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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    European journal of nutrition 22 (1983), S. 14-26 
    ISSN: 1436-6215
    Schlagwort(e): branched chain α-keto acids ; 4-methyl-2-oxopentanoate, 3-methyl-2-oxopentanoate ; 3-methyl-2-oxobutyrate ; dehydrogenation ; transamination ; pharmacokinetics ; absorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Michaelis-Konstanten und Aktivitäten von Dehydrogenasen und Transaminasen der drei verzweigten α-Ketosäuren Keto-Valin, Keto-Leucin und Keto-Isoleucin in Leber, Niere, Skeletmuskel und Gehirn von Ratten werden mitgeteilt. Nach oraler Zufuhr passieren nur 11–22% der Ketosäuren unverändert die Leber. Aus pharmakokinetischen und Resorptions-Untersuchungen erhaltene Blutspiegel an Ketosäuren werden zu den Michaelis-Konstanten in Beziehung gesetzt. Bei den geringen Konzentrationen an Ketosäuren nach oraler Zufuhr kann angenommen werden, daß die oxidativen Prozesse in den nichthepatischen Geweben über die Transaminierung überwiegen. Daten über die Wachstumseffizienz von verzweigtkettigen α-Ketosäuren im Vergleich zu den entsprechenden Aminosäuren stimmen mit dieser Vorstellung überein. Bei intravenöser Verabreichung müßten die Voraussetzungen für Transaminierung besser sein als nach oraler Zufuhr. Auf der Basis von Daten aus der Literatur werden die Übertragbarkeit unserer Befunde auf den Menschen und die verschiedenen Faktoren, welche die Effizienz der verzweigten α-Ketosäuren durch Einwirkung auf ihren Stoffwechsel beeinflussen können, diskutiert.
    Notizen: Summary Miehaelis-constants and enzyme activities for dehydrogenation and transamination of the three branched chainα-keto acids in liver, kidney, skeletal muscle, and brain of rats are reported. After oral load only 11–22 % of the keto acids pass the liver unchanged. Blood levels in pharmacokinetic and absorption studies are related to the Michaelis-constants. At the low keto-acid concentrations after oral application, dehydrogenation in the non-hepatic tissues is supposed to prevail over transamination. Data on feed efficiency of branched chain α-keto acids reported in the literature support this view. The chance for transamination is better after intravenous administration. The transferability of our data to humans, and various factors influencing the efficiency of branched chain α-keto acids are discussed in connection with data reported in the literature.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    ISSN: 1420-9071
    Schlagwort(e): Interferon ; immunomodulator ; catabolism ; pharmacokinetics ; administration routes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary When human recombinant interferon-α2 diluted in saline was injected s.c. into rabbits, the total amount recovered in thoracic lymph was less than 0.4%. Recoveries increased from 2- to 8-fold if interferon was injected in 4% albumin or with hyaluronidase, respectively. Albumin added to interferon acts as an interstitial fluid expander, thus favoring interferon absorption through lymphatics rather than blood capillaries. This strategy may increase the therapeutic index of interferon.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Development genes and evolution 195 (1986), S. 499-505 
    ISSN: 1432-041X
    Schlagwort(e): DNA replication ; Embryonic gene transcription ; Heat shock-like proteins ; Mouse
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Inhibition of DNA replication in the 1-cell mouse embryo causes arrest in interphase. In such arrested cells the pattern of protein synthesis progresses as normal through the first cell cycle but does not show the characteristic changes that are associated with mitosis. Synthesis does occur of the 68/70 kd heat shock-like proteins, on the earliest detectable embryonic transcripts synthesised shortly after first cleavage in control embryos. However, the quantitative change in the pattern of protein synthesis, indicative of the major activation of the embryonic genome that normally occurs during G2 of the second cell cycle, is prevented.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 35 (1983), S. 755-761 
    ISSN: 1432-0827
    Schlagwort(e): Magnesium ; Mouse ; Mineralization ; Resoprtion ; Osteoclasts ; Bone turnover
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary The effect of magnesium (Mg) supplementation on bone metabolism has been studied in the normal young mouse. Weanling male mice were given Mg-supplemented drinking water (5 mM or 32 mM Mg) for 4 weeks. Mineral and skeletal changes were assessed by biochemical methods and by histomorphometric analysis of endosteal bone formation and resorption parameters evaluated on tetracycline double-labeled, undecalcified caudal vertebrae. Magnesium supplementation increased serum and urinary Mg concentrations and bone Mg content. Both the calcification rate and the extent of tetracycline double-labeled osteoid surface increased progressively in Mg-treated mice, whereas the mineralization lag time was shortened. The osteoblastic surface was reduced, leading to a fall in osteoid surface. Stimulation of bone mineralization was associated with a rise in extracellular calcium (Ca) and phosphorus (P) concentrations whereas serum 25-OHD and 1,25(OH)2D levels remained normal. The Mg supplementation increased the number of acid phosphatase stained chondroclasts and osteoclasts and the extent of resorbing surface showing histochemically stained osteoclasts. Although urinary OH-proline increased above normal, Ca, P, and cyclic adenylic acid (cAMP) excretion and phosphate concentration (TmP/GFR) remained normal, suggesting that parathyroid hormone (PTH) secretion was not altered. The trabecular bone volume remained normal, showing that the increased bone resorption was balanced by the stimulated bone mineralization. The results show that Mg supplementation influenced both bone formation and resorption in the young mouse, and that the stimulation of bone mineralization was the result of increased extracellular mineral availability. On the other hand, stimulation of osteoclastic bone resorption appeared to occur independently of PTH or of increased 1,25(OH)2D production. Therefore, this study suggests that Mg may controlin vivo bone metabolism by directly influencing bone resorbing cells activity.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 10 (1972), S. 302-313 
    ISSN: 1432-0827
    Schlagwort(e): Diphosphonates ; Bone resorption ; Mouse ; Pyrophosphate ; Tissue culture ; 45Calcium
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Beschreibung / Inhaltsverzeichnis: Résumé Deux diphosphonates, le disodium-éthane-1-hydroxyle-1,1-diphosphonate (EHDP) et le disodium dichlorométhylène diphosphonate (Cl2MDP), inhibent la résorption osseuse, induite par des cellules au niveau de calottes craniennes, cultivées pendant 48 heuresin vitro, lorsque ces substances sont ajoutées au milieu. Le Cl2MDP est plus actif que l'EHDP, à des doses variant 0–16 μg P/ml. Le pyrophosphate et l'imidodiphosphate n'inhibent pas la résorption osseuse à des doses comparables. Lorsque les deux diphosphonates sont injectés à des sourisin vivo avant mise en culture, la résorption osseuse observéein vitro est considérablement réduite: à une dose de 10 μg P/g de poids corporel de Cl2MDP, elle est presque totalement inhibée. Cet effet est rapide et dure plusieurs jours. Les conséquences de ces résultats et la méthode d'essai d'inhibiteurs de la résorption osseuse par la méthode combinéein vivo/ in vitro sont envisagées.
    Kurzfassung: Zusammenfassung Zwei Diphosphonate, Dinatrium-äthan-1-hydroxy-1,1-diphosphonat (EHDP) und Dinatrium-Dichloromethylendiphosphonat (Cl2MDP), hemmen zellbedingte Knochenresorption von Mäuseschädeldächern, welche während 48 Stdin vitro kultiviert worden waren, wenn diese Substanzen dem Nährmedium zugegeben werden. Im Dosierungsbereich von 0–16 μg P/ml ist Cl2MDP wirksamer als EHDP. Pyrophosphat und Imidodiphosphat blockieren die Knochenresorption bei entsprechenden Dosen nicht. Wenn die zwei Diphosphonate Mäusenin vivo injiziert werden, bevor das Explantat hergestellt wird, ist die nachfolgende Knochenresorptionin vitro stark vermindert; bei einer Dosierung von 10 μg P/g Körpergewicht von Cl2MDP ist die Resorption fast gänzlich blockiert. Diese Wirkung erfolgt rasch und dauert während einigen Tagen an. Die Folgerungen aus diesen Ergebnissen sowie das Verfahren, Knochenresorptionshemmer mittels kombinierterin vivo/in vitro-Methode zu prüfen, werden diskutiert.
    Notizen: Abstract Two diphosphonates, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) and disodium dichloromethyle diphosphonate (Cl2MDP), inhibit cell-mediated bone resorption of mouse calvaria cultivated for 48 hoursin vitro, when the compounds are added to the medium. Cl2MDP is more effective than EHDP over the dose range 0–16 μg P/ml. Pyrophosphate and imidodiophosphate do not block bone resorption at comparable dose levels. When the two diphosphonates are injected into micein vivo before explants are prepared, subsequent bone resorptionin vitro is considerably reduced; at a dose level of 10 μg P/g body weight of Cl2MDP it is almost completely blocked. This effect is rapid and persists for several days. The implications of these results and the method of testing inhibitors of bone resorption by the combinedin vivo/in vitro method are discussed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 5 (1972), S. 44-52 
    ISSN: 1432-1041
    Schlagwort(e): alprenolol ; serum drug level ; exercise ; man ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of alprenolol on heart rate and systolic blood pressure were studied in healthy subjects during standardized exercise on a bicycle ergometer. In one series of experiments, in which serum concentrations of alprenolol were also measured, the effects of single oral doses of 50, 100 and 200 mg of alprenolol and a placebo were compared by a double blind cross-over technique. In a second series of experiments 100 mg alprenolol was given four times in one day and the effect was followed for up to eighteen hours after the last dose. — Alprenolol diminished the expected increase in heart rate and systolic blood pressure during exercise. The reduction of exercise tachycardia in a given individual was linearly related to the logarithm of the dose or the serum concentration of alprenolol. The serum concentrations required for a given reduction of exercise tachycardia varied almost one hundred-fold amongst the subjects studied. The biological availability of alprenolol was dose-dependent, probably due to a limited capacity biotransformation of the drug before it entered the general circulation. After a single dose the serum level of alprenolol and its chronotropic effect diminished at a rate corresponding to an elimination half life of about two hours. This rate of elimination was consistent with that calculated from the results of the four dose study.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 5 (1972), S. 58-61 
    ISSN: 1432-1041
    Schlagwort(e): Pralidoxime chloride ; pharmacokinetics ; anti-cholinesterase poisoning
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A dose of 1.0 g (10.0–14.0 mg/kg body weight) of pralidoxime mixed with various cholinolytics was given by i.m. injection to 29 healthy male subjects. A concentration of pralidoxime in blood of 4 µg/ml was reached after 5 to 10 min with all the mixtures and was maintained for about 1 to 2 h. The calculated half lives of pralidoxime in three groups of subjects were 62.2, 60.0 and 61.8 min., respectively. — The urinary excretions of pralidoxime during the first 4 h after the injections averaged 75.0, 79.6 and 69.6 per cent, respectively, of the total amount given. — The results are compared with published information about similar oximes.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 29 (1986), S. 721-723 
    ISSN: 1432-1041
    Schlagwort(e): domperidone ; levodopa ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of simultaneous oral administration of 20, 40, or 80 mg domperidone on the pharmacokinetics of an oral 500 mg dose of levodopa was studied in eight normal women. No significant differences in maximum plasma levodopa concentration, the time of its attainment, or the area under the plasma levodopa concentration versus time profile occurred. Domperidone significantly reduced the incidence of adverse gastrointestinal effects due to levodopa administration.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 4 (1972), S. 233-240 
    ISSN: 1432-1041
    Schlagwort(e): Sulphamethoxazole ; trimethoprim ; pharmacokinetics ; uraemia ; sulphonamides
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of sulphamethoxazole (SMZ) and trimethoprim (TMP) have been investigated in four healthy volunteers, 15 patients with stable chronic renal failure and 3 patients on regular dialysis. The dosage schedule was 400 mg of SMZ and 80 mg of TMP orally every 12 h. The plasma concentrations and urinary excretion have been analysed in terms of a one compartment open model, allowing for elimination by renal excretion and metabolic processes. — At equilibrium the plasma concentrations of unchanged sulphonamide showed no significant correlation with the degree of renal impairment. The accumulation of TMP increased slightly without affecting the concentration ratio of both agents in plasma. In contrast, increasing accumulation of metabolized SMZ was demonstrated in the presence of renal insufficiency. Indirect evidence indicates that rising metabolite levels under these circumstances may lead to a displacement of unchanged sulphonamide from protein binding sites. — The cumulative urinary excretion amounted to 82.4% of the dose of sulphonamide administered, which probably corresponds to the fraction of the compound absorbed. The urinary concentration of biologically active SMZ was slightly below the plasma level, especially in advanced renal failure, but it remained above the minimum inhibitory concentrations reported in the literature. The concentration of TMP in urine was considerably higher than in plasma, it decreased with loss of renal function as did active SMZ.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 31 (1986), S. 155-163 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; verapamil ; norverapamil ; pharmacokinetics ; dosing frequency
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Twelve hypertensive patients (WHO Stage I-II) were given oral verapamil (Isoptin) b.d. or t.d.s. as long-term treatment. The pharmacokinetics of verapamil and norverapamil were studied both after single and b.d. and t.d.s. doses of verapamil 240, 360 or 480 mg daily adjusted according to the blood pressure response. The apparent oral clearance of verapamil was decreased after both the twice and thrice daily dosage regimens (1.38 and 1.841/min, respectively) as compared to the single dose (4.39 l/min). The plasma half-life of verapamil was increased from 3.34 h (single dose) to 4.65 h (b.i.d.). Decreased elimination of norverapamil was also found after multiple doses of verapamil, as shown by an increase in the adjusted AUC of norverapamil (adjusted to a verapamil dose of 80 mg), namely from 574.9 h·ng·ml−1 (single dose) to 1172 h·ng·ml−1 (b.d.) and to 841 h·ng·ml−1 (t.d.s.). The plasma half-life of norverapamil increase from 5.68 h to 7.34 h during twice daily dosing. During thrice daily verapamil, no increase in plasma half-life was found either for verapamil or norverapamil, probably due to the relatively short sampling time (6 h). The plasma concentration of verapamil and the reduction in supine systolic and diastolic blood pressure were correlated. The mean decrease in supine systolic blood pressure was 5.8 mm Hg per 100 ng verapamil/ml plasma, and for diastolic pressure 2.9 mm Hg per 100 ng verapamil/ml plasma. The mean steadystate plasma concentrations of verapamil were similar after twice and thrice daily dosing regimens, which agrees with the clinical observation that blood pressure control in hypertensive patients is as good after verapamil b.d. and t.d.s.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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