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Inhibitory effect of melatonin on gastric mucosal injury induced by ischemia reperfusion in rat
AI086 AGA ABSTRACTS
GASTROENTEROLOGY Vol. 118, No.4
5030
5032
DOES LOCAL EXCISION OF RECTAL ADENOMAS AND CARCINOMAS LEAD TO INCREASED SYMPTOMATIC FAECAL INCONTINENCE? A PATIENT QUESTIONNAIRE STUDY. Tim A. Justin, Nick C. Armitage, Univ Hosp, Nottingham, United Kingdom; Univ Hosp, Nttingham, United Kingdom. Aim:To evaluate the bowel symptoms of patients who underwent local excision of rectal adenomas and carcinomas. Methods: This was a patient questionnaire study sent to patients with at least 12 months of follow up. Modified Kamm symptom scoring system was used. Score 0 was perfect continence and score 20 was total incontinence. Information on alteration in life style was not collected. Results: 68 out of 83 patients responded.( response rate 83%) 4 questionnaires were void leaving 64 questionnaires for analysis from 30 men and 34 women.23 female patients had vaginal delivaries in the past and 12/23 and 3/23 underwent episiotomy and forceps delivary respectively. Only 58% of female patients compared to 90% of men had Kamm scores of 0 to 5. Conclusion: As only 15% and 30% of female and male patients respectively had perfect continence (score 0) detailed symptom scoring is essential prior to local excision.
NO INDUCES DECREASE OF MITOCHONDRIAL MEMBRANE POTENTIAL IN PERIPHERAL BLOOD LYMPHOCYTES ESPECIALLY IN NK CELLS. Yasuhiro Kawai, Shingo Iwata, Michiyuki Kanai, Ryusuke Denno, Yoshiro Taki, Arimichi Takabayashi, Kitano Med Research Institute and Hosp, Osaka, Japan. During and after major surgery, nitric oxide (NO) is produced eminently in inflammatory condition. Increased levels of NO concentration at inflammatory site may affect the biological activity of lymphoid cells. We have previously demonstrated that the number of iNOS expressing cells correlate with the histological severity in acute appendicitis. To estimatethe effect of NO on the immune system, we have measured the mitochondrial membrane potential of peripheral blood lyrnphocytes(PBL) cultured in the presence of chemical NO donor. PBL from healthy volunteers were cultured in the presence of NOCI8 (chemical NO donor) in various concentration. The mitochondrial membrane potential of PBL, which may reflect biological condition of living cells, was measured by flow cytometry using 3.3-dihexiloxacarbocyanine iodide(DiOC6(3». Apoptosis was also detected by flow cytometry using propidium iodide (PI). < Results> NOCl8 induced decrease of the levels of mitochondrial membrane potential of PBL in a dose-dependent fashion and contrary increase of the levels of reactive oxygen species (ROS), and lead these cells to apoptosis. This effect was inhibited by carboxy-PTIO, which is known to eliminate NO. Two-color staining of mitochondrial membrane potential and lymphocyte surface markers (CD3, CD19 and CD56) demonstrated that CD3-, CD56+ natural killer cells are much more feasible to NO. We showed that the mitochondrial membrane potential of peripheral NK cells was decreased by NO, which might be involved in the decrease of biological activity in a local immune system such as infectious conditions.
Kammscores
score
TEMS Peranal excision Adenoma Carcinoma
sex M(28) F(31) M(2) F(3) M(28) F(27) M(2) F(7) F(7)
0-5 % 25 90 18 58 0 0 2 66 23 82 17 62 100 2 42 3 42 3
6-10 2 9 2 1 4 7 0 3 3
% 7 29 100 34 14 25 0 42 42
11-15 1 3 0 0 1 3 0 0 0
% 3 10 0 0 4 13 0 0 0
16-20 0 1 0 0 0 0 0 1 1
% 0 3 0 0 0 0 0 14 16
5031 INHIBITORY EFFECT OF MELATONIN ON GASTRIC MUCOSAL INJURY INDUCED BY ISCHEMIA REPERFUSION IN RAT. Kimitoshi Kato, Satoshi Asai, Ichiro Murai, Yukimoto Ishii, Noriko Nakajima, Shumpachi Miyamoto, Yoshiaki Matsuno, Toshihito Nagaishi, Fumio Kawamura, Ariyoshi Iwasaki, Kouichi Ishikawa, Yasuyuki Arakawa, Nihon Univ Sch of Medicine, Tokyo, Japan. Melatonin is known for its marked antioxidant properties and has been shown to have a gastroprotective effect on gastric mucosal lesions. We have previously demonstrated that centrally administered melatonin at low doses inhibits the induction of gastric lesions by 4-h water-immersion restraint stress, probably in part by inhibiting the secretion of gastric acid, in conscious rats (NeuroReport, 8; 2305, 1997; 9, 2447, 1998). In this study, we focused on the central and peripheral effects of melatonin on gastric mucosal injury induced by ischemia reperfusion (I-R). Methods: Under urethane anesthesia, fasted SD rats were injected intracisternally (ic) with vehicle or melatonin at 1.0 1Lg/1O rn1 or intraperitoneally(ip) with vehicle or melatonin at 1.0, 5.0 or 10 mg/kg, 30 min before I-R. The celiac artery was clamped for 30 min and reperfused for 60 min, and the percentage of corpus mucosa containing lesions was determined with a computerized image analyzer. The level of thiobarbituric acid (TBA) reactants in the gastric mucosa after I-R, an index of lipid peroxidation, was measured by the method of Ohkawa. Furthermore, we examined gastric acid secretion after I-R in pylorus ligated rats pretreated with melatonin or vehicle. Results: Melatonin administration (1-10 mg/kg, ip) dose-dependently inhibited gastric mucosal lesions induced by I-R (lesions: 1 mg: 10.9 ± 3.8%, 5 mg: 5.7 ± 1.4%, 10 mg: 5.4 ± 1.0%, compared with vehicle :20.5 ± 3.0%, P
5033 CYP2C19 GENOTYPE STATUS AND INTRAGASTRIC PH DURING LANSOPRAZOLE AND RABEPRAZOLE TREATMENT. Akira Kawamura, Kyoichi Adachi, Tomoko Katsube, Shunji Ishihara, Makoto Watanabe, Yoshikazu Kinoshita, Shimane Med Univ, Izumo, Japan. Purpose: To determine the effect of CYP2CI9 genotype status on intragastric pH during lansoprazole and rabeprazole treatments. Subjects and Methods: Twelve male volunteers with negative H. pylori infection were enrolled in the study after obtaining written informed consent. Monitoring of intra-gastric pH conditions was performed over a 24 hours period with a Mark III Digitrapper and antimony pH catheter placed on the gastric body. pH monitoring was performed three times, once without medication, and on the last day of a 7-day-Iong medication with rabeprazole and lansoprazole. After more than 2 weeks, each experiment was repeated, using the other medication. Median pH and pH < 4.0 holding time during the daytime (6:30 AM - 10:30 PM) and nighttime (10:30 PM - 6:30 AM) hours were analyzed separately. The CYP2C19 genotype status for two mutations (exon 4 and 5) was determined by a polymerase chain-restriction fragment length polymorphism method. Results: Subjects were subdivided into three groups by their CYP2CI9 genotype status: homozygous extensive metabolizers (homo-EMs, n=6), heterozygous extensive metabolizers (hetero-EMs, n=3), and poor metabolizers (PMs, n=3). The data for mean percentage time of intragastric pH < 4.0 is shown in the Table. We found that the acid suppressing effect of rabeprazole was not influenced by CYP2CI9 genotype. On the other hand, with lansoprazole treatment, the percentage time of pH < 4.0 in PMs was less than that in homo-EMs and hetero-EMs. The median pH results had a similar tendency as those of the percentage time of pH < 4.0. Conclusion: CYP2CI9 genotype status influenced gastric acid suppression by lansoprazole treatment, but not by rabeprazole. Mean percentage time ofintragastric pH < 4.0
daytime
nighttime
subtype
nomedication
rabeprazole
lansoprazole
homo-EMs hetero-EMs PMs homo-EMs hetero-EMs PMs
94.8 95.0 85.2 97.8 99.9 100
53.8 30.6 44.6 64.2 55.7 64.9
67.2 48.6 19.2 71.2 94.0 43.4
GASTROENTEROLOGY Vol. 118, No.4
5030
5032
DOES LOCAL EXCISION OF RECTAL ADENOMAS AND CARCINOMAS LEAD TO INCREASED SYMPTOMATIC FAECAL INCONTINENCE? A PATIENT QUESTIONNAIRE STUDY. Tim A. Justin, Nick C. Armitage, Univ Hosp, Nottingham, United Kingdom; Univ Hosp, Nttingham, United Kingdom. Aim:To evaluate the bowel symptoms of patients who underwent local excision of rectal adenomas and carcinomas. Methods: This was a patient questionnaire study sent to patients with at least 12 months of follow up. Modified Kamm symptom scoring system was used. Score 0 was perfect continence and score 20 was total incontinence. Information on alteration in life style was not collected. Results: 68 out of 83 patients responded.( response rate 83%) 4 questionnaires were void leaving 64 questionnaires for analysis from 30 men and 34 women.23 female patients had vaginal delivaries in the past and 12/23 and 3/23 underwent episiotomy and forceps delivary respectively. Only 58% of female patients compared to 90% of men had Kamm scores of 0 to 5. Conclusion: As only 15% and 30% of female and male patients respectively had perfect continence (score 0) detailed symptom scoring is essential prior to local excision.
NO INDUCES DECREASE OF MITOCHONDRIAL MEMBRANE POTENTIAL IN PERIPHERAL BLOOD LYMPHOCYTES ESPECIALLY IN NK CELLS. Yasuhiro Kawai, Shingo Iwata, Michiyuki Kanai, Ryusuke Denno, Yoshiro Taki, Arimichi Takabayashi, Kitano Med Research Institute and Hosp, Osaka, Japan.
Kammscores
score
TEMS Peranal excision Adenoma Carcinoma
sex M(28) F(31) M(2) F(3) M(28) F(27) M(2) F(7) F(7)
0-5 % 25 90 18 58 0 0 2 66 23 82 17 62 100 2 42 3 42 3
6-10 2 9 2 1 4 7 0 3 3
% 7 29 100 34 14 25 0 42 42
11-15 1 3 0 0 1 3 0 0 0
% 3 10 0 0 4 13 0 0 0
16-20 0 1 0 0 0 0 0 1 1
% 0 3 0 0 0 0 0 14 16
5031 INHIBITORY EFFECT OF MELATONIN ON GASTRIC MUCOSAL INJURY INDUCED BY ISCHEMIA REPERFUSION IN RAT. Kimitoshi Kato, Satoshi Asai, Ichiro Murai, Yukimoto Ishii, Noriko Nakajima, Shumpachi Miyamoto, Yoshiaki Matsuno, Toshihito Nagaishi, Fumio Kawamura, Ariyoshi Iwasaki, Kouichi Ishikawa, Yasuyuki Arakawa, Nihon Univ Sch of Medicine, Tokyo, Japan. Melatonin is known for its marked antioxidant properties and has been shown to have a gastroprotective effect on gastric mucosal lesions. We have previously demonstrated that centrally administered melatonin at low doses inhibits the induction of gastric lesions by 4-h water-immersion restraint stress, probably in part by inhibiting the secretion of gastric acid, in conscious rats (NeuroReport, 8; 2305, 1997; 9, 2447, 1998). In this study, we focused on the central and peripheral effects of melatonin on gastric mucosal injury induced by ischemia reperfusion (I-R). Methods: Under urethane anesthesia, fasted SD rats were injected intracisternally (ic) with vehicle or melatonin at 1.0 1Lg/1O rn1 or intraperitoneally(ip) with vehicle or melatonin at 1.0, 5.0 or 10 mg/kg, 30 min before I-R. The celiac artery was clamped for 30 min and reperfused for 60 min, and the percentage of corpus mucosa containing lesions was determined with a computerized image analyzer. The level of thiobarbituric acid (TBA) reactants in the gastric mucosa after I-R, an index of lipid peroxidation, was measured by the method of Ohkawa. Furthermore, we examined gastric acid secretion after I-R in pylorus ligated rats pretreated with melatonin or vehicle. Results: Melatonin administration (1-10 mg/kg, ip) dose-dependently inhibited gastric mucosal lesions induced by I-R (lesions: 1 mg: 10.9 ± 3.8%, 5 mg: 5.7 ± 1.4%, 10 mg: 5.4 ± 1.0%, compared with vehicle :20.5 ± 3.0%, P
5033 CYP2C19 GENOTYPE STATUS AND INTRAGASTRIC PH DURING LANSOPRAZOLE AND RABEPRAZOLE TREATMENT. Akira Kawamura, Kyoichi Adachi, Tomoko Katsube, Shunji Ishihara, Makoto Watanabe, Yoshikazu Kinoshita, Shimane Med Univ, Izumo, Japan. Purpose: To determine the effect of CYP2CI9 genotype status on intragastric pH during lansoprazole and rabeprazole treatments. Subjects and Methods: Twelve male volunteers with negative H. pylori infection were enrolled in the study after obtaining written informed consent. Monitoring of intra-gastric pH conditions was performed over a 24 hours period with a Mark III Digitrapper and antimony pH catheter placed on the gastric body. pH monitoring was performed three times, once without medication, and on the last day of a 7-day-Iong medication with rabeprazole and lansoprazole. After more than 2 weeks, each experiment was repeated, using the other medication. Median pH and pH < 4.0 holding time during the daytime (6:30 AM - 10:30 PM) and nighttime (10:30 PM - 6:30 AM) hours were analyzed separately. The CYP2C19 genotype status for two mutations (exon 4 and 5) was determined by a polymerase chain-restriction fragment length polymorphism method. Results: Subjects were subdivided into three groups by their CYP2CI9 genotype status: homozygous extensive metabolizers (homo-EMs, n=6), heterozygous extensive metabolizers (hetero-EMs, n=3), and poor metabolizers (PMs, n=3). The data for mean percentage time of intragastric pH < 4.0 is shown in the Table. We found that the acid suppressing effect of rabeprazole was not influenced by CYP2CI9 genotype. On the other hand, with lansoprazole treatment, the percentage time of pH < 4.0 in PMs was less than that in homo-EMs and hetero-EMs. The median pH results had a similar tendency as those of the percentage time of pH < 4.0. Conclusion: CYP2CI9 genotype status influenced gastric acid suppression by lansoprazole treatment, but not by rabeprazole. Mean percentage time ofintragastric pH < 4.0
daytime
nighttime
subtype
nomedication
rabeprazole
lansoprazole
homo-EMs hetero-EMs PMs homo-EMs hetero-EMs PMs
94.8 95.0 85.2 97.8 99.9 100
53.8 30.6 44.6 64.2 55.7 64.9
67.2 48.6 19.2 71.2 94.0 43.4