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  • Circulation  (2)
  • animal cell cultivation  (2)
  • 1
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and toxicity of the oxime HGG 12 in dogs (1985)
    Springer
    Archives of toxicology 57 (1985), S. 237-242 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Oximes ; HGG 12 ; Pharmacokinetics ; Circulation ; Respiration ; Toxicity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The pharmacokinetics, pharmacodynamics, and toxicity of the oxime HGG 12 were studied in conscious and anesthetized dogs. IV administration. The mean value of the half-time for terminal elimination of HGG 12 was 47 min; plasma clearance amounted to 4.6ml kg−1 min−1 and Vapp to 0.3151 kg−1. At doses above 1 umol/kg heart rate, left ventricular pressure and mean arterial pressure decreased, while central venous pressure and femoral blood flow increased. The dose-response curves were very flat. Repetitive administration of various doses of HGG 12 in 30 min intervals did not enhance the negative chronotropic effect when the preceding total dose amounted to about 1 μmol/ kg. IM administration. The half-times for the absorption of HGG 12 dichloride and HGG 12 dinitrate were about 3.5 min; the corresponding value for HGG 12 dibromide was 9.4 min. In the elimination phase the half-time was comparable with that of the IV experiments. About 60% of the oxime was excreted unchanged in the urine within 24 h. The circulatory changes showed the same tendency as after IV injection. Conscious dogs tolerated well daily doses of 10 μmol/kg for 6 weeks. At 30 umol/kg all dogs survived, displaying symptoms reminiscent of a cholinergic syndrome. Five out of eight dogs survived at 90 μmol/ kg. Macroscopic and microscopic examinations and blood chemistry data showed no abnormality.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00324784
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  • 2
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and pharmacodynamics of the oxime HI6 in dogs (1986)
    Springer
    Archives of toxicology 59 (1986), S. 272-278 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Oximes ; HI6 ; Pharmacokinetics ; Cere-brospinal fluid ; Blood-brain barrier ; Circulation ; Respiration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The pharmacokinetics and pharmacodynamics of the oxime HI6 were investigated in conscious and anesthetized beagle dogs following intramuscular injection. The absorption of HI6 (100 μmol/kg) was slower in conscious dogs as compared to the anesthetized dogs, and the maximum concentrations in plasma were lower (200 instead of 300 μmol/l). In comparison, the elimination of HI6 (100μmol/kg) was twice as rapid in the conscious dogs (ke=0.013 instead of 0.006 min−1) as in the anesthetized animals and was equal to the elimination after injection of 50 μmol/kg (likewise in anesthesia). The more rapid elimination was accompanied by a greater renal excretion of unchanged HI6 (60% instead of 40% in 3 h). HI6 penetrated the blood-brain barrier. The concentration of the oxime in CSF increased rapidly during the absorption phase (by 30 min after injection). The maximum concentrations (1–3 μmol/l) were reached between 60 and 120 min. The peak concentrations in plasma and CSF did not correlate with each other. In the anesthetized dogs the higher dose of HI6 (100 μmol/kg) caused a steady decrease in mean blood pressure (20 mm Hg) and blood flow (50%) in the femoral artery and a fall in left ventricular pressure (20 mm Hg), lasting for at least 60 min; the lower dose (50 μmol/kg) did not cause circulatory effects. EKG, respiration, hematocrit, arterial blood gases, and pH were not influenced.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00290550
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  • 3
    Digitale Medien
    Digitale Medien
    On-line gas analysis in animal cell cultivation: I. Control of dissolved oxygen and pH (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 45 (1995), S. 42-53 
    Details
    ISSN: 0006-3592
    Schlagwort(e): oxygen uptake rate ; animal cell cultivation ; dissolved oxygen and pH ; state space controller ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: To monitor gas reaction rates in animal cell culture at constant dissolved oxygen concentration (DO) and constant pH it was necessary to develop improved control methods. Decoupling of both controllrs was obtained by manipulation of molar fractions of oxygen and carbon dioxide in the gas phase. Two pairs of DO and pH controllers were designed and tested both in simulation and exprimental runs. The first controller pair was developed for headspace aeration only, whereas the second controller pair was designed for bubble aeration using a microsparger and flushing the headspace with helium. pH was controlled by a conventional discrete PID controller in its velocity form. For DO control two linear state space feedback controllers with parameter adaptation were established. In these controllers the oxygen uptake rate (OUR) was considered as a disturbance and was not included in the mathematical model. The feedback gain adaptation was based on the difference between the actual molar fraction of oxygen at time step n and the initial molar fraction. This difference is related to OUR and was used to increase or decrease the state feedback controller gain (k and k1, respectively) in a slow manner. With these controllers it was possible to get an excellent online estimate of OUR. In the case of bubble aeration a simple gas phase mass balance was sufficient, whereas during the headspace aeration a liquid phase balance was required. It has been shown that determination of OUR using gas balance requires a significantly better controller performance compared to just keeping DO and pH within reasonable limits. © 1995 John Wiley & Sons, Inc.
    Zusätzliches Material: 11 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/bit.260450107
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  • 4
    Digitale Medien
    Digitale Medien
    On-line gas analysis in animal cell cultivation: II. Methods for oxygen uptake rate estimation and its application to controlled feeding of glutamine (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 45 (1995), S. 54-62 
    Details
    ISSN: 0006-3592
    Schlagwort(e): oxygen uptake rate ; animal cell cultivation ; hybridoma ; monoclonal antibody ; glutamine ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: Different methods for oxygen uptake rate (OUR) determinations in animal cell cultivation were investigated using a high quality mass spectrometer. Dynamic measurements have considerable disadvantages because of disturbances of the growing cells by the necessary variations of dissolved oxygen concentration. Only infrequent discrete measurements are possible using this method. Stationary liquid phase balance yielded better results with much higher frequency. Gas phase balancing has the advantage of not requiring dissolved oxygen measurement and knowledge of KLa, both of them are easily biased. It was found that simple gas phase balancing is either very inaccurate (error larger than expected signal) or very slow, with gas phase residence times of several hours. Therefore, a new method of aeration was designed. Oxygen and CO2 transfer are mainly achieved via sparging. The gas released to the headspace is diluted with a roughly 100-fold stream of an inert gas (helium). Through this dilution, gas ratios are not changed for O2, CO2, Ar, and N2. The measurement of lower concentrations (parts per million and below) is easy using mass spectrometry with a secondary electron multiplier. With this new method an excellent accuracy and sufficient speed of analysis were obtained. All these on-line methods for OUR measurement were tested during the cultivation of animal cells. The new method allowed better study of the kinetics of animal cell cultures as was shown with a hybridoma cell line (HFN 7.1, ATCC CRL 1606) producing monoclonal antibodies against human fibronectin. With the aid of these methods it was possible to find a correlation between a rapid decrease in oxygen uptake rate (OUR) and glutamine concentration. The sudden decrease in OUR can be attributed to glutamine depletion. This provided a basis for the controlled addition of glutamine to reduce the formation of ammonia produced by hydrolysis. This control method based on OUR measurement resulted in increased cell concentration and threefold higher product concentration. © 1995 John Wiley & Sons, Inc.
    Zusätzliches Material: 9 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/bit.260450108
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