A kinetic model of prostaglandin metabolism in the lung

1979 ◽  
Vol 47 (2) ◽  
pp. 404-411 ◽  
Author(s):  
J. H. Linehan ◽  
C. A. Dawson

We have measured the instantaneous extraction of prostaglandin E1 (PGE1) after a single bolus injection of PGE1 and indocyanine green dye into the pulmonary artery of isolated cat lungs. The extraction ratio versus time curves exhibited a characteristic shape; at early times they were concave upward and later in time concave downward. To evaluate this date we utilized a model in which themechanism of PGE1 uptake is saturable and follows Michaelis-Menten kinetics. The model assumes heterogeneous perfusion of the exchanging region of the lung and can be solved by regression analysis to obtain Km and Vmax from the data collected from a single bolus injection. The results indicate that the shape of the extraction ratio curve manifests the influence of nonlinear uptake and heterogeneous perfusion and that the kinetic parameters may be calculated from the data obtained after a single bolus injection ofPGE1.

1991 ◽  
Vol 5 (1) ◽  
pp. 19-22 ◽  
Author(s):  
N.C. Hickey ◽  
C.P. Shearman ◽  
M.C. Crowson ◽  
M.H. Simms ◽  
H.R. Watson

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Joseph Malinzi

A mathematical model for the treatment of cancer using chemovirotherapy is developed with the aim of determining the efficacy of three drug infusion methods: constant, single bolus, and periodic treatments. The model is in the form of ODEs and is further extended into DDEs to account for delays as a result of the infection of tumor cells by the virus and chemotherapeutic drug responses. Analysis of the model is carried out for each of the three drug infusion methods. Analytic solutions are determined where possible and stability analysis of both steady state solutions for the ODEs and DDEs is presented. The results indicate that constant and periodic drug infusion methods are more efficient compared to a single bolus injection. Numerical simulations show that with a large virus burst size, irrespective of the drug infusion method, chemovirotherapy is highly effective compared to either treatments. The simulations further show that both delays increase the period within which a tumor can be cleared from body tissue.


2017 ◽  
Vol 39 (8) ◽  
pp. e64-e65
Author(s):  
A. Grošelj ◽  
M. Kržan ◽  
T. Kosjek ◽  
M. Bošnjak ◽  
G. Serša ◽  
...  

1981 ◽  
Vol 50 (2) ◽  
pp. 428-434 ◽  
Author(s):  
J. H. Linehan ◽  
C. A. Dawson ◽  
V. M. Wagner-Weber

The instantaneous extraction of prostaglandin E1 (PGE1) was measured after a bolus injection of PGE1 and [14C]dextran in to the pulmonary artery of isolated cat lungs perfused with a physiological salt solution [Krebs-Ringer-bicarbonate buffer (KRB)]. The extraction ratio vs. time curves exhibited characteristic shapes. For low injected doses of PGE1, the extraction ratios were constant early in time, whereas for high doses, they were concave upward. To evaluate the data, we used a model assuming homogeneous perfusion and a saturable uptake mechanism (Michaelis-Menten kinetics) for the PGE1. The model was used in a linear regression analysis to estimate Vmax and Km. The kinetic parameters were compared with our previous results for blood-perfused lungs, and it was found that the values of Km were significantly smaller than in blood-perfused lungs but that the values of Vmax were not significantly different. These results were consistent with the observation that PGE1 uptake was greater in KRB- than in blood-perfused lungs when the dose of PGE1 was low but that the difference disappeared at high doses. The absence of plasma protein binding in KRB-perfused lungs may be responsible for the lower Km.


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