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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    European journal of nutrition 36 (1997), S. 23-27 
    ISSN: 1436-6215
    Schlagwort(e): Vitamin E ; Fleisch ; Fettgewebe ; Leber ; Eigelb ; Vitamin E ; meat ; adipose tissue ; liver ; egg yolk
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Medizin
    Beschreibung / Inhaltsverzeichnis: 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.
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    European journal of nutrition 32 (1993), S. 187-197 
    ISSN: 1436-6215
    Schlagwort(e): Zinkdepletion ; Zwangsernährung ; Fettgehalt ; Fettsäurezusammensetzung ; Leber ; Gehirn ; Zinc deficiency ; force-feeding technique ; fat content ; fatty acid composition ; liver ; brain
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Medizin
    Beschreibung / Inhaltsverzeichnis: Summary In the present work the influence of zinc deficiency on fat content and fatty acid composition of liver and fatty acid composition of brain of rats with a high food intake was investigated. Using the force-feeding technique the rats were fed 14.5 g food daily at days 1 to 4, and then 11.6 g food for later days. After 7 days the zinc-deficient animals had a fatty liver which was characterized by an increase in fat content (68%) and dry matter (23%). The amounts of lauric acid, myristic acid, myristoleic acid, palmitic acid, palmitoleic acid, and oleic acid were also increased by 100 to 200% in the liver of zinc-deficient animals, whereas the amount of arachidonic acid was decreased by 29%. The amounts of phosphatidylcholine and phosphatidylethanolamine in the liver were not changed by zinc deficiency, but the fatty acid composition of these phospholipids was changed. The liver phospholipids of zinc-deficient animals had a decreased proportion of arachidonic acid, but an increased proportion of docosahexaenoic acid. In the zinc-deficient animals there also existed a positive correlation between the fat content in the liver and the ratio between linoleic and arachidonic acid in the liver and a negative correlation between the fat content in the liver and the amount of arachidonic acid in the liver. These correlations as well as the changes in liver fatty acid composition of zinc-deficient animals suggest that the fatty liver might be the result of a disturbed metabolism of linoleic acid. In contrast, zinc deficiency did not influence the fatty acid composition of brain. This means that brain is protected against the effects of short-term zinc deficiency.
    Notizen: Zusammenfassung In der vorliegenden Arbeit wurde der Einfluß von Zinkdepletion auf den Gesamtfettgehalt und die Fettsäurezusammensetzung der Leber sowie die Fettsäurezusammensetzung des Gehirns bei Ratten mit sehr hoher Futteraufnahme untersucht. Mit Hilfe der Zwangsernährung erhielten die Tiere in den ersten vier Versuchstagen täglich 14,5 g Futter und in den folgenden Tagen 11.6 g Futter. Es zeigte sich, daß die Depletionstiere bereits nach 7 Versuchstagen eine Fettleber entwickelt hatten, die durch einen um 68% erhöhten Gesamtfettgehalt und einen um 23% erhöhten Trockensubstanzgehalt gekennzeichnet war. Zugleich waren in der Leber der Depletionstiere die Gehalte der Laurinsäure, Myristinsäure, Myristoleinsäure, Palmitinsäure, Palmitoleinsäure und Ölsäure um 100 bis 200% erhöht, während der Gehalt der Arachidonsäure um 29% erniedrigt war. Die Gehalte der Phospholipide Phosphatidylcholin und Phosphatidylethanolamin waren bei den Depletionstieren im Vergleich zu den Kontrolltieren unverändert, jedoch zeigten sich Änderungen der Fettsäurezusammensetzung dieser Phospholipide, gekennzeichnet vor allem durch einen verminderten Anteil an Arachidonsäure (20:4) und einen erhöhten Anteil an Docosahexaensäure (22:6). Neben diesen Effekten bestand zwischen dem Gesamtfettgehalt der Leber und dem Quotienten aus Linolsäure und Arachidonsäure in der Leber bei den Depletionstieren eine positive Korrelation, zwischen dem Gesamtfettgehalt der Leber und dem Arachidonsäuregehalt der Leber eine negative Korrelation. Diese Korrelationen sowie die geänderte Fettsäurezusammensetzung in der Leber deuten darauf hin, daß die Fettleber Folge des im Zinkmangel gestörten Linolsäurestoffwechsels sein könnte. Im Gegensatz zur Leber traten im Gehirn keine Veränderungen der Fettsäurezusammensetzung sowie der Fettsäuregehalte auf. Dies deutet darauf hin, daß das Gehirn zumindest kurzfristig gegen Auswirkungen des Zinkmangels geschützt ist.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    BioMetals 10 (1997), S. 351-355 
    ISSN: 1572-8773
    Schlagwort(e): heart ; liver ; maghemite ; magnetite ; spleen
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    BioMetals 11 (1998), S. 49-53 
    ISSN: 1572-8773
    Schlagwort(e): copper ; liver ; manganese ; metals ; zinc
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    ISSN: 1572-8773
    Schlagwort(e): energy dispersive X-ray fluorescence ; liver ; lead toxicity ; inter-elemental effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    BioMetals 9 (1996), S. 205-209 
    ISSN: 1572-8773
    Schlagwort(e): iron ; liver ; human ; animal
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 46 (1990), S. 688-693 
    ISSN: 1420-9071
    Schlagwort(e): Metallothionein ; liver ; primary biliary cirrhosis ; copper ; zinc
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary A copper-containing protein was purified from the liver of a patient with primary biliary cirrhosis by a combination of gel filtration and anion exchange chromatography. This copper-protein had UV absorption and emission spectra, an amino acid composition, and a molecular mass which were characteristic for metallothionein (MT). From 8 livers (3 control, 1 fetal and 4 primary biliary cirrhosis) MT was extracted with non-reducing buffer and centrifuged, and the pellets were re-extracted with a 1% 2-mercaptoethanol-containing buffer. The non-reducing buffer extracted a predominantly copper-containing MT from the livers of patients with primary biliary cirrhosis and a predominantly zinc-containing MT from control lives and the fetal liver. Only from the fetal liver was a copper/zinc containing MT solubilized during the re-extraction with 2-mercaptoethanol-containing buffer. These results indicate that human MT is a unique metalloprotein with age and disease-dependent characteristics.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 46 (1990), S. 617-630 
    ISSN: 1420-9071
    Schlagwort(e): Fatty acid binding protein ; carrier proteins ; long-chain fatty acid ; liver ; intestine ; myocardium ; adipose tissue ; fatty acid metabolism ; cell growth
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Cytosolic fatty acid binding proteins (FABP) belong to a gene family of which eight members have been conclusively identified. These 14–15 kDa proteins are abundantly expressed in a highly tissue-specific manner. Although the functions of the cytosolic FABP are not clearly established, they appear to enhance the transfer of long-chain fatty acids between artificial and native lipid membranes, and also to have a stimulatory effect on a number of enzymes of fatty acid metabolism in vitro. These findings, as well as the tissue expression, ligand binding properties, ontogeny and regulation of these proteins provide a considerable body of indirect evidence supporting a broad role for the FABP in the intracellular transport and metabolism of long-chain fatty acids. The available data also support the existence of structure- and tissue-specific specialization of function among different members of the FABP gene family. Moreover, FABP may also have a possible role in the modulation of cell growth and proliferation, possibly by virtue of their affinity for ligands such as prostaglandins, leukotrienes and fatty acids, which are known to influence cell growth activity. FABP structurally unrelated to the cytosolic gene family have also been identified in the plasma membranes of several tissues (FABPpm). These proteins have not been fully characterized to date, but strong evidence suggests that they function in the transport of long-chain fatty acids across the plasma membrane.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    ISSN: 1420-9071
    Schlagwort(e): Thioredoxin ; thioredoxin reductase ; perinatal period ; liver ; pancreatic hormones ; corticosteroid
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The development and hormonal regulation of thioredoxin and of the thioredoxin-reductase system were investigated during the perinatal period in rat liver. An immunological procedure was developed in order to quantify thioredoxin in fetal and neonatal hepatocytes. Both immunoreactive thioredoxin and thioredoxin-reductase activity appeared on day 16.5 of pregnancy. The level of immunoreactive thioredoxin increased during the late fetal period, and its level was the same 24 h after birth. Moreover, its development was not subjected to hormonal regulation by corticosteroids and glucagon. In contrast, thioredoxin-reductase activity increased 3 times during the late fetal period and presented a marked increase 24 h after birth. In the absence of glucocorticoids there was no increase in the level of thioredoxin reductase, while administration of hydrocortisone acetate and glucagon to fetuses prematurely evoked its activity. This study suggests that if thioredoxin acts physiologically, this activity is related to the state of reduction of the molecule rather than to the total concentration in the liver.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 49 (1993), S. 332-334 
    ISSN: 1420-9071
    Schlagwort(e): Melatonin ; 2-Iodomelatonin ; glucocorticoid receptors ; brain ; thymus ; liver ; pituitary
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The effect of melatonin and 2-Iodomelatonin on nuclear and cytosolic glucocorticoid receptors in the brain, pituitary, thymus and liver has been examined. The results indicate that both melatonin and 2-Iodomelatonin administration is associated with marked changes in the density and the affinity of cytosolic and nuclear forms of glucocorticoid receptors. These observations are discussed in the context of a possible involvement of pineal melatonin in the mechanisms regulating the behaviour and metabolism of steroid receptors.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 11
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 50 (1994), S. 1092-1098 
    ISSN: 1420-9071
    Schlagwort(e): Aging ; liver ; transcription ; heat shock transcription factor ; rat ; senescence
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract An alteration in the ability of cells to express heat shock proteins could be physiologically important in aging because all living organisms show a reduced ability to respond to stress with increasing age. Using hepatocytes freshly isolated from young adult and old rats, we have shown that the induction of hsp70 expression by heat shock is reduced approximately 50% with age. The decrease in hsp70 expression occurs at the level of transcription and appears to arise from a defect in the heat shock transcription factor. Other investigators have also shown that the induction of hsp70 expression by heat shock as well as other stresses declines significantly with age in a variety of tissues from rats as well as mononuclear cells from human subjects. In addition, a decrease in the inducibility of hsp70 is observed with cell senescence in cultured cells. Therefore, it appears that a reduced ability to express hsp70 in response to stress may be a common phenomenon underlying the aging process.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 12
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 52 (1996), S. 554-557 
    ISSN: 1420-9071
    Schlagwort(e): Ion transport ; hepatocytes ; liver
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 13
    ISSN: 1420-9071
    Schlagwort(e): Latent iron deficiency ; liver ; kidney ; spleen ; metals ; rehabilitation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Feeding a marginally low iron content diet (18–20 mg iron/kg diet) to weaned (21-day-old) rats for 8 weeks produced a significant decrease in liver non-heme iron (66%, p〈0.001) but no change in blood hemoglobin. Total iron contents of liver (56%, p〈0.01), spleen (20%, p〈0.05), and kidney (19%, p〈0.05) were also found to decrease along with increased zinc, copper, calcium, manganese lead and cadmium in various organs. The magnitude of alteration of a metal was different in different organs. However, liver was found to be the most affected organ. Two weeks of rehabilitation with iron-sufficient diet (390 mg iron/kg diet) normalized these altered levels.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 14
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 52 (1996), S. 795-798 
    ISSN: 1420-9071
    Schlagwort(e): Estradiol ; progesterone ; polyamine oxidase ; diamine oxidase ; polyamines ; uterus ; liver
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 15
    ISSN: 1572-8773
    Schlagwort(e): 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)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 16
    ISSN: 1572-8773
    Schlagwort(e): cadmium ; kidneys ; liver ; metallothionein ; tissue injury
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 17
    ISSN: 1436-6215
    Schlagwort(e): Dietary cholesterol ; saturated fat ; fish oil ; lipid concentration ; fatty acid composition ; liver ; rat ; Nahrungscholesterin ; gesättigte Fette ; Fischöl ; Lipidgehalt ; Fettsäurezusammensetzung ; Leber ; Ratte
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung In der vorliegenden Arbeit wurde der Einfluß hyperlipidämischer Diätkomponenten und Fischöl auf den Fettgehalt und die Fettsäurezusammensetzung von Rattenlebern untersucht. Dazu erhielten in einem ersten Versuch männliche Sprague-Dawley Ratten über einen Zeitraum von 28 Tagen eine halbsynthetische fettarme, cholesterinfreie Diät mit 6,5% Kokosfett und 1,5% Distelöl bzw. eine fettreiche, hyperlipidämische Diät mit 7,3% Kokosfett, 7,3% Rindertalg, 0,4% Distelöl und 1,5% Cholesterin. Anschließend wurden 1,4%, 2,8% und 5,6% des gesättigten Fettes der hyperlipidämischen Diät durch Fischöl ersetzt und weitere 10 bzw. 20 Tage an die Tiere verabreicht. In einem zweiten Versuch wurden männliche Sprague-Dawley Ratten über 28 Tage fettarme bzw. fettreiche Diäten verabreicht, die kein oder 1,5% Cholesterin enthielten. Danach wurde ein Teil des Kokosfettes und Rindertalges durch 5,6% Fischöl ersetzt und weitere 20 Tage an die Hälfte aller Versuchtstiere verabreicht. Ratten, die die hyperlipidämische Diät aus Versuch 1 erhielten, entwickelten innerhalb von 28 Tagen stark vergrößerte Fettlebern. Versuch 2 zeigte, daß Cholesterin für die Anreicherung von Leberlipiden verantwortlich war. Durch die Zulage von Cholesterin fielen die Anteile der gesättigten Fettsäuren (SFA), besonders der 18:0, in der Leber ab, während die Anteile der Monoenfettsäuren (MUFA), vor allem 16:1 und 18:1 stark zunahmen. Im Gegensatz dazu verminderten Diäten mit Fischöl, trotz ihres hohen MUFA Gehaltes, die Anteile der MUFA in der Leber. Ratten, die die 18:2 n-6 arme, hyperlipidämische Diät erhielten, wiesen im Vergleich zu Ratten mit fettarmer und cholesterinfreier Diät einen niedrigeren Gehalt an 18:2 n-6 in der Leber auf. Auch der Anteil an 20:4 n-6 in der Leber erwies sich durch den Einsatz der hyperlipidämischen Diät und der Fischöldiäten als stark vermindert. Die Ergebnisse von Versuch 2 verdeutlichen, daß sowohl Cholesterin als auch Fischöl in der Diät den Anteil der 20:4 n-6 in den Leberlipiden reduzieren, was auf eine verminderte Desaturierung zurückzuführen sein dürfte. Fischölzulagen führten in beiden Versuchen zu einem Anstieg von allen langkettigen n-3 mehrfach ungesättigten Fettsäuren (PUFA). Die anteilsmäßige Zunahme dieser Fettsäuren war stark abhängig von der eingesetzten Fischöldosis und zeigte sich am größten bei Einsatz von 5,6% Fischöl. Der gleichzeitige Einsatz von Cholesterin verminderte hingegen den Anteil der 22:6 n-3 in den Rattenlebern, was ebenfalls auf eine gestörte Desaturierung der PUFA hindeuten dürfte.
    Notizen: Summary This investigation was attempted to clarify the effects of dietary hyperlipidemic components and fish oil on concentration of lipids in liver and liver fatty acid profile of rats. In a first experiment male Sprague-Dawley rats were maintained on a semipurified low-fat diet with 6.5% coconut oil and 1.5% safflower oil, but without added cholesterol, or a high-fat hyperlipidemic diet supplemented with 7.3% coconut oil, 7.3% beef tallow, 0.4% safflower oil, and 1.5% cholesterol for 28 days. Rats fed the hyperlipidemic diet were then switched to fish oil diets with 1.4%, 2.8%, and 5.6% fish oil in exchange for coconut oil and beef tallow for, respectively, 10 and 20 days. In a second experiment male Sprague-Dawley rats were fed low-fat or high-fat diets without or with 1.5% added cholesterol for 28 days. Half of each group was then changed to a fish oil diet (for 20 days) which contained 5.6% fish oil in exchange for coconut oil and beef tallow. In experiment 1, rats fed the hyperlipidemic diet had enlarged fatty livers within 28 days. Experiment 2 showed that cholesterol in the diet was responsible for the accumulating liver lipids. Feeding diets with added cholesterol, the proportions of saturated fatty acids (SFA), especially 18:0, were markedly reduced in liver, whereas levels of monounsaturated fatty acids (MUFA) were greatly increased compared to diets without added cholesterol. This increase was most pronounced with respect to 16:1 and 18:1. In contrast, fish oil diets lowered MUFA level in liver in spite of its high MUFA content. Rats fed the highly saturated hyperlipidemic diet low in 18:2 n-6 had reduced 18:2 n-6 levels in liver compared to rats fed the low-fat diet without added cholesterol. Also, 20:4 n-6 level in liver was markedly reduced after the administration of the hyperlipidemic diet or the fish oil diets. Results of experiment 2 elucidate that cholesterol as well as fish oil sharply lowered 20:4 n-6 level in liver, which might be due to a reduced desaturation. In both experiments feeding fish oil increased all long-chain n-3 polyunsaturated fatty acids (PUFA) in liver. This occurred in a dose-dependent fashion and reached a maximum level with 5.6% fish oil in the diet. When additional cholesterol was applied 22:6 n-3 level in liver fell. This indicates also an impaired desaturation of PUFA due to dietary cholesterol.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 18
    Digitale Medien
    Digitale Medien
    Springer
    European journal of nutrition 34 (1995), S. 220-223 
    ISSN: 1436-6215
    Schlagwort(e): Ascorbic acid ; glutathioneperoxidase ; lipid peroxides ; liver ; Ascorbinsäure ; Glutathion-Peroxidase ; Lipidperoxiden ; Leber
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Medizin
    Beschreibung / Inhaltsverzeichnis: 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.
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 19
    ISSN: 1436-6215
    Schlagwort(e): Riboflavin ; Milch ; Leber ; Restkörper ; Laktation ; Ratte ; Riboflavin ; milk ; liver ; carcass ; lactation ; rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Medizin
    Beschreibung / Inhaltsverzeichnis: 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.
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 20
    ISSN: 1436-6215
    Schlagwort(e): Environmental temperature ; energy expenditure ; ouabain-sensitive respiration ; duodenal mucosa ; liver ; rats ; Umgebungstemperatur ; Energieumsatz ; Quabain-sensitive Respiration ; Duodenalmukosa ; Leber ; Ratten
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Medizin
    Beschreibung / Inhaltsverzeichnis: 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.
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 21
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 50 (1994), S. 121-123 
    ISSN: 1420-9071
    Schlagwort(e): Eel ; hydrostatic pressure ; liver ; mitochondria ; phospholipids
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract Homeoviscous adaptation of membrane fluidity is known to exist in fish living at great depths. Is this adaptation also present in fish living near the surface but experimentally acclimated to high pressure? The composition of mitochondria-rich fractions extracted from the livers of eels acclimated for 15 days at 101 ATA was determined. The results show that pressure induced a significant increase (+100%) of total phospholipids (PL) and cholesterol without a change in their ratio. The increase of PL content was accompanied by a decrease in phosphatidylcholine in favour of phosphatidyl ethanolamine which, due to its preference for the H11 form, is able to compensate for the loss in fluidity induced by pressure.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 22
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 52 (1996), S. 661-663 
    ISSN: 1420-9071
    Schlagwort(e): Non-heart-beating donor ; liver ; oxygen ; persufflation ; aerobic ischemia ; transplantation ; preservation ; resuscitation ; viability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 23
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 46 (1990), S. 694-696 
    ISSN: 1420-9071
    Schlagwort(e): Metallothionein ; cadmium ; cadmium-binding protein ; testis ; liver ; kidney
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The incorporation of35S-cysteine and3H-glutamic acid was studied in mouse hepatic and renal metallothionein and in testicular cadmium-binding protein of similar molecular weight. Preferential incorporation of35S-cysteine over3H-glutamic acid was observed not only in hepatic and renal metallothionein, but also in testicular cadmium-binding protein. When the antigenic reactivity of these proteins was compared, all three proteins reacted with the metallothionein antibody. These similarities suggest that the low molecular weight testicular cadmium-binding protein is apparently metallothionein.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 24
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 49 (1993), S. 885-887 
    ISSN: 1420-9071
    Schlagwort(e): Amino sugar analogues ; liver ; intestine ; glycoproteins
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract Different radiolabelled N-acyl-derivatives of D-glucosamine were synthesized using D-glucosamine and the respective carbonic acid anhydride. Metabolism of these sugar analogues could be shown in vitro as well as in vivo. After the intraperitoneal administration of these radiolabelled N-acyl-D-glucosamines to mice, their rate of incorporation into glycoproteins of different organs was found to increase markedly with the length of the N-acyl side chain. Highest incorporation was measured in the whole intestine using N-pentanoyl-D-glucosamine as label.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 25
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 51 (1995), S. 589-591 
    ISSN: 1420-9071
    Schlagwort(e): Oyster mushroom (Pleurotus ostreatus) ; cholesterol ; serum ; lipoproteins ; liver ; HMG-CoA reductase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: 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%).
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 26
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 52 (1996), S. 687-690 
    ISSN: 1420-9071
    Schlagwort(e): Vitamin A ; diet ; rats ; plasma ; liver ; scavengers ; antioxidant enzymes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 27
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 45 (1993), S. 337-341 
    ISSN: 1432-1041
    Schlagwort(e): Minoxidil ; sulphotransferase ; liver ; extrahepatic tissues ; platelets ; interindividual variability ; adults ; neonates
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Minoxidil requires to be sulphated to exert its hypotensive effect. We report on interindividual variability in the rate of minoxidil sulphation in 118 specimens of human liver and in platelets obtained from 100 healthy subjects and 100 newborns. The frequency distribution histogram of the hepatic activity of minoxidil sulphotransferase was positively skewed; the mean was 631 pmol · min−1 · mg−1. After logarithmic transformation of the enzyme activity, the frequency distribution histogram became symmetrical and did not significantly deviate from normality. The rate of minoxidil sulphation was not different in platelets from adults (0.74 pmol · min−1 · mg−1) and newborns (1.16 pmol · min−1 · mg−1). The frequency distribution histograms were positively skewed and the results of normal equivalent deviation analysis was compatible with the presence of at least two subgroups of sulphotransferase in liver and platelets. Thus, two phenotypes of sulphotransferase exist in human liver and platelets, and the “extensive sulphator” phenotype contributes to skewing the frequency distribution. In platelets, the percentage of subjects that fall in the two subgroups is different at birth and in adulthood. This can explain the different shape of the frequency distribution in newborn and adult platelets and suggests that platelet minoxidil sulphotransferase undergoes modification after birth.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 28
    ISSN: 1432-1041
    Schlagwort(e): Budesonide ; liver ; man ; sulphotransferase ; testosterone ; drug metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Budesonide, a corticosteroid used in the treatment of asthma and allergic reactions, is almost entirely cleared by metabolism in man. We describe the sulphation of budesonide in human liver and lung and provide evidences that the sulphation of budesonide is catalysed by testosterone sulphotransferase. A rapid and reproducible radiometric assay for budesonide sulphotransferase is described. Liver specimens were obtained from 35 men and 65 women and lung specimens from 2 women and 17 men. The average hepatic budesonide sulphation rate was significantly higher in men (41.1 pmol·min−1·ml−1) than women (28.2 pmol·min−1·mg−1). In the lung, the mean budesonide sulphation rate was 5.0 pmol·min−1·mg−1. Testosterone strongly inhibited the hepatic sulphation of budesonide, whereas p-nitrophenol and dopamine were poor inhibitors; the IC50 was 7.0 uM (testosterone), 320 uM (p-nitrophenol) and 510 uM (dopamine). The hepatic rates of testosterone, p-nitrophenol and dopamine sulphation were measured in the same samples assayed for budesonide sulphotransferase. There was a correlation between the hepatic rates of budesonide and testosterone sulphation (P〈0.001; r=0.810). The activity of testosterone sulphotransferase was significantly greater in men than women (22.0 vs. 17.2 pmol·min−1·mg−1), wheres those of dopamine and p-nitrophenol sulphotransferase were not sex dependent. The hepatic activity of budesonide sulphotransferase parallels that of testosterone suggesting that sulphation is an important reaction in the metabolism of budesonide.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 29
    ISSN: 1432-1041
    Schlagwort(e): Key wordsProstaglandin E1 ; Carbonyl reductase; 13 ; 14-dihydro-15-keto-PGE1 ; 13 ; 14-dihydro-PGE1 ; human ; liver ; erythrocytes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 30
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 45 (1993), S. 483-487 
    ISSN: 1432-1041
    Schlagwort(e): Terbutaline ; Drug metabolism ; sulphotransferases ; liver ; intestine ; lung ; man ; stereoselective conjugation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The sulphation of (+) and (−) terbutaline was investigated in specimens of human intestinal mucosa isolated from the duodenum, ileum, ascending colon and sigmoid colon and in specimens of liver and lung. The lung specimens came from 8 current smokers and 11 ex-smokers, the latter having stopped at least 3 months before surgery. The rates (pmol·min−1·mg protein−1) of (+) and (−) terbutaline sulphation were 1195 and 948 (duodenum), 415 and 317 (ileum), 268 and 166 (ascending colon), 263 and 193 (sigmoid colon) and 45 and 34 (liver), respectively. Terbutaline sulphotransferase was more active in the small and large intestine than in the liver. In the lung, the rate of (+) terbutaline sulphation was 118 (ex-smokers) and 82 (smokers), and for (−) terbutaline it was 82 (ex-smokers) and 56 (smokers). In the gut, the activity of catechol sulphotransferase was significantly correlated with that of (+)- and (−)- terbutaline sulphotransferase whereas no correlation was found with phenol sulphotransferase. This correlation, the finding of the higher activity of terbutaline sulphotransferase in gut than in liver, and the pronounced thermal inactivation of the enzyme, are all consistent with the view that catechol sulphotransferase has a role in the sulphation of terbutaline.
    Materialart: Digitale Medien
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  • 31
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 47 (1994), S. 345-349 
    ISSN: 1432-1041
    Schlagwort(e): Chloroquine ; Stereoselectivity ; Histamine ; methyltransferase ; liver ; brain ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract This study was designed to determine whether both enantiomers of chloroquine inhibit histamine N-methyltransferase. The mean estimates of IC50 for the d- and l-enantiomers of chloroquine were 4.9 and 17.8 μM (liver), respectively and 6.9 and 21.6 μM (brain), respectively. Ki estimates were significantly lower with d- than with l-chloroquine; hence, d-chloroquine interacts with the enzyme more effectively than l-chloroquine. If the adverse effects of chloroquine are due to the inhibition of histamine N-methyltransferase, therapy with the l-enantiomer might have lower toxicity. The residual activity of histamine N-methyltransferase should reflect both the degree of inhibition by chloroquine and the level of enzyme expression. The rate of histamine methylation was measured in 100 human liver samples and its range and fold of variation were 29% and threefold, respectively. Susceptibility to chloroquine should be greater in subjects with limited expression of histamine N-methyltransferase.
    Materialart: Digitale Medien
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  • 32
    ISSN: 1432-1041
    Schlagwort(e): Key words 6-Mercaptopurine ; Thiopurine methyltransferase ; Polymorphism; erythrocytes ; liver ; kidney ; newborns ; adults
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 33
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 108 (1991), S. 29-38 
    ISSN: 1573-4919
    Schlagwort(e): cadmium ; catfish (Heteropneustes fossilis) ; metallothionein ; liver ; kidney ; induction ; turnover
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Summary Induction of metallothionein by cadmium in catfish was a dose-dependent, transcriptionally-controlled process. Metallothionein mRNA was detected after Cd-exposure. Chronic doses produced more metallothionein than a single acute dose. Zn and Cu induced metallothionein to a lower extent compared to Cd. A few other low molecular weight proteins were induced in cadmium-exposed catfish liver, besides metallothionein. Isoelectric point of catfish metallothionein was 3.9. The rate of depletion of Cd and metallothionein was very slow from liver and almost unchanged from kidney following its induction by cadmium.
    Materialart: Digitale Medien
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  • 34
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 123 (1993), S. 101-106 
    ISSN: 1573-4919
    Schlagwort(e): fatty acid-binding protein ; fatty acid oxidation ; peroxisomal fatty acid oxidation ; diet ; postnatal development ; liver ; muscle
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract A relation between fatty acid oxidation capacity and cytosolic FABP content was found in heart and various muscles of the rat. Other tissues do not show such a relation, since they are involved in more or other pathways of fatty acid metabolism. At postnatal development FABP content and fatty acid oxidation capacity rise concomitantly in heart and quadriceps muscle in contrast to in liver and kidney. A dietary fat content of 40 en. % increased only the FABP content of liver and adipose tissue. Peroxisomal proliferators increased fatty acid oxidation in both liver and kidney, but only the FABP content of liver, and had no effect on heart and skeletal muscle. The FABP content of muscle did not show adaptation to various conditions. Only it increased in fast-twitch muscles upon chronic electrostimulation and endurance training.
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  • 35
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 133-134 (1994), S. 69-83 
    ISSN: 1573-4919
    Schlagwort(e): mitochondria ; brain ; liver ; macromolecules ; localisation ; hexokinase ; mitochondrial creatine kinase ; oxidative phosphorylation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract Substitution of physiologically present macromolecules during isolation of mitochondria and investigation of their functions led to a significant change in regulation of oxidative phosphorylation. The differences compared to conventionally isolated mitochondria were that stimulation of oxidative phosphorylation appeared to rather depend on the activity of peripheral kinases than on the addition of free ADP. The localisation of peripheral kinases such as hexokinase and mitochondrial creatine kinase are described as well as the effects of macromolecules on the regulation of bound hexokinase and of oxidative phosphorylation via this enzyme.
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  • 36
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 139 (1994), S. 131-140 
    ISSN: 1573-4919
    Schlagwort(e): type 1 diabetes ; liver ; γ-glutamyltranspeptidase ; insulin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract The impact of type 1 diabetes mellitus on liver γ-glutamyltranspeptidase, a premalignant marker, was studied. Diabetes was induced in male Sprague Dawley and Fischer 344 rats by administration of Streptozotocin, which produced a stable and moderately severe diabetic state. In liver homogenates, γ-glutamyltranspeptidase was increased over control levels: 1.2, 8.1 and 13,2 fold in Strague-Dawley rats; 4.8, 58.4 and 84.7 fold in Fischer 344 rats; at 1, 3 and 6 weeks following Streptozotocin treatment. In plasma membranes isolated from the livers of Fischer 344 rats, γ-glutamyltranspeptidase was increased over control levels: 5.6, 75 and 127 fold at weeks 1, 3 and 6 following Streptozotocin treatment. The relative specific activity of 5′-nuleohdase was found to be similar: 9–14, indicating comparable degrees of plasma membrane purity. Plasma glutamate-pyruvate transaminase levels were minimally and similarly affected at all time points indicating lack of association of increasing γ-glutamyltranspeptidase activity with overt liver damage. Thyroid hormone replacement, with both T3 (0.6 μg/Kg) once a day and T4 (6.0 μg/kg) twice a day for three days elicited a further 30% increment in enzyme activity. Insulin replacement (20–40 units/200 g body weight) twice a day for five days reduced enzyme activity 51% at week 6. This was associated with an increase in γ-glutamyltranspeptidase in the plasma from 14 fold over control levels in the diabetic state at week 6 to 53 fold ever control levels after insulin replacement at week 6. It is proposed that the diabetes-induced increase in γ-glutamyltranspeptidase is reduced by an insulin-directed shedding of the enzyme into the plasma.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 37
    ISSN: 1573-4919
    Schlagwort(e): S-protein ; liver ; cell adhesion protein ; complement ; blood clotting
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Summary Human S-protein is a serum glycoprotein that binds and inhibits the activated complement complex, mediates coagulation through interaction with antithrombin III and plasminogen activator inhibitor I, and also functions as a cell adhesion protein through interactions with extracellular matrix and cell plasma membranes. A full length cDNA clone for human S-protein was isolated from a lambda gt11 cDNA library of mRNA from the HepG2 hepatocellular carcinoma cell line using mixed oligonucleotide sequences predicted from the amino-terminal amino acid sequence of human S-protein. The cDNA clone in lambda was subcloned into pUC18 for Southern and Northern blot experiments. Hybridization with radiolabeled human S-protein cDNA revealed a single copy gene encoding S-protein in human and mouse genomic DNA. In addition, the S-protein gene was detected in monkey, rat, dog, cow and rabbit genomic DNA. A 1.7 Kb mRNA for S-protein was detected in RNA from human liver and from the PLC/PRF5 human hepatoma cell line. No S-protein mRNA was detected in mRNA from human lung, placenta, or leukocytes or in total RNA from cultured human embryonal rhabdomyosarcoma (RD cell line) or cultured human fibroblasts from embryonic lung (IMR90 cell line) and neonatal foreskin. A 1.6 Kb mRNA for S-protein was detected in mRNA from mouse liver and brain. No S-protein mRNA was detected in mRNA from mouse skeletal muscle, kidney, heart or testis.
    Materialart: Digitale Medien
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  • 38
    ISSN: 1573-4919
    Schlagwort(e): DNA adducts ; liver ; fish ; 32P-postlabelling ; polycyclic aromatic hydrocarbons ; genotoxic biomarker
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 39
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 101 (1991), S. 167-174 
    ISSN: 1573-4919
    Schlagwort(e): rat protein phosphatase 2A ; liver ; heart ; diabetes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Summary Protein phosphatase 2A1 was purified from rat skeletal muscle and used to produce antisera to the three subunits of the holoenzyme. Affinity purified antibodies specific for the subunits of the phosphatase enzyme were found to recognize the type 2A1 and 2A2 phosphatase from rat skeletal muscle, heart, liver, brain and erythrocytes and were used to investigate the effects of diabetes on the levels of this enzyme in liver and heart. Phosphorylase phosphatase assays coupled with immunoblot analysis of fractionated rat liver and heart cytosol from normal and diabetic animals show no apparent differences in the quantity or activity of these enzymes following the induction of alloxan diabetes. When considering these results and the normal physiological concentrations of known effectors of these enzymes, it is likely that protein phosphatase 2A1 and 2A2 are not responsible for the dephosphorylation of phosphorylase a under physiological conditions.
    Materialart: Digitale Medien
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  • 40
    ISSN: 1573-4919
    Schlagwort(e): Bcl-2 ; Ca2+ ; hepatoma ; liver ; mitochondrial permeability transition ; tumor cells
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 41
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 109 (1992), S. 17-24 
    ISSN: 1573-4919
    Schlagwort(e): polyamines ; estradiol ; fish ; vitellogenesis ; liver ; skeletal muscle
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract Atlantic salmon (Salmo salar) were treated with 17-β estradiol to induce vitellogenin synthesis in liver. This led to an increase in liver wet weight and total DNA. After incubation with micrococcal nuclease (EC 3.1.31.1) less soluble chromatin was obtained from nuclei of the estradiol treated than the control fish, but active gene regions were solubilized by the nuclease. Thus, in the estradiol treated fish soluble mononucleosomes contained hybridizable vitellogenin gene sequences. As a result of estradiol treatment the content in total liver of putrescine rose 3-fold, that of spermidine 2-fold, while spermine was unchanged. In muscle no significant changes were observed. The regulatory functions of polyamines during gene expression were investigated by binding (14C)spermine to isolated liver nuclei depleted of endogenous polyamines. The number of binding sites was higher in nuclei of estradiol treated than control fish. (14C)spermine associated preferentially with micrococcal nuclease insensitive chromatin. Thus, the high content of putrescine and spermidine in liver supported the view of polyamine accumulation in proliferating tissues. The preferential binding to condensed chromatin indicated a stabilizing effect of polyamines on the organization of inactive chromatin structures.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 42
    ISSN: 1573-4919
    Schlagwort(e): atrial natriuretic factor ; cyclic GMP ; guanylate cyclase ; prohormone ; liver ; lung
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract The 98 amino acid (a. a.) N-terminus of the 126 a. a. atrial natriuretic factor (ANF) prohormone contains three peptides consisting of a. a. 1–30 (proANF 1–30), a. a. 31–67 (proANF 31–67) and a. a. 79–98 (proANF 79–98) with blood pressure lowering, sodium and/or potassium excreting properties similar to atrial natriuretic factor (a. a. 99–126, C-terminus of prohormone). ProANF 1–30 and proANF 31–67 have separate and distinct receptors from ANF in both vasculature and in the kidney to help mediate the above effects. At the cellular level proANFs 1–30, 31–67, and 79–98 as well as ANF's effects are mediated by enhancement of the guanylate cyclase (EC 4.6.1.2) — cyclic GMP system in vasculature and in the kidney. These peptides from the N-terminus of the ANF prohormone circulate normally in man and in all animal species tested. The object of the present investigation was to determine if these peptides have the ability to enhance either guanylate cyclase and/or adenylate cyclase in a variety of other tissues in addition to kidney and vasculature. ProANF 1–30, proANF 31–67, proANF 79–98, and ANF all increased rat lung, liver, heart and testes, but not spleen, particulate guanylate cyclase 2- to 3-fold at their 100 nM concentrations. Dose response curves revealed that maximal stimulation of particulate guanylate cyclase activity by these newly discovered peptides was at their 1 μM concentrations, with no further increase in activity above their 1 μM concentrations. Half-maximal (EC50) enhancement of particulate guanylate cyclase occurred at 0.15 ± 0.01, 0.3 ± 0.02, 0.5 ± 0.03, and 0.9 ± 0.03 nM for proANF 1–30, proANF 31–67, proANF 79–98 and ANF, respectively. ProANFs 1–30, 31–67, 79–98, and 99–126 (i.e., ANF) each increased cyclic GMP but not cyclic AMP levels in tissue slices of liver, lung, small intestine, heart, and testes. None of these peptides enhanced either adenylate cyclase or the soluble 100,000 G form of guanylate cyclase. The ability of these N-terminal peptides to enhance particulate guanylate cyclase activity in a wide variety of tissues suggests that they may have effects in a much wider variety of tissues than presently thought.
    Materialart: Digitale Medien
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  • 43
    ISSN: 1573-4919
    Schlagwort(e): liver ; γ-glutamyltranspeptidase ; development
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Summary Homogenates and plasma membranes were isolated from the livers of male Fischer 344 rats ranging in age from 19 hr to 92 days postnatal. These plasma membranes exhibited comparable levels of purity: protein yields were 2–2.5%; relative specific activities of 5′-nucleotidase and ouabain-sensitive Na+/K+-ATPase were from 8–11 and from 12–19, respectively. 5′-nucleotidase and ouabain-sensitive Na+-K+-ATPase displayed distinct and different developmental patterns. The activity of γ-glutamyltranspeptidase was found to be at exceptionally high levels in isolated plasma membranes immediately after birth and to decline precipitously thereafter achieving and maintaining low levels from days 3–21 postnatal. Liver plasma membrane γ-glutamyltranspeptidase activity was observed to increase 9.2 fold from this low point, first rising on day 21, peaking on day 40 and returning to low levels by day 56. From day 56 day to 92 postnatal, γ-glutamyltranspeptidase activity was expressed at a uniformly low level but a level 2 fold higher than that preceeding the rise at day 40. The hormone determinants of these developmental changes in γ-glutamyltranspeptidase activity are discussed.
    Materialart: Digitale Medien
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  • 44
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 116 (1992), S. 39-45 
    ISSN: 1573-4919
    Schlagwort(e): carnitine palmitoyltransferase ; malonyl-CoA ; heart ; liver ; fatty acid oxidation ; regulation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract Diminished sensitivity of hepatic carnitine palmitoyltransferase to inhibition by malonyl-CoA in the fasting and diabetic states is a well-recognized aspect of the regulatory mechanism forhepatic fatty acid oxidation. Inhibition of myocardial carnitine palmitoyltransferase by malonyl-CoA may play an important role in regulation of fatty acid oxidation in the heart, but there has been a discrepancy in data relating to changes in malonyl-CoA sensitivity of the myocardial carnitine palmitoyltransferase during fasting. Analysis of malonyl-CoA inhibition of myocardial carnitine palmitoyltransferase in fasting and fed states under a variety of conditions has indicated that under no condition could any difference be found in malonyl-CoA sensitivity that was attributable to fasting. Proteolysis of the outer carnitine palmitoyltransferase led to artifactual changes in sensitivity due to the appearance of partial inhibition. We have concluded that the sensitivity of myocardial carnitine palmitoyltransferase to malonyl-CoA does not change during fasting. Changes in fatty acid oxidation in the heart are probably due to changes in malonyl-CoA concentrations or to other inhibitors. (Mol Cell Biochem 116: 39–45, 1992)
    Materialart: Digitale Medien
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  • 45
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 120 (1993), S. 89-94 
    ISSN: 1573-4919
    Schlagwort(e): fatty acid binding protein ; microsomes ; long chain fatty acids ; acyl-CoA derivatives ; retinoids ; liver
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract This paper reviews characteristics of microsomal membrane structure; long chain fatty acids, acyl CoA derivatives, retinoids and the microsomal formation of acyl CoA derivatives and retinyl esters. It is analyzed how the movement of these molecules at the intracellular level is affected by their respective binding proteins (Fatty acid binding protein, acyl CoA binding protein and cellular retinol binding protein). Studies with model systems using these hydrophobic ligands and the lipid-binding or transfer proteins are also described. This topic is of interest especially because in the esterification of retinol the three substrates and the three binding proteins may interact. (Mol Cell Biochem20: 89–94, 1993)
    Materialart: Digitale Medien
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  • 46
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 122 (1993), S. 65-68 
    ISSN: 1573-4919
    Schlagwort(e): regucalcin ; calcium-binding protein ; tissue concentration ; liver ; kidney ; rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract The concentration of calcium-binding protein regucalcin in the tissues of rats was estimated by enzyme-linked immunoadsorbent assay (ELISA) with rabbit-anti-regucalcin IgG. In male rats (5 weeks old), regucalcin was most pronounced in the liver. Liver regulcalcin concentration was about 0.1μM, when it was calculated with regucalcin molecular weight of 28,800. The relatively higher level of regucalcin was also found in the kidney as compared with that of the skeletal muscle, duodenum, testis, lung, heart, spleen, cerebral cortex and hippocampus. Similarly in female rats, regulacalcin was remarkable in the liver, and appeared only slightly in the kidney. Thus, the tissue distribution of regucalcin in rats was specific in the liver. The concentration of regucalcin in the liver was altered with increasing age of rats; liver regucalcin level linearly increased during 5 weeks old after birth of male rats, and then began to decrease gradually. The results coincided with the previous observation of Northern blot analyses by using liver regucalcin cDNA as a probe. The present finding clearly demonstrates that regucalcin is specifically synthesized in the liver of rats.
    Materialart: Digitale Medien
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  • 47
    ISSN: 1573-4919
    Schlagwort(e): liver ; fatty acid-binding protein ; sterol binding protein ; L-cells ; fat ; cholesterol ; dehydroergosterol ; fatty acid ; cis-parinaric acid ; transport ; insulin ; epinephrine ; fluorescence
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract Fatty acid-binding proteins (FABP) are abundant cytosolic proteins whose level is responsive to nutritional, endocrine, and a variety of pathological states. Although FABPs have been investigatedin vitro for several decades, little is known of their physiological function. Liver L-FABP binds both fatty acids and cholesterol. Competitive binding analysis and molecular modeling studies of L-FABP indicate the presence of two ligand binding pockets that accomodate one fatty acid each. One fatty acid binding site is identical to the cholesterol binding site. To test whether these observations obtainedin vitro were physiologically relevant, the cDNA encoding L-FABP was transfected into L-cells, a cell line with very low endogenous FABP and sterol carrier proteins. Uptake of both ligands did not differ between control cells and low expression clones. In contrast, both fatty acid uptake and cholesterol uptake were stimulated in the high expression cells. In high expression cells, uptake of fluorescent cis-parinaric acid was enhanced more than that of trans-parinaric acid. This is consistent with the preferential binding of cis-fatty acids to L-FABP but in contrast to the preferential binding of trans-parinaric acid to the L-cell plasma membrane fatty acid transporter (PMFABP). These data show that the level of cytosolic fatty acids in intact cells can regulate both the extent and specificity of fatty acid uptake. Last, sphingomyelinase treatment of L-cells released cholesterol from the plasma membrane to the cytoplasm and stimulated microsomal acyl-CoA: cholesteryl acyl transferase (ACAT). This process was accelerated in high expression cells. These observations show for the first time in intact cells that L-FABP, a protein most prevalent in liver and intestine where much fat absorption takes place, may have a role in fatty acid and cholesterol absorption.
    Materialart: Digitale Medien
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  • 48
    ISSN: 1573-4919
    Schlagwort(e): endotoxin ; lipogenesis ; mammary gland ; liver ; chylomicrons ; lipoprotein lipase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract The aim of this study was to compare the effects of endotoxin on lipid metabolism and, in particular, lipogenesis in virgin and lactating rats. Intraperitoneal administration of bacterial endotoxin (lipopolysaccharide, LPS; 3 mg/kg body wt.) to fed virgin rats caused a 4-fold increase in lipogenic rate in liverin vivo. The stimulatory effect was not seen when glucose (6 mmol) was administered either orally or intraperitoneally to increase the basal rate. In contrast, the rate of lipogenesis in interscapular brown adipose tissue was inhibited, after LPS, and this was relieved by intraperitoneal glucose. In the lactating rat there were no significant changes in hepatic lipogenesis after the administration of endotoxin. However, LPS decreased the lipogenic rate in mammary gland of lactating rats and intraperitoneal glucose administration, but not oral, was able to restore the rate. In both virgin and lactating rats, LPS decreased glucose removal from the intestina tract. In lactating rats, LPS induced a rise in blood concentrations of lactate, and plasma triacylglycerols and non-esterified fatty acids, similar to those in endotoxin-treated virgin rats. The administration of LPS did not decrease the accumulation of radioactivity in lipid in either liver or in mammary gland after injection of3H-oleate. In contrast, LPS decreased the accumulation of radioactivity in mammary gland after injection of2H-chylomicrons and increased it in liver and plasma. These changes were accompanied by a decrease in mammary gland activity of lipoprotein lipase. Intraperitoneal glucose partially reversed these changes in chylomicron disposition. It is concluded that the inhibitory effect of LPS on mammary gland lipogenesis and uptake of exogenous lipid is primarily due to sensitivity of this tissue to the rate of delivery of glucose from the intestine.
    Materialart: Digitale Medien
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  • 49
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 153 (1995), S. 151-155 
    ISSN: 1573-4919
    Schlagwort(e): sodium orthovanadate ; diabetes ; N-myristoyltransferase ; liver ; membrane-associated ; vanadate ; obese Zucker rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 50
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 125 (1993), S. 127-136 
    ISSN: 1573-4919
    Schlagwort(e): AP-1 ; α2u-globulin ; liver ; intron
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract The hepatic expression of the α2u gene family is controlled by a variety of hormones including steroids, growth hormone and insulin. The mechanisms by which these hormones affect α-globulin expression are only partially understood. Recently we isolated and characterized clone RAP 01, an α2u-globulin gene expressed in the liver. In preliminary experiments we noted that partial hepatectomy, a procedure which results in a sharp rise in the level of the oncoproteins c-Fos and c-Jun, also causes a transient induction of the messenger RNA corresponding to clone RAP 01. Using the DNAseI footprinting technique we were able to show that this clone contains a TPA (phorbol 12-myristate 13-acetate)-responsive element (TRE) in its first intron. This element (denoted as element X) is identical to the consensus AP-1 binding site (TGACTCAG) and is protected by rat liver nuclear extracts as well as by purified c-Jun. Gel retardation experiments show that an oligonucleotide containing the TRE consensus sequence competes for binding of liver nuclear proteins to element X and that antibodies directed against the M2 peptide of the mouse Fos protein or the PEP-2 peptide of Jun prevent the formation of specific complexes with the same element. Moreover, element X functions as a TRE in transfected BWTG3 hepatoma cells treated with TPA. Co-transfection withfos andjun expression vectors mimics the effects of TPA suggesting that AP-1 is in fact the mediator of the observed response. It is concluded that the first intron of RAP 01 contains a functional Fos-Jun element.
    Materialart: Digitale Medien
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  • 51
    ISSN: 1573-4919
    Schlagwort(e): respiration ; ADP diffusion ; heart ; skeletal muscle ; liver ; brain ; in vivo regulation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 52
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 167 (1997), S. 73-80 
    ISSN: 1573-4919
    Schlagwort(e): cadmium ; zinc ; liver ; flavokinase ; thiol group
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: 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)
    Materialart: Digitale Medien
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  • 53
    ISSN: 1573-4919
    Schlagwort(e): antioxidant enzymes ; sub-cellular organelles ; liver ; ischemia-reperfusion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 54
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 92 (1990), S. 61-67 
    ISSN: 1573-4919
    Schlagwort(e): liver ; non-histone proteins ; chromatin ; nucleus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract Three antisera were prepared against non-histone protein classes named NHCP1, NHCP2 and dehistonized chromatin (with different affinity to DNA) from hamster liver. Two main antigenic bands of MW 17,000 and 36,000 were specific in the NHCP1 fraction and one antigen of MW 56,000 was specific for the NHCP2 fraction from nuclease-sensitive and especially nuclease-resistant chromatin. Other NHCP2 liver antigens of ] MW 22,000, 27,000, 30,000, 36,000, 37,000, 40,000, 45,000, 46,000, 51,000, 98,000 and 100,000 were present only in nuclease-resistant chromatin of hamster liver. Immunologically specific hamster liver non-histone proteins within the NHCP1 and NHCP2 fractions seem to be restricted to nuclease-resistant chromatin fraction of this tissue. The above mentioned liver specific antigens are absent or present only at trace amounts in analogous Kirkman-Robbins hepatoma fractions.
    Materialart: Digitale Medien
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  • 55
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 92 (1990), S. 99-106 
    ISSN: 1573-4919
    Schlagwort(e): db/db mouse ; type 2 diabetes ; glycogen metabolism ; insulin ; liver
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Summary Knowledge of the metabolic changes that occur in insulin-resistant type 2 diabetes is relatively lacking compared to insulin-deficient type 1 diabetes. This paper summarizes the importance of the C57BL/KsJ-db/db mouse as a model of type 2 diabetes, and illustrates the effects that insulin-deficient and insulin-resistant states have on hepatic glycogen metabolism. A longitudinal study of db/db mice of ages 2–15 weeks revealed that significant changes in certain parameters of hepatic glycogen metabolism occur during this period. The liver glycogen levels were similar between diabetic and control mice. However, glycogen particles from db/db mice were on average smaller in mass and had shorter exterior and interior chain lengths. Total phosphorylase and phosphorylase a activities were elevated in the genetically diabetic mice. This was primarily due to an increase in the amount of enzymic protein apparently the result of a decreased rate of degradation. It was not possible to find a consistent alteration in glycogen synthase activity in the db/db mice. Glycogen synthase and phosphorylase from diabetic liver revealed some changes in kinetic properties in the form of a decrease in Vmax, and altered sensitivity to inhibitors like ATP. The altered glycogen structure in db/db mice may have contributed to changes in the activities and properties of glycogen synthase and phosphorylase. The exact role played by hormones (insulin and glucagon) in these changes is not clear but further studies should reveal their contributions. The db/db mouse provides a good model for type 2 diabetes and for fluctuating insulin and glucagon ratios. Its use should clarify the regulation of hepatic glycogen metabolism and other metabolic processes known to be controlled by these hormones. The other animal models of type 2 diabetes, ob/ob mouse and fatty Zucker (fa/fa) rat, show similar impairment of hepatic glycogen metabolism. The concentrations of glycogen metabolizing enzymes are high and in vitro studies indicate enhanced rate of glycogen synthesis and breakdown. However, streptozotocin-induced diabetic animals and BB rats which resemble insulin-deficient type 1 diabetes are characterized by decreased glycogen turnover as a result of reduction in the levels of glycogen metabolizing enzymes.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 56
    ISSN: 1573-4919
    Schlagwort(e): mitochondria ; adenine nucleotides ; purine metabolism ; compartmentation ; liver ; hypoxia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Summary The degradation of intramitochondrial adenine nucleotides to nucleosides and bases was investigated by incubating isolated rat liver mitochondria at 37°C under non-phosphorylating conditions in the presence of oligomycin and carboxyatractyloside. Within 30 min the adenine nucleotides were degraded by about 25 per cent. The main products formed were adenosine and inosine the contents of which increased five- to sevenfold. Compartmentation studies revealed that about 50 to 60 per cent of the adenosine formed remained inside the organelles whereas inosine was almost completely released into the surrounding medium. Outside the mitochondria only very small amounts of adenine nucleotides were detected. Similar incubations in the presence of [14C]-adenosine yielded no [14C]-inosine ruling out extramitochondrial adenosine deamination. It is concluded that endogenous adenine nucleotides can be degraded in mitochondria via AMP dephosphorylation and subsequent adenosine deamination. A purine nucleoside transport system mediating at least the efflux of inosine from the mitochondria is suggested.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 57
    ISSN: 1573-4919
    Schlagwort(e): vitamin A ; glycosylation ; GDP-mannose ; liver ; lipid intermediates
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Summary The molecular mechanism of reduced incorporation of radioactively labeled mannose into hamster liver glycoconjugates during the progression of vitamin A deficiency was investigated. In particular the in vivo incorporation of [2-3H]mannose into GDP-mannose, dolichyl phosphate mannose (Dol-P-Man), lipid-linked oligosaccharides, and glycopeptides of hamster liver was examined. Hamsters maintained on a vitamin A-free diet showed a reduction in the incorporation of mannose into GDP-mannose about 10 days before clinical signs of vitamin A deficiency could be observed. The decrease in [2-3H]mannose incorporated into GDP-mannose was accompanied by a reduction in label incorporated into Dol-P-Man, lipid linked oligosaccharides and glycopeptides, which became more severe with the progression of vitamin A deficiency. By the time they reached a plateau stage of growth, hamsters fed the vitamin A-free diet showed a 50% reduction in the amount of [2-3H]mannose converted to GDP-mannose, and the radioactivity associated with Dol-P-Man and glycopeptides was reduced by approximately 60% as compared to retinoic acid-supplemented controls. These results strongly indicate that the reduced incorporation of mannose into lipidic intermediates and glycoproteins observed during vitamin A deficiency is due to impaired GDP-mannose synthesis.
    Materialart: Digitale Medien
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  • 58
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 98 (1990), S. 3-9 
    ISSN: 1573-4919
    Schlagwort(e): fatty acids ; fatty acid-binding protein ; peroxisomes ; β-oxidation ; intestine ; liver
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Summary Fatty acid-binding proteins (FABPs) were first identified in the cytosol of rat intestinal mucosa during studies on the regulation of intestinal fatty acid uptake. The subsequent finding of FABP activity in the cytosol of many other tissues initially was believed to reflect a single protein. However, the FABPs are now recognized as products of an ancient gene family comprised of at least 9 structurally related, soluble intracellular members, a number of which exhibit high-affinity binding of long-chain fatty acids. Despite recent insights into regulation and tissue-specific expression suggesting FABPs to subserve diverse roles, their precise biological functions remain to be elucidated.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 59
    ISSN: 1573-4919
    Schlagwort(e): liver fatty acid-binding protein ; immunohistochemistry ; in situ hybridization ; liver ; jejunum ; rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Summary The localization of liver fatty acid-binding protein (L-FABP) and its mRNA in the liver and jejunum was examined in normal and 3-day-fasted rats by means of immunohistochemistry using a specific antibody to L-FABP and in situ hybridization using a synthetic oligonucleotide complementary to L-FABP mRNA as probe. In the liver from normally fed rats, the signal for L-FABP mRNA in hepatocytes was distributed throughout the lobule, with higher intensity in the periportal than in the centrolobular region. After a 3-d fasting, the mRNA signal declined in intensity throughout the lobule, in accordance with the result of Northern blot analysis. Immunohistochemistry for L-FABP showed intralobular patterns of immunoreactivity similar to those of the mRNA signal in both fed and fasted animals. In the jejunum from fed rats, L-FABP-mRNA signal was abundant in the absorptive epithelial cells lining the lower two-thirds of villus and less abundant in the villus tip cells, while the intensity of L-FABP immunoreactivity remained high in the latter cells. Fasting brought about a downward shift of the mRNA signal to an area including the upper half of the crypt and the lower portions of villus, with decreased intensity in the rest of the villus. Immunohistochemistry also showed a downward extension of the immunoreactivity into the upper crypt area. The present results suggest that in situ hybridization is a useful tool to analyze regulations of the expression of L-FABP gene in the digestive organs in association with epithelial cell migration and dietary condition.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 60
    ISSN: 1573-4919
    Schlagwort(e): membrane fatty acid-binding protein ; mGOT ; fatty acid metabolism ; carrier mediated transport ; liver ; heart
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Summary For evaluation whether the membrane fatty acid-binding protein is related to mGOT, studies on the structure and function of both purified proteins were performed. Physicochemical characterization revealed that both proteins are different: the membrane fatty acid-binding protein has a molecular weight of 40 kD and a pI of 8.5–9.0, whereas rat mGOT has a molecular weight of 44 kD and a pI of 9.5–10.0. According to this distinct differences, they migrated separately on 2-dimensional electrophoresis. Furthermore, monospecific antibodies against the membrane fatty acid binding protein did not react with rat mGOT. In co-chromatography studies only the membrane fatty acid-binding protein showed affinity for long chain fatty acids, but not mGOT. Moreover, membrane binding studies were performed with the monospecific antibody to the membrane fatty acid binding protein. The inhibitory effect of this antibody on plasma membrane binding of oleate was reversed after preabsorption of the antibody with the membrane fatty acid binding protein, but was not affected after preabsorption with mGOT. These results indicate that the membrane fatty acid binding protein and mGOT are structurally and functionally not related. The data also support the significance of this membrane protein in the plasma membrane binding process of long chain fatty acids.
    Materialart: Digitale Medien
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  • 61
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 108 (1991), S. 105-112 
    ISSN: 1573-4919
    Schlagwort(e): liver ; protein synthesis ; protein-free diet ; alanine action
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract In contrast to what it is observed during starvation, animals maintained on a protein-free isocaloric diet showed an increase in the rate of hepatic peptide chain elongation as determined by measuring the ribosomal transit time in vivo. The loss of body nitrogen per se is insufficient to generate the signal(s) which arrests hepatic peptide chain elongation. This observation suggests that it is an increase in gluconeogenic demand, and not the negative nitrogen balance, which is implicated in determining reciprocal changes in the rate of protein synthesis. The rate of protein synthesis, as expressed per mg of DNA, does not change in protein deprived animals, while the RNA to DNA ratio decreased. These data also agree with a higher ribosomal efficiency at the elongation step. The animals maintained on a protein-free diet have a decreased hepatic content of protein and an increased concentration of valine, indicating an increased proteolysis. The enhanced rate of polypeptide elongation observed in animals kept on a protein-free diet was accompanied by decreases in the state of aggregation of polyribosomes and in the ability of liver extracts to form eIF-2 catalyzed ternary complexes. These observations suggest that the activity of the hepatic initiation factor in vivo may not be rate limiting. The administration of alanine in vivo to animals maintained on a protein-free diet showed a preferential effect in reaggregating polyribosomes. This action was neither accompanied by detectable effects on the rate of eIF-2 catalyzed ternary complexes formation nor by significant changes in the rate of elongation. It is concluded that factors other than eIF-2 activity or the rate of polypeptide elongation must be controlling the hepatic polyribosomal state of aggregation.
    Materialart: Digitale Medien
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  • 62
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 113 (1992), S. 33-41 
    ISSN: 1573-4919
    Schlagwort(e): liver ; glucose gavage ; glucose fate ; glycemia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract An oral gavage of either 3, 1 or 0.1 mmoles of glucose was given to rats under standard feeding conditions or food deprived for 24 hr. The blood flow of the portal and suprahepatic veins as well as the hepatic balances for glucose, lactate, alanine and pyruvate were estimated. In fed rats, after the administration of an oral 3 mmoles load, the liver actually released 310 µmoles of glucose and 90 of lactate, amounts that could be accounted for by the uptake of alanine (148 µmoles) and small loss of glycogen (275 µmoles of glycosyl residues). In starved rats, however, the liver took a very high proportion (c. 71%) of the glucose absorbed, both as glucose (780 µmoles), lactate and pyruvate (892 µmoles) or alanine (134 µmoles). The synthesis of glycogen was considerably limited, accounting for only 205 µmoles, and leaving practically one mmol of glucose equivalent energy available for liver function and the synthesis of other compounds. Practically all glycogen was synthesized directly from glucose, since the synthesis from 3 C carriers was less than a 5%. Smaller gavages (1 or 0.1 mmoles) resulted in a much lower liver uptake activity. The strikingly different activity of the liver with respect to the available glucose and 3 C fragments could not be explained alone by the circulating levels of these compounds, suggesting a very deep influence of the intestine in hepatic function. The liver plays a very passive role in fed animals, with a very small involvement in the disposal of a glucose load, whereas it takes on an important role when the overall availability of energy is diminished.
    Materialart: Digitale Medien
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  • 63
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 121 (1993), S. 37-43 
    ISSN: 1573-4919
    Schlagwort(e): acetaldehyde ; ethanol ; intoxication ; liver ; rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract It was found that chronic intoxication of rats with acetaldehyde results in a distinct, progressive increase of 5-3H-proline incorporation into collagen synthesized by liver. At the same time biosynthesis of other proline-containing (noncollagenous) proteins does not change significantly. On the other hand the collagen content in the rat liver did not increase in the early stage of acetaldehyde administration, but increased when acetaldehyde feeding was continued for 6 months. About 40% increase of total collagen content was found in livers of the intoxicated animals. All the investigated collagen types (I, III, IV and V) grew in the same degree. No changes in proportional relationships between collagens of different types were found.
    Materialart: Digitale Medien
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  • 64
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 135 (1994), S. 187-193 
    ISSN: 1573-4919
    Schlagwort(e): endotoxin ; peroxisomal β-oxidation system ; liver ; peroxisomes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract It is now clear that peroxisomes play a crucial role in many cellular processes, including the β-oxidation of very long chain fatty acids. Recently, mammalian peroxisomes have been shown to contain the antioxidant enzymes, superoxide dismutase and glutathione peroxidase, in addition to catalase. The presence of these enzymes in peroxisomes suggests that peroxisomes undergo oxidative stress in normal and disease states. As an indicator of the potential impact of an oxidative stress on peroxisomal functions, we evaluated the effect of endotoxin exposure on the β-oxidation enzyme system in rat liver. Peroxisomes were isolated from liver homogenates by differential and density gradient centrifugations. Endotoxin treatment decreased the β-oxidation of lignoceric acid to 56% of control values (p〈0.01). The specific activity of the rate limiting enzyme in the system, acyl-CoA oxidase, was decreased to 73% of control values (p〈0.05). Immunoblot analysis revealed a 25% decrease in the 21KD subunit of the acyl-CoA oxidase protein. In contrast, the protein levels of the other enzymes in the pathway, trifunctional protein and 3-ketoacyl-CoA thiolase, were increased by 10 and 15%, respectively. These findings suggest that impairment of β-oxidation of lignoceric acid by endotoxin treatment is due primarily to a reduction in the activity and protein level of the key enzyme, acyl-CoA oxidase. Oxidative stresses such as endotoxin exposure may have deleterious effects on important peroxisomal functions, such as β-oxidation of very long chain fatty acids.
    Materialart: Digitale Medien
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  • 65
    ISSN: 1573-4919
    Schlagwort(e): glucose-6 phosphatase ; messenger RNA ; liver ; kidney ; fasting
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 66
    ISSN: 1573-4919
    Schlagwort(e): cadmium ; glutathione S-transferase ; liver ; kidney
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: 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)
    Materialart: Digitale Medien
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  • 67
    ISSN: 1573-4919
    Schlagwort(e): vitamin-A ; cellular retinol-binding protein ; liver ; hepatic stellate cells ; lipocytes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 68
    ISSN: 1573-4919
    Schlagwort(e): chicken ; oviduct ; liver ; tissue-specific repression ; in vivo gene transfer ; gene gun
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 69
    ISSN: 1573-4919
    Schlagwort(e): trans polyunsaturated fatty acid ; linoleic acid ; desaturation elongation ; microsomes ; liver
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 70
    ISSN: 1573-4919
    Schlagwort(e): hyperplasia ; hypertrophy ; liver ; nucleic-acid concentration ; protein-growth rate ; protein-turnover rate ; rainbow trout (Oncorhynchus mykiss) ; starvation/re-feeding cycle
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 71
    ISSN: 1573-4919
    Schlagwort(e): vanadate ; diabetes ; glycogen synthase ; phosphorylase ; lipogenic enzymes ; liver
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 72
    ISSN: 1573-4919
    Schlagwort(e): fatty acid binding protein ; liver ; intestine ; growth factor ; TGFβ1
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 73
    ISSN: 1573-4919
    Schlagwort(e): carnitine palmitoyl transferase I ; mitochondrial HMG-CoA synthase ; dexamethasone ; suckling rats ; ketogenesis ; intestine ; liver
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 74
    ISSN: 1573-4927
    Schlagwort(e): alcohol dehydrogenase (ADH) ; liver ; stomach ; ADH− and ADH+ deermouse ; Class I, II, III, and IV ADH ; alcohol metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 75
    ISSN: 1573-4927
    Schlagwort(e): alcohol dehydrogenase (ADH) ; liver ; stomach ; ADH− and ADH+ deermouse ; Class I, II, III, and IV ADH ; alcohol metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 76
    ISSN: 1573-4935
    Schlagwort(e): lipid ; liver ; phospholipid ; regenerating liver ; somatostatin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Effects of somatostatin (SOM) on tissue contents of proteins, total lipids and phospholipids were investigated in regenerating and intact liver tissue of Y-59 rats. Whereas SOM inhibited protein accumulation in regenerating liver, the hormone evoked and increase in total lipids, and specially in phosphatidylcholine, phosphatidylethnolamine, phosphatidylserine (PS) and phosphatidylinositol (PI). Since the same effects were not seen when intact liver was analyzed, it is assumed that SOM acts primarily on tissue stimulated to rapid growth. The increase of PS+PI fractions indicates a specific effect of SOM on the metabolism of phosphatidylinositides. Such an effect might result from the interference of the hormone with the action of growth factors that accelerate phosphatidylinositol breakdown.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 77
    Digitale Medien
    Digitale Medien
    Springer
    Bioscience reports 11 (1991), S. 23-31 
    ISSN: 1573-4935
    Schlagwort(e): frog ; glycoproteins ; glycosyl transferases ; liver
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract The circannual behaviour of glycosylation and protein synthesis in frog liver slices was studied following the incorporation of3H-galactose and14C-glucosamine into glycolipids and glycoproteins and3H-leucine into proteins. The activity of two enzymes the galactosyl-transferase and the N-acetyl-glucosaminyl-1-P-transferase was determined. The incorporations of both sugars into the soluble fraction and into the lipid extract present a maximum during the spring-summer period. The incorporation into the protein fraction displays a different pattern:14C-Glucosamine and3H-leucine incorporation increases from winter to a maximum in autumn; the incorporation of3H-Galactose has a sharp peak during spring. The pattern of glycosyltransferase activities is similar to the pattern of incorporation of the two saccharides into proteins, indicating these enzymes as important control points for glycosylation in Anurae.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 78
    ISSN: 1573-4935
    Schlagwort(e): diabetes ; liver ; polysome ; pregnancy ; protein synthesis ; streptozotocin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 79
    Digitale Medien
    Digitale Medien
    Springer
    The protein journal 14 (1995), S. 487-497 
    ISSN: 1573-4943
    Schlagwort(e): Enolase ; isozymic structure ; pig ; purification ; properties ; liver ; muscle
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 80
    ISSN: 1352-8661
    Schlagwort(e): Magnetic resonance spectroscopy ; glycogen ; liver ; muscle
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin , Physik
    Notizen: Abstract We have used natural abundance13C magnetic resonance spectroscopy (MRS) to measure glycogen content of muscle and liver before and after heavy exercise, and after consumption of different carbohydrate-based drinks. After an overnight fast, five healthy men (mean±SEM age 23±1 years) exercised to exhaustion at 75% of VO2max on two occasions (mean work rate 165±8 W for 78±14 min) and then, in a single blind random order, consumed either of two drinks containing the same carbohydrate load (177 g). Spectra were recorded over Vastus Lateralis muscle and the liver before and after exercise, and hourly for 5 h after the carbohydrate load. In muscle, glycogen content after exercise was 37% and 31% of basal (preexercise) concentration before consuming the drinks. After carbohydrate loading, glycogen concentration had increased significantly (p〈0.05) to 70% and 64% of basal concentration respectively after 5 h. Hepatic glycogen concentration did not change significantly throughout. The study demonstrates the feasibility of sequential MRS measurement of muscle and liver glycogen before and after exercise and after carbohydrate loading.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 81
    ISSN: 1352-8661
    Schlagwort(e): liver ; mr contrast agent ; gadolinium ; contrast agent ; elimination ; transport systems
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin , Physik
    Notizen: Abstract Mutant Wistar rats (TR− rats) are characterized by a defect in the canalicular transport system for organic anions in the hepatocytes. Anionic hepatobiliary contrast agents for X-ray and MR imaging usually depend on this transport system for biliary secretion. The current study investigated in rats whether Gd-EOB-DTPA, a hepatocyte-directed MR contrast agent, can be completely eliminated in the absence of biliary excretion, and whether urinary elimination may compensate for the hepatic dysfunction. In TR/t- rats elimination of Gd-EOB-DTPA almost completely depended on renal excretion: following intravenous administration of 25µmol kg−1 Gd-EOB-DTPA only 2.4±0.4% of the injected dose underwent biliary excretion. Nevertheless only 2% of a 10-fold higher dose (250µmolkg−1 Gd-EOB-DTPA) was still detected in the body 24 hours p.a., and less than 0.5% 7 days p.a. (no statistically significant differences as compared to values in control rats). In TR− rats, renal and liver signal intensities on T1-weighted MR images returned to baseline within 24 hours following administration of 25µmol kg−1 Gd-EOB-DTPA. In control rats, return to baseline values was observed already 6 hours after injection of the contrast agent. In conclusion, the hepatobiliary MR contrast agent Gd-EOB-DTPA is effectively and completely cleared from the body even in the virtual absence of biliary excretion. The urinary elimination pathway is able to fully compensate for the deficient hepatic transport system.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 82
    ISSN: 1573-4986
    Schlagwort(e): 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.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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
    Materialart: Digitale Medien
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  • 83
    Digitale Medien
    Digitale Medien
    Springer
    Bulletin of experimental biology and medicine 109 (1990), S. 516-519 
    ISSN: 1573-8221
    Schlagwort(e): liver ; biological rhythms ; protein synthesis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 84
    ISSN: 1573-8221
    Schlagwort(e): cytochrome P-450 ; glutathione transferase ; heavy pyrolysis resin ; skin ; liver
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 85
    Digitale Medien
    Digitale Medien
    Springer
    Bulletin of experimental biology and medicine 111 (1991), S. 324-326 
    ISSN: 1573-8221
    Schlagwort(e): glutathione reductase ; liver ; paraquat ; toxic action ; embryonic period
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 86
    Digitale Medien
    Digitale Medien
    Springer
    Bulletin of experimental biology and medicine 111 (1991), S. 393-396 
    ISSN: 1573-8221
    Schlagwort(e): ultrasound ; liver ; resection
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 87
    Digitale Medien
    Digitale Medien
    Springer
    Bulletin of experimental biology and medicine 109 (1990), S. 145-147 
    ISSN: 1573-8221
    Schlagwort(e): fluorocarbon emulsions ; liver ; perfusion ; hypoxia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 88
    Digitale Medien
    Digitale Medien
    Springer
    Bulletin of experimental biology and medicine 109 (1990), S. 316-319 
    ISSN: 1573-8221
    Schlagwort(e): hydroxysteroid dehydrogenase ; steroid hormones ; binding of substrates ; coenzymes ; liver
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 89
    ISSN: 1573-8221
    Schlagwort(e): sexual differentiation ; liver ; estrogen receptors ; angiotensinogen
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 90
    Digitale Medien
    Digitale Medien
    Springer
    Bulletin of experimental biology and medicine 109 (1990), S. 463-465 
    ISSN: 1573-8221
    Schlagwort(e): hexachlorobenzene-induced porphyria ; uroporphyrinogen decarboxylase ; porphyrins in urine ; liver ; and kidneys
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 91
    ISSN: 1573-8221
    Schlagwort(e): endotoxins ; lipid peroxidation ; liver ; lungs ; unithiol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 92
    Digitale Medien
    Digitale Medien
    Springer
    Bulletin of experimental biology and medicine 110 (1990), S. 1639-1641 
    ISSN: 1573-8221
    Schlagwort(e): ethidium bromide ; chromatin ; viscosity ; liver ; denervation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 93
    ISSN: 1573-904X
    Schlagwort(e): protein targeting ; sugar recognition ; pharmacokinetics ; molecular weight ; liver
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 94
    ISSN: 1573-904X
    Schlagwort(e): multiple administration routes ; rat cannulation ; metabolism ; liver ; gut
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract A multiple cannulated rat model was utilized to investigate the relative contribution of the gut and liver as sites of first-pass metabolism of orally administered U-54494 A, an anticonvulsant drug candidate. Each rat received a dose of U-54494 A by oral, intraportal, and intravenous routes on three separate occasions. Intraportal and intravenous doses were administered through chronic cannulas surgically implanted in the portal vein and superior vena cava, respectively. Blood samples were collected over a 6-hr period from the superior vena cava cannula. The mean (n = 3) bioavailability of orally dosed U-54494A was 4.5 ± 1.1%, while that dosed intraportally was 19.1 ± 3.0%. The relative contribution of the gut and liver as sites of first-pass extraction and/or metabolism of orally administered drug was 69.9 ± 14.0% and 24.5 ± 12.2%, respectively. Approximately 35 to 40% of the total plasma clearance was attributed to the liver. The plasma concentrations of the four known metabolites of U-54494A were apparently higher for the oral and intraportal routes compared to that after intravenous administration. This investigation confirms that the low oral bioavailability of U-54494A in the rat can be primarily attributed to both extensive intestinal and hepatic first-pass metabolism.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 95
    ISSN: 1573-8744
    Schlagwort(e): cyclosporine ; dark Agouti rat ; kidney ; liver ; hydroxylation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Since oxidation plays a key role in the metabolism of cyclosporine A (CsA), the pharmacokinetics and the toxicity of CsA was investigated in female dark Agouti rats exhibiting a deficiency for debrisoquine hydroxylation and for dextromethorphan demethylation. When compared with Wistar rats (n=10), dark Agouti rats (n=10) had a higher mean clearance (4.8 ml/min per kg vs. 3.3 ml/min per kg) and a lower mean residence time (606 min vs. 1361 min) after intravenous dosing of CsA. The systemic availability of subcutaneous CsA was close to 100%. The steady state CsA concentrations assessed by HPLC in whole blood after subcutaneous dosing of 20 mg/kg per day for 23 days (n=10) were about 1000 ng/ml in dark Agouti rats. When compared with dark Agouti rats treated with cremophore (n=10) or not treated at all (n=12, dark Agouti rats on chronic subcutaneous CsA plus cremophore for 23 days (n=10) had no difference in kidney histology but had slightly increased liver fatty changes. Rats on CsA and/or cremophore had a decreased uric acid clearance and evidence of hypoaldosteronism. The urinary ratio of debrisoquine/4-hydroxydebrisoquine decreased in rats on CsA, whereas the O-demethylation and N-demethylation of liver obtained from rats on cremophore was impaired. Thus, dark Agouti rats show no difference in the metabolism of CsA and when given CsA for 23 days show drug-induced functional but no relevant structural light microscopic changes in the kidney, and functional and slight structural changes in the liver.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 96
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 233-256 
    ISSN: 1573-8744
    Schlagwort(e): pharmacokinetic model ; multiple indicator dilution ; binding kinetics ; liver ; tissue distribution ; cytoplasmic diffusion coefficient ; membrane permeability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 97
    ISSN: 1573-4935
    Schlagwort(e): Carbohydrate binding proteins ; liver ; plasma membrane ; MALDI-TOF mass spectrometry ; sequence analysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 98
    ISSN: 1573-8744
    Schlagwort(e): enalapril ; enalaprilat ; metabolite biliary excretion clearance ; metabolite formation organ ; liver ; physiological modeling ; single-pass and recirculating perfused rat liver preparation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Single-pass and recirculating rat liver perfusion studies were conducted with [14C]enalapril and [3H] enalaprilat, a precursor-product pair, and the data were modeled according to a physiological model to compare the different biliary clearances for the solely formed metabolite, [14C]enalaprilat, with that of preformed [3H]enalaprilat. With single-pass perfusion, the apparent extraction ratio (or biliary clearance) of formed [14C]enalaprilat was 15-fold the extraction ratio of preformed [3H] enalaprilat, an observation attributed to the presence of a barrier for cellular entry of the metabolite. Upon recirculation of bolus doses of [14C]enalapril and [3H]enalaprilat, the biliary clearance, estimated conventionally as metabolite excretion rate/midtime metabolite concentration, for formed [14C]enalaprilat was again 10-to 15-fold higher than the biliary clearance for preformed [3H]enalaprilat, but this decayed with perfusion time and gradually approached values for preformed [3H]enalaprilat. The decreasing biliary clearance of formed enalaprilat with recirculation was explained by the dual contribution of the circulating and intrahepatic metabolite (formed from circulating drug) to excretion. Physiological modeling predicted (i) an influx barrier (from blood to cell) at the sinusoidal membrane as the rate-limiting process in the overall removal of enalaprilat, (ii) a 15-fold greater extraction ratio or biliary clearance for formed [14C]enalaprilat over [3H]enalaprilat during single-pass perfusion, and (iii) the time-dependent and declining behaviour of the biliary clearance for formed [14C]enalaprilat during recirculation of the medium. In the absence of a direct knowledge of eliminating organs in vivo, this variable pattern for excretory clearance of the formed metabolite within the organ is indicative of a metabolite formation organ.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 99
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 23 (1995), S. 567-580 
    ISSN: 1573-8744
    Schlagwort(e): nifedipine ; first-pass metabolism ; intestinal ; liver ; metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 100
    ISSN: 1573-904X
    Schlagwort(e): hepatocyte growth factor ; receptor-mediated endocytosis ; pharmacokinetics ; liver
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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