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    Immortalized human hepatocytes as a tool for the study of hepatocytic (de-)differentiation (1997)
    Springer
    Cell biology and toxicology 13 (1997), S. 375-386 
    Details
    ISSN: 1573-6822
    Keywords: bile salts ; cell culture ; immortalization ; lipoproteins ; liver ; plasma proteins ; transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Primary human hepatocytes were immortalized by stable transfection with a recombinant plasmid containing the early region of simian virus (SV) 40. The cells were cultured in serum-free, hormonally defined medium during the immortalization procedure. Foci of dividing cells were seen after 3 months. Albumin- and fibrinogen-secreting cells were selected and cloned by limiting dilution to obtain homologous cell populations. The established IHH (immortalized human hepatocyte) cell lines were evaluated for their usefulness in studying the regulation of cell growth and of certain differentiated hepatocyte functions. IHH cells retain several differentiated features of normal hepatocytes. They display albumin secretion at a level comparable to cultured primary human hepatocytes (30 µg albumin/ml per day). A portion of the IHH cells are polarized, forming bile canaliculi-like vacuoles where exogeneous organic anions accumulate. The multidrug resistance (MDR) P-glycoprotein, known to be localized at the canalicular membrane, is also present in these vacuoles. The polarized features allowed the use of IHH cells for the study of localization of the newly characterized multidrug resistance protein MRP1. The homologues of MRP were found in hepatocytes, MRP1 and MRP2 (cMOAT), both functioning in ATP-dependent excretion of anionic conjugates. In differentiated hepatocytes, MRP1 expression is extremely low. In contrast, MRP1 is highly expressed in proliferating IHH cells, where it is localized in lateral membranes. A highly differentiated feature of short-term cultured primary hepatocytes which is not detectable in IHH cells is active uptake of the bile salt taurocholate. Furthermore, IHH cells secrete triglyceride (TG)-rich lipoproteins, apolipoprotein B (0.6 µg/ml per day), and apolipoprotein A-I (1 µg/ml per day). However, they secrete apoB-containing TG-rich lipoproteins mainly in the LDL density range, while short-term cultured primary hepatocytes mainly secrete TG-rich lipoproteins in the VLDL density range. In conclusion, functions that are rapidly lost in short-term hepatocyte cultures are, in general, not displayed by IHH cells. Immortalized human hepatocytes provide a valuable tool for studying the regulation of hepatocyte proliferation-related phenomena.
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    URL: http://dx.doi.org/10.1023/A:1007404028681
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    Liver and spleen enhancement after intravenous injection of carboxydextran magnetite: effect of dose, delay of imaging, and field strength in anex vivo model (1996)
    Springer
    Magnetic resonance materials in physics, biology and medicine 4 (1996), S. 225-230 
    Details
    ISSN: 1352-8661
    Keywords: liver ; spleen contrast enhancement ; carboxydextran magnetite ; dose ; delayed imaging ; field strengths dependence ; ex vivo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics
    Notes: Abstract It has been predicted that liver and spleen enhancement after administration of superparamagnetic contrast agents may be different, depending on the strength of the main magnetic field. With the use of anex vivo model, we investigated at 0.3, 0.5, and 1.5 T the effects on liver and spleen signal intensity of 5, 15, and 45 µmol/kg body weight of dextran magnetite (SHU 555A) in 54 rats. Nine rats served as controls. At different time delays since injection, the animals were killed, and after perfusion with saline, the liver, brain, and spleen were fixed in formalin. The specimens were embedded in an agar gel matrix and imaged with inversion recovery T1-weighted, proton density spin echo, and T2*-weighted gradient recalled echo (GRE) sequences. At each magnetic field strength, peak liver and spleen signal loss increased with increasing dose of the contrast medium. Signal loss was significantly more conspicuous after a dose of 15 than 5 µmol/kg body weight, but not after a dose of 45 compared with 15 µmol/kg. No signal change was observed in the brain. GRE images showed higher enhancement than proton density-weighted spin echo and inversion recovery images but were noisier. The enhancement showed a plateau between 30 min and 24 hours. Only the signal decrease of the liver after a low dose of contrast medium on GRE images was significantly higher (p〈0.01) at 1.5 than at 0.5 and 0.3 T. Other differences in respect to the field strength were less significant (p〈0.05) or nonsignificant. Differences in the spleen enhancement were nonsignificant. SHU 555A at a dose of 15 µmol/kg is an efficient intracellular contrast agent for liver and spleen at low, mid, and high field strength. Proton density spin echo images are probably the sequence of choice to exploit SHU 555A contrast effects and a wide time window for imaging after its intravenous injection does exist.
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    URL: http://dx.doi.org/10.1007/BF01772010
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    Improved estimation of tissue hydration and bound water fraction in rat liver tissue (1996)
    Springer
    Magnetic resonance materials in physics, biology and medicine 4 (1996), S. 55-59 
    Details
    ISSN: 1352-8661
    Keywords: proton NMR ; relaxation times ; liver ; cold storage ; water fractions ; tissue hydration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics
    Notes: Abstract Based on recent improvements in the field, biexponential data from fresh rat liver and monoexponential data from cold storage experiments allow quantification of three distinct relaxation components in liver tissue: bound water (4.2%, R1=12.0 ± 1.7 s−1, R2=440 ± 180 s−1); structured water (59%, R1 ≈ 3.3 ± 0.07 s−1, R2 ≈ 24.9 ±1.1 s−1); and free water (≈37%, R1=R2 ≈ 0.4 s−1). However, only the relaxation rates of the structured water component change with water content: R1A (s−1)=6.53 * Ms/Mw − 0.77 (r2=0.911); R2A (s−1)=71.15 * Ms/Mw − 3.09 (r2=0.956), respectively. This suggests a slow exchange between bound and structured water in liver cells.
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    URL: http://dx.doi.org/10.1007/BF01759780
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    Metabolic types of regulation of lactate dehydrogenase and alcohol dehydrogenase activity in the liver of intact animals (1995)
    Springer
    Bulletin of experimental biology and medicine 119 (1995), S. 408-409 
    Details
    ISSN: 1573-8221
    Keywords: lactate dehydrogenase ; alcohol dehydrogenase ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A possible relationship between metabolic types of regulation of liver oxidative enzymes (lactate dehydrogenase and alcohol dehydrogenase) and the blood level of cortisol and insulin in intact animals is explored. The liver enzyme activity is found to depend on the initial physiological state of the organism.
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    URL: http://dx.doi.org/10.1007/BF02445906
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    Regeneration of the liver after partial hepatectomy with a beam of ionized plasma (1995)
    Springer
    Bulletin of experimental biology and medicine 119 (1995), S. 418-419 
    Details
    ISSN: 1573-8221
    Keywords: liver ; regeneration ; ionized plasma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Eighty guinea pigs underwent resection of the left lateral lobe of the liver, performed with a beam of ionized plasma. Morphological analysis 32 and 45 hours after partial hepatectomy revealed minor damage to the parenchyma to a depth of 300–400 μ. Autoradiography showed proliferative activity in the organ to occur in the early post-operative period.
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    URL: http://dx.doi.org/10.1007/BF02445909
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    Changes of the total water content and magnetic relaxation characteristics of the liver and small intestine in vagotomy (1995)
    Springer
    Bulletin of experimental biology and medicine 120 (1995), S. 1070-1072 
    Details
    ISSN: 1573-8221
    Keywords: water ; time of magnetic relaxation ; liver ; small intestine ; vagotomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Bilateral subdiaphragmatic truncal vagotomy in rats results in a disturbance of water metabolism in the liver and small intestine which manifests itself in an increase of the total water content, prolongation of the spin-lattice and spin-spin relaxation, and in a distortion of the correlation between them. The dynamics of water metabolism is of a onepeak nature in the liver with a maximum after 7 days, whereas in the small intestine it is of a dual-peak type with peaks at 7 and 30 days. Near-normalization of the water balance in the digestive organs occurs 220 days later.
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    URL: http://dx.doi.org/10.1007/BF02444989
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  • 87
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    Effects of adaptation to hypoxia on cytochrome levels in the brain and liver of rats (1995)
    Springer
    Bulletin of experimental biology and medicine 120 (1995), S. 1193-1195 
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    ISSN: 1573-8221
    Keywords: adaptation ; hypoxia ; cytochromes ; brain ; liver ; individual resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract After a prolonged (for 30 days) adaptation of rats to intermittent hypoxia, their brains contained lowered levels of mitochondrial cytochromes, despite an increase in the number of mitochondria in the brain tissue mass, along with similar levels of high-energy compounds and more protein as compaired to the brains of unadapted controls. A mitochondrial population with novel properties presumably emerged in the brain. These effects were all more strongly marked in rats with an initially low resistance to hypoxia. In the liver of hypoxiaadapted animals, unlike in their brain, cytochrome levels in the mitochondrial and microsomal redox chains were lowered and the biogenesis of mitochondria was much less intensive.
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    URL: http://dx.doi.org/10.1007/BF02445568
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  • 88
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    Hepatoprotective properties of phospholiv, a preparation containing phosphatidylcholine from sunflower seeds and glycyrrhizic acid, in modeled cirrhosis of rat liver (1997)
    Springer
    Bulletin of experimental biology and medicine 124 (1997), S. 897-899 
    Details
    ISSN: 1573-8221
    Keywords: liver ; experimental cirrhosis ; RNA and protein synthesis ; phospholipid preparation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Hepatoprotective effect of Phospholiv, a phospholipid preparation containing phosphatidylcholine from sunflower seeds and glycyrrhizic acid trisodium salt, is studied using a model of CCl4-induced cirrhosis of the liver. Phospholiv protects hepatic tissues from necrotic and dystrophic changes and prevents the development of cirrhosis. Phospholiv restores impaired RNA and protein synthes is under conditions of chronic intoxication.
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    URL: http://dx.doi.org/10.1007/BF02446996
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    Opposite effects of adaptation to short-term stress and adaptation to periodic hypoxia on Na,K-ATPase activity in liver plasma membranes (1996)
    Springer
    Bulletin of experimental biology and medicine 121 (1996), S. 348-351 
    Details
    ISSN: 1573-8221
    Keywords: heart ; liver ; Na,K-ATPase ; lipid peroxidation ; stress ; adaptation to stress ; adaptation to hypoxia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Na,K-ATPase activity is shown to be lowered more than twice 2 hours after emotional pain stress in comparison with the initial level, remaining practically unchanged during the subsequent 24 hours. Adaptation to repeated stress results in a 50% activation of Na,K-ATPase. A protective effect is demonstrated in long-term stress against the background of preadaptation. Adaptation to periodic hypoxia inhibits liver Na,K-ATPase to the same extent as does acute stress. Against the background of preadaptation to periodic hypoxia, stress does not aggravate the drop of Na,K-ATPase activity. Adaptation to stress inhibits accumulation of products ofin vitro-induced lipid peroxidation in the heart 1.4-fold and does not affect it in the liver, whereas adaptation to hypoxia sharply accelerates the accumulation of oxidized products in both organs, which probably explains the activation of liver Na,K-ATPase in adaptation to stress and its inhibition in adaptation to hypoxia.
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    URL: http://dx.doi.org/10.1007/BF02446724
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    Ultrastructural changes in albino mouse liver caused by isogenous F1+ and F1− strains ofYersinia pestis and their correction with ceftriaxone (1996)
    Springer
    Bulletin of experimental biology and medicine 121 (1996), S. 533-536 
    Details
    ISSN: 1573-8221
    Keywords: experimental plague ; liver ; ceftriaxone ; ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Fatty dystrophy and partial cytoplasmic necrosis predominate during the preagonal period in parenchymatous organs of mice infected withYersinia pestis 231 F1+. Endothelial damage, fibrin precipitation, and microcirculatory disorders occur in sinusoidal capillaries. More pronounced changes in the liver develop during the preagonal period in mice infected withY. pestis 231 F1−. Treatment with ceftriaxone leads to 100% survival in both groups and substantial restoration of liver structure.
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    URL: http://dx.doi.org/10.1007/BF02446960
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    Effect of the catalase inhibitor 3-amino-1,2,4-triazole on oxidation-phosphorylation coupling and the state of the mitochondrial adenosine system in the liver of albino rats (1996)
    Springer
    Bulletin of experimental biology and medicine 121 (1996), S. 576-578 
    Details
    ISSN: 1573-8221
    Keywords: catalase inhibitors ; liver ; oxidative phosphorylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Incubation of the specific catalase inhibitor 3-amino-1,2,4-triazole with liver mitochondria and administration of this drug to intact rats are shown to uncouple oxidation and phosphorylation and to inhibit adenosine nucleotide synthesis in the animal liver. These disturbances apparently results from catalase inhibition.
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    URL: http://dx.doi.org/10.1007/BF02447121
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    Phospholipid composition of liver mitochondria in experimental hemorrhagic shock (1997)
    Springer
    Bulletin of experimental biology and medicine 124 (1997), S. 658-660 
    Details
    ISSN: 1573-8221
    Keywords: phospholipids ; mitochondria ; liver ; hemorrhagic shock
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Heparin used as an anticoagulant in modeled hemorrhagic shock decreases the phosphatidylcholine and increases the phosphatidylethanolamine contents in the mitochondria. Accumulation of lysophosphatidylcholine in whole mitochondria and their inner membrane is observed in hemorrhagic shock. At the same time, hemorrhagic shock decreases phosphatidylcholine content in the inner and outer mitochondrial membranes and increases phosphatidylethanolamine content in the outer membranes. Modification of phospholipid composition of mitochondrial membranes is a mechanism responsible for impaired energy production in liver mitochondria in hemorrhagic shock.
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    URL: http://dx.doi.org/10.1007/BF02445054
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    Effect of chorionic gonadotropin on irradiated animals (1999)
    Springer
    Bulletin of experimental biology and medicine 127 (1999), S. 483-484 
    Details
    ISSN: 1573-8221
    Keywords: chorionic gonadotropin ; irradiation ; blood ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Chorionic gonadotropin exerts a protective effect on irradiated animals: it increases survival rate and number of peripheral blood leukocytes, improves the structure of liver parenchyma, and increases body weight.
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    URL: http://dx.doi.org/10.1007/BF02434946
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    Growth-inhibitory activity of bone marrow cells during CCl4-induced liver cirrhosis (1999)
    Springer
    Bulletin of experimental biology and medicine 127 (1999), S. 587-589 
    Details
    ISSN: 1573-8221
    Keywords: liver ; CCl 4 ; cirrhosis ; bone marrow ; hemopoiesis ; macrophages ; tumor necrosis factor-α
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract During CCl4-induced liver cirrhosis, cells of the hemopoiesis-inducing microenvironment in the bone marrow of BALB/c mice produced activity inhibiting the growth of erythropoiesis and granulomonocytopoiesis precursors. Stimulation with yeast polysaccharide zymosan increased the inhibitory activity (especially in relation to granulomonocytic precursors). The highest growth-inhibitory activity was produced by the bone marrow adherent fraction (residual bone marrow macrophages). Tumor necrosis factor-α is probably responsible for the inhibition of the growth of myeloid precursors in mice with CCl4-induced liver cirrhosis.
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    URL: http://dx.doi.org/10.1007/BF02433285
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    Immediate and remote effects of antitumor drug on the morphology of rat liver (1998)
    Springer
    Bulletin of experimental biology and medicine 126 (1998), S. 1140-1143 
    Details
    ISSN: 1573-8221
    Keywords: liver ; platidiam ; pharmorubicine ; CCl 4-induced hepatitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Experiments performed on rats have shown that a single intravenous injection of the antitumor preparations platidiam and pharmorubicine in the maximum tolerated dose cause morphological changes in the liver which are preserved for 3 months after platidiam and for 6 moths after pharmorubicine. Instability of reparative processes in the liver was revealed when the rats were poisoned with CCl4, 1, 3, and 6 months after administration of the cytostatics.
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    URL: http://dx.doi.org/10.1007/BF02447256
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    Free-radical damage to the liver during its transplantation under conditions of oxidative stress (1995)
    Springer
    Bulletin of experimental biology and medicine 120 (1995), S. 1093-1095 
    Details
    ISSN: 1573-8221
    Keywords: liver ; transplantation ; free-radical damage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The role played by oxygenation of the recipient organism in the development of reperfusion-induced damage to the transplanted liver was evaluated in minipigs, and animals in which the transplant operations failed were found to have developed oxidative stress. The results indicate that free-radica oxidation has a role to play in the damage to cellular structures of the recipient and that it is important to correct this damage as early as possible by means of antioxidants and iron-chelating agents.
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    URL: http://dx.doi.org/10.1007/BF02445473
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    Structural changes in dog liver during adaptation to high altitude (1997)
    Springer
    Bulletin of experimental biology and medicine 123 (1997), S. 619-622 
    Details
    ISSN: 1573-8221
    Keywords: adaptation ; high altitude ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Vascular and tissue changes in the livers of dogs living on an altitude of 3200 m above sea level for various periods were studied by histological, morphometric, and electromicroscopic methods. Destructive changes were observed in hepatocytes after a month of exposure, which were due mainly to impaired hepatic microcirculation and increased from the center to the periphery of hepatic acinus. Ultrastructural changes occurred predominantly in the energy-producing and protein-synthesizing systems of hepatocytes.
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    URL: http://dx.doi.org/10.1007/BF02458097
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    Correction of hyperlipoproteinogenic microangiopathy and organ pathology with thymalin and leu-enkephalin in the early stages of atherogenesis (1996)
    Springer
    Bulletin of experimental biology and medicine 121 (1996), S. 100-103 
    Details
    ISSN: 1573-8221
    Keywords: thymalin ; leu-enkephalin ; hyperlipidemia ; microangiopathy ; myocardium ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The effects of thymalin and leu-enkephalin on lipid peroxidation and microcirculatory disorders in the early stages of atherogenesis are compared. Correction of the generalized microcirculatory response to hyperlipoproteinemia with the peptides manifested itself in the regression of atherosclerotic lesions in the aorta and restoration of the morphofunctional state of the myocardium and liver.
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    URL: http://dx.doi.org/10.1007/BF02445719
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    A quantitative study of dehydrogenase activity of hepatocytes in systemic endotoxinemia (1995)
    Springer
    Bulletin of experimental biology and medicine 119 (1995), S. 101-104 
    Details
    ISSN: 1573-8221
    Keywords: metabolism ; liver ; endotoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A histophotometric study of the liver dehydrogenase activity reveals the nature of changes of enzymatic homeostasis and its periodicity in the dynamics of endotoxinemia in dogs. A compensatory reaction to lipopolysaccharide administration develops during the first two hours. A decrease of dehydrogenase and diaphorase activity and the development of structural damage to hepatocytes appear later. It is shown that the activation of free-radical oxidation as well as an increase of the level of medium-sized molecules in the blood plasma play a key role in the pathogenesis of liver damage.
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    URL: http://dx.doi.org/10.1007/BF02445944
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    Toxicological study of king crab collagenase (1995)
    Springer
    Bulletin of experimental biology and medicine 119 (1995), S. 377-380 
    Details
    ISSN: 1573-8221
    Keywords: collagenase ; king crab ; toxicology ; blood components ; liver ; kidneys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A toxicological study of a preparation of king crab collagenase designed for local treatment of wounds shows that daily hypodermal administration of various concentrations of preparation (1.5 to 15 mg/ml) over 5 days does not affect erythrocyte morphology or hemoglobin content in laboratory animals (rats and rabbits). Systemic enzyme administration does not alter the histological structure of the kidneys (kidney is the target organ for enzyme) but leads to dose-dependent reversible degeneration of rat liver tissues. The milder effects of the preparation in comparison with a comparable dose of the widely used chymopsin affirm that this collagenase preparation is suitable for external use.
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    URL: http://dx.doi.org/10.1007/BF02445898
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