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| 2. |
- Klintman, Daniel, et al.
(författare)
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Leukocyte recruitment in hepatic injury: selectin-mediated leukocyte rolling is a prerequisite for CD18-dependent firm adhesion.
- 2002
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Ingår i: Journal of Hepatology. - 0168-8278. ; 36:1, s. 53-59
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: This study was designed to examine the role of selectins and CD18 in leukocyte recruitment in hepatic injury induced by tumor necrosis factor-alpha (TNF-alpha) and galactosamine (Gal) in vivo.Methods: Intravital fluorescence microscopy of the hepatic microcirculation was used to quantify leukocyte-endothelium interactions provoked by 24 h of systemic TNF-alpha/Gal challenge in rats. Hepatic injury was evaluated with liver enzymes.Results: When administered after 24 h of TNF-alpha/Gal challenge, fucoidan, a selectin-function inhibitor, reduced leukocyte rolling by 69%, whereas firm adhesion was unaltered. In contrast, passive immunization against CD18 decreased leukocyte adhesion by 60%, whereas rolling remained unchanged. Notably, when administered prior to TNF-alpha/Gal, fucoidan attenuated both leukocyte rolling and adhesion, by 57 and 69%, respectively. Pretreatment with an anti-CD18 antibody decreased TNF-alpha/Gal-induced rolling and firm adhesion by 25 and 90%, respectively. Moreover, pretreatment with fucoidan and the anti-CD18 antibody both protected against TNF-alpha/Gal-induced increases in liver enzymes. For example, the pretreatments reduced alanine aminotransferase by 59 and 87%, respectively.Conclusions: Our data suggest that TNF-alpha/Gal-induced leukocyte rolling is selectin-mediated and a precondition for CD18-dependent firm adhesion in hepatic venules. Thus, reducing leukocyte recruitment by inhibition of selectins or CD18 may be useful to control TNF-alpha-induced liver injury.
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| 3. |
- Klintman, Daniel, et al.
(författare)
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Protective effect of Linomide on TNF-alpha-induced hepatic injury.
- 2002
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Ingår i: Journal of Hepatology. - 0168-8278. ; 36:2, s. 226-232
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Linomide is an immunomodulator that ameliorates several autoimmune and inflammatory diseases. We assessed the effect of Linomide on microvascular perfusion failure, leukocyte recruitment and hepatocellular injury induced by tumor necrosis factor alpha (TNF-alpha) and D-Galactosamine (Gal).Methods: After 3 days of Linomide pretreatment (1, 10 and 100mg/kg/day), rats were challenged with TNF-alpha/Gal for 24h. Microvascular perfusion, leukocyte--endothelium interactions in hepatic postsinusoidal venules and leukocyte sequestration in sinusoids were evaluated using intravital microscopy. Liver enzymes were measured spectrophotometrically.Results: Challenge with TNF-alpha/Gal significantly reduced sinusoidal perfusion, and increased leukocyte rolling, adhesion and liver enzymes. Interestingly, pretreatment with Linomide (10 and 100mg/kg/day) significantly reduced TNF-alpha/Gal-induced leukocyte rolling by 65 and 63%, and leukocyte adhesion by 87 and 84%, respectively. Moreover, Linomide (10 and 100mg/kg/day) decreased sinusoidal sequestration of leukocytes by 71 and 51%, and markedly improved sinusoidal perfusion. Moreover, Linomide reduced aspartate aminotransferase by 87--97%, and alanine aminotransferase by 79--96%. However, Linomide had no protective effect when administered concomitantly with TNF-alpha/Gal.Conclusions: These data demonstrate a dose-dependent inhibitory effect of Linomide on perfusion failure, leukocyte recruitment and hepatocellular injury provoked by TNF-alpha. Indeed, these findings suggest that Linomide may be an effective substance for protection of the liver in sepsis.
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| 4. |
- Mangell, Peter, et al.
(författare)
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Lactobacillus plantarum 299v inhibits Escherichia coli-induced intestinal permeability.
- 2002
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Ingår i: Digestive Diseases and Sciences. - 1573-2568. ; 47:3, s. 511-516
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this work was to investigate whether a probiotic bacterium, Lactobacillus plantarum 299v, could affect Escherichia coli-induced passage of mannitol across the intestinal wall. Sprague-Dawley rats were pretreated for one week by either tube feeding with L. plantarum 299v twice daily, free access to L. plantarum 299v by adding the bacterium in the drinking water, or negative control receiving regular feeding. Intestinal segments were mounted in Ussing chambers and the mucosa was exposed to control medium, E. coli, and L. plantarum 299v (alone or together). [14C]Mannitol was added as a marker of intestinal permeability and samples were taken from the serosal side. E. coli exposure induced a 53% increase in mannitol passage across the intestinal wall (P < 0.05). One week of pretreatment with L. plantarum 299v in the drinking water abolished the E. coli-induced increase in permeability. Tube feeding for one week or short-term addition of L. plantarum 299v in the Ussing chambers had no effect on the permeability provoked by E. coli challenge. Notably, L. plantanum 299v itself did not change the intestinal passage of mannitol. These data demonstrate that pretreatment with L. plantarum 299v, which is a probiotic bacterium, protects against E. coli-induced increase in intestinal permeability, and that L. plantarum 299v alone has no influence on the intestinal permeability. Thus, this study supports the concept that probiotics may exert beneficial effects in the gastrointestinal tract.
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| 5. |
- Månsson, Peter, et al.
(författare)
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Anastomotic healing in the rat colon: comparison between a radiological method, breaking strength and bursting pressure.
- 2002
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Ingår i: International Journal of Colorectal Disease. - : Springer Science and Business Media LLC. - 1432-1262 .- 0179-1958. ; 17:6, s. 420-425
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: While mechanical parameters (breaking strength, bursting pressure) are used to measure colonic anastomotic healing, reported values are inconsistent. This study developed a novel approach to study colonic anastomotic repair and compared it with mechanical methods. Methods and materials: We created standardized four- and eight-suture colonic anastomoses and performed contrast enemas in rats. Results: All eight-suture anastomoses were tight at completion. In contrast, all four-suture anastomoses leaked immediately after the operation, but the integrity increased progressively, and at 12 h all were closed. No changes in breaking strength were observed up to 3 days postoperatively, in contrast to anastomotic bursting pressure which increased progressively over the same period. Integrity and bursting pressure increased in parallel to the anastomotic content of myeloperoxidase (MPO), indicating that neutrophil infiltration is not detrimental in normal healing. Moreover, local irradiation, which enhanced MPO activity, did not increase leakage, suggesting that neutrophil accumulation per se has no effect on the integrity of colonic anastomosis. In addition, administration of 5-fluorouracil, which decreased anastomotic MPO levels, increased anastomotic leakage. Conclusion: We present a novel approach to study anastomotic healing using radiological examination. While bursting pressure appears to be suitable for measuring early anastomotic healing in the colon, we demonstrate that breaking strength is not sufficiently sensitive to be used in examination of early healing. Moreover, our data suggest that the acute inflammatory response and associated neutrophil recruitment in the anastomosis does not negatively affect healing in the rat colon.
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| 6. |
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| 7. |
- Toth, Ervin, et al.
(författare)
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Evaluation of gastric acid secretion at endoscopy with a modified Congo red test.
- 2002
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Ingår i: Gastrointestinal Endoscopy. - : Elsevier BV. - 1097-6779 .- 0016-5107. ; 56:2, s. 254-259
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Markedly decreased or absent gastric acid production is associated with a number of clinically significant conditions, and identification of patients with hypo/achlorhydria may be important. However, current methods of assessing impaired acid secretion are unreliable, time-consuming, and/or complex. The aim of this prospective study was to evaluate a modified endoscopic Congo red test for the diagnosis of hypo/achlorhydria by correlation with a standard gastric acid secretory test. METHODS: One hundred six consecutive outpatients with or without dyspeptic symptoms referred for endoscopy were evaluated by using a modified endoscopic Congo red test and a standard test of gastric acid secretion. The modified endoscopic Congo red test suggested hypo/achlorhydria when there was no color shift or a shift of small extent (less than one third of fundic mucosa). Hypo/achlorhydria by the standard gastric acid secretory test was defined as a maximal acid output of less than 6.9 mmol/hour in men and 5.0 mmol/hour in women. RESULTS: The accuracy of the modified endoscopic Congo red test for the diagnosis of hypo/achlorhydria was 0.98 (95% CI [0.93, 0.99]). The sensitivity was 1.0 (95% CI [0.92, 1.00]) and specificity 0.96 (95% CI [0.88, 0.99]). All patients tolerated the modified endoscopic Congo red test well. CONCLUSION: The modified endoscopic Congo red is an accurate, simple, fast, inexpensive, and well-tolerated chromoendoscopic method for identification of patients with hypo/achlorhydria during routine upper endoscopy.
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| 8. |
- Wan, Ming Xiu, et al.
(författare)
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Leukocyte rolling is exclusively mediated by P-selectinin colonic venules.
- 2002
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Ingår i: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 135:7, s. 1749-1756
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Tidskriftsartikel (refereegranskat)abstract
- 1. The objective of the present study was to examine the role of the endothelial selectins (i.e. P- and E-selectin) in leukocyte-endothelium interactions in colonic venules by use of intravital microscopy. 2. Balb/c mice were exposed to dextran sodium sulphate (DSS) in the drinking water for 5 days or treated intraperitoneally (i.p.) with tumour necrosis factor-alpha (TNF-alpha) for 3 h. 3. In DSS-treated mice, mRNA of both P- and E-selectin were expressed and leukocyte rolling and adhesion was increased to 27+/-3 cells min(-1) and 36+/-8 cells mm(-1), respectively. An anti-P-selectin antibody abolished DSS-induced leukocyte rolling, whereas an antibody against E-selectin had no effect. Established leukocyte adhesion was insensitive to inhibition of the selectins. 4. DSS markedly increased production of TNF-alpha in the colon. TNF-alpha increased leukocyte rolling to 22+/-3 cells min(-1) and adhesion to 45+/-4 cells mm(-1). Only inhibition of P-selectin significantly reduced (>94%) leukocyte rolling provoked by TNF-alpha. Leukocyte adhesion was not changed by late anti-P-selectin antibody treatment. In contrast, pretreatment with the anti-P-selectin antibody not only abolished leukocyte rolling but also completely inhibited firm adhesion in response to TNF-alpha. 5. This study demonstrates that P-selectin plays an important role in leukocyte rolling in colonic venules, both in experimental colitis and when stimulated with TNF-alpha. Moreover, P-selectin-dependent leukocyte rolling was found to be a precondition for TNF-alpha-induced firm adhesion. Thus, these findings suggest that P-selectin may be a key target to reduce pathological recruitment of inflammatory cells in the colon.
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| 9. |
- Wan, M X, et al.
(författare)
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Protective effect of low molecular weight heparin on experimental colitis: role of neutrophil recruitment and TNF-alpha production.
- 2002
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Ingår i: Inflammation Research. - 1420-908X. ; 51:4, s. 182-187
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The purpose of this study was to examine the impact and mechanism of action of low molecular weight heparin (LMWH) in a model of murine colitis. MATERIALS AND METHODS: Balb/c mice were exposed to 5% dextran sodium sulfate (DSS) in the drinking water for five days. LMWH (500 units/kg/day) was administered by subcutaneous injection prior to and throughout the treatment period with DSS. Clinical disease activity index (DAI), including body weight loss, stool consistency and blood in feces were examined daily. Moreover, crypt height (CH), mucosal damage score (MDS), myeloperoxidase (MPO) activity and tumor necrosis factor-alpha (TNF-alpha) content in the colon were determined. RESULTS: DSS increased DAI, MDS, MPO activity and TNF-alpha production and decreased CH. Administration of LMWH markedly reduced DAI, MDS and reversed the CH-reduction. Moreover, in LMWH-treated animals, the MPO activity was reduced by more than 67% whereas mucosal levels of TNF-alpha was similar compared to DSS control mice. CONCLUSIONS: These findings suggest that LMWH inhibits murine colitis by interference with neutrophil recruitment and that LMWH may provide a novel pharmacological approach to treatment of inflammatory bowel disease.
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