A pilot study of transrectal endoscopic ultrasound elastography in inflammatory bowel disease

BACKGROUND: Using standard diagnostic algorithms it is not always possible to establish the correct phenotype of inflammatory bowel disease which is essential for therapeutical decisions. Endoscopic ultrasound elastography is a new endoscopic procedure which can differentiate the stiffness of normal and pathological tissue by ultrasound. Therefore, we aimed to investigate the role of transrectal ultrasound elastography in distiction between Crohn's disease and ulcerative colitis. ----- METHODS: A total 30 Crohn's disease, 25 ulcerative colitis, and 28 non-inflammatory bowel disease controls were included. Transrectal ultrasound elastography was performed in all patients and controls. In all ulcerative coltis patients and 80% of Crohn's disease patients endoscopy was performed to assess disease activity in the rectum. ----- RESULTS: Significant difference in rectal wall thickness and strain ratio was detected between patients with Crohn's disease and controls (p = 0.0001). CD patients with active disease had higher strain ratio than patients in remission (p = 0.02). In ulcerative colitis group a significant difference in rectal wall thickness was found between controls and patients with active disease (p = 0.03). A significant difference in rectal wall thickness (p = 0.02) and strain ratio (p = 0.0001) was detected between Crohn's disease and ulcerative colitis patient group. Crohn's disease patients with active disease had a significantly higher strain ratio compared to ulcerative colitis patients with active disease (p = 0.0001). ----- CONCLUSION: Transrectal ultrasound elastography seems to be a promising new diagnostic tool in the field of inflammatory bowel disease. Further study on a larger cohort of patients is needed to definitely assess the role of transrectal ultrasound elastography in inflammatory bowel disease

Detection of epithelial apoptosis in pelvic ileal pouches for ulcerative colitis and familial adenomatous polyposis

<p>Abstract</p> <p>Background</p> <p>Ileal pouch-anal anastomosis (IPAA) is the surgical procedure of choice for patients with refractory ulcerative colitis (UC) and for familial adenomatous polyposis (FAP) with many rectal polyps. Pouchitis is one of the more frequent complications after IPAA in UC patients; however, it is rare in FAP.</p> <p>Objective</p> <p>Evaluate pro-apoptotic activity in endoscopically and histological normal mucosa of the ileal pouch in patients with UC and FAP.</p> <p>Methods</p> <p>Eighteen patients (nine with UC and nine with FAP) with J pouch after total rectocolectomy were studied. Biopsies were obtained from the mucosa of the pouch and from normal ileum. The specimens were snap-frozen and the expressions of Bax and Bcl-2 were determined by immunoblot of protein extracts and by immunohistochemistry analysis. FADD, Caspase-8, APAF-1 and Caspase-9 were evaluated by immunoprecipitation and immunoblot.</p> <p>Results</p> <p>Patients with UC had significantly higher protein levels of Bax and APAF-1, Caspase-9 than patients with FAP, but were similar to controls. The expressions of Bcl-2 and FADD, Caspase-8 were similar in the groups. Immunohistochemistry for Bax showed less intensity of immunoreactions in FAP than in UC and Controls. Bcl-2 immunostaining was similar among the groups.</p> <p>Conclusion</p> <p>Patients with FAP present lower levels of pro-apoptotic proteins in all methods applied, even in the absence of clinical and endoscopic pouchitis and dysplasia in the histological analysis. These findings may explain a tendency of up-regulation of apoptosis in UC patients, resulting in higher rates of progression to pouchitis in these patients, which could correlate with mucosal atrophy that occurs in inflamed tissue. However, FAP patients had low pro-apoptotic activity in the mucosa, and it could explain the tendency to low cell turn over and presence of adenomas in this syndrome.</p

Development of modified apple polysaccharide capped silver nanoparticles loaded with mesalamine for effective treatment of ulcerative colitis

The objective of study was to develop modified apple polysaccharide (MAP) based silver nanoparticles (AgNPs) loaded with mesalamine (MES) for effective treatment of ulcerative colitis in acetic acid induced rat model. AgNPs were prepared by reducing silver nitrate using MAP solution. The size and zeta potential of AgNPs was 89 ± 3 nm and −16.3 ± 1.54 mV and AgNPs loaded with MES (AgNPs-MES) was 101 ± 9 nm and −14.27 ± 2.16 mV. The dissolution study revealed about 54% drug release after 5 h indicating release of drug at the colonic site. The in vivo study was carried out on acetic acid induced ulcerative colitis rats and efficacy of treatment was assessed through evaluation of disease activity index and level of antioxidants as well as tumor necrosis factor-α after 7th and 14th day of induction of colitis. Histopathological evaluation of colonic tissue was also carried out. The results revealed that AgNPs-MES (high dose) provided better therapeutic efficacy for the treatment of UC as compared to its low dose, MES alone, MES-MAP, AgNPs alone and MAP alone. It was concluded that MAP based AgNPs loaded with MES were successfully formulated and found to be effective in treating ulcerative colitis

Smart gated magnetic silica mesoporous particles for targeted colon drug delivery: New approaches for inflammatory bowel diseases treatment

[EN] Magnetic mesoporous silica microparticles were loaded with safranin O (S1) and with hydrocortisone (S2) and the outer surface functionalized with a bulky azo derivative bearing urea moieties. Aqueous suspensions of both solids at pH 7.4 showed negligible payload release whereas a marked delivery was observed in the presence of sodium dithionite due to the rupture of the azo bonds. Besides, a moderate cargo release was observed at acidic pH due to the hydrolysis of the urea bonds that linked the azo derivative onto the external surface of the inorganic scaffolds. In vitro digestion models showed that S1 and S2 microparticles could be used for the controlled release of payload in the reducing colon environment (in which azoreductase enzymes are present). On the other hand, in vivo pharmacokinetic studies in rats showed that safranine O release from S1 microparticles was concentrated in colon. The performance of S2 microparticles for the treatment of colitis in rats (induced by oral administration of a 2,4,6-trinitrobenzenesulfonic acid solution) was tested. The controlled release of hydrocortisone from S2 in the colon of injured rats induced marked reduction in colon/body weight ratio and in clinical activity score. Also, histological studies showed a marked decrease in inflammation followed by intensive regeneration and almost normal mucosal structure of the individuals treated with S2. Besides, the use of a magnetic belt increased the therapeutic performances of S2 due to an enhanced retention time of the particles in the colon.We thank the Spanish Government (projects MAT2015-64139-C4-1-R and AGL2015-70235-C2-2-R (MINECO/FEDER)) and the Generalitat Valenciana (project PROMETEOII/2014/047) for support. AHT thanks to the Spanish MEC for his FPU grant. The authors also thank the Electron Microscopy Service at the Universitat Politecnica de Valencia for support. SCSIE (Universitat de Valencia) is also gratefully acknowledged for all the equipment employed. NMR was registered at the U26 facility of ICTS "NANBIOSIS" at the Universitat de Valencia. The authors thanks Dr. L. A. Villaescusa for his helpful discussion about the 1H NMR analysis of the composition of loaded and functionalized supports.Teruel, AH.; Pérez-Esteve, É.; Gonzalez-Alvarez, I.; Gonzalez -Alvarez, M.; Costero, AM.; Ferri, D.; Parra Álvarez, M.... (2018). Smart gated magnetic silica mesoporous particles for targeted colon drug delivery: New approaches for inflammatory bowel diseases treatment. Journal of Controlled Release. 281:58-69. https://doi.org/10.1016/j.jconrel.2018.05.007S586928

Clinical Diagnosis and Phar-maceutical Management of Inflammatory Bowel Disease

Inflammatory bowel disease have an enormous impact on public health, medical systems, economies, and social conditions. Biologic therapy has ameliorated the treatment and clinical course of patients with inflammatory bowel disease. The efficacy and safety profiles of currently available therapies are still less that optimal in numerous ways, highlighting the requirement for new therapeutic targets. A bunch of new drug studies are underway in inflammatory bowel disease with promising results. This is an outlined guideline of clinical diagnosis and pharmaceutical therapy of inflammatory bowel disease. Outline delineates the overall recommendations on the modern principles of desirable practice to bolster the adoption of best implementations and exploration as well as inflammatory bowel disease patient, gastroenterologist, and other healthcare provider education. Inflammatory bowel disease encompasses Crohn’s disease and ulcerative colitis, the two unsolved medical inflammatory bowel disease-subtypes condition with no drug for cure. The signs and symptoms on first presentation relate to the anatomical localization and severity of the disease and less with the resulting diagnosis that can clinically and histologically be non-definitive to interpret and establish criteria, specifically in colonic inflammatory bowel disease when the establishment is inconclusive is classified as indeterminate colitis. Conservative pharmaceuticals and accessible avenues do not depend on the disease phenotype. The first line management is to manage symptoms and stabilize active disease; at the same time maintenance therapy is indicated. Nutrition and diet do not play a primary therapeutic role but is warranted as supportive care. There is need of special guideline that explore solution of groundwork gap in terms of access limitations to inflammatory bowel disease care, particularly in developing countries and the irregular representation of socioeconomic stratification with a strategic plan, for the unanswered questions and perspective for the future, especially during the surfaced global COVID-19 pandemic caused by coronavirus SARS-CoV2 impacting on both the patient’s psychological functioning and endoscopy services. Establishment of a global registry system and accumulated experiences have led to consensus for inflammatory bowel disease management under the COVID-19 pandemic. Painstakingly, the pandemic has influenced medical care systems for these patients. I briefly herein viewpoint summarize among other updates the telemedicine roles during the pandemic and how operationally inflammatory bowel disease centers managed patients and ensured quality of care. In conclusion: inflammatory bowel disease has become a global emergent disease. Serious medical errors are public health problem observed in developing nations i.e., to distinguish inflammatory bowel disease and infectious and parasitic diseases. Refractory inflammatory bowel disease is a still significant challenge in the management of patients with Crohn’s disease and ulcerative colitis. There are gaps in knowledge and future research directions on the recent newly registered pharmaceuticals. The main clinical outcomes for inflammatory bowel disease were maintained during the COVID-19 pandemic period.</jats:p

Abstract B33: Molecular targets in early detection and differentiation of inflammatory bowel disease associated colon-rectal-anal cancer disparities.

Abstract The inflammatory bowel disease (IBD), Crohn's (CC) and ulcerative colitis (UC), affect approximately 1–2 of every 1000 people in developed countries. These chronic inflammatory diseases result in significant morbidity and mortality. All IBD-associated colorectalanal cancers (CRAC) occurred in segments of colitis and are frequently diagnosed at an advanced stage. This presentation is a continuation of our work that investigates potential molecules that could define a unique classifier between CC and UC and early detection of CRAC. There are multiple challenges to identifying protein classifiers suggesting outcome prediction and differentiation for patients with IBD and/or IBD-CRAC from molecular interpretation standpoints is complex. While there are technical approach disagreements, the goal is clear: to produce scientific evidence which can provide personalized expert care to patients. We have developed an amenable proteomic methodology that supports the diagnostic feasibility to discriminate molecularly, different inflammatory colitis. The histologic layers of colectomy samples from patients with confirmed UC and CC tissues were analyzed using matrix-assisted laser de-sorption/ionization mass spectrometry (MALDI MS) for proteomic profiling. Our previous findings1 prompted further sample collection resulting in an increased sample size that would allow a more robust analysis. The samples from colon tissues collected in 2008 and samples collected in 2010 were re-randomized into training and independent test sets in order to avoid systematic differences between new and old data sets, typical for MALD-ToF spectra acquired in situ from tissue at different times. MALDI-ToF spectra were included in the analysis only for samples containing more than 3 unique spectra. The results have successfully identified 11 highly significant mass-to-charge ratio (m/z) signals (m/z 5045, 6139, 9245, 8413, 3666, 3595, 4122, 8774, 2778, 9232 and 9519) that distinguish CC from UC. These features are independent of the tissue of origin and represent disease specific markers. Some of these signatures were only found in the colonic mucosa (m/z 8413, 3666 &amp; 3595) or submucosa (m/z 4122, 8774, 2778, 9232 &amp; 9519) while others were found in both two layers (m/z 5045, 6139 &amp; 9245). This information may provide new avenues for the development of novel diagnostic, prognostic and therapeutic targets. We will analyze CRAC in IBD segments2,3 to look for these proteins that may help in studying their biological mechanisms in cancer transformation.. Support: 3U54CA091408-09S1 (to MMC-VICC Partnership: SE Adunyah &amp; HL Moses) References: 1. M'Koma AE, Seely EH, Washington MK, Schwartz DA, Muldoon RL, Herline AJ, Wise PE, Caprioli RM Proteomic Profiling of Mucosal and Submucosal Colonic Tissues Yields Protein Signatures that Differentiate the Inflammatory Colitides. Inflamm Bowel Dis 2011;17:875–83. 2. M'Koma AE, Moses HL, Adunyah SE. Inflammatory bowel disease-associated colorectal cancer: proctocolectomy andmucosectomy does not necessarily eliminate pouch related cancer incidences. Int J colorect Dis 2011;26:533–52. 3. Um JW, M'Koma AE. Pouch-related dysplasia and adenocarcinoma following restorative proctocolectomy for ulcerative colitis. Tech coloproctol 2011;15:7–16. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B33.</jats:p

Observations on essential biochemical data profile in connection with restorative proctocolectomy in humans : Vitamin B12 and fat absorption cited

PATIENTS: The material includes 99 patients who consecutively received handsawn pouch and ileoanal anastomosis, after mucosectomy. Sixty-five patients were men and forty-four were women. The mean-age was 31.4 (range 17-59) years. Fifty-nine patients initially underwent subtotal colectomy and ileostomy and 40 had colectomy at the time of pouch construction. Ninety-six patients suffered from ulcerative colitis, two had familial adenomatous polyposis and one was healthy but belonged to a dominant cancer inherited family. All patients obtained a loop ileostomy at the pouch operation. After loop ileostomy closure, the patients were followed up regarding homeostasis in a prospective fashion by the surgical team at 2, 6, 12, 18, 24 and 36 months after Surgery. ELECTROLYTES: Pathologic values of sodium and potassium in serum were rarely seen. Low values of calcium were found preoperatively among acutely operated. Sixteen percent of the patients with ileostomy had high values of zinc, while 2% to 5% had low values during the manipulative and follow-up phases. Magnesium was decreased at all stations in 16 to 36% of the patients. PROTEINS: Low albumin. values were seldom seen except for in patients who were to be acutely colectomized. In our observations, we noted an elevation of serum IgG and IgA with time during the functioning pouches after loop ileostorny closure and with serum IgM during the period with loop ileostomy, compared to preoperative values. LIVER ENZYMES: A high percentage of patients had increased ALAT and/ or ALP in serum (36% and 42% respectively) during the time with loop ileostomy compared to a preoperative percentage of 14% and 12% in the elective group and 13% and 14% in the acute group. Fifty percent of the patients with increased ALAT also had increased ALP. The levels of mean values did not normalise until after closure of loop ileostomy. HEMATOLOGY: More patients with low serum haemoglobin and iron were seen before colectomy (44% and 50%) than with ileostomy (18% and 23%) and/ or with loop ileostomy (12% and 16%). During the 6 to 36 months of IPAA follow-up, 7% to 14% and 11 to 21% had low values. Although only 3% and 11% of the ileal pouch anal anastomosed patient had low serum vitamin B12 at the 12 and 36 months follow-up, 31% and 36% had decreased Schilling test In five patients vitamin B12 deficiency began during the first 6 months of IPAA function. Ten percent of the patients have had substitutional therapy with vitamin B12. Five patients continue with substitution after 40 to 60 months. At 12 and 36 months follow-up, 35% and 41% had decreased 14C-triolein breath tests but no patient showed any symptoms of anorexia. LIPIDS: There was a significant difference of mean serum cholesterol preoperatively. between patients who were operated on electively versus on emergency basis. In electively operated patients, serum levels of cholesterol decreased when patients had loop ileostomy. The decrease was significantly correlated to the length of the excluded ileum but not the time duration with loop ileostomy. During the same period, serum triglyceride was significantly increased, but there was no relation to the length of the diverted ileum. Changed pattern of lipoproteins in serum was noted. Serum alpha-lipoprotein decreased (HDL) during the period with loop ileostomy. At 12 months after loop ileostomy closure, serum cholesterol, triglyceride and alpha, pre-beta- and beta-lipoprotein levels were not significantly changed compared to precolectomy time. In the emergency patients there was a tendency to increased serum cholesterol after colectomy with terminal ileostomy. After construction of the pouch and diverting loop ileostomy, serum cholesterol was not significantly changed while mean serum triglyceride was significantly increased compared to values prior to colectomy. GASTRIC ACID SECRETION and GI HORMONES and ENZYME: There was a significant increase in retention basic, and stimulated gastric acid secretion after 12 months with pouch in function, compared to preoperatively. An increased output of gastric acids may change/ decrease the intestinal passage time and contribute to looser stool. The levels of serum gastrin, pentagastrin and pepsinogen were identical

Inflammatory Bowel Disease: An Expanding Global Health Problem

This review provides a summary of the global epidemiology of inflammatory bowel diseases (IBD). It is now clear that IBD is increasing worldwide and has become a global emergence disease. IBD, which includes Crohn's disease (CD) and ulcerative colitis (UC), has been considered a problem in industrial-urbanized societies and attributed largely to a Westernized lifestyle and other associated environmental factors. Its incidence and prevalence in developing countries is steadily rising and has been attributed to the rapid modernization and Westernization of the population. There is a need to reconcile the most appropriate treatment for these patient populations from the perspectives of both disease presentation and cost. In the West, biological agents are the fastest-growing segment of the prescription drug market. These agents cost thousands of dollars per patient per year. The healthcare systems, and certainly the patients, in developing countries will struggle to afford such expensive treatments. The need for biological therapy will inevitably increase dramatically, and the pharmaceutical industry, healthcare providers, patient advocate groups, governments and non-governmental organizations should come to a consensus on how to handle this problem. The evidence that IBD is now affecting a much younger population presents an additional concern. Meta-analyses conducted in patients acquiring IBD at a young age also reveals a trend for their increased risk of developing colorectal cancer (CRC), since the cumulative incidence rates of CRC in IBD-patients diagnosed in childhood are higher than those observed in adults. In addition, IBD-associated CRC has a worse prognosis than sporadic CRC, even when the stage at diagnosis is taken into account. This is consistent with additional evidence that IBD negatively impacts CRC survival. A continuing increase in IBD incidence worldwide associated with childhood-onset of IBD coupled with the diseases’ longevity and an increase in oncologic transformation suggest a rising disease burden, morbidity, and healthcare costs. IBD and its associated neoplastic transformation appear inevitable, which may significantly impact pediatric gastroenterology and adult CRC care. Due to an infrastructure gap in terms of access to care between developed vs. developing nations and the uneven representation of IBD across socioeconomic strata, a plan is needed in the developing world regarding how to address this emerging problem