Effects of polyphenolic maqui (Aristotelia chilensis) extract on the inhibition of NLRP3 inflammasome and activation of mast cells in a mouse model of Crohn's disease-like colitis.

Introduction: Crohn's disease (CD) involves activation of mast cells (MC) and NF-кB in parallel with the PPAR-α/NLRP3 inflammasome/IL-1ß pathway in the inflamed colon. Whether polyphenols from maqui (Aristotelia chilensis) represent a natural alternative treatment for CD is unclear. Therefore, we used an animal model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD-like colitis to investigate protective effects of maqui extract through monitoring NLRP3 inflammasome and MC activation in colon tissue. Methods: Maqui extract was administered via orogastric route to mice after (post-Treatment group) or prior (pre-Treatment group) to TNBS-induction. Colon pathology was characterized by histoarchitectural imaging, disease activity index (DAI), and assessing NF-кB, p-NF-кB, PPAR-α/NLRP3 expression and IL-1ß levels. Results: Compared to mice treated with TNBS alone administration of anthocyanin-rich maqui extract improved the DAI, colon histoarchitecture and reduced both colon wet-weight and transmural inflammation. Induction with TNBS significantly increased colonic NLPR3 inflammasome activation, while co-treatment with maqui extract (either post- or pre-Treatment) significantly downregulated NLRP3, ASC and caspase-1 levels, which manifested as reduced colonic IL-1ß levels. Supplemented maqui extract marginally diminished NF-кB activity in epithelial cells but reached statistical significance in immune cells (as judged by decreased NF-кB phosphorylation). PPAR-α signaling was largely unaffected by Maqui whereas MC infiltration into the colon mucosa and submucosa decreased and their level of degranulation was suppressed. Conclusion: These outcomes show the post- and pre- Treatment effect of a polyphenolic extract rich in anthocyanins from maqui the acute phase of TNBS- induced CD-like colitis is linked to suppression of the NLRP3 inflammasome and reduced MC responses. These data indicate that maqui extract represents a potential nutraceutical for the treatment of inflammatory bowel disease (IBD).

Native Chilean Berries Preservation and In Vitro Studies of a Polyphenol Highly Antioxidant Extract from Maqui as a Potential Agent against Inflammatory Diseases.

The best conservation method for native Chilean berries has been investigated in combination with an implemented large-scale extract of maqui berry, rich in total polyphenols and anthocyanin to be tested in intestinal epithelial and immune cells. The methanolic extract was obtained from lyophilized and analyzed maqui berries using Folin-Ciocalteu to quantify the total polyphenol content, as well as 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC) to measure the antioxidant capacity. Determination of maqui's anthocyanins profile was performed by ultra-high-performance liquid chromatography (UHPLC-MS/MS). Viability, cytotoxicity, and percent oxidation in epithelial colon cells (HT-29) and macrophages cells (RAW 264.7) were evaluated. In conclusion, preservation studies confirmed that the maqui properties and composition in fresh or frozen conditions are preserved and a more efficient and convenient extraction methodology was achieved. In vitro studies of epithelial cells have shown that this extract has a powerful antioxidant strength exhibiting a dose-dependent behavior. When lipopolysaccharide (LPS)-macrophages were activated, noncytotoxic effects were observed, and a relationship between oxidative stress and inflammation response was demonstrated. The maqui extract along with 5-aminosalicylic acid (5-ASA) have a synergistic effect. All of the compiled data pointed out to the use of this extract as a potential nutraceutical agent with physiological benefits for the treatment of inflammatory bowel disease (IBD).

Polyphenolic Maqui Extract as a Potential Nutraceutical to Treat TNBS-Induced Crohn's Disease by the Regulation of Antioxidant and Anti-Inflammatory Pathways.

Nutraceuticals include a wide variety of bioactive compounds, such as polyphenols, which have been highlighted for their remarkable health benefits. Specially, maqui berries have shown great antioxidant activity and anti-inflammatory effects on some inflammatory diseases. The objectives of the present study were to explore the therapeutic effects of maqui berries on acute-phase inflammation in Crohn's disease. Balb/c mice were exposed to 2,4,6-trinitrobenzene sulfonic acid (TNBS) via intracolonic administration. Polyphenolic maqui extract (Ach) was administered orally daily for 4 days after TNBS induction (Curative Group), and for 7 days prior to the TNBS induction until sacrifice (Preventive Group). Our results showed that both preventive and curative Ach administration inhibited body weight loss and colon shortening, and attenuated the macroscopic and microscopic damage signs, as well as significantly reducing transmural inflammation and boosting the recovery of the mucosal architecture and its muco-secretory function. Additionally, Ach promotes macrophage polarization to the M2 phenotype and was capable of down-regulating significantly the expression of inflammatory proteins COX-2 and iNOS, and at the same time it regulates the antioxidant Nrf-2/HO-1 pathway. In conclusion, this is the first study in which it is demonstrated that the properties of Ach as could be used as a preventive and curative treatment in Crohn's disease.

Preparations for colon capsule endoscopy. Prospective and randomized comparative study between two preparations for colon capsule endoscopy: PEG 2 liters + ascorbic acid versus PEG 4 liters.

INTRODUCTION: PillCam© colon capsule endoscopy (CCE) enables the study of colonic diseases in a safe and non-invasive way, although there are aspects that need to be improved. Current methods of bowel preparation lead to discordant rates of adequate cleansing and CCE excretion. AIMS: To compare the efficacy of colon cleansing using two different regimes (2L PEG plus ascorbic acid versus 4L PEG alone) for PillCam Colon (C2) capsule endoscopy. METHODS: Fifty eight patients included in this prospective study and randomized to: Group A, PEG plus ascorbic acid regimen (n = 28, 12 F/16 M) or group B, PEG alone regimen (n = 30, 14 F/16 M). The degree of cleansing was categorized into "excellent-good" or "fair-poor", according to Leighton´s recently published preparation scale. CCE excretion rate and colon cleansing were assessed. Patients underwent to PillCam colon of second generation (C2). RESULTS: Cleansing was considered to be excellent-good in 78 % of cases in group A and in 64 % of cases in group B, with no significant difference between the groups (p = 0.252). Nevertheless, when the grade of cleansing was analyzed in segments, a significant difference was found in the cecum and transverse colon. No differences were observed in the bubble effect between preparations. The excretion rate was 93 % in group A versus 70 % in group B (p = 0.043). CONCLUSIONS: These results suggest that a 2L PEG plus ascorbic acid regimen is at least as effective as a 4L PEG regimen. This regimen may be considered an effective alternative which would improve compliance because a smaller volume is required.

Capsule endoscopy in patients refusing conventional endoscopy.

Capsule endoscopy is nowadays the diagnostic technique of choice in the study of small bowel pathologies, allowing the non-invasive study of the entire mucosa. This has led, together with new technical advances, to the creation of two new models (PillCam ESO and PillCam Colon) for the study of esophageal and colonic diseases. These two new capsules offer an interesting alternative to conventional endoscopy in the study of the upper and lower digestive tracts, because traditional endoscopy is often unpleasant and uncomfortable for the patient, can be painful, often requires moderate or deep sedation and is not without complications (hemorrhage, perforation, etc.). PillCam Colon is particularly important for its usefulness in the diagnosis of colonic polyps, and is a potentially useful tool in cases of incomplete colonoscopy or in colorectal cancer screening, even more when most patients are reluctant to undergo screening programs due to the said disadvantages of conventional colonoscopy. This article discusses the advantages of capsule endoscopy over conventional endoscopy, its current application possibilities and indications in routine clinical practice. In the various sections of the work, we assess the application of endoscopic capsule in different sections of the digestive tract (esophagus, stomach, and colon) and finally the potential role of panendoscopy with PillCam Colon.

Preparations for colon capsule endoscopy. Prospective and randomized comparative study between two preparations for colon capsule endoscopy: PEG 2 liters + ascorbic acid versus PEG 4 liters / Preparaciones para endoscopia del colon con cápsula. Estudio prospectivo, aleatorio y comparativo entre dos preparaciones del colon para cápsula endoscópica: 2 litros PEG + ácido ascórbico versus 4 litros PEG

Introduction: PillCam© colon capsule endoscopy (CCE) enables the study of colonic diseases in a safe and non-invasive way, although there are aspects that need to be improved. Current methods of bowel preparation lead to discordant rates of adequate cleansing and CCE excretion. Aims: To compare the efficacy of colon cleansing using two different regimes (2L PEG plus ascorbic acid versus 4L PEG alone) for PillCam Colon (C2) capsule endoscopy. Methods: Fifty eight patients included in this prospective study and randomized to: Group A, PEG plus ascorbic acid regimen (n = 28, 12 F/16 M) or group B, PEG alone regimen (n = 30, 14 F/16 M). The degree of cleansing was categorized into "excellentgood" or "fair-poor", according to Leighton's recently published preparation scale. CCE excretion rate and colon cleansing were assessed. Patients underwent to PillCam colon of second generation (C2). Results: Cleansing was considered to be excellent-good in 78 % of cases in group A and in 64 % of cases in group B, with no significant difference between the groups (p = 0.252). Nevertheless, when the grade of cleansing was analyzed in segments, a significant difference was found in the cecum and transverse colon. No differences were observed in the bubble effect between preparations. The excretion rate was 93 % in group A versus 70 % in group B (p = 0.043). Conclusions: These results suggest that a 2L PEG plus ascorbic acid regimen is at least as effective as a 4L PEG regimen. This regimen may be considered an effective alternative which would improve compliance because a smaller volume is required (AU)

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Capsule endoscopy in the small bowel Crohn's disease.

CD is a chronic inflammatory disorder associated to mucosal and transmural inflammation of the bowel wall. It is well known that CD can affect the entire gastrointestinal. Therefore, ileocolonoscopy and biopsies of the terminal ileum as well as of each colonic segment to look for microscopic evidence of CD are the first-line procedures to establish the diagnosis. However, it has been observed that up to 30% of the patients have only small bowel involvement. Evaluation of the small bowel has been made with radiological procedures, barium radiography, and abdominal computed tomography or by ileocolonoscopy or enteroscopy, but they have many recognized limitations. CE is undoubtedly a very useful diagnostic tool proposed to observe small-bowel lesions undetectable by conventional endoscopy or radiologic studies. We review different studies that have been published reporting the use of CE in suspected and evaluation of the extension or the recurrence in CD and also its use in pediatric population and its complications.

Application of colon capsule endoscopy (CCE) to evaluate the whole gastrointestinal tract: a comparative study of single-camera and dual-camera analysis.

BACKGROUND AND STUDY AIMS: Colon capsule endoscopy (CCE) was developed for the evaluation of colorectal pathology. In this study, our aim was to assess if a dual-camera analysis using CCE allows better evaluation of the whole gastrointestinal (GI) tract compared to a single-camera analysis. PATIENTS AND METHODS: We included 21 patients (12 males, mean age 56.20 years) submitted for a CCE examination. After standard colon preparation, the colon capsule endoscope (PillCam Colon™) was swallowed after reinitiation from its "sleep" mode. Four physicians performed the analysis: two reviewed both video streams at the same time (dual-camera analysis); one analyzed images from one side of the device ("camera 1"); and the other reviewed the opposite side ("camera 2"). We compared numbers of findings from different parts of the entire GI tract and level of agreement among reviewers. RESULTS: A complete evaluation of the GI tract was possible in all patients. Dual-camera analysis provided 16% and 5% more findings compared to camera 1 and camera 2 analysis, respectively. Overall agreement was 62.7% (kappa = 0.44, 95% CI: 0.373-0.510). Esophageal (kappa = 0.611) and colorectal (kappa = 0.595) findings had a good level of agreement, while small bowel (kappa = 0.405) showed moderate agreement. CONCLUSION: The use of dual-camera analysis with CCE for the evaluation of the GI tract is feasible and detects more abnormalities when compared with single-camera analysis.

Esophageal capsule endoscopy in patients refusing conventional endoscopy for the study of suspected esophageal pathology.

AIM: Esophageal capsule endoscopy is a well tolerated procedure that does not require sedation and has proved its value for the study of the esophagus. The aim of our study was to assess the feasibility, accuracy, safety and acceptability of esophageal capsule endoscopy for the study of gastroesophageal reflux disease and esophageal varices in patients who refused conventional upper gastrointestinal endoscopy. PATIENTS AND METHODS: Thirty consecutive examinations performed in 28 patients (15 men/13 women; mean age: 58.5+/-12.4 years; range: 23-87 years) were reviewed. Twenty-five examinations were performed in 23 patients presenting with chronic gastroesophageal reflux disease symptoms and the remaining five were carried out in patients with cirrhosis for screening of esophageal varices. The procedures were done with the new PillCam ESO that harbors two viewing cupules and takes a total of 14 frames/s. Technical data (total recording time, esophageal transit time and Z-line visualization), clinical findings (Savary-Miller grade; presence and characteristics of esophageal varices or portal hypertension gastropathy), and patient's opinion (quality and comfort questionnaire) were analyzed. RESULTS: All the patients ingested and excreted the capsule without complications. Two examinations in the gastroesophageal reflux disease group were repeated; one was issued as a follow-up and the other because no images were recorded in the first capsule endoscopy. From the former, only the satisfaction questionnaire was analyzed. Mean total recording time and esophageal transit time were 1224 and 243.79 s, respectively (range: 2-1192 s). Complete study of the Z-line was possible in 23 examinations (23/29; 79.3%). Esophageal erosions were seen in 58.33% (14/24) of the examinations carried out in patients with gastroesophageal reflux disease. Nine out of 14 patients (64.29%) presented with grade I esophagitis and the other five (35.71%) with grade II esophagitis. Among the five patients with cirrhosis, small varices were visualized in one (1/5; 20%), while large varices with red spots were evidenced in the remaining three (3/5; 60%). All four patients showing esophageal varices were found to have portal hypertension gastropathy. In most examinations, patients found the capsule easy to swallow (28/30; 93.33%), asymptomatic (29/30; 96.66%), evaluated the procedure as comfortable (29/30; 96.66%), and would repeat it if necessary (30/30; 100%). CONCLUSIONS: Esophageal capsule endoscopy is an adequate alternative diagnostic method for the study of gastroesophageal reflux disease and for the screening of esophageal varices in patients refusing to undergo conventional upper gastrointestinal endoscopy.