PROGRAM: MODEL FOR LIPID PEROXIDATION IN LIVER SLICES in vitro
'****DATA AND COMMANDS FOR RUN-TIME***                              '

'NOTE: Will run under SIMUSOLV or early versions of ACSL.           '
'For ACSL 11 + this file should be reformated.                      '
  
'      ******* LPOXLIV.CMD *******                                  '
'      ******* PART 2 0F 2 OF MODEL LPOXLIV *******                 '
'-------------------------------------------------------------------'

'SIMULATE PRODUCTION OF TBARS FROM PUFA IN LIVER SLICES in vitro    '
'BBPD MODEL FOR CHEMICALLY INDUCED LIPID PEROXIDATION IN  LIVER     '
'SLICES in vitro                                                    '

'Originally posted at PBPK-L Source Code Listing,                   '
'URL: http://www.navy.al.wpafb.af.mil/new.htm                       '
 
'DISCLAIMER: By using this PBPK source code you, the user,          '
' implicitly agrees with the conditions and rules stated in this    '
' PBPK-L public domain source code disclaimer. If you have not read '
' this yet, please read it now. If you do not agree with the        '
' conditions and rules stated in it, please dispose of all contents '
' of the PBPK source file and all related files now in your         '
' possession. The PBPK computer modeling programs are placed here by'
' their authors for the convenience of others interested in PBPK    '
' modeling. No representation of their suitability or correctness is'
' implied. Please understand that PBPK models are complex entities  '
' whose value is minimal when taken out of context. With that       '
' understanding, you are welcome to use this code for teaching and  '
' further development of the ideas that they represent. The         '
' information and/or opinions presented here are those of the       '
' authors and are not endorsed by the US Air Force, US Navy, US     '
' Army, Tri-Service Toxicology Consortium, Department of Defense, or'
' the US Government. The US Air Force, US Navy, US Army, Tri-Service'
' Toxicology Consortium, Department of Defense, or the US Government'
' and the authors of this PBPK source code accept no responsibility '
' for damages resulting from the use of the code and make no        '
' warranty or representation, either express or implied, including  '
' but not limited to, any implied warranty of merchantability or    '
' fitness for a particular purpose. PBPK source code is provided *as'
' is*, and you, its user, assume all risks when using it.           '

' Description of this program has been published: Byczkowski,J.Z.,  '
' Channel,S.R., Pravecek,T.L., and Miller,C.R. (1996)               '
' Mathematical model for chemically induced lipid peroxidation in   '
' precision-cut liver slices: Computer simulation and experimental  '
' calibration. Computer Methods Progr. Biomed. 50, 73-84.           '
' Reprints of his article are indicated as AL/OE-TR-1996-0081 by    '
' Armstrong Aerospace Medical Research Laboratory, Wright Patterson '
' Air Force Base, OH.                                               '
' Results of simulation and experimental details have been          '
' published: Byczkowski,J.Z., Channel,S.R., and Pravecek.L. (1995). ' 
' Development and experimental calibration of the mathematical      '
' model for lipid peroxidation in mouse liver slices. Reprints of   '
' this article are indicated as Technical Report, AL/OE-TR-1995-0179'
' by Armstrong Aerospace Medical Research Laboratory, Wright        ' 
' Patterson Air Force Base, OH.                                     '

'Key words: Biologically based pharmacodynamic model, BBPD, Liver   '
'           in vitro, Lipid peroxidation, Toxicology, tert-Butyl    '
'           hydroperoxide, Bromotrichloromethane, Mouse, Rat.       '

'     Please send comments to the authors E-mail address:           '
'                  JANUSZ.BYCZKOWSKI@USA.NET                        '
'^^^^^^^^^^^^^^^Please do not delete this message^^^^^^^^^^^^^^^^^^^'

'-------------------------------------------------------------------'
'CHEMICALLY INDUCED LIPID PEROXIDATION IN THE LIVER                 '
'BBPD MODEL FOR LIVER SLICES in vitro  *.CMD FILE                   '
'The Fig#s correspond to figures in Byczkowski et al. (1996)        '
'Computer Methods Progr. Biomed. 50, 73-84                          '

PROCED FIG2
'Fig. 2 '
SET TITLE='RAT LIVER SLICES WITH BrCCl3'
SET TSTOP=2., NRWITG=.F.,
PREPAR T,TBARS,ACTLOS,INDREM,ANOXRE,AUTOX,PXREDA,AUTOXA,HPUF
PREPAR PXHUFA,PXLUFA,PXREM,PXREDG,GSHREM,TPX,PXHUF,PXLUF,LPUF
PREPAR ANOXEF,ACTIND,ACTREM,INDEF,ACTEF,HPUFRE,LPUFRE,HPUF,INDLOS
SET PTIND1=4.1,ACTDGF=1.5,INDLF=0.12,ANOX1=0.005,IND1=5.

'     a.       c.      b.      d.     e.     f.     g.'
'[h] [micromole/0.1 g liver]'
DATA

T   TBARS    INDREM  ACTREM  ANOXRE LPUFRE HPUFRE  AUTOX
0.    0.     20.5    0.0003   0.005   3.0   4.0     0.  INITIAL
0.25 0.00293  .       .        .       .      .      .
1.   0.00507  .       .        .       .      .      .
1.5  0.00667  .       .        .       .      .      .
2.   0.00827 15.68   0.000249 0.00386 2.91 3.88   0.024

END      $'END OF DATA'
START
PLOT TBARS
END      $ END OF FILE'

PROCED FIG3 
'Fig. 3 '
SET TITLE='RAT LIVER SLICES WITH BrCCl3' 
SET TSTOP=2., NRWITG=.F.,
PREPAR T,TBARS,ACTLOS,INDREM,ANOXRE,AUTOX,PXREDA,AUTOXA,HPUF
PREPAR PXHUFA,PXLUFA,PXREM,PXREDG,GSHREM,TPX,PXHUF,PXLUF,LPUF
PREPAR ANOXEF,ACTIND,ACTREM,INDEF,ACTEF,HPUFRE,LPUFRE,HPUF,INDLOS
SET PTIND1=6.06,ACTDGF=3.75,INDLF=0.59,ANOX1=0.00463,IND1=5.

'[h]   [mcm/0.1g]'
DATA

T   TBARS                                                
0.    0.                                                       
0.25 0.00293                                            
1.   0.00507                                            
1.5  0.00667                                            
2.   0.00827                                            

END      $'END OF DATA'
START
PLOT TBARS
END      $ END OF FILE'

PROCED FIG4   
'Fig. 4 '
SET TITLE='RAT LIVER SLICES WITH TBOOH' 
SET TSTOP=2.,
PREPAR T,TBARS,ACTLOS,INDREM,ANOXRE,AUTOX,PXREDA,AUTOXA,HPUF
PREPAR PXHUFA,PXLUFA,PXREM,PXREDG,GSHREM,TPX,PXHUF,PXLUF,LPUF
PREPAR ANOXEF,ACTIND,ACTREM,INDEF,ACTEF,HPUFRE,LPUFRE,HPUF,INDLOS
SET PTIND1=6.9,IND1=5.,INDLF=0.275,ACTDGF=3.43,ANOX1=0.00463
SET NRWITG=.T., BCKGD=0.0014

START
SET BCKGD=0.

'[h]   [mcm/0.1g]'
DATA

T       TBARS           
0.      0.0014     INITIAL   
0.5     0.0060        
1.      0.0090        
1.5     0.0120         
2.      0.0156 
0.      0.0         INITIAL
0.5     0.0046         
1.      0.0076         
1.5     0.0106        
2.      0.0142         

END      $'END OF DATA'
START
PLOT TBARS 
END      $'END OF FILE'

PROCED FIG5    
'Fig. 5 '
SET TITLE= 'MOUSE LIVER SLICES WITH TBOOH'
SET TSTOP=2., NRWITG=.F., BCKGD=0.
PREPAR T,TBARS,ACTLOS,INDREM,ANOXRE,AUTOX,PXREDA,AUTOXA,HPUF
PREPAR PXHUFA,PXLUFA,PXREM,PXREDG,GSHREM,TPX,PXHUF,PXLUF,LPUF
PREPAR ANOXEF,ACTIND,ACTREM,INDEF,ACTEF,HPUFRE,LPUFRE,HPUF,INDLOS
SET PTIND1=6.9,ANOX1=0.0037,INDLF=0.275,ACTDGF=3.43,IND1=7.83

'[h]   [mcm/0.1g]  [mcm/0.1g]'
DATA

T       TBARS      IND1 
0.      0.0        9.1  
0.333   0.007      8.7
0.667   0.010      7.7
1.0     0.018      7.6
1.333   0.015      7.8
1.667   0.027      7.6
2.0     0.023      7.6

END      $'END OF DATA' 
START
PLOT TBARS
END      $'END OF FILE'

PROCED FIG6    
'Fig. 6 '
SET TITLE= 'DOSE-RESPONSE MOUSE LIVER SLICES WITH TBOOH'
'CONC=1.5 mM t-BOOH'
SET TSTOP=1., NRWITG=.T., BCKGD=0.00001
PREPAR T,TBARS,ACTLOS,INDREM,ANOXRE,AUTOX,PXREDA,AUTOXA,HPUF
PREPAR PXHUFA,PXLUFA,PXREM,PXREDG,GSHREM,TPX,PXHUF,PXLUF,LPUF
PREPAR ANOXEF,ACTIND,ACTREM,INDEF,ACTEF,HPUFRE,LPUFRE,HPUF,INDLOS
SET PTIND1=6.9,ANOX1=0.0037,INDLF=0.275,ACTDGF=3.43,IND1=8.35

SET IND1=5.92,BCKGD=0.00001
'CONC=1.0 mM t-BOOH' 
START

SET IND1=3.15,BCKGD=0.00001
'CONC=0.5 mM t-BOOH'
START

SET IND1=0.613,BCKGD=0.00001
'CONC=0.1 mM t-BOOH'

'[h]   [mcm/0.1g]'
DATA
T       TBARS           
0.      0.000001        INITIAL
1.      0.018672
0.      0.000001        INITIAL
1.      0.020764
0.      0.000001        INITIAL
1.      0.007818
0.      0.000001        INITIAL
1.      0.001885

END      $'END OF DATA' 
START
PLOT TBARS,'log','lo'=0.00001,'hi'=0.100
END      $'END OF FILE'

'              END OF LPOXLIV.CMD                         '
'---------------------------------------------------------'
'       ***** END OF PART 2 0F 2 OF MODEL LPOXLIV*****    '