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  • 1
    ISSN: 1432-0738
    Keywords: Acute CO Intoxication ; Venous Oxygen Pressure ; Blood Sugar Concentration ; High (Atmospheric) Pressure ; Effects of CO ; Akute Kohlenoxidvergiftung ; Venöser Sauerstoffdruck ; Blutzuckerverhalten ; Überdruck ; Spezifische Kohlenoxidwirkungen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In drei Versuchsreihen an Kaninchen werden nach 1stündiger Einwirkung hoher CO-Konzentrationen unter normalem und erhöhtem Luftdruck Blutzucker, Kohlenoxidhämoglobingehalt (COHb) und Sauerstoff-Partialdruck (pO2) in der V. jugularis gemessen. Hierzu werden analoge Versuche mit reinem Sauerstoffmangel, erzielt durch 1stündige Einwirkung von Sauerstoff-Stickstoffgemischen, in Beziehung gesetzt. Bei 2000 ppm CO in der Einatmungsluft steigt unter normalem atmosphärischen Druck im Mittel von 22 Versuchen der Blutzucker nach 1 Std um 87 % gegenüber dem Ausgangswert von 98,5 mg- % an. Der Sauerstoffdruck im venösen Blut fällt von etwa 45 Torr bereits nach 10 min auf die Hälfte ab und erreicht den Endwert von 9,5 Torr O2 schon nach 30 min. Der sich ebenfalls rasch einstellende COHb-Endwert beträgt 47,9 % im Mittel. Bei Einatmung eines Luftgemisches mit 2000 ppm CO unter einem Druck von 4 ata steigt der Blutzucker trotz annähernd gleichem COHb (43,1 % im Mittel) und etwa gleichem pCO im Gewebe nicht an. Hierbei ist von Bedeutung, daß der venöse pO2 nur auf einen Endwert von 20 Torr absinkt. Die Endwerte für pO2 und COHb sind bereits nach 10 min erreicht. Durch Inhalation eines sauerstoffarmen Stickstoff-Luftgemisches (4 bis 6 Vol- % O2 in der Einatmungsluft) läßt sich der venöse pO2-Abfall der ersten Versuchsreihe mit 2000 ppm CO in Luft unter 1 ata nachahmen. Es zeigt sich, daß pO2 auf etwa 10 Torr absinkt, während der Blutzucker um 100 % gegenüber dem Ausgangswert ansteigt. Nach diesen Untersuchungen scheint der Blutzuckeranstieg bei akuter CO-Vergiftung nicht spezifisch durch den CO-Gehalt von Blut und Geweben, sondern durch den unspezifischen Sauerstoffmangel der Gewebe — als Folge der hypoxischen Wirkung des Kohlenoxids — verursacht zu sein.
    Notes: Abstract In rabbits, exposed to high CO concentration at normal and increased atmospheric pressure for 1 h, we investigated the effects of CO intoxication of the level of blood sugar, on carboxyhemoglobin (COHb) concentration in blood and on the partial pressure of oxygen (pO2) in jugular venous blood. Analogous experiments were performed with rabbits exposed for 1 h to oxygen deficiency produced by breathing a mixture of oxygen and nitrogen. In animals exposed to 2000 ppm CO under normal atmospheric pressure the level of blood sugar increases after 1 h from 98,5 mg- % to 184 mg- % (mean value of 22 experiments). The partial pressure of oxygen in venous blood decreases within 10 min from 45 torr to about 23 torr and reaches a final value of 9,5 torr O2 after 30 min. The final value of COHb (mean value 47,5 %) is also reached within a short time. Breathing 2000 ppm CO under 4 ata the blood sugar concentration does not increase in spite of about the same CO Hb concentration (mean value 43,1 %) and similar pCO values at the same time. The venous pO2 decreases only to a final value of 20 torr. The final values of pO2 and CO Hb are reached within only 10 min. Breathing mixture of nitrogen and air (4 to 6 % O2 per volume) the venous decrease of pO2 is similar to effects described in the first series with 2000 ppm CO at 1 ata: decrease of pO2 to about 10 torr and increase of blood sugar of about 100% compared to the initial value were observed. These results support the hypothesis that the increase of blood sugar after carbon monoxide intoxication is induced by the nonspecific oxygen deficiency of the organism — caused by CO-poisoning — and is therefore not primarily specific for the CO concentration of blood and tissue.
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  • 2
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Probenecid (50 mg·kg−1) was found to induce an increase of the plasma concentration of14C-benzylpenicillin with a decrease of the concentration in liver and kidney. Accumulation in corresponding tissue slices was reduced by probenecid. Therefore, the well known increase of penicillin in plasma after probenecid seems to be not only due to an inhibition of renal excretion but also to a reduced tissue uptake in liver and kidney.
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  • 3
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The absorption of3H-digitoxin from perfused rat small intestine was inhibited by probenecid (1.0×10−2 M), ethacrynic acid (0.5×10−3 M), and mersalyl (8.0×10−3 M) indicating that digitoxin absorption is at least partly an active process.
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  • 4
    ISSN: 1432-1912
    Keywords: Digitoxin ; Plasma binding ; Tissue uptake ; Species differences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The content of cardiac glycosides in plasma and several organs of rats and mice was investigated 30 min and 12 hrs after i.p. administration of 160 μg/kg b.w. 3H-digitoxin. In rat plasma a glycoside concentration of 124.8 and 44.7 ng/ml resp. was found. The corresponding values in the liver were 834.7 and 579.7 ng/g w.w. An opposite liver/plasma distribution was obtained in mice: while in plasma 772.5 and 571.8 ng/ml were recovered, the glycoside concentration in liver was relatively small (284.8 and 235.6 ng/g w.w.). In order to find out the reason for such species differences observed in vivo, liver slices of rats and mice were incubated with 3H-digitoxin in a medium with and without various plasma proteins. The uptake of 3H-digitoxin into liver slices was drastically reduced by adding mouse plasma or albumin to the medium, while rat plasma lowered the uptake far less. These differences are well reflected by binding studies on agargel electrophoresis: only in mouse plasma a binding of 3H-digitoxin could be demonstrated. The binding rate and binding constant analyzed by equilibrium dialysis were higher in mouse than in rat plasma. It is concluded that the lower tissue accumulation in mice compared to rats must be due to the affinity of 3H-digitoxin to mouse plasma albumin. Moreover digitoxin has a higher affinity to the rat than to the mouse liver in the presence of mouse or rat plasma as well as of bovine serum albumin.
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  • 5
    ISSN: 1432-1912
    Keywords: Probenecid ; Cardiac Glykosides ; Distribution ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Distribution studies have been performed on mice with tritium labelled Digitoxin, Digoxin and Ouabain. Contrary to many other species Digitoxin does not lead to an accumulation of radioactivity in the mouse organs. Neither the liver, nor the muscle, nor the kidney concentrations ever reached plasma radioactivity levels; the highest organ concentrations in steady state were found in the liver,and attained between 40 and 50% of plasma radioactivity concentrations. Radiochromatographic controls of these experiments in the liver, bile and plasma showed that Digitoxin is metabolized to a very small extent only and is especially not subject to 12-β-hydroxylation: no Digoxin is demonstrable in liver, bile, plasma, and urine of the mouse following Digitoxin administration. Unlike with Digitoxin is the concentration of Digoxin and Ouabain in the mouse liver very effective. Liver radioactivity after 3H-Digoxin administration is found mostly to be 2–3 fold above plasma level concentrations whereas Ouabain—not metabolized in the mouse—may reach liver concentrations up to 35 times the plasma level. Radioactivity in bile reflects this behaviour: Ouabain bile levels reach the highest values (up to 200 fold) whereas Digitoxin never exceeds plasma radioactivity. When Probenecid was given together with the cardiac glykosides, Digitoxin plasma radioactivity fell to about half of the control values with a slight rise in liver and muscle concentrations. With Digoxin and even more with Ouabain Probenecid inhibited their accumulation in the liver leading to a redistribution into the plasma and muscles with subsequent higher muscle concentrations. The general Probenecid effect was to level out concentration gradients mostly pronounced in the Ouabain experiments where also the effect was achieved with the lowest Probenecid dose (20 mg/kg). A satisfactory explanation for this effet is not yet possible.
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  • 6
    ISSN: 1432-1912
    Keywords: Digitoxin ; Intestinal Transport ; Dose Dependence ; Functional Asymmetry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary On everted jejunal segments of mice the transfer and tissue uptake of 3H-digitoxin, over a concentration range from 2×10−10–1×10−4M, was investigated from the mucosal (“m”) to the serosal (“s”) side as well as in the opposite direction. 1. The time course of the absorption of 3H-digitoxin and some other compounds investigated (glucose, urea, p-aminohippurate) gave evidence of functional integrity throughout the 75 min-periods of the experiments. 2. When 3H-digitoxin was applied to the mucosal side the permeability coeffcient showed a dose-dependent increase but returned to lower values at higher concentrations. When 3H-digitoxin was administered to the serosal side the permeability coefficient showed a dose-dependent decrease at high concentrations. The ratio of both coefficients “m” → “s”/“s” → “m” increased dose-dependently from 0.4–2.6. 3. The uptake of 3H-digitoxin — applied on the serosal side — into the tissue was independent of dose. However, having administered 3H-digitoxin on the mucosal side the tissue accumulation was 2–5 fold higher and the tissue/medium (T/M) ratio increased within the concentration range from 3.0–9.0. 4. Under DNP (1 mM) the asymmetry and dose dependence of the permeability and tissue uptake of 3H-digitoxin observed in controls were almost abolished. Therefore it is likely that the transfer of 3H-digitoxin in the intestine involves a mechanism more complex than simple diffusion. The existence of more than a two compartment system and/or the contribution of an active transport mechanism is suggested.
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  • 7
    ISSN: 1432-1912
    Keywords: Protein Binding ; Phenol Red ; Digitoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The binding of phenol red and digitoxin to bovine albumin has been measured by means of equilibration dialysis and characterized by the following parameters: binding constant K 1, number of binding sites per albumin molecule n, and free binding energy DF o. Protein binding of phenol red yields a saturation type curve with saturation at about 11.3 mmole/l. Phenylbutazon and probenecid were able to displace phenol red from albumin binding sites in concentrations which are regularly reached after therapeutic doses. With digitoxin because of its hydrophobic character plasma binding could not be measured beyond concentrations of 0.82 mmole/l. Though in principle there is no difference between phenol red and digitoxin binding (a digitoxin binding curve could be calculated also for high concentrations) no displacement effect was seen with probenecid, phenylbutazon, salicylic acid and benzbromaron up to tenfold therapeutic plasma levels. These drugs were effective, however, in the displacement of digitoxin in diluted plasma albumin solutions. This indicates that for an effective displacement multiple molar concentrations of bound and displacing drug with respect to the binding protein are necessary. Displacement from plasma protein therefore plays no role in the possible interference of drugs if one of them is applied in doses far below the molar concentration of the binding proteins.
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