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EFFICACY OF POLAPREZINC TO ACUTE RADIATION PROCTITIS

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EFFICACY OF POLAPREZINC TO ACUTE RADIATION PROCTITIS Powered By Docstoc
					            Efficacy of Polaprezinc to acute radiation proctitis using an animal experimental model
                   H.Doi1), N.Kamikonya1), Y.Takada1), M.Fujiwara1), K.Tsuboi1), H.Inoue1), M.Tanooka1), T.Nakamura2), T.Shikata2), T.Tsujimura3) and
                   S.Hirota1)       1) Dept. of Radiology, 2) Dept. of Pharmacy, and 3) Dept. of Pathology, Hyogo College of Medicine
                                          1-1,Mukogawa-cho,Nishinomiya City, Hyogo,663-8501, Japan               E-Mail: h-doi@hyo-med.ac.jp

Purpose                                                                                          Results
 The purpose of this study was to standardize the experimental animal model of radiation-                                                                                                                                  Mild ;
                                                                                                    No irradiated rats died during the follow-up period.                                                                Severe ;
induced rectal disorders, and to examine the efficacy of Polaprezinc (PZ),
                                                                                                    Clinical Findings                  0                              2                      4
an anti-ulcer drug, for radiation proctitis.                                                                                                                                                                        PZ(+)
                                                                                                    PZ(+)                              4 (19.0)                       0 (0.0)                1 (4.8)
Materials and Methods                                                                               PZ(-)                              16 (76.2)                      10 (83.3)              19 (90.5)               PZ(-)

                                                                                                    Control                            1 (4.8)                        2 (16.7)               1 (4.8)              Control
 54 female Wistar rats (5 weeks old) were used, and were divided into three groups;
                                                                                                    Endoscopic          0                   1                 2                   3                4
                                                                                                                                                                                                                                 0        20        40             60             80        100        120



             PZ(+) : n=21 : treated with PZ (100 mg/kg/body)                                        Findings
                                                                                                                                                                                                                   PZ(+)
             PZ(-) : n=12 : treated with base (without PZ)                                          PZ(+)               6 (28.6)            9 (42.9)          4 (19.0)            1 (4.8)          1 (4.8)
             Control: n=21 : no medications                                                         PZ(-)               0 (0.0)             3 (25.0)          3 (25.0)            6 (50.0)         0 (0.0)
                                                                                                                                                                                                                    PZ(-)


  All rats were irradiated with a single fraction of 25 Gy to the pelvic region                     Control             0 (0.0)             3 (14.3)          12(57.1)            3 (14.3)         3 (14.3)       Control

 selectively.                                                                                       One specimen of the PZ(+) group was lost in the fixation process.
                                                                                                                                                                                                                             0       10        20   30        40        50        60   70         80    90




  PZ was prepared as an ointment. The ointment was administrated rectally each                      Apparent mucosal changes were observed in the all specimens.
 day after irradiation.
                                                                                                    Pathological Findings
  Each rat was observed daily for clinical findings of proctitis.
  All rats were sacrificed on the tenth day following irradiation.
  Colonoscopy was performed to evaluate the macroscopic findings, and the rectum
                                                                                                                                                                        Crypt architectural distortion
 was excised for a pathological evaluation.                                                                                                                              The columnar shape was lost to be planarized with loss of
  The pathological examination was described the morphological mucosal damage,                                                                                          epithelium.
 the degree of inflammation, and the depth of inflammation.
  In addition, the length of the apparent mucosal change was recorded.                                                                                                  Submucosal edema
  All results were graded from 0 to 4, and compared according to milder or more
                                                                                                                                                                         Degeneration of the muscle fibers
 severe status as applicable.
  Relationship between the groups was assessed using analysis of the chi-squared
                                                                                                     The PZ (+) group tended to show milder mucosal damage than the other groups according to all
 test.
Grading of Mucosal Changes in the rectum                                                            criteria. In addition, significant differences were observed between the PZ (+) group and the control
                                                                                                    group in the endoscopic findings, the degree of inflammation and the depth of inflammation.
   Clinical Findings                                                                                  The average length of crypt damage was 15.6 ±3.8 mm in the PZ(+) group, 15.6 ±3.0 mm in the PZ(-
                             mild                                                                   ) group, and 18.1 ± 3.5 mm in the control group. There were no apparent differences among the
    0 = no symptom
    2 = diarrhea                                                                                    groups (Turkey‘s all- pairwise-comparison test).
                             severe
    4 = gross bleeding                                                                                                                                                                                                          Mild ;
                                                                                                                                                                                                                             Severe ;
   Endoscopic Findings                                                                                Morphological mucosal 0                       1              2                  3                4
    0 = normal mucosa                                                                                 damages                                                                                                       PZ(+)
    1 = edema, mild hyperemia or decrease vasomucosa                        mild                      PZ(+)                 0 (0.0)                 0 (0.0)        16 (80.0)          2 (10.0)         2 (10.0)
    2 = diffuse hyperemia. Multiple punctuate areas of hemorrhage                                     PZ(-)                       0 (0.0)           0 (0.0)        7 (58.3)           2 (16.7)         3 (25.0)
                                                                                                                                                                                                                     PZ(-)
                                                                            severe
       or confluent areas of hemorrhage                                                               Control                     0 (0.0)           0 (0.0)        9 (42.9)           3 (14.3)         9 (42.9)   Control
    3 = presence of erosions or frank hemorrhage
                                                                                                      Degree of the          0                  1                 2               3                    4
    4 = ulcers
                                                                                                                                                                                                                                 0   10        20   30        40        50        60   70         80    90


                                                                                                      inflammation
                                                                                                                                                                                                                    PZ(+)
                                                                                                      PZ(+)                  0 (0.0)            0 (0.0)           6 (30.0)        11(55.0)             3 (15.0)
               Examination】
   【Pathological                                                                                      PZ(-)                  0 (0.0)            0 (0.0)           1 (8.3)         4 (33.3)             7 (58.3)      PZ(-)

   Morphological Mucosal Damages                                                                      Control                0 (0.0)            0 (0.0)           0 (0.0)         9 (42.9)             12(57.1)   Control
    0 = normal or minor alterations                                                                   Depth of the           0                  1                 2               3                    4                         0   10        20   30        40        50        60   70         80    90


    1 = slight crypt change without a loss of epithelium                                              inflammation
                                                                                                                                                                                                                    PZ(+)
    2 = crypt change with loss of epithelium equaling less than half      mild                        PZ(+)                  0 (0.0)            2(10.0)           8 (40.0)        0 (0.0)              10(50.0)
                                                                                                                                                                                                                     PZ(-)
    3 = a crypt change with loss of epithelium greater than half                                      PZ(-)                  0 (0.0)            0 (0.0)           4 (33.3)        0 (0.0)              8 (66.6)
                                                                          severe
    4 = loss of epithelium through muscularis mucosa                                                  Control                0 (0.0)            0 (0.0)           1 (4.8)         4 (19.0)             16(76.2)   Control


    Degree of Inflammation
                                                                                                                                                                                                                                 0         20            40                  60        80              100


                                                                                                 Discussion
    0   =   normal mucosa
    1   =   minor alterations                                                                       It was proven pathologically to irradiate to the rectum selectively using our technique without
    2   =   apparent inflammation (mild inflammation)                                              damage to other organs.
    3   =   more significant inflammation (moderate inflammation)      mild                         We standardized the animal experiment model of the radiation-induced rectal disorders.
    4   =   severe inflammation.                                       severe                       The PZ(+) group tended to show milder mucosal damage than the other two groups.
    Depth of Inflammation                                                                           The efficacy of rectal administration of PZ against the radiation rectal disorders was proven on
    0 = no apparent inflammation                                                                   the rat model.
    1 = inflammatory cells extend up to the edge of the mucosa                                      The PZ (-) group still exhibited milder damage than the control group.
      (epithelium, lamina propria) but not beyond                                                      It was possible to safely administer ointment into the rectum. PZ had additive benefits on
    2 = inflammatory cells extend through the mucosa and into the                  mild            the base.
       submucosa
    3 = inflammatory cells infiltrate through the submucosa and extends into       severe           The PZ (+) group showed apparently lower grades in not only the morphological changes but
       the muscularis propria                                                                      also the inflammation (the degree and the depth) than the other two groups.
    4 = inflammatory cells extend through the muscularis propria into                                  These results may be attributable to the anti-inflammatory effects of PZ.
      the subserosa.
                                                                                                 Further Study; A long term observation to establish an experimental rat model of radiation-
                                                                                                induced rectal disorders as late adverse event is under further investigation now.
Conclusions
                 We could standardize the animal experiment model of acute radiation proctitis.
                 Polaprezinc was proven to be effective against radiation proctitis using the animal experimental model.
                 This is the first report of the rectal administration of Polaprezinc for radiation-induced gastrointestinal injury.

				
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posted:10/25/2011
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