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Background: Colorectal cancer is the third cause of cancer worldwide and a quarter of them are in the rectum. DEK oncogene is involved in several nuclear processes and can accelerate tumorigenesis. Objective: This study aims to evaluate the immunoexpression of DEK and Phospho-P38 proteins before neoadjuvant therapy in patients with rectum adenocarcinoma and correlate it with a clinical response and survival. Methods: Patients with adenocarcinoma of the middle and low rectum who underwent chemotherapy and radiotherapy followed by surgical tumor resection were included. The expression and quantification were studied by immunohistochemistry in the tumor biopsy tissues using a HScore system. Score ≥4 were considered positive and those with

Background and aim Human gut microbiota play an important role in metabolism and host physiology. Perturbations of the gut microbial communities lead to the development of various diseases such as inflammatory bowel disease, celiac disease, allergic diseases, and metabolic diseases. Crohn's disease is a chronic inflammatory bowel disease characterized by periods of remission and relapse. Several studies suggest that intestinal inflammation arises due to an abnormal response of the intestinal immune system to the fecal microbiota. The goal of the study was to evaluate the relative amount of four bacterial groups in fecal samples of Crohn's disease patients and their relation to the inflammatory activity. Methods We studied stool samples of 105 individuals, 54 with Crohn's disease and 51 as a control group. The DNA extracted from the stool samples was subjected to real‐time polymerase chain reaction (qPCR) for quantification of the Bacteroidetes phylum, class Bacilli, and Bifidobacteriaceae and Enterobacteriaceae families. Results We found a significant increase in Bacteroidetes in Crohn's disease samples when compared to the control group (14 650 and 2060 CFU/ng DNA, respectively) (P = 0.014). On the other hand, we observed a significant reduction in Bacilli and Bifidobacteriaceae (13 and 58 CFU/ng DNA, respectively) (P, Gut microbiota is strongly associated with host physiology, and perturbations of the gut microbial communities lead to the development of various diseases. The goal of this study was to evaluate the relative amount of four bacterial groups in fecal samples of patients with Crohn's disease and their relation to the inflammatory activity. We observed that the commensal bacteria were decreased in fecal samples of participants with Crohn´s disease when compared to the control group. There was no relation between the disease localization and/or clinical condition with the microbiota.

STUDY OBJECTIVES: The pathogenesis of inflammatory bowel disease (IBD) is not well understood, and sleep disorders may be potential triggers for IBD. Thus, an evaluation of the sleep characteristics, fatigue symptoms, and cytokine levels was performed in patients with IBD during periods of active disease and remission. METHODS: A total of 20 participants presenting with Crohn's disease or ulcerative colitis, with active disease (n = 7) or in remission (n = 13), underwent home polysomnography (H-PSG). Pittsburgh Sleep Quality Index (PSQI) and Modified Fatigue Impact Scale (MFIS) were applied, in addition to the evaluation of interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNF-α) serum levels. Exploratory analysis, t test and Mann-Whitney U test were used. RESULTS: The mean sleep latency in patients with active disease was 133.07 minutes and 106.79 minutes in those in remission. The sleep efficiency and sleep fragmentation in patients with active disease and those in remission were 80.90% and 84.20% (median), and 76.36/min and 69.82/min (mean), respectively, although the H-PSG parameters did not differ between the groups. The PSQI scores indicated poor sleep quality (global score above 5) in all participants with IBD, and the participants with active disease presented more symptoms of fatigue (P = .032). IL-6 and TNF-α average levels were higher in the participants with disease remission, although with a larger dispersion of the data. CONCLUSIONS: No significant difference in the H-PSG characteristics was observed between the patients with IBD with active disease and those in remission; however, the perception of the participants with IBD showed significant effect on the sleep quality and fatigue symptoms. CITATION: Paixão DL, Poyares D, de Paula MS, Duarte JW, Castelo PM, Ambrogini-Júnior O, Miszputen SJ, Oshima CT, Chagas JR, Paiotti AP. Evaluation of home polysomnography findings, quality of sleep, and fatigue in inflammatory bowel disease: a case series. J Clin Sleep Med. 2019;15(1):39–45.

This study hypothesized that polyphenol- and fiber-rich Brazilian fruits could elicit preventive effects in inflammatory bowel diseases (IBDs), even when applied to obese subjects. Therefore, the purpose was to investigate the implications of the consumption of acai pulp and jaboticaba peel on obese mice with dextran sodium sulfate (DSS)-induced colitis. First, obesity was induced by a high-fat diet for 13 weeks, followed by the inclusion of DSS in the water for five days. Animals received during the whole experiment a standard or high-fat diet, with the last one containing or not 5% (w/w) freeze-dried acai or jaboticaba. The diets added with the fruits had a higher content in total phenolic compounds (1.1 mg GAE/g) and an increased antioxidant capacity (up to 25.32 μmol TE/g). The high-fat diet promoted weight gain starting from the eighth week of the experiment. While jaboticaba delayed and reduced body weight gain, acai highly exacerbated it, also increasing the accumulation of fats. Colitis was successfully induced as seen by the clinical signs and damaged colonic mucosa. The high-fat diets did not increase the severity of colitis in comparison with the standard regimen, despite promoting additional weight gain. Animals that received acai or jaboticaba did not have many symptoms of colitis and showed a grand recovery in colonic histological parameters. Additionally, acai increased the expression of tight-junction-related molecules. Despite being included in a high-fat diet, the fruits still managed to promote healing effects in colitis, therefore indicating their potential for trials with IBD patients.

Background Inflammatory bowel disease occurs when luminal antigens from microbiota stimulate the immune system of an intestinal barrier through defects in the tight junctions lead to an exacerbated response in the genetically predisposed individual. It is well known that the consumption of probiotics improves intestinal health. Specifically, the Lactobacillus sp. strains play a key role in the epithelial intestinal barrier, promote mucin secretion, better performance of tight junctions and prevent apoptosis of epithelial cells. This study aimed to evaluate the role of Kefir (Lactobacillus kefiranofaciens) on inflammation of dextran sodium sulphate (DSS)-induced colitis. Methods Forty male Wistar rats were randomised into five groups: Sham; 5% DSS-induced colitis; control Kefir; 5% DSS-induced colitis treated with Kefir; 5% DSS-induced colitis treated with Kefir + 5-ASA (125mg/kg/day) (Ethics Committee on the Use of Animals number 3627290119). The lactic culture of Kefir (Danisco Biolacta, Olstyn, Poland) was administered ad libitum per 6 days. The preparation of the matrix was carried out as follows: whole milk powder was reconstituted to 10% with distilled water and was incubated at 85°C for 15 min using a mechanical shaker. Subsequently, 20 mg freeze-dried Kefir culture was added to 100 ml of the treated milk and fermentation were carried out at 23°C for 16 h. When the desired pH of 4.6 was reached, the fermentation was stopped by cooling the flasks in ice bath and storing them under refrigeration at 4°C until utilisation. The rats were euthanised on day 9. Colonic samples were processed for transmission electron microscope (TEM) and conventional microscopy. Samples were analysed in a TEM EX II 1200 (JEOL, Japan) coupled to a digital camera system GATAN Orius (USA). Histopathological evaluation was performed by a pathologist under a light microscope. Parameters such as inflammation extent, regeneration and crypt damage were graded according to Dieleman et al.3 Statistical analysis was performed by one-way analysis of variance (ANOVA), followed by Tukey’s test using Graph Pad Prism (version 6.0). Results Kefir treatment reduces the severity of DSS-induced colitis evidenced by decreased abdominal discomfort and rectal bleeding. Histologically, there was a significant decreased of colonic damage and preservation of goblet cells (p < 0.0001) compared with DSS-colitis control group (Figure 1). The effect of Kefir was also verified by TEM analysis at the ultrastructural level, demonstrating the tight junctions preserved, decreased of reticulum edema and increased of autophagosomes (Figure 2). Conclusion Kefir promotes autophagy and protects the intestinal barrier against damage caused by DSS.

Background Iinflammatory bowel disease (IBD) is a chronic disease characterised by dysregulation of the immune function response and imbalanced release of cytokines and unresolved inflammatory progress associated with the intestinal mucosa. In this way, new drugs are constantly tested as a novel treatment option. Mimosa caesalpiniifolia (MC) has been described as a potent analgesic, anti-inflammatory, anti-haemorrhagic, astringent, anthelmintic and diuretic. This study aimed to evaluate the effect of MC extract on dextran sulphate sodium (DSS)-induced colitis in Wistar rats. Methods Forty male Wistar rats were randomised into five groups: Sham; 5% DSS-induced colitis; control MC extract (125 mg/kg/day); 5% DSS-induced colitis treated with MC (125 mg/kg/day); 5% DSS-induced colitis treated with MC + 5-ASA (125 mg/kg/day for both). Colitis was induced by administration of 5% DSS (MP Biomedicals), diluted in drinking water and offered ad libitum for 5 days. MC plant extract was diluted in water and administered by oral gavage per 6 days. The leaf extracts were prepared in 70 gl ethanol and dried in a Buchi B19 Mini-spray dryer using 20% aerosol. The selection of the operating conditions used was followed by the Laboratory of Medicinal and Phytotherapeutic Plants of Unifal-MG. After the induction of colitis, body weight, general health status and faecal characteristics will be evaluated daily. All rats were euthanised on the ninth day of the experiment. The entire colon was dissected and fixed in 10% neutral-buffered formalin at room temperature and embedded in paraffin to provide sections for histological evaluation (Ethics Committee on the Use of Animals number 4362180119). The severity of colitis was evaluated in sections stained with Hematoxylin and Eosin. Parameters such as inflammation extent, regeneration and crypt damage were graded according to Dieleman et al. Statistical analysis was performed by one-way analysis of variance (ANOVA), followed by Tukey post hoc test using Graph Pad Prism (version 6.0). Results MC extract treatment reduced significantly the severity of DSS-induced colitis evidenced by a decreased in clinical symptoms (p < 0.0001). The rats treated with MC extract showed a decreased in diarrhoea episodes and rectal bleeding. We observed histopathological changes of colon tissue between the DSS-treatment and control groups, however, without statistical significance. The MC extract treatment reduced the damage to the colonic tissue evidenced by a decreased of inflammatory cells, ulcerations, and goblet cell preservation. Conclusion MC extract reduces the clinical signs and suggests a potential anti-inflammatory effect on DSS-induced colitis.

Colorectal cancer is the third most common cancer worldwide in both sexes, with similar geographic patterns between genders. This neoplasm has good prognosis if the disease is diagnosed at early stages. The aim of this study was to evaluate the effect of red grape juice on the expression of COX-2 and Ki-67 expression following colon carcinogenesis induced by azoxymethane (AOM). Thirty-five rats were randomly distributed into seven groups (n=5 per group): G1: SHAM or negative control received only saline; G2 (positive control): animals received 15 mg/kg AOM; G3: animals received 1% red grape juice 2 weeks before the administration of AOM; G4: animals received 2% red grape juice 2 weeks before the administration of AOM; G5: animals received 1% red grape juice 4 weeks after the last administration of AOM; G6: animals received 2% red grape juice 4 weeks after the last administration of AOM; G7: animals received only 2% red grape juice. COX-2 mRNA expression was reduced in animals treated with 1% red grape juice before AOM induction or 2% red grape juice after AOM induction. COX-2 immunoexpression was also reduced to groups treated with red grape juice at 1% before and after AOM induction or 2% red grape juice after AOM induction. Decreased immunoexpression of Ki-67 positive cells was observed in animals treated with 1% grape juice before AOM-treated animals. Taken together, grape juice concentrate is able to exert some chemopreventive activity on rat colon carcinogenesis.

Objectives The aim of this study was to evaluate the preventive effects of extra virgin olive oil (EVOO) or flaxseed oil (FO) on dextran sodium sulfate (DSS)–induced acute ulcerative colitis in female mice. Methods Eighty C57BL/6J mice of 8-weeks-old were divided in four groups: Control (SO), 10%EVOO, 10%FO and 5%EVOO+5%FO. The oils were given through the AIN-93M diet. After 30 days, animals were divided in four more groups, in which half received 3%DSS in water for 5 days. Body weight loss, bleeding and stool consistency were verified for the Disease Activity Index (DAI). Animals were euthanized and their colon and spleen weighted and measured. Histopathological analysis, the concentrations of TNF-α, IL-1β, and IL-10 and the iNOS expression were evaluated in the colon samples. Results Animals that received DSS presented with elevated disease activity index values; increased colon weight-to-length ratio; augmented leukocyte infiltration into the lamina propria and submucosa; and increased production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, and greater inducible nitric oxide synthase expression in the distal colon. Individually or in combination, the oils were not able to reverse or mitigate any of the DSS-induced symptoms or damage. Additionally, the group of animals treated with DSS and supplemented with FO displayed increased spleen weight-to-body weight ratio, and the group that received a combination of EVOO and FO presented increased TNF-α levels compared with the respective control group. Conclusion Consumption of large amounts of EVOO and FO as a treatment for or prevention against ulcerative colitis could potentially elicit unwanted adverse effects.

The objective of this study was to evaluate the action of soy isoflavones and 17 beta estradiol on the extracellular matrix in the uterus and mammary gland of diabetic rats. Sixty adult female rats underwent ovariectomy, then randomized into seven groups of ten animals each: Non-diabetic: GI Sham control animals ovariectomized; and GII control ovariectomized that received propylene glycol vehicle. Diabetic: GIII Sham control diabetic animals ovariectomized; GIV ovariectomized diabetic animals receiving propylene glycol vehicle; GV diabetic ovariectomized animals treated with soy isoflavones (150 mg/kg by gavage); GVI ovariectomized diabetic rats treated with estrogen (17b-estradiol, 10 mg/kg, subcutaneously); GVII diabetic ovariectomized animals treated with soy isoflavones (150 mg/kg by gavage), and with estrogen (17b-estradiol, 10 mg/kg combination therapy). Treatments occurred during 30 consecutive days. After animals euthanasia, a portion of the uterus was immersed in liquid nitrogen for molecular biology analysis, the other portion of uterus and mammary glands were removed and processed for paraffin embedding. Soy isoflavones (GV) and 17b estradiol improved the production of compounds of extracellular matrix, such as small leucine-rich proteoglycans (SLRPs). The combination of both therapies had an additive effect in SLRPs expression. Soy isoflavones contribute to the uterine integrity of SLRPs of diabetic rats.

The aim of this study was to evaluate if grape juice concentrate is able to protect against experimental colon carcinogenesis.For this purpose, a total of 35 male Wistar rats were randomly distributed into seven groups: G1: SHAM animals receiving only saline; G2: animals receiving 15 mg/kg azoxymethane (AOM); G3: animals receiving 1% grape juice concentrate 2 weeks before the administration of AOM; G4: animals receiving 2% grape juice concentrate 2 weeks before the administration of AOM; G5: animals receiving 1% grape juice concentrate 4 weeks after the last administration of AOM; G6: animals receiving 2% grape juice concentrate 4 weeks after the last administration of AOM; G7: animals receiving only 2% grape juice concentrate.The group that received 2% grape juice concentrate before induction with AOM showed the decreased expression of Bcl-2 compared to those animals that were induced by AOM (positive control). Regarding Bax, animals that received grape juice at 2% decreased Bax immunoexpression when compared to AOM group. Furthermore, animals that intake grape juice at 1% after induced by AOM decreased Bax immunoexpression as well. 8-OHdGLI did not show significant statistically differences (p 0.05) among groups.In summary, our results demonstrate that grape juice is able to modulate rat colon carcinogenesis as a result of induction of apoptosis.

The aim of this study was to evaluate the preventive and/or protective action of Mimosa caesalpiniifolia (M. caesalpiniifolia) following experimental colitis in rats. The rats were randomized into ten groups (n=10 per group), as follows: G1 – Sham group:; G2 – TNBS group; G3, G4 –colitis and treated with hydroalcoholic extract of M. caesalpiniifolia 250 mg/kg/day after and before/after inducing colitis, respectively; G5, G6 – colitis and treated with hydroalcoholic extract of M. caesalpiniifolia at 125 mg/kg/day after and before/after inducing colitis respectively; G7,G8 – colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively; G9,G10 – colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively. Rats treated with hydroalcoholic extract of M. caesalpiniifolia for both doses showed lower tissue damage in the distal colon. Ethylacetate fraction was effective at the highest dose only when administrated after inducing colitis. A downregulation of COX-2 was detected to rats suffering colitis and treated with M. caesalpiniifolia at high dose. On the other hand, TNF-alpha immunoexpression decreased in groups treated with M. caesalpiniifolia at low dose after inducing colitis. In summary, our results suggest that M. caesalpiniifolia attenuated the lesions of the colon, reduced inflammation, and modulates the expression of COX-2 and TNF-α during chronic colitis induced by TNBS when using for therapeutic purposes on a dose-dependent manner.

Inflammatory bowel disease (IBD) is a common chronic gastrointestinal disorder characterized by alternating periods of remission and active intestinal inflammation. Flavonoids exert several biological activities, which are mainly related to their ability to inhibit inflammatory process and/or to their antioxidant properties, and are able to regulate the immune response. The aim of this study was to evaluate whether phenolic compounds present in grape juice could reduce the inflammatory effects induced by experimental colitis. A total of 41 male Wistar rats were randomized into seven groups, as follows: G1--Sham group: sham induced-colitis rats; G2--(2,4,6-rinitrobenzenesulfonic acid) TNBS group: nontreated induced-colitis; G3--2% grape juice control group; G4--1% grape juice 24h after TNBS colitis induction; G5--1% grape juice on day 7 after colitis induction; G6--2% grape juice 24h after colitis induction; G7--2% grape juice on day 7 after colitis induction. Genotoxicity was evaluated by comet assay. Immunohistochemistry was determined using the streptavidin-biotin-peroxidase method being analyzed in control (normal tissue) and "hot spot" areas i.e., presenting inflammatory process being graded as 1 (weak), 2 (moderate), or 3 (strong). Both parameters were evaluated in the cytoplasm of epithelial or inflammatory cells. TNF-immunoexpression and iNOS were reduced after drinking grape juice 24 h or after 7 days for all doses tested. COX-2 was reduced in the groups exposed to 1% grape juice 24 h or 7 days of exposure. The grape juice at 1% dose in the last 7 days of treatment as well as grape juice at 2% dose decreased the peripheral blood genotoxicity. Taken together, the grape juice mainly at 1% dose exerts anti-inflammatory effects in chronic colitis caused by TNBS as a result of down regulation in the expression of pro-inflammatory cytokines and reduction of genotoxicity in peripheral blood cells.

Reactive oxygen and nitrogen species (ROS/RNS) play a crucial role in inflammatory bowel disease (IBD) exacerbating the chronic inflammatory process. Endogenous and diet antioxidants can neutralize these compounds. The apple is widely consumed, with several antioxidant activity compounds. The present study evaluated the effects of concentrated apple extract (CAE) in acetic acid induced colitis. 29 Wistar male rats were randomized into 5 groups. G1–Sham/saline solution, G2–CAE/control, G3–acetic acid/control, G4–curative- CAE treatment and G5–preventive-CAE treatment. Eight days later, the animals were euthanized and the colonic segment resected for macroscopic and histological analysis. Gene expression was evaluated for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), catalase and copper and zinc superoxide dismutase (CuZnSOD) by quantitative real time PCR, while protein expression was assessed for iNOS, COX-2 and 8-hydroxy-20-deoxyguanosine (8-OHdG) via immunohistochemistry. The groups G3, G4 and G5 had weight loss, while G5 had weight increase at the end of the experiment. The treatment with CAE reduced the macroscopic and microscopic injury, decreased iNOS mRNA expression and increased CuZnSOD mRNA expression in animals with induced acetic acid-colitis. The findings of the present study suggest that CAE treatment exerts an antioxidant role by downregulating iNOS and upregulating CuZnSOD.

Melatonin has been described as a protective agent against cell death and oxidative stress in different tissues, including in the reproductive system. However, the information on the action of this hormone in rat uterine apoptosis is low. Our objective was to evaluate the effects of melatonin on mechanisms of cell death in uterus of rats exposed to continuous light stress. Twenty adult Wistar rats were divided into two groups: GContr (vehicle control) and GExp which were treated with melatonin (0.4 mg/mL), both were exposed to continuous light for 90 days. The uterus was removed and processed for quantitative real time PCR (qRT-PCR), using PCR-array plates of the apoptosis pathway; for immunohistochemistry and TUNEL. The results of qRT-PCR of GEXP group showed up-regulation of 13 and 7, pro-apoptotic and anti-apoptotic genes, respectively, compared to GContr group. No difference in pro-apoptotic proteins (Bax, Fas and Faslg) expression was observed by immunohistochemistry, although the number of TUNEL-positive cells was lower in the group treated with melatonin compared to the group not treated with this hormone. Our data suggest that melatonin influences the mechanism and decreases the apoptosis in uterus of rats exposed to continuous light.

Inflammatory bowel disease (IBD) is a common chronic gastrointestinal disorder characterized by alternating periods of remission and active intestinal inflammation. Some studies suggest that antiinflammatory drugs are a promising alternative for treatment of the disease. Thus, this study aimed to evaluate the effect of lumiracoxib, a selective-cyclooxygenase-2 (COX-2) inhibitor, on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. Wistar rats (n = 25) were randomized into four groups, as follows: Group (1) Sham group: sham induced-colitis rats; Group (2) TNBS group: nontreated induced-colitis rats; Group (3) Lumiracoxib control group; and Group (4) Lumiracoxib-treated induced-colitis rats. Our results showed that rats from groups 2 and 4 presented similar histopathological damage and macroscopic injury in the distal colon as depicted by significant statistically differences (P < 0.01; P < 0.05) compared to the other two groups. Weak expression of COX-2 mRNA was detected in normal colon cells, while higher levels of COX-2 mRNA were detected in group 2 and group 4. Therapy with lumiracoxib reduced COX-2 expression by 20–30%, but it was still higher and statistically significant compared to data obtained from the lumiracoxib control group. Treatment with the selective COX-2 inhibitor lumiracoxib did not reduce inflammation-associated colonic injury in TNBS-induced experimental colitis. Thus, the use of COX-2 inhibitors for treating IBD should be considered with caution and warrants further experimental investigation to elucidate their applicability.

The aim of this study was to evaluate the effects of grape juice on colon carcinogenesis induced by azoxymethane (AOM) and expression of NF-kB, iNOS and TNF- α. Methods: Forty male Wistar rats were divided into 7 groups: G1, control; G2, 15 mg/kg AOM; G3, 1% grape juice 2 weeks before AOM; G4, 2% grape juice 2 weeks before AOM; G5, 1% grape juice 4 weeks after AOM; G6, 2% grape juice 4 weeks after AOM; G7, 2% grape juice without AOM. Histological changes and aberrant crypt foci (ACF) were studied, while RNA expression of NF-kB, TNF- and iNOS was evaluated by qPCR. Results: The number of ACF was higher in G2, and G4 presented a smaller number of crypts per focus than G5 (p=0.009) and G6. Small ACF (1-3) were more frequent in G4 compared to G2, G5 and G6 (p=0.009, p=0.009 and p=0.041, respectively). RNA expression of NF-kB was lower in G3 and G4 compared to G2 (p=0.004 and p=0.002, respectively). A positive correlation was observed between TNF- α and NF-kB gene expression (p=0.002). In conclusion, the administration of 2% grape juice before AOM reduced the crypt multiplicity, attenuating carcinogenesis. Lower expression of NF-kB was observed in animals exposed to grape juice for a longer period of time, regardless of concentration. Keywords: Grape juice - NF-kappa B - TNF-α - iNOS - carcinogenesis

Chronic inflammatory bowel disease is characterised by an up-regulation of the synthesis and release of a variety of pro-inflammatory mediators leading to excessive tissue injury. Flavonoids are able to inhibit enzymes and/or due to their antioxidant properties regulate the immune response. The goal of the present study was to evaluate the mechanisms of action of phenolic compounds present in grape juice on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. A total of forty-one male Wistar rats were randomised into seven groups: negative control group; TNBS non-treated induced colitis; 2 % grape juice control group; 1 % grape juice 24 h after TNBS colitis induction; 1 % grape juice on day 7 after colitis induction; 2 % grape juice 24 h after colitis induction; 2 % grape juice on day 7 after colitis induction. The 1 % grape juice-treated induced colitis group showed marked clinical improvement when compared with the TNBS-induced colitis group. Rats that received 1 % grape juice, on day 7 after colitis induction, presented reduced intensity of macroscopic and histological scores. Statistically significant differences (PTNF-α and inducible NO synthase mRNA expression were detected in the groups treated with grape juice at the 1 % dose after inducing experimental colitis when compared with the TNBS group. Grape juice reduced the noxious effects induced by colitis caused by TNBS, especially at the 1 % dose.

The nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used in the management of pain and inflammation. Unfortunately, they are associated with dose-dependent gastrointestinal (GI) adverse events ranging from dyspepsia to symptomatic and complicated ulcers. The mechanism of NSAID action is attributed to the cyclooxygenase (COX) inhibition. New anti-inflammatory drugs have been synthesized, such as selective COX-2 inhibitors, however, these drugs may present side effects, such as modification of the epithelial barrier. Inflammatory bowel disease (IBD) is a common chronic gastrointestinal disorder characterized by alternating periods of remission and active intestinal inflammation. A possible association between the use of NSAIDs and the relapse of IBD has been repeatedly suggested. For this reason, many studies are conducted with the use of COX-2 in experimental models. The objective of this review is to describe the role of NSAIDs and COX-2 inhibitors in different experimental models of colitis. We reviewed controlled trials, original articles, case reports and reviews. The role of selective inhibition of COX-2 in the inflammatory process and the course of experimental and human colitis is controversially discussed. In conclusion, the relative role of COX-2 selective inhibitors on human and experimental colitis remains to be explored. Thus, the use of COX-2 inhibitors in IBD should be considered with caution.

Tissue repair is an excellent example of pathophysiological model for studying the role of cyclooxygenase-2 (COX-2) on eukaryotic cells. It has been established that two COX isoforms are expressed in human tissues: constitutive or induced. COX-1 activity is constitutive, present in nearly all cell types at a constant level; COX-2 activity is normally absent from cells, and when induced, the protein levels increase and decrease in a matter of hours after a single stimulus. Thus, the purpose of this review was to describe the role of COX-2 during tissue repair induced by low level laser therapy (LLLT) in humans and experimental models. COX-2 expression has been implicated in the onset or the exacerbation of inflammation during tissue repair induced by LLLT in a number of studies, Many studies are conducted to investigate the role of COX-2 during tissue repair induced by LLLT using different experimental protocols and dosages. Therefore, this is an area that warrants investigation, since the estimation of COX-2 expression from using such important techniques in therapeutics with respect to tissue repair will be added to those already established in the literature as a way to improve health status and prevention of side effects.

Since the introduction of acetylsalicylic acid (aspirin) as the first nonsteroidal antiinflammatory drug (NSAID) in 1897, NSAIDs have been widely used in the management of pain and inflammation (Botting, 2010; Vane et al., 1990; Wallace, 1997). Today, they are classified as traditional nonsteroidal antiinflammatory drugs (tNSAIDs), characterized by differing degrees of antiinflammatory, analgesic and antipyretic activity. tNSAIDs are among the most widely used medicines in the world. Unfortunately, they are associated with dose-dependent gastrointestinal (GI) adverse events ranging from dyspepsia (10-20%) to symptomatic and complicated ulcers (1-4%) (Scheiman, 2006; Wolfe et al., 1999). The mechanism of tNSAIDs action is attributed to the cyclooxygenase (COX) inhibition (Botting, 2010; Vane, 1971). Cyclooxygenase is a key rate-limiting enzyme that exists in at least two isoforms: COX-1 is observed constitutively expressed in various tissues, whereas COX-2 does not appear to be expressed except at very low levels in most tissues and is rapidly upregulated in response to growth factors and cytokines. More recently, COX-2 has been implicated in several distinct cellular mechanisms, such as angiogenesis, proliferation and the prevention of apoptosis (Dempke et al., 2001). New antiinflammatory drugs have been synthesized, such as selective COX-2 inhibitors (anti-COX-2), however, these drugs may present side effects, such as the ability to modify the epithelial barrier. Inflammatory bowel disease (IBD) is a common chronic gastrointestinal disorder characterized by alternating periods of remission and active intestinal inflammation. The precise etiology of IBD, including Crohn s disease (CD) and ulcerative colitis (UC), remains unclear. However, environmental factors, immunological disturbances, genetic influences and the presence of certain chemical mediators (cytokines) have been established as putative participants in the pathogenesis of the disease (Barbieri, 2000; Lashner, 1995; Podolsky, 2002). In the last few decades, the development of experimental models for studying IBD has greatly contributed to enhance understanding of the immunological mechanisms involved, such as changes in the gut epithelial barrier (Colpaert et al, 2001; Shorter et al, 1972). IBD seems to occur when luminal antigens from the bacterial flora stimulate the immune system

Crohn’s disease (CD) is associated with gut barrier dysfunction. Besides the baseline barrier defect, a subgroup of patients also expresses an intestinal barrier hyperresponsiveness to nonsteroidal anti-inflammatory drugs. On the other hand, the anti-tumour necrosis factor alpha (TNF-α) treatment has brought benefits to these patients. Thus, this study aimed to evaluate the effect of lumiracoxib, a selective-cyclooxygenase-2 (COX-2) inhibitor, and Etanercept (ETC), a TNF-α antagonist on the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. A total of 47 Wistar rats were randomized into seven groups, as follows: (1) Sham: sham induced-colitis; (2) TNBS: nontreated induced-colitis; (3) Lumiracoxib control; (4) Lumiracoxib-treated induced-colitis; (5) ETC control; (6) ETC-treated induced-colitis; (7) Lumiracoxib-ETC-treated induced-colitis. Rats from groups 6 and 7 presented significant improvement of macroscopic and histopathological damages in the distal colon. The gene expression of COX-2 mRNA, as well of TNF-α mRNA, decreased significantly in groups 6 and 7 compared to the TNBS nontreated and lumiracoxib-treated groups. The treatment only with lumiracoxib did not reduce the inflammation on TNBS-induced experimental colitis. ETC attenuated the damage seen in the colon and reduced the inflammation caused by TNBS. Our results suggest that down-regulation of TNF-α and COX-2 resulted in a decrease in inflammation caused by TNBS and thus provided some protection from the colonic damage caused by TNBS.

Crohn′s disease (CD) is associated with gut barrier dysfunction. Tumour necrosis factor-α (TNF-α) plays an important role into the pathogenesis of several inflammatory diseases because its expression is increased in inflamed mucosa of CD patients. Anti-TNF therapy improves significantly mucosal inflammation. Thus, this study aimed to evaluate the effect of Etanercept (ETC), a tumour necrosis factor alpha (TNF-α) antagonist on the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. A total of 18 Wistar rats were randomized into four groups, as follows: (1) Sham: sham induced-colitis; (2) TNBS: non-treated induced-colitis; (3) ETC control; (4) ETC-treated induced-colitis. Rats from group 4 presented significant improvement either of macroscopic or of histopathological damage in the distal colon. The gene expression of TNF-α mRNA, decreased significantly in this group compared to the TNBS non-treated group. The treatment with etanercept attenuated the colonic damages and reduced the inflammation caused by TNBS. Taken together, our results suggest that ETC attenuates intestinal colitis induced by TNBS in Wistar rats by TNF-α downregulation.

Ulcerative colitis (UC) is a disease of the colon and rectum characterized by a nonspecific chronic inflammation mediated by the concerted response of cellular and humoral events. Prostaglandins are synthesized by cyclooxygenase (COX)-1 and -2 and exhibit both pro- and anti-inflammatory activity. To evaluate COX-1 and COX-2 immunoexpression in 42 cases of UC and to correlate it with clinicopathological parameters, COX-1 and COX-2 expression was investigated by the immunohistochemistry method. Only patients with all pertinent clinical and evolutive data as well as with adequate biopsy material were included in the study. Fifteen samples of colorectal adenocarcinoma and 14 of large bowel with no histological changes were used for positive and negative controls, respectively. UC patients showed COX-1 immunoreactivity in epithelial cells in 29% of the cases and in inflammatory cells in 43%. COX-2 positivity in epithelial and inflammatory cells was found in 69% of the samples. The comparison between UC and the control groups revealed that the UC group had significantly more positive cases for COX-1 and COX-2 in inflammatory cells. Immunohistochemistry allowed the identification of COX-1 and COX-2 expression in epithelial and inflammatory cells in UC biopsies. No significant difference between COX-1 and COX-2 immunoreactivity in epithelial and inflammatory cells was observed regarding the clinicopathological parameters. COX-2 presented low expression in normal colon and high expression in colorectal adenocarcinoma. COX-2 might play a role in the pathophysiologic processes of inflammatory bowel disease and the development of neoplasia. Treatment with selective COX-2 inhibitors might be an additional option for therapy. Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Patologia Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina UNIFESP, EPM, Depto. de Patologia UNIFESP, EPM SciELO