Mercury in saliva and feces after removal of amalgam fillings

BACKGROUND & AIMS: Distal colitis induced in rats by trinitrobenzene sulfonic acid (TNBS) causes a suppression of [3H]noradrenaline release from the myenteric plexus, of inflamed distal colon, as well as in noninflamed regions of colon and ileum. The aim of this study was to explore the mechanisms underlying these neural changes in TNBS colitis. METHODS: Colitis was induced by intrarectal administration of TNBS, and the animals were killed on day 5. Inflammation was assessed by measuring myeloperoxidase (MPO) activity, and noradrenaline release was measured as 3H release from rats myenteric plexus preparations preloaded with [3H]noradrenaline. These end points were examined: (1) after administration of the locally active steroid budesonide; (2) in congenitally athymic rats; and (3) in rats treated with the interleukin 1 receptor antagonist (IL-1ra) to interleukin 1 beta. RESULTS: In colitis, both topical budesonide and systemic IL-1ra treatments attenuated the suppression of KCl-evoked 3H release from longitudinal muscle myenteric plexus in both inflamed and noninflamed segments. However, neither of these treatments altered MPO activity. A similar suppression of [3H]noradrenaline release was observed in athymic rats after TNBS, although there was a substantially greater increase in MPO activity compared with euthymic rats with colitis. CONCLUSIONS: TNBS-induced colitis alters myenteric nerve function at inflamed and noninflamed sites via a steroid-sensitive and interleukin 1-mediated process that does not require T lymphocytes.     

Effect of chronic nicotine administration on trinitrobenzene sulphonic acid-induced colitis

BACKGROUND: Smoking, probably due to nicotine, has a bivalent effect on inflammatory bowel disease, ameliorating disease activity in ulcerative colitis and with a deleterious effect on Crohn's disease. The effect of nicotine patches in ulcerative colitis is controversial. AIM: To investigate the effect of chronic nicotine use in a rat model of colitis. METHODS: Colitis was induced in Sprague-Dawley rats by rectal administration of 30 mg trinitrobenzene sulphonic acid (TNBS) in 50% ethanol. Nicotine was dissolved in drinking water (2.5, 12.5, 25 and 250 microg/ml), with rats drinking ad libitum. Nicotine administration started 10 days prior to damage induction and had no effect on weight gain or daily food intake of rats. Rats were sacrificed 1 and 5 days after TNBS administration, their colons resected, rinsed, weighed, damage assessed macroscopically (mm2) and microscopically and tissue processed for myeloperoxidase (MPO) and nitric oxide synthase (NOS) activities, leukotriene B4 (LTB4), prostaglandin E2 (PGE2) generation and interleukin-1 (IL-1) serum levels. RESULTS: Nicotine, by itself, caused no damage to the colon. Nicotine had a dose-dependent bivalent effect on colitis, significantly reducing macroscopic damage from 983 +/- 10 mm2 on TNBS alone to 429 +/- 118 mm2 on TNBS plus 12.5 microg/ml of nicotine, and escalating to 1086 +/- 262 mm2 on 250 microg/ml of nicotine. Segmental weight declined significantly (from 2.4 +/- 0.2 to 1.65 +/- 0.20 g/10 cm), on 12.5 microg/ml nicotine, as did MPO activity (from 3.2 +/- 0.4 to 0.7 +/- 0.1 units/g). All these parameters returned to the levels of TNBS alone when the dose of nicotine was increased to 250 microg/ml. Nicotine had no effect on NOS activity, PGE2 generation and serum IL-1 levels, but increased LTB4 generation. CONCLUSIONS: Nicotine has a dose-dependent bivalent effect on TNBS-induced colitis which is not due to reduction in IL-1 serum levels or PGE2 generation, and is not NOS-mediated.     

Pathophysiological role of nitric oxide in rat experimental colitis

Overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) may contribute to the pathophysiology of ulcerative colitis. A 2,4,6-trinitrobenzenesulfonic acid sodium salt (TNBS) colitis model was established to examine the effect of selective iNOS inhibition, by S-(2-aminoethyl) isothiouronium bromide (ITU), on colonic mucosal cell damage and inflammation. Rats, killed 7 days after TNBS, had increased colonic mucosal levels of iNOS and interleukin-8 (IL-8), in addition to severe colonic inflammation which was characterized by significantly increased colon weight, damage score and colonic myeloperoxidase activity (MPO) (a marker of neutrophil influx). TNBS-treated rats had markedly decreased body weight and thymus weight. Administration of colitic rats with ITU significantly inhibited iNOS activity/expression and tended to reduce mucosal levels of IL-8, but no effect on MPO activity was observed. Following ITU therapy, colitic rats had reduced colonic damage and losses in body weight and thymus weight were reversed. Improvement of TNBS colitis by ITU suggested that excess NO, produced by iNOS, may have contributed to the initiation/amplification of colonic disease, by mechanisms including enhancement of IL-8 release. NO-mediated enhancement of pro-inflammatory cytokine release was further investigated in vitro. Lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) stimulated release of nitrite, lactate dehydrogenase (LDH), TNF alpha, IL-1 beta and IL-8 from rat peritoneal macrophages, all of which were significantly reduced by ITU. This suggests that NO-mediated cell damage enhances pro-inflammatory mediator release from macrophages. In addition, enhancement of IL-8 and TNF alpha release was also partially NO-dependent in activated peritoneal neutrophils. Therefore, the amelioration of TNBS colitis by ITU could include inhibition of NO-mediated pro-inflammatory cytokine release.     

Effect of intracolonic benzalkonium chloride on trinitrobenzene sulphonic acid-induced colitis in the rat

BACKGROUND: We investigated the effects of benzalkonium chloride (BAC) on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. METHODS: TNBS was administered intrarectally before and/or after BAC treatment. In the first study, the effects of treatment with BAC 6, 12 or 24 h after TNBS were examined. In the second study, animals were treated with BAC before, after or before and after TNBS, and were examined 7 days later. The severity of colitis was assessed by macroscopic and histological scoring of the colonic damage and by determination of colonic myeloperoxidase (MPO) activity. Macrophages and CD4+ and CD8+ T cells were examined by immunohistochemistry. RESULTS: When BAC was instilled into the colon 6, 12 or 24 h after TNBS, weight loss and macroscopic and histological features of the colon were similar to that of controls (TNBS alone). In contrast, MPO activity was significantly reduced in all three groups post-treated with BAC. In the groups examined 7 days after TNBS treatment, rats post-treated with BAC exhibited increased weight gain and significantly reduced macroscopic damage and MPO activity compared to the TNBS control group. Rats pre-treated with BAC exhibited less macroscopic damage of the colon than rats receiving only TNBS, but histological damage, MPO and weight gain were unchanged from TNBS controls. Immunohistochemistry revealed that BAC pre-treatment increased the numbers of macrophages and T cells in the colon. After TNBS treatment, macrophage accumulation was evident in the colon, but T cells were scarce. However, these cells were preserved or enhanced in the colonic mucosa in TNBS-treated rats that had been pre-treated with BAC. CONCLUSIONS: Treatment with BAC, particularly after induction of colitis, produces a significant reduction in the severity of tissue injury and inflammation through mechanisms that are not fully understood.     

Novel inhibitors against the transglutaminase-catalysed crosslinking of lens proteins

We had previously reported that the protective effect of taurine against indomethacin-induced gastric mucosal injury was due to its antioxidant effects, which inhibited lipid peroxidation and neutrophil activation. In this study, we examined the effect of taurine on reducing the inflammatory parameters of trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) in rats. In order to induce IBD, ethanolic TNBS was given to rats intracolonically. Then they received 500 mg/kg/day of taurine orally and were sacrificed one week after IBD induction. While ulceration and inflammation of distal colon with formation of granuloma in the vehicle-treated IBD rats two days after administration of TNBS were observed, treatment with taurine ameliorated colonic damage and decreased the incidence of diarrhea and adhesion. Also, colon weight as an index of tissue edema, which was markedly increased in the IBD rats, became significantly lower after taurine treatment. Myeloperoxidase (MPO) activity in the vehicle-treated IBD rats was substantially increased, compared with that of normal control. The taurine-treated animals significantly reduced MPO activity (35% lower) when compared with that of the vehicle-treated animals. Taurine treatment decreased both basal and formyl-methionyl leucyl phenylalanine-stimulated reactive oxygen generation from colonic tissue in the IBD rats. These results suggest that the administration of taurine reduce the inflammatory parameters in this IBD rat model by increasing defending capacity against oxidative damage.     

Time-dependent actions of nitric oxide synthase inhibition on colonic inflammation induced by trinitrobenzene sulphonic acid in rats

The time-dependent actions following pretreatment or delayed administration of the nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) on colonic inflammation and inducible NO synthase activity following the intrarectal administration of trinitrobenzene sulphonic acid (TNBS) were evaluated in the rat. Intracolonic instillation of TNBS (30 mg in 0.25 ml of 50% ethanol) led to macroscopic injury, an increase of mucosal myeloperoxidase activity and the expression of the Ca2+-independent inducible NO synthase over 8 days. The inflammatory response following TNBS reached maximum levels between 12 and 72 h and then it declined until 14 days. Oral administration of L-NAME (25 mg/kg per 24 h in the drinking water) 2 days before TNBS augmented macroscopic damage and increased colonic inducible NO synthase activity 6, 12, 24 and 72 h after TNBS administration. In contrast, when L-NAME was administered 6 h after TNBS instillation, at time of expression of inducible NO synthase, the macroscopic lesions were reduced, as well as the enhanced inducible NO synthase activity, determined, over 72 h. Delayed (6 h after TNBS) administration of L-NAME also attenuated the colonic myeloperoxidase activity provoked by TNBS, after 24 h. This activity was not affected by pretreatment (2 days before TNBS) with L-NAME. These findings indicate that the timing of administration of non-selective NO synthase inhibitors such as L-NAME, in models of colitis is critical to the eventual outcome. Thus, pretreatment with L-NAME, which will inhibit constitutive NO synthase, exacerbates the subsequent damage following challenge. In contrast, delayed administration of L-NAME at the time of inducible NO synthase expression, has a beneficial action on the colonic injury and inflammation.     

Enhanced expression of anti-apoptotic proteins in human papillomavirus-immortalized and cigarette smoke condensate-transformed human endocervical cells: correlation with resistance to apoptosis induced by DNA damage

Nerves within the wall of the intestine may contribute to inflammatory responses, such as those occurring in inflammatory bowel disease. Studies in an experimental model of colitis have demonstrated that neuromodulation, through chemical sympathectomy or administration of lidocaine, can markedly attenuate granulocyte infiltration and tissue injury. Given the many pro-inflammatory effects of substance P, we have evaluated the effects of a tachykinin receptor (NK-1) antagonist, RP 67580, in models of acute colitis in the rat and guinea pig. While administration of RP 67580 and a second NK-1 antagonist (CP-96,345-1) significantly reduced the infiltration of granulocytes into colonic tissue during the first 12 h after induction of colitis in the rat, repeated administration of RP 67580 over a three day period failed to significantly affect granulocyte recruitment or the severity of tissue injury. In contrast, lidocaine enemas were effective in reducing both indices of inflammation/injury. In the guinea pig, similar observations were made. These observations demonstrate that blockade of NK-1 receptors over a three day period failed to significantly modify the course of experimental colitis. It remains possible that the beneficial effects of lidocaine may be due, in part, to inhibition of substance P release, and that the contribution of substance P to inflammation in experimental colitis occurs through NK-1 receptor-independent mechanisms.     

Antiinflammatory effects of human milk on chemically induced colitis in rats

We examined the effects of a human milk diet on rats with chemical colitis induced with a 4% acetic acid enema. Colonic myeloperoxidase activity was used as a surrogate marker for neutrophil infiltration. Control rats fed rat chow had little colonic myeloperoxidase activity; geometric mean, 0.27 U/g of tissue. Rats with colitis fed rat chow had significantly increased colonic myeloperoxidase activity (geometric mean, 6.76 U/g, p < 0.01 versus no colitis), as did rats with colitis fed infant formula or Pedialyte (geometric mean, 6.92 and 8.13 U/g, respectively, both p < 0.01 versus no colitis). Animals with colitis fed human milk had significantly lower colonic myeloperoxidase activity (geometric mean, 2.34 U/g) than did animals with colitis fed either chow or infant formula (p < 0.001). Similar effects were seen in rats with colitis fed infant formula supplemented with recombinant human IL-1 receptor antagonist (geometric mean, 1.95 U/g). These data show that orally administered human milk has an antiinflammatory effect on chemically induced colitis in rats, which may be mediated in part by IL-1 receptor antagonist contained in human milk.     

Selective ETA receptor antagonism with BQ-123 is insufficient to inhibit angioplasty induced neointima formation in the rat

OBJECTIVE: The aim was to assess whether or not the endothelin ETA receptor selective antagonist BQ-123 could inhibit neointima formation in vivo following balloon angioplasty. METHODS: The effect of either acute administration of BQ-123 (0.1 mg.kg-1.min-1 intra-arterial infusion for 1 h before and 1 h after angioplasty) or chronic administration (bolus intraperitoneal injection, 2.5 mg.kg-1 twice daily; continuous intraperitoneal infusion, 0.8 and 8 mg.kg-1.d-1) on neointima formation was examined in rats which had undergone left common carotid artery balloon angioplasty. RESULTS: Neither acute intra-arterial infusion nor either mode of chronic intraperitoneal administration of BQ-123 had a significant effect on the degree of neointima formation observed following balloon angioplasty. CONCLUSIONS: Neither acute nor chronic ETA receptor blockade is sufficient to inhibit angioplasty induced neointima formation in the rat. Since it was previously shown that the ETA/B antagonist SB 209670 was effective in this model, while the ETA selective antagonist BQ-123 is now found to be ineffective, the data implicate the ETB receptor subtype in the pathogenesis of neointima formation.     

Foetal outcome in women with inflammatory bowel disease treated during pregnancy with oral mesalazine microgranules

BACKGROUND: Little information is available about the safety of high doses of mesalazine during pregnancy. AIM: To study the fate of pregnancy and foetal outcome in women taking 1-4 g/day of mesalazine microgranules for inflammatory bowel disease. PATIENTS AND METHODS: Case reports were collected from the Pharmacovigilance Department of Ferring SA, France, from a survey conducted in three gastroenterology units, and from a teratology information service. The evolution of pregnancy and foetal outcome were assessed by questionnaire. RESULTS: The study covered a total of 123 pregnancies (126 foetuses). Ninety-six women took mesalazine during the first trimester, 85 during the second and 83 during the third. The mean daily dose was 2.1+/-0.8 g; 86 women received <3 g/day (low-dose group), 37 women received > or =3 g/day (high-dose group). The following abnormalities were observed in the low-dose and high-dose groups, respectively: ectopic pregnancy (1/0), spontaneous abortions (1/1), foetal death (0/1), premature deliveries (3/5, P < 0.05), congenital malformations (3/1) and one case of lethal oxalosis. Abnormalities were not considered to be related to mesalazine. CONCLUSIONS: The use of oral mesalazine microgranules during pregnancy is safe at doses < or =2 g/day, and probably also at a dose of 3 g/day.     

Beneficial effect of ursodeoxycholic acid on mucosal damage in trinitrobenzene sulphonic acid-induced colitis

BACKGROUND: Recently we observed that ursodeoxycholic acid (UDCA) ameliorates an experimental small intestinal inflammation induced by indomethacin in the rat. In this study, we have tested whether ursodeoxycholic acid also reduces mucosal damage in the bile-independent trinitrobenzene sulphonic acid (TNB) model of experimental colitis. METHODS: Intestinal inflammation (colitis) was induced in male Sprague-Dawley rats (250-300 g) by intracolonic administration of TNB (30 mg in 50% ethanol). Rats were treated with UDCA (10 mg/kg) either for 3 days starting with the administration of TNB for an acute inflammation (n = 11) or for 8 days starting one day after induction of colitis related to a more acute/chronic inflammation (n = 11). Rats were sacrificed at day 3 or day 9, respectively. Healing of induced colitis was assessed by macroscopic and blinded microscopic analysis as well as by measurement of bowel wet weight, daily body weight, and myeloperoxidase activity. All examinations were separately performed in three colon segments (S1 3-5 cm, S2 5.5-8 cm and S3 8.5-11 cm from anus). RESULTS: UDCA treatment significantly reduced macroscopically and microscopically detectable injury in acute inflammation in segments 1 and 2. The colitis-rats with acute/chronic inflammation had less marked mucosal damage. Nevertheless, UDCA treatment led to a significant decrease of visible injury parameters which was seen exclusively at the area of maximal ulceration (S2). Furthermore, a significant increase in body weight of UDCA-treated TNB rats compared to controls from day 5 on was found. CONCLUSION: Ursodeoxycholic acid attenuates the severity of acute inflammation and inhibits the development of acute/chronic inflammation predominantly around the area of maximal ulceration in TNB-induced colitis. In addition to our previous studies and results in indomethacin induced enteritis, these data may provide a rationale for studying how UDCA modulates functions of immune cells in the colonic mucosa.     

Balsalazide

Balsalazide is a prodrug of mesalazine which has an inert carrier molecule instead of the sulfapyridine moiety of sulfasalazine. Balsalazide 6.75 g/day was more effective than mesalazine 2.4 g/day in at least 1 trial and as effective as sulfasalazine 3 g/day for inducing remission in patients with acute ulcerative colitis in 8- and 12-week trials. Moreover, complete symptom relief occurred more promptly with balsalizide 6.75 g/day than with mesalazine 2.4g/day. In long term studies, balsalazide 2 g/day was as effective as sulfasalazine 2 g/day and balsalazide 6 g/day was as effective as mesalazine 1.5 g/day, in maintaining remission in patients with ulcerative colitis. The tolerability profile of balsalazide is significantly better than that of sulfasalazine; 70% of sulfasalazine-intolerant patients were able to tolerate balsalazide.     

Effects of chronic nitric oxide synthase inhibition on TNB-induced colitis in rats

Nitric oxide (NO) synthesis is increased in ulcerative colitis, but the role of NO in colitis is poorly understood. The present study employed Nw-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, in rats to evaluate the effect of NO on 2,4,6-trinitrobenzenesulphonic acid (TNB)-induced colitis. L-NAME solutions were placed in subcutaneous, osmotic mini-pumps which continuously released L-NAME at 0.042, 0.208, 0.417, or 1.667 mg kg-1 h-1. L-NAME dose-dependently enhanced lesions in TNB-induced colitis. The two higher doses of L-NAME significantly increased colonic mucosal damage, although there was slight, nonsignificant reduced lesion formation with the lowest dose of L-NAME. 0.042 mg kg-1 h-1. A single dose of L-NAME at 100 mg kg-1 subcutaneously injected daily in TNB-treated rats also increased lesions, and these ulcerogenic actions of L-NAME were reversed by L-arginine but not by D-arginine (both at 500 mg kg-1, s.c.). Only the highest dose of L-NAME (mini-pump) significantly depressed myeloperoxidase (MPO) activity. Faecal occult bleeding showed a close relationship with severity of colitis. These findings suggest that there may exist a balance between NO protective and aggressive effects. In TNB-induced colitis, antagonism of endogenous NO generation was intensified, whereas slight inhibition of NO synthesis reduced lesions. Variations in responses, related to timing or dose changes in L-NAME, may reflect the differences in inducible vs constitutive NO synthase isoforms.     

Characteristics associated with rapid decline in forced expiratory volume

Though the mechanism of tissue damage induced by colonic inflammation in ulcerative colitis is unknown, it has been established that the inflammatory mediator and potent neutrophil (PMN) chemotaxin, leukotriene B4(LTB4), is present in elevated amounts in the inflamed mucosa. The unique role of 5-lipoxygenase in the production of leukotrienes has made it a target for inhibition. This study used a rat model of acute colonic inflammation induced by a single IP injection of Mitomycin-C to test the efficacy of a specific and potent 5-lipoxygenase inhibitor zileuton in the treatment of colonic inflammation. We hypothesized that after inducing colitis in rats with mitomycin-C, the administration of oral zileuton would inhibit leukotriene production, thus preventing PMN infiltration and subsequent tissue damage. Zileuton decreased colonic tissue damage as measured by Histological score. However, zileuton did not significantly decrease neutrophil infiltration measured by mucosal PMN or myeloperoxidase (MPO) levels. Although zileuton was successful in significantly decreasing the frequency of severe colitis in our model, the fact that the decrease in PMN count and MPO level was not statistically significant suggests that another mechanism may be involved in its anti-inflammatory effect.     

Previous inflammation alters the response of the rat colon to stress

BACKGROUND & AIMS: Patients with inflammatory bowel disease have symptoms of irritable bowel syndrome (IBS) with a higher than expected prevalence. Stress is an important factor in the pathogenesis of IBS. Thus, previous inflammation may predispose to IBS by rendering the bowel more susceptible to the impact of stress. The aim of this study was to examine the effect of previous colitis on stress-induced responses in rats. METHODS: Acute colitis was induced in rats by intrarectal administration of trinitrobenzene sulfonic acid (TNBS), and the rats were allowed to recover for 6 weeks before application of mild restraint stress for 3 consecutive days. In vitro measurements included myeloperoxidase activity, plasma corticosterone levels, interleukin 1 beta messenger RNA expression, and [3H]noradrenaline release from the myenteric plexus. RESULTS: Six weeks after administration of TNBS, stress caused a significant increase in myeloperoxidase activity in TNBS-treated rats but not in stressed controls; plasma corticosterone responses were similar. Stress also caused an exaggerated and significant suppression of [3H]noradrenaline release in TNBS-treated stressed rats compared with stressed controls. This was accompanied by a significant decrease in interleukin 1 beta messenger RNA expression in the colon. CONCLUSIONS: Previous colitis rendered the colon more susceptible to effects of stress on enteric nerve function and also increased some parameters of inflammation in response to stress.     

Effect of putative phospholipase A2 inhibitors on acetic acid-induced acute colitis in the rat

Phospholipase activation may play an important role in ulcerative colitis. This hypothesis was tested by evaluating the effect of two non-selective phospholipase (PL) A2 inhibitors, quinacrine and p-bromophenacyl-bromide (pBPB), on acetic acid-induced colitis in the rat. The calcium antagonist verapamil, which may also act as a PLA2 inhibitor, was also tested. Acute colitis was induced in an isolated colonic segment by instillation of 4 per cent acetic acid for 15 s; this induces a uniform colitis after 4 days. The severity of colitis was evaluated histologically, by measuring myeloperoxidase (MPO) activity and by determining plasma exudation into the lumen of the colon (permeability) with 125I-labelled albumin given intravenously. All three putative PLA2 inhibitors tested were found to prevent the development of colitis. Intravenous administration of quinacrine 10 mg kg-1 at 30 min before instillation of acetic acid resulted in a normal mucosal appearance, normal MPO activity and a significantly reduced increase in plasma exudation into the colon. A similar effect was achieved using verapamil. Intracolonic administration of either quinacrine or pBPB also prevented acetic acid-induced colitis. However, three doses, starting immediately after acetic acid administration and repeated on the first and second days, were needed to achieve this, whereas one dose produced only a partial effect. PLA2 may play an important role in acetic acid-induced colitis and inhibition of its activity may offer an alternative mode of treatment in ulcerative colitis.     

Olsalazine versus mesalazine in the treatment of mild to moderate ulcerative colitis

AIM: To compare the efficacy and tolerability of olsalazine sodium with enteric-coated mesalazine in inducing endoscopic remission in patients with mild to moderate active ulcerative colitis. PATIENTS AND METHODS: Patients with mild to moderate active ulcerative colitis were randomized to receive either olsalazine sodium, 3 g/day (n = 88), or mesalazine, 3 g/day (n = 80), for up to 12 weeks. RESULTS: Of the patients treated with olsalazine sodium, 52.2% achieved endoscopic remission, compared with 48.8% of patients treated with mesalazine. This difference was not significant (P = 0.67). There was a nonsignificant trend for patients with left-sided colitis or a more severe endoscopic grade to achieve remission if they were treated with olsalazine sodium than if they were treated with mesalazine. Both treatments were comparable with respect to clinical activity index and an investigator's global assessment. Seventy patients reported one or more adverse events; adverse events were seen in 45% of olsalazine sodium-treated patients and in 36% of mesalazine-treated patients. Eleven patients treated with olsalazine sodium and nine patients treated with mesalazine withdrew from the study because of adverse events. One patient treated with olsalazine sodium compared with two treated with mesalazine stopped treatment because of diarrhoea. Serious adverse events occurred in three patients treated with olsalazine sodium and in four treated with mesalazine. CONCLUSION: Therapeutic effectiveness and tolerance to the treatment did not differ between olsalazine sodium, 3 g/day, and mesalazine, 3 g/day, in inducing endoscopic remission in patients with mild to moderate active ulcerative colitis within 12 weeks of treatment.     

Disturbed pyloric motility in Ws/Ws mutant rats due to deficiency of c-kit-expressing interstitial cells of Cajal

Interstitial cells of Cajal (ICC) are believed to initiate the basic contractile activity of the gastrointestinal tract. Interstitial cells of Cajal express c-kit receptor tyrosine kinase and are deficient in Ws/Ws mutant rats with a small deletion of the c-kit gene. As Ws/Ws rats show remarkable bile reflux to the stomach, the contraction pressure of the pylorus was compared between Ws/Ws and control +/+ rats. The contraction pressure of the pylorus was measured using a microtransducer, which was inserted through a pin-hole in the anterior wall of the stomach under anesthesia. The magnitude of bile reflux was estimated by measuring the content of bile acids in the stomach. The c-kit messenger RNA-expressing cells were detected by in situ hybridization. Frequency and the maximum pressure of the contraction were comparable between Ws/Ws and +/+ rats, but the duration of the contraction was significantly shorter in Ws/Ws rats than in +/+ rats. The number of c-kit messenger RNA-expressing ICC in the pylorus of Ws/Ws rats was 1.7% that of +/+ rats. The bile reflux observed in Ws/Ws rats was attributed to the decrease in the duration of the pyloric contraction, which appeared to result from the deficiency of c-kit messenger RNA-expressing ICC.     

Dietary monounsaturated n-3 and n-6 long-chain polyunsaturated fatty acids affect cellular antioxidant defense system in rats with experimental ulcerative colitis induced by trinitrobenzene sulfonic acid

The intrarectal administration of trinitrobenzene sulfonic acid in rats induces ulcerative colitis, which results in histological alterations of colonic mucosa, severe modification of the cellular antioxidant defense system, and enhanced production of inflammatory eicosanoids. This study evaluated the influence of different dietary fatty acids, i.e., monounsaturated, n-3, and n-3 + n-6 polyunsaturated fatty acids, on the recovery of the colonic mucosa histological pattern, the cellular antioxidant defense system of colon, and PGE2 and LTB4 colonic mucosa contents in a model of ulcerative colitis induced by intrarectal administration of trinitrobenzene sulfonic acid. Administration of dietary n-3 polyunsaturated fatty acids led to a minimum stenosis score, a higher histological recovery, lower colon alkaline phosphatase and gamma-glutamyltranspeptidase activities, and lower mucosal levels of PGE2 and LTB4 compared with the other two experimental groups. However, glutathione transferase, glutathione reductase, glutathione peroxidase, and catalase activities were lower in the group treated with n-3 polyunsaturated fatty acids than in the groups fed with either the monounsaturated or the n-6 + n-3 polyunsaturated enriched diet. We conclude that n-3 polyunsaturated fatty acids can be administered to prevent inflammation in ulcerative colitis, but they cause a decrease in the colonic antioxidant defense system, promoting oxidative injury at the site of inflammation.