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Helicobactor pylori infection and the expression of cyclooxygenase in the gastric mucosa
Concurrent Sessions Tuesday 22 July
EFA & Eicosanoids 1997- Edinburgh
T28
T29
Polyunsaturated fatty acids and Inflammatory Bowel Disease
Helicobactor Pylori Infection And Cyclooxygenase In The Gastric Mucosa
Andrea Belluzzi. Department of Emergency Medicine, Internal Medicine, S.Orsota Hospital, University of Bologna, Italy The rationale for omega-3 fatty acids supplementation in the
gastrointestinal tract, resides in the anti-inflammatory effects of these lipidic compounds and one of the first evidence on the importance of dietary intake of omega-3 polyunsaturated fatty acids derived from epidemiological observations about the very low incidence of inflammatory bowel disease in Eskimos. Aim of this lecture is to briefly review the literature concerning the use of omega-3 fatty acid in inflammatory bowel disease (ulcerative colitis and Crohn's disease), whose results seems to be rather controversial. The reasons of the discrepancies could reside in the different study design as well as in the various formulations and dosages which could actually lead to very high incidence of side effects. The importance of the formulation in lowering the incidence of side effect along with a careful selection of patients and experimental design seems to emphasize the therapeutical potential of these lipids in the therapy of inflammatory bowel disease.
The
Expression
199
Of
Shah AA, Cullen L, O'Neill A, Murray FE, Fitzgerald DL Royal College of Surgeonsin Ireland and BeaumontHospital, Dublin. Selective cyclooxygenase [COX]-2 inhibitors have been developed on the assumption that COX-I is the primary form expressed in the stomach. Potentially COX-2 is also expressed in patients with H. Pylori infection, who are at increased risk of peptic ulceration. We examined the formation of prostaglandin [PGE2] and prostacyclin [PGU in gastric biopsies obtained from 14 patients undergoingroutine endoscopy. H.Pylori infection was detected by CLO test, histology and culture. Biopsy samples were incubated for ten minutes at 37°C in the presence and absence of NS-398, a selective COX-2 inhibitor or aspirin. Samples were also treated with endotoxin in order to induce COX-2 expression. The tissues were also analysed for COX-2 expression using PCR. Finally, prostaglandinswere measuredin gastric aspirates. In 12 out of 14 patients H.pylori was detected by at least one of the three methods described above. The effect of H.pylori infection on PGE2 formation in ng/ml was as follows: Control Aspirin NS-398 L.P.S. L.P.S.& Gastric Aspirin Aspirate H.pylori + 38.55_+3.7 10.6-+4.3 36.2+4.5 209_.+3.1 7.1_+5.1 2.2_+1.05 H.pylori- 23.9_+2.3 34.7_+2.7 26.3_+5.4 7.2_+8.3 2.2_+2.4 0.93_+1.i The effect of H.Pylori infection on 6 Keto PGF~ in ng/ml was as follows: Control Aspirin NS-398 L.P.S. L.P.S.& Gastric Aspirin Aspirate H.pylori + 60.9_+10.2 13.l_+8.6 46.4_+9.4 54.9_+8.9 3.5_+1.2 10.4-+6.8 H.pylori- 25.1_+6,8 3.2-+1.1 30.3_+3.7 33.8_+9.3 6.4_+6.2 8.9+1.1 PCR analysis showed no expression of COX-2. Our data show a higher level of prostaglandins function in patients who arc positive for H.pylori. However, this was unaltered by NS-398 and there was no expression of COX-2 suggesting that the increase in prostaglandinformationreflected enhanced expressionof COX- I.
T30 Effects of Aerosolised Tridocosahexaenoyl-Glycerol Emulsion on a Murine Model of Allergic Pulmonary Inflammation.
A. Yokoyama, T. Hamazaki*, A. Ohshila, N. Kolmo, K. Sakai, Y. Hirasawa, K. Hiwada, M. Kobayashi*. 2nd Dept of Int Med, Ehime Univ, Ehime, and *lst Dept of lnt Med, Toyama Med Pharm Univ,Toyama.Japan O b j e c t i v e : To investigate effects of emulsified docosahexaenoyl-
glycerol (DHA-TG) on a murine model of ovalbumin (OVA)induced allergic pulmonary inflammation, we took a novel approach to administration, i.e., aerosolised DHA-TG, to optimise its effects on the lung. M e t h o d s : Mice (BALB/c, 6-8 wk old) were primed with OVA and
AI(OH)3 on days 0 and 7, and with aerosolised OVA on day 7. Primed mice were challenged by repeated exposure to aerosolised OVA (50 mg/ml for 20 rain, days 15-17). Just before each aerosotised OVA exposure, mice were also exposed to aerosol of emulsified DHA-TG, soybean oil or saline (days 7, 15-17). Bronchoalveolar lavage fluid (BALF; 0.8 m2, 6 times) was obtained at 24 hr after the last challenge (day 18). Lungs were histologically examined. Results: BALF of this model contained a total cell count of 19-25
× 105(5.5-6.5 × 105/ml) with predominant eosinophils (-70%). Exposure to DHA emulsion significantly reduced the total cell number in BALF (7.7-13 × 105 or 2.2-3.0 × 105/ml). The percent of eosinophils was also reduced to -55%. Exposure to soy-bean oil did not show any changes. The histological examinations confirmed reduced cell infiltration to the lung by exposure to DHATG but not to soybean oil. C o n c l u s i o n s : These results suggest that aerosolised DHA-TG has anti-inflammatory effects on allergic pulmonary inflammation, and that this approach could be applied to humans.
EFA & Eicosanoids 1997- Edinburgh
T28
T29
Polyunsaturated fatty acids and Inflammatory Bowel Disease
Helicobactor Pylori Infection And Cyclooxygenase In The Gastric Mucosa
Andrea Belluzzi. Department of Emergency Medicine, Internal Medicine, S.Orsota Hospital, University of Bologna, Italy The rationale for omega-3 fatty acids supplementation in the
gastrointestinal tract, resides in the anti-inflammatory effects of these lipidic compounds and one of the first evidence on the importance of dietary intake of omega-3 polyunsaturated fatty acids derived from epidemiological observations about the very low incidence of inflammatory bowel disease in Eskimos. Aim of this lecture is to briefly review the literature concerning the use of omega-3 fatty acid in inflammatory bowel disease (ulcerative colitis and Crohn's disease), whose results seems to be rather controversial. The reasons of the discrepancies could reside in the different study design as well as in the various formulations and dosages which could actually lead to very high incidence of side effects. The importance of the formulation in lowering the incidence of side effect along with a careful selection of patients and experimental design seems to emphasize the therapeutical potential of these lipids in the therapy of inflammatory bowel disease.
The
Expression
199
Of
Shah AA, Cullen L, O'Neill A, Murray FE, Fitzgerald DL Royal College of Surgeonsin Ireland and BeaumontHospital, Dublin. Selective cyclooxygenase [COX]-2 inhibitors have been developed on the assumption that COX-I is the primary form expressed in the stomach. Potentially COX-2 is also expressed in patients with H. Pylori infection, who are at increased risk of peptic ulceration. We examined the formation of prostaglandin [PGE2] and prostacyclin [PGU in gastric biopsies obtained from 14 patients undergoingroutine endoscopy. H.Pylori infection was detected by CLO test, histology and culture. Biopsy samples were incubated for ten minutes at 37°C in the presence and absence of NS-398, a selective COX-2 inhibitor or aspirin. Samples were also treated with endotoxin in order to induce COX-2 expression. The tissues were also analysed for COX-2 expression using PCR. Finally, prostaglandinswere measuredin gastric aspirates. In 12 out of 14 patients H.pylori was detected by at least one of the three methods described above. The effect of H.pylori infection on PGE2 formation in ng/ml was as follows: Control Aspirin NS-398 L.P.S. L.P.S.& Gastric Aspirin Aspirate H.pylori + 38.55_+3.7 10.6-+4.3 36.2+4.5 209_.+3.1 7.1_+5.1 2.2_+1.05 H.pylori- 23.9_+2.3 34.7_+2.7 26.3_+5.4 7.2_+8.3 2.2_+2.4 0.93_+1.i The effect of H.Pylori infection on 6 Keto PGF~ in ng/ml was as follows: Control Aspirin NS-398 L.P.S. L.P.S.& Gastric Aspirin Aspirate H.pylori + 60.9_+10.2 13.l_+8.6 46.4_+9.4 54.9_+8.9 3.5_+1.2 10.4-+6.8 H.pylori- 25.1_+6,8 3.2-+1.1 30.3_+3.7 33.8_+9.3 6.4_+6.2 8.9+1.1 PCR analysis showed no expression of COX-2. Our data show a higher level of prostaglandins function in patients who arc positive for H.pylori. However, this was unaltered by NS-398 and there was no expression of COX-2 suggesting that the increase in prostaglandinformationreflected enhanced expressionof COX- I.
T30 Effects of Aerosolised Tridocosahexaenoyl-Glycerol Emulsion on a Murine Model of Allergic Pulmonary Inflammation.
A. Yokoyama, T. Hamazaki*, A. Ohshila, N. Kolmo, K. Sakai, Y. Hirasawa, K. Hiwada, M. Kobayashi*. 2nd Dept of Int Med, Ehime Univ, Ehime, and *lst Dept of lnt Med, Toyama Med Pharm Univ,Toyama.Japan O b j e c t i v e : To investigate effects of emulsified docosahexaenoyl-
glycerol (DHA-TG) on a murine model of ovalbumin (OVA)induced allergic pulmonary inflammation, we took a novel approach to administration, i.e., aerosolised DHA-TG, to optimise its effects on the lung. M e t h o d s : Mice (BALB/c, 6-8 wk old) were primed with OVA and
AI(OH)3 on days 0 and 7, and with aerosolised OVA on day 7. Primed mice were challenged by repeated exposure to aerosolised OVA (50 mg/ml for 20 rain, days 15-17). Just before each aerosotised OVA exposure, mice were also exposed to aerosol of emulsified DHA-TG, soybean oil or saline (days 7, 15-17). Bronchoalveolar lavage fluid (BALF; 0.8 m2, 6 times) was obtained at 24 hr after the last challenge (day 18). Lungs were histologically examined. Results: BALF of this model contained a total cell count of 19-25
× 105(5.5-6.5 × 105/ml) with predominant eosinophils (-70%). Exposure to DHA emulsion significantly reduced the total cell number in BALF (7.7-13 × 105 or 2.2-3.0 × 105/ml). The percent of eosinophils was also reduced to -55%. Exposure to soy-bean oil did not show any changes. The histological examinations confirmed reduced cell infiltration to the lung by exposure to DHATG but not to soybean oil. C o n c l u s i o n s : These results suggest that aerosolised DHA-TG has anti-inflammatory effects on allergic pulmonary inflammation, and that this approach could be applied to humans.