Effects of statins on experimental colitis in normocholesterolemic rats

OBJECTIVE: The results of previous studies suggest that statins have a direct anti-inflammatory effect that is not directly related to their cholesterol-lowering activity. The aim of this study was to investigate the effect of simvastatin (SIM) and fluvastatin (FLU) on trinitrobenzene sulfonic acid (TNBS)-induced colonic inflammation in rats. MATERIAL AND METHODS: The drugs were given for 3 days (0.1 and 1 mg/kg day-1; intraperitoneally) after induction of colitis. The lesions in the distal colon were scored at the macroscopic and microscopic level. Tissue malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content were assessed and formation of reactive oxygen species and peroxynitrite was monitored by chemiluminescence (CL) assay. Trunk blood was collected for the measurement of serum tumor necrosis factor (TNF)-alpha level. RESULTS: Treatment with SIM reduced the lesion score of the colitis group at macroscopic level (p<0.05), but there was no effect of treatment with FLU. The increase in colonic MDA level of the colitis group was reduced by both drugs at all doses (p<0.05-0.001). The decrease in GSH and the an increase in MPO activity in the colitis group were reversed by SIM at all doses (p<0.01), but FLU had no effect. An increase in colonic lucigenin CL value in the colitis group was reduced by SIM and FLU at all doses (p<0.001) and an increase in peroxynitrite ratio in the colitis group showed a significant reduction in SIM-treated groups; FLU reduced this effect at a dose of 1 mg/kg (p<0.01). An increase in tissue collagen content and serum TNF-alpha level in the colitis group was reversed by both drugs at all doses (p<0.001). CONCLUSIONS: SIM and FLU seemed to be beneficial in a TNBS-induced rat colitis model through the prevention of lipid peroxidation, superoxide generation, cytokine production and neutrophil accumulation.     

Colonic responses to Lactobacillus farciminis treatment in trinitrobenzene sulphonic acid-induced colitis in rats

Background: It has recently been shown that Lactobacillus farciminis treatment exerts an anti-inflammatory effect in trinitrobenzene sulphonic acid (TNBS)-induced colitis partly through a nitric oxide release by this strain. The aim of this study was to evaluate whether L. farciminis treatment shares also the general mechanisms of action involved in the beneficial effect of probiotics in the colonic inflammatory process. Methods: Rats received L. farciminis for 15 days before and 4 days after intracolonic administration of TNBS or vehicle. The following parameters were evaluated: macroscopic damage of colonic mucosa, myeloperoxidase activity, cytokine mucosal levels, bacterial profile in colonic content and mucosa, bacterial translocation and colonic paracellular permeability. Results: In the absence of TNBS, L. farciminis treatment reduced colonic paracellular permeability and increased the IL-10 level in the colonic wall. TNBS administration induced colonic macroscopic damage, associated with an increase of myeloperoxidase activity, bacterial translocation, colonic paracellular permeability and IL-1β mucosal level, and a decrease in IL-10 mucosal level. Moreover, the bacterial profile of colonic content and mucosa was modified. All these alterations were abolished or significantly reduced by L. farciminis treatment. Conclusions: As previously shown, L. farciminis treatment improves TNBS-induced colitis. This study indicates that, in addition to the nitric oxide released by this bacterial strain, the anti-inflammatory action of L. farciminis involves also normalization of colonic microflora, prevention of bacterial translocation, enhancement of barrier integrity and a decrease in the IL-1β mucosal level.     

Protection by recombinant human interleukin-11 against experimental TNB-induced colitis in rats

The potential effect of recombinant human interleukin-11 (rhIL-11) on trinitrobenzene sulfonic acid (TNB) -induced colitis was investigated in rats. Intrarectal TNB (40 mg in 0.25 ml 40% ethanol) produced significant ulcerative colitis. The lesions were most severe at three days after TNB instillation, and then declined, but lesions were still observed after two weeks. TNB administration also significantly enhanced the colonic mucosal myeloperoxidase (MPO) levels, which paralleled the severity of colitis. The rhIL-11 at subcutaneous doses of 300 or 1000µg/kg daily for seven days, or 1000µg/kg for three days when given after TNB significantly decreased lesion formation in TNB-induced colitis. These treatments also significantly reduced colonic mucosal MPO levels. TNB enhanced colonic mucosal levels of PGE₂, LTB₄, and TxB₂, but these arachidonic acid derivatives were not affected by the present rhIL-11 treatments. TNB administration for three days caused a body weight loss that returned to normal after 14 days. The rhIL-11 significantly reduced colonic lesion severity and reduced colonic fecal blood loss. Given alone, rhIL-11 did not influence body weight. It can be concluded that rhIL-11 was protective against TNB-induced colitis and reactions of colonic MPO, but that these responses were not mediated through modulation of eicosanoid metabolism.Supported by Genetics Institute, Inc., Andover, Massachusetts.     

G protein-coupled receptor 55 (GPR55) expresses differently in patients with Crohn’s disease and ulcerative colitis

Aim: To investigate the levels of G protein-coupled receptor 55 (GPR55) expression in colonic tissue of inflammatory bowel disease (IBD) patients and healthy controls, and its potential implication in IBD treatment.

Methods: Fifty patients were enrolled in our prospective study: n?=?21 with Crohn’s disease (CD) and n?=?16 with ulcerative colitis (UC); 19 women and 18 men. Control consisted of 13 non-IBD patients. In each subject, two biopsies were taken from different colonic locations. In IBD patients, biopsies both from endoscopically inflamed and non-inflamed areas were drawn and the development of inflammation confirmed in histopathological examination. GPR55 mRNA and protein expression were measured using real-time PCR and Western blot, respectively.

Results: GPR55 expression at mRNA and protein level was detected in all samples tested. The level of GPR55 mRNA expression in non-inflamed colonic areas was comparable in all analyzed groups (p?=?.2438). However, in the inflamed tissues GPR55 mRNA expression was statistically significantly (p?<?.0001) higher (6.9 fold) in CD patients compared to UC. Moreover, CD patients manifested higher (12.5 fold) GPR55 mRNA expression in inflamed compared with non-inflamed colonic tissues (p?<?.0001). Although no significant differences were stated, GPR55 protein level tends to decrease in IBD as compared to control.

Conclusions: Different patterns of GPR55 expression at mRNA level were observed in IBD patients. We speculate that GPR55 is crucial for the mucosal inflammatory processes in IBD, particularly in CD and its expression may affect disease severity, and response to treatment. The GPR55 receptors may become an attractive target for novel therapeutic strategies in IBD.     

The association between antigenemia,histology with immunohistochemistry,and mucosal PCR in the diagnosis of ulcerative colitis with concomitant human cytomegalovirus infection

Background

Human cytomegalovirus (HCMV) colitis can be involved in active ulcerative colitis (UC) in patients refractory to steroid and immunosuppressive drugs. Histological examination with colonic biopsy specimens and antigenemia assays are the standard tests for diagnosing HCMV enterocolitis, and we have previously reported the usefulness of mucosal polymerase chain reaction (PCR) methods. However, the associations among histopathological tests, antigenemia assays, and mucosal PCR are unknown.

Methods

We retrospectively analyzed 82 UC patients who underwent mucosal biopsy from inflamed colonic tissues for histological evaluation and mucosal PCR to detect HCMV. We analyzed the relationships between the HCMV-DNA copy number in colonic mucosa and other HCMV tests.

Results

In total, 131 HCMV mucosal PCR tests from 82 UC patients were positive. The HCMV-DNA copy number was significantly higher in patients with positive immunohistochemistry (IHC) (p < 0.01) and was correlated with the number of positive cells for the antigenemia (C7-HRP, p < 0.01; C10/11, p < 0.01). Receiver operating characteristic curve analysis confirmed 1300 copies/μg of HCMV-DNA as the best diagnostic cut-off value to predict positive results of antigenemia (area under the curve = 0.80, 95% CI 0.68–0.93). HCMV-DNA copy number also correlated with the total UCEIS score (p = 0.013) and the bleeding score (p = 0.014). For each individual patient, a positive correlation between the change in total UCEIS score and HCMV-DNA copy number was observed (p = 0.040).

Conclusion

The antigenemia assay and histopathological test with IHC were significantly associated with the HCMV-DNA copy number in colonic tissues. Moreover, endoscopic examination with the UCEIS can help diagnose the HCMV colitis in UC patients.

     

Nitric oxide released by lactobacillus farciminis improvesTNBS‐induced colitis in rats

Background: Beneficial effects of lactobacilli have been reported in experimental colitis. On the other hand, despite the controversial role of nitric oxide (NO) in the inflammatory gut process, a protective action of exogenous NO in inflammation has been suggested. Consequently, this study aimed to determine the effect of (i) sodium nitroprusside (SNP), a NO donor and (ii) treatment with Lactobacillus farciminis, which produces NO in vitro, on trinitrobenzene sulphonic acid (TNBS)‐induced colitis in rats and to evaluate the role of exogenous NO in this effect. Methods: Rats were divided into three groups receiving one of the following: (i) a continuous intracolonic (IC) infusion of SNP for 4 days, (ii) L. farciminis orally for 19 days, or (iii) saline. On day 1 and day 15, respectively, TNBS and saline were administrated IC, followed by a continuous IC infusion of saline or haemoglobin, a NO scavenger. At the end of treatments, the following parameters were evaluated: macroscopic damage of colonic mucosa, myeloperoxidase and nitric oxide synthase activities and colonic luminal NO production. Results: In colitic rats, SNP and L. farciminis treatment significantly (P?Conclusion: NO released intraluminally by SNP infusion or by L. farciminis given orally improves TNBS‐induced colitis in rats. These results indicate a protective role of NO donation in colonic inflammation and show for the first time a mechanism involving NO delivery by a bacterial strain reducing an experimental colitis.     

Early effects of fibrin sealant on colonic anastomosis in rats: an experimental and case-control study

Background Leakage from colonic anastomoses leads to mortality and morbidity. Fibrin adhesives can be used to increase the strength of the anastomosis. In this study, we evaluated the early effects of fibrin sealant and hyaluronic acid-carboxymethylcellulose on colonic anastomosis in rats. Methods Anastomoses were made in the descending colon of 38 female Wistar-Albino rats, in three groups: control group (n=12), group 1 treated with hyaluronic acid-carboxymethylcellulose (n=16), and group 2 treated with fibrin sealant (n=10). After 72 hours, adhesion scores, bursting pressure, rupture strength and histopathologic healing scores were evaluated. Results Due to postoperative mortality, we evaluated 10, 10 and 9 rats in the control group and in groups 1 and 2, respectively. Of these, we excluded 4, 5 and 4 rats that had macroperforations at autopsy. In the remaining rats, bursting pressure (123.2±14.8 mmHg) and rupture strength (400±16 mg) in the fibrin sealant group were significantly greater than in the two other groups (Control: 68.0±10.6 p=0.006 and 325±52 p=0.009; Group 1: 74.0±9.8 p=0.03, 330±27 p=0.016). However, we did not observe any significant difference between adhesion scores (2.5±0.6, 2.0±0.7, 2.0±0.7, p=0.343). Conclusions In this experimental study, fibrin sealant increased bursting pressure and rupture strength of colonic anastomoses while hyaluronic acid-carboxymethylcellulose had no effetcs in rats, but both of them showed no effect on adhesion scores. In order to use fibrin sealant to decrease the rate of early leakages from colonic anastomoses, further studies have to be performed.     

Mycophenolate Mofetil Reduces Tissue Damage and Inflammation in an Experimental Model of Colitis in Rats

Background: Lymphocytes are widely believed to be responsible for persistent intestinal inflammation in inflammatory bowel diseases. Mycophenolate mofetil (MMF) is a potent immunosuppressant that inhibits lymphocyte proliferation and has been shown to be effective in preventing allograft rejection after organ transplantation. The purpose of this study was to assess the modulating effects of MMF on intestinal inflammation in an experimental model of colitis in rats. Methods: Colitis was induced by rectal instillation of trinitrobenzenesulfonic acid (TNBS) in ethanol in male Sprague-Dawley rats. One group of rats (n=10) was treated with MMF i.p. (25 mg/kg b.w.) daily for 1 week starting 24 h after induction of colitis. A second group of rats (n=10) was treated with MMF at the same dose 2 days, 1 day and 1 h prior to induction of colitis. Control animals (n=10) received vehicle only. After being killed, colonic tissue was macroscopically evaluated for necrosis and microscopically for ulcerations. Sections were stained and examined for the presence of granulocytes. Results: Administration of MMF after induction of TNBS colitis reduced macroscopic injury by 62% compared to control animals (P=0.01). Microscopic ulcerations were reduced by 64% compared to controls (P=0.009). In addition, posttreatment significantly reduced the number of granulocytes. MMF pretreatment did not significantly prevent macroscopic or microscopic tissue damage, or change the number of granulocytes. Conclusion: Systemic administration of MMF significantly ameliorates tissue damage in a model of experimental colitis in rats suggesting that this compound may play an important role as an immunosuppressant in the therapy of inflammatory bowel diseases.     

Emu Oil reduces disease severity in a mouse model of chronic ulcerative colitis

Objective: Ulcerative colitis (UC) is characterized by mucosal inflammation and ulceration of the large intestine. Emu Oil (EO) has been reported to protect the intestine against mucositis, NSAID-enteropathy, UC-associated colorectal cancer and acute UC. We aimed to determine whether EO could reduce the severity chronic UC in mice.

Methods: Female C57BL/6 mice (n?=?10/group) were orally administered (gavage) water (Groups 1–2) or EO (Groups 3: low dose-80?µl and 4: high dose-160?µl), thrice weekly. Group 1 mice consumed plain drinking water throughout the trial. Groups 2–4 mice underwent two cycles [each consisting of seven days dextran sulfate sodium (DSS; 2% w/v) and 14 days water], followed by a third DSS week. All mice were euthanized two days later (day 51). Bodyweight, disease activity index (DAI), burrowing activity, myeloperoxidase activity, crypt depth and histologically assessed damage severity were assessed. p?<?.05 was considered significant.

Results: DSS decreased bodyweight and increased DAI compared to normal controls (p?<?.05), which was partially attenuated by both EO doses (p?<?.05). Burrowing activity was impaired in DSS-controls compared to normal controls (days 27 and 40); an effect prevented by both EO doses (p?<?.05). DSS increased colonic myeloperoxidase activity and crypt depth compared to controls (p?<?.05), with no significant EO effect. Moreover, DSS increased colonic damage severity compared to normal controls (p?<?.001). Importantly, both EO doses decreased distal colonic damage severity compared to DSS-controls (p?<?.001).

Conclusions: Emu Oil attenuated clinically- and histologically-assessed disease severity in a mouse model of chronic UC. Emu Oil demonstrates promise as an adjunct to conventional treatment options for UC management.     

Blueberry husks,rye bran and multi-strain probiotics affect the severity of colitis induced by dextran sulphate sodium

Objective. The enteric microbiota is a pivotal factor in the development of intestinal inflammation in humans but probiotics, dietary fibres and phytochemicals can have anti-inflammatory effects. The aim of this study was to evaluate the therapeutic effect of multi-strain probiotics and two conceivable prebiotics in an experimental colitis model. Material and methods. Sprague-Dawley rats were fed a fibre-free diet alone or in combination with Lactobacillus crispatus DSM 16743, L. gasseri DSM 16737 and Bifidobacterium infantis DSM 15158 and/or rye bran and blueberry husks. Colitis was induced by 5% dextran sulphate sodium (DSS) given by oro-gastric tube. Colitis severity, inflammatory markers, gut-load of lactobacilli and Enterobacteriaceae, bacterial translocation and formation of carboxylic acids (CAs) were analysed. Results. The disease activity index (DAI) was lower in all treatment groups. Viable counts of Enterobacteriaceae were reduced and correlated positively with colitis severity, while DAI was negatively correlated with several CAs, e.g. butyric acid. The addition of probiotics to blueberry husks lowered the level of caecal acetic acid and increased that of propionic acid, while rye bran in combination with probiotics increased caecal CA levels and decreased distal colonic levels. Blueberry husks with probiotics reduced the incidence of bacterial translocation to the liver, colonic levels of myeloperoxidase, malondialdehyde and serum interleukin-12. Acetic and butyric acids in colonic content correlated negatively to malondialdehyde. Conclusions. A combination of probiotics and blueberry husks or rye bran enhanced the anti-inflammatory effects compared with probiotics or dietary fibres alone. These combinations can be used as a preventive or therapeutic approach to dietary amelioration of intestinal inflammation.     

Collagenase-3 (MMP-13) expression by inflamed mucosa in inflammatory bowel disease

Objective. To determine whether the expression of collagenase-3 (MMP-13) in biopsies from patients with inflammatory bowel disease is correlated with histological inflammation parameters. Material and methods. Fifty-nine patients with inflammatory bowel disease were included in the study. The control group comprised 20 patients free of inflammatory disease and ten patients with acute diverticulitis. MMP-13 expression was determined by immunohistochemical staining and the specimens were assigned a histological inflammation score. Results. It was found that 62.8% of patients with ulcerative colitis (UC) and 54.1% of patients with Crohn's disease (CD) showed MMP-13-positive immunostaining in biopsies from affected areas. MMP-13-positive staining was more intense in ulcerated colonic mucosa. A positive and significant correlation was found between MMP-13 expression and the histological inflammation scores in mucosal samples from patients with CD (r=0.74, p<0.0001) or UC (r=0.62, p<0.0001). However, no MMP-13-positive immunostaining was found in either the biopsy specimens of the control group or those biopsies taken from patients with UC or CD in microscopically confirmed non-affected areas of the colonic mucosa. Similarly, colonic mucosa samples of the 10 patients with acute diverticulitis did not show immunostaining for MMP-13. Conclusions. Our findings demonstrating the absence of MMP-13 expression in non-inflamed colonic mucosa or in acute diverticulitis, as well as a positive correlation between elevated MMP-13 expression and histological criteria of inflammation in patients with inflammatory bowel diseases (CD and UC) suggest a role of the protease in the pathogenesis of these latter processes.     

Effects of Exopolysaccharide-Producing Probiotic Strains on Experimental Colitis in Rats

Purpose Inflammatory bowel disease is suggested to result from a dysregulated immune response toward intestinal microflora, which may be restored by probiotic therapy based on the concept of healthy microflora. Ideal probiotic bacteria may be beneficial in inflammatory bowel disease; however, the mechanism of action and the clinical efficacy of probiotic usage are still unclear. In the present study, the effect of exopolysaccharide producing probiotics was evaluated on an experimental colitis model in rats. Methods Colitis was induced by intracolonic administration of acetic acid. Then, rats were treated daily with two probiotic strains, Lactobacillus delbrueckii subsp. bulgaricus B3 strain (exopolysaccharide of 211 mg/l: high-EPS group) or Lactobacillus delbrueckii subsp. bulgaricus A13 strain (EPS of 27 mg/l: low-EPS group), which were given into the stomach. The non-colitis–fed control group was only treated with high-exopolysaccharide strain. The model-control and control groups were treated only with tap water. Rats were killed after a seven-day treatment period. Disease activity was quantified by use of histologic scores and colonic myeloperoxidase activity, which is a marker of neutrophil infiltration during inflammation. Results The enhanced inflammatory response was accompanied by a higher level of myeloperoxidase activity in the colitis group. Histologic scores of colonic damage and myeloperoxidase activity were lower in both probiotic-treated groups compared with those of the colitis control group (P < 0.001), although the mentioned scores improved significantly more in the high-EPS group than in the low-EPS group (P < 0.001). Conclusions Exopolysaccharide-producing probiotics significantly attenuate experimental colitis, which may be mediated by exopolysaccharide in a dose-dependent manner. Therefore, exopolysaccharide-producing probiotics may be a promising therapeutic role in inflammatory bowel disease. Supported in part by the Scientific and Technological Research council of Turkey (TUBITAK), TBAG-2090 (101T129) (the probiotic properties of experimental studies and the isolations of the strains used in this study).     

Differences in colonic disease activity in patients with ulcerative colitis with and without primary sclerosing cholangitis

PURPOSE: A small group of patients with ulcerative colitis (UC) also suffer from primary sclerosing cholangitis (PSC). Genetic and immunologic differences exist between UC patients with and without concomitant PSC. Furthermore, UC patients with PSC are more prone to developing colonic dysplasia/aneuploidy compared with patients with UC only. Because colonic disease activity and treatment with sulfasalazine have been found to be of independent importance for development of colonic carcinoma in UC, this study aims to determine if differences exist concerning colonic disease activity in UC patients with and without PSC. METHODS: Twenty-nine PSC patients with total colitis were matched to two UC patients with total colitis but without liver disease. Case records and questionnaires were used to gain information on pharmacologic treatment and disease activity. RESULTS: Observation time was 20 (PSC group) and 23 years (UC only). Number of patients taking prophylactic treatment did not differ between groups. Patients with UC only had received treatment with systemic and local corticosteroids significantly more often than UC patients with PSC (P < 0.05 and P < 0.02). Patients with UC only were hospitalized because of colonic activity significantly more often (P < 0.02). Number of patients undergoing colectomy because of disease activity or number of patients with chronic continuous symptoms did not differ between the two groups. CONCLUSION: UC in patients with PSC runs a milder course than UC in patients without this complication, although the number of patients taking prophylactic treatment was the same. If lower disease activity reflects differences in pathogenesis of UC in patients with PSC or if it can explain increased risk to develop colonic malignancy in patients with both PSC and UC needs further elucidation.Supported by grants from Nanna Svartz Scholarship, Stockholm, Sweden.     

Dipeptidyl peptidase-4 inhibitor anagliptin facilitates restoration of dextran sulfate sodium-induced colitis

Abstract

Objective. Inflammatory bowel disease (IBD) is a chronic debilitating disease associated with severe damage to the intestinal mucosa. Glucagon-like peptide-2 (GLP-2) is a potent and specific gastrointestinal growth factor. GLP-2 released from enteroendocrine cells is inactivated by dipeptidyl peptidase-4 (DPP-4). The aim of this study was to examine whether the DPP-4 inhibitor anagliptin improves experimental murine colitis. Material and methods. Male C57BL/6 mice aged 8 weeks were exposed to 1.5% dextran sulfate sodium (DSS) in drinking water for 7 days to induce experimental colitis. Anagliptin (0.1% in diet) was administrated from 2 days before the beginning of DSS to 7 days after the end of DSS. Changes in body weight and disease activity index were evaluated daily. Histological colitis severity, cellular proliferation and gene expression were determined in colonic tissues. Results. Treatment with anagliptin clearly improved body weight loss and disease activity index in the recovery phase. Histological score in the DSS + anagliptin group at day 14 was significantly lower than that in the DSS alone group. Treatment with anagliptin increased the Ki67-positive rate at days 10 and 14, and tended to increase insulin-like growth factor-1 mRNA expression in the DSS + anagliptin group. Conclusion. In this model of experimental colitis, the DPP-4 inhibitor anagliptin facilitated the restoration of mucosal damage, thereby resulting in the acceleration of healing. These findings suggest a new and novel therapeutic approach for the treatment of IBD.     

The Effect of Hypericum perforatum (St. John’s Wort) on Experimental Colitis in Rat

The aim of the present study was to investigate the effect of Hypericum perforatum (HP) on the inflammatory and immune response of colonic mucosa in rat with induced inflammatory bowel disease and that on various enzyme activities in blood and bowel tissue. Male Wistar albino rats were divided into three main groups: control, third day, and seventh day of colitis. Third-day and seventh-day groups were divided into four subgroups. Colitis was induced in all groups except the control group by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The colitis group received saline; treatment groups received HP extract (50, 150, and 300 mg/kg/day, respectively). Glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) activities in blood were measured. Catalase, myeloperoxidase (MPO), glutathione peroxidase (GSH-Px), glutathione reductase (GR), malondialdehyde, and nitric oxide (NO) activities were measured from tissue samples. Colonic damage was significantly reduced by HP extract. Macroscopic scoring of colonic damage significantly reduced in groups given HP extract compared with in the colitis group (P < 0.001). Blood catalase levels were reduced in the HP (150 mg/kg/day) compared with the colitis group (P < 0.01). Blood GSH levels significantly increased in groups treated with HP compared with control (P < 0.001) on the third and seventh day. Tissue GR levels reduced in the colitis and HP (50 mg/kg/day) groups compared with control (P < 0.05). Tissue MPO activity increased in the colitis and treatment groups compared with control (P < 0.007). GSH-Px levels increased in the colitis group compared with control at day 3 (P = 0.006). HP has a protective effect on TNBS-induced inflammatory bowel disease (IBD), probably due to an anti-inflammatory and antioxidant mechanism.     

The healing of colon anastomosis covered with fibrin glue after early postoperative intraperitoneal chemotherapy

Background After colon resection for colonic cancer, the administration of antineoplastic agents may prolong survival by killing residual cancer calls and preventing metastasis, but may also slow anastomotic healing. This study was designed to determine the effects of 5-fluorouracil (5-FU) and leucovorin (LEV), injected intraperitoneally, on the healing of colonic anastomoses with or without fibrin glue (FG) covering. Methods Sixty rats were randomized to one of four groups. After resection of a transverse colon segment, an end-to-end sutured anastomosis was performed. Rats in the 5-FU+LEV and the 5- FU+LEV+FG groups received 5-FU+LEV intraperitoneally. The colonic anastomoses of the rats in the FG group and in the 5-FU+LEV+FG group were covered with fibrin glue. All rats were killed on postoperative day 8. Bursting pressure measurements were recorded and the anastomoses were examined macroscopically and histologically. Results The leakage rate of the anastomoses was significantly different among groups. Specifically, the leakage rate was significantly higher in the 5-FU+LEV group (40%) than in the FG and in the 5-FU+LEV+FG groups where there were no leakages (p=0.017). The mean adhesion formation score was significantly higher in rats of the 5-FU+LEV group, compared to the control (p=0.023), the FG (p=0.006) and the 5-FU+LEV+FG (p=0.006) groups. Bursting pressures were significantly lower in the 5-FU+LEV group than in the other groups (p<0.001). Also, bursting pressures were significantly lower in the control group compared to the FG and 5-FU+LEV+FG groups (p<0.001). Rats in the 5-FU+LEV+FG group had significantly greater neoangiogenesis and fibroblast activity than those in the 5-FU+LEV group (p=0.025). Conclusion The early intraperitoneal postoperative administration of 5-fluorouracil plus leucovorin impaired colonic wound healing. However, the application of fibrin glue prevented the deleterious effect of chemotherapy.     

Melatonin modulates adiponectin expression on murine colitis with sleep deprivation

AIM To determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep deprivation.METHODS The following five groups of C57BL/6 mice were used in this study:(1) group Ⅰ,control;(2) group Ⅱ,2% DSS induced colitis for 7 d;(3) group Ⅲ,2% DSS induced colitis and melatonin treatment;(4) group Ⅳ,2% DSS induced colitis with sleep deprivation(SD) using specially designed and modified multiple platform water baths; and(5) group V,2% DSS induced colitis with SD and melatonin treatment. Melatonin(10 mg/kg) or saline was intraperitoneally injected daily to mice for 4 d. The body weight was monitored daily. The degree of colitis was evaluated histologically after sacrificing the mice. Immunohistochemical staining and Western blot analysis was performed using anti-adiponectin antibody. After sampling by intracardiac punctures,levels of serum cytokines were measured by ELISA. RESULTS Sleep deprivation in water bath exacerbated DSS induced colitis and worsened weight loss. Melatonin injection not only alleviated the severity of mucosal injury,but also helped survival during stressful condition. The expression level of adiponectin in mucosa was decreased in colitis,with the lowest level observed in colitis combined with sleep deprivation. Melatonin injection significantly(P 0.05) recovered the expression of adiponectin. The expression levels of IL-6 and IL-17 were increased in the serum of mice with DSS colitis but decreased after melatonin injection. CONCLUSION This study suggested that melatonin modulated adiponectin expression in colonic tissue and melatonin and adiponectin synergistically potentiated antiinflammatory effects on colitis with sleep deprivation.     

The adherence to the therapy in inflammatory bowel disease: beyond the number of the tablets

Objectives: The therapy of the inflammatory bowel diseases is quite complex. A partial compliance increases the relapse probability and the health expenditure. The aim of the study is to correctly study the adherence to the therapy in a single centre eliminating the bias of a different relationship of trust with different doctors.

Materials and methods: We conducted a blind prospective study on the adherence evaluated for mesalazine.

Results: Three hundred and seventy-six patients were included in the final analysis. Of the patients, 57.4% never missed a single dose of mesalazine, 29.3% missed one or two doses, 7.4% missed three to four doses, 5.9% missed more than five doses. A greater adherence among males (p?=?.015) and, in ulcerative colitis, among the group with a disease duration of <2 years compared to the one with a disease duration between 2 and 5 years (p?=?.04) were found. In Crohn’s diseases, among the patients who had never undergone to surgical interventions, the adherence was 49.6%, compared to 51.9% among patients who underwent to one surgical resection and 78.6% among patients underwent to multiple surgical resections (p?=?.001).

Conclusions: The factors influencing the adherence to the therapy are only partly related to the prescribed therapy, but also to factors affecting the patient life: to increase the adherence rate it would be necessary not only interventions on the posology but also the psychological support to the patient at the time of the visit.