Page 4 - Gastric pentadecapeptide BPC 157
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M. Sture.tinic cpl ul. / Jourtiul of  Orthupuerlic Riwurch 21  (2003) 976-983   979
          Table  I
           Rat Achilles tendon  transection
            Assessed   Therapy   Time after Achilles tendon transection
            parameter
                                 Day 4               Day 7               Day  10             Day  14
                                 Med   Min    Max    Med   Min    Max    Med   Min    Max    Med    Min   Max
                                                                                                        ~~
            Failure    Healthy   58.30   47.22   67.29   61.28   47.22   67.29   75.20   58.00   83 10   63.50   58.30   97.27
              load     Saline   ____  12.781  27.710  15.637  39.258           is.526  7o.300             68.261
                                       3.223
                                 9.119
                       10 Pg     8.2556.892  13.098  30.701  26.513  36.084  56.445  43.945  71.094  63.500   58.301   97.266
                       10 ng     10.406  6.641   15.136  30.591  17.053  36.474  50.732  45.556  65.723  68.408  57.617   88.281
                       10 P6    ~~  10.821  2.673   14.013  31.762  25.879  43.774  47.412  26.196  61.474   73.096
            Failure    Healthy   11.28   8.99   12.82   11.28   8.99   12.82   13.50   12.60   15.00   12  10   1 I  10   18.53
              load per   Saline   ____  2.434        5.278   2.979       10.668  7.338   13.390  9952  6678  13.002
                                 1.737
                                       0.614
                                       1.314
                                 1.573
              area     10 Pg    ____  2.495          5.848  5.050  6.873  10.751  8.371  13.542  12.095   11.105   18.527
                       10 ng    ____  2.883          5.827  3.248  w  9.663  8.677  12.519  13.030   10.975   16.815
                                       1.265
                                 1.982
                                       0.509
                                 2.061
                       10 Pg    ____  2.669          6.05   4.929        9.031   4.990   11.709    4567  13.923
            Young’s    Healthy   10.44   5.77   13.90   7.69   5.66   13.90   11.80   11.30   13.90   10 70   5 66   15.08
              modulus of  Saline   2.2800.402   2.988   4.811  3.337     5.925   5.158   9.877     4454   8.795
              elasticity   10 Pg   _   1.030   3.958  ~ 5.333   3.722   7.183   7.887   $.771  17.632  10.702   5.662   15.077
                                 1.948
                                         _
                       10 ng    2.937  _  1.866   _ 3.758   5.723   2.034   6.395  4.206   8.875  m  5645   13.509
                                ~
                                          _
                       10 Pg    2.3310.855  3.775    4.921  3.446   6.049  5.974   3.552   7.791   6309  4.199   9.290
            Fibroblast   Saline   1326   1056   I430   1770   1626   I920   1976   1872   2100   I884   1626   2172
              number   10 Pg     1420   1350   1480   2014   I988   2097   2400   2100   2556   2196   1818   2460
                       10 ng     1377   1067   1563   2053   1889   2106   2266   2051   2456   1870   1670   1956
                       10 Pg     1255   1107   1580   I693   1623   1886   1934   1806   2106   1837   1677   2043
            Reticulin   Saline   0.350   0.320   0.370     ~      -     -      -      -
              proportion  10 Pg   0.540   0.500   0.590    -      -     -      -      -      -
                       10 ng    0.520   0.500   0.530   -   -            -     -      -      -     -      ~
                       10 Pg    0.360   0.320   0.380   -   -     -     -      -
            Collagen   Saline   -      -      -     0.24   0.19   0.29   0.321   0.254   0.367   0 396   0 356   0. 440
              proportion  10 Pg   -    -             0.40   0.30   0.46   0.506   0.485   0.520   0.521   0.465   0.610
                       10 ng                  -     0.38   0.28   0.48   0.480   0.465   0.510   0.502   0.43 7   0.589
                       10 Pg    -                   0.25   0.19   0.30   0.325   0.289   0.356   0 422   0.337   0.438
            Gape       Saline   6.4    5.6    7.8    2.95   2.2   2.8    0.15   0     0.5    01    0      0.2
              between the  10 LIE   2.6   2.0   3.2   0.05   0    0.2   0.2    0      0.6    01    0      0.2
              cut ends   10 ng   2.6   2.0    3.6    0.  I   0    0.3    0.1   0      0.2    01    0      1
                         .-
                       10 P?z   6.7    5.0    7.6    3.1   2.5    30     0.1   0      0.2    01    0      0.2
          Assessment at post-operative day 4, 7, 10, 14: (ij biomechanical (failure load (N), failure load per area (Nlmm’j,  Young’s  modulus of elasticity). (ii)
          microscopy (reticulin proportion, fibroblast number, collagen proportion per visual field), (iii) macroscopy (size of the defect (longest diameter. mm)
          in tendon between the cut ends. Agents (/kg b.w.,  i.p., once time daily) (gastric pentadecapeptide BPC 157 (10 pg,  10 ng or 10 pg) or saline (5.0 ml)).
          were firstly  applied  at 30 min after surgery, the last application at 24 h before autopsy. Median/Minimum/Maximum (Med/Min/Max). Kruskall-
          Wallis and Mann-Whitney  tests (due to Bonferroni correction, the values ofp < 0.016 or less were considered to be statistically relevant. vs. controls
          with tvansccted tendon. or GS.  normal  healthy rats).  (-)  not assessed.
          growth stimulation (Fig. 5). Adding BPC 157 after HNE   cpm/well  [3630-36901  vs.  2500  cpm/well  [2487-25121,
          results in a growth stimulation, while the peptide abol-   p  = 0.021).
          ished inhibiting effect of HNE.
                                                               Discussion
          Serurn deprived conditions
             TGF-PI strongly increased cultured tendocytes DNA   Stable  peptide  can  play  a  major  role  in  generating
          synthesis,  while  BPC  157  itself  did  not  change  the   therapy for tendon healing and this study focus was on a
          growth of the cells (Fig. 6).                        stable gastric  pentadecapeptide  BPC  157. Currently  in
             HNE alone showed  a  slight  inhibiting  activity  (me-   clinical trials for inflammatory bowel disease (PLD-116,
          dian  [minimum-maximum])  (485  cpm/well  [470490])   PL- 14736, Pliva),  it  ameliorates  internal  and  external
          compared  to  HNE  administered  after  BPC  157  (507   wound  healing  [8,12,16,17,19-21,31].  Here,  systemic
          cpm/well [499-512]), p  = 0.021.                     administration-improvement  of  an  injured  tendon  fol-
             Combined  with  TGF-Pl  HNE added  after  TGF-P1   lows  from  a  general  evidence  presenting  this  tendon
          resulted  in  more  pronounced  growth  inhibition  (3647   repair  similar  to the  repair  of  other  connective  tissues
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