Flow Chamber System for the Statistical Evaluation of Bacterial Colonization on Materials

PubMed Central

Menzel, Friederike; Conradi, Bianca; Rodenacker, Karsten; Gorbushina, Anna A.; Schwibbert, Karin

2016-01-01

Biofilm formation on materials leads to high costs in industrial processes, as well as in medical applications. This fact has stimulated interest in the development of new materials with improved surfaces to reduce bacterial colonization. Standardized tests relying on statistical evidence are indispensable to evaluate the quality and safety of these new materials. We describe here a flow chamber system for biofilm cultivation under controlled conditions with a total capacity for testing up to 32 samples in parallel. In order to quantify the surface colonization, bacterial cells were DAPI (4`,6-diamidino-2-phenylindole)-stained and examined with epifluorescence microscopy. More than 100 images of each sample were automatically taken and the surface coverage was estimated using the free open source software g’mic, followed by a precise statistical evaluation. Overview images of all gathered pictures were generated to dissect the colonization characteristics of the selected model organism Escherichia coli W3310 on different materials (glass and implant steel). With our approach, differences in bacterial colonization on different materials can be quantified in a statistically validated manner. This reliable test procedure will support the design of improved materials for medical, industrial, and environmental (subaquatic or subaerial) applications. PMID:28773891

Diverticular colitis of the ascending colon preceding the onset of ulcerative colitis.

PubMed

Maeshiro, Tatsuji; Hokama, Akira; Kinjo, Tetsu; Fujita, Jiro

2014-06-30

We present a case of diverticular colitis of the ascending colon preceding the onset of ulcerative colitis. A 58-year-old man presented with positive faecal occult blood test. Colonoscopy disclosed diverticular colitis of the ascending colon. After a year's follow-up, typical ulcerative colitis developed and diverticular colitis improved. Diverticular colitis is a newly established disorder of chronic segmental mucosal inflammation affected by diverticular disease. There is increasing recognition of such cases with diverticular colitis preceding ulcerative colitis. There may be a possible pathogenic relationship between the two diseases. 2014 BMJ Publishing Group Ltd.

Pectin-based oral drug delivery to the colon.

PubMed

Sande, Sverre Arne

2005-05-01

This review presents an overview of studies concerning oral formulations intended for site-specific drug delivery to the colon with pectin as the main excipient. The biological aspects covered include gastrointestinal transit and the enzymatic degradation of pectin. Scintigraphic methods demonstrating the functionality of pectin formulations are discussed. The main focus is on the various formulations reported, including matrix tablets, multiparticulate formulations as pellets and hydrogel beads, and pectin-based coatings. Also included is an evaluation of common excipients employed to improve colon specificity by crosslinking or increasing the hydrophobicity. Finally, properties of the pectin molecules that are important for successful formulations are examined. The conclusion is that the studies found in the literature provide an excellent platform for the development of pectin-based colon delivery systems.

Possible Protective Effects of Quercetin and Sodium Gluconate Against Colon Cancer Induction by Dimethylhydrazine in Mice.

PubMed

Saleem, T H; Attya, A M; Ahmed, E A; Ragab, S M M; Ali Abdallah, M A; Omar, H M

2015-01-01

Micronutrients in food have been found to have chemopreventive effects, supporting the conclusions from epidemiologie studies that consumption of fresh fruits and vegetables reduces cancer risk. The present study was carried out to evaluate the role of querctin (Q) and sodium gluconate (GNA) supplementation separately or in combination in ameliorating promotion of colon tumor development by dimethyl-hydrazine (DMH) in mice. Histopathological observation of colons in mice treated with DMH showed goblet cell dysplasia with inflammatory cell infiltration. This pathological finding was associated with significant alteration in oxidative stress markers in colon tissues and carcinoembryonic antigen (CEA) levels in plasma. Mice co-treated with GNA and Q showed mild changes of absorptive and goblet cells and inflammatory cell infiltration in lamina properia, with improvement in oxidative stress markers. In conclusion, findings of the present study indicate significant roles for reactive oxygen species (ROS) in pathogenesis of DMH-induced colon toxicity and initiation of colon cancer. Also, they suggest that Q, GNA or the combination of both have a positive beneficial effect against DMH induced colonic cancer induction in mice.

In vitro combinatorial anticancer effects of 5-fluorouracil and curcumin loaded N,O-carboxymethyl chitosan nanoparticles toward colon cancer and in vivo pharmacokinetic studies.

PubMed

Anitha, A; Sreeranganathan, Maya; Chennazhi, Krishna Prasad; Lakshmanan, Vinoth-Kumar; Jayakumar, R

2014-09-01

Colon cancer is the third most leading causes of death due to cancer worldwide and the chemo drug 5-fluorouracil's (5-FU) applicability is limited due to its non-specificity, low bioavailability and overdose. The efficacy of 5-FU in colon cancer chemo treatment could be improved by nanoencapsulation and combinatorial approach. In the present study curcumin (CUR), a known anticancer phytochemical, was used in combination with 5-FU and the work focuses on the development of a combinatorial nanomedicine based on 5-FU and CUR in N,O-carboxymethyl chitosan nanoparticles (N,O-CMC NPs). The developed 5-FU-N,O-CMC NPs and CUR-N,O-CMC NPs were found to be blood compatible. The in vitro drug release profile in pH 4.5 and 7.4 showed a sustained release profile over a period of 4 days. The combined exposure of the nanoformulations in colon cancer cells (HT 29) proved the enhanced anticancer effects. In addition, the in vivo pharmacokinetic data in mouse model revealed the improved plasma concentrations of 5-FU and CUR which prolonged up to 72 h unlike the bare drugs. In conclusion, the 5-FU and CUR released from the N,O-CMC NPs produced enhanced anticancer effects in vitro and improved plasma concentrations under in vivo conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Curcumin-encapsulated polymeric micelles suppress the development of colon cancer in vitro and in vivo.

PubMed

Yang, Xi; Li, Zhaojun; Wang, Ning; Li, Ling; Song, Linjiang; He, Tao; Sun, Lu; Wang, Zhihan; Wu, Qinjie; Luo, Na; Yi, Cheng; Gong, Changyang

2015-05-18

To develop injectable formulation and improve the stability of curcumin (Cur), Cur was encapsulated into monomethyl poly (ethylene glycol)-poly (ε-caprolactone)-poly (trimethylene carbonate) (MPEG-P(CL-co-TMC)) micelles through a single-step solid dispersion method. The obtained Cur micelles had a small particle size of 27.6 ± 0.7 nm with polydisperse index (PDI) of 0.11 ± 0.05, drug loading of 14.07 ± 0.94%, and encapsulation efficiency of 96.08 ± 3.23%. Both free Cur and Cur micelles efficiently suppressed growth of CT26 colon carcinoma cells in vitro. The results of in vitro anticancer studies confirmed that apoptosis induction and cellular uptake on CT26 cells had completely increased in Cur micelles compared with free Cur. Besides, Cur micelles were more effective in suppressing the tumor growth of subcutaneous CT26 colon in vivo, and the mechanisms included the inhibition of tumor proliferation and angiogenesis and increased apoptosis of tumor cells. Furthermore, few side effects were found in Cur micelles. Overall, our findings suggested that Cur micelles could be a stabilized aqueous formulation for intravenous application with improved antitumor activity, which may be a potential treatment strategy for colon cancer in the future.

Use of robotics in colon and rectal surgery.

PubMed

Pucci, Michael J; Beekley, Alec C

2013-03-01

The pace of innovation in the field of surgery continues to accelerate. As new technologies are developed in combination with industry and clinicians, specialized patient care improves. In the field of colon and rectal surgery, robotic systems offer clinicians many alternative ways to care for patients. From having the ability to round remotely to improved visualization and dissection in the operating room, robotic assistance can greatly benefit clinical outcomes. Although the field of robotics in surgery is still in its infancy, many groups are actively investigating technologies that will assist clinicians in caring for their patients. As these technologies evolve, surgeons will continue to find new and innovative ways to utilize the systems for improved patient care and comfort.

Bacillus spore-based oral carriers loading curcumin for the therapy of colon cancer.

PubMed

Yin, Liang; Meng, Zhan; Zhang, Yuxiao; Hu, Kaikai; Chen, Wuya; Han, Kaibin; Wu, Bao-Yan; You, Rong; Li, Chu-Hua; Jin, Ying; Guan, Yan-Qing

2018-02-10

Oral drug delivery has attracted substantial attention due to its advantages over other administration routes. Bacillus spores, as oral probiotic agents, are applied widely. In this paper, a novel Bacillus spore-based oral colon targeted carrier loading curcumin was developed for colon cancer treatment. Curcumin was linked covalently with the outer coat of Bacillus spore and folate, respectively (SPORE-CUR-FA). Bacillus spores are capable of delivering drugs to the colon area through gastric barrier, taking the advantage of its tolerance to the harsh conditions and disintegration of the outer coat of spores after germination in the colon. The drug release in vitro and in vivo of SPORE-CUR-FA was investigated. Results showed that SPORE-CUR-FA had the characteristics of colon-targeted drug release. Pharmacokinetic studies confirmed that Bacillus spore-based carriers could efficiently improve the oral bioavailability of curcumin. In vitro and in vivo anti-tumor studies showed that SPORE-CUR-FA had substantial ability for inhibiting colon cancer cells. These findings suggest that this Bacillus spore-based oral drug delivery system has a great potential for the treatment of colon cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Characteristics of right-sided colonic neoplasia and colonoscopy barriers limiting their early detection and prognosis: a review of the literature.

PubMed

Fischbach, Wolfgang; Elsome, Rory; Amlani, Bharat

2018-06-05

Colonoscopy provides less protection from colorectal cancer in the right colon than the left. Areas covered: This review examines patient outcomes and colonoscopy success rates to identify factors that limit the protective effect of colonoscopy in the right colon. The MEDLINE and Embase databases were searched for literature from 2000 onwards, on the long-term outcomes and differences in screening practice between the right and left colon. In total, 12 systematic reviews (including nine meta-analyses) and 44 primary data records were included. Differences in patient outcomes and colonoscopy practice were identified between the right and left colon, suggesting that several factors, many of which disproportionally affect the right colon, impact lesion detection rates. Shorter withdrawal times reduce detection rates, while longer times significantly increase detection; mostly of adenomas in the right colon. Colonoscope attachments often only show a significant improvement in detection rates in the right colon, suggesting detection is more challenging due to visibility of the right colonic mucosa. Higher bowel cleansing grades significantly improve detection rates in the right colon compared to the left. Expert commentary: These findings confirm the need for continued improvement of colonoscopy effectiveness, and obligatory quality assessment, overall and especially in the right colon.

How recent advances in molecular tests could impact the diagnosis of pneumonia.

PubMed

Murdoch, David R

2016-01-01

Molecular diagnostic tests have been the single major development in pneumonia diagnostics over recent years. Nucleic acid detection tests (NATs) have greatly improved the ability to detect respiratory viruses and bacterial pathogens that do not normally colonize the respiratory tract. In contrast, NATs do not yet have an established role for diagnosing pneumonia caused by bacteria that commonly colonize the nasopharynx due to difficulties discriminating between pathogens and coincidental carriage strains. New approaches are needed to distinguish infection from colonization, such as through use of quantitative methods and identification of discriminating cut-off levels. The recent realization that the lung microbiome exists has provided new insights into the pathogenesis of pneumonia involving the interaction between multiple microorganisms. New developments in molecular diagnostics must account for this new paradigm.

Pharmacokinetics of ketorolac tromethamine compression-coated tablets for colon delivery.

PubMed

Vemula, Sateesh Kumar; Veerareddy, Prabhakar Reddy; Devadasu, Venkat Ratnam

2014-08-01

Present research efforts are focused in developing compression-coated ketorolac tromethamine tablets to improve the drug levels in colon by retarding the drug release in the stomach and small intestine. To achieve this objective, core tablets containing ketorolac tromethamine were prepared by direct compression and compression coated with sodium alginate. The developed tablets were evaluated for physical properties, in vitro drug release, X-ray imaging, and pharmacokinetic studies in human volunteers. Based on the in vitro drug release study, the optimized formulation showed very little drug release (6.75 ± 0.49 %) in the initial lag period of 5 h, followed by progressive release up to 97.47 ± 0.93 % within 24 h. The X-ray imaging of tablets in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. From the pharmacokinetic study, the C max of colon-targeted tablets was 3,486.70 ng/ml at T max 10 h, whereas in the case of immediate-release tablets, the C max of 4,506.31 ng/ml at T max 2 h signifies the ability of compression-coated tablets to target the colon. In conclusion, compression-coated tablets are suitable to deliver ketorolac tromethamine to the colon.

Polarized near-infrared autofluorescence imaging combined with near-infrared diffuse reflectance imaging for improving colonic cancer detection.

PubMed

Shao, Xiaozhuo; Zheng, Wei; Huang, Zhiwei

2010-11-08

We evaluate the diagnostic feasibility of the integrated polarized near-infrared (NIR) autofluorescence (AF) and NIR diffuse reflectance (DR) imaging technique developed for colonic cancer detection. A total of 48 paired colonic tissue specimens (normal vs. cancer) were measured using the integrated NIR DR (850-1100 nm) and NIR AF imaging at the 785 nm laser excitation. The results showed that NIR AF intensities of cancer tissues are significantly lower than those of normal tissues (p<0.001, paired 2-sided Student's t-test, n=48). NIR AF imaging under polarization conditions gives a higher diagnostic accuracy (of ~92-94%) compared to non-polarized NIR AF imaging or NIR DR imaging. Further, the ratio imaging of NIR DR to NIR AF with polarization provides the best diagnostic accuracy (of ~96%) among the NIR AF and NIR DR imaging techniques. This work suggests that the integrated NIR AF/DR imaging under polarization condition has the potential to improve the early diagnosis and detection of malignant lesions in the colon.

Endoscopic detection of murine colonic dysplasia using a novel fluorescence-labeled peptide

NASA Astrophysics Data System (ADS)

Miller, Sharon J.; Joshi, Bishnu P.; Gaustad, Adam; Fearon, Eric R.; Wang, Thomas D.

2011-03-01

Current endoscopic screening does not detect all pre-malignant (dysplastic) colorectal mucosa, thus requiring the development of more sensitive, targeted techniques to improve detection. The presented work utilizes phage display to identify a novel peptide binder to colorectal dysplasia in a CPC;Apc mouse model. A wide-field, small animal endoscope capable of fluorescence excitation (450-475 nm) identified polyps via white light and also collected fluorescence images (510 nm barrier filter) of peptide binding. The peptide bound ~2-fold greater to the colonic adenomas when compared to the control peptide. We have imaged fluorescence-labeled peptide binding in vivo that is specific towards distal colonic adenomas.

Algorithms to identify colonic ischemia, complications of constipation and irritable bowel syndrome in medical claims data: development and validation.

PubMed

Sands, Bruce E; Duh, Mei-Sheng; Cali, Clorinda; Ajene, Anuli; Bohn, Rhonda L; Miller, David; Cole, J Alexander; Cook, Suzanne F; Walker, Alexander M

2006-01-01

A challenge in the use of insurance claims databases for epidemiologic research is accurate identification and verification of medical conditions. This report describes the development and validation of claims-based algorithms to identify colonic ischemia, hospitalized complications of constipation, and irritable bowel syndrome (IBS). From the research claims databases of a large healthcare company, we selected at random 120 potential cases of IBS and 59 potential cases each of colonic ischemia and hospitalized complications of constipation. We sought the written medical records and were able to abstract 107, 57, and 51 records, respectively. We established a 'true' case status for each subject by applying standard clinical criteria to the available chart data. Comparing the insurance claims histories to the assigned case status, we iteratively developed, tested, and refined claims-based algorithms that would capture the diagnoses obtained from the medical records. We set goals of high specificity for colonic ischemia and hospitalized complications of constipation, and high sensitivity for IBS. The resulting algorithms substantially improved on the accuracy achievable from a naïve acceptance of the diagnostic codes attached to insurance claims. The specificities for colonic ischemia and serious complications of constipation were 87.2 and 92.7%, respectively, and the sensitivity for IBS was 98.9%. U.S. commercial insurance claims data appear to be usable for the study of colonic ischemia, IBS, and serious complications of constipation. (c) 2005 John Wiley & Sons, Ltd.

Impact of a multimedia e-learning module on colon cancer literacy: a community-based pilot study.

PubMed

Holubar, Stefan D; Hassinger, J Peyton; Dozois, Eric J; Wolff, Bruce G; Kehoe, Michael; Cima, Robert R

2009-10-01

We aimed to determine if an e-learning module could improve colon cancer literacy in a community-based cohort, while obtaining variability estimates for subsequent study. A convenience sample of subjects attending a health-education fair was surveyed to determine colon cancer literacy before-and-after viewing a colon cancer e-learning module. The difference in cancer literacy scores was assessed for significance using univariate analysis. Twenty-two eligible subjects completed the survey: mean age 77.2+/-7.5 y, 55% women; 67% had at least some graduate-level education. Baseline colon cancer literacy was 72.6% +/- 11.6%; after the e-learning module, the mean colon cancer literacy score was 75.5% +/- 12.2%, representing a 3% improvement (P=0.33). After excluding a single problematic item identified by item analysis, the adjusted improvement was 7% (P=0.04). Invasiveness, malignant, and metastatic remained poorly understood concepts, while a large improvement (45%) was seen regarding the role of routine lymphadenectomy. Subject satisfaction with the module was universally (100%) high or very high. Use of an e-learning module is associated with high patient satisfaction, and has potential to improve colon cancer literacy in laypersons. Randomized study is warranted to determine the incremental impact of this and other multimedia educational interventions.

Use of Robotics in Colon and Rectal Surgery

PubMed Central

Pucci, Michael J.; Beekley, Alec C.

2013-01-01

The pace of innovation in the field of surgery continues to accelerate. As new technologies are developed in combination with industry and clinicians, specialized patient care improves. In the field of colon and rectal surgery, robotic systems offer clinicians many alternative ways to care for patients. From having the ability to round remotely to improved visualization and dissection in the operating room, robotic assistance can greatly benefit clinical outcomes. Although the field of robotics in surgery is still in its infancy, many groups are actively investigating technologies that will assist clinicians in caring for their patients. As these technologies evolve, surgeons will continue to find new and innovative ways to utilize the systems for improved patient care and comfort. PMID:24436647

Survival of patients with colon and rectal cancer in central and northern Denmark, 1998–2009

PubMed Central

Ostenfeld, Eva B; Erichsen, Rune; Iversen, Lene H; Gandrup, Per; Nørgaard, Mette; Jacobsen, Jacob

2011-01-01

Objective The prognosis for colon and rectal cancer has improved in Denmark over the past decades but is still poor compared with that in our neighboring countries. We conducted this population-based study to monitor recent trends in colon and rectal cancer survival in the central and northern regions of Denmark. Material and methods Using the Danish National Registry of Patients, we identified 9412 patients with an incident diagnosis of colon cancer and 5685 patients diagnosed with rectal cancer between 1998 and 2009. We determined survival, and used Cox proportional hazard regression analysis to compare mortality over time, adjusting for age and gender. Among surgically treated patients, we computed 30-day mortality and corresponding mortality rate ratios (MRRs). Results The annual numbers of colon and rectal cancer increased from 1998 through 2009. For colon cancer, 1-year survival improved from 65% to 70%, and 5-year survival improved from 37% to 43%. For rectal cancer, 1-year survival improved from 73% to 78%, and 5-year survival improved from 39% to 47%. Men aged 80+ showed most pronounced improvements. The 1- and 5-year adjusted MRRs decreased: for colon cancer 0.83 (95% confidence interval CI: 0.76–0.92) and 0.84 (95% CI: 0.78–0.90) respectively; for rectal cancer 0.79 (95% CI: 0.68–0.91) and 0.81 (95% CI: 0.73–0.89) respectively. The 30-day postoperative mortality after resection also declined over the study period. Compared with 1998–2000 the 30-day MRRs in 2007–2009 were 0.68 (95% CI: 0.53–0.87) for colon cancer and 0.59 (95% CI: 0.37–0.96) for rectal cancer. Conclusion The survival after colon and rectal cancer has improved in central and northern Denmark during the 1998–2009 period, as well as the 30-day postoperative mortality. PMID:21814467

Survival of patients with colon and rectal cancer in central and northern Denmark, 1998-2009.

PubMed

Ostenfeld, Eva B; Erichsen, Rune; Iversen, Lene H; Gandrup, Per; Nørgaard, Mette; Jacobsen, Jacob

2011-01-01

The prognosis for colon and rectal cancer has improved in Denmark over the past decades but is still poor compared with that in our neighboring countries. We conducted this population-based study to monitor recent trends in colon and rectal cancer survival in the central and northern regions of Denmark. Using the Danish National Registry of Patients, we identified 9412 patients with an incident diagnosis of colon cancer and 5685 patients diagnosed with rectal cancer between 1998 and 2009. We determined survival, and used Cox proportional hazard regression analysis to compare mortality over time, adjusting for age and gender. Among surgically treated patients, we computed 30-day mortality and corresponding mortality rate ratios (MRRs). The annual numbers of colon and rectal cancer increased from 1998 through 2009. For colon cancer, 1-year survival improved from 65% to 70%, and 5-year survival improved from 37% to 43%. For rectal cancer, 1-year survival improved from 73% to 78%, and 5-year survival improved from 39% to 47%. Men aged 80+ showed most pronounced improvements. The 1- and 5-year adjusted MRRs decreased: for colon cancer 0.83 (95% confidence interval CI: 0.76-0.92) and 0.84 (95% CI: 0.78-0.90) respectively; for rectal cancer 0.79 (95% CI: 0.68-0.91) and 0.81 (95% CI: 0.73-0.89) respectively. The 30-day postoperative mortality after resection also declined over the study period. Compared with 1998-2000 the 30-day MRRs in 2007-2009 were 0.68 (95% CI: 0.53-0.87) for colon cancer and 0.59 (95% CI: 0.37-0.96) for rectal cancer. The survival after colon and rectal cancer has improved in central and northern Denmark during the 1998-2009 period, as well as the 30-day postoperative mortality.

Review article: uncomplicated diverticular disease of the colon.

PubMed

Petruzziello, L; Iacopini, F; Bulajic, M; Shah, S; Costamagna, G

2006-05-15

Diverticular disease of the colon is the fifth most important gastrointestinal disease in terms of direct and indirect health care costs in western countries. Uncomplicated diverticular disease is defined as the presence of diverticula in the absence of complications such as perforation, fistula, obstruction and/or bleeding. The distribution of diverticula along the colon varies worldwide being almost always left-sided and directly related to age in western countries and right-sided where diet is rich in fibre. The pathophysiology of diverticular disease is complex and relates to abnormal colonic motility, changes in the colonic wall, chronic mucosal low-grade inflammation, imbalance in colonic microflora and visceral hypersensitivity. Moreover, there can be genetic factors involved in the development of colonic diverticula. The use of non-absorbable antibiotics is the mainstay of therapy in patients with mild to moderate symptoms, and the effect of fibre-supplementation alone does not appear to be significantly different from placebo, although no definite data are available. More recently, alternative treatments have been reported. Mesalazine acts as a local mucosal immunomodulator and has been shown to improve symptoms and prevent recurrence of diverticulitis. In addition, probiotics have also been shown to be beneficial by re-establishing a normal gut microflora. In this study, the current literature on uncomplicated diverticular disease of the colon is reviewed.

Chemopreventive effects of standardized ethanol extract from the aerial parts of Artemisia princeps Pampanini cv. Sajabal via NF-κB inactivation on colitis-associated colon tumorigenesis in mice.

PubMed

Chung, Kyung-Sook; Choi, Hye-Eun; Shin, Ji-Sun; Cho, Eu-Jin; Cho, Young-Wuk; Choi, Jung-Hye; Baek, Nam-In; Lee, Kyung-Tae

2015-01-01

Chronic inflammation is an underlying risk factor of colon cancer, and NF-κB plays a critical role in the development of inflammation-associated colon cancer in an AOM/DSS mouse model. The aim of this study was to determine whether the standardized ethanol extract obtained from the aerial parts of Artemisia princeps Pampanini cv. Sajabal (EAPP) is effective at preventing inflammation-associated colon cancer, and if so, to identify the signaling pathways involved. In the present study, protective efficacy of EAPP on tumor formation and the infiltrations of monocytes and macrophages in colons of an AOM/DSS mouse model were evaluated. It was found that colitis and tumor burdens showed statistically meaningful improvements after EAPP administration. Furthermore, these improvements were accompanied by a reduction in NF-κB activity and in the levels of NF-κB-dependent pro-survival proteins, that is, survivin, cFLIP, XIAP, and Bcl-2. In vitro, EAPP significantly reduced NF-κB activation and the levels of IL-1β and IL-8 mRNA and pro-survival proteins in HT-29 and HCT-116 colon cancer cells. Furthermore, EAPP caused caspase-dependent apoptosis. Based on these results, the authors suggest EAPP suppresses inflammatory responses and induces apoptosis partly via NF-κB inactivation, and that EAPP could be useful for the prevention of colitis-associated tumorigenesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Methicillin-resistant Staphylococcus aureus transmission and infections in a neonatal intensive care unit despite active surveillance cultures and decolonization: challenges for infection prevention.

PubMed

Popoola, Victor O; Budd, Alicia; Wittig, Sara M; Ross, Tracy; Aucott, Susan W; Perl, Trish M; Carroll, Karen C; Milstone, Aaron M

2014-04-01

To characterize the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) transmission and infections in a level IIIC neonatal intensive care unit (NICU) and identify barriers to MRSA control. Retrospective cohort study in a university-affiliated NICU with an MRSA control program including weekly nares cultures of all neonates and admission nares cultures for neonates transferred from other hospitals or admitted from home. Medical records were reviewed to identify neonates with NICU-acquired MRSA colonization or infection between April 2007 and December 2011. Compliance with hand hygiene and an MRSA decolonization protocol were monitored. Relatedness of MRSA strains were assessed using pulsed-field gel electrophoresis (PFGE). Of 3,536 neonates, 74 (2.0%) had a culture grow MRSA, including 62 neonates with NICU-acquired MRSA. Nineteen of 74 neonates (26%) had an MRSA infection, including 8 who became infected before they were identified as MRSA colonized, and 11 of 66 colonized neonates (17%) developed a subsequent infection. Of the 37 neonates that underwent decolonization, 6 (16%) developed a subsequent infection, and 7 of 14 (50%) that remained in the NICU for 21 days or more became recolonized with MRSA. Using PFGE, there were 14 different strain types identified, with USA300 being the most common (31%). Current strategies to prevent infections-including active identification and decolonization of MRSA-colonized neonates-are inadequate because infants develop infections before being identified as colonized or after attempted decolonization. Future prevention efforts would benefit from improving detection of MRSA colonization, optimizing decolonization regimens, and identifying and interrupting reservoirs of transmission.

Video capsule endoscopy: Perspectives of a revolutionary technique

PubMed Central

Bouchard, Simon; Ibrahim, Mostafa; Van Gossum, Andre

2014-01-01

Video capsule endoscopy (VCE) was launched in 2000 and has revolutionized direct endoscopic imaging of the gut. VCE is now a first-line procedure for exploring the small bowel in cases of obscure digestive bleeding and is also indicated in some patients with Crohn’s disease, celiac disease, and polyposis syndrome. A video capsule has also been designed for visualizing the esophagus in order to detect Barrett’s esophagus or esophageal varices. Different capsules are now available and differ with regard to dimensions, image acquisition rate, battery life, field of view, and possible optical enhancements. More recently, the use of VCE has been extended to exploring the colon. Within the last 5 years, tremendous developments have been made toward increasing the capabilities of the colon capsule. Although colon capsule cannot be proposed as a first-line colorectal cancer screening procedure, colon capsule may be used in patients with incomplete colonoscopy or in patients who are unwilling to undergo colonoscopy. In the near future, new technological developments will improve the diagnostic yield of VCE and broaden its therapeutic capabilities. PMID:25516644

Improving Outcomes Following Penetrating Colon Wounds

PubMed Central

Miller, Preston R.; Fabian, Timothy C.; Croce, Martin A.; Magnotti, Louis J.; Elizabeth Pritchard, F.; Minard, Gayle; Stewart, Ronald M.

2002-01-01

Introduction During World War II, failure to treat penetrating colon injuries with diversion could result in court martial. Based on this wartime experience, colostomy for civilian colon wounds became the standard of care for the next 4 decades. Previous work from our institution demonstrated that primary repair was the optimal management for nondestructive colon wounds. Optimal management of destructive wounds requiring resection remains controversial. To address this issue, we performed a study that demonstrated risk factors (pre or intraoperative transfusion requirement of more than 6 units of packed red blood cells, significant comorbid diseases) that were associated with a suture line failure rate of 14%, and of whom 33% died. Based on these outcomes, a clinical pathway for management of destructive colon wounds was developed. The results of the implementation of this pathway are the focus of this report. Methods Patients with penetrating colon injury were identified from the registry of a level I trauma center over a 5-year period. Records were reviewed for demographics, injury characteristics, and outcome. Patients with nondestructive injuries underwent primary repair. Patients with destructive wounds but no comorbidities or large transfusion requirement underwent resection and anastomosis, while patients with destructive wounds and significant medical illness or transfusion requirements of more than 6 units/blood received end colostomy. The current patients (CP) were compared to the previous study (PS) to determine the impact of the clinical pathway. Outcomes examined included colon related mortality and morbidity (suture line leak and abscess). Results Over a 5.5-year period, 231 patients had penetrating colon wounds. 209 survived more 24 hours and comprise the study population. Primary repair was performed on 153 (73%) patients, and 56 patients had destructive injuries (27%). Of these, 40 (71%) had resection and anastomosis and 16 (29%) had diversion. More destructive injuries were managed in the CP group (27% vs. 19%). Abscess rate was lower in the CP group (27% vs. 37%), as was suture line leak rate (7% vs. 14%). Colon related mortality in the CP group was 5% as compared with 12% in the PS group. Conclusions The clinical pathway for destructive colon wound management has improved outcomes as measured by anastomotic leak rates and colon related mortality. The data demonstrated the need for colostomy in the face of shock and comorbidities. Institution of this pathway results in colostomy for only 7% of all colon wounds. PMID:12035033

Improving outcomes following penetrating colon wounds: application of a clinical pathway.

PubMed

Miller, Preston R; Fabian, Timothy C; Croce, Martin A; Magnotti, Louis J; Elizabeth Pritchard, F; Minard, Gayle; Stewart, Ronald M

2002-06-01

During World War II, failure to treat penetrating colon injuries with diversion could result in court martial. Based on this wartime experience, colostomy for civilian colon wounds became the standard of care for the next 4 decades. Previous work from our institution demonstrated that primary repair was the optimal management for nondestructive colon wounds. Optimal management of destructive wounds requiring resection remains controversial. To address this issue, we performed a study that demonstrated risk factors (pre or intraoperative transfusion requirement of more than 6 units of packed red blood cells, significant comorbid diseases) that were associated with a suture line failure rate of 14%, and of whom 33% died. Based on these outcomes, a clinical pathway for management of destructive colon wounds was developed. The results of the implementation of this pathway are the focus of this report. Patients with penetrating colon injury were identified from the registry of a level I trauma center over a 5-year period. Records were reviewed for demographics, injury characteristics, and outcome. Patients with nondestructive injuries underwent primary repair. Patients with destructive wounds but no comorbidities or large transfusion requirement underwent resection and anastomosis, while patients with destructive wounds and significant medical illness or transfusion requirements of more than 6 units/blood received end colostomy. The current patients (CP) were compared to the previous study (PS) to determine the impact of the clinical pathway. Outcomes examined included colon related mortality and morbidity (suture line leak and abscess). Over a 5.5-year period, 231 patients had penetrating colon wounds. 209 survived more 24 hours and comprise the study population. Primary repair was performed on 153 (73%) patients, and 56 patients had destructive injuries (27%). Of these, 40 (71%) had resection and anastomosis and 16 (29%) had diversion. More destructive injuries were managed in the CP group (27% vs. 19%). Abscess rate was lower in the CP group (27% vs. 37%), as was suture line leak rate (7% vs. 14%). Colon related mortality in the CP group was 5% as compared with 12% in the PS group. The clinical pathway for destructive colon wound management has improved outcomes as measured by anastomotic leak rates and colon related mortality. The data demonstrated the need for colostomy in the face of shock and comorbidities. Institution of this pathway results in colostomy for only 7% of all colon wounds.

Functional Effects of Prebiotic Fructans in Colon Cancer and Calcium Metabolism in Animal Models.

PubMed

Rivera-Huerta, Marisol; Lizárraga-Grimes, Vania Lorena; Castro-Torres, Ibrahim Guillermo; Tinoco-Méndez, Mabel; Macías-Rosales, Lucía; Sánchez-Bartéz, Francisco; Tapia-Pérez, Graciela Guadalupe; Romero-Romero, Laura; Gracia-Mora, María Isabel

2017-01-01

Inulin-type fructans are polymers of fructose molecules and are known for their capacity to enhance absorption of calcium and magnesium, to modulate gut microbiota and energy metabolism, and to improve glycemia. We evaluated and compared the effects of Chicory inulin "Synergy 1®" and inulin from Mexican agave "Metlin®" in two experimental models of colon cancer and bone calcium metabolism in mice and rats. Inulins inhibited the development of dextran sulfate sodium-induced colitis and colon cancer in mice; these fructans reduced the concentration of tumor necrosis factor alpha and prevented the formation of intestinal polyps, villous atrophy, and lymphoid hyperplasia. On the other hand, inulin treatments significantly increased bone densitometry (femur and vertebra) in ovariectomized rats without altering the concentration of many serum biochemical parameters and urinary parameters. Histopathology results were compared between different experimental groups. There were no apparent histological changes in rats treated with inulins and a mixture of inulins-isoflavones. Our results showed that inulin-type fructans have health-promoting properties related to enhanced calcium absorption, potential anticancer properties, and anti-inflammatory effects. The use of inulin as a prebiotic can improve health and prevent development of chronic diseases such as cancer and osteoporosis.

Study on Dendrobium officinale O-Acetyl-glucomannan (Dendronan). 7. Improving Effects on Colonic Health of Mice.

PubMed

Zhang, Guan-ya; Nie, Shao-ping; Huang, Xiao-jun; Hu, Jie-lun; Cui, Steve W; Xie, Ming-yong; Phillips, Glyn O

2016-03-30

This research was aimed to study the effect of Dendrobium officinale polysaccharide (Dendronan) on colonic health. Mice were fed Dendronan at doses of 40, 80, and 160 mg/kg body weight for 0, 10, 20, and 30 days, respectively. Results showed that Dendronan, which has a special structure formed by mannose and glucose, rich in O-acetyl groups, exhibited improving effects on colonic and fecal parameters of Balb/c mice. After Dendronan feeding, the content of short-chain fatty acids (SCFAs), colon length and index, and fecal moisture were increased, whereas colonic pH was decreased and defecation time was shortened. All of these changes were significantly different between polysaccharide-treated groups and the control group (p < 0.05). These findings suggested that an adequate intake of Dendronan is beneficial to the process of fermentation and regulation of colonic microenvironment, thus playing a role in the maintenance of colonic health.

Efficient seeding and defragmentation of curvature streamlines for colonic polyp detection

NASA Astrophysics Data System (ADS)

Zhao, Lingxiao; Botha, Charl P.; Truyen, Roel; Vos, Frans M.; Post, Frits H.

2008-03-01

Many computer aided diagnosis (CAD) schemes have been developed for colon cancer detection using Virtual Colonoscopy (VC). In earlier work, we developed an automatic polyp detection method integrating flow visualization techniques, that forms part of the CAD functionality of an existing Virtual Colonoscopy pipeline. Curvature streamlines were used to characterize polyp surface shape. Features derived from curvature streamlines correlated highly with true polyp detections. During testing with a large number of patient data sets, we found that the correlation between streamline features and true polyps could be affected by noise and our streamline generation technique. The seeding and spacing constraints and CT noise could lead to streamline fragmentation, which reduced the discriminating power of our streamline features. In this paper, we present two major improvements of our curvature streamline generation. First, we adapted our streamline seeding strategy to the local surface properties and made the streamline generation faster. It generates a significantly smaller number of seeds but still results in a comparable and suitable streamline distribution. Second, based on our observation that longer streamlines are better surface shape descriptors, we improved our streamline tracing algorithm to produce longer streamlines. Our improved techniques are more effcient and also guide the streamline geometry to correspond better to colonic surface shape. These two adaptations support a robust and high correlation between our streamline features and true positive detections and lead to better polyp detection results.

Development and Testing of an Automated 4-Day Text Messaging Guidance as an Aid for Improving Colonoscopy Preparation.

PubMed

Walter, Benjamin Michael; Klare, Peter; Neu, Bruno; Schmid, Roland M; von Delius, Stefan

2016-06-21

In gastroenterology a sufficient colon cleansing improves adenoma detection rate and prevents the need for preterm repeat colonoscopies due to invalid preparation. It has been shown that patient education is of major importance for improvement of colon cleansing. Objective of this study was to assess the function of an automated text messaging (short message service, SMS)-supported colonoscopy preparation starting 4 days before colonoscopy appointment. After preevaluation to assess mobile phone usage in the patient population for relevance of this approach, a Web-based, automated SMS text messaging system was developed, following which a single-center feasibility study at a tertiary care center was performed. Patients scheduled for outpatient colonoscopy were invited to participate. Patients enrolled in the study group received automated information about dietary recommendations and bowel cleansing during colonoscopy preparation. Data of outpatient colonoscopies with regular preparation procedure were used for pair matching and served as control. Primary end point was feasibility of SMS text messaging support in colonoscopy preparation assessed as stable and satisfactory function of the system. Secondary end points were quality of bowel preparation according to the Boston Bowel Preparation Scale (BBPS) and patient satisfaction with SMS text messaging-provided information assessed by a questionnaire. Web-based SMS text messaging-supported colonoscopy preparation was successful and feasible in 19 of 20 patients. Mean (standard error of the mean, SEM) total BBPS score was slightly higher in the SMS group than in the control group (7.3, SEM 0.3 vs 6.4, SEM 0.2) and for each colonic region (left, transverse, and right colon). Patient satisfaction regarding SMS text messaging-based information was high. Using SMS for colonoscopy preparation with 4 days' guidance including dietary recommendation is a new approach to improve colonoscopy preparation. Quality of colonoscopy preparation was sufficient and patients were highly satisfied with the system during colonoscopy preparation.

Development and Testing of an Automated 4-Day Text Messaging Guidance as an Aid for Improving Colonoscopy Preparation

PubMed Central

Klare, Peter; Neu, Bruno; Schmid, Roland M; von Delius, Stefan

2016-01-01

Background In gastroenterology a sufficient colon cleansing improves adenoma detection rate and prevents the need for preterm repeat colonoscopies due to invalid preparation. It has been shown that patient education is of major importance for improvement of colon cleansing. Objective Objective of this study was to assess the function of an automated text messaging (short message service, SMS)–supported colonoscopy preparation starting 4 days before colonoscopy appointment. Methods After preevaluation to assess mobile phone usage in the patient population for relevance of this approach, a Web-based, automated SMS text messaging system was developed, following which a single-center feasibility study at a tertiary care center was performed. Patients scheduled for outpatient colonoscopy were invited to participate. Patients enrolled in the study group received automated information about dietary recommendations and bowel cleansing during colonoscopy preparation. Data of outpatient colonoscopies with regular preparation procedure were used for pair matching and served as control. Primary end point was feasibility of SMS text messaging support in colonoscopy preparation assessed as stable and satisfactory function of the system. Secondary end points were quality of bowel preparation according to the Boston Bowel Preparation Scale (BBPS) and patient satisfaction with SMS text messaging–provided information assessed by a questionnaire. Results Web-based SMS text messaging–supported colonoscopy preparation was successful and feasible in 19 of 20 patients. Mean (standard error of the mean, SEM) total BBPS score was slightly higher in the SMS group than in the control group (7.3, SEM 0.3 vs 6.4, SEM 0.2) and for each colonic region (left, transverse, and right colon). Patient satisfaction regarding SMS text messaging–based information was high. Conclusions Using SMS for colonoscopy preparation with 4 days’ guidance including dietary recommendation is a new approach to improve colonoscopy preparation. Quality of colonoscopy preparation was sufficient and patients were highly satisfied with the system during colonoscopy preparation. PMID:27329204

High frequency of multi drug resistant Gram-negative rods in two neonatal intensive care units in the Philippines

PubMed Central

Litzow, JM; Gill, CJ; Mantaring, JBV; Fox, M; Mendoza, M; Mendoza, S; Scobie, R; Huskins, WC; Goldman, DA; Hamer, DH

2013-01-01

Background Though hospital-acquired infections appear to be a growing threat to newborn survival in the developing world, the epidemiology of this problem remains poorly characterized. Methods Over a 10 month period, we conducted prospective longitudinal surveillance for colonization and bloodstream infections with Gram-negative rods (GNRs) among all infants admitted to the two largest neonatal intensive care units (NICUs) in Manila, the Philippines, determined antibiotic sensitivities, and calculated adjusted odds ratios (OR) for factors for bacteremia using multivariate logistic regression. Results Among 1,831 neonates enrolled over a 10-month period, 1017 (55%) became newly colonized and 358 (19.6%) became bacteremic with a resistant GNR, most commonly Klebsiella species, Enterobacter species, Acinetobacter species, and Pseudomonas aeruginosa. The proportion of invasive isolates with antibiotic resistance was: imipenem 20%, trimethoprim-sulfamethoxazole 41%, amikacin 52%, ampicillin/sulbactam 63%, ceftazidime 67%, and tobramycin 80%. Factors significantly associated with increased risk of bacteremia were mechanical ventilation and prematurity. Additionally, colonization with a resistant GNR was an independent risk for bacteremia. (OR 1.4, 95% CI 1.0 – 1.9) Conclusions Colonization with a resistant GNR was an independent risk factor for sepsis. If our data are typical, the unusually high intensity of colonization pressure and disease with multidrug-resistant GNRs at these two NICUs constitutes an emerging health care crisis in the developing world. Improved infection control methods are therefore critically needed in developing country settings. PMID:19435448

Overexpression of Nitrogen Permease Regulator Like-2 (NPRL2) Enhances Sensitivity to Irinotecan (CPT-11) in Colon Cancer Cells by Activating the DNA Damage Checkpoint Pathway.

PubMed

Liu, Shasha; Liu, Bingrong

2018-03-09

BACKGROUND Colorectal cancer (CRC) is the third most common cancer worldwide, making it is a serious threat to human health. It is imperative to develop new therapeutics to improve the CRC treatment efficiency. The aim of this study was to investigate the role of NPRL2 in improving sensitivity to CPT-11 in colon cancer cells. MATERIAL AND METHODS NPRL2 overexpression was established by transfecting the recombinant lentivirus-encoding NPRL2 gene into HCT116 colon cancer cells. Cell proliferation was identified using Cell Counting Kit-8 (CCK8) assay. Cell cycle and apoptosis were examined by flow cytometry. An immunofluorescence staining assay was conducted to examine the expression of γ-H2AX. Wound-healing and Transwell assays were utilized to show cell migration and invasion capability. The expression of apoptosis-related proteins (cleaved caspase-3, caspase-9, cleaved PARP, BAX, and Bcl-2), invasion-related proteins (MMP2, MMP9, p-PI3K, and p-AKT), and DNA damage checkpoint pathway proteins (p-ATM, p-Chk2, Cdc25C, Cdc2, and Cyclin B1) were quantified by Western blotting. RESULTS A CCK8 assay revealed that the overexpression of NPRL2 improved the sensitivity of CPT-11 in HCT116 cells (P<0.05). Functionally, NPRL2 overexpression elevated the sensitivity of CPT-11 by preventing colon cancer cell proliferation, cell movement, and invasion, and promoting cell apoptosis and G2/M cell cycle arrest. Mechanistically, NPRL2 overexpression enhanced CPT-11 sensitivity by activating the DNA damage checkpoint pathway. CONCLUSIONS NPRL2 overexpression enhances sensitivity to CPT-11 treatment in colon cancer cells, and it may serve as a molecular therapeutic agent to treat patients with CRC.

Preparation and Evaluation of Newly Developed Chitosan Salt Coating Dispersions for Colon Delivery without Requiring Overcoating.

PubMed

Yamada, Kyohei; Iwao, Yasunori; Bani-Jaber, Ahmad; Noguchi, Shuji; Itai, Shigeru

2015-01-01

Although chitosan (CS) has been recognized as a good material for colon-specific drug delivery systems, an overcoating with an enteric coating polymer on the surface of CS is absolutely necessary because CS is soluble in acidic conditions before reaching the colon. In the present study, to improve its stability in the presence of acid, a newly developed CS-laurate (CS-LA) material was evaluated as a coating dispersion for the development of colon-specific drug delivery systems. Two types of CS with different molecular weights, CS250 and CS600, were used to prepare CS-LA films by the casting method. The CS250-LA films had smooth surfaces, whereas the surfaces of the CS600-LA films were rough, indicating that the CS250-LA dispersion could form a denser film than CS600-LA. Both of these CS-LA films maintained a constant shape over 22 h in a pH 1.2 HCl/NaCl buffer, where the corresponding CS films rapidly disintegrated. In addition, the CS250-LA film showed specific colon degradability in a pH 6.0 phosphate buffered solution containing 1.0% (w/v) β-glucosidase. As a result of tensile strength and elongation at the break, both CS-LA films were found to have flexible film properties. Finally, the release of acetaminophen from disks coated with CS250-LA dispersions was significantly suppressed in fluids at pH 1.2 and 6.8, whereas disks coated with CS solution rapidly released the drug in pH 1.2 fluids. Taken together, this study shows that LA modification could be a useful approach in preparing CS films with acid stability and colonic degradability properties without requiring overcoating.

Neighborhood and habitat effects on vital rates: expansion of the Barred Owl in the Oregon Coast Ranges

USGS Publications Warehouse

Yackulic, Charles B.; Reid, Janice; Davis, Raymond; Hines, James E.; Nichols, James D.; Forsman, Eric

2012-01-01

In this paper, we modify dynamic occupancy models developed for detection-nondetection data to allow for the dependence of local vital rates on neighborhood occupancy, where neighborhood is defined very flexibly. Such dependence of occupancy dynamics on the status of a relevant neighborhood is pervasive, yet frequently ignored. Our framework permits joint inference about the importance of neighborhood effects and habitat covariates in determining colonization and extinction rates. Our specific motivation is the recent expansion of the Barred Owl (Strix varia) in western Oregon, USA, over the period 1990-2010. Because the focal period was one of dramatic range expansion and local population increase, the use of models that incorporate regional occupancy (sources of colonists) as determinants of dynamic rate parameters is especially appropriate. We began our analysis of 21 years of Barred Owl presence/nondetection data in the Tyee Density Study Area (TDSA) by testing a suite of six models that varied only in the covariates included in the modeling of detection probability. We then tested whether models that used regional occupancy as a covariate for colonization and extinction outperformed models with constant or year-specific colonization or extinction rates. Finally we tested whether habitat covariates improved the AIC of our models, focusing on which habitat covariates performed best, and whether the signs of habitat effects are consistent with a priori hypotheses. We conclude that all covariates used to model detection probability lead to improved AIC, that regional occupancy influences colonization and extinction rates, and that habitat plays an important role in determining extinction and colonization rates. As occupancy increases from low levels toward equilibrium, colonization increases and extinction decreases, presumably because there are more and more dispersing juveniles. While both rates are affected, colonization increases more than extinction decreases. Colonization is higher and extinction is lower in survey polygons with more riparian forest. The effects of riparian forest on extinction rates are greater than on colonization rates. Model results have implications for management of the invading Barred Owl, both through habitat alteration and removal.

Costus root granules improve ulcerative colitis through regulation of TGF-β mediation of the PI3K/AKT signaling pathway

PubMed Central

Wang, Xiaohong; Li, Dan; Zhang, Yong; Wu, Shuang; Tang, Fang

2018-01-01

Ulcerative colitis is a chronic nonspecific inflammatory disease that occurs in the colon and rectum. Costus root is a type of traditional Chinese medicine that exhibits antibacterial properties and serves an inhibitory role in the regeneration of gut bacteria. However, the molecular mechanisms underlying Costus root-mediated improvements in ulcerative colitis remain unclear. A complex formula of Costus root granules was created and investigated in the present study for its therapeutic effects in a rat model of ulcerative colitis. Ingredient dissolution into a traditional water decoction was used as a control. The potential mechanism mediated by Costus root granules was also analyzed in colonic epithelial cells isolated from the experimental rats. The results of the present study demonstrated that Costus root granule treatment inhibited inflammation in colonic tissue. Costus root granule treatment also suppressed the apoptosis of colonic epithelial cells isolated from the rat model of ulcerative colitis. Analyses of the underlying mechanisms of these effects indicated that the administration of Costus root granules increased transforming growth factor β expression, which activated the phosphoinositide 3-kinase/RAC-α serine/threonine-protein kinase signaling pathway in colonic epithelial cells. Notably, the administration of Costus root granules improved stomachache, diarrhea and hematochezia in and increased the body weight of, the ulcerative colitis rats. In conclusion, these results indicate that Costus root granules markedly ameliorate inflammation of the colonic epithelium, decrease the apoptosis of colonic epithelial cells and improve colonic function, which suggests that Costus root granules are an efficient agent for the treatment of ulcerative colitis. PMID:29731832

Risk factors associated with recurrent hemorrhage after the initial improvement of colonic diverticular bleeding.

PubMed

Nishikawa, Hiroki; Maruo, Takanori; Tsumura, Takehiko; Sekikawa, Akira; Kanesaka, Takashi; Osaki, Yukio

2013-03-01

We elucidated risk factors contributing to recurrent hemorrhage after initial improvement of colonic diverticular bleeding. 172 consecutive hospitalized patients diagnosed with colonic diverticular bleeding were analyzed. Recurrent hemorrhage after initial improvement of colonic diverticular bleeding is main outcome measure. We analyzed factors contributing to recurrent hemorrhage risk in univariate and multivariate analyses. The length of the observation period after improvement of colonic diverticular bleeding was 26.4 +/- 14.6 months (range, 1-79 months). The cumulative recurrent hemorrhage rate in all patients at 1 and 2 years was 34.8% and 41.8%, respectively. By univariate analysis, age > 70 years (P = 0.021), BMI > 25 kg/m2 (P = 0.013), the use of anticoagulant drugs (P = 0.034), the use of NSAIDs (P = 0.040), history of hypertension (P = 0.011), history of smoking (P = 0.030) and serum creatinine level > 1.5 mg/dL (P < 0.001) were found to be significant risk factors for recurrent colonic diverticular bleeding. By multivariate analysis, age > 70 years (Hazard ratio (HR), 1.905, 95% confidence interval (CI), 1.067-3.403, P = 0.029), history of hypertension (HR, 0.493, 95% CI, 0.245-0.993, P = 0.048) and serum creatinine level > 1.5 mg/dL (HR, 95% CI, 0.288-0.964, P = 0.044) were shown to be significant independent risk factors. Close observation after the initial improvement of colonic diverticular bleeding is needed, especially in elderly patients or patients with history of hypertension or renal deficiency.

Improved survival after an educational project on colon cancer management in the county of Stockholm--a population based cohort study.

PubMed

Bernhoff, R; Martling, A; Sjövall, A; Granath, F; Hohenberger, W; Holm, T

2015-11-01

Outcomes in rectal cancer have improved dramatically after the introduction of total mesorectal excision (TME). Recently, the TME concept has been transformed into that of complete mesocolic excision (CME) in an attempt to improve prognosis for patients with colon cancer. Multidisciplinary team (MDT) workshops including the CME concept were held annually between 2004 and 2008 at the Karolinska University Hospital. The workshops focused on preoperative staging, surgery and histopathology and included lectures and live surgery sessions. To compare survival before and after the "Stockholm Colon Cancer Project" all patients diagnosed with a right sided colon cancer between January 1, 2001 and December 31, 2003 (Group 1) and from January 1, 2006 until December 31, 2008 (Group 2) in Stockholm were identified from the Swedish ColoRectal Cancer Registry (SCRCR). The proportion of patients having a tumour resection and the proportion having emergency surgery was higher in Group 1. There were more early tumours and more R0 resections in Group 2. Overall survival in all diagnosed patients and disease free survival after tumour resection was improved in the second time period. Surgical teaching programmes may have an impact on the management and outcome in colon cancer. The exact impact from the "Stockholm Colon Cancer Project" cannot be established, however it is likely that it contributed to the improved survival. Copyright © 2015 Elsevier Ltd. All rights reserved.

Regulation of root morphogenesis in arbuscular mycorrhizae: what role do fungal exudates, phosphate, sugars and hormones play in lateral root formation?

PubMed Central

Fusconi, Anna

2014-01-01

Background Arbuscular mycorrhizae (AMs) form a widespread root–fungus symbiosis that improves plant phosphate (Pi) acquisition and modifies the physiology and development of host plants. Increased branching is recognized as a general feature of AM roots, and has been interpreted as a means of increasing suitable sites for colonization. Fungal exudates, which are involved in the dialogue between AM fungi and their host during the pre-colonization phase, play a well-documented role in lateral root (LR) formation. In addition, the increased Pi content of AM plants, in relation to Pi-starved controls, as well as changes in the delivery of carbohydrates to the roots and modulation of phytohormone concentration, transport and sensitivity, are probably involved in increasing root system branching. Scope This review discusses the possible causes of increased branching in AM plants. The differential root responses to Pi, sugars and hormones of potential AM host species are also highlighted and discussed in comparison with those of the non-host Arabidopsis thaliana. Conclusions Fungal exudates are probably the main compounds regulating AM root morphogenesis during the first colonization steps, while a complex network of interactions governs root development in established AMs. Colonization and high Pi act synergistically to increase root branching, and sugar transport towards the arbusculated cells may contribute to LR formation. In addition, AM colonization and high Pi generally increase auxin and cytokinin and decrease ethylene and strigolactone levels. With the exception of cytokinins, which seem to regulate mainly the root:shoot biomass ratio, these hormones play a leading role in governing root morphogenesis, with strigolactones and ethylene blocking LR formation in the non-colonized, Pi-starved plants, and auxin inducing them in colonized plants, or in plants grown under high Pi conditions. PMID:24227446

EURECCA colorectal: multidisciplinary management: European consensus conference colon & rectum.

PubMed

van de Velde, Cornelis J H; Boelens, Petra G; Borras, Josep M; Coebergh, Jan-Willem; Cervantes, Andres; Blomqvist, Lennart; Beets-Tan, Regina G H; van den Broek, Colette B M; Brown, Gina; Van Cutsem, Eric; Espin, Eloy; Haustermans, Karin; Glimelius, Bengt; Iversen, Lene H; van Krieken, J Han; Marijnen, Corrie A M; Henning, Geoffrey; Gore-Booth, Jola; Meldolesi, Elisa; Mroczkowski, Pawel; Nagtegaal, Iris; Naredi, Peter; Ortiz, Hector; Påhlman, Lars; Quirke, Philip; Rödel, Claus; Roth, Arnaud; Rutten, Harm; Schmoll, Hans J; Smith, Jason J; Tanis, Pieter J; Taylor, Claire; Wibe, Arne; Wiggers, Theo; Gambacorta, Maria A; Aristei, Cynthia; Valentini, Vincenzo

2014-01-01

Care for patients with colon and rectal cancer has improved in the last 20years; however considerable variation still exists in cancer management and outcome between European countries. Large variation is also apparent between national guidelines and patterns of cancer care in Europe. Therefore, EURECCA, which is the acronym of European Registration of Cancer Care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012, the first multidisciplinary consensus conference about cancer of the colon and rectum was held. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries. The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Consensus was achieved using the Delphi method. For the Delphi process, multidisciplinary experts were invited to comment and vote three web-based online voting rounds and to lecture on the subjects during the meeting (13th-15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. This manuscript covers all sentences of the consensus document with the result of the voting. The consensus document represents sections on diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and metastatic colorectal disease separately. Moreover, evidence based algorithms for diagnostics and treatment were composed which were also submitted to the Delphi process. The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members. Multidisciplinary consensus on key diagnostic and treatment issues for colon and rectal cancer management using the Delphi method was successful. This consensus document embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe. Copyright © 2013 Elsevier Ltd. All rights reserved.

Colonization of Lutzomyia shannoni (Diptera: Psychodidae) utilizing an artificial blood feeding technique.

PubMed

Mann, Rajinder S; Kaufman, Phillip E

2010-12-01

Laboratory colonization of hematophagous insects must include an efficient method of blood feeding, preferably by artificial means. Strict rules for obtaining animal use permits, extensive animal maintenance costs, and indirect anesthesia effects on animal health warrant the development of an artificial membrane feeding technique for sand fly colonization in laboratories. An attempt was made to colonize Lutzomyia shannoni using an artificial blood feeding membrane to replace the use of live animals commonly used for sand fly blood-feeding purposes. Lutzomyia shannoni readily fed through a pig intestine membrane exposed at an angle of 45°. However, it did not feed through a chicken skin membrane. Olfactory attractants were unable to improve blood-feeding efficiency. Plaster of Paris was the most suitable oviposition substrate. Female L. shannoni adults laid no eggs on moist sand substrate. Sand fly adults held in groups of ten or more laid higher numbers of eggs than did individually maintained sand flies. Inclusion of the L. longipalpis oviposition hormone dodecanoic acid or the presence of previously laid eggs did not stimulate L. shannoni oviposition. The average L. shannoni egg, larval, and pupal duration were 9.3, 36.7, and 17.8 days, respectively. The addition of a 20% sugar solution improved adult female longevity. Females survived longer (14.8 days) than males (11.9 days). Lutzomyia shannoni was successfully colonized in the laboratory for up to four generations using this artificial membrane technique. © 2010 The Society for Vector Ecology.

Mechanism of Action and Toxicities of Purgatives Used for Colonoscopy Preparation

PubMed Central

Adamcewicz, Margaret; Bearelly, Dilip; Porat, Gail; Friedenberg, Frank K.

2011-01-01

Importance of the field In developed countries colonoscopy volume has increased dramatically over the past 15 years and is the principle method used to screen for colon cancer. Preparations used for colon cleaning have evolved over the past 30 years. Some preparations have been shown to be unsafe and are now used on a limited basis. There has been progress on limiting the volume required and on taste improvement. Areas covered in this review This review provides an account of preparations used from 1980 when polyethylene glycol-based preparations became widely available, until the present day. The review highlights their mechanism of action and principle toxicities. The handling of solutes and solute-free fluid by the colon is also reviewed. What the reader will gain The reader will gain a perspective on the factors considered in developing colonic purgatives and the rationale for choosing selected preparations based on patient factors such as age, co-morbidities, and concomitant medications. Take home message Although generally safe and effective, colonic purgatives have both acute and permanent toxicities. The safest preparations utilize polyethylene glycol combined with a balanced electrolyte solution. Limitations of this preparation center on the volume required and poor taste. Alternative formulations are now available; however those using sodium phosphate have fallen out of favor due to a risk of renal toxicity. PMID:21162694

Improvement of side-effects and treatment on the experimental colitis in mice of a resin microcapsule-loading hydrocortisone sodium succinate.

PubMed

Dong, Kai; Zhang, Hefeng; Yan, Yan; Sun, Jinyao; Dong, Yalin; Wang, Ke; Zhang, Lu; Shi, Xianpeng; Xing, Jianfeng

2017-03-01

Extensive or long-time use of corticosteroids often causes many toxic side-effects. The ion exchange resins and the coating material, Eudragit, can be used in combination to form a new oral delivery system to deliver corticosteroids. The resin microcapsule (DRM) composed by Amberlite 717 and Eudragit S100 was used to target hydrocortisone (HC) to the colon in order to improve its treatment effect on ulcerative colitis (UC) and reduce its toxic side-effects. Hydrocortisone sodium succinate (HSS) was sequentially encapsulated in Amberlite 717 and Eudragit S100 to prepare the HSS-loaded resin microcapsule (HSS-DRM). The scanning electron microscopy (SEM) was employed to investigate the morphology and structure of HSS-DRM. The in vitro release and in vivo studies of pharmacokinetics and intestinal drug residues in rat were used to study the colon-targeting of HSS-DRM. The mouse induced by 2,4,6-trinitrobenzenesulfonic acid was used to study the treatment of HSS-DRM on experimental colitis. SEM study showed good morphology and structure of HSS-DRM. In the in vitro release study, > 80% of HSS was released in the colon environment (pH 7.4). The in vivo studies showed good colon-targeting of HSS-DRM (T max  = 0.97 h, C max  = 118.28 µg/mL of HSS; T max  = 2.16 h, C max  = 64.47 µg/mL of HSS-DRM). Moreover, the HSS-DRM could reduce adverse reactions induced by HSS and had good therapeutic effects on the experimental colitis. The resin microcapsule system has good colon-targeting and can be used in the development of colon-targeting preparations.

Colon Targeted Guar Gum Compression Coated Tablets of Flurbiprofen: Formulation, Development, and Pharmacokinetics

PubMed Central

Bontha, Vijaya Kumar

2013-01-01

The rationale of the present study is to formulate flurbiprofen colon targeted compression coated tablets using guar gum to improve the therapeutic efficacy by increasing drug levels in colon, and also to reduce the side effects in upper gastrointestinal tract. Direct compression method was used to prepare flurbiprofen core tablets, and they were compression coated with guar gum. Then the tablets were optimized with the support of in vitro dissolution studies, and further it was proved by pharmacokinetic studies. The optimized formulation (F4) showed almost complete drug release in the colon (99.86%) within 24 h without drug loss in the initial lag period of 5 h (only 6.84% drug release was observed during this period). The pharmacokinetic estimations proved the capability of guar gum compression coated tablets to achieve colon targeting. The C max of colon targeted tablets was 11956.15 ng/mL at T max of 10 h whereas it was 15677.52 ng/mL at 3 h in case of immediate release tablets. The area under the curve for the immediate release and compression coated tablets was 40385.78 and 78214.50 ng-h/mL and the mean resident time was 3.49 and 10.78 h, respectively. In conclusion, formulation of guar gum compression coated tablets was appropriate for colon targeting of flurbiprofen. PMID:24260738

Colon targeted guar gum compression coated tablets of flurbiprofen: formulation, development, and pharmacokinetics.

PubMed

Vemula, Sateesh Kumar; Bontha, Vijaya Kumar

2013-01-01

The rationale of the present study is to formulate flurbiprofen colon targeted compression coated tablets using guar gum to improve the therapeutic efficacy by increasing drug levels in colon, and also to reduce the side effects in upper gastrointestinal tract. Direct compression method was used to prepare flurbiprofen core tablets, and they were compression coated with guar gum. Then the tablets were optimized with the support of in vitro dissolution studies, and further it was proved by pharmacokinetic studies. The optimized formulation (F4) showed almost complete drug release in the colon (99.86%) within 24 h without drug loss in the initial lag period of 5 h (only 6.84% drug release was observed during this period). The pharmacokinetic estimations proved the capability of guar gum compression coated tablets to achieve colon targeting. The C(max) of colon targeted tablets was 11956.15 ng/mL at T max of 10 h whereas it was 15677.52 ng/mL at 3 h in case of immediate release tablets. The area under the curve for the immediate release and compression coated tablets was 40385.78 and 78214.50 ng-h/mL and the mean resident time was 3.49 and 10.78 h, respectively. In conclusion, formulation of guar gum compression coated tablets was appropriate for colon targeting of flurbiprofen.

Cellular metabolism in colorectal carcinogenesis: Influence of lifestyle, gut microbiome and metabolic pathways.

PubMed

Hagland, Hanne R; Søreide, Kjetil

2015-01-28

The interconnectivity between diet, gut microbiota and cell molecular responses is well known; however, only recently has technology allowed the identification of strains of microorganisms harbored in the gastrointestinal tract that may increase susceptibility to cancer. The colonic environment appears to play a role in the development of colon cancer, which is influenced by the human metabolic lifestyle and changes in the gut microbiome. Studying metabolic changes at the cellular level in cancer be useful for developing novel improved preventative measures, such as screening through metabolic breath-tests or treatment options that directly affect the metabolic pathways responsible for the carcinogenicity. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

In vivo endoscopic Doppler optical coherence tomography imaging of the colon

PubMed Central

Welge, Weston A.; Barton, Jennifer K.

2017-01-01

Background and Objective Colorectal cancer remains the second deadliest cancer in the United States. Several screening methods exist, however detection of small polyps remains a challenge. Optical coherence tomography has been demonstrated to be capable of detecting lesions as small as 1 mm in the mouse colon, but detection is based on measuring a doubling of the mucosa thickness. The colon microvasculature may be an attractive biomarker of early tumor development because tumor vessels are characterized by irregular structure and dysfunction. Our goal was to develop an endoscopic method of detecting and segmenting colon vessels using Doppler optical coherence tomography to enable future studies for improving early detection and development of novel chemopreventive agents. Method We conducted in vivo colon imaging in an azoxymethane (AOM)-treated mouse model of colorectal cancer using a miniature endoscope and a swept-source OCT system at 1040 nm with a 16 kHz sweep rate. We applied the Kasai autocorrelation algorithm to laterally oversampled OCT B-scans to resolve vascular flow in the mucosa and submucosa. Vessels were segmented by applying a series of image processing steps: (1) intensity thresholding, (2) two-dimensional matched filtering, and (3) histogram segmentation. Results We observed differences in the vessels sizes and spatial distribution in a mature adenoma compared to surrounding undiseased tissue and compared the results with histology. We also imaged flow in four young mice (2 AOM-treated and 2 control) showing no significant differences, which is expected so early after carcinogen exposure. We also present flow images of adenoma in a living mouse and a euthanized mouse to demonstrate that no flow is detected after euthanasia. Conclusion We present, to the best of our knowledge, the first Doppler OCT images of in vivo mouse colon collected with a fiber-based endoscope. We also describe a fast and robust image processing method for segmenting vessels in the colon. These results suggest that Doppler OCT is a promising imaging modality for vascular imaging in the colon that requires no exogenous contrast agents. PMID:27546786

Animal Models of Colorectal Cancer

PubMed Central

Johnson, Robert L.; Fleet, James C.

2012-01-01

Colorectal cancer is a heterogeneous disease that afflicts a large number of people in the United States. The use of animal models has the potential to increase our understanding of carcinogenesis, tumor biology, and the impact of specific molecular events on colon biology. In addition, animal models with features of specific human colorectal cancers can be used to test strategies for cancer prevention and treatment. In this review we provide an overview of the mechanisms driving human cancer, we discuss the approaches one can take to model colon cancer in animals, and we describe a number of specific animal models that have been developed for the study of colon cancer. We believe that there are many valuable animal models to study various aspects of human colorectal cancer. However, opportunities for improving upon these models exist. PMID:23076650

Celecoxib coupled to dextran via a glutamic acid linker yields a polymeric prodrug suitable for colonic delivery.

PubMed

Lee, Yonghyun; Kim, Jungyun; Kim, Wooseong; Nam, Joon; Jeong, Seongkeun; Lee, Sunyoung; Yoo, Jin-Wook; Kim, Min-Soo; Jung, Yunjin

2015-01-01

Celecoxib, a selective cyclooxygenase-2 inhibitor, is potentially useful for the treatment of colonic diseases such as colorectal cancer and colitis. However, the cardiovascular toxicity of celecoxib limits its routine use in the clinic. Generally, colon-specific delivery of a drug both increases the therapeutic availability in the large intestine and decreases the systemic absorption of the drug, most likely resulting in enhanced therapeutic effects against colonic diseases such as colitis and reduced systemic side effects. To develop a colon-specific prodrug of celecoxib that could reduce its cardiovascular toxicity and improve its therapeutic activity, dextran-glutamic acid-celecoxib conjugate (glutam-1-yl celecoxib-dextran ester [G1CD]) was prepared and evaluated. While stable in pH 1.2 and 6.8 buffer solutions and small-intestinal contents, G1CD efficiently released celecoxib in cecal contents. Oral administration of G1CD to rats delivered a larger amount of celecoxib to the large intestine than free celecoxib. G1CD prevented the systemic absorption of celecoxib and did not decrease the serum level of 6-ketoprostaglandin F1α, an inverse indicator of cardiovascular toxicity of celecoxib. Collectively, G1CD may be a polymeric colon-specific celecoxib prodrug with therapeutic and toxicological advantages.

Outcome for stage II and III rectal and colon cancer equally good after treatment improvement over three decades.

PubMed

Fischer, Joern; Joern, Fischer; Hellmich, Gunter; Gunter, Hellmich; Jackisch, Thomas; Thomas, Jackisch; Puffer, Erik; Erik, Puffer; Zimmer, Jörg; Jörg, Zimmer; Bleyl, Dorothea; Dorothea, Bleyl; Kittner, Thomas; Thomas, Kittner; Witzigmann, Helmut; Helmut, Witzigmann; Stelzner, Sigmar; Sigmar, Stelzner

2015-06-01

This study aimed to investigate the outcome for stage II and III rectal cancer patients compared to stage II and III colonic cancer patients with regard to 5-year cause-specific survival (CSS), overall survival, and local and combined recurrence rates over time. This prospective cohort study identified 3,355 consecutive patients with adenocarcinoma of the colon or rectum and treated in our colorectal unit between 1981 and 2011, for investigation. The study was restricted to International Union Against Cancer (UICC) stages II and III. Postoperative mortality and histological incomplete resection were excluded, which left 995 patients with colonic cancer and 726 patients with rectal cancer for further analysis. Five-year CSS rates improved for colonic cancer from 65.0% for patients treated between 1981 and 1986 to 88.1% for patients treated between 2007 and 2011. For rectal cancer patients, the respective 5-year CSS rates improved from 53.4% in the first observation period to 89.8% in the second one. The local recurrence rate for rectal cancer dropped from 34.2% in the years 1981-1986 to 2.1% in the years 2007-2011. In the last decade of observation, prognosis for rectal cancer was equal to that for colon cancer (CSS 88.6 vs. 86.7%, p = 0.409). Survival of patients with colon and rectal cancer has continued to improve over the last three decades. After major changes in treatment strategy including introduction of total mesorectal excision and neoadjuvant (radio)chemotherapy, prognosis for stage II and III rectal cancer is at least as good as for stage II and III colonic cancer.

Clinical practice guidelines for the surgical management of colon cancer: a consensus statement of the Hellenic and Cypriot Colorectal Cancer Study Group by the HeSMO*

PubMed Central

Xynos, Evaghelos; Gouvas, Nikolaos; Triantopoulou, Charina; Tekkis, Paris; Vini, Louiza; Tzardi, Maria; Boukovinas, Ioannis; Androulakis, Nikolaos; Athanasiadis, Athanasios; Christodoulou, Christos; Chrysou, Evangelia; Dervenis, Christos; Emmanouilidis, Christos; Georgiou, Panagiotis; Katopodi, Ourania; Kountourakis, Panteleimon; Makatsoris, Thomas; Papakostas, Pavlos; Papamichael, Demetris; Pentheroudakis, Georgios; Pilpilidis, Ioannis; Sgouros, Joseph; Vassiliou, Vassilios; Xynogalos, Spyridon; Ziras, Nikolaos; Karachaliou, Niki; Zoras, Odysseas; Agalianos, Christos; Souglakos, John

2016-01-01

Despite considerable improvement in the management of colon cancer, there is a great deal of variation in the outcomes among European countries, and in particular among different hospital centers in Greece and Cyprus. Discrepancy in the approach strategies and lack of adherence to guidelines for the management of colon cancer may explain the situation. The aim was to elaborate a consensus on the multidisciplinary management of colon cancer, based on European guidelines (ESMO and EURECCA), and also taking into account local special characteristics of our healthcare system. Following discussion and online communication among members of an executive team, a consensus was developed. Statements entered the Delphi voting system on two rounds to achieve consensus by multidisciplinary international experts. Statements with an agreement rate of ≥80% achieved a large consensus, while those with an agreement rate of 60-80% a moderate consensus. Statements achieving an agreement of <60% after both rounds were rejected and not presented. Sixty statements on the management of colon cancer were subjected to the Delphi methodology. Voting experts were 109. The median rate of abstain per statement was 10% (range: 0-41%). In the end of the voting process, all statements achieved a consensus by more than 80% of the experts. A consensus on the management of colon cancer was developed by applying the Delphi methodology. Guidelines are proposed along with algorithms of diagnosis and treatment. The importance of centralization, care by a multidisciplinary team, and adherence to guidelines is emphasized. PMID:26752945

Oyster Culinary-Medicinal Mushroom, Pleurotus ostreatus (Higher Basidiomycetes), Growth in Grain-Based Diet Improves Broiler Chicken Production.

PubMed

Santos, Mateus P; Marcante, Rafael C; Santana, Thiago T; Tanaka, Henrique S; Funari, Pascoal; Alberton, Luiz R; Faria, Eliete V; Valle, Juliana S; Colauto, Nelson B; Linde, Giani A

2015-01-01

Many alternative compounds have been tested to improve poultry performance but few of them have previously used mycelial-colonized substrate to partially replace standard diet in broiler chickens. The objective of this study was to evaluate broiler chicken production, health, and meat sensory characteristics, with partial replacement of the standard diet by Pleurotus ostreatus-colonized substrate. One hundred fifty 1-day-old male Cobb chicks were given standard diet partially replaced by 0, 5, 10, 100, or 200 g·kg⁻¹ of P. ostreatus-colonized substrate and randomly distributed into five treatments. Each treatment had three replicates, with 10 birds per replicate, totaling 30 birds. The replacement of the standard diet by 10 g·kg⁻¹ of colonized substrate increased (P≤0.05) chicken body mass up to 57% at 21 days, and up to 28% at 42 days. In general, partial replacement of standard diet by colonized substrate increased hematocrits and typical lymphocytes, and reduced low density lipoproteins. Also, it reduced chicken production period up to 21% and there is no meat taste alteration. The use of P. ostreatus-colonized substrate in chicken feeding is an alternative method to improve broiler chicken production.

Intraoperative bowel irrigation improves anastomotic collagen metabolism in the left-sided colonic obstruction but not covering colostomy.

PubMed

Duraker, N; Bender, O; Memişoğlu, K; Yalçiner, A

1998-01-01

This study investigated the effects of intraoperative colonic irrigation and proximal diverting end colostomy after segmental bowel resection in experimental left-colonic obstruction on anastomotic healing. Simple obstruction of descending colon was performed in male Sprague-Dawley rats. After 24 h we performed segmental colonic resection and anastomosis in the control group (n = 15); resection, anastomosis, and covering colostomy in the colostomy group (n = 14); resection and anastomosis after antegrade colonic lavage through cecum by using isotonic saline solution in the irrigation group (n = 13). In rats that were killed 7 days later anastomotic dehiscence and bursting pressure and tissue hydroxyproline concentration at the anastomosis were measured. No significant differences were observed between groups in terms of anastomotic dehiscence, bursting site, or pressure. The hydroxyproline concentration was significantly higher in the irrigation group than the control group (P = 0.025) and the colostomy group (P = 0.029), but no difference was noted between the control group and the colostomy group. These findings suggest that intraoperative antegrade colonic irrigation in the acute left-sided colonic obstruction positively affects collagen metabolism at the anastomotic site; if the anastomosis is performed without bowel cleansing, covering colostomy does not improve collagen metabolism.

Colon-targeted delivery of cyclosporine A using dual-functional Eudragit® FS30D/PLGA nanoparticles ameliorates murine experimental colitis.

PubMed

Naeem, Muhammad; Bae, Junhwan; Oshi, Murtada A; Kim, Min-Soo; Moon, Hyung Ryong; Lee, Bok Luel; Im, Eunok; Jung, Yunjin; Yoo, Jin-Wook

2018-01-01

Colon-targeted oral nanoparticles (NPs) have emerged as an ideal, safe, and effective therapy for ulcerative colitis (UC) owing to their ability to selectively accumulate in inflamed colonic mucosa. Cyclosporine A (CSA), an immunosuppressive agent, has long been used as rescue therapy in severe steroid-refractory UC. In this study, we developed CSA-loaded dual-functional polymeric NPs composed of Eudragit ® FS30D as a pH-sensitive polymer for targeted delivery to the inflamed colon, and poly(lactic-co-glycolic acid) (PLGA) as a sustained-release polymer. CSA-loaded Eudragit FS30D nanoparticles (ENPs), PLGA nanoparticles (PNPs), and Eudragit FS30D/PLGA nanoparticles (E/PNPs) were prepared using the oil-in-water emulsion method. Scanning electron microscope images and zeta size data showed successful preparation of CSA-loaded NPs. PNPs exhibited a burst drug release of >60% at pH 1.2 (stomach pH) in 0.5 h, which can lead to unwanted systemic absorption and side effects. ENPs effectively inhibited the burst drug release at pH 1.2 and 6.8 (proximal small intestine pH); however, nearly 100% of the CSA in ENPs was released rapidly at pH 7.4 (ileum-colon pH) owing to complete NP dissolution. In contrast to single-functional PNPs and ENPs, the dual-functional E/PNPs minimized burst drug release (only 18%) at pH 1.2 and 6.8, and generated a sustained release at pH 7.4 thereafter. Importantly, in distribution studies in the gastrointestinal tracts of mice, E/PNPs significantly improved CSA distribution to the colon compared with PNPs or ENPs. In a mouse model of colitis, E/PNP treatment improved weight loss and colon length, and decreased rectal bleeding, spleen weight, histological scoring, myeloperoxidase activity, macrophage infiltration, and expression of proinflammatory cytokines compared with PNPs or ENPs. Overall, this work confirms the benefits of CSA-loaded E/PNPs for efficiently delivering CSA to the colon, suggesting their potential for UC therapy.

Abdominal Manual Therapy Repairs Interstitial Cells of Cajal and Increases Colonic c-Kit Expression When Treating Bowel Dysfunction after Spinal Cord Injury

PubMed Central

Zhang, Wenyi; Zhu, Zhaojin; Xie, Bin; Yu, Jun

2017-01-01

Background This study aimed to evaluate the therapeutic effects of abdominal manual therapy (AMT) on bowel dysfunction after spinal cord injury (SCI), investigating interstitial cells of Cajal (ICCs) and related c-kit expression. Methods Model rats were divided as SCI and SCI with drug treatment (intragastric mosapride), low-intensity (SCI + LMT; 50 g, 50 times/min), and high-intensity AMT (SCI + HMT; 100 g, 150 times/min). After 14 days of treatment, weight, improved Basso-Beattie-Bresnahan (BBB) locomotor score, and intestinal movement were evaluated. Morphological structure of spinal cord and colon tissues were examined. Immunostaining, RT-PCR, and western blot were used to assess c-kit expression. Results In SCI rats, AMT could not restore BBB, but it significantly increased weight, shortened time to defecation, increased feces amounts, and improved fecal pellet traits and colon histology. AMT improved the number, distribution, and ultrastructure of colonic ICCs, increasing colonic c-kit mRNA and protein levels. Compared with the SCI + Drug and SCI + LMT groups, the SCI + HMT group showed better therapeutic effect in improving intestinal transmission function and promoting c-kit expression. Conclusions AMT is an effective therapy for recovery of intestinal transmission function. It could repair ICCs and increase c-kit expression in colon tissues after SCI, in a frequency-dependent and pressure-dependent manner. PMID:29349063

Texture-based CAD improves diagnosis for low-dose CT colonography

NASA Astrophysics Data System (ADS)

Liang, Zhengrong; Cohen, Harris; Posniak, Erica; Fiore, Eddie; Wang, Zigang; Li, Bin; Andersen, Joseph; Harrington, Donald

2008-03-01

Computed tomography (CT)-based virtual colonoscopy or CT colonography (CTC) currently utilizes oral contrast solutions to tag the colonic fluid and possibly residual stool for differentiation from the colon wall and polyps. The enhanced image density of the tagged colonic materials causes a significant partial volume (PV) effect into the colon wall as well as the lumen space (filled with air or CO II). The PV effect on the colon wall can "bury" polyps of size as large as 5mm by increasing their image densities to a noticeable level, resulting in false negatives. It can also create false positives when PV effect goes into the lumen space. We have been modeling the PV effect for mixture-based image segmentation and developing text-based computer-aided detection of polyp (CADpolyp) by utilizing the PV mixture-based image segmentation. This work presents some preliminary results of developing and applying texture-based CADpolyp technique to low-dose CTC studies. A total of 114 studies of asymptomatic patients older than 50, who underwent CTC and then optical colonoscopy (OC) on the same day, were selected from a database, which was accumulated in the past decade and contains various bowel preparations and CT scanning protocols. The participating radiologists found ten polyps of greater than 5 mm from a total of 16 OC proved polyps, i.e., a detection sensitivity of 63%. They scored 23 false positives from the database, i.e., a 20% false positive rate. Approximately 70% of the datasets were marked as imperfect bowel cleansing and/or presence of image artifacts. The impact of imperfect bowel cleansing and image artifacts on VC performance is significant. The texture-based CADpolyp detected all the polyps with an average of 2.68 false positives per patient. This indicates that texture-based CADpolyp can improve the CTC performance in the cases of imperfect cleansed bowels and presence of image artifacts.

EURECCA colorectal: multidisciplinary mission statement on better care for patients with colon and rectal cancer in Europe.

PubMed

van de Velde, Cornelis J H; Aristei, Cynthia; Boelens, Petra G; Beets-Tan, Regina G H; Blomqvist, Lennart; Borras, Josep M; van den Broek, Colette B M; Brown, Gina; Coebergh, Jan-Willem; Cutsem, Eric Van; Espin, Eloy; Gore-Booth, Jola; Glimelius, Bengt; Haustermans, Karin; Henning, Geoffrey; Iversen, Lene H; Han van Krieken, J; Marijnen, Corrie A M; Mroczkowski, Pawel; Nagtegaal, Iris; Naredi, Peter; Ortiz, Hector; Påhlman, Lars; Quirke, Philip; Rödel, Claus; Roth, Arnaud; Rutten, Harm J T; Schmoll, Hans J; Smith, Jason; Tanis, Pieter J; Taylor, Claire; Wibe, Arne; Gambacorta, Maria Antonietta; Meldolesi, Elisa; Wiggers, Theo; Cervantes, Andres; Valentini, Vincenzo

2013-09-01

Care for patients with colon and rectal cancer has improved in the last twenty years however still considerable variation exists in cancer management and outcome between European countries. Therefore, EURECCA, which is the acronym of European Registration of cancer care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012 the first multidisciplinary consensus conference about colon and rectum was held looking for multidisciplinary consensus. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries. The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Experts commented and voted on the two web-based online voting rounds before the meeting (between 4th and 25th October and between the 20th November and 3rd December 2012) as well as one online round after the meeting (4th-20th March 2013) and were invited to lecture on the subjects during the meeting (13th-15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. All sentences that were voted on are available on the EURECCA website www.canceraudit.eu. The consensus document was divided in sections describing evidence based algorithms of diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and stage IV separately. Consensus was achieved using the Delphi method. The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members. It is feasible to achieve European Consensus on key diagnostic and treatment issues using the Delphi method. This consensus embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe. Copyright © 2013 Elsevier Ltd. All rights reserved.

Risk Factors for Pneumococcal Colonization of the Nasopharynx in Alaska Native Adults and Children.

PubMed

Reisman, Jonathan; Rudolph, Karen; Bruden, Dana; Hurlburt, Debby; Bruce, Michael G; Hennessy, Thomas

2014-06-01

Alaska Native children have high invasive pneumococcal disease (IPD) rates, and lack of in-home running water has been shown to have a significant association with infection. Pneumococcal conjugate vaccines reduced IPD; however, this population saw substantial replacement disease and colonization with nonvaccine serotypes. We evaluated risk factors for nasopharyngeal pneumococcal colonization in Alaska Native adults and children. We conducted annual surveys from 2008 through 2011 of residents of all ages in 8 rural Alaskan villages. Interviews were conducted, medical charts were reviewed, and nasopharyngeal swabs were cultured for Streptococcus pneumoniae. Multivariate logistic regression models were developed for 3 age groups (under 10 years, 10-17 years, and 18 years and older) to determine risk factors for colonization. We obtained 12 535 nasopharyngeal swabs from 4980 participants. Our population lived in severely crowded conditions, and 48% of households lacked in-home running water. In children <10 years, colonization was associated with lack of in-home running water, household crowding, and more children in the home. Pneumococcal vaccination status was not associated with colonization. In older children and adults, increased number of persons in the household was associated with pneumococcal colonization. Higher colonization prevalence may partially explain increased IPD rates seen in those lacking in-home water services. Improving availability of sanitation services and reducing household crowding may reduce the burden of IPD in this population. © The Author 2013. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Shortened length of stay and hospital cost reduction with implementation of an accelerated clinical care pathway after elective colon resection.

PubMed

Stephen, Antonia E; Berger, David L

2003-03-01

Patient care pathways have been developed for operative procedures with documented improvements in length of stay and cost without compromising outcome. The average hospital stay after colonic resection is 5 to 10 days. This study describes a clinical pathway for colon resections and examines patient outcome before and after institution of the pathway. One hundred thirty-eight patients underwent elective colon resections at our institution by a single surgeon before (n = 52) and after (n = 86) introduction of a clinical pathway. Length of stay, postoperative complications, readmissions, and cost per patient were compared between the 2 groups. Mean total length of stay (+/- standard deviation [SD]) was less in the postclinical pathway patients (3.7 +/- 1.5 days) compared to preclinical pathway patients (6.6 +/- 3.3 days) (P <.001). When adjusted for age, sex, diagnosis, and type of operation, the difference in length of stay remains statistically significant (P <.001). There was 1 readmission in the prepathway group and 8 readmissions in the postpathway group. When the readmissions were added to the original admissions, the mean length of stay in the postpathway patients was 4.2 +/- 2.8 days and in the prepathway patients was 6.9 +/- 4.1 days (P <.001). The average cost per patient (+/- standard error of the mean), with readmission costs added, was 9310 +/- 5170 US dollars in the prepathway group and 7070 +/- 3670 US dollars in the postpathway group (P =.002). The institution of a clinical pathway for elective, open colon resections can be done safely with improvements in cost and length of stay.

Effectiveness of a multimedia-based educational intervention for improving colon cancer literacy in screening colonoscopy patients.

PubMed

Hassinger, James P; Holubar, Stefan D; Pendlimari, Rajesh; Dozois, Eric J; Larson, David W; Cima, Robert R

2010-09-01

Limited data exist regarding colon cancer literacy in screening colonoscopy patients. We aimed to prospectively assess baseline colon cancer literacy and to determine whether a multimedia educational intervention was associated with improved colon cancer literacy. Colon cancer literacy was assessed in a convenience sample of colonoscopy patients before and after educational intervention. Statistically significant associations with colon cancer literacy scores were assessed by use of multivariate logistic regression analysis. Results are frequency (proportion), mean +/- SD, and odds ratio (OR (95% CI)). Seventy-three subjects participated: mean age, 57 +/- 12 years, 35 (48%) were women, 41 (57%) had a college degree, 43 (59%) had prior colonoscopy, 21 (29%) were accompanying family, and 16 (22%) were health care employees. Multivariate factors associated with a higher baseline colon cancer literacy score included health care employee status (7.9 (95% CI, 1.6-63); P = .02) and family colon cancer history (5.3 (95% CI, 1.3-25); P = .02). After multimedia education, mean scores improved from 53% +/- 23% to 88% +/- 12% (Delta = 35%; P < .0001). On univariate analysis, college-educated subjects had higher final scores (91% vs 83%; P = .007), but this association was not significant on multivariate regression (P = .07). Only baseline score was associated with higher postintervention score (1.7 (95% CI, 1.2-2.6); P = .005). Sixty-two subjects (86%) were very satisfied, and 70 (97%) would recommend the module to friends and family. A knowledge deficit of colon cancer-related concepts is frequently observed in patients undergoing screening colonoscopy. Multimedia-based educational intervention was an effective, satisfying strategy for addressing cancer-specific knowledge deficit in laypersons.

Nitric oxide-releasing aspirin but not conventional aspirin improves healing of experimental colitis

PubMed Central

Zwolinska-Wcislo, Malgorzata; Brzozowski, Tomasz; Ptak-Belowska, Agata; Targosz, Aneta; Urbanczyk, Katarzyna; Kwiecien, Slawomir; Sliwowski, Zbigniew

2011-01-01

AIM: To determine the effect of non-selective cyclooxygenase (COX) inhibitors, selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis. METHODS: Rats with 2,4,6 trinitrobenzenesulfon-ic acid (TNBS)-induced colitis received intragastric (ig) treatment with vehicle, aspirin (ASA) (a non-selective COX inhibitor), celecoxib (a selective COX-2 inhibitor) or NO-releasing ASA for a period of ten days. The area of colonic lesions, colonic blood flow (CBF), myeloperoxidase (MPO) activity and expression of proinflammatory markers COX-2, inducible form of nitric oxide synthase (iNOS), IL-1β and tumor necrosis factor (TNF)-α were assessed. The effects of glyceryl trinitrate (GTN), a NO donor, and 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-​tetramethyl-1H-imidazolyl-1-oxy-3-oxide, onopotassium salt (carboxy-PTIO), a NO scavenger, administered without and with ASA or NO-ASA, and the involvement of capsaicin-sensitive afferent nerves in the mechanism of healing the experimental colitis was also determined. RESULTS: Rats with colitis developed macroscopic and microscopic colonic lesions accompanied by a significant decrease in the CBF, a significant rise in colonic weight, MPO activity and plasma IL-1β and TNF-α levels. These effects were aggravated by ASA and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560), but not celecoxib and counteracted by concurrent treatment with a synthetic prostaglandin E2 (PGE2) analog. Treatment with NO-ASA dose-dependently accelerated colonic healing followed by a rise in plasma NOx content and CBF, suppression of MPO and downregulation of COX-2, iNOS, IL-1β and TNF-α mRNAs. Treatment with GTN, the NO donor, significantly inhibited the ASA-induced colonic lesions and increased CBF, while carboxy-PTIO or capsaicin-denervation counteracted the NO-ASA-induced improvement of colonic healing and the accompanying increase in the CBF. These effects were restored by co-treatment with calcitonin gene related peptide (CGRP) and NO-ASA in capsaicin-denervated animals. CONCLUSION: NO-releasing ASA, in contrast to ASA, COX-1 inhibitors, and SC-560, accelerated the healing of colitis via a mechanism involving NO mediated improvement of microcirculation and activation of sensory nerves releasing CGRP. PMID:22039321

Agricultural practices to improve nitrogen use efficiency through the use of arbuscular mycorrhizae: Basic and agronomic aspects.

PubMed

Verzeaux, Julien; Hirel, Bertrand; Dubois, Frédéric; Lea, Peter J; Tétu, Thierry

2017-11-01

Nitrogen cycling in agroecosystems is heavily dependent upon arbuscular mycorrhizal fungi (AMF) present in the soil microbiome. These fungi develop obligate symbioses with various host plant species, thus increasing their ability to acquire nutrients. However, AMF are particularly sensitive to physical, chemical and biological disturbances caused by human actions that limit their establishment. For a more sustainable agriculture, it will be necessary to further investigate which agricultural practices could be favorable to maximize the benefits of AMF to improve crop nitrogen use efficiency (NUE), thus reducing nitrogen (N) fertilizer usage. Direct seeding, mulch-based cropping systems prevent soil mycelium disruption and increase AMF propagule abundance. Such cropping systems lead to more efficient root colonization by AMF and thus a better establishment of the plant/fungal symbiosis. In addition, the use of continuous cover cropping systems can also enhance the formation of more efficient interconnected hyphal networks between mycorrhizae colonized plants. Taking into account both fundamental and agronomic aspects of mineral nutrition by plant/AMF symbioses, we have critically described, how improving fungal colonization through the reduction of soil perturbation and maintenance of an ecological balance could be helpful for increasing crop NUE. Copyright © 2017 Elsevier B.V. All rights reserved.

Adjuvant 5FU plus levamisole in colonic or rectal cancer: improved survival in stage II and III

PubMed Central

Taal, B G; Van Tinteren, H; Zoetmulder, F A N

2001-01-01

Based on the first favourable results of adjuvant therapy of 5FU plus levamisole in Dukes C colonic cancer in 1990, we conducted a prospective trial. 1029 patients were randomised to receive one year 5FU plus levamisole or no further treatment following curative surgery for stage II or III colon (n = 730) or rectal cancer (n = 299). 45% were in stage II and 55% in stage III. With a median follow-up of 4 years and 9 months a significant reduction in odds of death (25%, SD 9%, P = 0.007) was observed for those with adjuvant treatment (65% at 5 year) compared to the observation group (55%). Improved relative survival was present in stage III (56% vs 44%), and in stage II patients (78% vs 70%). In rectal cancer a non-significant difference in disease-free or overall survival was observed. Distant metastases developed in 76%, while local recurrence alone occurred in 14%. An early start of adjuvant treatment (< 4 weeks) did not affect results. Compliance to 5FU plus levamisole was 69%. Severe toxicity did not occur. In conclusion, one year 5FU plus levamisole was of benefit in stage II and III colonic cancer; in rectal cancer a significant positive effect could not be demonstrated. © 2001 Cancer Research Campaign  http://www.bjcancer.com PMID:11720425

Pathophysiology and Therapeutic Strategies for Symptomatic Uncomplicated Diverticular Disease of the Colon.

PubMed

Scaioli, Eleonora; Colecchia, Antonio; Marasco, Giovanni; Schiumerini, Ramona; Festi, Davide

2016-03-01

Colonic diverticulosis imposes a significant burden on industrialized societies. The current accepted causes of diverticula formation include low fiber content in the western diet with decreased intestinal content and size of the lumen, leading to the transmission of muscular contraction pressure to the wall of the colon, inducing the formation of diverticula usually at the weakest point of the wall where penetration of the blood vessels occurs. Approximately 20 % of the patients with colonic diverticulosis develop abdominal symptoms (i.e., abdominal pain and discomfort, bloating, constipation, and diarrhea), a condition which is defined as symptomatic uncomplicated diverticular disease (SUDD). The pathogenesis of SUDD symptoms remains uncertain and even less is known about how to adequately manage bowel symptoms. Recently, low-grade inflammation, altered intestinal microbiota, visceral hypersensitivity, and abnormal colonic motility have been identified as factors leading to symptom development, thus changing and improving the therapeutic approach. In this review, a comprehensive search of the literature regarding on SUDD pathogenetic hypotheses and pharmacological strategies was carried out. The pathogenesis of SUDD, although not completely clarified, seems to be related to an interaction between colonic microbiota alterations, and immune, enteric nerve, and muscular system dysfunction (Cuomo et al. in United Eur Gastroenterol J 2:413-442, 2014). Greater understanding of the inflammatory pathways and gut microbiota composition in subjects affected by SUDD has increased therapeutic options, including the use of gut-directed antibiotics, mesalazine, and probiotics (Bianchi et al. in Aliment Pharmacol Ther 33:902-910, 2011; Comparato et al. in Dig Dis Sci 52:2934-2941, 2007; Tursi et al. in Aliment Pharmacol Ther 38:741-751, 2013); however, more research is necessary to validate the safety, effectiveness, and cost-effectiveness of these interventions.

Antagonizing pathways leading to differential dynamics in colon carcinogenesis in Shugoshin1 (Sgo1)-haploinsufficient chromosome instability model.

PubMed

Rao, Chinthalapally V; Sanghera, Saira; Zhang, Yuting; Biddick, Laura; Reddy, Arun; Lightfoot, Stan; Dai, Wei; Yamada, Hiroshi Y

2016-05-01

Colon cancer is the second most lethal cancer. It is predicted to claim 50,310 lives in 2014. Chromosome Instability (CIN) is observed in 80-90% of colon cancers, and is thought to contribute to colon cancer progression and recurrence. However, there are no animal models of CIN that have been validated for studies of colon cancer development or drug testing. In this study, we sought to validate a mitotic error-induced CIN model mouse, the Shugoshin1 (Sgo1) haploinsufficient mouse, as a colon cancer study model. Wild-type and Sgo1(-/+) mice were treated with the colonic carcinogen, azoxymethane (AOM). We tracked colon tumor development 12, 24, and 36 wk after treatment to assess progression of colon tumorigenesis. Initially, more precancerous lesions, Aberrant Crypt Foci (ACF), developed in Sgo1(-/+) mice. However, the ACF did not develop straightforwardly into larger tumors. At the 36-wk endpoint, the number of gross tumors in Sgo1(-/+) mice was no different from that in wild-type controls. However, Copy Number Variation (CNV) analysis indicated that fully developed colon tumor in Sgo1(-/+) mice carried 13.75 times more CNV. Immunohistological analyses indicated that Sgo1(-/+) mice differentially expressed IL-6, Bcl2, and p16(INK4A) . We propose that formation of ACF in Sgo1(-/+) mice is facilitated by the IL6-STAT3-SOCS3 oncogenic pathway and by the Bcl2-anti-apoptotic pathway, yet further development of the ACF to tumors is inhibited by the p16(INK4A) tumor suppressor pathway. Manipulating these pathways would be beneficial for inhibiting development of colon cancer with CIN. © 2015 Wiley Periodicals, Inc.

Fluorescently labeled chimeric anti-CEA antibody improves detection and resection of human colon cancer in a patient-derived orthotopic xenograft (PDOX) nude mouse model.

PubMed

Metildi, Cristina A; Kaushal, Sharmeela; Luiken, George A; Talamini, Mark A; Hoffman, Robert M; Bouvet, Michael

2014-04-01

The aim of this study was to evaluate a new fluorescently labeled chimeric anti-CEA antibody for improved detection and resection of colon cancer. Frozen tumor and normal human tissue samples were stained with chimeric and mouse antibody-fluorophore conjugates for comparison. Mice with patient-derived orthotopic xenografts (PDOX) of colon cancer underwent fluorescence-guided surgery (FGS) or bright-light surgery (BLS) 24 hr after tail vein injection of fluorophore-conjugated chimeric anti-CEA antibody. Resection completeness was assessed using postoperative images. Mice were followed for 6 months for recurrence. The fluorophore conjugation efficiency (dye/mole ratio) improved from 3-4 to >5.5 with the chimeric CEA antibody compared to mouse anti-CEA antibody. CEA-expressing tumors labeled with chimeric CEA antibody provided a brighter fluorescence signal on frozen human tumor tissues (P = 0.046) and demonstrated consistently lower fluorescence signals in normal human tissues compared to mouse antibody. Chimeric CEA antibody accurately labeled PDOX colon cancer in nude mice, enabling improved detection of tumor margins for more effective FGS. The R0 resection rate increased from 86% to 96% with FGS compared to BLS. Improved conjugating efficiency and labeling with chimeric fluorophore-conjugated antibody resulted in better detection and resection of human colon cancer in an orthotopic mouse model. © 2013 Wiley Periodicals, Inc.

Fate of Dyspeptic or Colonic Symptoms After Laparoscopic Cholecystectomy

PubMed Central

Kim, Gi Hyun; Lee, Hyo Deok; Kim, Min; Kim, Kyeongmin; Jeong, Yusook; Hong, Yong Joo; Kang, Eun Seok; Han, Joung-Ho; Choi, Jae-Woon; Park, Seon Mee

2014-01-01

Background/Aims Gallbladder diseases can give rise to dyspeptic or colonic symptoms in addition to biliary pain. Although most biliary pain shows improvement after cholecystectomy, the fates of dyspeptic or colonic symptoms still remain controversial. This study assessed whether nonspecific gastrointestinal symptoms improved after laparoscopic cholecystectomy (LC) and identified the characteristics of patients who experienced continuing or exacerbated symptoms following surgery. Methods Sixty-five patients who underwent LC for uncomplicated gallbladder stones or gallbladder polyps were enrolled. The patients were surveyed on their dyspeptic or colonic symptoms before surgery and again at 3 and 6 months after surgery. Patients' mental sanity was also assessed using a psychological symptom score with the Symptom Checklist-90-Revised questionnaire. Results Forty-four (67.7%) patients showed one or more dyspeptic or colonic symptoms before surgery. Among these, 31 (47.7%) and 36 (55.4%) patients showed improvement at 3 and 6 months after surgery, respectively. However, 18.5% of patients showed continuing or exacerbated symptoms at 6 months after surgery. These patients did not differ with respect to gallstone or gallbladder polyps, but differed in frequency of gastritis. These patients reported lower postoperative satisfaction. Patients with abdominal symptoms showed higher psychological symptom scores than others. However, poor mental sanity was not related to the symptom exacerbation. Conclusions Elective LC improves dyspeptic or colonic symptoms. Approximately 19% of patients reported continuing or exacerbated symptoms following LC. Detailed history-taking regarding gastritis before surgery can be helpful in predicting patients’ outcome after LC. PMID:24840378

In vivo endoscopic Doppler optical coherence tomography imaging of mouse colon

NASA Astrophysics Data System (ADS)

Welge, Weston A.; Barton, Jennifer K.

2016-03-01

Colorectal cancer remains the second deadliest cancer in the United States, despite the high sensitivity and specificity of colonoscopy and sigmoidoscopy. While these standard imaging procedures can accurately detect medium and large polyps, some studies have shown miss rates up to 25% for polyps less than 5 mm in diameter. An imaging modality capable of detecting small lesions could potentially improve patient outcomes. Optical coherence tomography (OCT) has been shown to be a powerful imaging modality for adenoma detection in a mouse model of colorectal cancer. While previous work has focused on analyzing the structural OCT images based on thickening of the mucosa and changes in light attenuation in depth, imaging the microvasculature of the colon may enable earlier detection of polyps. The structure and function of vessels grown to support tumor growth are markedly different from healthy vessels. Doppler OCT is capable of imaging microvessels in vivo. We developed a method of processing raw fringe data from a commercial swept-source OCT system using a lab-built miniature endoscope to extract microvessels. This method can be used to measure vessel count and density and to measure flow velocities. This may improve early detection and aid in the development of new chemopreventive and chemotherapeutic drugs. We present, to the best of our knowledge, the first endoscopic Doppler OCT images of in vivo mouse colon.

The herbal medicine Dai-Kenchu-To directly stimulates colonic motility.

PubMed

Kawahara, Hidejiro; Yanaga, Katsuhiko

2009-01-01

Dai-kenchu-to (DKT) has attracted attention as a drug that improves the symptoms of postoperative ileus. However, the detailed mechanism of its action still remains unknown. The effect of DKT on colonic motility was herein evaluated using an original method. Eight healthy male volunteers who understood the purpose of this study were enrolled. Dai-kenchu-to (5 g) was dissolved in saline and administered into the cecum using a colonoscope until the ascending colon became distended. Colonic motility was observed by extrasomatic ultrasonography for 30 min. Colonic contractions were observed 129.4 (range 110-145) s after DKT administration into the ascending colon. Every segment in the right colon divided by the crescentic folds contracted independently. On the other hand, no colonic contractions were observed in the right colon after saline solution alone was administered to the ascending colon. In conclusion, DKT stimulates colonic motility immediately after administration, in the same manner as it does for the upper alimentary tract.

Pilot study of pyridostigmine in constipated patients with autonomic neuropathy.

PubMed

Bharucha, Adil E; Low, Phillip A; Camilleri, Michael; Burton, Duane; Gehrking, Tonette L; Zinsmeister, Alan R

2008-08-01

The effects of cholinesterase inhibitors, which increase colonic motility in health, on chronic constipation are unknown. Our aims were to evaluate the efficacy of cholinesterase inhibitors for dysautonomia and chronic constipation and to assess whether acute effects could predict the long term response. In this single-blind study, 10 patients with autonomic neuropathy and constipation were treated with placebo (2 weeks), followed by an escalating dose of pyridostigmine to the maximum tolerated dose (i.e., 180-540 mg daily) for 6 weeks. Symptoms and gastrointestinal transit were assessed at 2 and 8 weeks. The acute effects of neostigmine on colonic transit and motility were also assessed. At baseline, 4, 6, and 3 patients had delayed gastric, small intestinal, and colonic transit respectively. Pyridostigmine was well tolerated in most patients, improved symptoms in 4 patients, and accelerated the geometric center for colonic transit at 24 h by > or =0.7 unit in 3 patients. The effects of i.v. neostigmine on colonic transit and compliance predicted (P < 0.05) the effects of pyridostigmine on colonic transit. Pyridostigmine improves colonic transit and symptoms in some patients with autonomic neuropathy and constipation. The motor response to neostigmine predicted the response to oral pyridostigmine.

A Challenging Case of Acute Mercury Toxicity

PubMed Central

Alghoula, Faysal; Holewinski, Christopher

2018-01-01

Background Mercury exists in multiple forms: elemental, organic, and inorganic. Its toxic manifestations depend on the type and magnitude of exposure. The role of colonoscopic decompression in acute mercury toxicity is still unclear. We present a case of acute elemental mercury toxicity secondary to mercury ingestion, which markedly improved with colonoscopic decompression. Clinical Case A 54-year-old male presented to the ED five days after ingesting five ounces (148 cubic centimeters) of elemental mercury. Examination was only significant for a distended abdomen. Labs showed elevated serum and urine mercury levels. An abdominal radiograph showed radiopaque material throughout the colon. Succimer and laxatives were initiated. The patient had recurrent bowel movements, and serial radiographs showed interval decrease of mercury in the descending colon with interval increase in the cecum and ascending colon. Colonoscopic decompression was done successfully. The colon was evacuated, and a repeat radiograph showed decreased hyperdense material in the colon. Three months later, a repeat radiograph showed no hyperdense material in the colon. Conclusion Ingested elemental mercury can be retained in the colon. Although there are no established guidelines for colonoscopic decompression, our patient showed significant improvement. We believe further studies on this subject are needed to guide management practices. PMID:29559996

The early effect of dextran sodium sulfate administration on carbachol-induced short-circuit current in distal and proximal colon during colitis development.

PubMed

Hock, M; Soták, M; Kment, M; Pácha, J

2011-01-01

Increased colonic Cl(-) secretion was supposed to be a causative factor of diarrhea in inflammatory bowel diseases. Surprisingly, hyporesponsiveness to Cl(-) secretagogues was later described in inflamed colon. Our aim was to evaluate changes in secretory responses to cholinergic agonist carbachol in distal and proximal colon during colitis development, regarding secretory activity of enteric nervous system (ENS) and prostaglandins. Increased responsiveness to carbachol was observed in both distal and proximal colon after 3 days of 2 % dextran sodium sulfate (DSS) administration. It was measured in the presence of mucosal Ba(2+) to emphasize Cl(-) secretion. The described increase was abolished by combined inhibitory effect of tetrodotoxin (TTX) and indomethacin. Indomethacin also significantly reduced TTX-sensitive current. On the 7th day of colitis development responsiveness to carbachol decreased in distal colon (compared to untreated mice), but did not change in proximal colon. TTX-sensitive current did not change during colitis development, but indomethacin-sensitive current was significantly increased the 7th day. Decreased and deformed current responses to serosal Ba(2+) were observed during colitis induction, but only in proximal colon. We conclude that besides inhibitory effect of DSS on distal colon responsiveness, there is an early stimulatory effect that manifests in both distal and proximal colon.

An oral colon-targeting controlled release system based on resistant starch acetate: synthetization, characterization, and preparation of film-coating pellets.

PubMed

Pu, Huayin; Chen, Ling; Li, Xiaoxi; Xie, Fengwei; Yu, Long; Li, Lin

2011-05-25

An oral colon-targeting controlled release system based on resistant starch acetate (RSA) as a film-coating material was developed. The RSA was successfully synthesized, and its digestion resistibility could be improved by increasing the degree of substitution (DS), which was favorable for the colon-targeting purpose. As a delivery carrier material, the characteristics of RSA were investigated by polarized light microscopy, FTIR spectroscopy, and X-ray diffraction. The results revealed a decrease of the crystallinity of RSA and a change of its crystalline structure from B + V hydrid type to V type. To evaluate the colon-targeting release performance, the RSA film-coated pellets loaded with different bioactive components were prepared by extrusion-spheronization and then by fluid bed coating. The effects of the DS, plasticizer content, and coating thickness of the RSA film and those of the content and molecular weight of the loaded bioactive component on the colon-targeting release performance of the resulting delivery system were investigated. By adjusting the DS, the coating thickness, and the plasticizer content of the RSA film, either the pellets loaded with a small molecular bioactive component such as 5-aminosalicylic acid or those with a macromolecular bioactive peptide or protein such as bovine serum albumin, hepatocyte growth-promoting factor, or insulin showed a desirable colon-targeting release performance. The release percentage was less than 12% in simulated upper gastrointestinal tract and went up to 70% over a period of 40 h in simulated colonic fluid. This suggests that the delivery system based on RSA film has an excellent colon-targeting release performance and the universality for a wide range of bioactive components.

Aspergillus Colonization of the Lung Allograft is a Risk Factor for Bronchiolitis Obliterans Syndrome

PubMed Central

Weigt, S. Samuel; Elashoff, Robert M.; Huang, Cathy; Ardehali, Abbas; Gregson, Aric L.; Kubak, Bernard; Fishbein, Michael C.; Saggar, Rajeev; Keane, Michael P.; Saggar, Rajan; Lynch, Joseph P.; Zisman, David A.; Ross, David J.; Belperio, John A.

2014-01-01

Multiple infections have been linked with the development of bronchiolitis obliterans syndrome (BOS) post-lung transplantation. Lung allograft airway colonization by Aspergillus species is common among lung transplant recipients. We hypothesized that Aspergillus colonization may promote the development of BOS and may decrease survival post-lung transplantation. We reviewed all lung transplant recipients transplanted in our center between 1/2000 and 6/2006. Bronchoscopy was performed according to a surveillance protocol and when clinically indicated. Aspergillus colonization was defined as a positive culture from bronchoalveolar lavage or two sputum cultures positive for the same Aspergillus species, in the absence of invasive pulmonary Aspergillosis. We found that Aspergillus colonization was strongly associated with BOS and BOS related mortality in Cox regression analyses. Aspergillus colonization typically preceded the development of BOS by a median of 261 days (95% CI 87 to 520). Furthermore, in a multivariate Cox regression model, Aspergillus colonization was a distinct risk factor for BOS, independent of acute rejection. These data suggest a potential causative role for Aspergillus colonization in the development of BOS post-lung transplantation and raise the possibility that strategies aimed to prevent Aspergillus colonization may help delay or reduce the incidence of BOS. PMID:19459819

Ecological studies on the revegetation process of surface coal mined areas in North Dakota. 4. Soil and vegetation development on topsoiled areas. Final report Aug 75-Jun 82

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iverson, L.R.; Wali, M.K.

1982-06-01

Four North Dakota reclaimed mined sites one to four years in age were studied for patterns of species colonization, biochemical interaction among species, competitive phenomena, and management applications. Kochia scoparia, a colonizer, was the dominant species for the first two years, but was completely eliminated by the fourth year; the planted Agropyron grasses concomitantly increased during this four year period. Competition experiments between Kochia and Agropyron revealed that Kochia initially acted as a 'nurse' crop for Agropyron establishment. Mowing of the first year colonizing species (especially Kochia) just prior to seed set proved to be very effective at reducing weedmore » populations and improving planted Agropyron populations in the second year. This method is highly recommended for use in hastening the establishment of planted species after mining.« less

Yeasts from skin colonization are able to cross the acellular dermal matrix.

PubMed

Jarros, Isabele Carrilho; Okuno, Érika; Costa, Maiara Ignacio; Veiga, Flávia Franco; de Souza Bonfim-Mendonça, Patricia; Negri, Melyssa Fernanda Norman; Svidzinski, Terezinha Inez Estivalet

2018-04-01

In recent decades, the prognosis for burn patients has improved considerably with the development of specialized care. The acellular dermal matrix (ADM) is a totally artificial acellular device that functions to control water loss, prevent penetration by bacteria and allow migration of endothelial cells and fibroblasts from patient tissues. However, little is known about its effectiveness against yeasts. The present study evaluated the capacity of colonization and migration of some human commensal yeasts. Three clinical isolates from skin scales, identified as Candida parapsilosis, Candida glabrata and Rhodotorula mucilaginosa, were used. Their ability to cross the ADM was evaluated. After three days, all isolates had crossed the ADM. C. parapsilosis showed the lowest growth, while R. mucilaginosa showed intermediate and C. glabrata the highest growth. In the plates incubated for seven days, the growth of C. parapsilosis and C. glabrata increased by 1 log over the third day. All isolates have the capacity to colonize and migrate through the matrix, increasing the potential risk to burn patients, who can develop severe and even fatal infections by invasive fungi. Copyright © 2018 Elsevier Ltd. All rights reserved.

Untargeted metabolomics of colonic digests reveals kynurenine pathway metabolites, dityrosine and 3-dehydroxycarnitine as red versus white meat discriminating metabolites

PubMed Central

Rombouts, Caroline; Hemeryck, Lieselot Y.; Van Hecke, Thomas; De Smet, Stefaan; De Vos, Winnok H.; Vanhaecke, Lynn

2017-01-01

Epidemiological research has demonstrated that the consumption of red meat is an important risk factor for the development of colorectal cancer (CRC), diabetes mellitus and cardiovascular diseases. However, there is no holistic insight in the (by-) products of meat digestion that may contribute to disease development. To address this hiatus, an untargeted mass spectrometry (MS)-based metabolomics approach was used to create red versus white meat associated metabolic fingerprints following in vitro colonic digestion using the fecal inocula of ten healthy volunteers. Twenty-two metabolites were unequivocally associated with simulated colonic digestion of red meat. Several of these metabolites could mechanistically be linked to red meat-associated pathways including N’-formylkynurenine, kynurenine and kynurenic acid (all involved in tryptophan metabolism), the oxidative stress marker dityrosine, and 3-dehydroxycarnitine. In conclusion, the used MS-based metabolomics platform proved to be a powerful platform for detection of specific metabolites that improve the understanding of the causal relationship between red meat consumption and associated diseases. PMID:28195169

Carbapenem-resistant Enterobacteriaceae colonization (CRE) and subsequent risk of infection and 90-day mortality in critically ill patients, an observational study.

PubMed

McConville, Thomas Howe; Sullivan, Sean Berger; Gomez-Simmonds, Angela; Whittier, Susan; Uhlemann, Anne-Catrin

2017-01-01

Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as an urgent public health threat. Intestinal colonization with CRE has been identified as a risk factor for the development of systemic CRE infection, but has not been compared to colonization with third and/or fourth generation cephalosporin-resistant (Ceph-R) Enterobacteriaceae. Moreover, the risk conferred by colonization on adverse outcomes is less clear, particularly in critically ill patients admitted to the intensive care unit (ICU). We carried out a cohort study of consecutive adult patients screened for rectal colonization with CRE or Ceph-R upon ICU entry between April and July 2013. We identified clinical variables and assessed the relationship between CRE or Ceph-R colonization and subsequent systemic CRE infection within 30 days (primary outcome) and all-cause mortality within 90 days (secondary outcome). Among 338 ICU patients, 94 (28%) were colonized with either Ceph-R or CRE. 26 patients developed CRE infection within 30 days of swab collection; 47% (N = 17/36) of CRE-colonized and 3% (N = 2/58) of Ceph-R colonized patients. 36% (N = 13/36) of CRE-colonized patients died within 90 days compared to 31% (N = 18/58) of Ceph-R-colonized and 15% (N = 37/244) of non-colonized patients. In a multivariable analysis, CRE colonization independently predicted development of a systemic CRE infection at 30 days (aOR 10.8, 95% CI2.8-41.9, p = 0.0006); Ceph-R colonization did not (aOR 0.5, 95% CI0.1-3.3, p = 0.5). CRE colonization was associated with increased 90-day mortality in a univariable analysis (p-value 0.001), in a multivariable model, previous hospitalization and medical ICU admission were independent predictors of 90-day mortality whereas CRE colonization approached significance (aOR 2.3, 95% CI1.0-5.3, p = 0.056). Our study highlights the increased risk of CRE infection and mortality in patients with CRE colonization at the time of ICU admission. Future studies are needed to assess how CRE colonization can guide empiric antibiotic choices and to develop novel decolonization strategies.

Registration of central paths and colonic polyps between supine and prone scans in computed tomography colonography: Pilot study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Ping; Napel, Sandy; Acar, Burak

2004-10-01

Computed tomography colonography (CTC) is a minimally invasive method that allows the evaluation of the colon wall from CT sections of the abdomen/pelvis. The primary goal of CTC is to detect colonic polyps, precursors to colorectal cancer. Because imperfect cleansing and distension can cause portions of the colon wall to be collapsed, covered with water, and/or covered with retained stool, patients are scanned in both prone and supine positions. We believe that both reading efficiency and computer aided detection (CAD) of CTC images can be improved by accurate registration of data from the supine and prone positions. We developed amore » two-stage approach that first registers the colonic central paths using a heuristic and automated algorithm and then matches polyps or polyp candidates (CAD hits) by a statistical approach. We evaluated the registration algorithm on 24 patient cases. After path registration, the mean misalignment distance between prone and supine identical anatomic landmarks was reduced from 47.08 to 12.66 mm, a 73% improvement. The polyp registration algorithm was specifically evaluated using eight patient cases for which radiologists identified polyps separately for both supine and prone data sets, and then manually registered corresponding pairs. The algorithm correctly matched 78% of these pairs without user input. The algorithm was also applied to the 30 highest-scoring CAD hits in the prone and supine scans and showed a success rate of 50% in automatically registering corresponding polyp pairs. Finally, we computed the average number of CAD hits that need to be manually compared in order to find the correct matches among the top 30 CAD hits. With polyp registration, the average number of comparisons was 1.78 per polyp, as opposed to 4.28 comparisons without polyp registration.« less

Inulin based glutathione-responsive delivery system for colon cancer treatment.

PubMed

Wang, Dongdong; Sun, Feifei; Lu, Chunbo; Chen, Peng; Wang, Zhaojie; Qiu, Yuanhao; Mu, Haibo; Miao, Zehong; Duan, Jinyou

2018-05-01

Colorectal cancer is one of the most common types of tumor in the world. Here we developed a lipoic acid esterified polysaccharide (inulin) delivery system for tanshinone IIA to treat colorectal cancer in vitro. The release of tanshinone IIA in the system was highly responsive to glutathione, which is commonly abundant in cancer cells. In addition, this drug delivery system was proliferative to Bifidobacterium longum, the common inhabitant of human intestine. Thus, this strategy might be useful to improve colon cancer therapy efficacy of anticancer drugs and meanwhile promote the growth of beneficial commensal flora in the gut. Copyright © 2018 Elsevier B.V. All rights reserved.

Gamma-cyclodextrin/usnic acid thin film fabricated by MAPLE for improving the resistance of medical surfaces to Staphylococcus aureus colonization

NASA Astrophysics Data System (ADS)

Iordache, Florin; Grumezescu, Valentina; Grumezescu, Alexandru Mihai; Curuţiu, Carmen; Diţu, Lia Mara; Socol, Gabriel; Ficai, Anton; Truşcă, Roxana; Holban, Alina Maria

2015-05-01

This study reports on the successful deposition of γ-cyclodextrin/usnic acid (γCD/UA) thin film by Matrix Assisted Pulsed Laser Evaporation (MAPLE) as anti-adherent coating on medical surfaces against microbial colonization. The obtained results demonstrate that these bioactive thin films inhibit Staphylococcus aureus biofilm formation at all stages, starting with their initiation. The antibiofilm effect was constant along the bacterial incubation time. Furthermore, the γCD/UA coatings show a great biocompatibility which means that this material is suitable for the development of modern medical devices with antimicrobial properties.

Ginseng Berry Extract Attenuates Dextran Sodium Sulfate-Induced Acute and Chronic Colitis

PubMed Central

Zhang, Wei; Xu, Li; Cho, Si-Young; Min, Kyung-Jin; Oda, Tatsuya; Zhang, LiJun; Yu, Qing; Jin, Jun-O

2016-01-01

This study investigates the in vivo functions of ginseng berry extract (GB) as a therapy for dextran sodium sulfate (DSS)-induced colitis. C57BL/6 mice were given drinking water containing DSS (3%) for eight days to induce acute colitis. At the same time, the mice received an oral dose of GB (50 mg/kg) once daily. The GB-treated mice were less susceptible to the development of acute colitis than were control mice treated with saline, as determined by weight loss, disease activity, and colon histology. The administration of GB to DSS-treated mice also reduced the numbers and inhibited the activation of colon-infiltrating T cells, neutrophils, intestinal CD103−CD11c+ dendritic cells (cDCs), and macrophages. In addition, GB treatment promoted the migration of CD103+CD11c+ cDCs and expansion of Foxp3+ regulatory T cells in the colons of DSS-treated mice. Similarly, in the DSS-induced chronic colitis model, GB treatment improved the macroscopic and histological appearance of the colon wall when compared to untreated control mice, as indicated by longer colon length and lower histological scores. This is the first report to show that oral administration of GB suppresses immune activation and protects against experimentally induced colitis. PMID:27058552

Natural products to improve quality of life targeting for colon drug delivery.

PubMed

Kim, Hyunjo

2012-03-01

The colon is largely being investigated as a site for administration of protein and peptides, which are degraded by digestive enzymes in the upper GIT. Also for local diseases of the colon such as inflammatory bowel disease, colorectal cancer and ameobiasis, drug administration to the site of action can not only reduce the dose to be administered, but also decrease the side effects. Inflammatory Bowel Disease (IBD) such as Ulcerative colitis and Crohn's disease are characterized by chronic intestinal inflammation. Intestinal bacteria initiate the activation of intestinal inflammatory processes, which are mediated by pro-inflammatory cytokines and chemokine. Increased chemokine expression has also been observed in epithelial cells, endothelial cells, and smooth muscle cells. Future trials of specific agents capable of inhibiting chemokine synthesis and secretion or blocking chemokine-chemokine receptor interaction will be important to study in patients with ulcerative colitis and Crohn's disease. Many important bioactive compounds have been discovered from natural sources using bioactivity directed fractionation and isolation (BDFl) Continuing discovery has also been facilitated by the recent development of new bioassay methods. These bioactive compounds are mostly plant secondary metabolites, and many naturally occurring pure compounds have become medicines, dietary supplements, and other useful commercial products. The present review includes various approaches investigated for colon drug delivery and their site specificity. To achieve successful colonic delivery, a drug needs to be protected from absorption and the environment of the upper gastrointestinal tract and then be abruptly released into the proximal colon, which is considered the optimum site for colon targeted delivery of drugs.

A morel improved growth and suppressed Fusarium infection in sweet corn.

PubMed

Yu, Dan; Bu, Fangfang; Hou, Jiaojiao; Kang, Yongxiang; Yu, Zhongdong

2016-12-01

A post-fire morel collected from Populus simonii stands in Mt. Qingling was identified as Morchella crassipes Mes-20 by using nuclear ribosomal DNA internal transcribed spacer phylogeny. It was inoculated into sweet corn to observe colonized roots in purified culture and in greenhouse experiments. The elongation and maturation zones of sweet corn were remarkably colonized at the cortex intercellular and intracellular cells, vessel cells, and around the Casparian strip, forming ectendomycorrhiza-like structures. Colonization was also observed in the zone of cell division proximal to the root cap. Greenhouse assays with sweet corn showed that this morel stimulated the development of the root system and significantly increased the dry root biomass. M. crassipes also significantly reduced the incidence of Fusarium verticillioides in the kernels of mature ears when inoculated into young ears before Fusarium inoculation and prevented Fusarium infection in corn ears compared with that of the control in the greenhouse. When grown under axenic conditions, M. crassipes produced the phytohormones abscisic acid, indole-3-acetic acid, and salicylic acid. The benefits to plants elicited by M. crassipes may result from these phytohormones which may improve the drought resistance, biomass growth and resistance to Fusarium.

Combinatorial anticancer effects of curcumin and 5-fluorouracil loaded thiolated chitosan nanoparticles towards colon cancer treatment.

PubMed

Anitha, A; Deepa, N; Chennazhi, K P; Lakshmanan, Vinoth-Kumar; Jayakumar, R

2014-09-01

Evaluation of the combinatorial anticancer effects of curcumin/5-fluorouracil loaded thiolated chitosan nanoparticles (CRC-TCS-NPs/5-FU-TCS-NPs) on colon cancer cells and the analysis of pharmacokinetics and biodistribution of CRC-TCS-NPs/5-FU-TCS-NPs in a mouse model. CRC-TCS-NPs/5-FU-TCS-NPs were developed by ionic cross-linking. The in vitro combinatorial anticancer effect of the nanomedicine was proven by different assays. Further the pharmacokinetics and biodistribution analyses were performed in Swiss Albino mouse using HPLC. The 5-FU-TCS-NPs (size: 150±40nm, zeta potential: +48.2±5mV) and CRC-TCS-NPs (size: 150±20nm, zeta potential: +35.7±3mV) were proven to be compatible with blood. The in vitro drug release studies at pH4.5 and 7.4 showed a sustained release profile over a period of 4 days, where both the systems exhibited a higher release in acidic pH. The in vitro combinatorial anticancer effects in colon cancer (HT29) cells using MTT, live/dead, mitochondrial membrane potential and cell cycle analysis measurements confirmed the enhanced anticancer effects (2.5 to 3 fold). The pharmacokinetic studies confirmed the improved plasma concentrations of 5-FU and CRC up to 72h, unlike bare CRC and 5-FU. To conclude, the combination of 5-FU-TCS-NPs and CRC-TCS-NPs showed enhanced anticancer effects on colon cancer cells in vitro and improved the bioavailability of the drugs in vivo. The enhanced anticancer effects of combinatorial nanomedicine are advantageous in terms of reduction in the dosage of 5-FU, thereby improving the chemotherapeutic efficacy and patient compliance of colorectal cancer cases. Copyright © 2014 Elsevier B.V. All rights reserved.

Phytoplasma Effector SAP54 Hijacks Plant Reproduction by Degrading MADS-box Proteins and Promotes Insect Colonization in a RAD23-Dependent Manner

PubMed Central

MacLean, Allyson M.; Orlovskis, Zigmunds; Kowitwanich, Krissana; Zdziarska, Anna M.; Angenent, Gerco C.; Immink, Richard G. H.; Hogenhout, Saskia A.

2014-01-01

Pathogens that rely upon multiple hosts to complete their life cycles often modify behavior and development of these hosts to coerce them into improving pathogen fitness. However, few studies describe mechanisms underlying host coercion. In this study, we elucidate the mechanism by which an insect-transmitted pathogen of plants alters floral development to convert flowers into vegetative tissues. We find that phytoplasma produce a novel effector protein (SAP54) that interacts with members of the MADS-domain transcription factor (MTF) family, including key regulators SEPALLATA3 and APETALA1, that occupy central positions in the regulation of floral development. SAP54 mediates degradation of MTFs by interacting with proteins of the RADIATION SENSITIVE23 (RAD23) family, eukaryotic proteins that shuttle substrates to the proteasome. Arabidopsis rad23 mutants do not show conversion of flowers into leaf-like tissues in the presence of SAP54 and during phytoplasma infection, emphasizing the importance of RAD23 to the activity of SAP54. Remarkably, plants with SAP54-induced leaf-like flowers are more attractive for colonization by phytoplasma leafhopper vectors and this colonization preference is dependent on RAD23. An effector that targets and suppresses flowering while simultaneously promoting insect herbivore colonization is unprecedented. Moreover, RAD23 proteins have, to our knowledge, no known roles in flower development, nor plant defence mechanisms against insects. Thus SAP54 generates a short circuit between two key pathways of the host to alter development, resulting in sterile plants, and promotes attractiveness of these plants to leafhopper vectors helping the obligate phytoplasmas reproduce and propagate (zombie plants). PMID:24714165

Improved sustainability of feedstock production with sludge and interacting mycorrhiza.

PubMed

Seleiman, Mahmoud F; Santanen, Arja; Kleemola, Jouko; Stoddard, Frederick L; Mäkelä, Pirjo S A

2013-05-01

Recycling nutrients saves energy and improves agricultural sustainability. Sewage sludge contains 2.6% P and 3.1% N, so the availability of these nutrients was investigated using four crops grown in either soil or sand. Further attention was paid to the role of mycorrhiza in improvement of nutrient availability. The content of heavy metals and metalloids in the feedstock was analyzed. Sewage sludge application resulted in greater biomass accumulation in ryegrass than comparable single applications of either synthetic fertilizer or digested sludge. Sewage sludge application resulted in more numerous mycorrhizal spores in soil and increased root colonization in comparison to synthetic fertilizer. All plants studied had mycorrhizal colonized roots, with the highest colonization rate in maize, followed by hemp. Sewage sludge application resulted in the highest P uptake in all soil-grown plants. In conclusion, sewage sludge application increased feedstock yield, provided beneficial use for organic wastes, and contributed to the sustainability of bioenergy feedstock production systems. It also improves the soil conditions and plant nutrition through colonization by mycorrhizal fungi as well as reducing leaching and need of synthetic fertilizers. Copyright © 2013 Elsevier Ltd. All rights reserved.

New rodent models for studies of chemopreventive agents.

PubMed

Lipkin, M

1997-01-01

Some recent studies of the effects of chemopreventive agents have begun to use new rodent models to improve the analysis of stages of colonic preneoplasia, and how chemopreventive agents modify progressive abnormal cell development. In one of the models of inherited predisposition to colon cancer, mice carrying a truncated Apc allele with a nonsense mutation in exon 15 have been generated by gene targeting and embryonic stem cell technology (Apc1638 mice). These mice develop multiple gastrointestinal lesions, including adenomas and carcinomas, focal areas of high-grade dysplasia (FAD), and polypoid hyperplasias with FADS. The incidence of inherited colonic neoplasms has now been modulated by a chemopreventive regimen. Colonic lesions significantly increased in Apc1638 mice on a Western-style diet, which has higher fat content and lower calcium and vitamin D compared to the same mice on AIN-76A diet. In another rodent model, Min mice were treated with sulindac, which markedly reduced the incidence of intestinal tumors. A third new rodent model containing a targeted mutation in the gene Mcc (mutated in colorectal cancer) recently became available for chemoprevention studies. These mice develop multiple types of neoplasms including adenocarcinomas, focal areas of gastrointestinal dysplasia, papillomas of the forestomach, and tumors in other organs including lung, liver, and lymphoid tissue. Feeding a Western-style diet to the Mcc mutant mice also resulted in significantly increased gastrointestinal lesions. These nutrient modifications also have been given to normal mice, demonstrating without any chemical carcinogen that a Western-style diet induced colonic tumorigenesis. Western-style diets also have now induced modulation of cell proliferation in other organs including mammary gland, pancreas, and prostate. These findings help develop new preclinical rodent models to aid the analysis of genetic and environmental factors leading to neoplasia, as well as new methods for evaluating the chemopreventive efficacy of specific nutrients and pharmacological agents.

The Value of Continuity between Primary Care and Surgical Care in Colon Cancer.

PubMed

Hussain, Tanvir; Chang, Hsien-Yen; Luu, Ngoc-Phuong; Pollack, Craig Evan

2016-01-01

Improving continuity between primary care and cancer care is critical for improving cancer outcomes and curbing cancer costs. A dimension of continuity, we investigated how regularly patients receive their primary care and surgical care for colon cancer from the same hospital and whether this affects mortality and costs. Using Surveillance, Epidemiology, and End Results Program Registry (SEER)-Medicare data, we performed a retrospective cohort study of stage I-III colon cancer patients diagnosed between 2000 and 2009. There were 23,305 stage I-III colon cancer patients who received primary care in the year prior to diagnosis and underwent operative care for colon cancer. Patients were assigned to the hospital where they had their surgery and to their primary care provider's main hospital, and then classified according to whether these two hospitals were same or different. Outcomes examined were hazards for all-cause mortality, subhazard for colon cancer specific mortality, and generalized linear estimate for costs at 12 months, from propensity score matched models. Fifty-two percent of stage I-III colon patients received primary care and surgical care from the same hospital. Primary care and surgical care from the same hospital was not associated with reduced all-cause or colon cancer specific mortality, but was associated with lower inpatient, outpatient, and total costs of care. Total cost difference was $8,836 (95% CI $2,746-$14,577), a 20% reduction in total median cost of care at 12 months. Receiving primary care and surgical care at the same hospital, compared to different hospitals, was associated with lower costs but still similar survival among stage I-III colon cancer patients. Nonetheless, health care policy which encourages further integration between primary care and cancer care in order to improve outcomes and decrease costs will need to address the significant proportion of patients receiving health care across more than one hospital.

Airway fungal colonization compromises the immune system allowing bacterial pneumonia to prevail.

PubMed

Roux, Damien; Gaudry, Stéphane; Khoy-Ear, Linda; Aloulou, Meryem; Phillips-Houlbracq, Mathilde; Bex, Julie; Skurnik, David; Denamur, Erick; Monteiro, Renato C; Dreyfuss, Didier; Ricard, Jean-Damien

2013-09-01

To study the correlation between fungal colonization and bacterial pneumonia and to test the effect of antifungal treatments on the development of bacterial pneumonia in colonized rats. Experimental animal investigation. University research laboratory. Pathogen-free male Wistar rats weighing 250-275 g. Rats were colonized by intratracheal instillation of Candida albicans. Fungal clearance from the lungs and immune response were measured. Both colonized and noncolonized animals were secondarily instilled with different bacterial species (Pseudomonas aeruginosa, Escherichia coli, or Staphylococcus aureus). Bacterial phagocytosis by alveolar macrophages was evaluated in the presence of interferon-gamma, the main cytokine produced during fungal colonization. The effect of antifungal treatments on fungal colonization and its immune response were assessed. The prevalence of P. aeruginosa pneumonia was compared in antifungal treated and control colonized rats. C. albicans was slowly cleared and induced a Th1-Th17 immune response with very high interferon-gamma concentrations. Airway fungal colonization favored the development of bacterial pneumonia. Interferon-gamma was able to inhibit the phagocytosis of unopsonized bacteria by alveolar macrophages. Antifungal treatment decreased airway fungal colonization, lung interferon-gamma levels and, consequently, the prevalence of subsequent bacterial pneumonia. C. albicans airway colonization elicited a Th1-Th17 immune response that favored the development of bacterial pneumonia via the inhibition of bacterial phagocytosis by alveolar macrophages. Antifungal treatment decreased the risk of bacterial pneumonia in colonized rats.

Nasopharyngeal colonization by potentially pathogenic bacteria found in healthy semi-captive wild-born chimpanzees in Uganda.

PubMed

Mugisha, Lawrence; Köndgen, Sophie; Kaddu-Mulindwa, Deogratias; Gaffikin, Lynne; Leendertz, Fabian H

2014-02-01

Information on the chimpanzee nasopharygeal colonization in captive sanctuaries and in the wild is rare. This study was undertaken to establish the nasopharygeal colonization and potential bacterial pathogens in sanctuary chimpanzees as a basis for improving chimpanzee and employee health. Nasopharygeal colonization of 39 healthy chimpanzees were analyzed by microbiological cultivation method and polymerase chain reaction (PCR) targeting the bacterial 16S rRNA gene. We report four major phyla dominated by Proteobacteria (50%), Fermicutes (35.7%), Bacteriodes (7.1%), and Cynobacteria (7.1%) in healthy semi-captive chimpanzees. Further classification based on 7-base oligomers revealed the following genera: Streptococcus, Veillonella, Neisseria, Prevotella, Kingella and unclassified Cynobacteria, Actinobacillus, Bacteriodes and Pasteurellaceae. On microbiological cultivation we were able to identify and characterize some of the bacteria to species level as Klebsiella pneumonie and Pseudomonas aeruginosa being dominant bacteria with 54.7% and 50% colonization, respectively. Of these, Streptococcus, Neisseria, Klebsiella, and Haemophillus have representatives known to potentially cause severe respiratory disease. Our data present important information on chimpanzee nasopharygeal colonization as a guide to understanding disease processes and pharmaceutical therapies required for improving the health of chimpanzees. The results from this study will guide the processes to improve procedures for routine management of sanctuary chimpanzees and use it as a basis for evaluation of future reintroduction possibilities. © 2013 Wiley Periodicals, Inc.

Inner Plant Values: Diversity, Colonization and Benefits from Endophytic Bacteria

PubMed Central

Liu, Hongwei; Carvalhais, Lilia C.; Crawford, Mark; Singh, Eugenie; Dennis, Paul G.; Pieterse, Corné M. J.; Schenk, Peer M.

2017-01-01

One of the most exciting scientific advances in recent decades has been the realization that the diverse and immensely active microbial communities are not only ‘passengers’ with plants, but instead play an important role in plant growth, development and resistance to biotic and abiotic stresses. A picture is emerging where plant roots act as ‘gatekeepers’ to screen soil bacteria from the rhizosphere and rhizoplane. This typically results in root endophytic microbiome dominated by Proteobacteria, Actinobacteria and to a lesser extent Bacteroidetes and Firmicutes, but Acidobacteria and Gemmatimonadetes being almost depleted. A synthesis of available data suggest that motility, plant cell-wall degradation ability and reactive oxygen species scavenging seem to be crucial traits for successful endophytic colonization and establishment of bacteria. Recent studies provide solid evidence that these bacteria serve host functions such as improving of plant nutrients through acquisition of nutrients from soil and nitrogen fixation in leaves. Additionally, some endophytes can engage ‘priming’ plants which elicit a faster and stronger plant defense once pathogens attack. Due to these plant growth-promoting effects, endophytic bacteria are being widely explored for their use in the improvement of crop performance. Updating the insights into the mechanism of endophytic bacterial colonization and interactions with plants is an important step in potentially manipulating endophytic bacteria/microbiome for viable strategies to improve agricultural production. PMID:29312235

Application of Aspergillus niger-treated agrowaste residue and Glomus mosseae for improving growth and nutrition of Trifolium repens in a Cd-contaminated soil.

PubMed

Medina, A; Vassilev, N; Barea, J M; Azcón, R

2005-04-06

The microbial transformation of sugar beet (SB) agrowaste with or without rock-phosphate (RP) has utility for the improvement of plant growth in a Cd (5 microg g-1) artificially contaminated soil, particularly when the soil is co-inoculated with arbuscular mycorrhizal (AM) fungus Glomus mosseae isolated from a Cd-polluted area. Under such Cd-polluted conditions, the limited growth, mineral nutrition, symbiotic developments (nodulation and AM-colonization) and soil enzymatic activities were stimulated using SB or SB+RP as soil amendments and G. mosseae as inoculant. G. mosseae enhanced plant establishment in a higher extent in amended soil; it is probably due to the interactive effect increasing the potential fertility of such compounds and its ability for decreasing Cd transfer from soil to plant. The amount of Cd transferred from soil solution to biomass of AM-colonized plants ranged from 0.09 microg Cd g-1 (in SB+RP-amended soil) to 0.6 microg Cd g-1 (in non-amended soil). Nodule formation was more sensitive to Cd than AM-colonization, and both symbioses were stimulated in amended soils. Not only AM-colonization but also amendments were critical for plant growth and nutrition in Cd-polluted soil. The high effectiveness of AM inoculum increasing nutrients and decreasing Cd in amended soil indicated the positive interaction of these treatments in increasing plant tolerance to Cd contamination.

A fungal root symbiont modifies plant resistance to an insect herbivore.

PubMed

Borowicz, Victoria A

1997-11-01

Vesicular-arbuscular mycorrhizal (VAM) fungi are common root-colonizing symbionts that affect nutrient uptake by plants and can alter plant susceptibility to herbivores. I conducted a factorial experiment to test the hypotheses that colonization by VAM fungi (1) improves soybean (Glycine max) tolerance to grazing by folivorous Mexican bean beetle (Epilachna varivestis), and (2) indirectly affects herbivores by increasing host resistance. Soybean seedlings were inoculated with the VAM fungus Glomus etunicatum or VAM-free filtrate and fertilized with high-[P] or low-[P] fertilizer. After plants had grown for 7 weeks first-instar beetle larvae were placed on bagged leaves. Growth of soybean was little affected by grazing larvae, and no effects of treatments on tolerance of soybeans to herbivores were evident. Colonization by VAM fungus doubled the size of phosphorus-stressed plants but these plants were still half the size of plants given adequate phosphorus. High-[P] fertilizer increased levels of phosphorus and soluble carbohydrates, and decreased levels of soluble proteins in leaves of grazed plants. Colonization of grazed plants by VAM fungus had no significant effect on plant soluble carbohydrates, but increased concentration of phosphorus and decreased levels of proteins in phosphorus-stressed plants to concentrations similar to those of plants given adequate phosphorus. Mexican bean beetle mass at pupation, pupation rate, and survival to eclosion were greatest for beetles reared on phosphorus-stressed, VAM-colonized plants, refuting the hypothesis that VAM colonization improves host plant resistance. VAM colonization indirectly affected performance of Mexician bean beetle larvae by improving growth and nutrition of the host plant.

Favorable surgical treatment outcomes for chronic constipation with features of colonic pseudo-obstruction

PubMed Central

Han, Eon Chul; Oh, Heung-Kwon; Ha, Heon-Kyun; Choe, Eun Kyung; Moon, Sang Hui; Ryoo, Seung-Bum; Park, Kyu Joo

2012-01-01

AIM: To determine long-term outcomes of surgical treatments for patients with constipation and features of colonic pseudo-obstruction. METHODS: Consecutive 42 patients who underwent surgery for chronic constipation within the last 13 years were prospectively collected. We identified a subgroup with colonic pseudo-obstruction (CPO) features, with dilatation of the colon proximal to the narrowed transitional zone, in contrast to typical slow-transit constipation (STC), without any dilated colonic segments. The outcomes of surgical treatments for chronic constipation with features of CPO were analyzed and compared with outcomes for STC. RESULTS: Of the 42 patients who underwent surgery for constipation, 33 patients had CPO with dilatation of the colon proximal to the narrowed transitional zone. There were 16 males and 17 females with a mean age of 51.2 ± 16.1 years. All had symptoms of chronic intestinal obstruction, including abdominal distension, pain, nausea, or vomiting, and the mean duration of symptoms was 67 mo (range: 6-252 mo). Preoperative defecation frequency was 1.5 ± 0.6 times/wk (range: 1-2 times/wk). Thirty-two patients underwent total colectomy, and one patient underwent diverting transverse colostomy. There was no surgery-related mortality. Postoperative histologic examination showed hypoganglionosis or agangliosis in 23 patients and hypoganglionosis combined with visceral neuropathy or myopathy in 10 patients. In contrast, histology of STC group revealed intestinal neuronal dysplasia type B (n = 6) and visceral myopathy (n = 3). Early postoperative complications developed in six patients with CPO; wound infection (n = 3), paralytic ileus (n = 2), and intraabdominal abscess (n = 1). Defecation frequencies 3 mo after surgery improved to 4.2 ± 3.2 times/d (range: 1-15 times/d). Long-term follow-up (median: 39.7 mo) was available in 32 patients; all patients had improvements in constipation symptoms, but two patients needed intermittent medication for management of diarrhea. All 32 patients had distinct improvements in constipation symptoms (with a mean bowel frequency of 3.3 ± 1.3 times/d), social activities, and body mass index (20.5 kg/m2 to 22.1 kg/m2) and were satisfied with the results of their surgical treatment. In comparison with nine patients who underwent colectomy for STC without colon dilatation, those in the CPO group had a lower incidence of small bowel obstructions (0% vs 55.6%, P < 0.01) and less difficulty with long-distance travel (6.7% vs 66.7%, P = 0.007) on long-term follow-up. CONCLUSION: Chronic constipation patients with features of CPO caused by narrowed transitional zone in the left colon had favorable outcomes after total colectomy. PMID:22969211

Colon-targeted oral drug delivery systems: design trends and approaches.

PubMed

Amidon, Seth; Brown, Jack E; Dave, Vivek S

2015-08-01

Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, Crohn's disease, irritable bowel syndrome, chronic pancreatitis, and colonic cancer. In addition, the colon can be a potential site for the systemic absorption of several drugs to treat non-colonic conditions. Drugs such as proteins and peptides that are known to degrade in the extreme gastric pH, if delivered to the colon intact, can be systemically absorbed by colonic mucosa. In order to achieve effective therapeutic outcomes, it is imperative that the designed delivery system specifically targets the drugs into the colon. Several formulation approaches have been explored in the development colon-targeted drug delivery systems. These approaches involve the use of formulation components that interact with one or more aspects of gastrointestinal (GI) physiology, such as the difference in the pH along the GI tract, the presence of colonic microflora, and enzymes, to achieve colon targeting. This article highlights the factors influencing colon-specific drug delivery and colonic bioavailability, and the limitations associated with CDDS. Further, the review provides a systematic discussion of various conventional, as well as relatively newer formulation approaches/technologies currently being utilized for the development of CDDS.

Linked color imaging reduces the miss rate of neoplastic lesions in the right colon: a randomized tandem colonoscopy study.

PubMed

Paggi, Silvia; Mogavero, Giuseppe; Amato, Arnaldo; Rondonotti, Emanuele; Andrealli, Alida; Imperiali, Gianni; Lenoci, Nicoletta; Mandelli, Giovanna; Terreni, Natalia; Conforti, Francesco Simone; Conte, Dario; Spinzi, Giancarlo; Radaelli, Franco

2018-04-01

 Linked color imaging (LCI) is a newly developed image-enhancing endoscopy technology that provides bright endoscopic images and increases color contrast. We investigated whether LCI improves the detection of neoplastic lesions in the right colon when compared with high definition white-light imaging (WLI).  Consecutive patients undergoing colonoscopy were randomized (1:1) after cecal intubation into right colon inspection at first pass by LCI or by WLI. At the hepatic flexure, the scope was reintroduced to the cecum under LCI and a second right colon inspection was performed under WLI in previously LCI-scoped patients (LCI-WLI group) and vice versa (WLI-LCI group). Lesions detected on first- and second-pass examinations were used to calculate detection and miss rates, respectively. The primary outcome was the right colon adenoma miss rate.  Of the 600 patients enrolled, 142 had at least one adenoma in the right colon, with similar right colon adenoma detection rates (r-ADR) in the two groups (22.7 % in LCI-WLI and 24.7 % in WLI-LCI). At per-polyp analysis, double inspection of the right colon in the LCI-WLI and WLI-LCI groups resulted in an 11.8 % and 30.6 % adenoma miss rate, respectively ( P  < 0.001). No significant difference in miss rate was found for advanced adenomas or sessile serrated lesions. At per-patient analysis, at least one adenoma was identified in the second pass only (incremental ADR) in 2 of 300 patients (0.7 %) in the LCI - WLI group and in 13 of 300 patients (4.3 %) in the WLI - LCI group ( P  = 0.01).  LCI could reduce the miss rate of neoplastic lesions in the right colon. © Georg Thieme Verlag KG Stuttgart · New York.

Pilot study of pyridostigmine in constipated patients with autonomic neuropathy

PubMed Central

Bharucha, Adil E.; Camilleri, Michael; Burton, Duane; Low, Phillip A.; Gehrking, Tonette L.; Zinsmeister, Alan R.

2008-01-01

Background The effects of cholinesterase inhibitors, which increase colonic motility in health, on chronic constipation are unknown. Our aims were to evaluate the efficacy of cholinesterase inhibitors for dysautonomia and chronic constipation and to assess whether acute effects could predict the long term response. Methods In this single-blind study, 10 patients with autonomic neuropathy and constipation were treated with placebo (2 weeks), followed by an escalating dose of pyridostigmine to the maximum tolerated dose (i.e., 180–540 mg daily) for 6 weeks. Symptoms and gastrointestinal transit were assessed at 2 and 8 weeks. The acute effects of neostigmine on colonic transit and motility were also assessed. Results At baseline, 4, 6, and 3 patients had delayed gastric, small intestinal, and colonic transit respectively. Pyridostigmine was well tolerated in most patients, improved symptoms in 4 patients, and accelerated the geometric center for colonic transit at 24 h by ≥0.7 unit in 3 patients. The effects of i.v. neostigmine on colonic transit and compliance predicted (P < 0.05) the effects of pyridostigmine on colonic transit. Conclusions Pyridostigmine improves colonic transit and symptoms in some patients with autonomic neuropathy and constipation. The motor response to neostigmine predicted the response to oral pyridostigmine. PMID:18622640

Automated image-based colon cleansing for laxative-free CT colonography computer-aided polyp detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linguraru, Marius George; Panjwani, Neil; Fletcher, Joel G.

2011-12-15

Purpose: To evaluate the performance of a computer-aided detection (CAD) system for detecting colonic polyps at noncathartic computed tomography colonography (CTC) in conjunction with an automated image-based colon cleansing algorithm. Methods: An automated colon cleansing algorithm was designed to detect and subtract tagged-stool, accounting for heterogeneity and poor tagging, to be used in conjunction with a colon CAD system. The method is locally adaptive and combines intensity, shape, and texture analysis with probabilistic optimization. CTC data from cathartic-free bowel preparation were acquired for testing and training the parameters. Patients underwent various colonic preparations with barium or Gastroview in divided dosesmore » over 48 h before scanning. No laxatives were administered and no dietary modifications were required. Cases were selected from a polyp-enriched cohort and included scans in which at least 90% of the solid stool was visually estimated to be tagged and each colonic segment was distended in either the prone or supine view. The CAD system was run comparatively with and without the stool subtraction algorithm. Results: The dataset comprised 38 CTC scans from prone and/or supine scans of 19 patients containing 44 polyps larger than 10 mm (22 unique polyps, if matched between prone and supine scans). The results are robust on fine details around folds, thin-stool linings on the colonic wall, near polyps and in large fluid/stool pools. The sensitivity of the CAD system is 70.5% per polyp at a rate of 5.75 false positives/scan without using the stool subtraction module. This detection improved significantly (p = 0.009) after automated colon cleansing on cathartic-free data to 86.4% true positive rate at 5.75 false positives/scan. Conclusions: An automated image-based colon cleansing algorithm designed to overcome the challenges of the noncathartic colon significantly improves the sensitivity of colon CAD by approximately 15%.« less

The development of colon innervation in trisomy 16 mice and Hirschsprungs disease

PubMed Central

Li, Ji Cheng; Mi, Kai Hong; Zhou, Ji Lin; Busch, LC; Kuhnel, W

2001-01-01

AIM: To study the colon innervation of trisomy 16 mouse, an animal model for Down’s syndrome, and the expression of protein gene product 9.5 (PGP 9.5) in the stenosed segment of colon in Hirschsprungs disease (HD). METHODS: Trisomy 16 mouse breeding; cytogenetic analysis of trisomy 16 mice; and PGP 9.5 immunohistochemistry of colons of trisomy 16 mice and HD were carried out. RESULTS: Compared with their normal littermates, the nervous system of colon in trisomy 16 mice was abnormally developed. There existed developmental delay of muscular plexuses of colon, no submucosal plexus was found in the colon, and there was 5 mm aganglionic bowel aparting from the anus in trisomy 16 mice. The mesentery nerve fibers were as well developed as shown in their normal littermates. Abundant proliferation of PGP 9.5 positive nerve fibers was evealed in the stenosed segment of HD colon. CONCLUSION: Trisomy 16 mice could serve as an animal model for Hirschsprung’s disease for aganglionic bowel in the distal part of colon. Abundant proliferation of PGP 9.5 positive fibers resulted from extrinsic nerve compensation, since no ganglionic cells were observed in the stenosed segment of the colon in HD. HD has a genetic tendency. PMID:11819726

The Effect of Right Colon Retroflexion on Adenoma Detection: A Systematic Review and Meta-analysis.

PubMed

Cohen, Jonah; Grunwald, Douglas; Grossberg, Laurie B; Sawhney, Mandeep S

2017-10-01

Although colonoscopy with polypectomy can prevent up to 80% of colorectal cancers, a significant adenoma miss rate still exists, particularly in the right colon. Previous studies addressing right colon retroflexion have revealed discordant evidence regarding the benefit of this maneuver on adenoma detection with concomitant concerns about safety and rates of maneuver success. In this meta-analysis, we sought to determine the effect of right colon retroflexion on improving adenoma detection compared with conventional colonoscopy without retroflexion, as well as determine the rates of retroflexion maneuver success and adverse events. Multiple databases including MEDLINE, Embase, and Web of Science were searched for studies on right colon retroflexion and its impact on adenoma detection compared with conventional colonoscopy. Pooled analyses of adenoma detection and retroflexion success were based on mixed-effects and random-effects models with heterogeneity analyses. Eight studies met the inclusion criteria (N=3660). The primary analysis comparing colonoscopy with right-sided retroflexion versus conventional colonoscopy to determine the per-adenoma miss rate in the right colon was 16.9% (95% confidence interval, 12.5%-22.5%). The overall rate of successful retroflexion was 91.9% (95% confidence interval, 86%-95%) and rate of adverse events was 0.03%. Colonoscopy with right-sided retroflexion significantly increases the detection of adenomas in the right colon compared with conventional colonoscopy with a high rate of maneuver success and small risk of adverse events. Thus, reexamination of the right colon in retroflexed view should be strongly considered in future standard of care colonoscopy guidelines for quality improvement in colon cancer prevention.

Progress in digestive endoscopy: Flexible Spectral Imaging Colour Enhancement (FICE)-technical review.

PubMed

Negreanu, L; Preda, C M; Ionescu, D; Ferechide, D

2015-01-01

Background. A substantial advance in digestive endoscopy that has been made during the last decade is represented by digital chromoendoscopy, which was developed as a quicker and sometimes better alternative to the gold standard of dye spraying. Fujifilm developed a virtual coloration technique called Flexible spectral Imaging Color Enhancement (FICE). FICE provides a better detection of lesions of "minimal" esophagitis, of dysplasia in Barrett's esophagus and of squamous cell esophageal cancer. The use of FICE resulted in an improvement in the visualization of the early gastric cancer, being less invasive, and time consuming than the classic dye methods. Current evidence does not support FICE for screening purposes in colon cancer but it definitely improves characterization of colonic lesions. Its use in inflammatory bowel disease is still controversial and in video capsule endoscopy is considered a substantial progress. Conclusions. The use of FICE endoscopy in routine clinical practice can increase the diagnostic yield and can provide a better characterization of lesions. Future studies to validate its use, the good choice of channels, and the "perfect indications" and to provide common definitions and classifications are necessary.

Appendicostomy irrigation for facilitating colonic evacuation in colostomy patients. Preliminary report.

PubMed

Kotanagi, H; Koyama, K; Sato, Y; Takahashi, K

1998-08-01

A method for bowel irrigation through an appendicostomy (antegrade colonic enema) for patients with a left colostomy is described. The appendicostomy is easily constructed without morbidity. Irrigation through the appendicostomy is performed with minimum equipment, uses a small volume of irrigation water, and takes a relatively short time. This may improve colonic evacuation in patients with left colostomy.

Perinatal supplementation of 4-phenylbutyrate and glutamine attenuates endoplasmic reticulum stress and improves colonic epithelial barrier function in rats born with intrauterine growth restriction.

PubMed

Désir-Vigné, Axel; Haure-Mirande, Vianney; de Coppet, Pierre; Darmaun, Dominique; Le Dréan, Gwenola; Segain, Jean-Pierre

2018-05-01

Intrauterine growth restriction (IUGR) can affect the structure and function of the intestinal barrier and increase digestive disease risk in adulthood. Using the rat model of maternal dietary protein restriction (8% vs. 20%), we found that the colon of IUGR offspring displayed decreased mRNA expression of epithelial barrier proteins MUC2 and occludin during development. This was associated with increased mRNA expression of endoplasmic reticulum (ER) stress marker XBP1s and increased colonic permeability measured in Ussing chambers. We hypothesized that ER stress contributes to colonic barrier alterations and that perinatal supplementation of dams with ER stress modulators, phenylbutyrate and glutamine (PG) could prevent these defects in IUGR offspring. We first demonstrated that ER stress induction by tunicamycin or thapsigargin increased the permeability of rat colonic tissues mounted in Ussing chamber and that PG treatment prevented this effect. Therefore, we supplemented the diet of control and IUGR dams with PG during gestation and lactation. Real-time polymerase chain reaction and histological analysis of colons from 120-day-old offspring revealed that perinatal PG treatment partially prevented the increased expression of ER stress markers but reversed the reduction of crypt depth and goblet cell number in IUGR rats. In dextran sodium sulfate-induced injury and recovery experiments, the colon of IUGR rats without perinatal PG treatment showed higher XBP1s mRNA levels and histological scores of inflammation than IUGR rats with perinatal PG treatment. In conclusion, these data suggest that perinatal supplementation with PG could alleviate ER stress and prevent epithelial barrier dysfunction in IUGR offspring. Copyright © 2017 Elsevier Inc. All rights reserved.

Results of Four-Year Rectal Vancomycin-Resistant Enterococci Surveillance in a Pediatric Hematology-Oncology Ward: From Colonization to Infection.

PubMed

Aktürk, Hacer; Sütçü, Murat; Somer, Ayper; Karaman, Serap; Acar, Manolya; Ünüvar, Ayşegül; Anak, Sema; Karakaş, Zeynep; Özdemir, Aslı; Sarsar, Kutay; Aydın, Derya; Salman, Nuran

2016-09-05

To investigate the clinical impact of vancomycin-resistant enterococci (VRE) colonization in patients with hematologic malignancies and associated risk factors. Patients colonized and infected with VRE were identified from an institutional surveillance database between January 2010 and December 2013. A retrospective case-control study was performed to identify the risk factors associated with development of VRE infection in VRE-colonized patients. Fecal VRE colonization was documented in 72 of 229 children (31.4%). Seven VRE-colonized patients developed subsequent systemic VRE infection (9.7%). Types of VRE infections included bacteremia (n=5), urinary tract infection (n=1), and meningitis (n=1). Enterococcus faecium was isolated in all VRE infections. Multivariate analysis revealed severe neutropenia and previous bacteremia with another pathogen as independent risk factors for VRE infection development in colonized patients [odds ratio (OR): 35.4, confidence interval (CI): 1.7-72.3, p=0.02 and OR: 20.6, CI: 1.3-48.6, p=0.03, respectively]. No deaths attributable to VRE occurred. VRE colonization has important consequences in pediatric cancer patients.

Collaboration Between Surgeons and Medical Oncologists and Outcomes for Patients With Stage III Colon Cancer.

PubMed

Hussain, Tanvir; Chang, Hsien-Yen; Veenstra, Christine M; Pollack, Craig E

2015-05-01

Collaboration between specialists is essential for achieving high-value care in patients with complex cancer needs. We explore how collaboration between oncologists and surgeons affects mortality and cost for patients requiring multispecialty cancer care. This was a retrospective cohort study of patients with stage III colon cancer from SEER-Medicare diagnosed between 2000 and 2009. Patients were assigned to a primary treating surgeon and oncologist. Collaboration between surgeon and oncologist was measured as the number of patients shared between them; this has been shown to reflect advice seeking and referral relationships between physicians. Outcomes included hazards for all-cause mortality, subhazards for colon cancer-specific mortality, and cost of care at 12 months. A total of 9,329 patients received care from 3,623 different surgeons and 2,319 medical oncologists, representing 6,827 unique surgeon-medical oncologist pairs. As the number of patients shared between specialists increased from to one to five (25th to 75th percentile), patients experienced an approximately 20% improved survival benefit from all-cause and colon cancer-specific mortalities. Specifically, for each additional patient shared between oncologist and surgeon, all-cause mortality improved by 5% (hazard ratio, 0.95; 95%CI, 0.92 to 0.97), and colon cancer-specific mortality improved by 5% (subhazard ratio, 0.95; 95% CI, 0.91 to 0.97). There was no association with cost. Specialist collaboration is associated with lower mortality without increased cost among patients with stage III colon cancer. Facilitating formal and informal collaboration between specialists may be an important strategy for improving the care of patients with complex cancers. Copyright © 2015 by American Society of Clinical Oncology.

In vitro digestion-assisted development of a β-cryptoxanthin-rich functional beverage; in vivo validation using systemic response and faecal content.

PubMed

Hernández-Alvarez, E; Blanco-Navarro, I; Pérez-Sacristán, B; Sánchez-Siles, L M; Granado-Lorencio, F

2016-10-01

Bioavailability of carotenoids is low and significant amounts reach the colon where they may be biologically active. We aimed to optimize a previously developed beverage designed to improve cardiovascular and bone remodelling markers in post-menopausal women. By assessing different lipid emulsions (soy lecithin, milkfat globule membrane (MFGM) and olive oil) on the in vitro bioaccessibility of β-Cryptoxanthin and phytosterols, a MFGM containing beverage was selected and resulted stable over time (recovery >95%) under in vitro digestion and simulated anaerobic conditions. This beverage was tested in a randomized human trial (n=38) by evaluating systemic response and the colonic availability of β-Cryptoxanthin. Consumption for six weeks provoked an increment in serum β-Cryptoxanthin of 38.9μg/dl (CI 95%; 31.0, 46.8; p<0.001). In faeces, free β-Cryptoxanthin, tentatively identified β-Cryptoxanthin esters and the ratio cis-/trans-β-carotene approached the profile in the beverage and after in vitro digestion but it was different from serum. In conclusion, in vitro digestion-assisted approach appears adequate to develop functional foods although in vivo validation should consider both systemic response and the availability at the colon. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of plant growth-promoting rhizobacteria on root colonization potential and life cycle of Rhizophagus irregularis following co-entrapment into alginate beads.

PubMed

Loján, P; Demortier, M; Velivelli, S L S; Pfeiffer, S; Suárez, J P; de Vos, P; Prestwich, B D; Sessitsch, A; Declerck, S

2017-02-01

This study aimed at evaluating the impact of seven plant growth-promoting rhizobacteria (PGPR) on root colonization and life cycle of Rhizophagus irregularis MUCL 41833 when co-entrapped in alginate beads. Two in vitro experiments were conducted. The first consisted of the immobilization of R. irregularis and seven PGPR isolates into alginate beads to assess the effect of the bacteria on the pre-symbiotic growth of the fungus. In the second experiment, the best performing PGPR from experiment 1 was tested for its ability to promote the symbiotic development of the AMF in potato plantlets from three cultivars. Results showed that only one isolate identified as Pseudomonas plecoglossicida (R-67094) promoted germ tube elongation and hyphal branching of germinated spores during the pre-symbiotic phase of the fungus. This PGPR further promoted the symbiotic development of the AMF in potato plants. The co-entrapment of Ps. plecoglossicida R-67094 and R. irregularis MUCL 41833 in alginate beads improved root colonization by the AMF and its further life cycle under the experimental conditions. Co-entrapment of suitable AMF-PGPR combinations within alginate beads may represent an innovative technology that can be fine-tuned for the development of efficient consortia-based bioformulations. © 2016 The Society for Applied Microbiology.

Objective assessment of technique in laparoscopic colorectal surgery: what are the existing tools?

PubMed

Foster, J D; Francis, N K

2015-01-01

Assessment can improve the effectiveness of surgical training and enable valid judgments of competence. Laparoscopic colon resection surgery is now taught within surgical residency programs, and assessment tools are increasingly used to stimulate formative feedback and enhance learning. Formal assessment of technical performance in laparoscopic colon resection has been successfully applied at the specialist level in the English "LAPCO" National Training Program. Objective assessment tools need to be developed for training and assessment in laparoscopic rectal cancer resection surgery. Simulation may have a future role in assessment and accreditation in laparoscopic colorectal surgery; however, existing virtual reality models are not ready to be used for assessment of this advanced surgery.

Effects of potato fiber and potato-resistant starch on biomarkers of colonic health in rats fed diets containing red meat.

PubMed

Paturi, Gunaranjan; Nyanhanda, Tafadzwa; Butts, Christine A; Herath, Thanuja D; Monro, John A; Ansell, Juliet

2012-10-01

The effects of red meat consumption with and without fermentable carbohydrates on indices of large bowel health in rats were examined. Sprague-Dawley rats were fed cellulose, potato fiber, or potato-resistant starch diets containing 12% casein for 2 wk, then similar diets containing 25% cooked beef for 6 wk. After week 8, cecal and colonic microbiota composition, fermentation end-products, colon structure, and colonocyte DNA damage were analyzed. Rats fed potato fiber had lower Bacteroides-Prevotella-Porphyromonas group compared to other diet groups. Colonic Bifidobacterium spp. and/or Lactobacillus spp. were higher in potato fiber and potato-resistant starch diets than in the cellulose diet. Beneficial changes were observed in short-chain fatty acid concentrations (acetic, butyric, and propionic acids) in rats fed potato fiber compared with rats fed cellulose. Phenol and p-cresol concentrations were lower in the cecum and colon of rats fed potato fiber. An increase in goblet cells per crypt and longer crypts were found in the colon of rats fed potato fiber and potato-resistant starch diets. Fermentable carbohydrates had no effect on colonic DNA damage. Dietary combinations of red meat with potato fiber or potato-resistant starch have distinctive effects in the large bowel. Future studies are essential to examine the efficacy of different types of nondigestible carbohydrates in maintaining colonic health during long-term consumption of high-protein diets. Improved understanding of interactions between the food consumed and gut microbiota provides knowledge needed to make healthier food choices for large bowel health. The impact of red meat on large bowel health may be ameliorated by consuming with fermentable dietary fiber, a colonic energy source that produces less harmful by-products than the microbial breakdown of colonic protein for energy. Developing functional red meat products with fermentable dietary fiber could be one way to promote a healthy and balanced macronutrient diet. © 2012 The New Zealand Institute for Plant and Food-Research Limited Journal of Food Science © 2012 Institute of Food Technologists®

Consumption of guar gum and retrograded high-amylose corn resistant starch increases IL-10 abundance without affecting pro-inflammatory cytokines in the colon of pigs fed a high-fat diet.

PubMed

Fan, M Z; Archbold, T; Lackeyram, D; Liu, Q; Mine, Y; Paliyath, G

2012-12-01

Increases in dietary intake of viscous and nonviscous soluble fiber are reported to improve bowel health. However, related biological mechanisms are not very clear. This study was conducted to examine if colonic inflammation would occur in a typical Western diet model and determine if consumption of soluble fiber components would attenuate potential detrimental effects by differentially affecting colonic abundances of anti-inflammatory cytokine IL-10 and 2 pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and IL-6 in pigs fed a high-fat basal diet supplemented, respectively, with 15% viscous soluble fiber guar gum (GG) and 15% nonviscous soluble fiber, that is, retrograded high-amylose corn (Zea mays) resistant starch (RS). A total of 24 Yorkshire growing barrows were assigned into a standard corn and soybean (Glycine max) meal (SBM)-based grower diet as a positive control (PC), an animal protein-based high-fat basal diet as the negative control (NC), and 2 NC basal diets supplemented with 15% GG and 15% RS, respectively, according to a completely randomized block design for 4 wk. Abundance of these cytokines in homogenized and extracted colonic tissue supernatant samples was measured by ELISA. Although colonic IL-10 abundance was lower (P < 0.05) in the corn and SBM-based PC group than that in the high-fat basal NC group, there were no differences (P > 0.05) in colonic abundances of TNF-α and IL-6 between NC and PC groups and among all of the treatment groups. Compared with the NC group, consumption of GG and RS at 15% increased (P < 0.05) colonic IL-10 abundance. Moreover, there was no difference (P > 0.05) in colonic IL-10 abundance between the 15% GG and the 15% RS groups. Thus, consumption of a typical high-fat Western diet did not induce colonic inflammation. Diets supplemented with 15% GG or 15% RS may protect the colon from developing inflammation by enhancing IL-10 abundance.

The effectiveness of simethicone in improving visibility during colonoscopy when given with a sodium phosphate solution: a double-bind randomized study.

PubMed

Sudduth, R H; DeAngelis, S; Sherman, K E; McNally, P R

1995-11-01

Oral sodium phosphate solution is better tolerated than polyethylene glycol when used for colonoscopy preparation, but visibility of the lumen can be impaired because of the presence of bubbles. We studied 86 patients receiving either simethicone (n = 42) or placebo (n = 44) in addition to oral sodium phosphate to determine if simethicone improved visibility during colonoscopy. Colonoscopy was performed by a single blinded investigator. Five areas of the colon (rectosigmoid, descending, transverse, ascending, and cecum) were assessed for the presence of bubbles on withdrawal of the endoscope. Bubbles were scored as follows: 0, minimal or none; 1, covering half the lumen; 2, covering the entire circumference; 3 filling the entire lumen. Thirteen patients in the placebo group and only one in the simethicone had significant bubbles ( > or = 1). Additionally, the mean bubble scores were greater in the placebo group in each region of the colon (p < or = 0.05 in rectosigmoid and ascending colon). This study indicates that taking simethicone with an oral sodium phosphate preparation can improve colonic visibility by diminishing the presence of bubbles. Better visualization could improve detection of mucosal pathologic lesions.

SND1, a component of RNA-induced silencing complex, is up-regulated in human colon cancers and implicated in early stage colon carcinogenesis.

PubMed

Tsuchiya, Naoto; Ochiai, Masako; Nakashima, Katsuhiko; Ubagai, Tsuneyuki; Sugimura, Takashi; Nakagama, Hitoshi

2007-10-01

Colon cancers have been shown to develop after accumulation of multiple genetic and epigenetic alterations with changes in global gene expression profiles, contributing to the establishment of widely diverse phenotypes. Transcriptional and posttranscriptional regulation of gene expression by small RNA species, such as the small interfering RNA and microRNA and the RNA-induced silencing complex (RISC), is currently drawing major interest with regard to cancer development. SND1, also called Tudor-SN and p100 and recently reported to be a component of RISC, is among the list of highly expressed genes in human colon cancers. In the present study, we showed remarkable up-regulation of SND1 mRNA in human colon cancer tissues, even in early-stage lesions, and also in colon cancer cell lines. When mouse Snd1 was stably overexpressed in IEC6 rat intestinal epithelial cells, contact inhibition was lost and cell growth was promoted, even after the cells became confluent. Intriguingly, IEC6 cells with high levels of Snd1 also showed an altered distribution of E-cadherin from the cell membrane to the cytoplasm, suggesting loss of cellular polarity. Furthermore, the adenomatous polyposis coli (Apc) protein was coincidentally down-regulated, with no significant changes in the Apc mRNA level. Immunohistochemical analysis using chemically induced colonic lesions developed in rats revealed overexpression of Snd1 not only in colon cancers but also in aberrant crypt foci, putative precancerous lesions of the colon. Up-regulation of SND1 may thus occur at a very early stage in colon carcinogenesis and contribute to the posttranscriptional regulation of key players in colon cancer development, including APC and beta-catenin.

Aspirin alone and combined with a statin suppresses eicosanoid formation in human colon tissue.

PubMed

Gottschall, Heike; Schmöcker, Christoph; Hartmann, Dirk; Rohwer, Nadine; Rund, Katharina; Kutzner, Laura; Nolte, Fabian; Ostermann, Annika I; Schebb, Nils Helge; Weylandt, Karsten H

2018-05-01

Eicosanoids, including prostaglandins (PGs) and thromboxanes, are broadly bioactive lipid mediators and increase colon tumorigenesis possibly through chronic inflammatory mechanisms. Epidemiological and experimental data suggest that acetylsalicylic acid (ASA) helps prevent colorectal cancer (CRC), possibly through cyclooxygenase (COX)-mediated suppression of eicosanoid, particularly PGE 2 , formation. Recent studies suggest that statins prevent CRC and improve survival after diagnosis. We identified patients on ASA and/or statin treatment undergoing routine colonoscopy and measured eicosanoid levels in colonic mucosa with targeted metabolomics technology (LC-MS/MS). ASA-treated individuals (n = 27) had significantly lower tissue eicosanoid levels of most COX-derived metabolites than untreated individuals (n = 31). In contrast, COX-derived lipid metabolites tended to be higher in patients with statin treatment (n = 7) as compared with those not receiving statins (n = 24). This effect was not discernible in subjects treated with ASA and statins (n = 11): Individuals treated with both drugs showed a pronounced suppression of COX-derived eicosanoids in colon tissue, even compared with subjects treated with ASA alone. Our data from a routine clinical setting support the hypothesis that ASA and statins could inhibit CRC development via lipid mediator modification. Further studies should directly investigate the effect of dual ASA and statin treatment on colon tumorigenesis in humans. Copyright © 2018 by the American Society for Biochemistry and Molecular Biology, Inc.

A Multiparticulate Delivery System for Potential Colonic Targeting Using Bovine Serum Albumin as a Model Protein : Theme: Formulation and Manufacturing of Solid Dosage Forms Guest Editors: Tony Zhou and Tonglei Li.

PubMed

Jiang, Bowen; Yu, Hua; Zhang, Yongrong; Feng, Hanping; Hoag, Stephen W

2017-12-01

There are many important diseases whose treatment could be improved by delivering a therapeutic protein to the colon, for example, Clostridium difficile infection, ulcerative colitis and Crohn's Disease. The goal of this project was to investigate the feasibility of colonic delivery of proteins using multiparticulate beads. In this work, bovine serum albumin (BSA) was adopted as a model protein. BSA was spray layered onto beads, followed by coating of an enteric polymer EUDRAGIT® FS 30 D to develop a colonic delivery system. The secondary and tertiary structure change and aggregation of BSA during spray layering process was examined. The BSA layered beads were then challenged in an accelerated stability study using International Council for Harmonization (ICH) conditions. The in vitro release of BSA from enteric coated beads was examined using United States Pharmacopeia (USP) dissolution apparatus 1. No significant changes in the secondary and tertiary structure or aggregation profile of BSA were observed after the spray layering process. Degradation of BSA to different extents was detected after storing at 25°C and 40°C for 38 days. Enteric coated BSA beads were intact in acidic media while released BSA in pH 7.4 phosphate buffer. We showed the feasibility of delivering proteins to colon in vitro using multiparticulate system.

The role of calcium intake in preventing bone fragility, hypertension, and certain cancers.

PubMed

Barger-Lux, M J; Heaney, R P

1994-08-01

This paper examines the evidence that connects calcium intake and vitamin D status to bone fragility, hypertension, colon cancer, and breast cancer. Human calcium physiology, with an intestinal absorptive barrier and inefficient conservation, reflects the abundance of calcium in the primordial human food supply. The calcium intake of stone-age adults is estimated at 50 to 75 mmol/d, three to five times the median calcium intake of present-day U.S. adults. Long-term calcium restriction and/or insufficient vitamin D may promote the development of bone fragility, high blood pressure, colon cancer, and breast cancer in susceptible individuals. Conversely, improvement in calcium intake and/or in vitamin D status may help to prevent these serious health problems. At least 12 intervention studies have established the skeletal benefit of increased calcium intake among women in the late postmenopause. Other reports suggest that adequate calcium may protect against salt-sensitive and pregnancy-associated hypertension. High intakes of both dietary calcium and vitamin D are associated with reduced development of precancerous changes in colonic mucosa. Preliminary findings also suggest that vitamin D has a protective effect against breast cancer.

The Fermi paradox: An approach based on percolation theory

NASA Technical Reports Server (NTRS)

Landis, Geoffrey A.

1993-01-01

If even a very small fraction of the hundred billion stars in the galaxy are home to technological civilizations which colonize over interstellar distances, the entire galaxy could be completely colonized in a few million years. The absence of such extraterrestrial civilizations visiting Earth is the Fermi paradox. A model for interstellar colonization is proposed using the assumption that there is a maximum distance over which direct interstellar colonization is feasible. Due to the time lag involved in interstellar communications, it is assumed that an interstellar colony will rapidly develop a culture independent of the civilization that originally settled it. Any given colony will have a probability P of developing a colonizing civilization, and a probability (1-P) that it will develop a non-colonizing civilization. These assumptions lead to the colonization of the galaxy occuring as a percolation problem. In a percolation problem, there will be a critical value of percolation probability, P(sub c). For P less than P(sub c), colonization will always terminate after a finite number of colonies. Growth will occur in 'clusters', with the outside of each cluster consisting of non-colonizing civilizations. For P greater than P(sub c), small uncolonized voids will exist, bounded by non-colonizing civilizations. For P approximately = to P(sub c), arbitrarily large filled regions exist, and also arbitrarily large empty regions.

Intragastric Dai-Kenchu-To, a Japanese herbal medicine, stimulates colonic motility via transient receptor potential cation channel subfamily V member 1 in dogs.

PubMed

Kikuchi, Daisuke; Shibata, Chikashi; Imoto, Hirofumi; Naitoh, Takeshi; Miura, Koh; Unno, Michiaki

2013-08-01

Japanese herbal medicine, also known as Kampo, is used for various diseases in Japan. One of those medicines, Dai-Kenchu-To (DKT), is considered clinically effective for adhesive bowel obstruction and chronic constipation. Although scientific evidence of DKT to improve adhesive bowel obstruction was shown in several previous reports, mechanism of DKT to improve constipation remains unknown. Our aim was to study the effect of intragastric DKT on colonic motility and defecation, and the involvement of various receptors in DKT-induced colonic contractions. Five beagle dogs were instructed with serosal strain-gauge force transducers to measure circular muscle activity at the proximal, middle, and distal colon. Dogs are suitable for a present study to administer the drugs repeatedly to the same individual and look at its effect on colonic motility. We studied the effects of DKT (2.5 or 5 g) administered into the stomach on colonic motility. Muscarinic receptor antagonist atropine, nicotinic receptor antagonist hexamthonium, or 5-hydroxytryptamine-3 receptor antagonist ondansetron was injected intravenously 10 min before DKT administration. Capsazepine, an antagonist to transient receptor potential cation channel subfamily V member 1 (TRPV1), was administered into the stomach 5 min before DKT administration. Intragastric DKT (2.5 or 5 g) induced colonic contractions within 10 min after administration but did not induce defecation. Pretreatment with atropine, hexamthonium, ondansetron, or capsazepine inhibited DKT-induced colonic contractions. These results indicate that orally administered DKT stimulates colonic motility via TRPV1, muscarinic, nicotinic, and 5-hydroxytryptamine-3 receptors, thereby providing scientific support for the efficacy of oral DKT in chronic constipation.

Modeling habitat connectivity to inform reintroductions: a case study with the Chiricahua Leopard Frog

USGS Publications Warehouse

Jarchow, Christopher J.; Hossack, Blake R.; Sigafus, Brent H.; Schwalbe, Cecil R.; Muths, Erin L.

2016-01-01

Managing species with intensive tools such as reintroduction may focus on single sites or entire landscapes. For vagile species, long-term persistence will require colonization and establishment in neighboring habitats. Therefore, both suitable colonization sites and suitable dispersal corridors between sites are required. Assessment of landscapes for both requirements can contribute to ranking and selection of reintroduction areas, thereby improving management success. Following eradication of invasive American Bullfrogs (Lithobates catesbeianus) from most of Buenos Aires National Wildlife Refuge (BANWR; Arizona, United States), larval Chiricahua Leopard Frogs (Lithobates chiricahuensis) from a private pond were reintroduced into three stock ponds. Populations became established at all three reintroduction sites followed by colonization of neighboring ponds in subsequent years. Our aim was to better understand colonization patterns by the federally threatened L. chiricahuensis which could help inform other reintroduction efforts. We assessed the influence of four landscape features on colonization. Using surveys from 2007 and information about the landscape, we developed a habitat connectivity model, based on electrical circuit theory, that identified potential dispersal corridors after explicitly accounting for imperfect detection of frogs. Landscape features provided little insight into why some sites were colonized and others were not, results that are likely because of the uniformity of the BANWR landscape. While corridor modeling may be effective in more-complex landscapes, our results suggest focusing on local habitat will be more useful at BANWR. We also illustrate that existing data, even when limited in spatial or temporal resolution, can provide information useful in formulating management actions.

Bilateral paracoccidioidomycotic iliopsoas abscess associated with ileo-colonic lesion.

PubMed

Duani, Helena; Nunes, Vinícius Rodrigues Taranto; Assumpção, Anísio Borges; Saraiva, Isadora Sofia Borges; Rosa, Rodrigo Macedo; Neiva, Augusto Motta; Pedroso, Enio Roberto Pietra

2012-10-01

This case report shows the clinical development of a patient with systemic paracoccidioidomycosis presenting with lymphatic-intestinalmanifestation. The patient initially had a substantial clinical improvement but had a recrudescence after six months of sulfamethoxazoletrimethoprim oral treatment, with the emergence of feverish syndrome, lumbar pain, and intermittent claudication, characterizing a bilateral iliopsoas muscle abscess, necessitating clinicosurgical therapeutics.

Engineered Chimeric Peptides as Antimicrobial Surface Coating Agents toward Infection-Free Implants

PubMed Central

Yazici, Hilal; O'Neill, Mary B.; Kacar, Turgay; Wilson, Brandon R.; Oren, E. Emre; Sarikaya, Mehmet; Tamerler, Candan

2016-01-01

Prevention of bacterial colonization and consequent biofilm formation remains a major challenge in implantable medical devices. Implant-associated infections are not only a major cause of implant failures but also their conventional treatment with antibiotics brings further complications due to the escalation in multidrug resistance to a variety of bacterial species. Owing to their unique properties, antimicrobial peptides (AMPs) have gained significant attention as effective agents to combat colonization of microorganisms. These peptides have been shown to exhibit a wide spectrum of activities with specificity to a target cell while having a low tendency for developing bacterial resistance. Engineering biomaterial surfaces that feature AMP properties, therefore, offer a promising approach to prevent implant infections. Here, we engineered a chimeric peptide with bifunctionality that both forms a robust solid-surface coating while presenting antimicrobial property. The individual domains of the chimeric peptides were evaluated for their solid-binding kinetics to titanium substrate as well as for their antimicrobial properties in solution. The antimicrobial efficacy of the chimeric peptide on the implant material was evaluated in vitro against infection by a variety of bacteria, including Streptococcus mutans, Staphylococcus. epidermidis, and Escherichia coli, which are commonly found in oral and orthopedic implant related surgeries. Our results demonstrate significant improvement in reducing bacterial colonization onto titanium surfaces below the detectable limit. Engineered chimeric peptides with freely displayed antimicrobial domains could be a potential solution for developing infection-free surfaces by engineering implant interfaces with highly reduced bacterial colonization property. PMID:26795060

Engineered Chimeric Peptides as Antimicrobial Surface Coating Agents toward Infection-Free Implants.

PubMed

Yazici, Hilal; O'Neill, Mary B; Kacar, Turgay; Wilson, Brandon R; Oren, E Emre; Sarikaya, Mehmet; Tamerler, Candan

2016-03-02

Prevention of bacterial colonization and consequent biofilm formation remains a major challenge in implantable medical devices. Implant-associated infections are not only a major cause of implant failures but also their conventional treatment with antibiotics brings further complications due to the escalation in multidrug resistance to a variety of bacterial species. Owing to their unique properties, antimicrobial peptides (AMPs) have gained significant attention as effective agents to combat colonization of microorganisms. These peptides have been shown to exhibit a wide spectrum of activities with specificity to a target cell while having a low tendency for developing bacterial resistance. Engineering biomaterial surfaces that feature AMP properties, therefore, offer a promising approach to prevent implant infections. Here, we engineered a chimeric peptide with bifunctionality that both forms a robust solid-surface coating while presenting antimicrobial property. The individual domains of the chimeric peptides were evaluated for their solid-binding kinetics to titanium substrate as well as for their antimicrobial properties in solution. The antimicrobial efficacy of the chimeric peptide on the implant material was evaluated in vitro against infection by a variety of bacteria, including Streptococcus mutans, Staphylococcus. epidermidis, and Escherichia coli, which are commonly found in oral and orthopedic implant related surgeries. Our results demonstrate significant improvement in reducing bacterial colonization onto titanium surfaces below the detectable limit. Engineered chimeric peptides with freely displayed antimicrobial domains could be a potential solution for developing infection-free surfaces by engineering implant interfaces with highly reduced bacterial colonization property.

Transit time affects the community stability of Lactobacillus and Bifidobacterium species in an in vitro model of human colonic microbiotia.

PubMed

Rodes, Laetitia; Paul, Arghya; Coussa-Charley, Michael; Al-Salami, Hani; Tomaro-Duchesneau, Catherine; Fakhoury, Marc; Prakash, Satya

2011-12-01

Retention time, which is analogous to transit time, is an index for bacterial stability in the intestine. Its consideration is of particular importance to optimize the delivery of probiotic bacteria in order to improve treatment efficacy. This study aims to investigate the effect of retention time on Lactobacilli and Bifidobacteria stability using an established in vitro human colon model. Three retention times were used: 72, 96, and 144 h. The effect of retention time on cell viability of different bacterial populations was analyzed with bacterial plate counts and PCR. The proportions of intestinal Bifidobacteria, Lactobacilli, Enterococci, Staphylococci and Clostridia populations, analyzed by plate counts, were found to be the same as that in human colonic microbiota. Retention time in the human colon affected the stability of Lactobacilli and Bifidobacteria communities, with maximum stability observed at 144 h. Therefore, retention time is an important parameter that influences bacterial stability in the colonic microbiota. Future clinical studies on probiotic bacteria formulations should take into consideration gastrointestinal transit parameters to improve treatment efficacy.

Colonization with Heligmosomoides polygyrus suppresses mucosal IL-17 production.

PubMed

Elliott, David E; Metwali, Ahmed; Leung, John; Setiawan, Tommy; Blum, Arthur M; Ince, M Nedim; Bazzone, Lindsey E; Stadecker, Miguel J; Urban, Joseph F; Weinstock, Joel V

2008-08-15

Helminth exposure appears to protect hosts from inappropriate inflammatory responses, such as those causing inflammatory bowel disease. A recently identified, strongly proinflammatory limb of the immune response is characterized by T cell IL-17 production. Many autoimmune type inflammatory diseases are associated with IL-17 release. Because helminths protect from these diseases, we examined IL-17 production in helminth-colonized mice. We colonized mice with Heligmosomoides polygyrus, an intestinal helminth, and analyzed IL-17 production by lamina propria mononuclear cells (LPMC) and mesenteric lymph node (MLN) cells. Colonization with H. polygyrus reduces IL-17A mRNA by MLN cells and inhibits IL-17 production by cultured LPMC and MLN cells. Helminth exposure augments IL-4 and IL-10 production. Blocking both IL-4 and IL-10, but not IL-10 alone, restores IL-17 production in vitro. Colonization of colitic IL-10-deficient mice with H. polygyrus suppresses LPMC IL-17 production and improves colitis. Ab-mediated blockade of IL-17 improves colitis in IL-10-deficient mice. Thus, helminth-associated inhibition of IL-17 production is most likely an important mechanism mediating protection from inappropriate intestinal inflammation.

Rhizosphere pseudomonads as probiotics improving plant health.

PubMed

Kim, Young Cheol; Anderson, Anne J

2018-04-20

Many root-colonizing microbes are multifaceted in traits that improve plant health. Although isolates designated as biological control agents directly reduce pathogen growth, many exert additional beneficial features that parallel changes induced in animal and other hosts by health-promoting microbes termed probiotics. Both animal and plant probiotics cause direct antagonism of pathogens and induce systemic immunity in the host to pathogens and other stresses. They also alter host development, and improve host nutrition. The probiotic root-colonizing pseudomonads are generalists in terms of plant hosts, soil habitats and the array of stress responses that are ameliorated in the plant. This review illustrates how the probiotic pseudomonads, nurtured by the C and N sources released by the plant in root exudates, form protective biofilms on the root surface and produce the metabolites or enzymes to boost plant health. The findings reveal the multifunctional nature of many of the microbial metabolites in the plant-probiotic interplay. The beneficial effects of probiotics on plant function can contribute to sustainable yield and quality in agricultural production. This article is protected by copyright. All rights reserved. © 2018 BSPP and John Wiley & Sons Ltd.

Colorectal specialization and survival in colorectal cancer.

PubMed

Hall, G M; Shanmugan, S; Bleier, J I S; Jeganathan, A N; Epstein, A J; Paulson, E C

2016-02-01

It is recognized that higher surgeon volume is associated with improved survival in colorectal cancer. However, there is a paucity of national studies that have evaluated the relationship between surgical specialization and survival. We used the Surveillance, Epidemiology, and End Results Medicare cancer registry to examine the association between colorectal specialization (CRS) and disease-specific survival (DSS) between 2001 and 2009. A total of 21,432 colon cancer and 5893 rectal cancer patients who underwent elective surgical resection between 2001 and 2009 were evaluated. Univariate and multivariate Cox survival analysis was used to identify the association between surgical specialization and cancer-specific survival. Colorectal specialists performed 16.3% of the colon and 27% of the rectal resections. On univariate analysis, specialization was associated with improved survival in Stage II and Stage III colon cancer and Stage II rectal cancer. In multivariate analysis, however, CRS was associated with significantly improved DSS only in Stage II rectal cancer [hazard ratio (HR) 0.70, P = 0.03]. CRS was not significantly associated with DSS in either Stage I (colon HR 1.14, P = 0.39; rectal HR 0.1.26, P = 0.23) or Stage III (colon HR 1.06, P = 0.52; rectal HR 1.08, P = 0.55) disease. When analysis was limited to high volume surgeons only, the relationship between CRS and DSS was unchanged. CRS is associated with improved DSS following resection of Stage II rectal cancer. A combination of factors may contribute to long-term survival in these patients, including appropriate surgical technique, multidisciplinary treatment decisions and guideline-adherent surveillance. CRS probably contributes positively to these factors resulting in improved survival. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

Rhizosphere effect of colonizer plant species on the development of soil microbial community during primary succession on postmining sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elhottova, D.; Kristufek, V.; Maly, S.

2009-07-01

The impact of pioneer plant species Tussilago farfara on structural, functional, and growth characterization of microbial community colonizing the spoil colliery substrate was studied in a laboratory microcosm experiment. Microcosms consisting of spoil substrate (0.7 dm{sup 3} of tertiary alkaline clay sediment from Sokolov brown-coal mine area) from a pioneer site (without vegetation, 5 years after heaping) were cultivated in a greenhouse with one plant of this species. Plant roots substantially increased microbial diversity and biomass after one season (7 months) of cultivation. Roots influenced the microbial community and had nearly twice the size, higher growth, and metabolic potential inmore » comparison to the control. The development of microbial specialists improves the plant nutrient status. Bacterial nitrogen (N{sub 2}) fixators (Bradyrhizobium japonicum, Rhizobium radiobacter) and arbuscular mycorrhizal fungi were confirmed in the rhizosphere of Tussilago farfara.« less

Improved Phytophthora resistance in commercial chickpea (Cicer arietinum) varieties negatively impacts symbiotic gene signalling and symbiotic potential in some varieties.

PubMed

Plett, Jonathan M; Plett, Krista L; Bithell, Sean L; Mitchell, Chris; Moore, Kevin; Powell, Jeff R; Anderson, Ian C

2016-08-01

Breeding disease-resistant varieties is one of the most effective and economical means to combat soilborne diseases in pulse crops. Commonalities between pathogenic and mutualistic microbe colonization strategies, however, raises the concern that reduced susceptibility to pathogens may simultaneously reduce colonization by beneficial microbes. We investigate here the degree of overlap in the transcriptional response of the Phytophthora medicaginis susceptible chickpea variety 'Sonali' to the early colonization stages of either Phytophthora, rhizobial bacteria or arbuscular mycorrhizal fungi. From a total of 6476 genes differentially expressed in Sonali roots during colonization by any of the microbes tested, 10.2% were regulated in a similar manner regardless of whether it was the pathogenic oomycete or a mutualistic microbe colonizing the roots. Of these genes, 49.7% were oppositely regulated under the same conditions in the moderately Phytophthora resistant chickpea variety 'PBA HatTrick'. Chickpea varieties with improved resistance to Phytophthora also displayed lower colonization by rhizobial bacteria and mycorrhizal fungi leading to an increased reliance on N and P from soil. Together, our results suggest that marker-based breeding in crops such as chickpea should be further investigated such that plant disease resistance can be tailored to a specific pathogen without affecting mutualistic plant:microbe interactions. © 2016 John Wiley & Sons Ltd.

Benzenediamine analog FC-99 inhibits TLR2 and TLR4 signaling in peritoneal macrophage in vitro.

PubMed

Yang, Liu; Dou, Huan; Song, Yuxian; Hou, Yayi

2016-01-01

Inflammatory bowel disease (IBD) is an inflammatory disorder, characterized by abnormally increased expression of Toll-like receptors TLR2 and TLR4 in the colon and increased pro-inflammatory cytokine production by macrophages. In the present study, we explored the effect of FC-99, a novel benzenediamine analog, on dextran sulfate sodium (DSS)-induced mouse colitis and investigated its potential mechanism. The results revealed that FC-99 improved the colon morphology and the clinical parameters in DSS-induced mouse colitis. FC-99 inhibited the increase of DSS-induced T helper cells (Th) 1 and Th17 and enhanced the number of regulatory T cells (Treg) in mesenteric lymph nodes (MLN), but had no effect on Th2 cells. FC-99 also suppressed the DSS-induced secretion of interleukin (IL)-1β, IL-6, and the tumor necrosis factor (TNF)-α in the colon and hindered the infiltration of macrophages into colon lamina propria. Flow cytometric analysis also confirmed that FC-99 reduced CD11b(+)F4/80(+) colon macrophages, and down-regulated TNF-α level in situ. Moreover, FC-99 inhibited concentration-dependently the expression of TNF-α and IL-6 in vitro from mouse peritoneal macrophages, which were induced by TLR ligands: PamCSK4 and peptidoglycan (PGN, TLR2 ligand) as well as LPS (TLR4 ligand). Of note, FC-99 also suppressed the activation of TLR2 and TLR4 signaling pathways and the downstream nuclear factor-κB (NF-κB) in the DSS-induced mouse colitis. FC-99 improved the condition of DSS-induced mouse colitis by inhibiting the activation of TLR2 and TLR4 signaling pathways in macrophage. These results suggest that FC-99 may be developed as a new therapeutic drug for IBD. Copyright © 2015 Elsevier Inc. All rights reserved.

Nutraceuticals as potential therapeutic agents for colon cancer: a review

PubMed Central

Kuppusamy, Palaniselvam; Yusoff, Mashitah M.; Maniam, Gaanty Pragas; Ichwan, Solachuddin Jauhari Arief; Soundharrajan, Ilavenil; Govindan, Natanamurugaraj

2014-01-01

Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis. PMID:26579381

Nutraceuticals as potential therapeutic agents for colon cancer: a review.

PubMed

Kuppusamy, Palaniselvam; Yusoff, Mashitah M; Maniam, Gaanty Pragas; Ichwan, Solachuddin Jauhari Arief; Soundharrajan, Ilavenil; Govindan, Natanamurugaraj

2014-06-01

Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis.

Risk Factors for the Development of Gastrointestinal Colonization With Fluoroquinolone-Resistant Escherichia coli in Residents of Long-Term Care Facilities

PubMed Central

Han, Jennifer H.; Maslow, Joel; Han, Xiaoyan; Xie, Sharon X.; Tolomeo, Pam; Santana, Evelyn; Carson, Lesley; Lautenbach, Ebbing

2014-01-01

Background. The objective of this study was to assess risk factors for the development of fluoroquinolone (FQ)–resistant Escherichia coli gastrointestinal tract colonization in long-term care facility (LTCF) residents. Methods. A prospective cohort study was conducted from 2006 to 2008 at 3 LTCFs. Residents initially colonized with FQ-susceptible E. coli were followed by means of serial fecal sampling for new FQ-resistant E. coli colonization for up to 12 months or until discharge or death. A Cox proportional hazards regression model was developed to identify risk factors for new FQ-resistant E. coli colonization, with antibiotic and device exposures modeled as time-varying covariates. Results. Fifty-seven (47.5%) of 120 residents became newly colonized with FQ-resistant E. coli, with a median time to colonization of 57 days. Fecal incontinence (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.04–3.06; P = .04) was significantly associated with FQ-resistant E. coli acquisition. Receipt of amoxicillin-clavulanate (HR, 6.48; 95% CI, 1.43–29.4; P = .02) and the presence of a urinary catheter (HR, 3.81; 95% CI, 1.06–13.8; P = .04) during LTCF stay increased the risk of new FQ-resistant E. coli colonization. Conclusions. Acquisition of FQ-resistant E. coli was common, with nearly half of LTCF residents developing new FQ-resistant E. coli colonization. Further studies are needed on interventions to limit the emergence of FQ-resistant E. coli in LTCFs. PMID:23986544

Colon cancer information as a source of exercise motivation for relatives of patients with colon cancer.

PubMed

McGowan, Erin L; Prapavessis, Harry

2010-12-01

Using a Protection Motivation Theory (PMT) framework, this study examined whether factual colon cancer information is a meaningful source of exercise motivation for relatives of patients with colon cancer. One hundred sixty-six inactive relatives were randomly assigned to one of two treatment conditions: PMT group (intervention); and non-PMT group (attention control). At baseline (T1) participants completed demographic information, a questionnaire designed to assess their beliefs toward exercise and colon cancer as well as their exercise intentions. At T2 (one week following T1) participants watched one of two DVD videos that were created for the study. The intervention DVD contained exercise and colon cancer information that was yoked within the four major components of PMT: perceived vulnerability (PV); perceived severity (PS); response efficacy (RE); and self-efficacy (SE), while the attention control DVD contained general diet and cancer information. Immediately following watching the DVD, participants completed the same measures as in T1. Participants assigned to the PMT intervention group showed significant improvement in PV, RE, SE and exercise intentions, whereas participants assigned to the attention control group showed significant improvement only in RE. RE, SE, and PS made significant and unique contributions to prediction of exercise intention. Overall, the results of the present study demonstrate that a single exposure media intervention grounded in a PMT framework can change individuals' exercise and colon cancer beliefs, as well as change their exercise intentions. Implications of these findings and direction for future research are discussed.

Alleviation of Drought Stress and Metabolic Changes in Timothy (Phleum pratense L.) Colonized with Bacillus subtilis B26

PubMed Central

Gagné-Bourque, François; Bertrand, Annick; Claessens, Annie; Aliferis, Konstantinos A.; Jabaji, Suha

2016-01-01

Drought is a major limiting factor of crop productivity worldwide and its incidence is predicted to increase under climate change. Drought adaptation of cool-season grasses is thus a major challenge to secure the agricultural productivity under current and future climate conditions. Endophytes are non-pathogenic plant-associated bacteria that can play an important role in conferring resistance and improving plant tolerance to drought. In this study, the effect of inoculation of the bacterial endophyte Bacillus subtilis strain B26 on growth, water status, photosynthetic activity and metabolism of timothy (Phleum pratense L.) subjected to drought stress was investigated under controlled conditions. Under both drought-stress and non-stressed conditions, strain B26 successfully colonized the internal tissues of timothy and had a positive impact on plant growth. Exposure of inoculated plant to a 8-week drought-stress led to significant increase in shoot and root biomass by 26.6 and 63.8%, and in photosynthesis and stomatal conductance by 55.2 and 214.9% respectively, compared to non-inoculated plants grown under similar conditions. There was a significant effect of the endophyte on plant metabolism; higher levels of several sugars, notably sucrose and fructans and an increase of key amino acids such as, asparagine, glutamic acid and glutamine were recorded in shoots and roots of colonized plants compared to non-colonized ones. The accumulation of the non-protein amino acid GABA in shoots of stressed plants and in roots of stressed and unstressed plants was increased in the presence of the endophyte. Taken together, our results indicate that B. subtilis B26 improves timothy growth under drought stress through the modification of osmolyte accumulation in roots and shoots. These results will contribute to the development of a microbial agent to improve the yield of grass species including forage crops and cereals exposed to environmental stresses. PMID:27200057

DA-9701 improves colonic transit time and symptoms in patients with functional constipation: A prospective study.

PubMed

Kim, Su Young; Woo, Hyun Sun; Kim, Kyoung Oh; Choi, Sung Han; Kwon, Kwang An; Chung, Jun-Won; Kim, Yoon Jae; Kim, Jung Ho; Kim, Su Ji; Park, Dong Kyun

2017-12-01

DA-9701, a newly developed prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber, has been shown to effectively treat functional dyspepsia. Recently, it has also been suspected to improve gastrointestinal motor function. The aims of this study were to assess the effect of DA-9701 on colonic transit time (CTT) and symptoms of functional constipation. Thirty-three patients with functional constipation based on the Rome III criteria were prospectively enrolled. The patients received 30-mg DA-9701 three times a day for 24 days. CTT was estimated initially and at the end of treatment. Symptoms such as spontaneous bowel movements, straining, stool form, feeling of incomplete emptying and anorectal blockage, abdominal discomfort and pain, overall defecation satisfaction, and incidence of adverse events were also analyzed. Twenty-seven patients completed the study. DA-9701 was associated with a significantly reduced CTT from 34.9 ± 17.6 to 23.7 ± 19.1 h (P = 0.001). Segmental CTT also significantly decreased after treatment (right CTT: from 16.8 [0.0-28.8] to 6.0 [0.0-25.2] hours, P < 0.001; rectosigmoid transit time: from 13.2 [0.0-38.4] to 6.0 [0.0-33.6] hours, P = 0.021). In addition, all constipation-related subjective symptoms, including spontaneous bowel movement frequency, significantly improved compared with those before treatment. Serious adverse events did not occur. DA-9701 accelerates colonic transit and safely improves symptoms in patients with functional constipation. Therefore, we suggest that this novel agent could help to treat patients with this condition. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Similarities in the Age-Specific Incidence of Colon and Testicular Cancers.

PubMed

Soto-Ortiz, Luis; Brody, James P

2013-01-01

Colon cancers are thought to be an inevitable result of aging, while testicular cancers are thought to develop in only a small fraction of men, beginning in utero. These models of carcinogenesis are, in part, based upon age-specific incidence data. The specific incidence for colon cancer appears to monotonically increase with age, while that of testicular cancer increases to a maximum value at about 35 years of age, then declines to nearly zero by the age of 80. We hypothesized that the age-specific incidence for these two cancers is similar; the apparent difference is caused by a longer development time for colon cancer and the lack of age-specific incidence data for people over 84 years of age. Here we show that a single distribution can describe the age-specific incidence of both colon carcinoma and testicular cancer. Furthermore, this distribution predicts that the specific incidence of colon cancer should reach a maximum at about age 90 and then decrease. Data on the incidence of colon carcinoma for women aged 85-99, acquired from SEER and the US Census, is consistent with this prediction. We conclude that the age specific data for testicular cancers and colon cancers is similar, suggesting that the underlying process leading to the development of these two forms of cancer may be similar.

Mast Cell Targeted Chimeric Toxin Can Be Developed as an Adjunctive Therapy in Colon Cancer Treatment

PubMed Central

Wang, Shan; Li, Linmei; Shi, Renren; Liu, Xueting; Zhang, Junyan; Zou, Zehong; Hao, Zhuofang; Tao, Ailin

2016-01-01

The association of colitis with colorectal cancer has become increasingly clear with mast cells being identified as important inflammatory cells in the process. In view of the relationship between mast cells and cancer, we studied the effect and mechanisms of mast cells in the development of colon cancer. Functional and mechanistic insights were gained from ex vivo and in vivo studies of cell interactions between mast cells and CT26 cells. Further evidence was reversely obtained in studies of mast cell targeted Fcε-PE40 chimeric toxin. Experiments revealed mast cells could induce colon tumor cell proliferation and invasion. Cancer progression was found to be related to the density of mast cells in colonic submucosa. The activation of MAPK, Rho-GTPase, and STAT pathways in colon cancer cells was triggered by mast cells during cell-to-cell interaction. Lastly, using an Fcε-PE40 chimeric toxin we constructed, we confirmed the promoting effect of mast cells in development of colon cancer. Mast cells are a promoting factor of colon cancer and thus also a potential therapeutic target. The Fcε-PE40 chimeric toxin targeting mast cells could effectively prevent colon cancer in vitro and in vivo. Consequently, these data may demonstrate a novel immunotherapeutic approach for the treatment of tumors. PMID:26978404

Update on the prevention of local recurrence and peritoneal metastases in patients with colorectal cancer.

PubMed

Sugarbaker, Paul H

2014-07-28

The prevention of a disease process has always been superior to the treatment of the same disease throughout the history of medicine and surgery. Local recurrence and peritoneal metastases occur in approximately 8% of colon cancer patients and 25% of rectal cancer patients and should be prevented. Strategies to prevent colon or rectal cancer local recurrence and peritoneal metastases include cytoreductive surgery and hyperthermic perioperative chemotherapy (HIPEC). These strategies can be used at the time of primary colon or rectal cancer resection if the HIPEC is available. At institutions where HIPEC is not available with the treatment of primary malignancy, a proactive second-look surgery is recommended. Several phase II studies strongly support the proactive approach. If peritoneal metastases were treated along with the primary colon resection, 5-year survival was seen and these results were superior to the results of treatment after peritoneal metastases had developed as recurrence. Also, prophylactic HIPEC improved survival with T3/T4 mucinous or signet ring colon cancers. A second-look has been shown to be effective in two published manuscripts. Unpublished data from MedStar Washington Cancer Institute also produced favorable date. Rectal cancer with peritoneal metastases may not be so effectively treated. There are both credits and debits of this proactive approach. Selection factors should be reviewed by the multidisciplinary team for individualized management of patients with or at high risk for peritoneal metastases.

Colonization strategy of the endophytic plant growth-promoting strains of Pseudomonas fluorescens and Klebsiella oxytoca on the seeds, seedlings and roots of the epiphytic orchid, Dendrobium nobile Lindl.

PubMed

Pavlova, A S; Leontieva, M R; Smirnova, T A; Kolomeitseva, G L; Netrusov, A I; Tsavkelova, E A

2017-04-29

Orchids form strong mycorrhizal associations, but their interactions with bacteria are poorly understood. We aimed to investigate the distribution of plant growth promoting rhizobacteria (PGPR) at different stages of orchid development and to study if there is any selective specificity in choosing PGPR partners. Colonization patterns of gfp-tagged Pseudomonas fluorescens and Klebsiella oxytoca were studied on roots, seeds, and seedlings of Dendrobium nobile. Endophytic rhizobacteria rapidly colonized velamen and core parenchyma entering through exodermis and the passage cells, whereas at the early stages, they stayed restricted to the surface and the outer layers of the protocorms and rhizoids. The highest amounts of auxin (indole-3-acetic acid) were produced by K. oxytoca and P. fluorescens in the nitrogen-limiting and NO 3 -containing media respectively. Bacterization of D. nobile seeds resulted in promotion of their in vitro germination. The plant showed no selective specificity to the tested strains. Klebsiella oxytoca demonstrated more intense colonization activity and more efficient growth promoting impact under tryptophan supplementation, while P. fluorescens revealed its growth-promoting capacity without tryptophan. Both strategies are regarded as complementary, improving adaptive potentials of the orchid when different microbial populations colonize the plant. This study enlarges our knowledge on orchid-microbial interactions, and provides new features on application of the nonorchid PGPR in orchid seed germination and conservation. © 2017 The Society for Applied Microbiology.

Differential regulation of EGFR-MAPK signaling by deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) in colon cancer.

PubMed

Centuori, Sara M; Martinez, Jesse D

2014-10-01

A high-fat diet coincides with increased levels of bile acids. This increase in bile acids, particularly deoxycholic acid (DCA), has been strongly associated with the development of colon cancer. Conversely, ursodeoxycholic acid (UDCA) may have chemopreventive properties. Although structurally similar, DCA and UDCA present different biological and pathological effects in colon cancer progression. The differential regulation of cancer by these two bile acids is not yet fully understood. However, one possible explanation for their diverging effects is their ability to differentially regulate signaling pathways involved in the multistep progression of colon cancer, such as the epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) pathway. This review will examine the biological effects of DCA and UDCA on colon cancer development, as well as the diverging effects of these bile acids on the oncogenic signaling pathways that play a role in colon cancer development, with a particular emphasis on bile acid regulation of the EGFR-MAPK pathway.

Differential regulation of EGFR-MAPK signaling by deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) in colon cancer

PubMed Central

Centuori, Sara M.; Martinez, Jesse D.

2014-01-01

A high fat diet coincides with elevated levels of bile acids. This elevation of bile acids, particularly deoxycholic acid (DCA), has been strongly associated with the development of colon cancer. Conversely, ursodeoxycholic acid (UDCA) may have chemopreventive properties. Although structurally similar, DCA and UDCA present different biological and pathological effects in colon cancer progression. The differential regulation of cancer by these two bile acids is not yet fully understood. However, one possible explanation for their diverging effects is their ability to differentially regulate signaling pathways involved in the multistep progression of colon cancer, such as the epidermal growth factor receptor (EGFR) mitogen-activated protein kinase (MAPK) pathway. This review will examine the biological effects of DCA and UDCA on colon cancer development, as well as the diverging effects of these bile acids on the oncogenic signaling pathways that play a role in colon cancer development, with a particular emphasis on bile acid regulation of the EGFR-MAPK pathway. PMID:25027205

Deciphering the factors associated with the colonization of rice plants by cyanobacteria.

PubMed

Bidyarani, Ngangom; Prasanna, Radha; Chawla, Gautam; Babu, Santosh; Singh, Rajendra

2015-04-01

Cyanobacteria-rice plant interactions were analyzed using a hydroponics experiment. The activity of plant defense and pathogenesis-related enzymes, scanning electron microscopy, growth, nitrogen fixation (measured as ARA), and DNA fingerprinting assays proved useful in illustrating the nature of associations of cyanobacteria with rice plants. Microscopic analyses revealed the presence of short filaments and coiled masses of filaments of cyanobacteria near the epidermis and cortex of roots and shoot tissues. Among the six cyanobacterial strains employed, Calothrix sp. (RPC1), Anabaena laxa (RPAN8), and Anabaena azollae (C16) were the best performing strains, in terms of colonization in roots and stem. These strains also enhanced nitrogen fixation and stimulated the activity of plant defense/cell wall-degrading enzymes. A significantly high correlation was also recorded between the elicited plant enzymes, growth, and ARA. DNA fingerprinting using highly iterated palindromic sequences (HIP-TG) further helped in proving the establishment of inoculated organisms in the roots/shoots of rice plants. This study illustrated that the colonization of cyanobacteria in the plant tissues is facilitated by increased elicitation of plant enzymes, leading to improved plant growth, nutrient mobilization, and enhanced plant fitness. Such strains can be promising candidates for developing "cyanobacteria colonized-nitrogen-fixing rice plants" in the future. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genetic variability in arbuscular mycorrhizal fungi compatibility supports the selection of durum wheat genotypes for enhancing soil ecological services and cropping systems in Canada.

PubMed

Singh, A K; Hamel, C; Depauw, R M; Knox, R E

2012-03-01

Crop nutrient- and water-use efficiency could be improved by using crop varieties highly compatible with arbuscular mycorrhizal fungi (AMF). Two greenhouse experiments demonstrated the presence of genetic variability for this trait in modern durum wheat ( Triticum turgidum L. var. durum Desf.) germplasm. Among the five cultivars tested, 'AC Morse' had consistently low levels of AM root colonization and DT710 had consistently high levels of AM root colonization, whereas 'Commander', which had the highest colonization levels under low soil fertility conditions, developed poor colonization levels under medium fertility level. The presence of genetic variability in durum wheat compatibility with AMF was further evidenced by significant genotype × inoculation interaction effects in grain and straw biomass production; grain P, straw P, and straw K concentrations under medium soil fertility level; and straw K and grain Fe concentrations at low soil fertility. Mycorrhizal dependency was an undesirable trait of 'Mongibello', which showed poor growth and nutrient balance in the absence of AMF. An AMF-mediated reduction in grain Cd under low soil fertility indicated that breeding durum wheat for compatibility with AMF could help reduce grain Cd concentration in durum wheat. Durum wheat genotypes should be selected for compatibility with AMF rather than for mycorrhizal dependency.

Vanillin-Ameliorated Development of Azoxymethane/Dextran Sodium Sulfate-Induced Murine Colorectal Cancer: The Involvement of Proteasome/Nuclear Factor-κB/Mitogen-Activated Protein Kinase Pathways.

PubMed

Li, Jung-Miao; Lee, Yu-Chen; Li, Chia-Cheng; Lo, Hsin-Yi; Chen, Feng-Yuan; Chen, Yi-Siou; Hsiang, Chien-Yun; Ho, Tin-Yun

2018-06-06

Vanillin is a natural dietary flavoring widely used in the food industry. Colorectal cancer (CRC) is one of the common malignancies in the world. Chronic intestinal inflammation is a risk factor for the development of CRC. We have previously found that vanillin improves and prevents colitis in mice. Here we evaluated the inhibitory activities of vanillin on a mouse model of colitis-induced CRC. Mice were challenged intraperitoneally with azoxymethane (AOM) and orally with dextran sodium sulfate (DSS). Various dosages of vanillin were orally administered for 13 consecutive weeks. Vanillin alleviated the development of tumors in AOM/DSS-induced mice. The total number of tumors in 100 mg/kg vanillin group was significantly reduced by 57.14 ± 7.67%, compared with sham group. Gene expression analysis showed that vanillin downregulated the expression levels of proteasome genes in colon tissues. Moreover, vanillin at 10 mM significantly suppressed proteasome activities in HCT-116 cells by 41.27 ± 0.41%. Furthermore, vanillin diminished the phosphorylation of mitogen-activated protein kinases (MAPKs) and reduced the number of p65-positive cells, proliferating cells, and granulocytes in colon tissues with statistical significance. In conclusion, our data suggested that vanillin was a bioactive compound that ameliorated the development of AOM/DSS-induced colon cancer in mice. Moreover, the amelioration of vanillin might be associated with the downregulation of proteasome, nuclear factor-κB, and MAPK pathways.

Genome-wide identification of bacterial plant colonization genes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cole, Benjamin J.; Feltcher, Meghan E.; Waters, Robert J.

Diverse soil-resident bacteria can contribute to plant growth and health, but the molecular mechanisms enabling them to effectively colonize their plant hosts remain poorly understood. We used randomly barcoded transposon mutagenesis sequencing (RB-TnSeq) in Pseudomonas simiae, a model root-colonizing bacterium, to establish a genome-wide map of bacterial genes required for colonization of the Arabidopsis thaliana root system. We identified 115 genes (2% of all P. simiae genes) with functions that are required for maximal competitive colonization of the root system. Among the genes we identified were some with obvious colonization-related roles in motility and carbon metabolism, as well as 44more » other genes that had no or vague functional predictions. Independent validation assays of individual genes confirmed colonization functions for 20 of 22 (91%) cases tested. To further characterize genes identified by our screen, we compared the functional contributions of P. simiae genes to growth in 90 distinct in vitro conditions by RB-TnSeq, highlighting specific metabolic functions associated with root colonization genes. Here, our analysis of bacterial genes by sequence-driven saturation mutagenesis revealed a genome-wide map of the genetic determinants of plant root colonization and offers a starting point for targeted improvement of the colonization capabilities of plant-beneficial microbes.« less

Genome-wide identification of bacterial plant colonization genes

DOE PAGES

Cole, Benjamin J.; Feltcher, Meghan E.; Waters, Robert J.; ...

2017-09-22

Diverse soil-resident bacteria can contribute to plant growth and health, but the molecular mechanisms enabling them to effectively colonize their plant hosts remain poorly understood. We used randomly barcoded transposon mutagenesis sequencing (RB-TnSeq) in Pseudomonas simiae, a model root-colonizing bacterium, to establish a genome-wide map of bacterial genes required for colonization of the Arabidopsis thaliana root system. We identified 115 genes (2% of all P. simiae genes) with functions that are required for maximal competitive colonization of the root system. Among the genes we identified were some with obvious colonization-related roles in motility and carbon metabolism, as well as 44more » other genes that had no or vague functional predictions. Independent validation assays of individual genes confirmed colonization functions for 20 of 22 (91%) cases tested. To further characterize genes identified by our screen, we compared the functional contributions of P. simiae genes to growth in 90 distinct in vitro conditions by RB-TnSeq, highlighting specific metabolic functions associated with root colonization genes. Here, our analysis of bacterial genes by sequence-driven saturation mutagenesis revealed a genome-wide map of the genetic determinants of plant root colonization and offers a starting point for targeted improvement of the colonization capabilities of plant-beneficial microbes.« less

Advancing nutritional therapy: A novel polymeric formulation attenuates intestinal inflammation in a murine colitis model and suppresses pro-inflammatory cytokine production in ex-vivo cultured inflamed colonic biopsies.

PubMed

Alhagamhmad, Moftah H; Lemberg, Daniel A; Day, Andrew S; Tan, Li-Zsa; Ooi, Chee Y; Krishnan, Usha; Gupta, Nitin; Munday, John S; Leach, Steven T

2017-04-01

Nutritional therapy is a viable therapeutic option for the treatment of Crohn disease (CD). Therefore improving nutritional therapy would greatly benefit CD patients. The aim of this study was to define the anti-inflammatory properties of a novel nutritional polymeric formula (PF) in comparison to a currently available standard PF. Dextran sodium sulfate (DSS) was utilized to induce colitis in C57BL/6 mice with mice randomized to receive either standard PF or novel PF in addition to control groups. Changes in body weight were recorded and colonic damage was assessed histologically and biochemically. Additional experiments were also included where the cytokine response of colonic biopsies from pediatric CD patients was measured following exposure to standard PF or novel PF. DSS induced significant body weight loss, morphological changes in the colon, increased myeloperoxidase (MPO) activity and up-regulated colonic mRNA expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12 and monocyte chemoattractant protein (MCP)-1, as well as associated histological changes. Other than histological damage, these inflammatory changes were reversed by both novel and standard PF. However, the novel PF, but not standard PF, completely suppressed TNF-α, IL-6 and IL-8 levels from cultured biopsies. Newly developed nutritional formula reproducibly ameliorated DSS-induced colitis in a murine model, although this response was not measurably different to standard PF. However, the novel PF was significantly superior in suppressing inflammatory cytokine release from cultured colonic biopsies. Collectively, these findings support a possible role for novel PF in advancing nutritional therapy for CD patients. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Generation of an inducible colon-specific Cre enzyme mouse line for colon cancer research.

PubMed

Tetteh, Paul W; Kretzschmar, Kai; Begthel, Harry; van den Born, Maaike; Korving, Jeroen; Morsink, Folkert; Farin, Henner; van Es, Johan H; Offerhaus, G Johan A; Clevers, Hans

2016-10-18

Current mouse models for colorectal cancer often differ significantly from human colon cancer, being largely restricted to the small intestine. Here, we aim to develop a colon-specific inducible mouse model that can faithfully recapitulate human colon cancer initiation and progression. Carbonic anhydrase I (Car1) is a gene expressed uniquely in colonic epithelial cells. We generated a colon-specific inducible Car1 CreER knock-in (KI) mouse with broad Cre activity in epithelial cells of the proximal colon and cecum. Deletion of the tumor suppressor gene Apc using the Car1 CreER KI caused tumor formation in the cecum but did not yield adenomas in the proximal colon. Mutation of both Apc and Kras yielded microadenomas in both the cecum and the proximal colon, which progressed to macroadenomas with significant morbidity. Aggressive carcinomas with some invasion into lymph nodes developed upon combined induction of oncogenic mutations of Apc, Kras, p53, and Smad4 Importantly, no adenomas were observed in the small intestine. Additionally, we observed tumors from differentiated Car1-expressing cells with Apc/Kras mutations, suggesting that a top-down model of intestinal tumorigenesis can occur with multiple mutations. Our results establish the Car1 CreER KI as a valuable mouse model to study colon-specific tumorigenesis and metastasis as well as cancer-cell-of-origin questions.

Exteriorized colon anastomosis for unprepared bowel: An alternative to routine colostomy

PubMed Central

Asfar, Sami K; Al-Sayer, Hilal M; Juma, Talib H

2007-01-01

AIM: To see the possibility of avoiding routine colostomy in patients presenting with unprepared bowel. METHODS: The cohort is composed of 103 patients, of these, 86 patients presented as emergencies (self-inflected and iatrogenic colon injuries, stab wounds and blast injury of the colon, volvulus sigmoid, obstructing left colon cancer, and strangulated ventral hernia). Another 17 patients were managed electively for other colon pathologies. During laparotomy, the involved segment was resected and the two ends of the colon were brought out via a separate colostomy wound. One layer of interrupted 3/0 silk was used for colon anastomosis. The exteriorized segment was immediately covered with a colostomy bag. Between the 5th and 7th postoperative day, the colon was easily dropped into the peritoneal cavity. The defect in the abdominal wall was closed with interrupted nonabsorbable suture. The skin was left open for secondary closure. RESULTS: The mean hospital stay (± SD) was 11.5 ± 2.6 d (8-20 d). The exteriorized colon was successfully dropped back into the peritoneal cavity in all patients except two. One developed a leak from oesophago-jejunostomy and from the exteriorized colon. She subsequently died of sepsis and multiple organ failure (MOF). In a second patient the colon proximal to the exteriorized anastomosis prolapsed and developed severe serositis, an elective ileo-colic anastomosis (to the left colon) was successfully performed. CONCLUSION: Exteriorized colon anastomosis is simple, avoids the inconvenience of colostomy and can be an alternative to routine colostomy. It is suitable where colostomy is socially unacceptable or the facilities and care is not available. PMID:17589900

Salt Reduction in a Model High-Salt Akawi Cheese: Effects on Bacterial Activity, pH, Moisture, Potential Bioactive Peptides, Amino Acids, and Growth of Human Colon Cells.

PubMed

Gandhi, Akanksha; Shah, Nagendra P

2016-04-01

This study evaluated the effects of sodium chloride reduction and its substitution with potassium chloride on Akawi cheese during storage for 30 d at 4 °C. Survival of probiotic bacteria (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium longum) and starter bacteria (Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus), angiotensin-converting enzyme-inhibitory and antioxidant activities, and concentrations of standard amino acids as affected by storage in different brine solutions (10% NaCl, 7.5% NaCl, 7.5% NaCl+KCl [1:1], 5% NaCl, and 5% NaCl+KCl [1:1]) were investigated. Furthermore, viability of human colon cells and human colon cancer cells as affected by the extract showing improved peptide profiles, highest release of amino acids and antioxidant activity (that is, from cheese brined in 7.5% NaCl+KCl) was evaluated. Significant increase was observed in survival of probiotic bacteria in cheeses with low salt after 30 d. Calcium content decreased slightly during storage in all cheeses brined in various solutions. Further, no significant changes were observed in ACE-inhibitory activity and antioxidant activity of cheeses during storage. Interestingly, concentrations of 4 essential amino acids (phenylalanine, tryptophan, valine, and leucine) increased significantly during storage in brine solutions containing 7.5% total salt. Low concentration of cheese extract (100 μg/mL) significantly improved the growth of normal human colon cells, and reduced the growth of human colon cancer cells. Overall, the study revealed that cheese extracts from reduced-NaCl brine improved the growth of human colon cells, and the release of essential amino acids, but did not affect the activities of potential bioactive peptides. © 2016 Institute of Food Technologists®

Methicillin-resistant Staphylococcus aureus colonization, behavioral risk factors, and skin and soft-tissue infection at an ambulatory clinic serving a large population of HIV-infected men who have sex with men.

PubMed

Szumowski, John D; Wener, Kenneth M; Gold, Howard S; Wong, Michael; Venkataraman, Lata; Runde, Carrie A; Cohen, Daniel E; Mayer, Kenneth H; Wright, Sharon B

2009-07-01

We conducted a prospective cohort study of 795 outpatients, many of whom were human immunodeficiency virus-infected men who have sex with men, to characterize risk of skin and soft-tissue infection (SSTI) associated with methicillin-resistant Staphylococcus aureus (MRSA) nares and perianal colonization. Multivariate analysis revealed that perianal colonization, drug use, and prior SSTIs were strongly associated with development of an SSTI. Of the patients who were colonized with MRSA at study entry, 36.7% developed an SSTI during the ensuing 12 months, compared with 8.1% of persons who were not colonized with MRSA.

Influence of an elemental diet on 5-fluorouracil-induced morphological changes in the mouse salivary gland and colon.

PubMed

Kawashima, Rei; Fujimaki, Mio; Ikenoue, Yuka; Danjo, Keiko; Koizumi, Wasaburo; Ichikawa, Takafumi

2016-04-01

The elemental diet (ED) Elental® reportedly reduces adverse reactions to chemotherapy in digestive system cancer patients; however, the mechanism is unclear. Therefore, we verified the protective effect of ED against gastrointestinal disorders induced by the antineoplastic drug 5-fluorouracil (5-FU). After 5 days of tail vein injections of 40 mg/kg/day 5-FU in female BALB/c mice, the mice were given oral ED (ED group) or dextrin with the same number of calories (control group). We measured the weight of salivary glands and the PAS-positive area of colonic mucosa and verified the antitumor effect in tumor-bearing mice given 5-FU and ED. Although body weight decreased after 5-FU treatment, ED group mice weighed more than control group mice. Additionally, although control mice developed diarrhea after 5-FU treatment, the ED group showed only loose stools. The control group saliva volume was approximately one sixth of the vehicle group volume after 5-FU treatment; this was improved to approximately half in the ED group. The area ratio of PAS-positive cells in the colonic mucosa was reduced by 5-FU treatment, with the ratio being higher in the ED group than that in the control group. Similar tumor growth suppression was observed in the 5-FU and ED groups. ED alleviated adverse reactions to 5-FU without affecting antitumor activity. Protection against 5-FU-induced weight loss was potentially due to both improved nutritional support with combined ingredients and prevention of diarrhea that is associated with reduced colonic goblet cells and decreased saliva production from reduced salivary gland contraction.

Postnatal colonization with human "infant-type" Bifidobacterium species alters behavior of adult gnotobiotic mice.

PubMed

Luk, Berkley; Veeraragavan, Surabi; Engevik, Melinda; Balderas, Miriam; Major, Angela; Runge, Jessica; Luna, Ruth Ann; Versalovic, James

2018-01-01

Accumulating studies have defined a role for the intestinal microbiota in modulation of host behavior. Research using gnotobiotic mice emphasizes that early microbial colonization with a complex microbiota (conventionalization) can rescue some of the behavioral abnormalities observed in mice that grow to adulthood completely devoid of bacteria (germ-free mice). However, the human infant and adult microbiomes vary greatly, and effects of the neonatal microbiome on neurodevelopment are currently not well understood. Microbe-mediated modulation of neural circuit patterning in the brain during neurodevelopment may have significant long-term implications that we are only beginning to appreciate. Modulation of the host central nervous system by the early-life microbiota is predicted to have pervasive and lasting effects on brain function and behavior. We sought to replicate this early microbe-host interaction by colonizing gnotobiotic mice at the neonatal stage with a simplified model of the human infant gut microbiota. This model consortium consisted of four "infant-type" Bifidobacterium species known to be commensal members of the human infant microbiota present in high abundance during postnatal development. Germ-free mice and mice neonatally-colonized with a complex, conventional murine microbiota were used for comparison. Motor and non-motor behaviors of the mice were tested at 6-7 weeks of age, and colonization patterns were characterized by 16S ribosomal RNA gene sequencing. Adult germ-free mice were observed to have abnormal memory, sociability, anxiety-like behaviors, and motor performance. Conventionalization at the neonatal stage rescued these behavioral abnormalities, and mice colonized with Bifidobacterium spp. also exhibited important behavioral differences relative to the germ-free controls. The ability of Bifidobacterium spp. to improve the recognition memory of both male and female germ-free mice was a prominent finding. Together, these data demonstrate that the early-life gut microbiome, and human "infant-type" Bifidobacterium species, affect adult behavior in a strongly sex-dependent manner, and can selectively recapitulate the results observed when mice are colonized with a complex microbiota.

Black raspberries in cancer clinical trials: Past, present and future.

PubMed

Kresty, Laura A; Mallery, Susan R; Stoner, Gary D

Black raspberries (BRB) inhibit a broad range of cancers in preclinical models, including in vivo models of oral, esophageal, colon, breast and skin cancer. Promising preclinical results have led to clinical evaluations in cancer patients or patients at increased risk for cancer development. To summarize clinical investigations targeting cancer or precancerous lesions with BRB and discuss future directions. A thorough literature search was conducted through December 1, 2015 to identify all published studies evaluating BRB in cancer focused clinical trials. Research investigating BRB in clinical settings report positive effects on preneoplastic lesions or cancers of the oral cavity, esophagus and colon. BRB treatment resulted in: histologic regression of oral intraepithelial neoplasia associated with improved histologic grade and significantly reduced loss of heterozygosity at tumor suppressor gene loci, modulated genes linked to RNA processing and growth factor recycling; in the colon, BRB inhibited FAP-associated polyp progression, demethylated tumor suppressor genes and improved plasma cytokine profiles; in Barrett's patients, BRB consumption increased tissue levels of GST-pi and decreased 8-isoprostane, a marker of lipid peroxidation/oxidative stress. The precise dose, duration and optimum mode of BRB delivery for cancer inhibition remains to be fully elucidated. Common themes across studies support that BRB are anti-proliferative, anti- inflammatory, reduce oxidative stress and restore tumor suppressive activity. Future directions are included in the conclusions section.

Registration of prone and supine CT colonography scans using correlation optimized warping and canonical correlation analysis

PubMed Central

Wang, Shijun; Yao, Jianhua; Liu, Jiamin; Petrick, Nicholas; Van Uitert, Robert L.; Periaswamy, Senthil; Summers, Ronald M.

2009-01-01

Purpose: In computed tomographic colonography (CTC), a patient will be scanned twice—Once supine and once prone—to improve the sensitivity for polyp detection. To assist radiologists in CTC reading, in this paper we propose an automated method for colon registration from supine and prone CTC scans. Methods: We propose a new colon centerline registration method for prone and supine CTC scans using correlation optimized warping (COW) and canonical correlation analysis (CCA) based on the anatomical structure of the colon. Four anatomical salient points on the colon are first automatically distinguished. Then correlation optimized warping is applied to the segments defined by the anatomical landmarks to improve the global registration based on local correlation of segments. The COW method was modified by embedding canonical correlation analysis to allow multiple features along the colon centerline to be used in our implementation. Results: We tested the COW algorithm on a CTC data set of 39 patients with 39 polyps (19 training and 20 test cases) to verify the effectiveness of the proposed COW registration method. Experimental results on the test set show that the COW method significantly reduces the average estimation error in a polyp location between supine and prone scans by 67.6%, from 46.27±52.97 to 14.98 mm±11.41 mm, compared to the normalized distance along the colon centerline algorithm (p<0.01). Conclusions: The proposed COW algorithm is more accurate for the colon centerline registration compared to the normalized distance along the colon centerline method and the dynamic time warping method. Comparison results showed that the feature combination of z-coordinate and curvature achieved lowest registration error compared to the other feature combinations used by COW. The proposed method is tolerant to centerline errors because anatomical landmarks help prevent the propagation of errors across the entire colon centerline. PMID:20095272

Registration of prone and supine CT colonography scans using correlation optimized warping and canonical correlation analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Shijun; Yao Jianhua; Liu Jiamin

Purpose: In computed tomographic colonography (CTC), a patient will be scanned twice--Once supine and once prone--to improve the sensitivity for polyp detection. To assist radiologists in CTC reading, in this paper we propose an automated method for colon registration from supine and prone CTC scans. Methods: We propose a new colon centerline registration method for prone and supine CTC scans using correlation optimized warping (COW) and canonical correlation analysis (CCA) based on the anatomical structure of the colon. Four anatomical salient points on the colon are first automatically distinguished. Then correlation optimized warping is applied to the segments defined bymore » the anatomical landmarks to improve the global registration based on local correlation of segments. The COW method was modified by embedding canonical correlation analysis to allow multiple features along the colon centerline to be used in our implementation. Results: We tested the COW algorithm on a CTC data set of 39 patients with 39 polyps (19 training and 20 test cases) to verify the effectiveness of the proposed COW registration method. Experimental results on the test set show that the COW method significantly reduces the average estimation error in a polyp location between supine and prone scans by 67.6%, from 46.27{+-}52.97 to 14.98 mm{+-}11.41 mm, compared to the normalized distance along the colon centerline algorithm (p<0.01). Conclusions: The proposed COW algorithm is more accurate for the colon centerline registration compared to the normalized distance along the colon centerline method and the dynamic time warping method. Comparison results showed that the feature combination of z-coordinate and curvature achieved lowest registration error compared to the other feature combinations used by COW. The proposed method is tolerant to centerline errors because anatomical landmarks help prevent the propagation of errors across the entire colon centerline.« less

Structure-based design of peptides against HER2 with cytotoxicity on colon cancer.

PubMed

Cha, Nier; Han, Xiuhua; Jia, Baoqing; Liu, Yanheng; Wang, Xiaoli; Gao, Yanwei; Ren, Jun

2017-05-01

In this study, we found that four novel peptides designed by molecular modeling techniques were successfully applicated with cytotoxicity on colon cancer cells sw620. First, the interactions between the Herstatin and the HER2 were explored by ational-designed approaches, which were combined with homology modeling, protein/protein docking, and structural superimposition analysis. Then, based on the results derived from theoretical analysis, four novel peptides were designed, synthesized, and experimentally evaluated for biological function; it was found that they showed a remarkable enhancement on Herceptin to inhibit the genesis and development of colon cancers, and no significant side effects on normal colon cells NCM460 were observed but Doxorubicin had. These results indicated that it is a feasible way to use the well-designed peptides derived from Herstatin to enhance the efficacy of clinical drugs Herceptin and to kill colon cancer cells selectively without harming normal colon cells. We believe that our research might provide a new way to develop the potential therapies for colon cancers.

Seasonal differences in extinction and colonization drive occupancy dynamics of an imperilled amphibian.

PubMed

Randall, Lea A; Smith, Des H V; Jones, Breana L; Prescott, David R C; Moehrenschlager, Axel

2015-01-01

A detailed understanding of the population dynamics of many amphibian species is lacking despite concerns about declining amphibian biodiversity and abundance. This paper explores temporal patterns of occupancy and underlying extinction and colonization dynamics in a regionally imperiled amphibian species, the Northern leopard frog (Lithobates pipiens) in Alberta. Our study contributes to elucidating regional occupancy dynamics at northern latitudes, where climate extremes likely have a profound effect on seasonal occupancy. The primary advantage of our study is its wide geographic scale (60,000 km2) and the use of repeat visual surveys each spring and summer from 2009-2013. We find that occupancy varied more dramatically between seasons than years, with low spring and higher summer occupancy. Between spring and summer, colonization was high and extinction low; inversely, colonization was low and extinction high over the winter. The dynamics of extinction and colonization are complex, making conservation management challenging. Our results reveal that Northern leopard frog occupancy was constant over the last five years and thus there is no evidence of decline or recovery within our study area. Changes to equilibrium occupancy are most sensitive to increasing colonization in the spring or declining extinction in the summer. Therefore, conservation and management efforts should target actions that are likely to increase spring colonization; this could be achieved through translocations or improving the quality or access to breeding habitat. Because summer occupancy is already high, it may be difficult to improve further. Nevertheless, summer extinction could be reduced by predator control, increasing water quality or hydroperiod of wetlands, or increasing the quality or quantity of summer habitat.

Giardia Colonizes and Encysts in High-Density Foci in the Murine Small Intestine

PubMed Central

Barash, N. R.; Nosala, C.; Pham, J. K.; McInally, S. G.; Gourguechon, S.; McCarthy-Sinclair, B.

2017-01-01

ABSTRACT Giardia lamblia is a highly prevalent yet understudied protistan parasite causing significant diarrheal disease worldwide. Hosts ingest Giardia cysts from contaminated sources. In the gastrointestinal tract, cysts excyst to become motile trophozoites, colonizing and attaching to the gut epithelium. Trophozoites later differentiate into infectious cysts that are excreted and contaminate the environment. Due to the limited accessibility of the gut, the temporospatial dynamics of giardiasis in the host are largely inferred from laboratory culture and thus may not mirror Giardia physiology in the host. Here, we have developed bioluminescent imaging (BLI) to directly interrogate and quantify the in vivo temporospatial dynamics of Giardia infection, thereby providing an improved murine model to evaluate anti-Giardia drugs. Using BLI, we determined that parasites primarily colonize the proximal small intestine nonuniformly in high-density foci. By imaging encystation-specific bioreporters, we show that encystation initiates shortly after inoculation and continues throughout the duration of infection. Encystation also initiates in high-density foci in the proximal small intestine, and high density contributes to the initiation of encystation in laboratory culture. We suggest that these high-density in vivo foci of colonizing and encysting Giardia likely result in localized disruption to the epithelium. This more accurate visualization of giardiasis redefines the dynamics of the in vivo Giardia life cycle, paving the way for future mechanistic studies of density-dependent parasitic processes in the host. IMPORTANCE Giardia is a single-celled parasite causing significant diarrheal disease in several hundred million people worldwide. Due to limited access to the site of infection in the gastrointestinal tract, our understanding of the dynamics of Giardia infections in the host has remained limited and largely inferred from laboratory culture. To better understand Giardia physiology and colonization in the host, we developed imaging methods to quantify Giardia expressing bioluminescent physiological reporters in two relevant animal models. We discovered that parasites primarily colonize and encyst in the proximal small intestine in discrete, high-density foci. We also show that high parasite density contributes to encystation initiation. PMID:28656177

Similarities in the Age-Specific Incidence of Colon and Testicular Cancers

PubMed Central

Soto-Ortiz, Luis; Brody, James P.

2013-01-01

Colon cancers are thought to be an inevitable result of aging, while testicular cancers are thought to develop in only a small fraction of men, beginning in utero. These models of carcinogenesis are, in part, based upon age-specific incidence data. The specific incidence for colon cancer appears to monotonically increase with age, while that of testicular cancer increases to a maximum value at about 35 years of age, then declines to nearly zero by the age of 80. We hypothesized that the age-specific incidence for these two cancers is similar; the apparent difference is caused by a longer development time for colon cancer and the lack of age-specific incidence data for people over 84 years of age. Here we show that a single distribution can describe the age-specific incidence of both colon carcinoma and testicular cancer. Furthermore, this distribution predicts that the specific incidence of colon cancer should reach a maximum at about age 90 and then decrease. Data on the incidence of colon carcinoma for women aged 85–99, acquired from SEER and the US Census, is consistent with this prediction. We conclude that the age specific data for testicular cancers and colon cancers is similar, suggesting that the underlying process leading to the development of these two forms of cancer may be similar. PMID:23840520

Smad3 mutant mice develop colon cancer with overexpression of COX-2

PubMed Central

Zhu, Yu-Ping; Liu, Zhuo; Fu, Zhi-Xuan; Li, De-Chuan

2017-01-01

Colon cancer is the second most common cause of cancer-associated mortality in human populations. The aim of the present study was to identify the role of cyclooxygenase-2 (COX-2) in Smad3 mutant mice, which are known to develop colon cancer. Homozygous Smad3 (−/−) mutant mice were generated from inbred and hybrid Smad3 mouse strains by intercrossing the appropriate heterozygotes. Immunohistochemistry with COX-2 antibody was performed throughout this experiment and the data was validated and cross-checked with reverse transcription-polymerase chain reaction (RT-PCR). Homozygous mutant Smad3 mice were generated and the overexpression pattern of COX-2 was identified by immunohistochemistry and validated with RT-PCR. The results of the present study demonstrated a link between the Smad3 mutant mice, colon cancer and COX-2. In addition, the overexpression pattern of COX-2 in Smad3 mutant mice that develop colon cancer was identified. PMID:28454287

Systemic Chromosome Instability Resulted in Colonic Transcriptomic Changes in Metabolic, Proliferation, and Stem Cell Regulators in Sgo1-/+ Mice.

PubMed

Rao, Chinthalapally V; Sanghera, Saira; Zhang, Yuting; Biddick, Laura; Reddy, Arun; Lightfoot, Stan; Janakiram, Naveena B; Mohammed, Altaf; Dai, Wei; Yamada, Hiroshi Y

2016-02-01

Colon cancer is the second most lethal cancer and is predicted to claim 49,700 lives in the United States this year. Chromosome instability (CIN) is observed in 80% to 90% of colon cancers and is thought to contribute to colon cancer progression and recurrence. To investigate the impact of CIN on colon cancer development, we developed shugoshin-1 (Sgo1) haploinsufficient (-/+) mice, an animal model focusing on mitotic error-induced CIN. In this study, we analyzed signature changes in the colonic transcriptome of Sgo1(-/+) mice to examine the molecular events underlying the altered carcinogenesis profiles in Sgo1(-/+) mice. We performed next-generation sequencing of normal-looking colonic mucosal tissue from mice treated with the carcinogen azoxymethane after 24 weeks. Transcriptome profiling revealed 349 hits with a 2-fold expression difference threshold (217 upregulated genes, 132 downregulated genes, P < 0.05). Pathway analyses indicated that the Sgo1-CIN tissues upregulated pathways known to be activated in colon cancer, including lipid metabolism (z score 4.47), Notch signaling (4.47), insulin signaling (3.81), and PPAR pathways (3.75), and downregulated pathways involved in immune responses including allograft rejection (6.69) and graft-versus-host disease (6.54). Notably, stem cell markers were also misregulated. Collectively, our findings demonstrate that systemic CIN results in transcriptomic changes in metabolism, proliferation, cell fate, and immune responses in the colon, which may foster a microenvironment amenable to cancer development. Therefore, therapeutic approaches focusing on these identified pathways may be valuable for colon cancer prevention and treatment. ©2016 American Association for Cancer Research.

Targeting the 19S proteasomal subunit, Rpt4, for the treatment of colon cancer.

PubMed

Boland, Karen; Flanagan, Lorna; McCawley, Niamh; Pabari, Ritesh; Kay, Elaine W; McNamara, Deborah A; Murray, Frank; Byrne, Annette T; Ramtoola, Zebunnissa; Concannon, Caoimhín G; Prehn, Jochen H M

2016-06-05

Deregulation of the ubiquitin-proteasome pathway has been frequently observed in a number of malignancies. Using quantitative Western blotting of normal and matched tumour tissue, we here identified a significant increase in the 19S proteasome subunit Rpt4 in response to chemoradiation in locally advanced rectal cancer patients with unfavourable outcome. We therefore explored the potential of Rpt4 reduction as a therapeutic strategy in colorectal cancer (CRC). Utilizing siRNA to down regulate Rpt4 expression, we show that silencing of Rpt4 reduced proteasomal activity and induced endoplasmic reticulum stress. Gene silencing of Rpt4 also inhibited cell proliferation, reduced clonogenic survival and induced apoptosis in HCT-116 colon cancer cells. We next developed a cell penetrating peptide-based nanoparticle delivery system to achieve in vivo gene silencing of Rpt4. Administration of Rpt4 siRNA nanoparticles reduced tumour growth and improved survival in a HCT-116 colon cancer xenograft tumour model in vivo. Collectively, our data suggest that inhibition of Rpt4 represents a novel strategy for the treatment of CRC. Copyright © 2016 Elsevier B.V. All rights reserved.

Targeting colon cancer stem cells using a new curcumin analogue, GO-Y030

PubMed Central

Lin, L; Liu, Y; Li, H; Li, P-K; Fuchs, J; Shibata, H; Iwabuchi, Y; Lin, J

2011-01-01

Background: Persistent activation of signal transducers and activators of transcription 3 (STAT3) is commonly detected in many types of cancer, including colon cancer. To date, whether STAT3 is activated and the effects of STAT3 inhibition by a newly developed curcumin analogue, GO-Y030, in colon cancer stem cells are still unknown. Methods: Flow cytometry was used to isolate colon cancer stem cells, which are characterised by both aldehyde dehydrogenase (ALDH)-positive and CD133-positive subpopulations (ALDH+/CD133+). The levels of STAT3 phosphorylation and the effects of STAT3 inhibition by a newly developed curcumin analogue, GO-Y030, that targets STAT3 in colon cancer stem cells were examined. Results: Our results observed that ALDH+/CD133+ colon cancer cells expressed higher levels of phosphorylated STAT3 than ALDH-negative/CD133-negative colon cancer cells, suggesting that STAT3 is activated in colon cancer stem cells. GO-Y030 and curcumin inhibited STAT3 phosphorylation, cell viability, tumoursphere formation in colon cancer stem cells. GO-Y030 also reduced STAT3 downstream target gene expression and induced apoptosis in colon cancer stem cells. Furthermore, GO-Y030 suppressed tumour growth of cancer stem cells from both SW480 and HCT-116 colon cancer cell lines in the mouse model. Conclusion: Our results indicate that STAT3 is a novel therapeutic target in colon cancer stem cells, and inhibition of activated STAT3 in cancer stem cells by GO-Y030 may offer an effective treatment for colorectal cancer. PMID:21694723

Targeting colon cancer stem cells using a new curcumin analogue, GO-Y030.

PubMed

Lin, L; Liu, Y; Li, H; Li, P-K; Fuchs, J; Shibata, H; Iwabuchi, Y; Lin, J

2011-07-12

Persistent activation of signal transducers and activators of transcription 3 (STAT3) is commonly detected in many types of cancer, including colon cancer. To date, whether STAT3 is activated and the effects of STAT3 inhibition by a newly developed curcumin analogue, GO-Y030, in colon cancer stem cells are still unknown. Flow cytometry was used to isolate colon cancer stem cells, which are characterised by both aldehyde dehydrogenase (ALDH)-positive and CD133-positive subpopulations (ALDH(+)/CD133(+)). The levels of STAT3 phosphorylation and the effects of STAT3 inhibition by a newly developed curcumin analogue, GO-Y030, that targets STAT3 in colon cancer stem cells were examined. Our results observed that ALDH(+)/CD133(+) colon cancer cells expressed higher levels of phosphorylated STAT3 than ALDH-negative/CD133-negative colon cancer cells, suggesting that STAT3 is activated in colon cancer stem cells. GO-Y030 and curcumin inhibited STAT3 phosphorylation, cell viability, tumoursphere formation in colon cancer stem cells. GO-Y030 also reduced STAT3 downstream target gene expression and induced apoptosis in colon cancer stem cells. Furthermore, GO-Y030 suppressed tumour growth of cancer stem cells from both SW480 and HCT-116 colon cancer cell lines in the mouse model. Our results indicate that STAT3 is a novel therapeutic target in colon cancer stem cells, and inhibition of activated STAT3 in cancer stem cells by GO-Y030 may offer an effective treatment for colorectal cancer.

[Dietary fiber--adequate intake and effects on metabolism health].

PubMed

Bernaud, Fernanda Sarmento Rolla; Rodrigues, Ticiana C

2013-08-01

The positive effects of dietary fiber are related, in part, to the fact that a portion of the fermentation of components takes place in the large intestine, which has an impact on the speed of digestion, pH of the colon, and production of by-products with important physiological functions. Individuals with high fiber intake seem to have lower risk of developing coronary artery disease, hypertension, obesity, diabetes, and colon cancer. The increase in fiber intake reduces serum cholesterol, improves blood glucose in patients with diabetes, reduces body weight, and is associated with lower serum ultrasensitive C-reactive protein. Increased fiber intake and intake of more fiber than the currently recommended level (14 g/1,000 kcal) may provide greater health benefits, including reducing low-grade inflammation.

Persistent Pneumocystis colonization leads to the development of chronic obstructive pulmonary disease (COPD) in a non-human primate model of AIDS

PubMed Central

Shipley, Timothy W.; Kling, Heather M.; Morris, Alison; Patil, Sangita; Kristoff, Jan; Guyach, Siobhan E.; Murphy, Jessica M.; Shao, Xiuping; Sciurba, Frank C.; Rogers, Robert M.; Richards, Thomas; Thompson, Paul; Montelaro, Ronald C.; Coxson, Harvey O.; Hogg, James C.; Norris, Karen A.

2010-01-01

HIV-infected patients are at increased risk for development of pulmonary complications, including chronic obstructive pulmonary disease (COPD). Inflammation associated with sub-clinical infection has been postulated to promote COPD. Persistence of Pneumocystis (Pc) is associated with HIV and COPD, although a causal relationship has not been established. We used a simian/human immunodeficiency virus (SHIV) model of HIV infection to study pulmonary effects of Pc colonization. SHIV-infected/Pc-colonized monkeys developed progressive obstructive pulmonary disease characterized by increased emphysematous tissue and bronchial-associated lymphoid tissue. Elevated Th2 cytokines and pro-inflammatory mediators in bronchoalveolar lavage fluid coincided with Pc colonization and pulmonary function decline. These results support the concept that an infectious agent contributes to development of HIV-associated lung disease and suggests that Pc colonization may be a risk factor for the development of HIV-associated COPD. Furthermore, this model allows examination of early host responses important to disease progression thus identifying potential therapeutic targets for COPD. PMID:20533880

Different waves of effector genes with contrasted genomic location are expressed by Leptosphaeria maculans during cotyledon and stem colonization of oilseed rape.

PubMed

Gervais, Julie; Plissonneau, Clémence; Linglin, Juliette; Meyer, Michel; Labadie, Karine; Cruaud, Corinne; Fudal, Isabelle; Rouxel, Thierry; Balesdent, Marie-Hélène

2017-10-01

Leptosphaeria maculans, the causal agent of stem canker disease, colonizes oilseed rape (Brassica napus) in two stages: a short and early colonization stage corresponding to cotyledon or leaf colonization, and a late colonization stage during which the fungus colonizes systemically and symptomlessly the plant during several months before stem canker appears. To date, the determinants of the late colonization stage are poorly understood; L. maculans may either successfully escape plant defences, leading to stem canker development, or the plant may develop an 'adult-stage' resistance reducing canker incidence. To obtain an insight into these determinants, we performed an RNA-sequencing (RNA-seq) pilot project comparing fungal gene expression in infected cotyledons and in symptomless or necrotic stems. Despite the low fraction of fungal material in infected stems, sufficient fungal transcripts were detected and a large number of fungal genes were expressed, thus validating the feasibility of the approach. Our analysis showed that all avirulence genes previously identified are under-expressed during stem colonization compared with cotyledon colonization. A validation RNA-seq experiment was then performed to investigate the expression of candidate effector genes during systemic colonization. Three hundred and seven 'late' effector candidates, under-expressed in the early colonization stage and over-expressed in the infected stems, were identified. Finally, our analysis revealed a link between the regulation of expression of effectors and their genomic location: the 'late' effector candidates, putatively involved in systemic colonization, are located in gene-rich genomic regions, whereas the 'early' effector genes, over-expressed in the early colonization stage, are located in gene-poor regions of the genome. © 2016 BSPP AND JOHN WILEY & SONS LTD.

Biofilm in voice prosthesis: a prospective cohort study and laboratory tests using sonication and SEM analysis.

PubMed

Galli, Jacopo; Calo', Lea; Meucci, Duino; Giuliani, Monica; Lucidi, Daniela; Paludetti, Gaetano; Torelli, Riccardo; Sanguinetti, Maurizio; Parrilla, Claudio

2018-05-16

The objective of the study was to compare the biofilm growing pattern and its morphological extent on silicone and a teflon-like material using a sonication process and a Scanning Electron Microscope (SEM). A prospective cohort study and a laboratory study. Otolaryngology -Head and Neck surgery Department and the Microbiology Institute. The participants included fifteen laryngectomized patients with phonatory prostheses, which were removed due to device failure, and two different kinds of phonatory prostheses from the laboratory (Provox 2 and ActiValve) that were artificially colonized by Candida albicans. Tracheo-esophageal puncture (TEP) is currently considered the gold standard for post-laryngectomy voice rehabilitation. "Leakage" represents the most common cause of substitution and is generated by biofilm colonization of the prosthesis by mixed mycotic and bacterial agents. New biomaterials have been developed that are deemed to be more resistant to the colonization of micro-organisms and material deformation. The devices showed colonization by mixed bacterial flora (Staphylococci 13%, Streptococci 9%, and H. influenzae 5%) and by yeasts (Candida albicans 12%). Moreover, we observed a different distribution of biofilm layers in Provox ActiValve (22.56%) compared to Provox 2 (56.82%) after experimental colonization by the previous isolated Candida strain. Resident microbiological species from the upper airways unavoidably colonize the polymer surfaces, and no strategies have been effective except for the manipulation of the chemical-physical properties of the device's polymer. Our study confirms that Provox ActiValve, which is made with a fluoroplastic material (teflon-like), is less subject to in vitro colonization by Candida, and thus showed a higher clinical resistance to biofilm and a longer lifespan. The sonication seems to significantly improve the knowledge of bacterial and mycotic flora in biofilm colonization. The design of a device for the daily cleaning capable to reach and brush the esophageal flange of the prosthesis preserving the valve mechanism could represent a practical and simple help in this still unsolved problem. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

XFM demonstrates preferential accumulation of a vanadyl-based MRI contrast agent in murine colonic tumors

PubMed Central

Mustafi, Devkumar; Ward, Jesse; Dougherty, Urszula; Bissonnette, Marc; Hart, John; Vogt, Stefan; Karczmar, Gregory S.

2016-01-01

Contrast agents that specifically enhance cancers on MRI would allow earlier detection. Vanadyl-based chelates (VCs) selectively enhance rodent cancers on MRI, suggesting selective uptake of VCs by cancers. Here we report X-ray fluorescence microscopy (XFM) of VC uptake by murine colon cancer. Colonic tumors in mice treated with azoxymethane/dextran sulfate sodium were identified by MRI. Then a gadolinium-based contrast agent and a VC were injected I.V.; mice were sacrificed and colons sectioned. VC distribution was sampled at 120 minutes after injection to evaluate the long term accumulation. Gadolinium distribution was sampled at 10 minutes after injection due to its rapid washout. XFM was performed on 72 regions of normal and cancerous colon from 5 normal mice and 4 cancer-bearing mice. XFM showed that all gadolinium was extracellular with similar concentrations in colon cancers and normal colon. In contrast, the average VC concentration was 2-fold higher in cancers vs. normal tissue (p<0.002). Cancers also contained numerous ‘hot spots’ with intracellular VC concentrations 6-fold higher than the concentration in normal colon (p<0.0001). No ‘hot spots’ were detected in normal colon. This is the first direct demonstration that VCs selectively accumulate in cancer cells, and thus may improve cancer detection. PMID:25813904

A Germline Variant on Chromosome 4q31.1 Associates with Susceptibility to Developing Colon Cancer Metastasis

PubMed Central

Schmit, Stephanie L.; Stadler, Zsofia K.; Joseph, Vijai; Zhang, Lu; Willis, Joseph E.; Scacheri, Peter; Veigl, Martina; Adams, Mark D.; Raskin, Leon; Sullivan, John F.; Stratton, Kelly; Shia, Jinru; Ellis, Nathan; Rennert, Hedy S.; Manschreck, Christopher; Li, Li; Offit, Kenneth; Elston, Robert C.; Rennert, Gadi; Gruber, Stephen B.

2016-01-01

We tested for germline variants showing association to colon cancer metastasis using a genome-wide association study that compared Ashkenazi Jewish individuals with stage IV metastatic colon cancers versus those with stage I or II non-metastatic colon cancers. In a two-stage study design, we demonstrated significant association to developing metastatic disease for rs60745952, that in Ashkenazi discovery and validation cohorts, respectively, showed an odds ratio (OR) = 2.3 (P = 2.73E-06) and OR = 1.89 (P = 8.05E-04) (exceeding validation threshold of 0.0044). Significant association to metastatic colon cancer was further confirmed by a meta-analysis of rs60745952 in these datasets plus an additional Ashkenazi validation cohort (OR = 1.92; 95% CI: 1.28–2.87), and by a permutation test that demonstrated a significantly longer haplotype surrounding rs60745952 in the stage IV samples. rs60745952, located in an intergenic region on chromosome 4q31.1, and not previously associated with cancer, is, thus, a germline genetic marker for susceptibility to developing colon cancer metastases among Ashkenazi Jews. PMID:26751797

Pineal gland function is required for colon antipreneoplastic effects of physical exercise in rats.

PubMed

Frajacomo, F T T; de Paula Garcia, W; Fernandes, C R; Garcia, S B; Kannen, V

2015-10-01

Light-at-night exposure enhances the risk of cancer. Colon cancer is among the most dangerous tumors affecting humankind. Physical exercise has shown positive effects against colon cancer. Here, we investigated whether pineal gland modulates antipreneoplastic effects of physical exercise in the colon. Surgical and non-surgical pineal impairments were performed to clarify the relationship between the pineal gland activity and manifestation of colonic preneoplastic lesions. Next, a progressive swimming training was applied in rats exposed or not to either non-surgical pineal impairment or carcinogen treatment for 10 weeks. Both surgical and non-surgical pineal impairments increased the development of colon preneoplasia. It was further found that impairing the pineal gland function, higher rates of DNA damage were induced in colonic epithelial and enteric glial cells. Physical exercise acted positively against preneoplasia, whereas impairing the pineal function with constant light exposure disrupts its positive effects on the development of preneoplastic lesions in the colon. This was yet related to increased DNA damage in glial cells and enteric neuronal activation aside from serum melatonin levels. Our findings suggest that protective effects of physical exercise against colon cancer are dependent on the pineal gland activity. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

Lamine, F; Eutamène, H; Fioramonti, J; Buéno, L; Théodorou, V

2004-12-01

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. 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. 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-1beta 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. 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-1beta mucosal level.

Quantitative evaluation of protocorm growth and fungal colonization in Bletilla striata (Orchidaceae) reveals less-productive symbiosis with a non-native symbiotic fungus.

PubMed

Yamamoto, Tatsuki; Miura, Chihiro; Fuji, Masako; Nagata, Shotaro; Otani, Yuria; Yagame, Takahiro; Yamato, Masahide; Kaminaka, Hironori

2017-02-21

In nature, orchid plants depend completely on symbiotic fungi for their nutrition at the germination and the subsequent seedling (protocorm) stages. However, only limited quantitative methods for evaluating the orchid-fungus interactions at the protocorm stage are currently available, which greatly constrains our understanding of the symbiosis. Here, we aimed to improve and integrate quantitative evaluations of the growth and fungal colonization in the protocorms of a terrestrial orchid, Blettila striata, growing on a plate medium. We achieved both symbiotic and asymbiotic germinations for the terrestrial orchid B. striata. The protocorms produced by the two germination methods grew almost synchronously for the first three weeks. At week four, however, the length was significantly lower in the symbiotic protocorms. Interestingly, the dry weight of symbiotic protocorms did not significantly change during the growth period, which implies that there was only limited transfer of carbon compounds from the fungus to the protocorms in this relationship. Next, to evaluate the orchid-fungus interactions, we developed an ink-staining method to observe the hyphal coils in protocorms without preparing thin sections. Crushing the protocorm under the coverglass enables us to observe all hyphal coils in the protocorms with high resolution. For this observation, we established a criterion to categorize the stages of hyphal coils, depending on development and degradation. By counting the symbiotic cells within each stage, it was possible to quantitatively evaluate the orchid-fungus symbiosis. We describe a method for quantitative evaluation of orchid-fungus symbiosis by integrating the measurements of plant growth and fungal colonization. The current study revealed that although fungal colonization was observed in the symbiotic protocorms, the weight of the protocorm did not significantly increase, which is probably due to the incompatibility of the fungus in this symbiosis. These results suggest that fungal colonization and nutrition transfer can be differentially regulated in the symbiosis. The evaluation methods developed in this study can be used to study various quantitative aspects of the orchid-fungus symbiosis.

Discovery and preclinical development of a novel prodrug conjugate of mesalamine with eicosapentaenoic acid and caprylic acid for the treatment of inflammatory bowel diseases.

PubMed

Kandula, Mahesh; Sunil Kumar, K B; Palanichamy, Sivanesan; Rampal, Ashok

2016-11-01

Mesalamine (5-ASA) is one of the drugs indicated as first line therapy in ulcerative colitis for induction and maintenance of remission. Sulfasalazine and formulations of 5-ASA (pH-dependent and controlled release formulations) were developed to minimize the systemic absorption and maximize the delivery of the mesalamine to colon. Although, its efficacy and safety is well documented there are approximately 30% nonresponders to 5-ASA therapy. This necessitates the need for novel therapeutic options to improve the efficacy and safety of the currently available 5-ASA therapy. CLX-103 is a novel, patented prodrug molecular conjugate of mesalamine, eicosapentaenoic acid and caprylic acid designed to offer incremental benefits over the currently approved 5-ASA formulations. Results of in vitro and in vivo studies showed that CLX-103, was stable in simulated gastric fluid, but undergoes enzymatic hydrolysis in the small/large intestines to release the active moiety. Our data also showed that the active moiety is retained in the targeted intestinal tissues (ileum and colon) over a longer period of time in relation to sulfasalazine. The in vitro data supports the observed in vivo plasma kinetics of 5-ASA characterized by longer T max , low C max after the oral administration of CLX-103. Efficacy study of CLX-103 in acute dextran sodium sulfate (DSS) mouse colitis model showed improved potency measured as Disease Activity Index (DAI) and histological scores in the colon as compared to sulfasalazine. These findings indicate that CLX-103 could offer a differentiated drug product which is more efficacious and safer than the currently approved 5-ASA formulations in the treatment of inflammatory bowel diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparative Analysis of Bacterial Community Composition and Structure in Clinically Symptomatic and Asymptomatic Central Venous Catheters

PubMed Central

Stressmann, Franziska A.; Couve-Deacon, Elodie; Chainier, Delphine; Chauhan, Ashwini; Wessel, Aimee; Durand-Fontanier, Sylvaine; Escande, Marie-Christine; Kriegel, Irène; Francois, Bruno; Ploy, Marie-Cécile

2017-01-01

ABSTRACT Totally implanted venous access ports (TIVAPs) are commonly used catheters for the management of acute or chronic pathologies. Although these devices improve health care, repeated use of this type of device for venous access over long periods of time is also associated with risk of colonization and infection by pathogenic bacteria, often originating from skin. However, although the skin microbiota is composed of both pathogenic and nonpathogenic bacteria, the extent and the consequences of TIVAP colonization by nonpathogenic bacteria have rarely been studied. Here, we used culture-dependent and 16S rRNA gene-based culture-independent approaches to identify differences in bacterial colonization of TIVAPs obtained from two French hospitals. To explore the relationships between nonpathogenic organisms colonizing TIVAPs and the potential risk of infection, we analyzed the bacterial community parameters between TIVAPs suspected (symptomatic) or not (asymptomatic) of infection. Although we did not find a particular species assemblage or community marker to distinguish infection risk on an individual sample level, we identified differences in bacterial community composition, diversity, and structure between clinically symptomatic and asymptomatic TIVAPs that could be explored further. This study therefore provides a new view of bacterial communities and colonization patterns in intravascular TIVAPs and suggests that microbial ecology approaches could improve our understanding of device-associated infections and could be a prognostic tool to monitor the evolution of bacterial communities in implants and their potential susceptibility to infections. IMPORTANCE Totally implanted venous access ports (TIVAPs) are commonly used implants for the management of acute or chronic pathologies. Although their use improves the patient’s health care and quality of life, they are associated with a risk of infection and subsequent clinical complications, often leading to implant removal. While all TIVAPs appear to be colonized, only a fraction become infected, and the relationship between nonpathogenic organisms colonizing TIVAPs and the potential risk of infection is unknown. We explored bacteria present on TIVAPs implanted in patients with or without signs of TIVAP infection and identified differences in phylum composition and community structure. Our data suggest that the microbial ecology of intravascular devices could be predictive of TIVAP infection status and that ultimately a microbial ecological signature could be identified as a tool to predict TIVAP infection susceptibility and improve clinical management. PMID:28959736

Development and Validation of an in vitro Experimental GastroIntestinal Dialysis Model with Colon Phase to Study the Availability and Colonic Metabolisation of Polyphenolic Compounds.

PubMed

Breynaert, Annelies; Bosscher, Douwina; Kahnt, Ariane; Claeys, Magda; Cos, Paul; Pieters, Luc; Hermans, Nina

2015-08-01

The biological effects of polyphenols depend on their mechanism of action in the body. This is affected by bioconversion by colon microbiota and absorption of colonic metabolites. We developed and validated an in vitro continuous flow dialysis model with colon phase (GastroIntestinal dialysis model with colon phase) to study the gastrointestinal metabolism and absorption of phenolic food constituents. Chlorogenic acid was used as model compound. The physiological conditions during gastrointestinal digestion were mimicked. A continuous flow dialysis system simulated the one-way absorption by passive diffusion from lumen to mucosa. The colon phase was developed using pooled faecal suspensions. Several methodological aspects including implementation of an anaerobic environment, adapted Wilkins Chalgren broth medium, 1.10(8) CFU/mL bacteria suspension as inoculum, pH adaptation to 5.8 and implementation of the dialysis system were conducted. Validation of the GastroIntestinal dialysis model with colon phase system showed a good recovery and precision (CV < 16 %). Availability of chlorogenic acid in the small intestinal phase (37 ± 3 %) of the GastroIntestinal dialysis model with colon phase is comparable with in vivo studies on ileostomy patients. In the colon phase, the human faecal microbiota deconjugated chlorogenic acid to caffeic acid, 3,4-dihydroxyphenyl propionic acid, 4-hydroxybenzoic acid, 3- or 4-hydroxyphenyl acetic acid, 2-methoxy-4-methylphenol and 3-phenylpropionic acid. The GastroIntestinal dialysis model with colon phase is a new, reliable gastrointestinal simulation system. It permits a fast and easy way to predict the availability of complex secondary metabolites, and to detect metabolites in an early stage after digestion. Isolation and identification of these metabolites may be used as references for in vivo bioavailability experiments and for investigating their bioactivity in in vitro experiments. Georg Thieme Verlag KG Stuttgart · New York.

Recruitment to and pilot results of the PACES randomized trial of physical exercise during adjuvant chemotherapy for colon cancer.

PubMed

van Waart, Hanna; Stuiver, Martijn M; van Harten, Wim H; Geleijn, Edwin; de Maaker-Berkhof, Marianne; Schrama, Jolanda; Geenen, Maud M; Meerum Terwogt, Jetske M; van den Heiligenberg, Simone M; Hellendoorn-van Vreeswijk, Jeannette A J H; Sonke, Gabe S; Aaronson, Neil K

2018-01-01

We report the recruitment rate, reasons for and factors influencing non-participation, and descriptive results of a randomized controlled trial of two different exercise programs for patients with colon cancer undergoing adjuvant chemotherapy. Participants were randomized to a low-intensity, home-based program (Onco-Move), a moderate- to high-intensity, combined supervised resistance and aerobic exercise program (OnTrack), or Usual Care. Non-participants provided reasons for non-participation and were asked to complete a questionnaire assessing behavioral and attitudinal variables. Trial participants completed performance-based and self-reported outcome measures prior to randomization, at the end of chemotherapy, and at the 6-month follow-up. Twenty-three of 63 referred patients agreed to participate in the trial. All 40 non-participants provided reasons for non-participation. Forty-five percent of the non-participants completed the questionnaire. Those who did not want to exercise had higher fatigue scores at baseline and a more negative attitude toward exercise. Compliance to both programs was high and no adverse events occurred. On average, the colon cancer participants were able to maintain or improve their physical fitness levels and maintain or decrease their fatigue levels during chemotherapy and follow-up. Recruitment of patients with colon cancer to a physical exercise trial during adjuvant chemotherapy proved to be difficult, underscoring the need to develop more effective strategies to increase participation rates. Both home-based and supervised programs are safe and feasible in patients with colon cancer undergoing chemotherapy. Effectiveness needs to be established in a larger trial. Netherlands Trial Register - NTR2159.

Negative impact of bone-marrow-derived mesenchymal stem cells on dextran sulfate sodium-induced colitis

PubMed Central

Nam, Young-Sun; Kim, Nayoun; Im, Keon-Il; Lim, Jung-Yeon; Lee, Eun-Sol; Cho, Seok-Goo

2015-01-01

AIM: To investigate the effects of mesenchymal stem cells (MSCs) on dextran sulfate sodium-induced inflammatory bowel disease (IBD). METHODS: C57BL/6 mice were fed 3.5% (g/L) dextran sulfate sodium. On day seven, the mice received intraperitoneal injections of 1 × 106 MSCs. The survival rate, disease activity index values, and body weight, were monitored daily. On day ten, colon lengths and histopathologic changes were assessed. In addition, immunoregulatory changes following MSC administration were evaluated by determining the levels of effector T cell responses in the spleen and mesenteric lymph nodes, and the expression levels of inflammatory cytokines in homogenized colons. RESULTS: Intraperitoneal administration of MSCs did not prevent development of colitis and did not reduce the clinicopathologic severity of IBD. No significant difference was evident in either survival rate or disease activity index score between the control and MSC-treated group. Day ten-sacrificed mice exhibited no significant difference in either colon length or histopathologic findings. Indeed, the MSC-treated group exhibited elevated levels of interleukin (IL)-6 and transforming growth factor-β, and a reduced level of IL-10, in spleens, mesenteric lymph nodes, and homogenized colons. The IL-17 level was lower in the mesenteric lymph nodes of the MSC-treated group (P = 0.0126). In homogenized colons, the IL-17 and tumor necrosis factor-α (P = 0.0092) expression levels were also lower in the treated group. CONCLUSION: MSC infusion provided no significant histopathologic or clinical improvement, thus representing a limited therapeutic approach for IBD. Functional enhancement of MSCs is needed in further study. PMID:25717235

Racial and ethnic differences in lymph node examination after colon cancer resection do not completely explain disparities in mortality.

PubMed

Rhoads, Kim F; Cullen, Jennifer; Ngo, Justine V; Wren, Sherry M

2012-01-15

In 1999, a multidisciplinary panel of experts in colorectal cancer reviewed the relevant medical literature and issued a consensus recommendation for a 12-lymph node (LN) minimum examination after resection for colon cancer. Some authors have shown racial/ethnic differences in receipt of this evidence-based care. To date, however, none has investigated the correlation between disparities in LN examination and disparities in outcomes after colon cancer treatment. This retrospective analysis used California Cancer Registry linked to California Office of Statewide Health Planning and Development discharge data (1996-2006). Chi-square analysis, logistic regression, and Cox proportional hazard models predicted disparities in receipt of an adequate examination and the effect of an inadequate exam on mortality and disparities. Patients with stage I and II colon cancers undergoing surgery in California were included; patients with stage III and IV disease were excluded. A total of 37,911 records were analyzed. Adequate staging occurred in fewer than half of cases. An inadequate examination (<12 LNs) was associated with higher mortality rates. Hispanics had the lowest odds of receiving an adequate exam; however, blacks, not Hispanics, had the highest risk of mortality compared with whites. This disparity was not completely explained by inadequate LN examination. Inadequate LN exam occurs often and is associated with increased mortality. There are disparities in receipt of the minimum exam, but this only explains a small part of the observed disparity in mortality. Improving the quality of LN examination alone is unlikely to correct colon cancer disparities. Copyright © 2011 American Cancer Society.

Effect of vitamin C on azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated early colon cancer in mice.

PubMed

Jeon, Hee-Jin; Yeom, Yiseul; Kim, Yoo-Sun; Kim, Eunju; Shin, Jae-Ho; Seok, Pu Reum; Woo, Moon Jea; Kim, Yuri

2018-04-01

The objective of this study was to investigate the effects of vitamin C on inflammation, tumor development, and dysbiosis of intestinal microbiota in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced inflammation-associated early colon cancer mouse model. Male BALB/c mice were injected intraperitoneally with AOM [10 mg/kg body weight (b.w)] and given two 7-d cycles of 2% DSS drinking water with a 14 d inter-cycle interval. Vitamin C (60 mg/kg b.w. and 120 mg/kg b.w.) was supplemented by gavage for 5 weeks starting 2 d after the AOM injection. The vitamin C treatment suppressed inflammatory morbidity, as reflected by disease activity index (DAI) in recovery phase and inhibited shortening of the colon, and reduced histological damage. In addition, vitamin C supplementation suppressed mRNA levels of pro-inflammatory mediators and cytokines, including cyclooxygenase-2, microsomal prostaglandin E synthase-2, tumor necrosis factor-α, Interleukin (IL)-1β , and IL-6 , and reduced expression of the proliferation marker, proliferating cell nuclear antigen, compared to observations of AOM/DSS animals. Although the microbial composition did not differ significantly between the groups, administration of vitamin C improved the level of inflammation-related Lactococcus and JQ084893 to control levels. Vitamin C treatment provided moderate suppression of inflammation, proliferation, and certain inflammation-related dysbiosis in a murine model of colitis associated-early colon cancer. These findings support that vitamin C supplementation can benefit colonic health. Long-term clinical studies with various doses of vitamin C are warranted.

Distinctive features of gastrointestinal stromal tumors arising from the colon and rectum

PubMed Central

Zhu, Rebecca; Liu, Fangfang; Grisotti, Gabriella; Pérez-Irizarry, Javier; Cha, Charles H.; Johnson, Caroline H.; Boffa, Daniel J.; Han, Dale; Johung, Kimberly L.; Zhang, Yawei

2018-01-01

Background Colon and rectal gastrointestinal stromal tumors (GISTs) are rare and poorly characterized. Because the majority of treatment guidelines for GISTs are extrapolated from tumors of gastric and small bowel origin, our aim was to better characterize the unique clinicopathologic features and prognostic factors of colon and rectal GISTs to guide clinical care. Methods The National Cancer Data Base (NCDB) was queried from 2006 to 2013 for cases of GISTs in the stomach, colon, and rectum. Patient demographics, clinical characteristics, and survival were compared. Results A total of 11,302 gastric GISTs were compared to 398 colon and 393 rectal GISTs. After propensity matching, compared to gastric GISTs, rectal GISTs had improved overall survival (HR =0.695, P=0.0264), while colon GISTs had worse overall survival (HR =1.6, P=0.0005). Surgical treatment for rectal GISTs was more likely to be local excision compared to colonic GISTs (51.1% vs. 8.4%, P<0.0001). Colon and gastric GISTs were less likely to receive systemic therapy compared to rectal GISTs (34.2% vs. 34.0% vs. 55.2%, P<0.0001). Adjuvant systemic therapy conveyed a survival advantage to rectal GISTs (HR =0.47, P=0.042) but not colon GISTs. There was a negative impact of adjuvant therapy on survival for colon GISTs <5 cm (HR =3.41, P=0.032). Conclusions Patients with rectal GISTs live longer than those with colon and gastric GISTs, and adjuvant therapy prolongs their survival. Many patients with colon GISTs are treated with adjuvant therapy despite a detrimental effect on survival. Tumor biology of colon and rectal GISTs needs to be better studied to tailor treatment.

[Colonoscopy for early detection and prevention of colorectal cancer].

PubMed

Niv, Yaron

2010-08-01

Colonoscopy has a limited success in the prevention of colorectal cancer of the right colon. Thus, there is place for improvement. The potential reasons for colonoscopy failure are the different biology of polyps on the right side of the colon or procedure quality. Preparation, withdrawal time, detection of all polyps and their removal using the best technique will overcome this problem. Furthermore, the implementation of a computerized database and report that includes quality assurance fields, will improve colonoscopy success rates.

Clostridium septicum aortitis with synchronous ascending colon and rectal adenocarcinoma.

PubMed

Jain, Deepanshu; Kistler, Andrew C; Kozuch, Patricia

2017-01-01

Clostridium septicum ( C. septicum ) aortitis is a rare condition frequently associated with colon adenocarcinoma and carries a poor prognosis. We report the case of a 66-year-old man who presented with abdominal pain, blood in the stool, fever and chills. Laboratory tests were significant for leukocytosis and microcytic anemia. Abdominal imaging revealed a right colon mass and aortitis. Colonoscopy confirmed the right colon mass and also discovered a rectal mass, both adenocarcinomas. Treatment consisted of antibiotics, aortic repair, right hemi-colectomy and later trans-anal excision of the rectal mass. Blood cultures and the aortic specimen grew C. septicum . The patient improved and was doing well in follow up.

Clostridium septicum aortitis with synchronous ascending colon and rectal adenocarcinoma

PubMed Central

Jain, Deepanshu; Kistler, Andrew C.; Kozuch, Patricia

2017-01-01

Clostridium septicum (C. septicum) aortitis is a rare condition frequently associated with colon adenocarcinoma and carries a poor prognosis. We report the case of a 66-year-old man who presented with abdominal pain, blood in the stool, fever and chills. Laboratory tests were significant for leukocytosis and microcytic anemia. Abdominal imaging revealed a right colon mass and aortitis. Colonoscopy confirmed the right colon mass and also discovered a rectal mass, both adenocarcinomas. Treatment consisted of antibiotics, aortic repair, right hemi-colectomy and later trans-anal excision of the rectal mass. Blood cultures and the aortic specimen grew C. septicum. The patient improved and was doing well in follow up. PMID:28655990

Automatic colonic lesion detection and tracking in endoscopic videos

NASA Astrophysics Data System (ADS)

Li, Wenjing; Gustafsson, Ulf; A-Rahim, Yoursif

2011-03-01

The biology of colorectal cancer offers an opportunity for both early detection and prevention. Compared with other imaging modalities, optical colonoscopy is the procedure of choice for simultaneous detection and removal of colonic polyps. Computer assisted screening makes it possible to assist physicians and potentially improve the accuracy of the diagnostic decision during the exam. This paper presents an unsupervised method to detect and track colonic lesions in endoscopic videos. The aim of the lesion screening and tracking is to facilitate detection of polyps and abnormal mucosa in real time as the physician is performing the procedure. For colonic lesion detection, the conventional marker controlled watershed based segmentation is used to segment the colonic lesions, followed by an adaptive ellipse fitting strategy to further validate the shape. For colonic lesion tracking, a mean shift tracker with background modeling is used to track the target region from the detection phase. The approach has been tested on colonoscopy videos acquired during regular colonoscopic procedures and demonstrated promising results.

Health-related quality of life in rehabilitants with different cancer entities.

PubMed

Lamprecht, J; Thyrolf, A; Mau, W

2017-09-01

The focus of the study is the analysis of changes in health-related quality of life in various cancer entities during and after an inpatient rehabilitation programme. In a multicentre longitudinal study, a total of 211 cancer patients (breast cancer: N = 84; prostate cancer: N = 90; colon cancer: N = 37) were asked about their quality of life (EORTC QLQ-C30; HADS) at the beginning, the end and 3 months after the end of the rehabilitation programme. In different domains of quality of life significant and mostly clinically relevant improvements were found during rehabilitation. The breast and prostate cancer patients improved most in emotional functioning, colon cancer patients in global quality of life. With regard to the severity of symptoms, the fatigue burden improved in breast and colon cancer patients, nausea in the prostate cancer patients. However, they are increases 3 months after rehabilitation. Functional burdens improved 3 months after the end of rehabilitation in the physical domain for all cancer patients. For breast cancer patients, emotional functioning decreased significantly 3 months after rehabilitation. An inpatient oncological rehabilitation programme can lead to an improvement in quality of life. © 2016 John Wiley & Sons Ltd.

Altered Innate Defenses in the Neonatal Gastrointestinal Tract in Response to Colonization by Neuropathogenic Escherichia coli

PubMed Central

Birchenough, George M. H.; Johansson, Malin E. V.; Stabler, Richard A.; Dalgakiran, Fatma; Hansson, Gunnar C.; Wren, Brendan W.; Luzio, J. Paul

2013-01-01

Two-day-old (P2), but not 9-day-old (P9), rat pups are susceptible to systemic infection following gastrointestinal colonization by Escherichia coli K1. Age dependency reflects the capacity of colonizing K1 to translocate from gastrointestinal (GI) tract to blood. A complex GI microbiota developed by P2, showed little variation over P2 to P9, and did not prevent stable K1 colonization. Substantial developmental expression was observed over P2 to P9, including upregulation of genes encoding components of the small intestinal (α-defensins Defa24 and Defa-rs1) and colonic (trefoil factor Tff2) mucus barrier. K1 colonization modulated expression of these peptides: developmental expression of Tff2 was dysregulated in P2 tissues and was accompanied by a decrease in mucin Muc2. Conversely, α-defensin genes were upregulated in P9 tissues. We propose that incomplete development of the mucus barrier during early neonatal life and the capacity of colonizing K1 to interfere with mucus barrier maturation provide opportunities for neuropathogen translocation into the bloodstream. PMID:23798529

Management of pediatric patients with refractory constipation who fail cecostomy.

PubMed

Bonilla, Silvana F; Flores, Alejandro; Jackson, Carl-Christian A; Chwals, Walter J; Orkin, Bruce A

2013-09-01

Antegrade continence enema (ACE) is a recognized therapeutic option in the management of pediatric refractory constipation. Data on the long-term outcome of patients who fail to improve after an ACE-procedure are lacking. To describe the rate of ACE bowel management failure in pediatric refractory constipation, and the management and long term outcome of these patients. Retrospective analysis of a cohort of patients that underwent ACE-procedure and had at least 3-year-follow-up. Detailed analysis of subsequent treatment and outcome of those patients with a poor functional outcome was performed. 76 patients were included. 12 (16%) failed successful bowel management after ACE requiring additional intervention. Mean follow-up was 66.3 (range 35-95 months) after ACE-procedure. Colonic motility studies demonstrated colonic neuropathy in 7 patients (58%); abnormal motility in 4 patients (33%), and abnormal left-sided colonic motility in 1 patient (9%). All 12 patients were ultimately treated surgically. Nine patients (75%) had marked clinical improvement, whereas 3 patients (25%) continued to have poor function issues at long term follow-up. Colonic resection, either segmental or total, led to improvement or resolution of symptoms in the majority of patients who failed cecostomy. However, this is a complex and heterogeneous group and some patients will have continued issues. Copyright © 2013 Elsevier Inc. All rights reserved.

Improvement of colonic healing by preoperative oral partially hydrolyzed guar gum (Benefiber) in rats which underwent preoperative radiotherapy.

PubMed

Sevinc, Ali Ibrahim; Aydogan, Baki; Canda, Aras Emre; Cetinayak, Oguz; Terzi, Cem; Oktay, Gulgun; Gurel, Duygu; Fuzun, Mehmet

2013-12-09

Abstract Background: Neoadjuvant radiotherapy in rectal cancer could interfere with anastomotic healing. We investigated the effects of preoperative oral administration of Benefiber on the healing irradiated colonic anastomosis. Methods: Forty male Wistar rats were divided into four groups. Group I (control group), Group II (Benefiber® pretreatment group), Group III (preoperative radiotherapy group) and Group IV (preoperative radiotherapy and Benefiber® pretreatment group). All animals underwent 1 cm left colon resection and primary anastomosis. On the 3rd and 7th postoperative days, all the rats were anesthetized to assess the anastomotic healing clinically, mechanically, histologically and biochemically. Results: The mean bursting pressure was significantly lower in-group III and significantly higher in-group II on day 7. The histologic parameters of anastomotic healing, such as epithelial regeneration and formation of granulation tissue, were significantly improved by use of preoperative Benefiber® on day 7. The amount of acid-soluble collagen concentrations significantly increased in-group IV compared to group III on day 3. The amount of salt-soluble collagen concentrations significantly increased in group II compared to group III on day 3. Conclusions: Colonic anastomotic healing can be adversely affected by preoperative radiotherapy, but orogastric feeding with Benefiber may improve the healing process.

Use of a colon simulation technique to assess the effect of live yeast on fermentation parameters and microbiota of the colon of pig.

PubMed

Pinloche, E; Williams, M; D'Inca, R; Auclair, E; Newbold, C J

2012-12-01

The impact of 2 doses of a Saccharomyces cerevisiae were evaluated, 5 × 10(10) cfu/kg of feed (L1) and 5 × 10(11) cfu/kg of feed (L2) against a control (CON) with no added yeast, using an in vitro model [colon simulation technique (Cositec)] to mimic digestion in the pig colon. The L2 (but not L1) dose significantly improved DM digestibility compared to CON (61 v 58%) and increased NH(3) concentrations (+15%). Volatile fatty acid concentrations increased with L2 compared to CON--isobutyrate (+13.5%), propionate (+8.5%), isovalerate (+17.8%), and valerate (+25%)--but only valerate was increased with L1 (+14.2%). The analysis of microbiota from the liquid associated bacteria (LAB) and solid associated bacteria (SAB) revealed an interaction between the fraction and treatment (P < 0.05). Indeed, L2 had a significant impact on SAB and LAB (P < 0.01) whereas L1 only tended to change the structure of the population in the SAB (P < 0.1). Overall, this study showed that a live yeast probiotic could improve digestion in a colonic simulation model but only at the higher dose used and this effect was associated with a shift in the bacterial population therein.

Resistant starch: promise for improving human health.

PubMed

Birt, Diane F; Boylston, Terri; Hendrich, Suzanne; Jane, Jay-Lin; Hollis, James; Li, Li; McClelland, John; Moore, Samuel; Phillips, Gregory J; Rowling, Matthew; Schalinske, Kevin; Scott, M Paul; Whitley, Elizabeth M

2013-11-01

Ongoing research to develop digestion-resistant starch for human health promotion integrates the disciplines of starch chemistry, agronomy, analytical chemistry, food science, nutrition, pathology, and microbiology. The objectives of this research include identifying components of starch structure that confer digestion resistance, developing novel plants and starches, and modifying foods to incorporate these starches. Furthermore, recent and ongoing studies address the impact of digestion-resistant starches on the prevention and control of chronic human diseases, including diabetes, colon cancer, and obesity. This review provides a transdisciplinary overview of this field, including a description of types of resistant starches; factors in plants that affect digestion resistance; methods for starch analysis; challenges in developing food products with resistant starches; mammalian intestinal and gut bacterial metabolism; potential effects on gut microbiota; and impacts and mechanisms for the prevention and control of colon cancer, diabetes, and obesity. Although this has been an active area of research and considerable progress has been made, many questions regarding how to best use digestion-resistant starches in human diets for disease prevention must be answered before the full potential of resistant starches can be realized.

Resistant Starch: Promise for Improving Human Health12

PubMed Central

Birt, Diane F.; Boylston, Terri; Hendrich, Suzanne; Jane, Jay-Lin; Hollis, James; Li, Li; McClelland, John; Moore, Samuel; Phillips, Gregory J.; Rowling, Matthew; Schalinske, Kevin; Scott, M. Paul; Whitley, Elizabeth M.

2013-01-01

Ongoing research to develop digestion-resistant starch for human health promotion integrates the disciplines of starch chemistry, agronomy, analytical chemistry, food science, nutrition, pathology, and microbiology. The objectives of this research include identifying components of starch structure that confer digestion resistance, developing novel plants and starches, and modifying foods to incorporate these starches. Furthermore, recent and ongoing studies address the impact of digestion-resistant starches on the prevention and control of chronic human diseases, including diabetes, colon cancer, and obesity. This review provides a transdisciplinary overview of this field, including a description of types of resistant starches; factors in plants that affect digestion resistance; methods for starch analysis; challenges in developing food products with resistant starches; mammalian intestinal and gut bacterial metabolism; potential effects on gut microbiota; and impacts and mechanisms for the prevention and control of colon cancer, diabetes, and obesity. Although this has been an active area of research and considerable progress has been made, many questions regarding how to best use digestion-resistant starches in human diets for disease prevention must be answered before the full potential of resistant starches can be realized. PMID:24228189

Medical Treatment of Diverticular Disease: Antibiotics.

PubMed

Lué, Alberto; Laredo, Viviana; Lanas, Angel

2016-10-01

Diverticular disease (DD) of the colon represents the most common disease affecting the large bowel in western countries. Its prevalence is increasing. Recent studies suggest that changes in gut microbiota could contribute to development of symptoms and complication. For this reason antibiotics play a key role in the management of both uncomplicated and complicated DD. Rifaximin has demonstrated to be effective in obtaining symptoms relief at 1 year in patients with uncomplicated DD and to improve symptoms and maintain periods of remission following acute colonic diverticulitis (AD). Despite absence of data that supports the routine use of antibiotic in uncomplicated AD, they are recommended in selected patients. In patients with AD that develop an abscess, conservative treatment with broad-spectrum antibiotics is successful in up to 70% of cases. In patients on conservative treatment where percutaneous drainage fails or peritonitis develops, surgery is considered the standard therapy. In conclusion antibiotics seem to remain the mainstay of treatment in symptomatic uncomplicated DD and AD. Inpatient management and intravenous antibiotics are necessary in complicated AD, while outpatient management is considered the best strategy in the majority of uncomplicated patients.

Dual RNA-seq transcriptional analysis of wheat roots colonized by Azospirillum brasilense reveals up-regulation of nutrient acquisition and cell cycle genes.

PubMed

Camilios-Neto, Doumit; Bonato, Paloma; Wassem, Roseli; Tadra-Sfeir, Michelle Z; Brusamarello-Santos, Liziane C C; Valdameri, Glaucio; Donatti, Lucélia; Faoro, Helisson; Weiss, Vinicius A; Chubatsu, Leda S; Pedrosa, Fábio O; Souza, Emanuel M

2014-05-16

The rapid growth of the world's population demands an increase in food production that no longer can be reached by increasing amounts of nitrogenous fertilizers. Plant growth promoting bacteria (PGPB) might be an alternative to increase nitrogenous use efficiency (NUE) in important crops such wheat. Azospirillum brasilense is one of the most promising PGPB and wheat roots colonized by A. brasilense is a good model to investigate the molecular basis of plant-PGPB interaction including improvement in plant-NUE promoted by PGPB. We performed a dual RNA-Seq transcriptional profiling of wheat roots colonized by A. brasilense strain FP2. cDNA libraries from biological replicates of colonized and non-inoculated wheat roots were sequenced and mapped to wheat and A. brasilense reference sequences. The unmapped reads were assembled de novo. Overall, we identified 23,215 wheat expressed ESTs and 702 A. brasilense expressed transcripts. Bacterial colonization caused changes in the expression of 776 wheat ESTs belonging to various functional categories, ranging from transport activity to biological regulation as well as defense mechanism, production of phytohormones and phytochemicals. In addition, genes encoding proteins related to bacterial chemotaxi, biofilm formation and nitrogen fixation were highly expressed in the sub-set of A. brasilense expressed genes. PGPB colonization enhanced the expression of plant genes related to nutrient up-take, nitrogen assimilation, DNA replication and regulation of cell division, which is consistent with a higher proportion of colonized root cells in the S-phase. Our data support the use of PGPB as an alternative to improve nutrient acquisition in important crops such as wheat, enhancing plant productivity and sustainability.

Chronic administration of dietary grape seed extract increases colonic expression of gut tight junction protein occludin and reduces fecal calprotectin: a secondary analysis of healthy Wistar Furth rats.

PubMed

Goodrich, Katheryn M; Fundaro, Gabrielle; Griffin, Laura E; Grant, Ar'quette; Hulver, Matthew W; Ponder, Monica A; Neilson, Andrew P

2012-10-01

Animal studies have demonstrated the potential of grape seed extract (GSE) to prevent metabolic syndrome, obesity, and type 2 diabetes. Recently, metabolic endotoxemia induced by bacterial endotoxins produced in the colon has emerged as a possible factor in the etiology of metabolic syndrome. Improving colonic barrier function may control endotoxemia by reducing endotoxin uptake. However, the impact of GSE on colonic barrier integrity and endotoxin uptake has not been evaluated. We performed a secondary analysis of samples collected from a chronic GSE feeding study with pharmacokinetic end points to examine potential modulation of biomarkers of colonic integrity and endotoxin uptake. We hypothesized that a secondary analysis would indicate that chronic GSE administration increases colonic expression of intestinal tight junction proteins and reduces circulating endotoxin levels, even in the absence of an obesity-promoting stimulus. Wistar Furth rats were administered drinking water containing 0.1% GSE for 21 days. Grape seed extract significantly increased the expression of gut junction protein occludin in the proximal colon and reduced fecal levels of the neutrophil protein calprotectin, compared with control. Grape seed extract did not significantly reduce serum or fecal endotoxin levels compared with control, although the variability in serum levels was widely increased by GSE. These data suggest that the improvement of gut barrier integrity and potential modulation of endotoxemia warrant investigation as a possible mechanism by which GSE prevents metabolic syndrome and associated diseases. Further investigation of this mechanism in high-fat feeding metabolic syndrome and obesity models is therefore justified. Copyright © 2012 Elsevier Inc. All rights reserved.

Worm Proteins of Schistosoma mansoni Reduce the Severity of Experimental Chronic Colitis in Mice by Suppressing Colonic Proinflammatory Immune Responses

PubMed Central

Heylen, Marthe; Ruyssers, Nathalie E.; De Man, Joris G.; Timmermans, Jean-Pierre; Pelckmans, Paul A.; Moreels, Tom G.; De Winter, Benedicte Y.

2014-01-01

Although helminthic therapy as a possible new option to treat inflammatory bowel disease is a well-established concept by now, the search for immunomodulatory helminth-derived compounds and their mechanisms of action is still ongoing. We investigated the therapeutic potential and the underlying immunological mechanisms of Schistosoma mansoni soluble worm proteins (SmSWP) in an adoptive T cell transfer mouse model of chronic colitis. Both a curative and a preventive treatment protocol were included in this study. The curative administration of SmSWP (started when colitis was established), resulted in a significant improvement of the clinical disease score, colonoscopy, macroscopic and microscopic inflammation score, colon length and myeloperoxidase activity. The therapeutic potential of the preventive SmSWP treatment (started before colitis was established), was less pronounced compared with the curative SmSWP treatment but still resulted in an improved clinical disease score, body weight loss, colon length and microscopic inflammation score. Both the curative and preventive SmSWP treatment downregulated the mRNA expression of the proinflammatory cytokines IFN-γ and IL-17A and upregulated the mRNA expression of the anti-inflammatory cytokine IL-4 in the colon at the end of the experiment. This colonic immunomodulatory effect of SmSWP could not be confirmed at the protein level. Moreover, the effect of SmSWP appeared to be a local colonic phenomenon, since the flow cytometric T cell characterization of the mesenteric lymph nodes and the cytokine measurements in the serum did not reveal any effect of SmSWP treatment. In conclusion, SmSWP treatment reduced the severity of colitis in the adoptive transfer mouse model via the suppression of proinflammatory cytokines and the induction of an anti-inflammatory response in the colon. PMID:25313594

Trends in colorectal cancer survival in northern Denmark: 1985-2004.

PubMed

Iversen, L H; Nørgaard, M; Jepsen, P; Jacobsen, J; Christensen, M M; Gandrup, P; Madsen, M R; Laurberg, S; Wogelius, P; Sørensen, H T

2007-03-01

The prognosis for colorectal cancer (CRC) is less favourable in Denmark than in neighbouring countries. To improve cancer treatment in Denmark, a National Cancer Plan was proposed in 2000. We conducted this population-based study to monitor recent trends in CRC survival and mortality in four Danish counties. We used hospital discharge registry data for the period January 1985-March 2004 in the counties of north Jutland, Ringkjøbing, Viborg and Aarhus. We computed crude survival and used Cox proportional hazards regression analysis to compare mortality over time, adjusted for age and gender. A total of 19,515 CRC patients were identified and linked with the Central Office of Civil Registration to ascertain survival through January 2005. From 1985 to 2004, 1-year and 5-year survival improved both for patients with colon and rectal cancer. From 1995-1999 to 2000-2004, overall 1-year survival of 65% for colon cancer did not improve, and some age groups experienced a decreasing 1-year survival probability. For rectal cancer, overall 1-year survival increased from 71% in 1995-1999 to 74% in 2000-2004. Using 1985-1989 as reference period, 30-day mortality did not decrease after implementation of the National Cancer Plan in 2000, neither for patients with colon nor rectal cancer. However, 1-year mortality for patients with rectal cancer did decline after its implementation. Survival and mortality from colon and rectal cancer improved before the National Cancer Plan was proposed; after its implementation, however, improvement has been observed for rectal cancer only.

Physiologically Based Pharmacokinetic and Absorption Modeling for Osmotic Pump Products.

PubMed

Ni, Zhanglin; Talattof, Arjang; Fan, Jianghong; Tsakalozou, Eleftheria; Sharan, Satish; Sun, Dajun; Wen, Hong; Zhao, Liang; Zhang, Xinyuan

2017-07-01

Physiologically based pharmacokinetic (PBPK) and absorption modeling approaches were employed for oral extended-release (ER) drug products based on an osmotic drug delivery system (osmotic pumps). The purpose was to systemically evaluate the in vivo relevance of in vitro dissolution for this type of formulation. As expected, in vitro dissolution appeared to be generally predictive of in vivo PK profiles, because of the unique feature of this delivery system that the in vitro and in vivo release of osmotic pump drug products is less susceptible to surrounding environment in the gastrointestinal (GI) tract such as pH, hydrodynamic, and food effects. The present study considered BCS (Biopharmaceutics Classification System) class 1, 2, and 3 drug products with half-lives ranging from 2 to greater than 24 h. In some cases, the colonic absorption models needed to be adjusted to account for absorption in the colon. C max (maximum plasma concentration) and AUCt (area under the concentration curve) of the studied drug products were sensitive to changes in colon permeability and segmental GI transit times in a drug product-dependent manner. While improvement of the methodology is still warranted for more precise prediction (e.g., colonic absorption and dynamic movement in the GI tract), the results from the present study further emphasized the advantage of using PBPK modeling in addressing product-specific questions arising from regulatory review and drug development.

In vitro Multi-Species Biofilms of Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa and Their Host Interaction during In vivo Colonization of an Otitis Media Rat Model

PubMed Central

Yadav, Mukesh K.; Chae, Sung-Won; Go, Yoon Young; Im, Gi Jung; Song, Jae-Jun

2017-01-01

Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) are known to cause biofilm-related infections. MRSA and PA have been frequently isolated from chronically infected wounds, cystic fibrosis, chronic suppurative otitis media (CSOM), and from indwelling medical devices, and these bacteria co-exist; however, their interaction with each-other or with the host is not well known. In this study, we investigated MRSA and PA multi-species biofilm communities in vitro and their interaction with the host during in vivo colonization using an OM rat-model. In-vitro biofilm formation and in-vivo colonization were studied using CV-microtiter plate assay and OM rat-model respectively. The biofilms were viewed under scanning electron microscope and bacteria were enumerated using cfu counts. The differential gene expressions of rat mucosa colonized with single or multi-species of MRSA or PA were studied using RNA-sequencing of total transcriptome. In multi-species in-vitro biofilms PA partially inhibited SA growth. However, no significant inhibition of MRSA was detected during in-vivo colonization of multi-species in rat bullae. A total of 1,797 genes were significantly (p < 0.05) differentially expressed in MRSA or PA or MRSA + PA colonized rat middle ear mucosa with respect to the control. The poly-microbial colonization of MRSA and PA induced the differential expression of a significant number of genes that are involved in immune response, inflammation, signaling, development, and defense; these were not expressed with single species colonization by either MRSA or PA. Genes involved in defense, immune response, inflammatory response, and developmental process were exclusively up-regulated, and genes that are involved in nervous system signaling, development and transmission, regulation of cell growth and development, anatomical and system development, and cell differentiation were down-regulated after multi-species inoculation. These results indicate that poly-microbial colonization induces a host response that is different from that induced by single species infection. PMID:28459043

Strain-specific quantification of root colonization by plant growth promoting rhizobacteria Bacillus firmus I-1582 and Bacillus amyloliquefaciens QST713 in non-sterile soil and field conditions.

PubMed

Mendis, Hajeewaka C; Thomas, Varghese P; Schwientek, Patrick; Salamzade, Rauf; Chien, Jung-Ting; Waidyarathne, Pramuditha; Kloepper, Joseph; De La Fuente, Leonardo

2018-01-01

Bacillus amyloliquefaciens QST713 and B. firmus I-1582 are bacterial strains which are used as active ingredients of commercially-available soil application and seed treatment products Serenade® and VOTiVO®, respectively. These bacteria colonize plant roots promoting plant growth and offering protection against pathogens/pests. The objective of this study was to develop a qPCR protocol to quantitate the dynamics of root colonization by these two strains under field conditions. Primers and TaqMan® probes were designed based on genome comparisons of the two strains with publicly-available and unpublished bacterial genomes of the same species. An optimized qPCR protocol was developed to quantify bacterial colonization of corn roots after seed treatment. Treated corn seeds were planted in non-sterile soil in the greenhouse and grown for 28 days. Specific detection of bacteria was quantified weekly, and showed stable colonization between ~104-105 CFU/g during the experimental period for both bacteria, and the protocol detected as low as 103 CFU/g bacteria on roots. In a separate experiment, streptomycin-resistant QST713 and rifampicin-resistant I-1582 strains were used to compare dilution-plating on TSA with the newly developed qPCR method. Results also indicated that the presence of natural microflora and another inoculated strain does not affect root colonization of either one of these strains. The same qPCR protocol was used to quantitate root colonization by QST713 and I-1582 in two corn and two soybean varieties grown in the field. Both bacteria were quantitated up to two weeks after seeds were planted in the field and there were no significant differences in root colonization in either bacteria strain among varieties. Results presented here confirm that the developed qPCR protocol can be successfully used to understand dynamics of root colonization by these bacteria in plants growing in growth chamber, greenhouse and the field.

Arbuscular mycorrhizal colonization in soil fertilized by organic and mineral fertilizers

NASA Astrophysics Data System (ADS)

Dvořáčková, Helena; Záhora, Jaroslav; Mikajlo, Irina; Elbl, Jakub; Kynický, Jindřich; Hladký, Jan; Brtnický, Martin

2017-04-01

The level of arbuscular mycorrhizal colonization of roots represents one of the best parameters for assessing soil quality. This special type of symbiosis helps plants to obtain nutrients of the distant area which are unavailable without cooperation with arbuscular mycorrhizal fungi. For example the plant available form of phosphorus is of the most important elements in plant nutrition. This element can't move (significantly) throw the soil and it could be unachievable for root system of plant. The same situation also applies to other important nutrients and water. Colonization of individual roots by arbuscular mycorrhizal fungi has a direct effect on the enlargement of the root system but plant needs to invest sugar substance for development of fungi. It's very difficult to understand when fungi colonization represents indicator of good soil condition. And when it provides us with information "about plant stress". The main goal of our work was to compare the effect of different fertilizers application on development of arbuscular mycorrhizal colonization. We worked with organic fertilizers such as biochar from residual biomass, biochar from sewage sludge and ageing biochar and with mineral fertilizer DAM 390 (mixture of ammonium 25 %, nitrate 25 % and urea nitrogen 50 %). Effect of different types of the above fertilizers on development of arbuscular mycorrhizal colonization was tested by pot experiment with indicator plant Lactuca sativa L. The highest (P < 0.05) colonization of roots was found in variant with biochar from sewage sludge. The lower colonization was recognized in control variant and variant with addition of mineral fertilizer. Our results indicate positive effect of modified biochar application to soil on increase in level of arbuscular mycorrhizal colonization of roots.

BAG3-dependent expression of Mcl-1 confers resistance of mutant KRAS colon cancer cells to the HSP90 inhibitor AUY922.

PubMed

Wang, Chun Yan; Guo, Su Tang; Croft, Amanda; Yan, Xu Guang; Jin, Lei; Zhang, Xu Dong; Jiang, Chen Chen

2018-02-01

Past studies have shown that mutant KRAS colon cancer cells are susceptible to apoptosis induced by the HSP90 inhibitor AUY922. Nevertheless, intrinsic and acquired resistance remains an obstacle for the potential application of the inhibitor in the treatment of the disease. Here we report that Mcl-1 is important for survival of colon cancer cells in the presence of AUY922. Mcl-1 was upregulated in mutant KRAS colon cancer cells selected for resistance to AUY922-induced apoptosis. This was due to its increased stability mediated by Bcl-2-associated athanogene domain 3 (BAG3), which was also increased in resistant colon cancer cells by heat shock factor 1 (HSF1) as a result of chronic endoplasmic reticulum (ER) stress. Functional investigations demonstrated that inhibition of Mcl-1, BAG3, or HSF1 triggered apoptosis in resistant colon cancer cells, and rendered AUY922-naïve colon cancer cells more sensitive to the inhibitor. Together, these results identify that the HSF1-BAG3-Mcl-1 signal axis is critical for protection of mutant KRAS colon cancer cells from AUY922-induced apoptosis, with potential implications for targeting HSF1/BAG3/Mcl-1 to improve the efficacy of AUY922 in the treatment of colon cancer. © 2017 Wiley Periodicals, Inc.

Pre-treatment with Bifidobacterium breve UCC2003 modulates Citrobacter rodentium-induced colonic inflammation and organ specificity.

PubMed

Collins, James W; Akin, Ali R; Kosta, Artemis; Zhang, Ning; Tangney, Mark; Francis, Kevin P; Frankel, Gad

2012-11-01

Citrobacter rodentium, which colonizes the gut mucosa via formation of attaching and effacing (A/E) lesions, causes transmissible colonic hyperplasia. The aim of this study was to evaluate whether prophylactic treatment with Bifidobacterium breve UCC2003 can improve the outcome of C. rodentium infection. Six-week-old albino C57BL/6 mice were pre-treated for 3 days with B. breve, challenged with bioluminescent C. rodentium and administered B. breve or PBS-C for 8 days post-infection; control mice were either administered B. breve and mock-infected with PBS, or mock-treated with PBS-C and mock-infected with PBS. C. rodentium colonization was monitored by bacterial enumeration from faeces and by a combination of both 2D bioluminescence imaging (BLI) and composite 3D diffuse light imaging tomography with µCT imaging (DLIT-µCT). At day 8 post-infection, colons were removed and assessed for crypt hyperplasia, histology by light microscopy, bacterial colonization by immunofluorescence, and A/E lesion formation by electron microscopy. Prophylactic administration of B. breve did not prevent C. rodentium colonization or A/E lesion formation. However, this treatment did alter C. rodentium distribution within the large intestine and significantly reduced colonic crypt hyperplasia at the peak of bacterial infection. These results show that B. breve could not competitively exclude C. rodentium, but reduced pathogen-induced colonic inflammation.

Gut bacteria are rarely shared by co-hospitalized premature infants, regardless of necrotizing enterocolitis development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raveh-Sadka, Tali; Thomas, Brian C.; Singh, Andrea

Premature infants are highly vulnerable to aberrant gastrointestinal tract colonization, a process that may lead to diseases like necrotizing enterocolitis. Thus, spread of potential pathogens among hospitalized infants is of great concern. Here, we reconstructed hundreds of high-quality genomes of microorganisms that colonized co-hospitalized premature infants, assessed their metabolic potential, and tracked them over time to evaluate bacterial strain dispersal among infants. We compared microbial communities in infants who did and did not develop necrotizing enterocolitis. Surprisingly, while potentially pathogenic bacteria of the same species colonized many infants, our genome-resolved analysis revealed that strains colonizing each baby were typically distinct.more » In particular, no strain was common to all infants who developed necrotizing enterocolitis. The paucity of shared gut colonizers suggests the existence of significant barriers to the spread of bacteria among infants. Furthermore, we demonstrate that strain-resolved comprehensive community analysis can be accomplished on potentially medically relevant time scales.« less

Gut bacteria are rarely shared by co-hospitalized premature infants, regardless of necrotizing enterocolitis development

DOE PAGES

Raveh-Sadka, Tali; Thomas, Brian C.; Singh, Andrea; ...

2015-03-03

Premature infants are highly vulnerable to aberrant gastrointestinal tract colonization, a process that may lead to diseases like necrotizing enterocolitis. Thus, spread of potential pathogens among hospitalized infants is of great concern. Here, we reconstructed hundreds of high-quality genomes of microorganisms that colonized co-hospitalized premature infants, assessed their metabolic potential, and tracked them over time to evaluate bacterial strain dispersal among infants. We compared microbial communities in infants who did and did not develop necrotizing enterocolitis. Surprisingly, while potentially pathogenic bacteria of the same species colonized many infants, our genome-resolved analysis revealed that strains colonizing each baby were typically distinct.more » In particular, no strain was common to all infants who developed necrotizing enterocolitis. The paucity of shared gut colonizers suggests the existence of significant barriers to the spread of bacteria among infants. Furthermore, we demonstrate that strain-resolved comprehensive community analysis can be accomplished on potentially medically relevant time scales.« less

Gut bacteria are rarely shared by co-hospitalized premature infants, regardless of necrotizing enterocolitis development

PubMed Central

Raveh-Sadka, Tali; Thomas, Brian C; Singh, Andrea; Firek, Brian; Brooks, Brandon; Castelle, Cindy J; Sharon, Itai; Baker, Robyn; Good, Misty; Morowitz, Michael J; Banfield, Jillian F

2015-01-01

Premature infants are highly vulnerable to aberrant gastrointestinal tract colonization, a process that may lead to diseases like necrotizing enterocolitis. Thus, spread of potential pathogens among hospitalized infants is of great concern. Here, we reconstructed hundreds of high-quality genomes of microorganisms that colonized co-hospitalized premature infants, assessed their metabolic potential, and tracked them over time to evaluate bacterial strain dispersal among infants. We compared microbial communities in infants who did and did not develop necrotizing enterocolitis. Surprisingly, while potentially pathogenic bacteria of the same species colonized many infants, our genome-resolved analysis revealed that strains colonizing each baby were typically distinct. In particular, no strain was common to all infants who developed necrotizing enterocolitis. The paucity of shared gut colonizers suggests the existence of significant barriers to the spread of bacteria among infants. Importantly, we demonstrate that strain-resolved comprehensive community analysis can be accomplished on potentially medically relevant time scales. DOI: http://dx.doi.org/10.7554/eLife.05477.001 PMID:25735037

Effect of Dietary-Resistant Starch on Inhibition of Colonic Preneoplasia and Wnt Signaling in Azoxymethane-Induced Rodent Models.

PubMed

Nelson, Bridget; Cray, Nicole; Ai, Yongfeng; Fang, Yinan; Liu, Peng; Whitley, Elizabeth M; Birt, Diane

2016-01-01

Dietary fiber has been reported to prevent preneoplastic colon lesions. The aim of this study was to determine the effect of resistant starches, novel dietary fibers, on the development of colonic preneoplasia and Wnt signaling in azoxymethane (AOM)-treated rats and mice fed resistant starches at 55% of the diet after AOM treatment. Another objective was to determine the effect of resistant starches on the development of preneoplasia in rats treated with antibiotics (Ab), administered between AOM treatment and resistant starch feeding. Diets containing resistant starches, high-amylose (HA7), high-amylose-octenyl succinic anhydride (OS-HA7), or high-amylose-stearic acid (SA-HA7) were compared with control cornstarch (CS). The resistant starch content of the diets did not alter the yield of colonic lesions but animals treated with AOM and fed the diet with the highest resistant starch content, SA-HA7 developed the highest average aberrant crypt foci (ACF) per animal. Mice fed the OS-HA7 diet had decreased expression of some upstream Wnt genes in the colonic crypts. This study suggests that further research is needed to determine if resistant starch impacts colon carcinogenesis in rodents.

Interactions between the arbuscular mycorrhizal (AM) fungus Glomus intraradices and nontransformed tomato roots of either wild-type or AM-defective phenotypes in monoxenic cultures.

PubMed

Bago, Alberto; Cano, Custodia; Toussaint, Jean-Patrick; Smith, Sally; Dickson, Sandy

2006-09-01

Monoxenic symbioses between the arbuscular mycorrhizal (AM) fungus Glomus intraradices and two nontransformed tomato root organ cultures (ROCs) were established. Wild-type tomato ROC from cultivar "RioGrande 76R" was employed as a control for mycorrhizal colonization and compared with its mutant line (rmc), which exhibits a highly reduced mycorrhizal colonization (rmc) phenotype. Structural features of the two root lines were similar when grown either in soil or under in vitro conditions, indicating that neither monoxenic culturing nor the rmc mutation affected root development or behavior. Colonization by G. intraradices in monoxenic culture of the wild-type line was low (<10%) but supported extensive development of extraradical mycelium, branched absorbing structures, and spores. The reduced colonization of rmc under monoxenic conditions (0.6%) was similar to that observed previously in soil. Extraradical development of runner hyphae was low and proportional to internal colonization. Few spores were produced. These results might suggest that carbon transfer may be modified in the rmc mutant. Our results support the usefulness of monoxenically obtained mycorrhizas for investigation of AM colonization and intraradical symbiotic functioning.

Removal and prevention of dental plaque with d-tagatose.

PubMed

Lu, Y; Levin, G V

2002-08-01

Dental plaque develops when early bacterial colonizers adhere to the acquired pellicle (saliva-derived proteinous coating on the tooth surface) followed by adhesion of late interspecies colonizers to form this type of biofilm (coaggregation). In developing a d-tagatose-based toothpaste, we examined 15 oral isolates, including both early colonizers (Streptococcus and Actinomyces) and late colonizers (Fusobacterium, Porphyromonas, Prevotella, Veillonella, Capnocytophaga, and Actinobacillus), and tested them for their ability to coaggregate with each other. We then tested the ability of d-tagatose to reverse any such coaggregations. Coaggregation was examined visually and scored by using a system ranging from 0, for no visible coaggregation to 4, for maximum coaggregation. d-Tagatose, at a concentration of less than 750 mm, completely reversed the coaggregation of 17 (60%) of 28 strongly coaggregating pairs (coaggregation score = 2 or higher) tested. In contrast, d-sorbitol had little reversal effect. d-Tagatose-sensitive coaggregations were d-galactose-reversible as well. d-Tagatose acted on both early and late colonizers; both groups, especially the late colonizers, were frequently involved in periodontal diseases. Thus, d-tagatose has the potential for preventing and removing plaque development and for altering the subgingival microbiota. These effective qualities offer conservative control of gingival and periodontal disease.

Surgical Management of Colonic Inertia

PubMed Central

McCoy, Jacob A.; Beck, David E.

2012-01-01

For the select small number of constipated patients that cannot be managed medically, surgical options should be considered. Increases in our knowledge of colorectal physiology and experience have fostered improvements in patient evaluation and surgical management. Currently, patients with refractory colonic inertia are offered total abdominal colectomy and ileorectal anastomosis, often with laparoscopic techniques. With proper patient selection, the results have been excellent for resolving the frequency and quality of bowel movements. However, symptoms such as bloating and abdominal pain, which may be related to irritable bowel syndrome rather than the colonic inertia, may persist. PMID:23449085

Primary T-cell Lymphoma of the Colon

PubMed Central

Son, Hee Jung; Rhee, Poong Lyul; Kim, Jae-Jun; Koh, Kwang Choel; Paik, Seong Woon; Rhee, Jong Chul; Koh, Young Hae

1997-01-01

A 40-year-old woman had been diagnosed with Crohns disease in September 1994, but later examinations revealed a primary T-cell lymphoma of the colon. Colonoscopic and histological examination showed ulcerative lesions simulating Crohns disease involving the entire colon and the terminal ileum, and she was first diagnosed as having Crohns disease. Differential therapeutic strategies, including corticosteroid, had improved the symptoms which were dominated by abdominal pain. When she visited our institute in April 1995, she presented with bloody stool twice a day, 7kg weight loss in a period of six months and a slightly painful abdomen. Colonoscopic finding showed geographic ulceration on the entire colon, especially rectum and terminal ileum. The histologic examination of specimens from colonoscopic biopsy showed primary peripheral T-cell lymphoma of the colon. Any dense lymphocyte infiltrates seen in the biopsy specimens obtained from lesions simulating ulcerative colitis or Crohns disease should be assessed to exclude intestinal lymphoma PMID:9439161

Early diagnosis of fungal infections in lung transplant recipients, colonization versus invasive disease?

PubMed

Herrera, Sabina; Husain, Shahid

2018-05-21

The diagnosis of invasive aspergillosis remains challenging in solid organ transplants in general, and in lung transplant recipients, in particular, because of colonization. Lung transplant recipients may be over treated with antifungal drugs because of the lack of appropriate diagnostic tools. A review of the new developments of diagnostic tools and whether this help distinguishing colonization from invasive disease is presented. Efforts are being made to develop new tools that will allow us to identify which patients will develop IPA, and those who will be able to control the disease.

Medicago truncatula Mtha1-2 mutants loose metabolic responses to mycorrhizal colonization.

PubMed

Hubberten, Hans-Michael; Sieh, Daniela; Zöller, Daniela; Hoefgen, Rainer; Krajinski, Franziska

2015-01-01

Bidirectional nutrient transfer is one of the key features of the arbuscular mycorrhizal symbiosis. Recently we were able to identify a Medicago truncatula mutant (mtha1-2) that is defective in the uptake of phosphate from the periarbuscular space due to a lack of the energy providing proton gradient provided by the symbiosis specific proton ATPase MtHA1 In order to further characterize the impact of fungal colonization on the plant metabolic status, without the beneficial aspect of improved mineral nutrition, we performed leaf ion analyses in mutant and wildtype plants with and without fungal colonization. Although frequency of fungal colonization was unaltered, the mutant did not show a positive growth response to mycorrhizal colonization. This indicates that nutrient transfer into the plant cell fails in the truncated arbuscules due to lacking expression of a functional MtHA1 protein. The leaves of wildtype plants showed clear metabolic responses to root mycorrhizal colonization, whereas no changes of leaf metabolite levels of mycorrhizal mtha1-2 plants were detected, even though they were colonized. These results show that MtHa1 is indispensable for a functional mycorrhizal symbiosis and, moreover, suggest that fungal root colonization per se does not depend on nutrient transfer to the plant host.

Complete remission in a colon cancer patient with a large, irresectable liver metastasis after XELOX/cetuximab/bevacizumab treatment.

PubMed

Weihrauch, Martin R; Stippel, Dirk; Fries, Jochen W U; Arnold, Dirk; Bovenschulte, Henning; Coutelle, Oliver; Hacker, Ulrich

2008-09-01

Stage IV colorectal cancer is usually an incurable disease. However, patients with resectable metastases have 5-year disease-free survival rates of up to 30%. Even with primarily irresectable disease, cure can be achieved in patients who become operable after neoadjuvant treatment. To improve the prognosis of these patients, highly effective neoadjuvant regimens need to be developed. Here, we report the case of a 62-year-old male patient who had been diagnosed with International Union against Cancer (UICC) stage III colon cancer 7 years previously and now presented with a large, irresectable liver metastasis and enlarged perihepatic lymph nodes. After neoadjuvant treatment with cetuximab, bevacizumab and XELOX, the patient showed a complete remission and underwent surgery. Histopathologically, the resected tissue and lymph nodes were free of residual tumor. To our knowledge, this is the first report of a complete pathological response in a patient with irresectable colorectal cancer after intensive chemotherapy/anti-EGFR/ VEGF antibody therapy. This combination regimen may help to improve the survival rates for patients with irresectable disease. Copyright 2008 S. Karger AG, Basel.

Pharmacokinetics of colon-specific pH and time-dependent flurbiprofen tablets.

PubMed

Vemula, Sateesh Kumar; Veerareddy, Prabhakar Reddy; Devadasu, Venkat Ratnam

2015-09-01

Present research deals with the development of compression-coated flurbiprofen colon-targeted tablets to retard the drug release in the upper gastro intestinal system, but progressively release the drug in the colon. Flurbiprofen core tablets were prepared by direct compression method and were compression coated using sodium alginate and Eudragit S100. The formulation is optimized based on the in vitro drug release study and further evaluated by X-ray imaging and pharmacokinetic studies in healthy humans for colonic delivery. The optimized formulation showed negligible drug release (4.33 ± 0.06 %) in the initial lag period followed by progressive release (100.78 ± 0.64 %) for 24 h. The X-ray imaging in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. The C max of colon-targeted tablets was 12,374.67 ng/ml at T max 10 h, where as in case of immediate release tablets the C max was 15,677.52 ng/ml at T max 3 h, that signifies the ability of compression-coated tablets to target the colon. Development of compression-coated tablets using combination of time-dependent and pH-sensitive approaches was suitable to target the flurbiprofen to colon.

Late Streptococcus bovis infection of total knee replacement complicated by infective endocarditis and associated with colonic ulcers

PubMed Central

Nagy, Mathias Thomas; Hla, Sann Minn; Keys, Graham Watson

2013-01-01

Streptococcus bovis is rare cause of late infections after total knee replacement (TKR). This report presents a case of confirmed late septic arthritis following TKR caused by S bovis that was further complicated with infective endocarditis resulting in aortic valve insufficiency in an immunecompetent patient. As an association between S bovis and gastrointestinal malignancies is suggested, a workup for such malignancies was performed that revealed non-malignant ulcers in patient's ascending colon. The patient is currently recovering from his aortic valve replacement surgery and is scheduled to have annual colonoscopies. His knee joint has improved; however, he developed constant pain because of underlying chronic infection in the affected joint and has difficulties mobilising. Therefore, a revision TKR is considered but postponed until he fully recovers from his heart valve surgery. PMID:23744853

Voluntary exercise prevents colonic inflammation in high-fat diet-induced obese mice by up-regulating PPAR-γ activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Wei-Xin, E-mail: weixinliu@yahoo.com; Wang, Ting; Zhou, Feng

Obesity is associated with increased colonic inflammation, which elevates the risk of colon cancer. Although exercise exerts anti-inflammatory actions in multiple chronic diseases associated with inflammation, it is unknown whether this strategy prevents colonic inflammation in obesity. We hypothesized that voluntary exercise would suppress colonic inflammation in high-fat diet (HFD)-induced obesity by modulation of peroxisome proliferator-activated receptor (PPAR)-γ. Male C57Bl/6J mice fed either a control diet (6.5% fat, CON) or a high-fat diet (24% fat, HFD) were divided into sedentary, voluntary exercise or voluntary exercise with PPAR-γ antagonist GW9662 (10 mg/kg/day). All interventions took place for 12 weeks. Compared with CON-sedentarymore » group, HFD-sedentary mice gained significantly more body weight and exhibited metabolic disorders. Molecular studies revealed that HFD-sedentary mice had increased expression of inflammatory mediators and activation of nuclear factor (NF)-κB in the colons, which were associated with decreased expression and activity of PPAR-γ. Voluntary exercise markedly attenuated body weight gain, improved metabolic disorders, and normalized the expression of inflammatory mediators and activation of NF-κB in the colons in HFD-mice while having no effects in CON-animals. Moreover, voluntary exercise significantly increased expression and activity of PPAR-γ in the colons in both HFD- and CON-animals. However, all of these beneficial effects induced by voluntary exercise were abolished by GW9662, which inhibited expression and activity of PPAR-γ. The results suggest that decreased PPAR-γ activity in the colon of HFD-induced obesity may facilitate the inflammatory response and colon carcinogenesis. Voluntary exercise prevents colonic inflammation in HFD-induced obesity by up-regulating PPAR-γ activity. - Highlights: • Obesity down-regulates PPAR-γ in the colon. • Down-regulated colonic PPAR-γ may facilitate inflammatory response. • Exercise prevents colonic inflammation in obesity by up-regulating PPAR-γ.« less

Parenteral nutrition with short- and long-chain triglycerides: triacetin reduces atrophy of small and large bowel mucosa and improves protein metabolism in burned rats.

PubMed

Karlstad, M D; Killeffer, J A; Bailey, J W; DeMichele, S J

1992-05-01

The effect of total parenteral nutrition with combinations of long-chain triglycerides (LCTs) and triacetin, the water-soluble triglyceride of acetate, on structural components of the gastrointestinal tract and protein metabolism was assessed in burned (30% body surface area) rats. Rats received isovolemic, isocaloric, and isonitrogenous diets that delivered 672 kJ.kg-1.d-1 (160 kcal.kg-1.d-1), 9.6 g amino acids.kg-1.d-1, and 30% nonprotein calories as 90% triacetin/10% LCTs, 50% triacetin/50% LCTs, or 100% LCTs for 7 d. Daily and cumulative nitrogen balances and whole-body leucine kinetics and fractional protein synthetic rates in rectus muscle and liver were determined on the last day of nutrition. DNA, protein, and total weight were determined in mucosal scrapings from segments of jejunum and colon. Plasma acetate concentrations were substantially higher in both triacetin groups. Parenteral nutrition with 50% triacetin and 50% LCTs promoted a positive nitrogen balance similar to that of 100% LCTs, increased protein in rectus muscle and liver, smaller and more numerous mucosal cells in jejunum and colon, and increased colonic mucosal weight compared with the other groups. Triacetin did not appreciably affect whole-body and tissue leucine kinetics. The equicaloric provision of triacetin and LCTs improved protein utilization and structural components of the small and large bowel and reduced the development of intestinal mucosal atrophy associated with conventional parenteral nutrition in burn injury.

Risk and outcomes of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia among patients admitted with and without MRSA nares colonization.

PubMed

Marzec, Natalie S; Bessesen, Mary T

2016-04-01

The risk of nosocomial methicillin-sensitive Staphylococcus aureus bacteremia in patients with nasal colonization on admission is 3-fold higher than in patients who are not colonized. Limited data on this question have been reported for methicillin-resistant S aureus (MRSA). This is an observational cohort study of patients admitted to a tertiary care medical center from October 1, 2007-September 30, 2013, who underwent active screening for nasal colonization with MRSA. There were 29,371 patients who underwent screening for nasal MRSA colonization; 3,262 (11%) were colonized with MRSA. There were 32 cases of MRSA bacteremia among colonized patients, for an incidence of 1%. Thirteen cases of bacteremia occurred in non-MRSA-colonized patients, for an incidence of 0.05%. The odds of developing MRSA bacteremia for patients who were nasally colonized with MRSA compared with those who were not colonized were 19.89. There was no difference between colonized and noncolonized subjects with bacteremia in all-cause mortality at 30 days or 1 year. In a setting with active screening for MRSA, the risk of MRSA bacteremia is 19.89-fold higher among colonized than noncolonized patients. Published by Elsevier Inc.

Management of Colorectal Trauma

PubMed Central

2011-01-01

Although the treatment strategy for colorectal trauma has advanced during the last part of the twentieth century and the result has improved, compared to other injuries, problems, such as high septic complication rates and mortality rates, still exist, so standard management for colorectal trauma is still a controversial issue. For that reason, we designed this article to address current recommendations for management of colorectal injuries based on a review of literature. According to the reviewed data, although sufficient evidence exists for primary repair being the treatment of choice in most cases of nondestructive colon injuries, many surgeons are still concerned about anastomotic leakage or failure, and prefer to perform a diverting colostomy. Recently, some reports have shown that primary repair or resection and anastomosis, is better than a diverting colostomy even in cases of destructive colon injuries, but it has not fully established as the standard treatment. The same guideline as that for colonic injury is applied in cases of intraperitoneal rectal injuries, and, diversion, primary repair, and presacral drainage are regarded as the standards for the management of extraperitoneal rectal injuries. However, some reports state that primary repair without a diverting colostomy has benefit in the treatment of extraperitoneal rectal injury, and presacral drainage is still controversial. In conclusion, ideally an individual management strategy would be developed for each patient suffering from colorectal injury. To do this, an evidence-based treatment plan should be carefully developed. PMID:21980586

Hypothalamic beta-endorphin neurons suppress preneoplastic and neoplastic lesions development in 1,2-dimethylhydrazine induced rat colon cancer model.

PubMed

Murugan, Sengottuvelan; Dave, Yatee; Rakhit, Ankush; Sarkar, Dipak K

2017-01-01

In recent years, experimental studies demonstrated negative impacts of impaired body stress response on colonic pathologies. In this study, we tested if reducing body stress response by the use of β-endorphin (BEP) neuronal transplants in the hypothalamus suppresses pre-neoplastic and neoplastic lesions. Colon cancer was induced by injecting 1,2-dimethylhydrazine (DMH) for sixteen weeks in Sprague Dawley rats with BEP neuron transplants or control neuron transplants, and their colonic histopathologies, colon tissue levels of pro-inflammatory cytokines and epithelial-mesenchymal transition (EMT) proteins and splenic levels of cytotoxic proteins were measured. Our results revealed that DMH induced tumors in colon at 100% incidence in control rats but failed to induce colonic tumors in 70% of animal with BEP neuronal transplants. The mean volume of tumor at the colon was smaller in BEP neurons transplanted rats than those in controls. Histopathologies of colon tissues revealed that BEP neurons transplanted animals had lesser tissue lesions such as aberrant crypt foci (ACF) and adenocarcinoma development in the colon than those in control groups. Immunohistochemical and western blot analyses identified reduced expression of Ki-67, TNF-α and NF-κB nuclear translocation in colonic tissues of BEP neurons transplanted rats than those in controls. BEP neurons transplanted rats also showed reduced expressions of transcription factors linked to EMT like Snail, Twist, and N-cadherin, but increased the levels of an epithelial cell marker E-cadherin in colon tissue. Furthermore, splenic NK cells cytolytic proteins such as perforin, granzyme B and IFN-γ levels in BEP neurons transplanted rats were higher than those in control rats. These data suggest that BEP neuron transplants suppress the growth and progression of colonic tumors possibly by decreasing inflammatory mileu and EMT via activation of innate immune responses.

Risk factors for infection development after transrectal prostate biopsy and the role of resistant bacteria in colonic flora.

PubMed

Eruz, Emine Dilek; Yalci, Aysun; Ozden, Eriz; Aslaner, Halide; Ogucu-Durgun, Suna; Koseoglu-Taymur, Deniz Derya; Memikoglu, Kemal Osman; Erdem, Hakan; Kurt, Halil

2017-02-28

In this study, we aimed to identify risk factors for the development of infectious complications after prostate biopsy and to investigate the role of intestinal colonization of bacteria that are resistant to prophylactic antibiotics. A total of 168 patients who had undergone transrectal prostate biopsy (TRPB) under ciprofloxacin and gentamycin prophylaxis were included in the study. Stool cultures and subsequent antibiotic susceptibility testing were performed in all patients before the start of antibiotic prophylaxis. Of the 168 patients, 17 (10.1%) developed urinary tract infection (UTI), while 6 (3.57%) developed sepsis within seven days after biopsy. Ciprofloxacin-resistant bacterial colonization was detected in 81 (48.2%) of the patients. None of the patients with ciprofloxacin-sensitive bacteria in intestinal flora developed a UTI. The colonization of intestinal ciprofloxacin-resistant bacteria increased UTI risk significantly after TRPB (p < 0.0001). Urolithiasis history, presence of permanent urinary catheterization, hospitalization history for more than 48 hours in the last year, and recent antibiotic usage significantly increased UTI risk after TRPB. Development of an infection was more frequent in patients with resistant bacterial colonization. We hope to guide more comprehensive studies designed to find a standard prophylactic regimen for TRPB that can be used all over the world.

Candida colonization as a risk marker for invasive candidiasis in mixed medical-surgical intensive care units: development and evaluation of a simple, standard protocol.

PubMed

Lau, Anna F; Kabir, Masrura; Chen, Sharon C-A; Playford, E Geoffrey; Marriott, Deborah J; Jones, Michael; Lipman, Jeffrey; McBryde, Emma; Gottlieb, Thomas; Cheung, Winston; Seppelt, Ian; Iredell, Jonathan; Sorrell, Tania C

2015-04-01

Colonization with Candida species is an independent risk factor for invasive candidiasis (IC), but the minimum and most practicable parameters for prediction of IC have not been optimized. We evaluated Candida colonization in a prospective cohort of 6,015 nonneutropenic, critically ill patients. Throat, perineum, and urine were sampled 72 h post-intensive care unit (ICU) admission and twice weekly until discharge or death. Specimens were cultured onto chromogenic agar, and a subset underwent molecular characterization. Sixty-three (86%) patients who developed IC were colonized prior to infection; 61 (97%) tested positive within the first two time points. The median time from colonization to IC was 7 days (range, 0 to 35). Colonization at any site was predictive of IC, with the risk of infection highest for urine colonization (relative risk [RR]=2.25) but with the sensitivity highest (98%) for throat and/or perineum colonization. Colonization of ≥2 sites and heavy colonization of ≥1 site were significant independent risk factors for IC (RR=2.25 and RR=3.7, respectively), increasing specificity to 71% to 74% but decreasing sensitivity to 48% to 58%. Molecular testing would have prompted a resistance-driven decision to switch from fluconazole treatment in only 11% of patients infected with C. glabrata, based upon species-level identification alone. Positive predictive values (PPVs) were low (2% to 4%) and negative predictive values (NPVs) high (99% to 100%) regardless of which parameters were applied. In the Australian ICU setting, culture of throat and perineum within the first two time points after ICU admission captures 84% (61/73 patients) of subsequent IC cases. These optimized parameters, in combination with clinical risk factors, should strengthen development of a setting-specific risk-predictive model for IC. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Defining the role of polyamines in colon carcinogenesis using mouse models

PubMed Central

Ignatenko, Natalia A.; Gerner, Eugene W.; Besselsen, David G.

2011-01-01

Genetics and diet are both considered important risk determinants for colorectal cancer, a leading cause of death in the US and worldwide. Genetically engineered mouse (GEM) models have made a significant contribution to the characterization of colorectal cancer risk factors. Reliable, reproducible, and clinically relevant animal models help in the identification of the molecular events associated with disease progression and in the development of effictive treatment strategies. This review is focused on the use of mouse models for studying the role of polyamines in colon carcinogenesis. We describe how the available mouse models of colon cancer such as the multiple intestinal neoplasia (Min) mice and knockout genetic models facilitate understanding of the role of polyamines in colon carcinogenesis and help in the development of a rational strategy for colon cancer chemoprevention. PMID:21712957

Surgical Capabilities for Exploration and Colonization Space Flight - An Exploratory Symposium

NASA Technical Reports Server (NTRS)

Pantalos, George; Strangman, Gary; Doarn, Charles R.; Broderick, Timothy; Antonsen, Erik

2015-01-01

Identify realistic and achievable pathways for surgical capabilities during exploration and colonization space operations and develop a list of recommendations to the NASA Human Research Program to address challenges to developing surgical capabilities.

Immunotherapy for pulmonary squamous cell carcinoma and colon carcinoma with pembrolizumab: A case report.

PubMed

Nozawa, Yoshihiro; Oka, Yuka; Oosugi, Jun; Takemura, Shinichi

2018-05-01

Novel treatment strategies such as immunotherapy are being evaluated to further improve the outcomes of colorectal cancer patients. To our knowledge, this is the first report to show both the successful treatment of pulmonary squamous cell carcinoma (SCC) with pembrolizumab alongside histological and immunohistochemical findings of resected colon cancer under immunotherapy for lung cancer. This patient was a 70-year-old man who presented with a right lung tumor and simultaneous adenocarcinoma of the sigmoid colon. Biopsy examination revealed squamous cell carcinoma in the right lung and adenocarcinoma of the sigmoid colon. The patient underwent successful pembrolizumab treatment as first-line immunotherapy for lung cancer, as demonstrated by computed tomography, and the sigmoid colon tumor was excised during an immunotherapy-free window. No unusual tumor growth in the right lung or abnormal abdominal signs was observed during the 9-month follow-up. Microscopically, the resected colon cancer specimen was characterized by numerous lymphoid cells in the partial stroma, with a large number of infiltrating lymphocytes consisting of CD3+, CD8+ T cells. In summary, this case demonstrates how immunotherapy affects PD-L1-negative colon cancer and indicates future treatment prospects.

Medicago truncatula shows distinct patterns of mycorrhiza-related gene expression after inoculation with three different arbuscular mycorrhizal fungi.

PubMed

Feddermann, Nadja; Boller, Thomas; Salzer, Peter; Elfstrand, Sara; Wiemken, Andres; Elfstrand, Malin

2008-02-01

Different arbuscular mycorrhizal fungi (AMF) alter growth and nutrition of a given plant differently. Plant gene expression patterns in response to fungal colonization show a certain overlap when colonized by fungi of the Glomeraceae. However, little is known of plant responses to fungi of different fungal taxa, e.g. the Gigasporaceae. We therefore compared the impact of colonization by three taxonomically different AMF species (Glomus intraradices, Glomus mosseae and Scutellospora castanea) on Medicago truncatula at the physiological and transcriptional level using quantitative-PCR. Each AMF developed a species-typical colonization pattern, with a colonization degree of 60% for G. intraradices and 30% for G. mosseae. Both species developed appressoria, intraradical hyphae, arbuscules and vesicles. S. castanea showed a colonization degree of 10% and developed appressoria, intraradical hyphae, arbuscules and arbusculate coils. All AMF enhanced the plant biomass accumulation and nutritional status although not in correlation with the colonization degree. The expression of 10 mycorrhiza-specific or mycorrhiza-associated plant genes could be separated into two clusters. The first cluster, containing arbuscule-induced genes, was highly induced in interactions with G. intraradices and G. mosseae but also slightly induced by S. castanea. The second cluster of genes contained genes that were induced primarily by S. castanea. In conclusion, genes that respond to colonization by fungi of the genus Glomus also respond to Scutellospora. However, there is also a group of genes that is significantly induced only by Scutellospora and not by Glomus species in this study. Our data indicate that genes may be differentially regulated in response to the different AM fungi.

Epsin is required for Dishevelled stability and Wnt signaling activation in colon cancer development

PubMed Central

Chang, Baojun; Tessneer, Kandice L.; McManus, John; Liu, Xiaolei; Hahn, Scott; Pasula, Satish; Wu, Hao; Song, Hoogeun; Chen, Yiyuan; Cai, Xiaofeng; Dong, Yunzhou; Brophy, Megan L.; Rahman, Ruby; Ma, Jian-Xing; Xia, Lijun; Chen, Hong

2015-01-01

Uncontrolled canonical Wnt signaling supports colon epithelial tumor expansion and malignant transformation. Understanding the regulatory mechanisms involved is crucial for elucidating the pathogenesis of and will provide new therapeutic targets for colon cancer. Epsins are ubiquitin-binding adaptor proteins upregulated in several human cancers; however, epsins’ involvement in colon cancer is unknown. Here we show that loss of intestinal epithelial epsins protects against colon cancer by significantly reducing the stability of the crucial Wnt signaling effector, dishevelled (Dvl2), and impairing Wnt signaling. Consistently, epsins and Dvl2 are correspondingly upregulated in colon cancer. Mechanistically, epsin binds Dvl2 via its epsin N-terminal homology domain and ubiquitin-interacting motifs and prohibits Dvl2 polyubiquitination and degradation. Our findings reveal an unconventional role for epsins in stabilizing Dvl2 and potentiating Wnt signaling in colon cancer cells to ensure robust colon cancer progression. Epsins’ pro-carcinogenic role suggests they are potential therapeutic targets to combat colon cancer. PMID:25871009

The role of colonic metabolism in lactose intolerance.

PubMed

He, T; Venema, K; Priebe, M G; Welling, G W; Brummer, R-J M; Vonk, R J

2008-08-01

Lactose maldigestion and intolerance affect a large part of the world population. The underlying factors of lactose intolerance are not fully understood. In this review, the role of colonic metabolism is discussed, i.e. fermentation of lactose by the colonic microbiota, colonic processing of the fermentation metabolites and how these processes would play a role in the pathophysiology of lactose intolerance. We suggest that the balance between the removal and production rate of osmotic-active components (lactose, and intermediate metabolites, e.g. lactate, succinate, etc.) in the colon is a key factor in the development of symptoms. The involvement of the colon may provide the basis for designing new targeted strategies for dietary and clinical management of lactose intolerance.

Colonization with hospital flora and its associated risk factors in neonates hospitalized in neonatal ward of a teaching center in Isfahan, Iran.

PubMed

Shirani, Kiana; Mostafavizadeh, Kamyar; Ataei, Behrouz; Akhani, Khatere

2018-01-01

Due to the high incidence and prevalence of infection in neonatal ward, especially Neonatal Intensive Care Units (NICUs) reported by different studies and the important role of colonization with hospital germs in the development of nosocomial infections, we intended to evaluate the risk of colonization with hospital germs in neonates and its associated risk factors. This cross-sectional, descriptive-analytical study was conducted in 2016 in a Teaching Center in Iran. In total, 51 neonates were selected based on the inclusion criteria, and after recording their information in a checklist, samples were taken by swab from outer ear, axilla, and groin for culture. Neonates with negative culture from mentioned regions were enrolled in the study. The swab samples again were taken and sent for culture from mentioned regions in at least 3 days after hospitalization. Culture results from first and second sampling were collected and analyzed statistically. This study was conducted on 51 neonates. The mean gestational age among the neonates ranged from 35.25 (Week) ± 2.98. 22 girls (43.1%) and 29 boys (56.9%), most of them were born by cesarean. Based on the results of logistic regression, a significant association was found between the occurrence of colonization of hospital flora and the place hospitalization of the newborns (odds ratio (OR): 4.750; 95% confidence interval (CI): 1.26-17.85). This study revealed that the only risk factors of colonization with hospital flora in neonates are the type of delivery and place of hospitalization. Based on findings of the study, it is recommended to focus on efforts in increasing the rate of natural birth as well as improving conditions of infection control in NICUs to reduce the number of incidences of colonization with hospital flora in neonates.

The Administration of Escherichia coli Nissle 1917 Ameliorates Development of DSS-Induced Colitis in Mice

PubMed Central

Rodríguez-Nogales, Alba; Algieri, Francesca; Garrido-Mesa, José; Vezza, Teresa; Utrilla, Maria P.; Chueca, Natalia; Fernández-Caballero, Jose A.; García, Federico; Rodríguez-Cabezas, Maria E.; Gálvez, Julio

2018-01-01

The beneficial effects of probiotics on immune-based pathologies such as inflammatory bowel disease (IBD) have been well reported. However, their exact mechanisms have not been fully elucidated. Few studies have focused on the impact of probiotics on the composition of the colonic microbiota. The aim of the present study was to correlate the intestinal anti-inflammatory activity of the probiotic Escherichia coli Nissle 1917 (EcN) in the dextran sodium sulfate (DSS) model of mouse colitis with the changes induced in colonic microbiota populations. EcN prevented the DSS-induced colonic damage, as evidenced by lower disease activity index (DAI) values and colonic weight/length ratio, when compared with untreated control mice. The beneficial effects were confirmed biochemically, since the probiotic treatment improved the colonic expression of different cytokines and proteins involved in epithelial integrity. In addition, it restored the expression of different micro-RNAs (miR-143, miR-150, miR-155, miR-223, and miR-375) involved in the inflammatory response that occurs in colitic mice. Finally, the characterization of the colonic microbiota by pyrosequencing showed that the probiotic administration was able to counteract the dysbiosis associated with the intestinal inflammatory process. This effect was evidenced by an increase in bacterial diversity in comparison with untreated colitic mice. The intestinal anti-inflammatory effects of the probiotic EcN were associated with an amelioration of the altered gut microbiome in mouse experimental colitis, especially when considering bacterial diversity, which is reduced in these intestinal conditions. Moreover, this probiotic has shown an ability to modulate expression levels of miRNAs and different mediators of the immune response involved in gut inflammation. This modulation could also be of great interest to understand the mechanism of action of this probiotic in the treatment of IBD.

A Randomized Phase II Dose-Response Exercise Trial among Colon Cancer Survivors: Purpose, Study Design, Methods, and Recruitment Results

PubMed Central

Brown, Justin C.; Troxel, Andrea B.; Ky, Bonnie; Damjanov, Nevena; Zemel, Babette S.; Rickels, Michael R.; Rhim, Andrew D.; Rustgi, Anil K.; Courneya, Kerry S.; Schmitz, Kathryn H.

2016-01-01

Background Observational studies indicate that higher volumes of physical activity are associated with improved disease outcomes among colon cancer survivors. The aim of this report is to describe the purpose, study design, methods, and recruitment results of the COURAGE trial, a National Cancer Institute (NCI) sponsored, phase II, randomized, dose-response exercise trial among colon cancer survivors. Methods/Results The primary objective of the COURAGE trial is to quantify the feasibility, safety, and physiologic effects of low-dose (150 min·wk−1) and high-dose (300 min·wk−1) moderate-intensity aerobic exercise compared to usual-care control group over six months. The exercise groups are provided with in-home treadmills and heart rate monitors. Between January and July 2015, 1,433 letters were mailed using a population-based state cancer registry; 126 colon cancer survivors inquired about participation, and 39 were randomized onto the study protocol. Age was associated with inquiry about study participation (P<0.001) and randomization onto the study protocol (P<0.001). No other demographic, clinical, or geographic characteristics were associated with study inquiry or randomization. The final trial participant was randomized in August 2015. Six month endpoint data collection was completed in February 2016. Discussion The recruitment of colon cancer survivors into an exercise trial is feasible. The findings from this trial will inform key design aspects for future phase 2 and phase 3 randomized controlled trials to examine the efficacy of exercise to improve clinical outcomes among colon cancer survivors. PMID:26970181

Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients.

PubMed

Dienstmann, Rodrigo; Salazar, Ramon; Tabernero, Josep

2015-06-01

For more than three decades, postoperative chemotherapy-initially fluoropyrimidines and more recently combinations with oxaliplatin-has reduced the risk of tumor recurrence and improved survival for patients with resected colon cancer. Although universally recommended for patients with stage III disease, there is no consensus about the survival benefit of postoperative chemotherapy in stage II colon cancer. The most recent adjuvant clinical trials have not shown any value for adding targeted agents, namely bevacizumab and cetuximab, to standard chemotherapies in stage III disease, despite improved outcomes in the metastatic setting. However, biomarker analyses of multiple studies strongly support the feasibility of refining risk stratification in colon cancer by factoring in molecular characteristics with pathologic tumor staging. In stage II disease, for example, microsatellite instability supports observation after surgery. Furthermore, the value of BRAF or KRAS mutations as additional risk factors in stage III disease is greater when microsatellite status and tumor location are taken into account. Validated predictive markers of adjuvant chemotherapy benefit for stage II or III colon cancer are lacking, but intensive research is ongoing. Recent advances in understanding the biologic hallmarks and drivers of early-stage disease as well as the micrometastatic environment are expected to translate into therapeutic strategies tailored to select patients. This review focuses on the pathologic, molecular, and gene expression characterizations of early-stage colon cancer; new insights into prognostication; and emerging predictive biomarkers that could ultimately help define the optimal adjuvant treatments for patients in routine clinical practice. © 2015 by American Society of Clinical Oncology.

Microbial colonization is required for normal neurobehavioral development in zebrafish..

EPA Science Inventory

Host-associated microbiota are a dynamic system that shapes organismal development. There is growing evidence that microbiota modify the toxicokinetics and/or toxicodynamics of environmental chemicals. To delineate the neurobehavioral consequences of microbial colonization, we ex...

Microbial colonization is required for normal neurobehavioral development in zebrafish.

EPA Science Inventory

Host-associated microbiota are a dynamic system that shapes organismal development. There is growing evidence that microbiota modify the toxicokinetics and/or toxicodynamics of environmental chemicals. To delineate the neurobehavioral consequences of microbial colonization, we ex...

Cinnamate of inulin as a vehicle for delivery of colonic drugs.

PubMed

López-Molina, Dorotea; Chazarra, Soledad; How, Chee Wun; Pruidze, Nikolov; Navarro-Perán, Enma; García-Cánovas, Francisco; García-Ruiz, Pedro Antonio; Rojas-Melgarejo, Francisco; Rodríguez-López, José Neptuno

2015-02-01

Colon diseases are difficult to treat because oral administrated drugs are absorbed at the stomach and intestine levels and they do not reach colon; in addition, intravenous administrated drugs are eliminated from the body before reaching colon. Inulin is a naturally occurring polysaccharide found in many plants. It consists of β 2-1 linked D-fructose molecules having a glucosyl unit at the reducing end. Various inulin and dextran hydrogels have been developed that serve as potential carrier for introduction of drugs into the colon. Because inulin is not absorbed in the stomach or in the small intestine, and inulin is degraded by colonic bacteria, drugs encapsulated in inulin-coated vesicles could be specifically liberated in the colon. Therefore, the use of inulin-coated vesicles could represent an advance for the treatment of colon diseases. Here, we study the use of a cinnamoylated derivative of chicory inulin as a vehicle for the controlled delivery of colonic drugs. The encapsulation of methotrexate in inulin vesicles and its release and activity was studied in colon cancer cells in cultures. Copyright © 2014 Elsevier B.V. All rights reserved.

Vanadium inhibits DNA-protein cross-links and ameliorates surface level changes of aberrant crypt foci during 1,2-dimethylhydrazine induced rat colon carcinogenesis.

PubMed

Kanna, P Suresh; Saralaya, M G; Samanta, K; Chatterjee, M

2005-01-01

The trace mineral vanadium inhibits cancer development in a variety of experimental animal models. The present study was to gain insight into a putative anticancer effect of vanadium in a rat model of colon carcinogenesis. The in vivo study was intended to clarify the effect of vanadium on DNA-protein cross-links (DPC), surface level changes of aberrant crypt foci (ACF) and biotransformation status during 1,2-dimethylhydrazine (1,2-DMH) induced preneoplastic rat colon carcinogenesis. The comet assay showed statistically higher mean base values of DNA-protein mass (p<0.01) and mean frequencies of tailed cells (p<0.001) in the carcinogen-induced group after treatment with proteinase K. Treatment with vanadium in the form of ammonium monovanadate supplemented ad libitum in drinking water for the entire experimental period caused a significant (p<0.02) reduction (40%) in DNA-protein cross-links in colon cells. Further, the biotransformation status of vanadium was ascertained measuring the drug metabolising enzymes, glutathione S-transferase (GST) and cytochrome P-450 (Cyt P-450). Significantly, there was an increase in glutathione S-transferase and cytochrome P-450 levels (p<0.01 and p<0.02, respectively) in rats supplemented with vanadium as compared to their carcinogen controls. As an endpoint marker, we also evaluated the effect of vanadium on surface level changes of aberrant crypt foci induced by 1,2-DMH by scanning electron microscopy. Animals induced with 1,2-DMH and supplemented with vanadium showed a marked improvement in colonic architecture with less number of aberrant crypt foci in contrast to the animals induced with 1,2-DMH alone, thereby exhibiting its anti-carcinogenicity by modulating the markers studied herein.

Effect of vitamin C on azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated early colon cancer in mice

PubMed Central

2018-01-01

BACKGROUND/OBJECTIVES The objective of this study was to investigate the effects of vitamin C on inflammation, tumor development, and dysbiosis of intestinal microbiota in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced inflammation-associated early colon cancer mouse model. MATERIALS/METHODS Male BALB/c mice were injected intraperitoneally with AOM [10 mg/kg body weight (b.w)] and given two 7-d cycles of 2% DSS drinking water with a 14 d inter-cycle interval. Vitamin C (60 mg/kg b.w. and 120 mg/kg b.w.) was supplemented by gavage for 5 weeks starting 2 d after the AOM injection. RESULTS The vitamin C treatment suppressed inflammatory morbidity, as reflected by disease activity index (DAI) in recovery phase and inhibited shortening of the colon, and reduced histological damage. In addition, vitamin C supplementation suppressed mRNA levels of pro-inflammatory mediators and cytokines, including cyclooxygenase-2, microsomal prostaglandin E synthase-2, tumor necrosis factor-α, Interleukin (IL)-1β, and IL-6, and reduced expression of the proliferation marker, proliferating cell nuclear antigen, compared to observations of AOM/DSS animals. Although the microbial composition did not differ significantly between the groups, administration of vitamin C improved the level of inflammation-related Lactococcus and JQ084893 to control levels. CONCLUSION Vitamin C treatment provided moderate suppression of inflammation, proliferation, and certain inflammation-related dysbiosis in a murine model of colitis associated-early colon cancer. These findings support that vitamin C supplementation can benefit colonic health. Long-term clinical studies with various doses of vitamin C are warranted. PMID:29629026

Therapeutic effect of kakkonto in a mouse model of food allergy with gastrointestinal symptoms.

PubMed

Yamamoto, Takeshi; Fujiwara, Kanae; Yoshida, Minako; Kageyama-Yahara, Natsuko; Kuramoto, Hirofumi; Shibahara, Naotoshi; Kadowaki, Makoto

2009-01-01

The number of patients with food allergy has increased dramatically over the last several decades. However, there is no effective drug for food allergies. In the present study, we evaluated the effects of kakkonto, a traditional Japanese herbal medicine, in a mouse model of food allergy with gastrointestinal symptoms. BALB/c mice were systemically sensitized twice with ovalbumin (OVA) and then were repeatedly given OVA by oral intubation (OVA mice). Kakkonto was administered orally before the OVA challenges. The OVA mice developed allergic diarrhea (91.8 +/- 3.8% after 6 OVA challenges), and myeloperoxidase (MPO) activity was dramatically elevated in the colons of the OVA mice. Kakkonto significantly suppressed the occurrence of allergic diarrhea and MPO activity in the OVA mice. Furthermore, the number of mucosal mast cells was greatly increased in the proximal colons of the OVA mice, and this was also suppressed by kakkonto. Interestingly, mRNA expression of helper T cell type 1 (Th1) cytokines (IFN-gamma) and Th2 cytokines (IL-4, IL-5 and IL-10) were significantly upregulated in the proximal colons of the OVA mice, an effect which was also reduced by kakkonto. Transcriptome analysis detected increased mRNA expression of suppressor of cytokine signaling-3 in the proximal colons of OVA mice, which was decreased by kakkonto administration. Kakkonto has immunosuppressive effects and interferes with the infiltration of mucosal mast cells in the colons of mice with induced food allergy, leading to improvement of allergic symptoms. Kakkonto has potential as a therapeutic drug for treatment of allergic symptoms induced by the disruption of intestinal mucosal immunity. (c) 2008 S. Karger AG, Basel.

A Novel Approach to Flurbiprofen Pulsatile Colonic Release: Formulation and Pharmacokinetics of Double-Compression-Coated Mini-Tablets.

PubMed

Vemula, Sateesh Kumar

2015-12-01

A significant plan is executed in the present study to study the effect of double-compression coating on flurbiprofen core mini-tablets to achieve the pulsatile colonic delivery to deliver the drug at a specific time as per the patho-physiological need of the disease that results in improved therapeutic efficacy. In this study, pulsatile double-compression-coated tablets were prepared based on time-controlled hydroxypropyl methylcellulose K100M inner compression coat and pH-sensitive Eudragit S100 outer compression coat. Then, the tablets were evaluated for both physical evaluation and drug-release studies, and to prove these results, in vivo pharmacokinetic studies in human volunteers were conducted. From the in vitro drug-release studies, F6 tablets were considered as the best formulation, which retarded the drug release in the stomach and small intestine (3.42 ± 0.12% in 5 h) and progressively released to the colon (99.78 ± 0.74% in 24 h). The release process followed zero-order release kinetics, and from the stability studies, similarity factor between dissolution data before and after storage was found to be 88.86. From the pharmacokinetic evaluation, core mini-tablets producing peak plasma concentration (C max) was 14,677.51 ± 12.16 ng/ml at 3 h T max and pulsatile colonic tablets showed C max = 12,374.67 ± 16.72 ng/ml at 12 h T max. The area under the curve for the mini and pulsatile tablets was 41,238.52 and 72,369.24 ng-h/ml, and the mean resident time was 3.43 and 10.61 h, respectively. In conclusion, development of double-compression-coated tablets is a promising way to achieve the pulsatile colonic release of flurbiprofen.

Exosomes Derived from Dendritic Cells Treated with Schistosoma japonicum Soluble Egg Antigen Attenuate DSS-Induced Colitis

PubMed Central

Wang, Lifu; Yu, Zilong; Wan, Shuo; Wu, Feng; Chen, Wei; Zhang, Beibei; Lin, Datao; Liu, Jiahua; Xie, Hui; Sun, Xi; Wu, Zhongdao

2017-01-01

Exosomes are 30–150 nm small membrane vesicles that are released into the extracellular medium via cells that function as a mode of intercellular communication. Dendritic cell (DC)-derived exosomes modulate immune responses and prevent the development of autoimmune diseases. Moreover, Schistosoma japonicum eggs show modulatory effects in a mouse model of colitis. Therefore, we hypothesized that exosomes derived from DCs treated with S. japonicum soluble eggs antigen (SEA; SEA-treated DC exosomes) would be useful for treating inflammatory bowel disease (IBD). Exosomes were purified from the supernatant of DCs treated or untreated with SEA and identified via transmission electron microscopy, western blotting and NanoSight. Acute colitis was induced via the administration of dextran sulfate sodium (DSS) in drinking water (5.0%, wt/vol). Treatment with exosomes was conducted via intraperitoneal injection (i.p.; 50 μg per mouse) from day 0 to day 6. Clinical scores were calculated based on weight loss, stool type, and bleeding. Colon length was measured as an indirect marker of inflammation, and colon macroscopic characteristics were determined. Body weight loss and the disease activity index of DSS-induced colitis mice decreased significantly following treatment with SEA-treated DC exosomes. Moreover, the colon lengths of SEA-treated DC exosomes treated colitis mice improved, and their mean colon macroscopic scores decreased. In addition, histologic examinations and histological scores showed that SEA-treated DC exosomes prevented colon damage in acute DSS-induced colitis mice. These results indicate that SEA-treated DC exosomes attenuate the severity of acute DSS-induced colitis mice more effectively than DC exosomes. The current work suggests that SEA-treated DC exosomes may be useful as a new approach to treat IBD. PMID:28959207

Prevalence of and Risk Factors for Multidrug-Resistant Acinetobacter baumannii Colonization Among High-Risk Nursing Home Residents

PubMed Central

Mody, Lona; Gibson, Kristen E.; Horcher, Amanda; Prenovost, Katherine; McNamara, Sara E.; Foxman, Betsy; Kaye, Keith S.; Bradley, Suzanne

2015-01-01

OBJECTIVE To characterize the epidemiology of multidrug-resistant (MDR) Acinetobacter baumannii colonization in high-risk nursing home (NH) residents. DESIGN Nested case-control study within a multicenter prospective intervention trial. SETTING Four NHs in Southeast Michigan. PARTICIPANTS Case patients and control subjects were NH residents with an indwelling device (urinary catheter and/or feeding tube) selected from the control arm of the Targeted Infection Prevention study. Cases were residents colonized with MDR (resistant to ≥3 classes of antibiotics) A. baumannii; controls were never colonized with MDR A. baumannii. METHODS For active surveillance cultures, specimens from the nares, oropharynx, groin, perianal area, wounds, and device insertion site(s) were collected upon study enrollment, day 14, and monthly thereafter. A. baumannii strains and their susceptibilities were identified using standard microbiologic methods. RESULTS Of 168 NH residents, 25 (15%) were colonized with MDR A. baumannii. Compared with the 143 controls, cases were more functionally disabled (Physical Self-Maintenance Score >24; odds ratio, 5.1 [95% CI, 1.8–14.9]; P < .004), colonized with Proteus mirabilis (5.8 [1.9–17.9]; P < .003), and diabetic (3.4 [1.2–9.9]; P < .03). Most cases (22 [88%]) were colonized with multiple antibiotic-resistant organisms and 16 (64%) exhibited co-colonization with at least one other resistant gram-negative bacteria. CONCLUSION Functional disability, P. mirabilis colonization, and diabetes mellitus are important risk factors for colonization with MDR A. baumannii in high-risk NH residents. A. baumannii exhibits widespread antibiotic resistance and a preference to colonize with other antibiotic-resistant organisms, meriting enhanced attention and improved infection control practices in these residents. PMID:26072936

Clinically compatible flexible wide-field multi-color fluorescence endoscopy with a porcine colon model

PubMed Central

Oh, Gyugnseok; Park, Youngrong; Yoo, Su Woong; Hwang, Soonjoo; Chin-Yu, Alexey V. Dan; Ryu, Yeon-Mi; Kim, Sang-Yeob; Do, Eun-Ju; Kim, Ki Hean; Kim, Sungjee; Myung, Seung-Jae; Chung, Euiheon

2017-01-01

Early detection of structural or molecular changes in dysplastic epithelial tissues is crucial for cancer screening and surveillance. Multi-targeting molecular endoscopic fluorescence imaging may improve noninvasive detection of precancerous lesions in the colon. Here, we report the first clinically compatible, wide-field-of-view, multi-color fluorescence endoscopy with a leached fiber bundle scope using a porcine model. A porcine colon model that resembles the human colon is used for the detection of surrogate tumors composed of multiple biocompatible fluorophores (FITC, ICG, and heavy metal-free quantum dots (hfQDs)). With an ex vivo porcine colon tumor model, molecular imaging with hfQDs conjugated with MMP14 antibody was achieved by spraying molecular probes on a mucosa layer that contains xenograft tumors. With an in vivo porcine colon embedded with surrogate tumors, target-to-background ratios of 3.36 ± 0.43, 2.70 ± 0.72, and 2.10 ± 0.13 were achieved for FITC, ICG, and hfQD probes, respectively. This promising endoscopic technology with molecular contrast shows the capacity to reveal hidden tumors and guide treatment strategy decisions. PMID:28270983

Disturbed Colonic Motility Contributes to Anorectal Symptoms and Dysfunction After Radiotherapy for Carcinoma of the Prostate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yeoh, Eric K., E-mail: eric.yeoh@health.sa.gov.a; Bartholomeusz, Dylan L.; Holloway, Richard H.

2010-11-01

Purpose: To evaluate the role of colonic motility in the pathogenesis of anorectal symptoms and dysfunction after radiotherapy (RT) for carcinoma of the prostate. Patients and Methods: Thirty-eight patients, median age 71 (range, 50-81) years with localized prostate carcinoma randomized to one of two radiation dose schedules underwent colonic transit scintigraphy and assessment of anorectal symptoms (questionnaire), anorectal function (manometry), and anal sphincteric morphology (endoanal ultrasound) before and at 1 month and 1 year after RT. Results: Whole and distal colonic transit increased 1 month after RT, with faster distal colonic transit only persisting at 1 year. Frequency and urgencymore » of defecation, fecal incontinence, and rectal bleeding increased 1 month after RT and persisted at 1 year. Basal anal pressures remained unchanged, but progressive reductions occurred in anal squeeze pressures and responses to increased intra-abdominal pressure. Rectal compliance decreased progressively in the patients, although no changes in anorectal sensory function ensued. Radiotherapy had no effect on the morphology of the internal and external anal sphincters. Distal colonic retention was weakly related to rectal compliance at 1 month, but both faster colonic transit and reduced rectal compliance were more frequent with increased fecal urgency. At 1 year, a weak inverse relationship existed between colonic half-clearance time and frequency of defecation, although both faster whole-colonic transit and reduced rectal compliance occurred more often with increased stool frequency. Conclusion: Colonic dysmotility contributes to anorectal dysfunction after RT for carcinoma of the prostate. This has implications for improving the management of anorectal radiation sequelae.« less

Purified rutin and rutin-rich asparagus attenuates disease severity and tissue damage following dextran sodium sulfate-induced colitis.

PubMed

Power, Krista A; Lu, Jenifer T; Monk, Jennifer M; Lepp, Dion; Wu, Wenqing; Zhang, Claire; Liu, Ronghua; Tsao, Rong; Robinson, Lindsay E; Wood, Geoffrey A; Wolyn, David J

2016-11-01

This study investigated the effects of cooked whole asparagus (ASP) versus its equivalent level of purified flavonoid glycoside, rutin (RUT), on dextran sodium sulfate (DSS)-induced colitis and subsequent colitis recovery in mice. C57BL/6 male mice were fed an AIN-93G basal diet (BD), or BD supplemented with 2% cooked ASP or 0.025% RUT for 2 wks prior to and during colitis induction with 2% DSS in water for 7 days, followed by 5 days colitis recovery. In colitic mice, both ASP and RUT upregulated mediators of improved barrier integrity and enhanced mucosal injury repair (e.g. Muc1, IL-22, Rho-A, Rac1, and Reg3γ), increased the proportion of mouse survival, and improved disease activity index. RUT had the greatest effect in attenuating DSS-induced colonic damage indicated by increased crypt and goblet cell restitution, reduced colonic myeloperoxidase, as well as attenuated DSS-induced microbial dysbiosis (reduced Enterobacteriaceae and Bacteroides, and increased unassigned Clostridales, Oscillospira, Lactobacillus, and Bifidobacterium). These findings demonstrate that dietary cooked ASP and its flavonoid glycoside, RUT, may be useful in attenuating colitis severity by modulating the colonic microenvironment resulting in reduced colonic inflammation, promotion of colonic mucosal injury repair, and attenuation of colitis-associated microbial dysbiosis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preparation and characterization of glycoprotein-resistant starch complex as a coating material for oral bioadhesive microparticles for colon-targeted polypeptide delivery.

PubMed

Situ, Wenbei; Li, Xiaoxi; Liu, Jia; Chen, Ling

2015-04-29

For effective oral delivery of polypeptide or protein and enhancement their oral bioavailability, a new resistant starch-glycoprotein complex bioadhesive carrier and an oral colon-targeted bioadhesive delivery microparticle system were developed. A glycoprotein, concanavalin A (Con A), was successfully conjugated to the molecules of resistant starch acetate (RSA), leading to the formation of resistant starch-glycoprotein complex. This Con A-conjugated RSA film as a coating material showed an excellent controlled-release property. In streptozotocin (STZ)-induced type II diabetic rats, the insulin-loaded microparticles coated with this Con A-conjugated RSA film exhibited good hypoglycemic response for keeping the plasma glucose level within the normal range for totally 44-52 h after oral administration with different insulin dosages. Oral glucose tolerance tests indicated that successive oral administration of these colon-targeted bioadhesive microparticles with insulin at a level of 50 IU/kg could achieve a hypoglycemic effect similar to that by injection of insulin at 35 IU/kg. Therefore, the potential of this new Con A-conjugated RSA film-coated microparticle system has been demonstrated to be capable of improving the oral bioavailability of bioactive proteins and peptides.

Dietary Nanosized Lactobacillus plantarum Enhances the Anticancer Effect of Kimchi on Azoxymethane and Dextran Sulfate Sodium-Induced Colon Cancer in C57BL/6J Mice.

PubMed

Lee, Hyun Ah; Kim, Hyunung; Lee, Kwang-Won; Park, Kun-Young

2016-01-01

This study was undertaken to evaluate enhancement of the chemopreventive properties of kimchi by dietary nanosized Lactobacillus (Lab.)plantarum (nLp) in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated colorectal cancer C57BL/6J mouse model. nLp is a dead, shrunken, processed form of Lab. Plantarum isolated from kimchi that is 0.5-1.0 µm in size. The results obtained showed that animals fed kimchi with nLp (K-nLp) had longer colons and lower colon weights/length ratios and developed fewer tumors than mice fed kimchi alone (K). In addition, K-nLp administration reduced levels of proinflammatory cytokine serum levels and mediated the mRNA and protein expressions of inflammatory, apoptotic, and cell-cycle markers to suppress inflammation and induce tumor-cell apoptosis and cell-cycle arrest. Moreover, it elevated natural killer-cell cytotoxicity. The study suggests adding nLp to kimchi could improve the suppressive effect of kimchi on AOM/DSS-induced colorectal cancer. These findings indicate nLp has potential use as a functional chemopreventive ingredient in the food industry.

Comorbidity and survival of Danish patients with colon and rectal cancer from 2000–2011: a population-based cohort study

PubMed Central

Ostenfeld, Eva Bjerre; Nørgaard, Mette; Thomsen, Reimar Wernich; Iversen, Lene Hjerrild; Jacobsen, Jacob Bonde; Søgaard, Mette

2013-01-01

Objective To evaluate recent trends in the prevalence and impact of comorbidity on colorectal cancer (CRC) survival in the Central Region of Denmark. Material and methods Using the Danish National Registry of Patients, we identified 5,777 and 2,964 patients with a primary colon or rectal cancer, respectively, from 2000 through 2011. We estimated survival according to Charlson Comorbidity Index scores and computed mortality rate ratios (MRRs) using Cox proportional hazard regression analysis, adjusting for age and sex. Results More than one-third of CRC patients had comorbidity at diagnosis. During the study period, 1-year survival increased substantially in colon cancer patients with Charlson score 0 (72% to 80%) and modestly for Charlson score 3+ patients (43% to 46%). Using colon cancer patients with Charlson score 0 as reference, adjusted 1-year MRRs in patients with Charlson score 3+ were 2.19 (95% confidence interval [CI]: 1.57–3.05) in 2000–2002 and 2.56 (95% CI: 1.96–3.35) in 2009–2011. One-year survival after rectal cancer improved from 81% to 87% in patients with Charlson score 0 and from 56% to 60% in Charlson score 3+. Corresponding MRRs in patients with Charlson 3+ were 2.21 (95% CI: 1.33–3.68) in 2000–2002 and 3.09 (95% CI: 1.91–5.00) in 2009–2011 using Charlson score 0 as reference. Five-year MRRs did not differ substantially from 1-year MRRs. Conclusion Comorbidity was common among CRC patients and was associated with poorer prognosis. We observed improved survival from 2000 to 2011 for all comorbidity levels, with least improvement for colon cancer patients with comorbid conditions. PMID:24227924

Dietary phytic acid modulates characteristics of the colonic luminal environment and reduces serum levels of proinflammatory cytokines in rats fed a high-fat diet.

PubMed

Okazaki, Yukako; Katayama, Tetsuyuki

2014-12-01

Dietary phytic acid (PA; myo-inositol [MI] hexaphosphate) is known to inhibit colon carcinogenesis in rodents. Dietary fiber, which is a negative risk factor of colon cancer, improves characteristics of the colonic environment, such as the content of organic acids and microflora. We hypothesized that dietary PA would improve the colonic luminal environment in rats fed a high-fat diet. To test this hypothesis, rats were fed diets containing 30% beef tallow with 2.04% sodium PA, 0.4% MI, or 1.02% sodium PA + 0.2% MI for 3 weeks. Compared with the control diet, the sodium PA diet up-regulated cecal organic acids, including acetate, propionate, and n-butyrate; this effect was especially prominent for cecal butyrate. The sodium PA + MI diet also significantly increased cecal butyrate, although this effect was less pronounced when compared with the sodium PA diet. The cecal ratio of Lactobacillales, cecal and fecal mucins (an index of intestinal barrier function), and fecal β-glucosidase activity were higher in rats fed the sodium PA diet than in those fed the control diet. The sodium PA, MI, and sodium PA + MI diets decreased levels of serum tumor necrosis factor α, which is a proinflammatory cytokine. Another proinflammatory cytokine, serum interleukin-6, was also down-regulated by the sodium PA and sodium PA + MI diets. These data showed that PA may improve the composition of cecal organic acids, microflora, and mucins, and it may decrease the levels of serum proinflammatory cytokines in rats fed a high-fat, mineral-sufficient diet. Copyright © 2014 Elsevier Inc. All rights reserved.

Optical Measurement of Cell Colonization Patterns on Individual Suspended Sediment Aggregates

NASA Astrophysics Data System (ADS)

Nguyen, Thu Ha; Tang, Fiona H. M.; Maggi, Federico

2017-10-01

Microbial processes can make substantial differences to the way in which particles settle in aquatic environments. A novel method (OMCEC, optical measurement of cell colonization) is introduced to systematically map the biological spatial distribution over individual suspended sediment aggregates settling through a water column. OMCEC was used to investigate (1) whether a carbon source concentration has an impact on cell colonization, (2) how cells colonize minerals, and (3) if a correlation between colonization patterns and aggregate geometry exists. Incubations of Saccharomyces cerevisiae and stained montmorillonite at four sucrose concentrations were tested in a settling column equipped with a full-color microparticle image velocimetry system. The acquired high-resolution images were processed to map the cell distribution on aggregates based on emission spectra separation. The likelihood of cells colonizing minerals increased with increasing sucrose concentration. Colonization patterns were classified into (i) scattered, (ii) well touched, and (iii) poorly touched, with the second being predominant. Cell clusters in well-touched patterns were found to have lower capacity dimension than those in other patterns, while the capacity dimension of the corresponding aggregates was relatively high. A strong correlation of colonization patterns with aggregate biomass fraction and properties suggests dynamic colonization mechanisms from cell attachment to minerals, to joining of isolated cell clusters, and finally cell growth over the entire aggregate. This paper introduces a widely applicable method for analyses of microbial-affected sediment dynamics and highlights the microbial control on aggregate geometry, which can improve the prediction of large-scale morphodynamics processes.

The importance of appropriate initial bacterial colonization of the intestine in newborn, child and adult health

PubMed Central

Walker, W. Allan

2017-01-01

The fetus does not reside in a sterile intrauterine environment and is exposed to commensal bacteria from the maternal gut/blood stream which crosses the placenta and enters the amniotic fluid. This intestinal exposure to colonizing bacteria continues at birth and during the first year of life and has a profound influence on lifelong health. Why is this important? Intestinal crosstalk with colonizing bacteria in the developing intestine affects the infant’s adaptation to extrauterine life (immune homeostasis) and provides protection against disease expression (allergy, autoimmune disease, obesity, etc.) later in life. Colonizing intestinal bacteria are critical to the normal development of host defense. Disrupted colonization (dysbiosis) due to maternal dysbiosis, cesarean section delivery, use of perinatal antibiotics or premature delivery may adversely affect gut development of host defense and predispose to inflammation rather than homeostasis leading to increased susceptibility to disease later in life. Babies born by cesarean section have a higher incidence of allergy, type 1 diabetes and obesity. Infants given repeated antibiotic regimens during the first year of life are more likely to have asthma as adolescents. This research breakthrough helps to explain the shift in disease paradigms from infections to immune mediated in children from developed countries. This review will develop this research breakthrough. PMID:28426649

Effects of Sulfamethoxazole-Trimethoprim on Airway Colonization with Pneumocystis jirovecii.

PubMed

Kushima, Hisako; Ishii, Hiroshi; Tokimatsu, Issei; Umeki, Kenji; Sato, Takako; Kadota, Jun-Ichi

2016-05-20

Reactivation of latent infection is considered to be the main mechanism underlying the development of Pneumocystis pneumonia in immunosuppressed patients. We retrospectively assessed the effects of prophylactic administration of sulfamethoxazole-trimethoprim on the development of P. pneumonia and airway colonization with P. jirovecii in patients undergoing examinations to diagnose or rule out P. pneumonia. Polymerase chain reaction was performed to detect P. jirovecii in bronchoalveolar lavage fluid or sputum of 60 consecutive patients between 2004 and 2012. No patients who received the prophylactic administration of sulfamethoxazole-trimethoprim (n = 10) developed P. pneumonia or demonstrated airway colonization with P. jirovecii, and none of the patients who developed P. pneumonia (n = 11) or showed colonization (n = 9) had received prophylactic treatment. Furthermore, 20 (40%) of 50 patients without prophylactic treatment showed positive results on the P. jirovecii DNA polymerase chain reaction, but all 10 patients who had prophylactic treatment showed negative results (Fisher's exact test, P = 0.02). Therefore, the prophylactic administration of sulfamethoxazole-trimethoprim has potential to be effective in preventing P. pneumonia as well as eliminating airway colonization with P. jirovecii. Further studies targeting large cohorts of patients with a variety of underlying diseases are required to develop recommendations regarding the prophylactic administration of sulfamethoxazole-trimethoprim.

The significance of Campylobacter jejuni infection in poultry: a review.

PubMed

Shane, S M

1992-01-01

Campylobacter is a significant cause of enterocolitis in consumers of undercooked poultry meat. Campylobacter jejuni is the most significant of the three thermophilic Campylobacter species, and is responsible for intestinal colonization in poultry and food-borne enteritis in humans. Generally, C. jejuni is apathogenic in poultry, although newly hatched chicks and turkeys may develop a transient diarrhoea following infection. Modern intensive poultry production favours the introduction of infection into commercial growing units, resulting in intestinal colonization during the second to fourth weeks inclusive. Routes of infection include contaminated fomites, infected water supply, rodents, insects, and free-living birds. Vertical transmission is considered unlikely. Contamination of poultry meat is enhanced by deficiencies in transport and processing of broilers and turkeys. Scalding, defeathering and evisceration represent the significant points of cross-contamination during processing. Epidemiological correlation has been established between consumption of contaminated chicken and outbreaks of human campylobacteriosis. Amelioration of infection by application of improved standards of hygiene and decontamination is possible in the context of commercial poultry production. Improvement in washing of carcasses, and the application of chemical disinfectants and gamma irradiation have the potential to reduce the prevalence of C. jejuni contamination in poultry meat. These innovations, together with improved storage and handling of meat products, will reduce the risk of campylobacteriosis to consumers.

Carrying Capacity and Colonization Dynamics of Curvibacter in the Hydra Host Habitat

PubMed Central

Wein, Tanita; Dagan, Tal; Fraune, Sebastian; Bosch, Thomas C. G.; Reusch, Thorsten B. H.; Hülter, Nils F.

2018-01-01

Most eukaryotic species are colonized by a microbial community – the microbiota – that is acquired during early life stages and is critical to host development and health. Much research has focused on the microbiota biodiversity during the host life, however, empirical data on the basic ecological principles that govern microbiota assembly is lacking. Here we quantify the contribution of colonizer order, arrival time and colonization history to microbiota assembly on a host. We established the freshwater polyp Hydra vulgaris and its dominant colonizer Curvibacter as a model system that enables the visualization and quantification of colonizer population size at the single cell resolution, in vivo, in real time. We estimate the carrying capacity of a single Hydra polyp as 2 × 105 Curvibacter cells, which is robust among individuals and time. Colonization experiments reveal a clear priority effect of first colonizers that depends on arrival time and colonization history. First arriving colonizers achieve a numerical advantage over secondary colonizers within a short time lag of 24 h. Furthermore, colonizers primed for the Hydra habitat achieve a numerical advantage in the absence of a time lag. These results follow the theoretical expectations for any bacterial habitat with a finite carrying capacity. Thus, Hydra colonization and succession processes are largely determined by the habitat occupancy over time and Curvibacter colonization history. Our experiments provide empirical data on the basic steps of host-associated microbiota establishment – the colonization stage. The presented approach supplies a framework for studying habitat characteristics and colonization dynamics within the host–microbe setting. PMID:29593687

Staphylococcus aureus Colonization: Modulation of Host Immune Response and Impact on Human Vaccine Design

PubMed Central

Brown, Aisling F.; Leech, John M.; Rogers, Thomas R.; McLoughlin, Rachel M.

2014-01-01

In apparent contrast to its invasive potential Staphylococcus aureus colonizes the anterior nares of 20–80% of the human population. The relationship between host and microbe appears particularly individualized and colonization status seems somehow predetermined. After decolonization, persistent carriers often become re-colonized with their prior S. aureus strain, whereas non-carriers resist experimental colonization. Efforts to identify factors facilitating colonization have thus far largely focused on the microorganism rather than on the human host. The host responds to S. aureus nasal colonization via local expression of anti-microbial peptides, lipids, and cytokines. Interplay with the co-existing microbiota also influences colonization and immune regulation. Transient or persistent S. aureus colonization induces specific systemic immune responses. Humoral responses are the most studied of these and little is known of cellular responses induced by colonization. Intriguingly, colonized patients who develop bacteremia may have a lower S. aureus-attributable mortality than their non-colonized counterparts. This could imply a staphylococcal-specific immune “priming” or immunomodulation occurring as a consequence of colonization and impacting on the outcome of infection. This has yet to be fully explored. An effective vaccine remains elusive. Anti-S. aureus vaccine strategies may need to drive both humoral and cellular immune responses to confer efficient protection. Understanding the influence of colonization on adaptive response is essential to intelligent vaccine design, and may determine the efficacy of vaccine-mediated immunity. Clinical trials should consider colonization status and the resulting impact of this on individual patient responses. We urgently need an increased appreciation of colonization and its modulation of host immunity. PMID:24409186

Constitutive formulations for the mechanical investigation of colonic tissues.

PubMed

Carniel, Emanuele Luigi; Gramigna, Vera; Fontanella, Chiara Giulia; Stefanini, Cesare; Natali, Arturo N

2014-05-01

A constitutive framework is provided for the characterization of the mechanical behavior of colonic tissues, as a fundamental tool for the development of numerical models of the colonic structures. The constitutive analysis is performed by a multidisciplinary approach that requires the cooperation between experimental and computational competences. The preliminary investigation pertains to the review of the tissues histology. The complex structural configuration of the tissues and the specific distributions of fibrous elements entail the nonlinear mechanical behavior and the anisotropic response. The identification of the mechanical properties requires to perform mechanical tests according to different loading situations, as different loading directions. Because of the typical functionality of colon structures, the tissues mechanics is investigated by tensile tests, which are performed on taenia coli and haustra specimens from fresh pig colons. Accounting for the histological investigation and the results from the mechanical tests, a specific hyperelastic framework is provided within the theory of fiber-reinforced composite materials. Preliminary analytical formulations are defined to identify the constitutive parameters by the inverse analysis of the experimental tests. Finite element models of the specimens are developed accounting for the actual configuration of the colon structures to verify the quality of the results. The good agreement between experimental and numerical model results suggests the reliability of the constitutive formulations and parameters. Finally, the developed constitutive analysis makes it possible to identify the mechanical behavior and properties of the different colonic tissues. Copyright © 2013 Wiley Periodicals, Inc.

Risk of vancomycin-resistant enterococci bloodstream infection among patients colonized with vancomycin-resistant enterococci.

PubMed

Kara, Ahu; Devrim, İlker; Bayram, Nuri; Katipoğlu, Nagehan; Kıran, Ezgi; Oruç, Yeliz; Demiray, Nevbahar; Apa, Hurşit; Gülfidan, Gamze

2015-01-01

Vancomycin-resistant enterococci colonization has been reported to increase the risk of developing infections, including bloodstream infections. In this study, we aimed to share our experience with the vancomycin-resistant enterococci bloodstream infections following gastrointestinal vancomycin-resistant enterococci colonization in pediatric population during a period of 18 months. A retrospective cohort of children admitted to a 400-bed tertiary teaching hospital in Izmir, Turkey whose vancomycin-resistant enterococci colonization was newly detected during routine surveillances for gastrointestinal vancomycin-resistant enterococci colonization during the period of January 2009 and December 2012 were included in this study. All vancomycin-resistant enterococci isolates found within 18 months after initial detection were evaluated for evidence of infection. Two hundred and sixteen patients with vancomycin-resistant enterococci were included in the study. Vancomycin-resistant enterococci colonization was detected in 136 patients (62.3%) while they were hospitalized at intensive care units; while the remaining majority (33.0%) were hospitalized at hematology-oncology department. Vancomycin-resistant enterococci bacteremia was present only in three (1.55%) patients. All these patients were immunosuppressed due to human immunodeficiency virus (one patient) and intensive chemotherapy (two patients). In conclusion, our study found that 1.55% of vancomycin-resistant enterococci-colonized children had developed vancomycin-resistant enterococci bloodstream infection among the pediatric intensive care unit and hematology/oncology patients; according to our findings, we suggest that immunosupression is the key point for developing vancomycin-resistant enterococci bloodstream infections. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

The effect of a multidisciplinary regional educational programme on the quality of colon cancer resection.

PubMed

Sheehan-Dare, G E; Marks, K M; Tinkler-Hundal, E; Ingeholm, P; Bertelsen, C A; Quirke, P; West, N P

2018-02-01

Mesocolic plane surgery with central vascular ligation produces an oncologically superior specimen following colon cancer resection and appears to be related to optimal outcomes. We aimed to assess whether a regional educational programme in optimal mesocolic surgery led to an improvement in the quality of specimens. Following an educational programme in the Capital and Zealand areas of Denmark, 686 cases of primary colon cancer resected across six hospitals were assessed by grading the plane of surgery and undertaking tissue morphometry. These were compared to 263 specimens resected prior to the educational programme. Across the region, the mesocolic plane rate improved from 58% to 77% (P < 0.001). One hospital had previously implemented optimal surgery as standard prior to the educational programme and continued to produce a high rate of mesocolic plane specimens (68%) with a greater distance between the tumour and the high tie (median for all fresh cases: 113 vs 82 mm) and lymph node yield (33 vs 18) compared to the other hospitals. Three of the other hospitals showed a significant improvement in the plane of surgical resection. A multidisciplinary regional educational programme in optimal mesocolic surgery improved the oncological quality of colon cancer specimens as assessed by mesocolic planes; however, there was no significant effect on the amount of tissue resected centrally. Surgeons who attempt central vascular ligation continue to produce more radical specimens suggesting that such educational programmes alone are not sufficient to increase the amount of tissue resected around the tumour. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

Active Ingredients of Hange-shashin-to, Baicalelin and 6-Gingerol, Inhibit 5-Fluorouracil-Induced Upregulation of CXCL1 in the Colon to Attenuate Diarrhea Development.

PubMed

Sakai, Hiroyasu; Tabata, Shoko; Kimura, Minami; Yabe, Saori; Isa, Yosuke; Kai, Yuki; Sato, Fumiaki; Yumoto, Tetsuro; Miyano, Kanako; Narita, Minoru; Uezono, Yasuhito

2017-01-01

5-Fluorouracil (5-FU) is widely used as an anti cancer drug and is known to cause severe diarrhea. Recently we suggested that levels of chemokine (C-X-C motif) ligand 1 (CXCL1) and neutrophil recruitment in the colonic mucosa were drastically increased by the 5-FU administration in mice. Hange-shashin-to (HST) is prescribed in Japan for treat gastritis, stomatitis, and inflammatory diarrhea. We therefore examined the effects of HST and its active ingredients on 5-FU-induced CXCL1 upregulation in cultured colon tissue, and also examined the effects of HST on 5-FU-induced diarrhea development in the mouse. The distal colon isolated from the mouse was incubated with 5-FU and HST. Mice were given 5-FU (50 mg/kg, intraperitoneally (i.p.)) daily for four days. HST (300 mg/kg, per os (p.o.)) was administered 30 min before mice received 5-FU. mRNA levels of CXCL1 in the colon were examined using quantitative RT-PCR. 5-FU enhanced CXCL1 mRNA in the colon but the effect by 5-FU was markedly suppressed by application of HST and its active ingredients, baicalein and 6-gingerol. Nuclear factor kappa B (NF-κB) was activated by 5-FU treatment in cultured colon tissue, which was also suppressed by HST and the combination of baicalein and 6-gingerol. Furthermore, HST reduced 5-FU-induced diarrhea development. Under such experimental condition, CXCL1 gene, protein levels of neutrophil elastase and myeloperoxidase upregulation induced by 5-FU in the colon was attenuated by HST. These findings suggest that HST, especially baicalein and 6-gingerol, prevent the development of neutrophil recruitment and diarrhea by the inhibition of NF-κB activity.

Laboratory colonization of the blow flies, Chrysomya megacephala (Diptera: Calliphoridae) and Chrysomya rufifacies (Diptera: Calliphoridae)

USDA-ARS?s Scientific Manuscript database

Chrysomya rufifacies is a blow fly commonly found in corpses at crime scene investigations. This study was designed to develop laboratory colonization methods for Ch. rufifacies and utilize Chrysomya megacephala as its larval food source. Both fly species were collected in the wild and easily colon...

Dietary folate does not significantly affect the intestinal microbiome, inflammation or tumorigenesis in azoxymethane-dextran sodium sulphate-treated mice.

PubMed

MacFarlane, Amanda J; Behan, Nathalie A; Matias, Fernando M G; Green, Judy; Caldwell, Don; Brooks, Stephen P J

2013-02-28

Inflammatory bowel disease (IBD) is a risk factor for the development of colon cancer. Environmental factors including diet and the microflora influence disease outcome. Folate and homocysteine have been associated with IBD-mediated colon cancer but their roles remain unclear. We used a model of chemically induced ulcerative colitis (dextran sodium sulphate (DSS)) with or without the colon carcinogen azoxymethane (AOM) to determine the impact of dietary folic acid (FA) on colonic microflora and the development of colon tumours. Male mice (n 15 per group) were fed a FA-deficient (0 mg/kg), control (2 mg/kg) or FA-supplemented (8 mg/kg) diet for 12 weeks. Folate status was dependent on the diet (P< 0·001) and colitis-induced treatment (P= 0·04) such that mice with colitis had lower circulating folate. FA had a minimal effect on tumour initiation, growth and progression, although FA-containing diets tended to be associated with a higher tumour prevalence in DSS-treated mice (7-20 v. 0%, P= 0·08) and the development of more tumours in the distal colon of AOM-treated mice (13-83% increase, P= 0·09). Folate deficiency was associated with hyperhomocysteinaemia (P< 0·001) but homocysteine negatively correlated with tumour number (r - 0·58, P= 0·02) and load (r - 0·57, P= 0·02). FA had no effect on the intestinal microflora. The present data indicate that FA intake has no or little effect on IBD or IBD-mediated colon cancer in this model and that hyperhomocysteinaemia is a biomarker of dietary status and malabsorption rather than a cause of IBD-mediated colon cancer.

Mediation of acetylcholine and substance P induced contractions by myosin light chain phosphorylation in feline colonic smooth muscle.

PubMed

Washabau, Robert J; Holt, David E; Brockman, Daniel J

2002-05-01

To determine the role of myosin light chain phosphorylation in feline colonic smooth muscle contraction. Colonic tissue was obtained from eight 12- to 24-month-old cats. Colonic longitudinal smooth muscle strips were attached to isometric force transducers for measurements of isometric stress. Myosin light chain phosphorylation was determined by isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Stress and phosphorylation were determined following stimulation with ACh or SP, in the absence or presence of a calmodulin antagonist (W-7; 0.1 to 1.0 mM), myosin light chain kinase inhibitor (ML-9; 1 to 10 microM), or extracellular calcium free solutions. Unstimulated longitudinal colonic smooth muscle contained low amounts (6.9+/-3.2%) of phosphorylated myosin light chain. Phosphorylation of the myosin light chains was dose and time dependent with maximal values of 58.5% at 30 seconds of stimulation with 100 microM Ach and 60.2% at 45 seconds of stimulation with 100 nM SP Active isometric stress development closely paralleled phosphorylation of the myosin light chains in ACh- or SP-stimulated muscle. W-7 and ML-9 dose dependently inhibited myosin light chain phosphorylation and isometric stress development associated with ACh or SP stimulation. Removal of extracellular calcium inhibited myosin light chain phosphorylation and isometric stress development in ACh-stimulated smooth muscle. Feline longitudinal colonic smooth muscle contraction is calcium-, calmodulin-, and myosin light chain kinase-dependent. Myosin light chain phosphorylation is necessary for the initiation of contraction in feline longitudinal colonic smooth muscle. These findings may prove useful in determining the biochemical and molecular defects that accompany feline colonic motility disorders.

THE PREVALENCE OF COLONIC POLYPS IN PATIENTS WITH ACROMEGALY: A CASE-CONTROL, NESTED IN A COHORT COLONOSCOPIC STUDY.

PubMed

Gonzalez, Baldomero; Vargas, Guadalupe; Mendoza, Victoria; Nava, Mariana; Rojas, Moisés; Mercado, Moisés

2017-05-01

Acromegaly is associated with an increased risk of colonic polyps. The magnitude of such risk is controversial, and the characteristics that distinguish patients who develop polyps from those who do not are not well established. This study was performed to determine the prevalence of colonic polyps upon the diagnosis of acromegaly and to compare the clinical and biochemical features of patients with and without polyps. Out of 165 patients who underwent a full colonoscopy upon diagnosis of acromegaly, 53 were found to harbor colonic lesions (cases), whereas the remaining 112 were used as controls. Demographic, clinical, and biochemical characteristics were compared between the 2 groups. The prevalence of colonic polyps was 32%, with an estimated relative risk of 6.21 (95% confidence interval [CI] 4.08-9.48). Adenomatous and nonadenomatous polyps were found in 22 and 31 patients, respectively. The most common location was the descending colon. Compared to patients without polyps, subjects with polyps were somewhat older and had significantly higher insulin-like growth factor-1 (IGF-1) levels and a higher prevalence of diabetes. Upon multivariate analysis, only IGF-1 level at diagnosis remained significantly associated with colonic polyps in general and with hyperplastic polyps in particular. Acromegaly is associated with an elevated risk of developing colonic polyps, particularly, distally located hyperplastic lesions. Except for a higher IGF-1 level at diagnosis, no distinctive clinical or biochemical features can be found among those who develop polyps compared to those who do not. CI = confidence interval GH = growth hormone IGF-1 = insulin-like growth factor 1 IQR = inter-quartile range RR = relative risk ULN = upper limit of normal.

Simultaneous development of ulcerative colitis in the colon and sigmoid neovagina.

PubMed

Webster, Toni; Appelbaum, Heather; Weinstein, Toba A; Rosen, Nelson; Mitchell, Ian; Levine, Jeremiah J

2013-03-01

Vaginoplasty using sigmoid colon is a common technique for creation of a neovagina. However, special consideration must be given to potential long term consequences of using a colonic conduit for vaginal replacement. We report on the youngest described case in which a patient developed ulcerative colitis refractory to medical therapy with simultaneous involvement of a sigmoid neovagina requiring total proctocolectomy and neovaginectomy. A 17 year old XY female with a history of gonadal dysgenesis and sigmoid graft vaginoplasty presented with a history of bloody, mucoid vaginal discharge, abdominal pain, bloody diarrhea and weight loss. Colonic and neovaginal biopsies demonstrated active colitis with diffuse ulcerations, consistent with ulcerative colitis. Despite aggressive immunosuppressive treatment she had persistent neovaginal and colonic bleeding requiring multiple transfusions, subtotal colectomy and ultimately completion proctectomy and neovaginectomy. It is imperative to recognize that colectomy alone may be an inadequate surgical intervention in patients with ulcerative colitis and a colonic neovaginal graft and that a concomitant neovaginectomy may be integral in providing appropriate treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

Analysis of 162 colon injuries in patients with penetrating abdominal trauma: concomitant stomach injury results in a higher rate of infection.

PubMed

O'Neill, Patricia A; Kirton, Orlando C; Dresner, Lisa S; Tortella, Bartholomew; Kestner, Mark M

2004-02-01

Fecal contamination from colon injury has been thought to be the most significant factor for the development of surgical site infection (SSI) after trauma. However, there are increasing data to suggest that other factors may play a role in the development of postinjury infection in patients after colon injury. The purpose of this study was to determine the impact of gastric wounding on the development of SSI and nonsurgical site infection (NSSI) in patients with colon injury. Post hoc analysis was performed on data prospectively collected for 317 patients presenting with penetrating hollow viscus injury. One hundred sixty-two patients with colon injury were subdivided into one of three groups: patients with isolated colon wounds (C), patients with colon and stomach wounds with or without other organ injury (C+S), and patients with colon and other organ injury but no stomach injury (C-S) and assessed for the development of SSI and NSSI. Infection rates were also determined for patients who sustained isolated gastric injury (S) and gastric injury in combination with other injuries other than colon (S-C). Penetrating Abdominal Trauma Index, operative times, and transfusion were assessed. Discrete variables were analyzed by Cochran-Mantel-Haenszel chi2 test and Fisher's exact test. Risk factor analysis was performed by multivariate logistic regression. C+S patients had a higher rate of SSI infection (31%) than C patients (3.6%) (p=0.008) and C-S patients (13%) (p=0.021). Similarly, the incidence of NSSI was also significantly greater in the C+S group (37%) compared with the C patients (7.5%) (p=0.07) and the C-S patients (17%) (p=0.019). There was no difference in the rate of SSI or NSSI between the C and C-S groups (p=0.3 and p=0.24, respectively). The rate of SSI was significantly greater in the C+S patients when compared with the S-C patients (31% vs. 10%, p=0.008), but there was no statistical difference in the rate of NSSI in the C+S group and the S-C group (37% vs. 24%, p=0.15). The addition of a gastric injury to a colon injury has a synergistic effect on the rate of postoperative infection.

Gene Expression Profiling of Bronchoalveolar Lavage Cells During Aspergillus Colonization of the Lung Allograft.

PubMed

Weigt, S Samuel; Wang, Xiaoyan; Palchevskiy, Vyacheslav; Patel, Naman; Derhovanessian, Ariss; Shino, Michael Y; Sayah, David M; Lynch, Joseph P; Saggar, Rajan; Ross, David J; Kubak, Bernie M; Ardehali, Abbas; Palmer, Scott; Husain, Shahid; Belperio, John A

2018-06-01

Aspergillus colonization after lung transplant is associated with an increased risk of chronic lung allograft dysfunction (CLAD). We hypothesized that gene expression during Aspergillus colonization could provide clues to CLAD pathogenesis. We examined transcriptional profiles in 3- or 6-month surveillance bronchoalveolar lavage fluid cell pellets from recipients with Aspergillus fumigatus colonization (n = 12) and without colonization (n = 10). Among the Aspergillus colonized, we also explored profiles in those who developed CLAD (n = 6) or remained CLAD-free (n = 6). Transcription profiles were assayed with the HG-U133 Plus 2.0 microarray (Affymetrix). Differential gene expression was based on an absolute fold difference of 2.0 or greater and unadjusted P value less than 0.05. We used NIH Database for Annotation, Visualization and Integrated Discovery for functional analyses, with false discovery rates less than 5% considered significant. Aspergillus colonization was associated with differential expression of 489 probe sets, representing 404 unique genes. "Defense response" genes and genes in the "cytokine-cytokine receptor" Kyoto Encyclopedia of Genes and Genomes pathway were notably enriched in this list. Among Aspergillus colonized patients, CLAD development was associated with differential expression of 69 probe sets, representing 64 unique genes. This list was enriched for genes involved in "immune response" and "response to wounding", among others. Notably, both chitinase 3-like-1 and chitotriosidase were associated with progression to CLAD. Aspergillus colonization is associated with gene expression profiles related to defense responses including cytokine signaling. Epithelial wounding, as well as the innate immune response to chitin that is present in the fungal cell wall, may be key in the link between Aspergillus colonization and CLAD.

Development and validation of a highly sensitive urine-based test to identify patients with colonic adenomatous polyps.

PubMed

Wang, Haili; Tso, Victor; Wong, Clarence; Sadowski, Dan; Fedorak, Richard N

2014-03-20

Adenomatous polyps are precursors of colorectal cancer; their detection and removal is the goal of colon cancer screening programs. However, fecal-based methods identify patients with adenomatous polyps with low levels of sensitivity. The aim or this study was to develop a highly accurate, prototypic, proof-of-concept, spot urine-based diagnostic test using metabolomic technology to distinguish persons with adenomatous polyps from those without polyps. Prospective urine and stool samples were collected from 876 participants undergoing colonoscopy examination in a colon cancer screening program, from April 2008 to October 2009 at the University of Alberta. Colonoscopy reference standard identified 633 participants with no colonic polyps and 243 with colonic adenomatous polyps. One-dimensional nuclear magnetic resonance spectra of urine metabolites were analyzed to define a diagnostic metabolomic profile for colonic adenomas. A urine metabolomic diagnostic test for colonic adenomatous polyps was established using 67% of the samples (un-blinded training set) and validated using the other 33% of the samples (blinded testing set). The urine metabolomic diagnostic test's specificity and sensitivity were compared with those of fecal-based tests. Using a two-component, orthogonal, partial least-squares model of the metabolomic profile, the un-blinded training set identified patients with colonic adenomatous polyps with 88.9% sensitivity and 50.2% specificity. Validation using the blinded testing set confirmed sensitivity and specificity values of 82.7% and 51.2%, respectively. Sensitivities of fecal-based tests to identify colonic adenomas ranged from 2.5 to 11.9%. We describe a proof-of-concept spot urine-based metabolomic diagnostic test that identifies patients with colonic adenomatous polyps with a greater level of sensitivity (83%) than fecal-based tests.

Prebiotic effect of fructooligosaccharide in the simulator of the human intestinal microbial ecosystem (SHIME® model).

PubMed

Sivieri, Katia; Morales, Martha L Villarreal; Saad, Susana M I; Adorno, Maria A Tallarico; Sakamoto, Isabel Kimiko; Rossi, Elizeu A

2014-08-01

Maintaining "gut health" is a goal for scientists throughout the world. Therefore, microbiota management models for testing probiotics, prebiotics, and synbiotics have been developed. The SHIME(®) model was used to study the effect of fructooligosaccharide (FOS) on the fermentation pattern of the colon microbiota. Initially, an inoculum prepared from human feces was introduced into the reactor vessels and stabilized over 2 weeks using a culture medium. This stabilization period was followed by a 2-week control period during which the microbiota was monitored. The microbiota was then subjected to a 4-week treatment period by adding 5 g/day-1 FOS to vessel one (the "stomach" compartment). Plate counts, Denaturing Gradient Gel Electrophoresis (DGGE), short-chain fatty acid (SCFA), and ammonium analyses were used to observe the influence of FOS treatment in simulated colon compartments. A significant increase (P<.01) in the Lactobacillus spp. and Bifidobacterium spp. populations was observed during the treatment period. The DGGE obtained showed the overall microbial community was changed in the ascending colon compartment of the SHIME reactor. FOS induced increase of the SCFA concentration (P<.05) during the treatment period, mainly due to significant increased levels of acetic and butyric acids. However, ammonium concentrations increased during the same period (P<.01). This study indicates the usefulness of in vitro methods that simulate the colon region as part of research towards the improvement of human health.

Jussara (Euterpe edulis Mart.) Supplementation during Pregnancy and Lactation Modulates the Gene and Protein Expression of Inflammation Biomarkers Induced by trans-Fatty Acids in the Colon of Offspring

PubMed Central

Almeida Morais, Carina; Oyama, Lila Missae; de Oliveira, Juliana Lopez; Carvalho Garcia, Márcia; de Rosso, Veridiana Vera; Sousa Mendes Amigo, Laís; do Nascimento, Claudia Maria Oller; Pisani, Luciana Pellegrini

2014-01-01

Maternal intake of trans-fatty acids (TFAs) in the perinatal period triggers a proinflammatory state in offspring. Anthocyanins contained in fruit are promising modulators of inflammation. This study investigated the effect of Jussara supplementation in the maternal diet on the proinflammatory state of the colon in offspring exposed to perinatal TFAs. On the first day of pregnancy rats were divided into four groups: control diet (C), control diet with 0.5% Jussara supplementation (CJ), diet enriched with hydrogenated vegetable fat, rich in TFAs (T), or T diet supplemented with 0.5% Jussara (TJ) during pregnancy and lactation. We showed that Jussara supplementation in maternal diet (CJ and TJ groups) reduced carcass lipid/protein ratios, serum lipids, glucose, IL-6, TNF-α, gene expression of IL-6R, TNF-αR (P < 0.05), TLR-4 (P < 0.01), and increase Lactobacillus spp. (P < 0.05) in the colon of offspring compared to the T group. The IL-10 (P = 0.035) and IL-10/TNF-α ratio (P < 0.01) was higher in the CJ group than in the T group. The 0.5% Jussara supplementation reverses the adverse effects of perinatal TFAs, improving lipid profiles, glucose levels, body composition, and gut microbiota and reducing low-grade inflammation in the colon of 21-day-old offspring, and could contribute to reducing chronic disease development. PMID:25276060

Colonization of a newly constructed urban wetland by mosquitoes in England: implications for nuisance and vector species.

PubMed

Medlock, Jolyon M; Vaux, Alexander G C

2014-12-01

Urban wetlands are being created in the UK as part of sustainable urban drainage strategies, to create wetland habitats lost during development, to provide a habitat for protected species, and to increase the public's access to 'blue-space' for the improvement of health and well-being. Sewage treatment reedbeds are also being incorporated into newly constructed wetlands to offer an alternative approach to dealing with sewage. This field study aims to provide the first UK evidence of how such newly constructed aquatic habitats are colonized by mosquitoes. A number of new aquatic habitats were surveyed for immature mosquitoes every fortnight over the first two years following wetland construction. The majority of mosquitoes collected were Culex sp. and were significantly associated with the sewage treatment reedbed system, particularly following storm events and sewage inflow. Other more natural aquatic habitats that were subject to cycles of drying and re-wetting contributed the majority of the remaining mosquitoes colonizing. Colonization of permanent habitats was slow, particularly where fluctuations in water levels inhibited emergent vegetation growth. It is recommended that during the planning process for newly constructed wetlands consideration is given on a case-by-case basis to the impact of mosquitoes, either as a cause of nuisance or as potential vectors. Although ornithophagic Culex dominated in this wetland, their potential role as enzootic West Nile virus vectors should not be overlooked. © 2014 The Society for Vector Ecology.

Crohn’s Disease Successfully Treated With Infliximab in a Patient Receiving Hemodialysis: Case Report and Review of the Literature

PubMed Central

Chiba, Mitsuro; Tsuda, Satoko; Tsuji, Tsuyotoshi; Nakane, Kunio; Komatsu, Masafumi; Miura, Yoshiko; Ishida, Toshiya; Shibahara, Toru; Nishimoto, Tadashi

2014-01-01

Abstract There is limited information in the use of antitumor necrosis factor α, infliximab, in patients on hemodialysis. In Crohn’s disease (CD), only 3 cases are reported. A 76-year-old man on hemodialysis for renal failure caused by immunoglobulin A nephropathy developed diarrhea and abdominal pains. A marked edema was observed in the pretibia and ankle. An increase of C-reactive protein (CRP) and erythrocyte sedimentation rate, hypoalbuminemia, hypocholesterolemia, and moderate anemia was found. Ultrasonography and computed tomography (CT) found wall thickness in the left colon. Sigmoidoscopy revealed multiple ulcers in the sigmoid colon and noncaseating epithelioid granuloma was found in the biopsy specimen. Barium enema study exhibited collar button signs and longitudinal ulcers in the left colon. A severe form of CD was diagnosed. Metronidazole seemed to decrease CRP but was ineffective in ameliorating diarrhea. Infliximab rather than steroid hormone was chosen for the treatment. Standard induction therapy with infliximab was initiated. Symptoms rapidly improved then disappeared. CD activity index decreased from 747 to a remission level of 134 after 2 infusions of infliximab. Scheduled maintenance infliximab therapy was administered after the induction therapy. Ultrasonography and CT showed a disappearance of the wall thickness of the colon. Adverse reactions were not observed. Infliximab was effective and safe in a patient with CD on hemodialysis. Our case has added additional literature in accordance with previous reports supporting infliximab as effective and safe in patients on hemodialysis. PMID:25101989

Addition of senna improves quality of colonoscopy preparation with magnesium citrate.

PubMed

Vradelis, Stergios; Kalaitzakis, Evangelos; Sharifi, Yalda; Buchel, Otto; Keshav, Satish; Chapman, Roger W; Braden, Barbara

2009-04-14

To prospectively investigate the effectiveness and patient's tolerance of two low-cost bowel cleansing preparation protocols based on magnesium citrate only or the combination of magnesium citrate and senna. A total of 342 patients who were referred for colonoscopy underwent a colon cleansing protocol with magnesium citrate alone (n = 160) or magnesium citrate and senna granules (n = 182). The colonoscopist rated the overall efficacy of colon cleansing using an established score on a 4-point scale. Patients were questioned before undergoing colonoscopy for side effects and symptoms during bowel preparation. The percentage of procedures rescheduled because of insufficient colon cleansing was 7% in the magnesium citrate group and 4% in the magnesium citrate/senna group (P = 0.44). Adequate visualization of the colonic mucosa was rated superior under the citramag/senna regimen (P = 0.004). Both regimens were well tolerated, and did not significantly differ in the occurrence of nausea, bloating or headache. However, abdominal cramps were observed more often under the senna protocol (29.2%) compared to the magnesium citrate only protocol (9.9%, P < 0.0003). The addition of senna to the bowel preparation protocol with magnesium citrate significantly improves the cleansing outcome.

Addition of senna improves quality of colonoscopy preparation with magnesium citrate

PubMed Central

Vradelis, Stergios; Kalaitzakis, Evangelos; Sharifi, Yalda; Buchel, Otto; Keshav, Satish; Chapman, Roger W; Braden, Barbara

2009-01-01

AIM: To prospectively investigate the effectiveness and patient’s tolerance of two low-cost bowel cleansing preparation protocols based on magnesium citrate only or the combination of magnesium citrate and senna. METHODS: A total of 342 patients who were referred for colonoscopy underwent a colon cleansing protocol with magnesium citrate alone (n = 160) or magnesium citrate and senna granules (n = 182). The colonoscopist rated the overall efficacy of colon cleansing using an established score on a 4-point scale. Patients were questioned before undergoing colonoscopy for side effects and symptoms during bowel preparation. RESULTS: The percentage of procedures rescheduled because of insufficient colon cleansing was 7% in the magnesium citrate group and 4% in the magnesium citrate/senna group (P = 0.44). Adequate visualization of the colonic mucosa was rated superior under the citramag/senna regimen (P = 0.004). Both regimens were well tolerated, and did not significantly differ in the occurrence of nausea, bloating or headache. However, abdominal cramps were observed more often under the senna protocol (29.2%) compared to the magnesium citrate only protocol (9.9%, P < 0.0003). CONCLUSION: The addition of senna to the bowel preparation protocol with magnesium citrate significantly improves the cleansing outcome. PMID:19360920

Personalized Colon Cancer Care in 2010

PubMed Central

Catenacci, Daniel V.T.; Kozloff, Mark; Kindler, Hedy L.; Polite, Blase

2011-01-01

Colon cancer therapies have improved patient outcomes significantly over the last decades in both the adjuvant and metastatic settings. With the introduction of a number of novel agents, both traditional chemotherapies and biologically targeted agents, the need to identify subgroups that are likely and not likely to respond to a particular treatment regimen is paramount. This will allow patients who are likely to benefit to receive optimal care, while sparing those unlikely to benefit from unnecessary toxicity and cost. With the identification of several novel biomarkers and a variety of technologies to interrogate the genome, we are already able to rapidly study patient tumor or blood samples and normal tissues to generate a large dataset of aberrations within the cancer. How to digest this complex information to obtain accurate, reliable, and meaningful results that will allow us to provide truly personalized care for colon cancer patients is just starting to be addressed. In this article, we briefly review the history of colon cancer treatment, with an emphasis on current clinical standards that incorporate a ‘personalized medicine’ approach. We then review strategies which will potentially improve our ability to individualize therapy in the future. PMID:21421118

The Use of Arbuscular Mycorrhizal Fungi to Improve Strawberry Production in Coir Substrate

PubMed Central

Robinson Boyer, Louisa; Feng, Wei; Gulbis, Natallia; Hajdu, Klara; Harrison, Richard J.; Jeffries, Peter; Xu, Xiangming

2016-01-01

Strawberry is an important fruit crop within the UK. To reduce the impact of soil-borne diseases and extend the production season, more than half of the UK strawberry production is now in substrate (predominantly coir) under protection. Substrates such as coir are usually depleted of microbes including arbuscular mycorrhizal fungi (AMF) and consequently the introduction of beneficial microbes is likely to benefit commercial cropping systems. Inoculating strawberry plants in substrate other than coir has been shown to increase plants tolerance to soil-borne pathogens and water stress. We carried out studies to investigate whether AMF could improve strawberry production in coir under low nitrogen input and regulated deficit irrigation. Application of AMF led to an appreciable increase in the size and number of class I fruit, especially under either deficient irrigation or low nitrogen input condition. However, root length colonization by AMF was reduced in strawberry grown in coir compared to soil and Terragreen. Furthermore, the appearance of AMF colonizing strawberry and maize roots grown in coir showed some physical differences from the structure in colonized roots in soil and Terragreen: the colonization structure appeared to be more compact and smaller in coir. PMID:27594859

Engineering bacterial thiosulfate and tetrathionate sensors for detecting gut inflammation.

PubMed

Daeffler, Kristina N-M; Galley, Jeffrey D; Sheth, Ravi U; Ortiz-Velez, Laura C; Bibb, Christopher O; Shroyer, Noah F; Britton, Robert A; Tabor, Jeffrey J

2017-04-03

There is a groundswell of interest in using genetically engineered sensor bacteria to study gut microbiota pathways, and diagnose or treat associated diseases. Here, we computationally identify the first biological thiosulfate sensor and an improved tetrathionate sensor, both two-component systems from marine Shewanella species, and validate them in laboratory Escherichia coli Then, we port these sensors into a gut-adapted probiotic E. coli strain, and develop a method based upon oral gavage and flow cytometry of colon and fecal samples to demonstrate that colon inflammation (colitis) activates the thiosulfate sensor in mice harboring native gut microbiota. Our thiosulfate sensor may have applications in bacterial diagnostics or therapeutics. Finally, our approach can be replicated for a wide range of bacterial sensors and should thus enable a new class of minimally invasive studies of gut microbiota pathways. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Synthetic Hydrogels for Human Intestinal Organoid Generation and Colonic Wound Repair

PubMed Central

Cruz-Acuña, Ricardo; Quirós, Miguel; Farkas, Attila E.; Dedhia, Priya H.; Huang, Sha; Siuda, Dorothée; García-Hernández, Vicky; Miller, Alyssa J.; Spence, Jason R.; Nusrat, Asma; García, Andrés J.

2017-01-01

In vitro differentiation of human intestinal organoids (HIOs) from pluripotent stem cells is an unparalleled system for creating complex, multi-cellular 3D structures capable of giving rise to tissue analogous to native human tissue. Current methods for generating HIOs rely on growth in an undefined tumor-derived extracellular matrix (ECM), which severely limits use of organoid technologies for regenerative and translational medicine. Here, we developed a fully defined, synthetic hydrogel based on a four-armed, maleimide-terminated poly(ethylene glycol) macromer that supports robust and highly reproducible in vitro growth and expansion of HIOs such that 3D structures are never embedded in tumor-derived ECM. We also demonstrate that the hydrogel serves as an injectable HIO vehicle that can be delivered into injured intestinal mucosa resulting in HIO engraftment and improved colonic wound repair. Together, these studies show proof-of-concept that HIOs may be used therapeutically to treat intestinal injury. PMID:29058719

Guargum and Eudragit ® coated curcumin liquid solid tablets for colon specific drug delivery.

PubMed

S Kumar, Vrinda; Rijo, John; M, Sabitha

2018-04-15

Colorectal cancer, also known as bowel cancer, is the uncontrolled cell growth in the colon or rectum (parts of the large intestine), or in the appendix. The colon specific drug delivery would alleviate the systemic side effects and would assure the safe therapy for colonic disorders with minimum dose and duration of therapy. The liquisolid technique refers to solubilisation of drug in a non-volatile solvent combined with inclusion of appropriate carrier and coating agent required for tableting. Colon specific degradation of natural polymer, guar gum and pH dependant degradative (pH-7) property of eudragit L100 restricts the delivery of curcumin in gastric and intestinal pH. Formulated curcumin liquisolid powder was evaluated for the micrometric properties, solubility and by differential thermal analysis, X ray powder diffraction and scanning electron microscopy. Curcumin loaded liquisolid tablet showed more anticancer activity against HCT-15 compared with free curcumin. Bioavailability study of the coated and uncoated liquisolid tablets were performed using Newzealand white rabbits. The present study concludes that liquisolid technique is a promising alternative for improving oral bioavailability and dissolution rate of water insoluble drug and coating liquisolid tablet with colon sensitive polymers showed site specific release of drug in the colon. Copyright © 2018 Elsevier B.V. All rights reserved.

Contrasting colonization and plant growth promoting capacity between wild type and gfp-derative of the endophyte Pseudomonas putida W619 in hybrid poplar

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weyens N.; van der Lelie D.; Boulet, J.

2011-06-09

This study aims to investigate the colonization of poplar by the endophyte Pseudomonas putida W619 and its capacity to promote plant growth. Poplar cuttings were inoculated with P. putida W619 (wild-type or gfp-labelled). The colonization of both strains was investigated and morphological, physiological and biochemical parameters were analyzed to evaluate plant growth promotion. Inoculation with P. putida W619 (wild-type) resulted in remarkable growth promotion, decreased activities of antioxidative defence related enzymes, and reduced stomatal resistance, all indicative of improved plant health and growth in comparison with the non-inoculated cuttings. In contrast, inoculation with gfp-labelled P. putida W619 did not promotemore » growth; it even had a negative effect on plant health and growth. Furthermore, compared to the wildtype strain, colonization by the gfp-labelled P. putida W619::gfp1 was much lower; it only colonized the rhizosphere and root cortex while the wild-type strain also colonized the root xylem vessels. Despite the strong plant growth promoting capacity of P. putida W619 (wild-type), after gfp labelling its growth promoting characteristics disappeared and its colonization capacity was strongly influenced; for these reasons gfp labelling should be applied with sufficient caution.« less

[A case of obstruction due to right-sided colon cancer in which good quality of life was achieved after colonic stenting].

PubMed

Nakao, Shigetomi; Hori, Takeshi; Miura, Kotaro; Tendo, Masashige; Nakata, Bunzo; Ishikawa, Tetsuro; Hirakawa, Kosei

2013-11-01

We report a case of a 60-year-old woman with abdominal distension who was treated with self-expandable metal stent (SEMS) placement in the proximal transverse colon. She was found to have severe bowel obstruction due to advanced transverse colon cancer on plain computed tomography (CT) and colonoscopy. We performed colonic stenting safely, and the symptom promptly improved. Defecation and flatus were observed on the same day of stenting, and the patient was able to start drinking and eating on the next day. Enhanced abdominal CT revealed multiple liver metastasis, peritoneal dissemination, ascites, and cystic ovarian tumor. After treatment with 1 course of 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX6), the patient was discharged on day 14 after admission. The rapidly enlarging ovarian tumors and primary colonic lesion with SEMS were surgically removed after treatment with mFOLFOX6 for 4 months in an outpatient basis. The patient has been alive with a good quality of life (QOL) and being treated with bevacizumab plus mFOLFOX6/Leucovorin, 5-fluorouracil, and irinotecan( FOLFIRI) for 6 months. SEMS placement could be safe and effective for the treatment of obstruction of the right colon, and could maintain a good QOL in patients.

Potentiating NK cell activity by combination of Rosuvastatin and Difluoromethylornithine for effective chemopreventive efficacy against Colon Cancer

PubMed Central

Janakiram, Naveena B.; Mohammed, Altaf; Bryant, Taylor; Zhang, Yuting; Brewer, Misty; Duff, Ashley; Biddick, Laura; Singh, Anil; Lightfoot, Stan; Steele, Vernon E; Rao, Chinthalapally V.

2016-01-01

Colorectal cancer (CRC) is the second highest cause of cancer-related deaths. A successful strategy to improve chemopreventive efficacies is by down-regulating tumor polyamines and enhancing NK cell activities. Colonic carcinogenesis was induced by azoxymethane (AOM) in male F344 rats. Eight weeks after AOM treatment, animals were fed diets containing Rosuvastatin and difluromethylornithine (DFMO) individually and in combination for 40 weeks. Both agents showed significant suppression of adenocarcinoma multiplicity and incidence with no toxicity compared to untreated rats. Low-dose Rosuvastatin plus DFMO suppressed colon adenocarcinoma multiplicity by 76% compared to low-dose Rosuvastatin (29%) and DFMO (46%), suggesting additive efficacy. Furthermore, low-dose combination caused a delay in colonic adenocarcinoma progression. DFMO, Rosuvastatin and/or combinations significantly decreased polyamine content and increased intra-tumoral NK cells expressing perforin plus IFN-γ compared to untreated colon tumors. Further ex-vivo analysis of splenic NK cells exposed to DFMO, Rosuvastatin or combination resulted in an increase of NKs with perforin expression. This is the first report on Rosuvastatin alone or combination strategy using clinically relevant statin plus DFMO doses which shows a significant suppression of colon adenocarcinomas, and their potential in increasing functional NK cells. This strategy has potential for further testing in high risk individuals for colon cancer. PMID:27841323

Colon cancer: personality factors predictive of onset and stage of presentation.

PubMed

Kavan, M G; Engdahl, B E; Kay, S

1995-11-01

This study examined premorbid personality correlates of colon cancer and stage of presentation of colon cancer to health care providers. Sixty-one male veterans who completed the MMPI between 1947 and 1975 and were then diagnosed with colon cancer between 1977 and 1988 were matched with control patients. A 21-factor solution of the MMPI [1] was used to seek potential personality differences between colon cancer cases and their controls in terms of presence of colon cancer and stage of presentation for this disease. A stepwise conditional regression analysis found significant differences between the colon cancer and control groups on the Aggressive Hostility variable (p < 0.018). A multivariate analysis of variance conducted across the stages of colon cancer presentation found that patients who presented later on for colon cancer had higher Phobia scores (p < 0.05). Religious Fundamentalism was also related to presentation (p < 0.05), but in a nonlinear manner. Discussion is related to previous findings regarding the relationship between personality and development of cancer, as well as to implications for patient screening.

Is it worth screening for vancomycin-resistant Enterococcus faecium colonization?: Financial burden of screening in a developing country.

PubMed

Ulu-Kilic, Aysegul; Özhan, Esra; Altun, Dilek; Perçin, Duygu; Güneş, Tamer; Alp, Emine

2016-04-01

The screening of critically ill patients at high risk of vancomycin resistant enterococci (VRE) colonization, to detect and isolate colonized patients, is recommended to prevent and control the transmission of VRE. Screening asymptomatic carriers brings financial burden for institutions. In this study, we performed risk analysis for VRE colonization and determined the financial burden of screening in a middle-income country, Turkey. We retrospectively analyzed the VRE surveillance data from a pediatric hospital between 2010 and 2014. A case-control study was conducted to identify the risk factors of colonization. Total cost of VRE screening and additional costs for a VRE colonized patient (including active surveillance cultures and contact isolation) were calculated. During the 4-year period, 6,372 patients were screened for perirectal VRE colonization. The rate of culture-positive specimens among all patients screened was 239 (3.75%). The rate of VRE infection was 0.04% (n = 3) among all patients screened. Length of hospital stay, malignancy, and being transferred from another institution were independently associated risk factors for colonization. Annual estimated costs for the laboratory were projected as $19,074 (76,295/4) for all patients screened. Cost of contact isolation for each patient colonized in a ward and an intensive care unit was $270 and $718, respectively. In developing countries, institutions should identify their own high-risk patients; screening priorities should be based on prevalence of infection and hospital financial resources. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Polysaccharide-based micro/nanocarriers for oral colon-targeted drug delivery.

PubMed

Zhang, Lin; Sang, Yuan; Feng, Jing; Li, Zhaoming; Zhao, Aili

2016-08-01

Oral colon-targeted drug delivery has attracted many researchers because of its distinct advantages of increasing the bioavailability of the drug at the target site and reducing the side effects. Polysaccharides that are precisely activated by the physiological environment of the colon hold greater promise for colon targeting. Considerable research efforts have been directed towards developing polysaccharide-based micro/nanocarriers. Types of polysaccharides for colon targeting and in vitro/in vivo assessments of polysaccharide-based carriers for oral colon-targeted drug delivery are summarised. Polysaccharide-based microspheres have gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon (colon cancer, inflammatory bowel disease (IBD), amoebiasis and irritable bowel syndrome (IBS)), but also for it's potential for the delivery of anti-rheumatoid arthritis and anti-chronic stable angina drugs. Besides, Polysaccharide-based micro/nanocarriers such as microbeads, microcapsules, microparticles, nanoparticles, nanogels and nanospheres are also introduced in this review.

Noni (Morinda citrifolia L.) Fruit Extracts Improve Colon Microflora and Exert Anti-Inflammatory Activities in Caco-2 Cells.

PubMed

Huang, Hsin-Lun; Liu, Cheng-Tzu; Chou, Ming-Chih; Ko, Chien-Hui; Wang, Chin-Kun

2015-06-01

Intestinal microflora and inflammation are associated with the risk of inflammatory bowel diseases. Noni (Morinda citrifolia L.) has various bioactivities, but its effect on colon health remains unknown. This study focused on the effects of fermented noni fruit extracts on colon microflora and inflammation of colon epithelial cells. The anti-inflammatory activities of ethanol and ethyl acetate extracts on Caco-2 cells were evaluated including interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2). The growth of Lactobacillus and Bifidobacterium species was promoted by ethanol extract. Ethyl acetate extract decreased intracellular reactive oxygen species and significantly suppressed COX-2, IL-8, and prostaglandin E2 production and neutrophil chemotaxis by suppressing the translocation of the p65 subunit. Quercetin was the main contributor to the anti-inflammatory activity. The fermented noni fruit promoted probiotic growths and downregulated the intracellular oxidation and inflammation in Caco-2 cells. These results suggest that fermented noni fruit might protect against inflammatory diseases of the colon.

Coadministration of the Campylobacter jejuni N-Glycan-Based Vaccine with Probiotics Improves Vaccine Performance in Broiler Chickens

PubMed Central

Perez-Muñoz, M. E.; Gouveia, G. J.; Wanford, J. J.; Lango-Scholey, L.; Panagos, C. G.; Srithayakumar, V.; Plastow, G. S.; Coros, C.; Bayliss, C. D.; Edison, A. S.; Walter, J.

2017-01-01

ABSTRACT Source attribution studies report that the consumption of contaminated poultry is the primary source for acquiring human campylobacteriosis. Oral administration of an engineered Escherichia coli strain expressing the Campylobacter jejuni N-glycan reduces bacterial colonization in specific-pathogen-free leghorn chickens, but only a fraction of birds respond to vaccination. Optimization of the vaccine for commercial broiler chickens has great potential to prevent the entry of the pathogen into the food chain. Here, we tested the same vaccination approach in broiler chickens and observed similar efficacies in pathogen load reduction, stimulation of the host IgY response, the lack of C. jejuni resistance development, uniformity in microbial gut composition, and the bimodal response to treatment. Gut microbiota analysis of leghorn and broiler vaccine responders identified one member of Clostridiales cluster XIVa, Anaerosporobacter mobilis, that was significantly more abundant in responder birds. In broiler chickens, coadministration of the live vaccine with A. mobilis or Lactobacillus reuteri, a commonly used probiotic, resulted in increased vaccine efficacy, antibody responses, and weight gain. To investigate whether the responder-nonresponder effect was due to the selection of a C. jejuni “supercolonizer mutant” with altered phase-variable genes, we analyzed all poly(G)-containing loci of the input strain compared to nonresponder colony isolates and found no evidence of phase state selection. However, untargeted nuclear magnetic resonance (NMR)-based metabolomics identified a potential biomarker negatively correlated with C. jejuni colonization levels that is possibly linked to increased microbial diversity in this subgroup. The comprehensive methods used to examine the bimodality of the vaccine response provide several opportunities to improve the C. jejuni vaccine and the efficacy of any vaccination strategy. IMPORTANCE Campylobacter jejuni is a common cause of human diarrheal disease worldwide and is listed by the World Health Organization as a high-priority pathogen. C. jejuni infection typically occurs through the ingestion of contaminated chicken meat, so many efforts are targeted at reducing C. jejuni levels at the source. We previously developed a vaccine that reduces C. jejuni levels in egg-laying chickens. In this study, we improved vaccine performance in meat birds by supplementing the vaccine with probiotics. In addition, we demonstrated that C. jejuni colonization levels in chickens are negatively correlated with the abundance of clostridia, another group of common gut microbes. We describe new methods for vaccine optimization that will assist in improving the C. jejuni vaccine and other vaccines under development. PMID:28939610

Coca-colonization and hybridization of diets among the Tz'utujil Maya.

PubMed

Nagata, Jason M; Barg, Frances K; Valeggia, Claudia R; Bream, Kent D W

2011-01-01

Biomedical health professionals express increasing concern that rising consumption of soft drinks and processed foods in Mayan and Latin American eating patterns may lead to detrimental nutritional and health consequences. Scholars debate whether the pervading presence of Coca-Cola and Pepsi in developing countries represents "Coca-Colonization," synonymous with cultural imperialism, or cultural hybridization. Using mixed qualitative and quantitative research methods, including participant observation and semi-structured interviews, this study explores the development of Coca-Colonization and cultural hybridization among the Tz'utujil Maya of Santiago Atitlán, Guatemala. By specifically examining biomedical perspectives, cycles of conquest, the political economy, religion, celebrations, and the physical environment through the lens of soft drinks, this study finds that Coca-Colonization and cultural hybridization are complementary rather than mutually exclusive processes that contribute to dietary transitions, economic development, and differential health beliefs related to soft drink consumption.

Influence of dietary fiber on inflammatory bowel disease and colon cancer: importance of fermentation pattern.

PubMed

Rose, Devin J; DeMeo, Mark T; Keshavarzian, Ali; Hamaker, Bruce R

2007-02-01

The benefits of dietary fiber on inflammatory bowel disease may be related to the fermentative production of butyrate in the colon, which appears to decrease the inflammatory response. The benefits of dietary fiber against colon cancer may be related to both fermentative and non-fermentative processes, although poorly fermentable fibers appear more influential. Dietary fiber fermentation profiles are important in determining optimal fibers for colonic health, and may be a function of structure, processing conditions, and other food components. A greater understanding of the relationships between fermentation rate and dietary fiber structure would allow for development of dietary fibers for optimum colonic health.

Metabolism links bacterial biofilms and colon carcinogenesis

PubMed Central

Johnson, Caroline H.; Dejea, Christine M.; Edler, David; Hoang, Linh T.; Santidrian, Antonio F.; Felding, Brunhilde H.; Cho, Kevin; Wick, Elizabeth C.; Hechenbleikner, Elizabeth M.; Uritboonthai, Winnie; Goetz, Laura; Casero, Robert A.; Pardoll, Drew M.; White, James R.; Patti, Gary J.; Sears, Cynthia L.; Siuzdak, Gary

2015-01-01

SUMMARY Bacterial biofilms in the colon alter the host tissue microenvironment. A role for biofilms in colon cancer metabolism has been suggested but to date has not been evaluated. Using metabolomics, we investigated the metabolic influence that microbial biofilms have on colon tissues and the related occurrence of cancer. Patient-matched colon cancers and histologically normal tissues, with or without biofilms, were examined. We show the upregulation of polyamine metabolites in tissues from cancer hosts with significant enhancement of N1, N12-diacetylspermine in both biofilm positive cancer and normal tissues. Antibiotic treatment, which cleared biofilms, decreased N1, N12-diacetylspermine levels to those seen in biofilm negative tissues, indicating that host cancer and bacterial biofilm structures contribute to the polyamine metabolite pool. These results show that colonic mucosal biofilms alter the cancer metabolome, to produce a regulator of cellular proliferation and colon cancer growth potentially affecting cancer development and progression. PMID:25959674

Metabolism links bacterial biofilms and colon carcinogenesis.

PubMed

Johnson, Caroline H; Dejea, Christine M; Edler, David; Hoang, Linh T; Santidrian, Antonio F; Felding, Brunhilde H; Ivanisevic, Julijana; Cho, Kevin; Wick, Elizabeth C; Hechenbleikner, Elizabeth M; Uritboonthai, Winnie; Goetz, Laura; Casero, Robert A; Pardoll, Drew M; White, James R; Patti, Gary J; Sears, Cynthia L; Siuzdak, Gary

2015-06-02

Bacterial biofilms in the colon alter the host tissue microenvironment. A role for biofilms in colon cancer metabolism has been suggested but to date has not been evaluated. Using metabolomics, we investigated the metabolic influence that microbial biofilms have on colon tissues and the related occurrence of cancer. Patient-matched colon cancers and histologically normal tissues, with or without biofilms, were examined. We show the upregulation of polyamine metabolites in tissues from cancer hosts with significant enhancement of N(1), N(12)-diacetylspermine in both biofilm-positive cancer and normal tissues. Antibiotic treatment, which cleared biofilms, decreased N(1), N(12)-diacetylspermine levels to those seen in biofilm-negative tissues, indicating that host cancer and bacterial biofilm structures contribute to the polyamine metabolite pool. These results show that colonic mucosal biofilms alter the cancer metabolome to produce a regulator of cellular proliferation and colon cancer growth potentially affecting cancer development and progression. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of Replacing Soybean Meal by Raw or Extruded Pea Seeds on Growth Performance and Selected Physiological Parameters of the Ileum and Distal Colon of Pigs

PubMed Central

Taciak, Marcin; Barszcz, Marcin; Święch, Ewa; Bachanek, Ilona; Skomiał, Jacek

2017-01-01

The use of pea seeds is limited due to the content of antinutritional factors that may affect gut physiology. Heat treatment such as extrusion may reduce heat-labile antinutritional factors and improve the nutritional value of pea seeds. This study determined the effect of partial replacement of soybean meal in pig diets by raw or extruded pea seeds on growth performance, nitrogen balance and physiology of the ileum and distal colon. The experiment was carried out in 18 castrated male piglets of initial body weight of 11 kg, divided into three groups. The animals were fed cereal-based diets with soybean meal (C), which was partly replaced by raw (PR) or extruded pea (PE) seeds. Nitrogen balance was measured at about 15 kg body weight. After 26 days of feeding, tissue samples were taken from the ileum and distal colon for histological measurements, and colonic digesta samples for analyses of microbial activity indices. The animals fed the PE diet had a significantly greater average daily gain than those fed the C diet and better apparent protein digestibility than those on the PR diet. Pigs fed the PR diet had a significantly greater butyric acid concentration and lower pH in the colon than pigs fed PE and C diets. There was no significant effect of the diet on other indices of microbial activity or morphological parameters. In conclusion, feeding a diet with extruded pea seeds improved growth performance of pigs, did not affect intestinal morphology and had a negligible effect on microbial activity in the distal colon. PMID:28060879

[Preparation of coated tablets of glycyrrhetic acid-HP-beta-cyclodextrin tablets for colon-specific release].

PubMed

Cui, Qi-Hua; Cui, Jing-Hao; Zhang, Jin-Jin

2008-10-01

To prepare coated tablets of glycyrrhetinic acid and hydroxypropyl-beta-cyclodextrin (GTA-HP-beta-CYD) inclusion complex tablets for colon-specific release. In order to improve the solubility of GTA, the GTA-HP-beta-CYD inclusion complex was prepared by ultrasonic-lyophilization technique and its formation were characterized by X-ray powder diffraction profiles and infrared spectrometry. The effects of inclusion condition on the inclusion efficiency and stability coefficient of inclusion complex were investigated, respectively. After prepared GTA-HP-beta-CYD tablets by powder direct compression, the pH dependant polymer Eudragit III and/or mixed with Eudragit II were used for further coating materials in fluid-bed coater. The influences of coating weight on the GTA release in different pH conditions were evaluated to establish the method for prepering colon specific delivery tablets with pulsed release properties. The formation of inclusion complexes were proved by X-ray powder diffraction profile and phase solubility curve. The effect of pH value of solvent was played critical role on the preparation of GTA- HP-beta-CYD inclusion complex. And the inclusion efficiency of GTA was 9. 3% and the solubility was increased to 54. 6 times at optimized method. The Eudragit III coated GTA- HP-beta-CYD tablets with coating weight 10% and 16% were showed pH dependant colon specific release profiles with slow release rate. The release profile of tablets coated with the mixture of Eudragit II and Eudragit III (1:2) were indicated typical pH dependant colon specific and pulsed release properties while the coating weight was 17%. The preliminary method for preparation of colon specific release tablets containing glycyrrhetinic acid with improved solubility was established for further in vivo therapeutic experiment.

Investigation of disorders of the anorectum and colon.

PubMed Central

Henry, M. M.; Snooks, S. J.; Barnes, P. R.; Swash, M.

1985-01-01

Previously, investigation of disorders of the anorectum and colon have been limited to manometric, external anal sphincter muscle electromyographic and contrast radiological techniques. In this paper we describe other investigative techniques recently developed at St. Mark's Hospital, London and their application in the investigation of certain disorders of the anorectum and colon. Images Fig. 3 PMID:3878123

Induction of Colon Cancer in Mice with 1,2-Dimethylhydrazine.

PubMed

Gurley, Kay E; Moser, Russell D; Kemp, Christopher J

2015-09-01

In this protocol, colon cancer is induced in mice through a series of injections with 1,2-dimethylhydrazine. Mice will develop primarily colon tumors starting at about 3 mo after the first injection. Tumors in the lung, uterus, and small intestine may also be seen, as well as lymphomas. © 2015 Cold Spring Harbor Laboratory Press.

Look-normal: the colonized child of developmental science.

PubMed

Varga, Donna

2011-05-01

This article provides an analysis of the techniques, methods, materials, and discourses of child study observation to illuminate its role in the sociohistorical colonization of childhood. Through analysis of key texts it explains how early 20th-century child study provided for the transcendence of historical, racial, and social contexts for understanding human development. The colonizing project of child study promoted the advancement of Eurocentric culture through a generic "White" development. What a child is and can be, and the meaning of childhood has been disembodied through observation, record keeping, and analytical processes in which time and space are abstracted from behavior, and development symbolized as a universal ideal.

High-order TRAIL oligomer formation in TRAIL-coated lipid nanoparticles enhances DR5 cross-linking and increases antitumour effect against colon cancer.

PubMed

De Miguel, Diego; Gallego-Lleyda, Ana; Ayuso, José María; Pejenaute-Ochoa, Dolores; Jarauta, Vidal; Marzo, Isabel; Fernández, Luis J; Ochoa, Ignacio; Conde, Blanca; Anel, Alberto; Martinez-Lostao, Luis

2016-12-28

During the last years, a great effort has been invested into developing new TRAIL formulations with increased bioactivity, trying to overcome the resistance to conventional soluble TRAIL (sTRAIL) exhibited by many primary tumours. In our group, we have generated artificial lipid nanoparticles decorated with sTRAIL (LUV-TRAIL), emulating the physiological TRAIL-containing exosomes by which T-cells release TRAIL upon activation. We already demonstrated that LUV-TRAIL has greater cytotoxicity against both chemoresistant haematologic tumour cells and epithelial carcinoma cells compared to a form of sTRAIL similar to that used in clinical trials. In this study we have tested LUV-TRAIL in several human colon cancer cell lines with different sensitivity to sTRAIL. LUV-TRAIL significantly improved sTRAIL cytotoxicity in all colon cancer cell lines tested. Trying to ascertain the molecular mechanism by which LUV-TRAIL exhibited improved cytotoxicity, we demonstrated that TRAIL-coated lipid nanoparticles were able to activate DR5 more efficiently than sTRAIL, and this relied on LUV-TRAIL ability to promote DR5 clustering on the cell surface. Moreover, we show that TRAIL molecules are arranged in higher order oligomers only in LUV-TRAIL, which may explain their enhanced DR5 clustering ability. Finally, LUV-TRAIL showed significantly better antitumour activity than sTRAIL in an in vivo model using HCT-116 xenograft tumours in nude mice, validating its potential clinical application. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Usnic acid-loaded biocompatible magnetic PLGA-PVA microsphere thin films fabricated by MAPLE with increased resistance to staphylococcal colonization.

PubMed

Grumezescu, V; Holban, A M; Grumezescu, A M; Socol, G; Ficai, A; Vasile, B S; Truscă, R; Bleotu, C; Lazar, V; Chifiriuc, C M; Mogosanu, G D

2014-09-01

Due to their persistence and resistance to the current therapeutic approaches, Staphylococcus aureus biofilm-associated infections represent a major cause of morbidity and mortality in the hospital environment. Since (+)-usnic acid (UA), a secondary lichen metabolite, possesses antimicrobial activity against Gram-positive cocci, including S. aureus, the aim of this study was to load magnetic polylactic-co-glycolic acid-polyvinyl alcohol (PLGA-PVA) microspheres with UA, then to obtain thin coatings using matrix-assisted pulsed laser evaporation and to quantitatively assess the capacity of the bio-nano-active modified surface to control biofilm formation by S. aureus, using a culture-based assay. The UA-loaded microspheres inhibited both the initial attachment of S. aureus to the coated surfaces, as well as the development of mature biofilms. In vitro bioevalution tests performed on the fabricated thin films revealed great biocompatibility, which may endorse them as competitive candidates for the development of improved non-toxic surfaces resistant to S. aureus colonization and as scaffolds for stem cell cultivation and tissue engineering.

Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.

PubMed

Pardanaud, Luc; Pibouin-Fragner, Laurence; Dubrac, Alexandre; Mathivet, Thomas; English, Isabel; Brunet, Isabelle; Simons, Michael; Eichmann, Anne

2016-08-19

Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood. We set out to identify factors that promote arterial endothelial cell fate in vivo. We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors. These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease. © 2016 American Heart Association, Inc.

Differential gene expression in tomato fruit and Colletotrichum gloeosporioides during colonization of the RNAi-SlPH tomato line with reduced fruit acidity and higher pH.

PubMed

Barad, Shiri; Sela, Noa; Dubey, Amit K; Kumar, Dilip; Luria, Neta; Ment, Dana; Cohen, Shahar; Schaffer, Arthur A; Prusky, Dov

2017-08-04

The destructive phytopathogen Colletotrichum gloeosporioides causes anthracnose disease in fruit. During host colonization, it secretes ammonia, which modulates environmental pH and regulates gene expression, contributing to pathogenicity. However, the effect of host pH environment on pathogen colonization has never been evaluated. Development of an isogenic tomato line with reduced expression of the gene for acidity, SlPH (Solyc10g074790.1.1), enabled this analysis. Total RNA from C. gloeosporioides colonizing wild-type (WT) and RNAi-SlPH tomato lines was sequenced and gene-expression patterns were compared. C. gloeosporioides inoculation of the RNAi-SlPH line with pH 5.96 compared to the WT line with pH 4.2 showed 30% higher colonization and reduced ammonia accumulation. Large-scale comparative transcriptome analysis of the colonized RNAi-SlPH and WT lines revealed their different mechanisms of colonization-pattern activation: whereas the WT tomato upregulated 13-LOX (lipoxygenase), jasmonic acid and glutamate biosynthesis pathways, it downregulated processes related to chlorogenic acid biosynthesis II, phenylpropanoid biosynthesis and hydroxycinnamic acid tyramine amide biosynthesis; the RNAi-SlPH line upregulated UDP-D-galacturonate biosynthesis I and free phenylpropanoid acid biosynthesis, but mainly downregulated pathways related to sugar metabolism, such as the glyoxylate cycle and L-arabinose degradation II. Comparison of C. gloeosporioides gene expression during colonization of the WT and RNAi-SlPH lines showed that the fungus upregulates ammonia and nitrogen transport and the gamma-aminobutyric acid metabolic process during colonization of the WT, while on the RNAi-SlPH tomato, it mainly upregulates the nitrate metabolic process. Modulation of tomato acidity and pH had significant phenotypic effects on C. gloeosporioides development. The fungus showed increased colonization on the neutral RNAi-SlPH fruit, and limited colonization on the WT acidic fruit. The change in environmental pH resulted in different defense responses for the two tomato lines. Interestingly, the WT line showed upregulation of jasmonate pathways and glutamate accumulation, supporting the reduced symptom development and increased ammonia accumulation, as the fungus might utilize glutamate to accumulate ammonia and increase environmental pH for better expression of pathogenicity factors. This was not found in the RNAi-SlPH line which downregulated sugar metabolism and upregulated the phenylpropanoid pathway, leading to host susceptibility.

Oral delivery of Lactococcus lactis that secretes bioactive heme oxygenase-1 alleviates development of acute colitis in mice.

PubMed

Shigemori, Suguru; Watanabe, Takafumi; Kudoh, Kai; Ihara, Masaki; Nigar, Shireen; Yamamoto, Yoshinari; Suda, Yoshihito; Sato, Takashi; Kitazawa, Haruki; Shimosato, Takeshi

2015-11-25

Mucosal delivery of therapeutic proteins using genetically modified strains of lactic acid bacteria (gmLAB) is being investigated as a new therapeutic strategy. We developed a strain of gmLAB, Lactococcus lactis NZ9000 (NZ-HO), which secretes the anti-inflammatory molecule recombinant mouse heme oxygenase-1 (rmHO-1). The effects of short-term continuous oral dosing with NZ-HO were evaluated in mice with dextran sulfate sodium (DSS)-induced acute colitis as a model of inflammatory bowel diseases (IBD). We identified the secretion of rmHO-1 by NZ-HO. rmHO-1 was biologically active as determined with spectroscopy. Viable NZ-HO was directly delivered to the colon via oral administration, and rmHO-1 was secreted onto the colonic mucosa in mice. Acute colitis in mice was induced by free drinking of 3 % DSS in water and was accompanied by an increase in the disease activity index score and histopathological changes. Daily oral administration of NZ-HO significantly improved these colitis-associated symptoms. In addition, NZ-HO significantly increased production of the anti-inflammatory cytokine interleukin (IL)-10 and decreased the expression of pro-inflammatory cytokines such as IL-1α and IL-6 in the colon compared to a vector control strain. Oral administration of NZ-HO alleviates DSS-induced acute colitis in mice. Our results suggest that NZ-HO may be a useful mucosal therapeutic agent for treating IBD.

Segmentation and classification of colon glands with deep convolutional neural networks and total variation regularization.

PubMed

Kainz, Philipp; Pfeiffer, Michael; Urschler, Martin

2017-01-01

Segmentation of histopathology sections is a necessary preprocessing step for digital pathology. Due to the large variability of biological tissue, machine learning techniques have shown superior performance over conventional image processing methods. Here we present our deep neural network-based approach for segmentation and classification of glands in tissue of benign and malignant colorectal cancer, which was developed to participate in the GlaS@MICCAI2015 colon gland segmentation challenge. We use two distinct deep convolutional neural networks (CNN) for pixel-wise classification of Hematoxylin-Eosin stained images. While the first classifier separates glands from background, the second classifier identifies gland-separating structures. In a subsequent step, a figure-ground segmentation based on weighted total variation produces the final segmentation result by regularizing the CNN predictions. We present both quantitative and qualitative segmentation results on the recently released and publicly available Warwick-QU colon adenocarcinoma dataset associated with the GlaS@MICCAI2015 challenge and compare our approach to the simultaneously developed other approaches that participated in the same challenge. On two test sets, we demonstrate our segmentation performance and show that we achieve a tissue classification accuracy of 98% and 95%, making use of the inherent capability of our system to distinguish between benign and malignant tissue. Our results show that deep learning approaches can yield highly accurate and reproducible results for biomedical image analysis, with the potential to significantly improve the quality and speed of medical diagnoses.

Segmentation and classification of colon glands with deep convolutional neural networks and total variation regularization

PubMed Central

Kainz, Philipp; Pfeiffer, Michael

2017-01-01

Segmentation of histopathology sections is a necessary preprocessing step for digital pathology. Due to the large variability of biological tissue, machine learning techniques have shown superior performance over conventional image processing methods. Here we present our deep neural network-based approach for segmentation and classification of glands in tissue of benign and malignant colorectal cancer, which was developed to participate in the GlaS@MICCAI2015 colon gland segmentation challenge. We use two distinct deep convolutional neural networks (CNN) for pixel-wise classification of Hematoxylin-Eosin stained images. While the first classifier separates glands from background, the second classifier identifies gland-separating structures. In a subsequent step, a figure-ground segmentation based on weighted total variation produces the final segmentation result by regularizing the CNN predictions. We present both quantitative and qualitative segmentation results on the recently released and publicly available Warwick-QU colon adenocarcinoma dataset associated with the GlaS@MICCAI2015 challenge and compare our approach to the simultaneously developed other approaches that participated in the same challenge. On two test sets, we demonstrate our segmentation performance and show that we achieve a tissue classification accuracy of 98% and 95%, making use of the inherent capability of our system to distinguish between benign and malignant tissue. Our results show that deep learning approaches can yield highly accurate and reproducible results for biomedical image analysis, with the potential to significantly improve the quality and speed of medical diagnoses. PMID:29018612

Mast cells boost myeloid-derived suppressor cell activity and contribute to the development of tumor-favoring microenvironment.

PubMed

Danelli, Luca; Frossi, Barbara; Gri, Giorgia; Mion, Francesca; Guarnotta, Carla; Bongiovanni, Lucia; Tripodo, Claudio; Mariuzzi, Laura; Marzinotto, Stefania; Rigoni, Alice; Blank, Ulrich; Colombo, Mario P; Pucillo, Carlo E

2015-01-01

Inflammation plays crucial roles at different stages of tumor development and may lead to the failure of immune surveillance and immunotherapy. Myeloid-derived suppressor cells (MDSC) are one of the major components of the immune-suppressive network that favors tumor growth, and their interaction with mast cells is emerging as critical for the outcome of the tumor-associated immune response. Herein, we showed the occurrence of cell-to-cell interactions between MDSCs and mast cells in the mucosa of patients with colon carcinoma and in the colon and spleen of tumor-bearing mice. Furthermore, we demonstrated that the CT-26 colon cancer cells induced the accumulation of CD11b(+)Gr1(+) immature MDSCs and the recruitment of protumoral mast cells at the tumor site. Using ex vivo analyses, we showed that mast cells have the ability to increase the suppressive properties of spleen-derived monocytic MDSCs, through a mechanism involving IFNγ and nitric oxide production. In addition, we demonstrated that the CD40:CD40L cross-talk between the two cell populations is responsible for the instauration of a proinflammatory microenvironment and for the increase in the production of mediators that can further support MDSC mobilization and tumor growth. In light of these results, interfering with the MDSC:mast cell axis could be a promising approach to abrogate MDSC-related immune suppression and to improve the antitumor immune response. ©2014 American Association for Cancer Research.

Optical coherence tomography imaging of colonic crypts in a mouse model of colorectal cancer

NASA Astrophysics Data System (ADS)

Welge, Weston A.; Barton, Jennifer K.

2016-03-01

Aberrant crypt foci (ACF) are abnormal epithelial lesions that precede development of colonic polyps. As the earliest morphological change in the development of colorectal cancer, ACF is a highly studied phenomenon. The most common method of imaging ACF is chromoendoscopy using methylene blue as a contrast agent. Narrow- band imaging is a contrast-agent-free modality for imaging the colonic crypts. Optical coherence tomography (OCT) is an attractive alternative to chromoendoscopy and narrow-band imaging because it can resolve the crypt structure at sufficiently high sampling while simultaneously providing depth-resolved data. We imaged in vivo the distal 15 mm of colon in the azoxymethane (AOM) mouse model of colorectal cancer using a commercial swept-source OCT system and a miniature endoscope designed and built in-house. We present en face images of the colonic crypts and demonstrate that different patterns in healthy and adenoma tissue can be seen. These patterns correspond to those reported in the literature. We have previously demonstrated early detection of colon adenoma using OCT by detecting minute thickening of the mucosa. By combining mucosal thickness measurement with imaging of the crypt structure, OCT can be used to correlate ACF and adenoma development in space and time. These results suggest that OCT may be a superior imaging modality for studying the connection between ACF and colorectal cancer.

Influence of short-chain fatty acids on iron absorption by proximal colon.

PubMed

Bouglé, D; Vaghefi-Vaezzadeh, N; Roland, N; Bouvard, G; Arhan, P; Bureau, F; Neuville, D; Maubois, J L

2002-09-01

Short-chain fatty acids produced by bacterial fermentation in the colon enhance the local absorption of cations, such as calcium, that could be used to improve the bioavailability of iron if a significant colonic absorption of iron were to occur. Iron (iron gluconate, 100 microM) absorption by the caecum of the rat was compared with that in proximal sites of the small bowel using the Ussing chamber model; the influence of probiotic bacteria (Propionibacterium freudenreichii) on iron absorption was assessed and compared with that of two of their fermentation products (acetic and propionic acids) using the Ussing chamber and the ligated colon with gamma emitting iron as experimental models. The caecum absorbed less iron than the duodenum, but significantly more than the jejunum and ileum. This occurred mainly through an enhanced mucosal transfer of iron uptake. Propionibacteria enhanced iron absorption from the proximal colon; the same effect was observed in the presence of viable bacteria, or the culture medium free of viable bacteria, or acetate and propionate or propionate alone. The proximal colon could be a significant site available for iron absorption; this absorption can be enhanced by local production of short-chain fatty acids such as propionate.

Chai-Qin-Cheng-Qi Decoction and Carbachol Improve Intestinal Motility by Regulating Protein Kinase C-Mediated Ca2+ Release in Colonic Smooth Muscle Cells in Rats with Acute Necrotising Pancreatitis

PubMed Central

Zhang, Chen-Long; Lin, Zi-Qi; Zhang, Xiao-Xin; Guo, Jia; Wu, Wei; Shi, Na; Deng, Li-Hui; Chen, Wei-Wei; Zhang, Xiao-Ying; Bharucha, Shameena; Huang, Wei; Sutton, Robert; Windsor, John A.

2017-01-01

Chai-Qin-Cheng-Qi decoction (CQCQD) improves intestinal motility in acute pancreatitis (AP), but the mechanism(s) require elucidation. We investigated the effects of CQCQD and carbachol, a prokinetic agent, on colonic smooth muscle cells (SMCs) in L-arginine-induced necrotising AP model in rats. In treatment groups, intragastric CQCQD (20 g/kg, 2 hourly × 3 doses) or intraperitoneal carbachol (60 μg/kg) was given 24 hours after induction of AP. Both CQCQD and carbachol decreased the severity of pancreatic and colonic histopathology (all P < 0.05). Both CQCQD and carbachol reduced serum intestinal fatty acid binding protein, vasoactive intestinal peptide, and substance P and increased motility levels. CQCQD upregulated SMC phospholipase C-beta 1 (PLC-β1) mRNA and PLC protein (both P < 0.05), while both treatments upregulated protein kinase C-alpha (PKC-α) mRNA and PKC protein and downregulated adenylate cyclase (AC) mRNA and protein compared with no treatment (all P < 0.05). Neither treatment significantly altered L-arginine-induced PKC-β1 and PKC-ε mRNA reduction. Both treatments significantly increased fluorescence intensity of SMC intracellular calcium concentration [Ca2+]i (3563.5 and 3046.9 versus 1086.9, both P < 0.01). These data suggest CQCQD and carbachol improve intestinal motility in AP by increasing [Ca2+]i in colonic SMCs via upregulating PLC, PKC and downregulating AC. PMID:28529530

Online resources for the identification of North American wood decay fungi

Treesearch

Jessie A. Glaeser

2012-01-01

The ability to identify wood decay fungi is an important skill for an arborist. Knowing which fungus is colonizing a tree can be used to better assess the type, amount, and position of decay in the tree, and its subsequent effects on wood strength. Distinguishing species of fungi that colonize sapwood, heartwood, or roots can provide information to improve the quality...

[Efficiency of autogenous training in medical rehabilitation of patients with irritable colon syndrome with constipation dominance].

PubMed

Pakhomova, I V; Aĭvazian, T A; Zaĭtsev, V P; Gusakova, E V; Molina, L P

2008-01-01

It was established that use of autogenous training makes possible to increase efficiency of the therapy, leading to considerable more evident improvement of somatic and psychotic state, decrease of pain syndrome. Predictors of efficiency of autogenous training were marked out. Indications for use the method in medical rehabilitation of patients with irritable colon syndrome with constipation dominance were elaborated.

Surgical Management of Functional Constipation: Preliminary Report of a New Approach Using a Laparoscopic Sigmoid Resection Combined with a Malone Appendicostomy.

PubMed

Gasior, Alessandra; Brisighelli, Giulia; Diefenbach, Karen; Lane, Victoria Alison; Reck, Carlos; Wood, Richard J; Levitt, Marc

2017-08-01

Introduction  Functional constipation is a common problem in children. It usually can be managed with laxatives but a small subset of patients develop intolerable cramps and need to be temporarily treated with enemas. The senior author has previously reported: 1) open sigmoid resection as a surgical option, but this did not sufficiently reduce the laxative need, then 2) a transanal approach (with resection of rectosigmoid), but this led to a high rate of soiling due to extensive stretching of the anal canal and loss of the rectal reservoir. The understanding of these procedures' results has led us to use a laparoscopic sigmoid ± left colonic resection with a Malone appendicostomy for these patients, to decrease the laxative requirements, temporarily treat with antegrade flushes, and to reduce postoperative soiling. Methods  A single-institution retrospective review (3/2014-9/2015) included patients who failed our laxative protocol, and therefore were considered surgical candidates. Patients with anorectal malformation (ARM), Hirschsprung disease, spina bifida, tethered cord, trisomy 21, cerebral palsy, mitochondrial disease, prior colon resection at other facilities, or those that did not participate in our laxative program were excluded. Demographics, duration of symptoms, prior treatments, postoperative complications, and postoperative bowel regimens were evaluated. Results  A total of 6 patients (3 males; median age of 12.5 years) presented with soiling related to constipation and intolerance to laxatives. Four patients failed preoperative cecostomy (done prior to referral to us). An average of 4.7 medication treatments were previously tried. In all, 4 patients had required in-patient disimpactions. Duration of symptoms was 7.5 years (median). The median senna dose was 30 mg (range, 15-150 mg), and all patients had intolerable symptoms or failed to empty their colon, which we considered a failed laxative trial. All had contrast enemas that demonstrated a dilated and/or redundant sigmoid colon, and colonic manometry was abnormal in 4. All patients underwent laparoscopic sigmoid and left colon resection, or only sigmoid resection (a low anterior resection). Two patients had postoperative colitis treated with oral antibiotics. The median follow-up was 52 days (range, 8-304 days). Five patients are on antegrade enemas with plans to convert to laxatives at 6 months, 1 is taking laxatives alone at a 33% lower dosage. Five of six are completely clean, 1 soils occasionally and their daily flush is being adjusted. Conclusion  Only a minority of patients with functional constipation are medically unmanageable. This preliminary report shows that laparoscopic colon resection combined with antegrade flushes is an effective surgical technique to treat that group. A laparoscopic approach, guided by contrast enema and colonic manometry, allows for a defined resection of the abnormal segment of colon with the advantages of minimally invasive surgery including allowing for an extensive rectal resection (an improvement over open sigmoid resection) and avoidance of overstretching of the anal canal and removal of the rectal reservoir (an improvement over the transanal approach). Having antegrade access is useful to manage soiling and avoiding cramping from laxatives in the early postoperative period. Although our series is small, we believe that long-term most patients can avoid antegrade flushes and be on no, or a dramatically reduced, laxative dose. Georg Thieme Verlag KG Stuttgart · New York.

Development of a chitosan based double layer-coated tablet as a platform for colon-specific drug delivery

PubMed Central

Kim, Min Soo; Yeom, Dong Woo; Kim, Sung Rae; Yoon, Ho Yub; Kim, Chang Hyun; Son, Ho Yong; Kim, Jin Han; Lee, Sangkil; Choi, Young Wook

2017-01-01

A double layer-coated colon-specific drug delivery system (DL-CDDS) was developed, which consisted of chitosan (CTN) based polymeric subcoating of the core tablet containing citric acid for microclimate acidification, followed by an enteric coating. The polymeric composition ratio of Eudragit E100 and ethyl cellulose and amount of subcoating were optimized using a two-level factorial design method. Drug-release characteristics in terms of dissolution efficiency and controlled-release duration were evaluated in various dissolution media, such as simulated colonic fluid in the presence or absence of CTNase. Microflora activation and a stepwise mechanism for drug release were postulated. Consequently, the optimized DL-CDDS showed drug release in a controlled manner by inhibiting drug release in the stomach and intestine, but releasing the drug gradually in the colon (approximately 40% at 10 hours and 92% at 24 hours in CTNase-supplemented simulated colonic fluid), indicating its feasibility as a novel platform for CDD. PMID:28053506

Effect of Dai-kenchu-to (Da-Jian-Zhong-Tang) on the delayed intestinal propulsion induced by chlorpromazine in mice.

PubMed

Satoh, Kazuko; Kase, Yoshio; Yuzurihara, Mitsutoshi; Mizoguchi, Kazushige; Kurauchi, Kouji; Ishige, Atsushi

2003-05-01

This study was conducted to evaluate the effect of Dai-kenchu-to on chlorpromazine-induced hypoperistalsis in mice. Oral administration of Dai-kenchu-to (30-300 mg/kg) dose-dependently improved small intestinal and distal colonic propulsion decreased by chlorpromazine (3 mg/kg, p.o.). Although the improvement of small intestinal propulsion due to Dai-kenchu-to was partially inhibited by atropine (1 mg/kg, s.c.), this action was completely inhibited by the concomitant administration of lorglumide (10 mg/kg, i.p.), a CCKA receptor antagonist. The distal colonic propulsion-improving effect of Dai-kenchu-to was abolished by atropine (1 mg/kg, s.c.). When the effects of the respective components of Dai-kenchu-to were evaluated, oral administration of Zanthoxylum Fruit improved both delayed small intestinal and distal colonic propulsion caused by chlorpromazine. On the other hand, Malt Sugar was effective against only delayed small intestinal propulsion. The action of Zanthoxylum Fruit was completely inhibited by atropine (1 mg/kg, s.c.), and the effect of Malt Sugar was inhibited by lorglumide (10 mg/kg, i.p.). These results demonstrated that Dai-kenchu-to improves chlorpromazine-induced hypoperistalsis via cholinergic systems and that Zanthoxylum Fruit is the main contributor to this action of Dai-kenchu-to. In addition, endogenous CCK due to Malt Sugar may also contribute to this effect of Dai-kenchu-to.

α-fetoprotein involvement during glucocorticoid-induced precocious maturation in rat colon

PubMed Central

Chen, Min; Sun, Peng; Liu, Xiao-Yan; Dong, Dan; Du, Jun; Gu, Luo; Ge, Ying-Bin

2011-01-01

AIM: To investigate the role of α-fetoprotein (AFP), a cancer-associated fetal glycoprotein, in glucocorticoid-induced precocious maturation in rat colon. METHODS: Colons from suckling Sprague-Dawley rats were used in this study. Corticosterone acetate at a dose of 100 μg/g body weight was given to normal pups on days 7, 9 and 11 after birth to induce hypercorticoidism. Control animals were injected with identical volumes of normal saline. Some rats receiving corticosterone 7 d after birth were also treated with mifepristone (RU38486), a glucocorticoid cytoplasm receptor antagonist to investigate the effects of glucocorticoids (GCs). The morphological changes of the crypt depth and villous height of the villous zone in colon were observed as indices of colon maturation. Expression levels of AFP in colons were detected by reverse transcriptase polymerase chain reaction and Western blotting. To identify the cellular localization of AFP in developing rat colons, double-immunofluorescent staining was performed using antibodies to specific mesenchymal cell marker and AFP. RESULTS: Corticosterone increased the crypt depth and villous height in the colon of 8- and 10-d-old rats with hypercorticoidism compared with that in the control animals (120% in 8-d-old rats and 118% in 10-d-old rats in villous height, P = 0.021; 145% in 8-d-old rats and 124% in 10-d-old rats in crypt depth, P = 0.017). These increases were accompanied by an increase of AFP expression in both mRNA and protein (2.5-folds in 8-d-old and 2.5-folds in 10-d-old rats higher than in control animals, P = 0.035; 1.8-folds in 8-d-old and 1.3-folds in 10-d-old rats higher than in control animals, P = 0.023). Increased crypt depth and villous height and increased expression of AFP in the colon of rats with hypercorticoidism were blocked by mifepristone. Both had positive staining for AFP or vimentin, and overlapped in mesenchymal cells at each tested colon. CONCLUSION: GCs promote the development of rat colon. AFP appears to be involved, in part, in mediating the effects of GCs in the developmental colon. PMID:21734804

Temperature-dependent development and emergence pattern of Hypothenemus hampei (Coleoptera: Curculionidae: Scolytinae) from coffee berries.

PubMed

Jaramillo, Juliana; Chabi-Olaye, Adenirin; Borgemeister, Christian

2010-08-01

The coffee berry borer, Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae: Scolytinae), is the most important constrain for coffee production throughout the world. Knowledge on the emergence pattern of H. hampei females to infest new berries is crucial to effectively plan control measures. In this laboratory study, we assessed the development of immature stages and the emergence pattern of H. hampei females from the berries by exposing them to temperatures that are typical for high-altitude plantations (> or = 1,700 m above sea level [masl] ) or when coffee is grown under shade trees (20-22 degrees C), and optimum altitude plantations (1,200-1,600 masl) or nonshaded coffee (25-30 degrees C). Fecundity and emergence pattern of H. hampei females from coffee berries varied with temperature. Temperature played a crucial role determining the rate of H. hampei development and therefore the emergence of the females to start a new infestation cycle. The emergence and colonization phases of new colonizing females in coffee plantations with mean temperatures of 20, 25, or 30 degrees C would take place at different moments in the development of the coffee berries, and in some cases more than once. The implications of our findings for an improved, site-specific timing of control interventions against H. hampei are discussed.

Prevention of microbial biofilms - the contribution of micro and nanostructured materials.

PubMed

Grumezescu, Alexandru Mihai; Chifiriuc, Carmen Mariana

2014-01-01

Microbial biofilms are associated with drastically enhanced resistance to most of the antimicrobial agents and with frequent treatment failures, generating the search for novel strategies which can eradicate infections by preventing the persistent colonization of the hospital environment, medical devices or human tissues. Some of the current approaches for fighting biofilms are represented by the development of novel biomaterials with increased resistance to microbial colonization and by the improvement of the current therapeutic solutions with the aid of nano (bio)technology. This special issues includes papers describing the applications of nanotechnology and biomaterials science for the development of improved drug delivery systems and nanostructured surfaces for the prevention and treatment of medical biofilms. Nanomaterials display unique and well-defined physical and chemical properties making them useful for biomedical applications, such as: very high surface area to volume ratio, biocompatibility, biodegradation, safety for human ingestion, capacity to support surface modification and therefore, to be combined with other bioactive molecules or substrata and more importantly being seemingly not attracting antimicrobial resistance. The use of biomaterials is significantly contributing to the reduction of the excessive use of antibiotics, and consequently to the decrease of the emergence rate of resistant microorganisms, as well as of the associated toxic effects. Various biomaterials with intrinsic antimicrobial activity (inorganic nanoparticles, polymers, composites), medical devices for drug delivery, as well as factors influencing their antimicrobial properties are presented. One of the presented papers reviews the recent literature on the use of magnetic nanoparticles (MNP)-based nanomaterials in antimicrobial applications for biomedicine, focusing on the growth inhibition and killing of bacteria and fungi, and, on viral inactivation. The anti-pathogenic activity of the most common types of metallic/metal oxide nanoparticles, as well as the photocontrolled targeted drug-delivery system and the development of traditional Chinese herbs nanoparticles are some of the highlights of another paper of this issue. The applications of synthetic, biodegradable polymers for the improvement of antiinfective therapeutic and prophylactic agents (i.e., antimicrobial and anti-inflammatory agents and vaccines) activity, as well as for the design of biomaterials with increased biocompatibility and resistance to microbial colonization are also discussed, as well as one of the most recent paradigms of the pharmaceutical field and nanobiotechnology, represented by the design of smart multifunctional polymeric nanocarriers for controlled drug delivery. These systems are responding to physico-chemical changes and as a result, they can release the active substances in a controlled and targeted manner. The advantages and limitations of the main routes of polymerization by which these nanovehicles are obtained, as well as the practical appllications in the field of drug nanocarriers are presented. The authors describe the therapeutic applications of dendrimers, which are unimolecular, monodisperse nanocarriers with unique branched tree-like globular structure. The applications of nanotechnology for the stabilization and improved release of anti-pathogenic natural or synthetic compounds, which do not interfere with the microbial growth, but inhibit different features of microbial pathogenicity are also highlighted. We expect this special issue would offer a comprehensive update and give new directions for the design of micro/nano engineered materials to inhibit microbial colonization on the surfaces or to potentiate the efficiency of the current/ novel/alternative antimicrobial agents by improving their bioavailability and pharmacokinetic features.

Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens

PubMed Central

Pamer, Eric G.

2016-01-01

The intestinal microbiota, which is composed of diverse populations of commensal bacterial species, provides resistance against colonization and invasion by pathogens. Antibiotic treatment can damage the intestinal microbiota and, paradoxically, increase susceptibility to infections. Reestablishing microbiota-mediated colonization resistance after antibiotic treatment could markedly reduce infections, particularly those caused by antibiotic-resistant bacteria. Ongoing studies are identifying commensal bacterial species that can be developed into next-generation probiotics to reestablish or enhance colonization resistance. These live medicines are at various stages of discovery, testing, and production and are being subjected to existing regulatory gauntlets for eventual introduction into clinical practice. The development of next-generation probiotics to reestablish colonization resistance and eliminate potential pathogens from the gut is warranted and will reduce health care–associated infections caused by highly antibiotic-resistant bacteria. PMID:27126035

NASA Applications of Molecular Nanotechnology

NASA Technical Reports Server (NTRS)

Globus, Al; Bailey, David; Han, Jie; Jaffe, Richard; Levit, Creon; Merkle, Ralph; Srivastava, Deepak

1998-01-01

Laboratories throughout the world are rapidly gaining atomically precise control over matter. As this control extends to an ever wider variety of materials, processes and devices, opportunities for applications relevant to NASA's missions will be created. This document surveys a number of future molecular nanotechnology capabilities of aerospace interest. Computer applications, launch vehicle improvements, and active materials appear to be of particular interest. We also list a number of applications for each of NASA's enterprises. If advanced molecular nanotechnology can be developed, almost all of NASA's endeavors will be radically improved. In particular, a sufficiently advanced molecular nanotechnology can arguably bring large scale space colonization within our grasp.

Passiflora edulis peel intake and ulcerative colitis: approaches for prevention and treatment.

PubMed

Cazarin, Cinthia Bb; da Silva, Juliana K; Colomeu, Talita C; Batista, Angela G; Vilella, Conceição A; Ferreira, Anderson L; Junior, Stanislau Bogusz; Fukuda, Karina; Augusto, Fabio; de Meirelles, Luciana R; Zollner, Ricardo de L; Junior, Mário R Maróstica

2014-05-01

Inflammatory bowel disease is a chronic relapsing disease that affects millions of people worldwide; its pathogenesis is influenced by genetic, environmental, microbiological, and immunological factors. The aim of this study was to evaluate the effects of short- and long-term Passiflora edulis peel intake on the antioxidant status, microbiota, and short-chain fatty acids formation in rats with 2,4,6-trinitrobenzenesulphonic acid-induced colitis using two "in vivo" experiments: chronic (prevention) and acute (treatment). The colitis damage score was determined using macroscopic and microscopic analyses. In addition, the antioxidant activity in serum and other tissues (liver and colon) was evaluated. Bifidobacteria, lactobacilli, aerobic bacteria and enterobacteria, and the amount of short-chain fatty acids (acetic, butyric, and propionic acids) in cecum content were counted. Differences in the colon damage scores were observed; P. edulis peel intake improved serum antioxidant status. In the treatment protocol, decreased colon lipid peroxidation, a decreased number of aerobic bacteria and enterobacteria, and an improvement in acetic and butyric acid levels in the feces were observed. An improvement in the bifidobacteria and lactobacilli was observed in the prevention protocol. These results suggested that P. edulis peel can modulate microbiota and could be used as source of fiber and polyphenols in the prevention of oxidative stress through the improvement of serum and tissue antioxidant status.

In vivo deep tissue fluorescence imaging of the murine small intestine and colon

NASA Astrophysics Data System (ADS)

Crosignani, Viera; Dvornikov, Alexander; Aguilar, Jose S.; Stringari, Chiara; Edwards, Roberts; Mantulin, Williams; Gratton, Enrico

2012-03-01

Recently we described a novel technical approach with enhanced fluorescence detection capabilities in two-photon microscopy that achieves deep tissue imaging, while maintaining micron resolution. This technique was applied to in vivo imaging of murine small intestine and colon. Individuals with Inflammatory Bowel Disease (IBD), commonly presenting as Crohn's disease or Ulcerative Colitis, are at increased risk for developing colorectal cancer. We have developed a Giα2 gene knock out mouse IBD model that develops colitis and colon cancer. The challenge is to study the disease in the whole animal, while maintaining high resolution imaging at millimeter depth. In the Giα2-/- mice, we have been successful in imaging Lgr5-GFP positive stem cell reporters that are found in crypts of niche structures, as well as deeper structures, in the small intestine and colon at depths greater than 1mm. In parallel with these in vivo deep tissue imaging experiments, we have also pursued autofluorescence FLIM imaging of the colon and small intestine-at more shallow depths (roughly 160μm)- on commercial two photon microscopes with excellent structural correlation (in overlapping tissue regions) between the different technologies.

Maternal influences on fetal microbial colonization and immune development

PubMed Central

Romano-Keeler, Joann; Weitkamp, Jörn-Hendrik

2014-01-01

While critical for normal development, the exact timing of establishment of the intestinal microbiome is unknown. For example, although preterm labor and birth have been associated with bacterial colonization of the amniotic cavity and fetal membranes for many years, the prevailing dogma of a sterile intrauterine environment during normal term pregnancies has been challenged more recently. While found to be a key contributor of evolution in the animal kingdom, maternal transmission of commensal bacteria may also constitute a critical process during healthy pregnancies in humans with yet unclear developmental importance. Metagenomic sequencing has elucidated a rich placental microbiome in normal term pregnancies likely providing important metabolic and immune contributions to the growing fetus. Conversely, an altered microbial composition during pregnancy may produce aberrant metabolites impairing fetal brain development and life-long neurological outcomes. Here we review the current understanding of microbial colonization at the feto-maternal interface and explain how normal gut colonization drives a balanced neonatal mucosal immune system, while dysbiosis contributes to aberrant immune function early in life and beyond. We discuss how maternal genetics, diet, medications, and probiotics inform the fetal microbiome in preparation for perinatal and postnatal bacterial colonization. PMID:25310759

Current status of colonic endoscopic mucosal resection in the west and the interface with endoscopic submucosal dissection.

PubMed

Bourke, Michael

2009-07-01

Endoscopic Mucosal Resection (EMR) is now widely practised by western endoscopists to treat large sessile colonic polyps or laterally spreading tumours. Despite its widespread application, the technique of colonic EMR is not standardised. A lesion specific endoscopic treatment approach is also lacking. For lesions larger than 25mm, EMR is limited by its inability to achieve en-bloc resection. En-bloc resection has many theoretical advantages including more accurate histological assessment, reduced recurrence and potentially curative treatment for low risk submucosal invasive neoplasia particularly in patients with significant co-morbidity. Hence, Japanese endoscopists, having pioneered endoscopic submucosal dissection (ESD) in the upper gastrointestinal tract for the en-bloc resection of superficial neoplasia, now advocate the use of ESD for laterally spreading tumours of the colon greater than 25-30mm. This treatment strategy is not widely accepted or practised in the west and has its own inherent problems. The absence of suitable gastric lesions on which to develop ESD skills is also another significant barrier to the development of colonic ESD. It is also possible that modification and refinement in EMR technique may increase the size limit for colonic EMR.

Obesity-related colon cancer: dietary factors and their mechanisms of anticancer action.

PubMed

Zeng, Huawei; Lazarova, Darina L

2012-02-01

Overweight/obesity is an epidemic in the US as well as in other developed countries, affecting two-thirds of Americans and an estimated 2.3 billion people worldwide. Obesity increases the risk for Type 2 diabetes, cardiovascular disease and cancer. For example, epidemiological studies have established a strong association between obesity and colon cancer. It is generally accepted that metabolic changes associated with overweight/obesity, particularly abdominal obesity and changes in adipocyte function, contribute to the increased risk of colon cancer. Understanding the mechanisms underlying this association is important for the development of preventive strategies for colon cancer. Part of these preventive strategies may be based on dietary factors, such as vitamins, minerals (e.g. selenium), fibre, phytochemicals and phenolic compounds. These anticancer nutrients may counteract the molecular changes associated with obesity. The present article reviews the evidence that inflammation and insulin resistance induced by obesity are the molecular mediators of the association between obesity and colon cancer. We also evaluate the evidence for the ability of dietary factors to target the obesity-induced changes and, thus, protect against colon cancer. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.

Multicongenic fate mapping quantification of dynamics of thymus colonization.

PubMed

Ziętara, Natalia; Łyszkiewicz, Marcin; Puchałka, Jacek; Witzlau, Katrin; Reinhardt, Annika; Förster, Reinhold; Pabst, Oliver; Prinz, Immo; Krueger, Andreas

2015-09-21

Postnatal T cell development depends on continuous colonization of the thymus by BM-derived T lineage progenitors. Both quantitative parameters and the mechanisms of thymus seeding remain poorly understood. Here, we determined the number of dedicated thymus-seeding progenitor niches (TSPNs) capable of supporting productive T cell development, turnover rates of niche occupancy, and feedback mechanisms. To this end, we established multicongenic fate mapping combined with mathematical modeling to quantitate individual events of thymus colonization. We applied this method to study thymus colonization in CCR7(-/-)CCR9(-/-) (DKO) mice, whose TSPNs are largely unoccupied. We showed that ∼160-200 TSPNs are present in the adult thymus and, on average, 10 of these TSPNs were open for recolonization at steady state. Preconditioning of wild-type mice revealed a similar number of TSPNs, indicating that preconditioning can generate space efficiently for transplanted T cell progenitors. To identify potential cellular feedback loops restricting thymus colonization, we performed serial transfer experiments. These experiments indicated that thymus seeding was directly restricted by the duration of niche occupancy rather than long-range effects, thus challenging current paradigms of thymus colonization. © 2015 Ziętara et al.

Wheat bran extract alters colonic fermentation and microbial composition, but does not affect faecal water toxicity: a randomised controlled trial in healthy subjects.

PubMed

Windey, Karen; De Preter, Vicky; Huys, Geert; Broekaert, Willem F; Delcour, Jan A; Louat, Thierry; Herman, Jean; Verbeke, Kristin

2015-01-28

Wheat bran extract (WBE), containing arabinoxylan-oligosaccharides that are potential prebiotic substrates, has been shown to modify bacterial colonic fermentation in human subjects and to beneficially affect the development of colorectal cancer (CRC) in rats. However, it is unclear whether these changes in fermentation are able to reduce the risk of developing CRC in humans. The aim of the present study was to evaluate the effects of WBE on the markers of CRC risk in healthy volunteers, and to correlate these effects with colonic fermentation. A total of twenty healthy subjects were enrolled in a double-blind, cross-over, randomised, controlled trial in which the subjects ingested WBE (10 g/d) or placebo (maltodextrin, 10 g/d) for 3 weeks, separated by a 3-week washout period. At the end of each study period, colonic handling of NH3 was evaluated using the biomarker lactose[15N, 15N']ureide, colonic fermentation was characterised through a metabolomics approach, and the predominant microbial composition was analysed using denaturing gradient gel electrophoresis. As markers of CRC risk, faecal water genotoxicity was determined using the comet assay and faecal water cytotoxicity using a colorimetric cell viability assay. Intake of WBE induced a shift from urinary to faecal 15N excretion, indicating a stimulation of colonic bacterial activity and/or growth. Microbial analysis revealed a selective stimulation of Bifidobacterium adolescentis. In addition, WBE altered the colonic fermentation pattern and significantly reduced colonic protein fermentation compared with the run-in period. However, faecal water cytotoxicity and genotoxicity were not affected. Although intake of WBE clearly affected colonic fermentation and changed the composition of the microbiota, these changes were not associated with the changes in the markers of CRC risk.

Effects of modified Sanhuang decoction () enema on serum tumor necrosis factor-α and colonic mucosa interleukin-1β, interleukin-6 levels in ulcerative colitis rats.

PubMed

Wang, Shuai; Zhou, Tao; Zhai, Jun-Peng; Wang, Li-Hua; Chen, Jing

2014-11-01

To investigate the effects of Modified Sanhuang Decoction (, MSD) enema on the serum tumor necrosis factor alpha (TNF-α) and colonic mucosa interleukin-1β (IL-1β), interleukin-6 (IL-6) levels in experimental ulcerative colitis (UC) rats. Forty-five male Wistar rats were randomly divided into 4 groups: normal group (n=12), model group (n=11), salazosulfapyridine (SASP) group (n=11) and MSD group (n=11). The UC model was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol solution. Rats in the normal group and model group were clystered with 0.9% normal saline, while in the SASP group and MSD group were clystered with SASP and MSD enema, respectively. After drug administration (10 mL/kg body weight, for 7 days), colonic gross changes and colonic mucosa histology were observed, serum TNF-α and colonic mucosa IL-1β, IL-6 levels were tested by enzyme linked immunosorbent assay and radioimmunoassay, respectively. As compared with the normal group, the experimental UC rats, the colonic mucosal damage index scores (CMDIs), histopathological scores (HS) and the serum TNF-α and colonic mucosa IL-1β, IL-6 levels significantly increased (P<0.05 or P<0.01). In the MSD and SASP groups, the ulcer area significantly reduced, and edema disappeared. The CMDIs, HS, the serum TNF-α and colonic mucosa IL-1β, IL-6 levels in the MSD and SASP groups significantly decreased (P<0.05 or P<0.01) compared with the model group. The CMDIs in the MSD group were lower than that in the SASP group (P<0.05), but there were no significant differences in HS, serum TNF-α or colonic mucosa IL-1β, IL-6 levels between the MSD and SASP groups. MSD enema can improve colonic mucosa impairment and decrease serum TNF-α and colonic mucosa IL-1β, IL-6 levels in experimental UC.

Antibiotic consumption and Enterobacteriaceae skin colonization in hospitalized adults.

PubMed

Kirby, A; Berry, C; West, R

2017-01-01

Enterobacteriaceae are increasingly antibiotic resistant, and skin colonization may contribute to their spread in hospitals. This study screened 100 hospitalized adults for Enterobacteriaceae skin colonization, and assessed potential risk factors, including antibiotic consumption. Multi-variable analysis found that antibiotic consumption whilst an inpatient [odds ratio (OR) 3.16, 95% confidence interval (CI) 1.19-8.4] and male sex (OR 2.92, 95% CI 1.06-8.4) were risk factors for Enterobacteriaceae skin colonization. If these risk factors are confirmed, work to understand the biological mechanism involved may lead to the development of interventions to prevent Enterobacteriaceae skin colonization. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Lack of chemoprevention of dietary Agaricus blazei against rat colonic aberrant crypt foci.

PubMed

Ziliotto, L; Barbisan, L F; Rodrigues, M A M

2008-06-01

The mushroom Agaricus blazei (Ab) has been widely used in folk medicine to treat various diseases including cancer. No information is available on its possible protective effects on the development of colon cancer. The potential blocking effect of Ab intake on the initiation stage of colon carcinogenesis was investigated in a short-term (4-week) bioassay using aberrant crypt foci (ACF) as biomarker. Male Wistar rats were given four subcutaneous injections of the carcinogen 1,2-dimethylhydrazine (DMH, 40 mg/kg bw, twice a week), during 2 weeks to induce ACF. The diet containing Ab at 5% was given 2 weeks before and during carcinogen treatment to investigate the potential beneficial effects of this edible mushroom on DMH-induced ACF. All groups were killed at the end of the fourth week. The colons were analyzed for ACF formation in 1% methylene blue whole-mount preparations and for cell proliferation in histological sections immunohistochemically stained for the proliferating cell nuclear antigen (PCNA). All DMH-treated rats developed ACF mainly in the middle and distal colon. Agaricus blazei intake at 5% did not alter the number of ACF induced by DMH or the PCNA indices in the colonic mucosa. Thus, the results of the present study did not confirm a chemopreventive activity of Ab on the initiation stage of rat colon carcinogenesis.

Percutaneous endoscopic colostomy of the left colon: a new technique for management of intractable constipation in children.

PubMed

Rawat, David J; Haddad, Munther; Geoghegan, Niamh; Clarke, Simon; Fell, John M

2004-07-01

The antegrade colonic enema is accepted as effective for management of intractable constipation in children when conventional bowel management has failed. This study describes experience with a new, minimally invasive technique, the distal antegrade colonic enema, which involves percutaneous endoscopic colostomy of the left colon. Fifteen children with refractory constipation and soiling who had radiographic evidence of megarectum and/or distal colonic delay were selected for the procedure. The junction of the descending and the sigmoid colon was identified colonoscopically, and the percutaneous endoscopic colostomy tube, through which antegrade distal colonic enema are administered, was inserted. Fourteen children underwent distal percutaneous endoscopic colostomy insertion. The median time required for the procedure was 30 minutes (20-50 minutes). Excluding one child (technical difficulties with percutaneous endoscopic colostomy placement), median post-procedural hospital stay was 4 days (2-27 days). Thirteen children were no longer soiling, and improvement in quality of life was reported at 2 months' follow-up. At 6 months' follow-up, 90% of children were clean during intervals between enemas. All children evaluated at 12 months' follow-up remained clean. Median duration of follow-up was 12.5 months (2-51 months). The distal percutaneous endoscopic colostomy is a simple alternative to established methods for delivery of antegrade enemas. It is less invasive and on reversal leaves only minor scarring.

The single-center experience with the standardization of single-site laparoscopic colectomy for right-sided colon cancer.

PubMed

Takahashi, Hidekazu; Takemasa, Ichiro; Haraguchi, Naotsugu; Nishimura, Junichi; Hata, Taishi; Yamamoto, Hirofumi; Matsuda, Chu; Mizushima, Tsunekazu; Doki, Yuichiro; Mori, Masaki

2017-08-01

Complete mesocolic excision (CME) with central vascular ligation (CVL) has been widely accepted as a surgical treatment for right-sided colon cancer. Single-site laparoscopic colectomy (SLC) is associated with reduced pain and improved cosmesis, in comparison to the multi-site laparoscopic colectomy (MCL). Although the feasibility of CME + CVL under MCL has been reported, SLC for right-sided colon cancer is generally challenging. The purpose of this study is to demonstrate our efforts to standardize the SLC for right-sided colon cancer. This retrospective study enrolled 202 consecutive patients with right-sided colon cancer who underwent laparoscopic colectomy for right-sided colon cancer, using an inferior approach and intraoperative navigation surgery, between 2008 and 2014. The patients were divided into 3 groups, based on the period of treatment, as follows: Period I (2008-2009, n = 56), Period II (2010-2011, n = 70), and Period III (2012-2014, n = 76). The patient's baseline characteristics did not differ among the three periods. The ratio of SLC significantly increased with the passage of the time. The short-term outcomes were similar among the three periods. As for oncological clearance, there was a significant increase in the number of resected lymph nodes with the passage of the time (P < 0.05). We successfully standardized SLC for right-sided colon cancer.

A randomized dose-response trial of aerobic exercise and health-related quality of life in colon cancer survivors.

PubMed

Brown, Justin C; Damjanov, Nevena; Courneya, Kerry S; Troxel, Andrea B; Zemel, Babette S; Rickels, Michael R; Ky, Bonnie; Rhim, Andrew D; Rustgi, Anil K; Schmitz, Kathryn H

2018-04-01

To examine the dose-response effects of aerobic exercise on health-related quality of life (HRQoL) among colon cancer survivors. Thirty-nine stage I to III colon cancer survivors were randomized to 1 of 3 groups: usual-care control, 150 min·wk -1 of aerobic exercise (low-dose) and 300 min·wk -1 of aerobic exercise (high-dose) for 6 months. HRQoL outcomes included the Short Form (SF)-36 physical and mental component summary, Functional Assessment of Cancer Therapy-Colorectal, Pittsburgh Sleep Quality Index, Fear of Cancer Recurrence Inventory, Fatigue Symptom Inventory, and North Central Cancer Treatment Group bowel function questionnaire, assessed at baseline and post intervention. The primary hypothesis was that exercise would improve HRQoL outcomes in a dose-response fashion, such that high-dose aerobic exercise would yield the largest improvements in HRQoL outcomes. Over 6 months, the low-dose group completed 141 ± 10 min·wk -1 of aerobic exercise, and the high-dose group completed 247 ± 11 min·wk -1 of aerobic exercise. Over 6 months, exercise improved the physical component summary score of the SF-36 (P trend  = 0.002), the Functional Assessment of Cancer Therapy-Colorectal (P trend  = 0.025), the Pittsburgh Sleep Quality Index (P trend  = 0.049), and the Fatigue Symptom Inventory (P trend  = 0.045) in a dose-response fashion. Between-group standardized mean difference effects sizes for the above-described findings were small to moderate in magnitude (0.35-0.75). No dose-response effects were observed for the mental component summary score of the SF-36, the Fear of Cancer Recurrence Inventory, or bowel function. Higher doses of aerobic exercise, up to 300 min·wk -1 , improve multiple HRQoL outcomes among stage I to III colon cancer survivors. These findings provide evidence that aerobic exercise may provide multiple health benefits for colon cancer survivors. Copyright © 2018 John Wiley & Sons, Ltd.

Combined Inoculation with Multiple Arbuscular Mycorrhizal Fungi Improves Growth, Nutrient Uptake and Photosynthesis in Cucumber Seedlings.

PubMed

Chen, Shuangchen; Zhao, Hongjiao; Zou, Chenchen; Li, Yongsheng; Chen, Yifei; Wang, Zhonghong; Jiang, Yan; Liu, Airong; Zhao, Puyan; Wang, Mengmeng; Ahammed, Golam J

2017-01-01

Mycorrhizal inoculation stimulates growth, photosynthesis and nutrient uptake in a wide range of host plants. However, the ultimate effects of arbuscular mycorrhyzal (AM) symbiosis vary with the plants and fungal species involved in the association. Therefore, identification of the appropriate combinations of AM fungi (AMF) that interact synergistically to improve their benefits is of high significance. Here, three AM fungal compositions namely VT ( Claroideoglomus sp., Funneliformis sp., Diversispora sp., Glomus sp., and Rhizophagus sp.) and BF ( Glomus intraradices , G. microageregatum BEG and G. Claroideum BEG 210), and Funneliformis mosseae (Fm) were investigated with respect to the growth, gas exchange parameters, enzymes activities in Calvin cycles and related gene expression in cucumber seedlings. The results showed that VT, BF and Fm could successfully colonize cucumber root to a different degree with the colonization rates 82.38, 74.65, and 70.32% at 46 days post inoculation, respectively. The plant height, stem diameter, dry weight, root to shoot ratio of cucumber seedlings inoculated with AMF increased significantly compared with the non-inoculated control. Moreover, AMF colonization greatly increased the root activity, chlorophyll content, net photosynthetic rate, light saturated rate of the CO 2 assimilation ( A sat), maximum carboxylation rate ( V cmax ) and maximum ribulose-1,5-bis-phosphate (RuBP) regeneration rate ( J max), which were increased by 52.81, 30.75, 58.76, 47.00, 69.15, and 65.53% when inoculated with VT, respectively. The activities of some key enzymes such RuBP carboxylase/oxygenase (RuBisCO), D-fructose-1,6-bisphosphatase (FBPase), D-fructose-6-phosphatase (F6P) and ribulose-5-phosphate kinase (Ru5PK), and related gene expression involved in the Calvin cycle including RCA , FBPase , FBPA , SBPase , rbcS and rbcL were upregulated by AMF colonization. AMF inoculation also improved macro- and micro nutrient contents such as N, P, K, S, Ca, Cu, Fe, Mn, Mg, and Zn in roots. Further analysis revealed that inoculation with VT had relatively better effect on growth of cucumber seedling followed by BF and Fm, indicating that AMF composition consisting of distant AMF species may have a better effect than a single or closely related AMF spp. This study advances the understanding of plant responses to different AM fungi toward development of strategies on AMF-promoted vegetable production.

[Multiple colonic anastomoses in the surgical treatment of short bowel syndrome. A new technique].

PubMed

Robledo-Ogazón, Felipe; Becerril-Martínez, Guillermo; Hernández-Saldaña, Víctor; Zavala-Aznar, Marí Luisa; Bojalil-Durán, Luis

2008-01-01

Some surgical pathologies eventually require intestinal resection. This may lead to an extended procedure such as leaving 30 cm of proximal jejunum and left and sigmoid colon. One of the most important consequences of this type of resection is "intestinal failure" or short bowel syndrome. This complex syndrome leads to different metabolic and water and acid/base imbalances, as well as nutritional and immunological challenges along with the problem accompanying an abdomen subjected to many surgical procedures and high mortality. Many surgical techniques have been developed to improve quality of life of patients. We designed a non-transplant surgical approach and performed the procedure on two patients with postoperative short bowel syndrome with <40 cm of proximal jejunum and left colon. There are a variety of non-transplant surgical procedures that, due to their complex technique or high mortality rate, have not resolved this important problem. However, the technique we present in this work can be performed by a large number of surgeons. The procedure has a low morbimortality rate and offers the opportunity for better control of metabolic and acid/base balance, intestinal transit and proper nutrition. We consider that this technique offers a new alternative for the complex management required by patients with short bowel syndrome and facilitates their long-term nutritional control.

Dietary Phenethyl Isothiocyanate Protects Mice from Colitis Associated Colon Cancer.

PubMed

Liu, Yi; Dey, Moul

2017-09-06

We have previously reported alleviation of dextran sodium sulfate (DSS)-induced ulcerative colitis signs in phenethyl isothiocyanate (PEITC)-treated mice. Here we investigated chemoprotective activities of PEITC in mice with Azoxymethane-DSS induced colitis associated colon carcinogenesis. We also examined the molecular mediators associated with the PEITC effects using relevant cell lines. A 0.12% PEITC-enriched mouse-diet reduced mucosal and submucosal inflammation as well as glandular atypia by 12% and the frequency of adenocarcinoma by 17% with a concomitant improvement in overall disease activity indices compared to the diseased control group. Lipopolysaccharide-induced in vitro up-regulation of key mediators of inflammation, immune response, apoptosis, and cell proliferation were attenuated by 10 μM PEITC. Three of these mediators showed concentration-dependent reduction in respective mRNAs. Furthermore, PEITC inhibited Nuclear factor kappa B1 (NFκB1) proteins in a concentration-dependent manner. The NFκB1 mRNA expression inversely correlated ( r = −0.940, p = 0.013) with tri-methylation of lysine 27 on histone 3 near its promoter region in a time-dependent manner. These results indicate that PEITC may slow down the development of colon carcinogenesis in an inflammatory intestinal setting which is potentially associated with epigenetic modulation of NFκB1 signaling.

A perspective on the complexity of dietary fiber structures and their potential effect on the gut microbiota.

PubMed

Hamaker, Bruce R; Tuncil, Yunus E

2014-11-25

Even though there are many factors that determine the human colon microbiota composition, diet is an important one because most microorganisms in the colon obtain energy for their growth by degrading complex dietary compounds, particularly dietary fibers. While fiber carbohydrates that escape digestion in the upper gastrointestinal tract are recognized to have a range of structures, the vastness in number of chemical structures from the perspective of the bacteria is not well appreciated. In this article, we introduce the concept of "discrete structure" that is defined as a unique chemical structure, often within a fiber molecule, which aligns with encoded gene clusters in bacterial genomes. The multitude of discrete structures originates from the array of different fiber types coupled with structural variations within types due to genotype and growing environment, anatomical parts of the grain or plant, discrete regions within polymers, and size of oligosaccharides and small polysaccharides. These thousands of discrete structures conceivably could be used to favor bacteria in the competitive colon environment. A global framework needs to be developed to better understand how dietary fibers can be used to obtain predicted changes in microbiota composition for improved health. This will require a multi-disciplinary effort that includes biological scientists, clinicians, and carbohydrate specialists. Copyright © 2014 Elsevier Ltd. All rights reserved.

Candida spp. airway colonization: A potential risk factor for Acinetobacter baumannii ventilator-associated pneumonia.

PubMed

Tan, Xiaojiang; Zhu, Song; Yan, Dongxing; Chen, Weiping; Chen, Ruilan; Zou, Jian; Yan, Jingdong; Zhang, Xiangdong; Farmakiotis, Dimitrios; Mylonakis, Eleftherios

2016-08-01

This retrospective study was conducted to identify potential risk factors for Acinetobacter baumannii (A. baumannii) ventilator-associated pneumonia (VAP) and evaluate the association between Candida spp. airway colonization and A. baumannii VAP. Intensive care unit (ICU) patients who were on mechanical ventilation (MV) for ≥48 hours were divided into the following groups: patients with and without Candida spp. airway colonization; colonized patients receiving antifungal treatment or not; patients with A. baumannii VAP and those without VAP. Logistic regression analysis and propensity score matching were used to identify factors independently associated with A. baumannii VAP. Among 618 eligible patients, 264 (43%) had Candida spp. airway colonization and 114 (18%) developed A. baumannii VAP. Along with MV for ≥7 days (adjusted odds ratio [aOR] 8.9, 95% confidence intervals [95% CI] 4.9-15.8) and presence of a central venous catheter (aOR 3.2, 95% CI 1.1-9), Candida spp. airway colonization (aOR 2.6, 95% CI 1.6-4.3) was identified as an independent risk factor for A. baumannii VAP. Patients with Candida spp. airway colonization were more likely to develop A. baumannii VAP than non-colonized patients (23% vs 15%, P=.01 and 34% vs. 15%, P<.001 in propensity score-matched subgroups). Administration of antifungal agents was not associated with A. baumannii VAP (29% vs. 21%, P=.153) but with higher in-hospital mortality (53% vs. 39%, P=.037). Candida spp. airway colonization (43%) and A. baumannii VAP (18%) were common in ICU patients who were on mechanical ventilation for at least 48 hours. Candida spp. airway colonization was an independent risk factor for subsequent A. baumannii VAP. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A novel folate-modified self-microemulsifying drug delivery system of curcumin for colon targeting.

PubMed

Zhang, Lin; Zhu, Weiwei; Yang, Chunfen; Guo, Hongxia; Yu, Aihua; Ji, Jianbo; Gao, Yan; Sun, Min; Zhai, Guangxi

2012-01-01

The objective of this study was to prepare, characterize, and evaluate a folate-modified self-microemulsifying drug delivery system (FSMEDDS) with the aim to improve the solubility of curcumin and its delivery to the colon, facilitating endocytosis of FSMEDDS mediated by folate receptors on colon cancer cells. Ternary phase diagrams were constructed in order to obtain the most efficient self-emulsification region, and the formulation of curcumin-loaded SMEDDS was optimized by a simplex lattice experiment design. Then, three lipophilic folate derivatives (folate-polyethylene glycol-distearoylphosphatidylethanolamine, folate-polyethylene glycol-cholesteryl hemisuccinate, and folate-polyethylene glycol-cholesterol) used as a surfactant were added to curcumin-loaded SMEDDS formulations. An in situ colon perfusion method in rats was used to optimize the formulation of FSMEDDS. Curcumin-loaded FSMEDDS was then filled into colon-targeted capsules and the in vitro release was investigated. Cytotoxicity studies and cellular uptake studies was used in this research. The optimal formulation of FSMEDDS obtained with the established in situ colon perfusion method in rats was comprised of 57.5% Cremophor(®) EL, 32.5% Transcutol(®) HP, 10% Capryol™ 90, and a small amount of folate-polyethylene glycol-cholesteryl hemisuccinate (the weight ratio of folate materials to Cremophor EL was 1:100). The in vitro release results indicated that the obtained formulation of curcumin could reach the colon efficiently and release the drug immediately. Cellular uptake studies analyzed with fluorescence microscopy and flow cytometry indicated that the FSMEDDS formulation could efficiently bind with the folate receptors on the surface of positive folate receptors cell lines. In addition, FSMEDDS showed greater cytotoxicity than SMEDDS in the above two cells. FSMEDDS-filled colon-targeted capsules are a potential carrier for colon delivery of curcumin.

Inhibitory effects of astaxanthin on azoxymethane-induced colonic preneoplastic lesions in C57/BL/KsJ-db/db mice.

PubMed

Kochi, Takahiro; Shimizu, Masahito; Sumi, Takafumi; Kubota, Masaya; Shirakami, Yohei; Tanaka, Takuji; Moriwaki, Hisataka

2014-12-17

Obesity and related metabolic abnormalities, including excess oxidative stress and chronic inflammation, are associated with colorectal carcinogenesis. Astaxanthin, a xanthophyll carotenoid found in aquatic animals, is known to possess antioxidant, anti-inflammatory, and antineoplastic properties. The present study examined the effects of astaxanthin on the development of azoxymethane (AOM)-induced colonic premalignant lesions in C57BL/KsJ-db/db (db/db) obese mice. Male db/db mice were administered 4 weekly subcutaneous injections of AOM (15 mg/kg body weight) from 5 weeks of age and subsequently, from 1 week after the last injection of AOM, were fed a diet containing 200 ppm astaxanthin throughout the experiment (8 weeks). The development of colonic premalignant lesions, i.e., aberrant crypt foci and β-catenin accumulated crypts, was significantly inhibited in mice treated with astaxanthin than in mice fed the basal diet. Astaxanthin administration markedly reduced urinary levels of 8-OHdG and serum levels of d-ROMs, which are oxidative stress markers, while increasing the expression of mRNA for the antioxidant enzymes GPx1, SOD1, and CAT in the colonic mucosa of AOM-treated db/db mice. The expression levels of IL-1β, IL-6, F4/80, CCL2, and CXCL2 mRNA in the colonic mucosa of AOM-treated mice were significantly decreased by astaxanthin. Dietary feeding with astaxanthin also resulted in a reduction in the numbers of NF-κB- and PCNA-positive cells that were increased by AOM exposure, in the colonic epithelium. These findings suggest that astaxanthin inhibits the development of colonic premalignant lesions in an obesity-related colorectal carcinogenesis model by reducing oxidative stress, attenuating chronic inflammation, and inhibiting NF-κB activation and cell proliferation in the colonic mucosa. Astaxanthin, therefore, may be a potential candidate as a chemoprevention agent against colorectal carcinogenesis in obese individuals.

MECHANISTIC INFORMATION ON DISINFECTION BY-PRODUCTS FOR RISK ASSESSMENT

EPA Science Inventory

Colon cancer is the second most common cancer in people from developed countries, and populations exposed t o 50?g/L or more of trihalomethanes for at 1east 35 years have been estimated to be 1.5 times more likely to develop colon cancer. Trihalomethanes are one of the classes ...

Consequences of pre-inoculation with native arbuscular mycorrhizae on root colonization and survival of Artemisia tridentata ssp. wyomingensis (Wyoming big sagebrush) seedlings after transplanting

Treesearch

Bill Eugene Davidson

2015-01-01

Inoculation of seedlings with arbuscular mycorrhizal fungi (AMF) is a common practice aimed at improving seedling establishment. The success of this practice largely depends on the ability of the inoculum to multiply and colonize the growing root system after transplanting. These events were investigated in Artemisia tridentata ssp. wyomingensis (Wyoming big sagebrush...

Mode of Birth Influences Preterm Infant Intestinal Colonization with Bacteroides Over the Early Neonatal Period

PubMed Central

Gregory, Katherine E.; LaPlante, Rose D.; Shan, Gururaj; Kumar, Deepak Vijaya; Gregas, Matt

2015-01-01

Background Intestinal colonization during infancy is important to short and long term health outcomes. Bacteroides, an early member of the intestinal microbiome, are necessary for breaking down complex molecules within the intestine and function to assist the body’s immune system in fighting against potentially harmful pathogens. Little is known about the colonization pattern of Bacteroides in preterm infants during the early neonatal period. Purpose This study measured Bacteroides colonization during the early neonatal period in a population of preterm infants based on clinical factors including mode of birth, antibiotics, and nutrition. Methods Bacterial DNA was isolated from 144 fecal samples from 29 preterm infants and analyzed using quantitative real time polymerase chain reaction (PCR). Analyses included liner mixed models to determine which clinical factors affect Bacteroides colonization of the infant gut. Results We found that infants born via vaginal canal had a higher rate of increase in Bacteroides than infants born via Cesarean section (p<.001). We did not find significant associations between antibiotic administration and differences in nutritional exposures with Bacteroides colonization. Implications for Practice These findings highlight the significant influence of mode of birth on Bacteroides colonization. While mode of birth is not always modifiable, these study findings may help develop interventions for preterm infants born via Cesarean section aimed at overcoming delayed Bacteroides colonization. Implications for Research Greater study of the intestinal microbiome and the clinical factors relevant to the preterm infant is needed so that interventions may be developed and tested, resulting in optimal microbial and immune health. PMID:26551793

Microbial community development in a dynamic gut model is reproducible, colon region specific, and selective for Bacteroidetes and Clostridium cluster IX.

PubMed

Van den Abbeele, Pieter; Grootaert, Charlotte; Marzorati, Massimo; Possemiers, Sam; Verstraete, Willy; Gérard, Philippe; Rabot, Sylvie; Bruneau, Aurélia; El Aidy, Sahar; Derrien, Muriel; Zoetendal, Erwin; Kleerebezem, Michiel; Smidt, Hauke; Van de Wiele, Tom

2010-08-01

Dynamic, multicompartment in vitro gastrointestinal simulators are often used to monitor gut microbial dynamics and activity. These reactors need to harbor a microbial community that is stable upon inoculation, colon region specific, and relevant to in vivo conditions. Together with the reproducibility of the colonization process, these criteria are often overlooked when the modulatory properties from different treatments are compared. We therefore investigated the microbial colonization process in two identical simulators of the human intestinal microbial ecosystem (SHIME), simultaneously inoculated with the same human fecal microbiota with a high-resolution phylogenetic microarray: the human intestinal tract chip (HITChip). Following inoculation of the in vitro colon compartments, microbial community composition reached steady state after 2 weeks, whereas 3 weeks were required to reach functional stability. This dynamic colonization process was reproducible in both SHIME units and resulted in highly diverse microbial communities which were colon region specific, with the proximal regions harboring saccharolytic microbes (e.g., Bacteroides spp. and Eubacterium spp.) and the distal regions harboring mucin-degrading microbes (e.g., Akkermansia spp.). Importantly, the shift from an in vivo to an in vitro environment resulted in an increased Bacteroidetes/Firmicutes ratio, whereas Clostridium cluster IX (propionate producers) was enriched compared to clusters IV and XIVa (butyrate producers). This was supported by proportionally higher in vitro propionate concentrations. In conclusion, high-resolution analysis of in vitro-cultured gut microbiota offers new insight on the microbial colonization process and indicates the importance of digestive parameters that may be crucial in the development of new in vitro models.

Combination Effect of Regulatory T-Cell Depletion and Ionizing Radiation in Mouse Models of Lung and Colon Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Son, Cheol-Hun; Department of Biochemistry, Pusan National University School of Medicine, Yangsan; Bae, Jae-Ho

2015-06-01

Purpose: To investigate the potential of low-dose cyclophosphamide (LD-CTX) and anti-CD25 antibody to prevent activation of regulatory T cells (Tregs) during radiation therapy. Methods and Materials: We used LD-CTX and anti-CD25 monoclonal antibody as a means to inhibit Tregs and improve the therapeutic effect of radiation in a mouse model of lung and colon cancer. Mice were irradiated on the tumor mass of the right leg and treated with LD-CTX and anti-CD25 antibody once per week for 3 weeks. Results: Combined treatment of LD-CTX or anti-CD25 antibody with radiation significantly decreased Tregs in the spleen and tumor compared with control andmore » irradiation only in both lung and colon cancer. Combinatorial treatments resulted in a significant increase in the effector T cells, longer survival rate, and suppressed irradiated and distal nonirradiated tumor growth. Specifically, the combinatorial treatment of LD-CTX with radiation resulted in outstanding regression of local and distant tumors in colon cancer, and almost all mice in this group survived until the end of the study. Conclusions: Our results suggest that Treg depletion strategies may enhance radiation-mediated antitumor immunity and further improve outcomes after radiation therapy.« less

Bitter Melon Component and Colon Cancer Prevention | Division of Cancer Prevention

Cancer.gov

Despite the best screening efforts to identify and remove colon polyps, colon cancer remains a leading cause of cancer related morbidity and mortality, both in the US and around the world. Also, current therapeutics while good in removing most cancer cells are not adequate because they leave some cells behind. This is because these cells can reemerge and develop a fresh tumor,

Maintaining physical activity during refeeding improves body composition, intestinal hyperpermeability and behavior in anorectic mice

PubMed Central

Achamrah, Najate; Nobis, Séverine; Breton, Jonathan; Jésus, Pierre; Belmonte, Liliana; Maurer, Brigitte; Legrand, Romain; Bôle-Feysot, Christine; Rego, Jean Luc do; Goichon, Alexis; Rego, Jean Claude do; Déchelotte, Pierre; Fetissov, Sergueï O; Claeyssens, Sophie; Coëffier, Moïse

2016-01-01

A role of gut-brain axis emerges in the pathophysiology of anorexia nervosa and maintaining adapted physical activity during refeeding remains discussed. We aimed to assess gastrointestinal protein metabolism and investigate the contribution of physical activity during refeeding in C57BL/6 mice with activity-based anorexia (ABA). ABA mice exhibited lower body weight and food intake with increase of lean mass/fat mass ratio and fat oxidation. Colonic permeability was increased in ABA. Ad libitum food access was then restored and ABA group was divided into two subgroups, with access to running wheel (ABA-PA) or not (ABA-NPA). After refeeding, fat free mass was completely restored only in ABA-PA. Colonic permeability was enhanced in ABA-NPA. Finally, muscle kynurenine conversion into kynurenic acid was lower in ABA-NPA who also exhibited altered behavior. Maintaining physical activity during refeeding may thus limit colonic hyperpermeability and improve behavior in anorectic mice. PMID:26906060

Methicillin-Resistant Staphylococcus aureus Infections: A Comprehensive Review and a Plastic Surgeon's Approach to the Occult Sites.

PubMed

Hunter, Cedric; Rosenfield, Lorne; Silverstein, Elena; Petrou-Zeniou, Panayiota

2016-08-01

Up to 20 percent of the general population is persistently colonized with Staphylococcus aureus, and 1 to 3 percent of the population is colonized with community-acquired methicillin-resistant S. aureus. Currently, the knowledge of methicillin-resistant Staphylococcus aureus carriage sites other than the nose, and their effect on surgical site infections in cosmetic surgery, is lacking. A comprehensive literature review using the PubMed database to analyze prevalence, anatomical carrier sites, current screening and decontamination protocols and guidelines, and methicillin-resistant S. aureus in cosmetic surgery was performed. The senior author's (L.R.) methicillin-resistant S. aureus infection experience and prevention protocols were also reviewed. Nasal swabs detect only 50.5 percent of methicillin-resistant S. aureus colonization, and broad screening has noted the presence of methicillin-resistant S. aureus in the ear canal and umbilicus. Decolonization protocols within the orthopedic and cardiothoracic surgery literature have reduced rates of methicillin-resistant S. aureus surgical-site infections. There are no decolonization guidelines for plastic surgeons. Since instituting their decolonization protocol, the authors have had no cases of methicillin-resistant S. aureus infection in nearly 1000 cosmetic surgery procedures. There are very limited, if any, Level I or II data regarding methicillin-resistant S. aureus screening and decolonization. As the sequelae of a surgical-site infection can be disastrous, expert opinions recommend that plastic surgeons vigorously address methicillin-resistant S. aureus colonization and infection. The authors have developed and recommend a simple decolonization protocol that includes treatment of the umbilicus, ear canal, and nares to limit surgical-site infection and improve surgical outcomes.

Fecal colonization with P-fimbriated Escherichia coli in newborn children and relation to development of extraintestinal E. coli infections.

PubMed

Tullus, K

1987-01-01

The incidence of E. coli pyelonephritis before the age of one year among the children born at Danderyd Hospital during a ten year period was studied. During the study period, 4 or 5 outbreaks of E. coli pyelonephritis occurred among the children who had previously been staying in the hospital's neonatal ward. These outbreaks seemed to have been caused by nosocomial spread of and fecal colonization with certain virulent E. coli strains among the children staying in the ward during certain periods of time. The strains that were spread in the ward seemed to belong to certain pyelonephritogenic E. coli clones of the serotypes O6:K5, O4:K3 and possibly O6:K2. Although the children became fecally colonized with the strains in the neonatal ward, most fell ill some time after they had left the ward. The mean age at the development of their first pyelonephritis was 3.4 months for the boys and 6.2 months for the girls, who had been cared for in this ward. A correlation between the number of infections and the bed occupancy of the ward could be found (p less than 0.01). The risk for a child staying in the ward during an outbreak to develop pyelonephritis was about 5-10%. There was a baseline incidence rate of 0.6-0.7% during non-epidemic periods. During one of the outbreaks there was also an increased incidence rate of E. coli septicemia among the children staying in the neonatal ward. The predictive value of fecal colonization with P-fimbriated E. coli for the later development of extraintestinal E. coli infections was studied in a 2.5 year prospective study. During this study period there was a baseline incidence rate of 10-20% fecal colonization with P-fimbriated E. coli among the children staying in both the neonatal and maternity wards, interrupted only by minor peaks of colonization with such strains. Length of stay in the neonatal ward and a high bed occupancy of the neonatal ward were statistically correlated to fecal colonization with P-fimbriated E. coli strains (p less than 0.01). During the prospective study there was no difference in the incidence rates of pyelonephritis before the age of one year between the neonatal and maternity ward children. These incidence rates were 0.59% and 0.66%, respectively. Only one of the 113 children from the neonatal ward who were fecally colonized with P-fimbriated E. coli strains later developed pyelonephritis. Thus, there was no predictive value of fecal colonization with P-fimbriated strains for the later development of pyelonephritis.(ABSTRACT TRUNCATED AT 400 WORDS)

Curcumin conjugated with PLGA potentiates sustainability, anti-proliferative activity and apoptosis in human colon carcinoma cells.

PubMed

Waghela, Bhargav N; Sharma, Anupama; Dhumale, Suhashini; Pandey, Shashibahl M; Pathak, Chandramani

2015-01-01

Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid) and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116). The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy.

Choroidal and skin metastases from colorectal cancer.

PubMed

Ha, Joo Young; Oh, Edward Hynseung; Jung, Moon Ki; Park, Song Ee; Kim, Ji Tak; Hwang, In Gyu

2016-11-21

Choroidal and skin metastasis of colon cancer is rare. In women, the frequency of cutaneous metastasis from colon cancer as the primary lesion in is 9% and skin metastasis occurs in 0.81% of all colorectal cancers. We report a patient with colonic adenocarcinoma who presented with visual disorder in her right eye and scalp pain as her initial symptoms. Contrast-enhance orbital magnetic resonance imaging with fat suppression revealed an infrabulbar mass, and skin biopsy of the posterior parietal scalp confirmed adenocarcinoma. These symptoms were diagnosed as being caused by choroidal and skin metastases of colonic adenocarcinoma. We started palliative chemotherapy with oral capecitabine (1000 mg/m 2 , twice a day, on days 1-14) every 3 wk, which was effective at shrinking the brain masses and improving the visual disorder. This is the first report that capecitabine is effective at reducing a choroidal and cutaneous metastatic lesion from right-sided colorectal cancer.

A case of leptospirosis simulating colon cancer with liver metastases

PubMed Central

Granito, Alessandro; Ballardini, Giorgio; Fusconi, Marco; Volta, Umberto; Muratori, Paolo; Sambri, Vittorio; Battista, Giuseppe; Bianchi, Francesco B.

2004-01-01

We report a case of a 61-year-old man who presented with fatigue, abdominal pain and hepatomegaly. Computed tomography (CT) of the abdomen showed hepatomegaly and multiple hepatic lesions highly suggestive of metastatic diseases. Due to the endoscopic finding of colon ulcer, colon cancer with liver metastases was suspected. Biochemically a slight increase of transaminases, alkaline phosphatase and gammaglutamyl transpeptidase were present; α - fetoprotein, carcinoembryogenic antigen and carbohydrate 19-9 antigen serum levels were normal. Laboratory and instrumental investigations, including colon and liver biopsies revealed no signs of malignancy. In the light of spontaneous improvement of symptoms and CT findings, his personal history was revaluated revealing direct contact with pigs and their tissues. Diagnosis of leptospirosis was considered and confirmed by detection of an elevated titer of antibodies to leptospira. After two mo, biochemical data, CT and colonoscopy were totally normal. PMID:15285043

Immune responses and parasitological observations induced during probiotic treatment with medicinal Trichuris suis ova in a healthy volunteer.

PubMed

Williams, Andrew R; Dige, Anders; Rasmussen, Tue Kruse; Hvas, Christian L; Dahlerup, Jens F; Iversen, Lars; Stensvold, C Rune; Agnholt, Jørgen; Nejsum, Peter

2017-08-01

Ingestion of eggs (ova) of the porcine nematode parasite Trichuris suis (TSO) may reduce the severity of autoimmune disorders, however the development of TSO treatment as a useful therapy for autoimmune diseases is hampered by a lack of knowledge on the development of the parasite and the nature of the local immune responses in humans. Here, we used colonoscopy to investigate the development of T. suis and related mucosal and systemic immune responses during TSO treatment in an intestinally healthy male volunteer. TSO treatment induced T. suis-specific serum antibodies, a transient blood eosinophilia, and increases in IFNγ + and IL4 + cells within the circulating CD4 + T-cell population. Increased expression of genes encoding cytokines (IL4, IL10, IL17 and TGF-β), and transcription factors (FOXP3, GATA3 and RORC) were apparent in the ascending and transverse colon (the predilection site of the worms), whereas only limited changes in gene expression were observed proximally (ileum) and distally (descending colon) to the infected tissue. We further show that T. suis is able to colonise the human colon, with a number of worms developing to a similar size and morphology observed in the natural pig host, and a small number of unembryonated eggs were passed in the faeces, indicating patent infection. Notably, the volunteer experienced a substantial improvement in psoriasis during the course of TSO treatment. Thus, TSO treatment induced a mixed Th1/Th2/T regulatory response at the local site of infection, which was also reflected to some extent in the peripheral circulation. These results, together with the first definitive observations that T. suis can mature to adult size and reproduce in humans, shed new light on the interaction between the human immune system and probiotic helminth treatment, which should facilitate further development of this novel therapeutic option. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Structure, viability and bacterial kinetics of an in vitro biofilm model using six bacteria from the subgingival microbiota.

PubMed

Sánchez, M C; Llama-Palacios, A; Blanc, V; León, R; Herrera, D; Sanz, M

2011-04-01

There are few in vitro models available in the scientific literature for study of the structure, formation and development of the subgingival biofilm. The purpose of this study was to develop and validate an in vitro biofilm model, using representative selected bacteria from the subgingival microbiota. Six standard reference strains were used to develop biofilms over sterile ceramic calcium hydroxyapatite discs coated with saliva within the wells of presterilized polystyrene tissue culture plates. The selected species represent initial (Streptococcus oralis and Actinomyces naeslundii), early (Veillonella parvula), secondary (Fusobacterium nucleatum) and late colonizers (Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans). The structure of the biofilm obtained was studied using a vital fluorescence technique in conjunction with confocal laser scanning microscopy. The biofilm bacterial kinetics were studied by terminal restriction fragment length polymorphism analysis. After 12 h, initial and early colonizers were the first microorganisms detected adhering to the calcium hydroxyapatite discs. The intermediate colonizer F. nucleatum was not detected in the model until 24 h of incubation. Late colonizers A. actinomycetemcomitans and P. gingivalis could be measured inside the biofilm after 48 h. The biofilm reached its steady state between 72 and 96 h after inoculation, with bacterial vitality increasing from the hydroxyapatite surface to the central part of the biofilm. An in vitro biofilm model was developed and validated, demonstrating a pattern of bacterial colonization and maturation similar to the in vivo development of the subgingival biofilm. © 2011 John Wiley & Sons A/S.

Planting sentinel European trees in eastern Asia as a novel method to identify potential insect pest invaders.

PubMed

Roques, Alain; Fan, Jian-Ting; Courtial, Béatrice; Zhang, Yan-Zhuo; Yart, Annie; Auger-Rozenberg, Marie-Anne; Denux, Olivier; Kenis, Marc; Baker, Richard; Sun, Jiang-Hua

2015-01-01

Quarantine measures to prevent insect invasions tend to focus on well-known pests but a large proportion of the recent invaders were not known to cause significant damage in their native range, or were not even known to science before their introduction. A novel method is proposed to detect new potential pests of woody plants in their region of origin before they are introduced to a new continent. Since Asia is currently considered to be the main supplier of insect invaders to Europe, sentinel trees were planted in China during 2007-2011 as an early warning tool to identify the potential for additional Asian insect species to colonize European trees. Seedlings (1-1.5 m tall) of five broadleaved (Quercus petraea, Q. suber, Q. ilex, Fagus sylvatica, and Carpinus betulus) and two conifer species (Abies alba and Cupressus sempervirens) were planted in blocks of 100 seedlings at two widely separated sites (one in a nursery near Beijing and the other in a forest environment near Fuyang in eastern China), and then regularly surveyed for colonization by insects. A total of 104 insect species, mostly defoliators, were observed on these new hosts, and at least six species were capable of larval development. Although a number of the insects observed were probably incidental feeders, 38 species had more than five colonization events, mostly infesting Q. petraea, and could be considered as being capable of switching to European trees if introduced to Europe. Three years was shown to be an appropriate duration for the experiment, since the rate of colonization then tended to plateau. A majority of the identified species appeared to have switched from agricultural crops and fruit trees rather than from forest trees. Although these results are promising, the method is not appropriate for xylophagous pests and other groups developing on larger trees. Apart from the logistical problems, the identification to species level of the specimens collected was a major difficulty. This situation could be improved by the development of molecular databases.

Planting Sentinel European Trees in Eastern Asia as a Novel Method to Identify Potential Insect Pest Invaders

PubMed Central

Roques, Alain; Fan, Jian-ting; Courtial, Béatrice; Zhang, Yan-zhuo; Yart, Annie; Auger-Rozenberg, Marie-Anne; Denux, Olivier; Kenis, Marc; Baker, Richard; Sun, Jiang-hua

2015-01-01

Quarantine measures to prevent insect invasions tend to focus on well-known pests but a large proportion of the recent invaders were not known to cause significant damage in their native range, or were not even known to science before their introduction. A novel method is proposed to detect new potential pests of woody plants in their region of origin before they are introduced to a new continent. Since Asia is currently considered to be the main supplier of insect invaders to Europe, sentinel trees were planted in China during 2007-2011 as an early warning tool to identify the potential for additional Asian insect species to colonize European trees. Seedlings (1-1.5 m tall) of five broadleaved (Quercus petraea, Q. suber, Q. ilex, Fagus sylvatica, and Carpinus betulus) and two conifer species (Abies alba and Cupressus sempervirens) were planted in blocks of 100 seedlings at two widely separated sites (one in a nursery near Beijing and the other in a forest environment near Fuyang in eastern China), and then regularly surveyed for colonization by insects. A total of 104 insect species, mostly defoliators, were observed on these new hosts, and at least six species were capable of larval development. Although a number of the insects observed were probably incidental feeders, 38 species had more than five colonization events, mostly infesting Q. petraea, and could be considered as being capable of switching to European trees if introduced to Europe. Three years was shown to be an appropriate duration for the experiment, since the rate of colonization then tended to plateau. A majority of the identified species appeared to have switched from agricultural crops and fruit trees rather than from forest trees. Although these results are promising, the method is not appropriate for xylophagous pests and other groups developing on larger trees. Apart from the logistical problems, the identification to species level of the specimens collected was a major difficulty. This situation could be improved by the development of molecular databases. PMID:25993342

Colonization on Cucumber Root and Enhancement of Chlorimuron-ethyl Degradation in the Rhizosphere by Hansschlegelia zhihuaiae S113 and Root Exudates.

PubMed

Zhang, Hao; Chen, Feng; Zhao, Hua-Zhu; Lu, Jia-Sen; Zhao, Meng-Jun; Hong, Qing; Huang, Xing

2018-05-09

The colonization of Hansschlegelia zhihuaiae S113 and its degradation of the herbicide chlorimuron-ethyl in the cucumber rhizosphere was investigated. The results reveal that S113 colonized the cucumber roots (2.14 × 10 5 cells per gram of roots) and were able to survive in the rhizosphere (maintained for 20 d). The root exudates promoted colonization on roots and increased the degradation of chlorimuron-ethyl by S113. Five organic acids in cucumber-root exudates were detected and identified by HPLC. Citric acid and fumaric acid significantly stimulated S113 colonization on cucumber roots, with 18.4 and 15.5% increases, respectively, compared with the control. After irrigation with an S113 solution for 10 days, chlorimuron-ethyl could not be detected in the roots, seedlings, or rhizosphere soil, which allowed for improved cucumber growth. Therefore, the degradation mechanism of chlorimuron-ethyl residues by S113 in the rhizosphere could be applied in situ for the bioremediation of chlorimuron-ethyl contaminated soil to ensure crop safety.

The association between oral health status and respiratory pathogen colonization with pneumonia risk in institutionalized adults.

PubMed

Hong, Chl; Aung, M M; Kanagasabai, K; Lim, C A; Liang, S; Tan, K S

2018-05-01

This study aimed to assess the oral health and the prevalence of pre-existing oral colonization with respiratory pathogens in dependent elderly, and whether these factors influence pneumonia development. Participants residing in a long-term care facility received bedside oral examinations, and information on their oral health (caries status, calculus index and debris index) was obtained. Samples from the tongue and teeth were collected at baseline and at time of pneumonia development. Sputum was collected at the time of pneumonia diagnosis. Samples were assessed for Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pneumoniae by polymerase chain reaction. This was a 1-year longitudinal study of 60 dependent elderly (mean age: 64.2 ± 14.1 years). Seventeen patients (28.3%) developed pneumonia. The mean Decayed, Missing and Filled Teeth and Simplified Oral Hygiene Index were 22.8 ± 9.2 and 4.0 ± 1.0, respectively. At baseline, 48.3% were orally colonized with ≥1 respiratory pathogens. The presence of H. influenzae (P = .002) and P. aeruginosa (P = .049) in the sputum was significantly associated with their colonization on the tongue at baseline. In the bivariate analyses, pneumonia development was associated with naso-gastric feeding tube (P = .0001), H. influenzae (P = .015) and P. aeruginosa (P = .003) tongue colonization at baseline and calculus index (P = .002). Multivariate analyses revealed that calculus index (P = .09) and the presence of tracheostomy (P = .037) were associated with pneumonia. The calculus amount and tongue colonization with respiratory pathogens are risk factors for pneumonia development. Oral hygiene measures to remove tongue biofilm and calculus may reduce pneumonia development. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparative study of the optical properties of colon mucosa and colon precancerous polyps between 400 and 1000 nm

NASA Astrophysics Data System (ADS)

Carvalho, Sónia; Gueiral, Nuno; Nogueira, Elisabete; Henrique, Rui; Oliveira, Luís.; Tuchin, Valery V.

2017-03-01

Optical properties of biological tissues are unique and may be used for tissue identification, tissue discrimination or even to identify pathologies. Early stage colorectal cancer evolves from adenomatous polyps that arise in the inner layer of the colorectal tube - the mucosa. The identification of different optical properties between healthy and pathological colorectal tissues might be used to identify different tissue components and to develop an early stage diagnosis method using optical technologies. Since most of the biomedical optics techniques use light within the visible and near infrared wavelength ranges, we used the inverse adding-doubling method to make a fast estimation of the optical properties of colorectal mucosa and early stage adenocarcinoma between 400 and 1000 nm. The estimated wavelength dependencies have provided information about higher lipid content in healthy mucosa and higher blood content in pathological tissue. Such data has also indicated that the wavelength dependence of the scattering coefficient for healthy mucosa is dominated by Rayleigh scattering and for pathological mucosa it is dominated by Mie scattering. Such difference indicates smaller scatterer size in healthy mucosa tissue. Such information can now be used to develop new diagnosis or treatment methods for early cancer detection or removal. One possibility is to use optical clearing technique to improve tissue transparency and create localized and temporary tissue dehydration for image contrast improvement during diagnosis or polyp laser removal. Such techniques can now be developed based on the different results that we have found for healthy and pathological colorectal mucosa.

O-polysaccharide is important for Salmonella Pullorum survival in egg albumen, and virulence and colonization in chicken embryos.

PubMed

Guo, Rongxian; Li, Zhuoyang; Jiao, Yang; Geng, Shizhong; Pan, Zhiming; Chen, Xiang; Li, Qiuchun; Jiao, Xinan

2017-10-01

The pathogen Salmonella Pullorum is the causative agent of persistent systemic infection of poultry, leading to economic losses in developing countries due to morbidity, mortality and reduction in egg production. These infections may result in vertical transmission to eggs or progeny. Limited information is available regarding the mechanisms involved in the survival of Salmonella Pullorum in egg albumen and developing chicken embryos. Hence, we investigated the role of O-polysaccharide in the contamination of eggs and the colonization of chicken embryos. Compared with the wild-type strain, the isogenic waaL mutant exhibited an O-antigen-deficient rough phenotype, and increased sensitivity to egg albumen and chicken serum, as well as reduced adherence to DF-1 cells. Infection with Salmonella Pullorum lacking O-polysaccharide resulted in significantly reduced embryo lethality and bacterial colonization. These results suggest that O-polysaccharide is essential for Salmonella Pullorum colonization in eggs, both post-lay and developing embryos. The chicken embryo infection model could be used to characterize the interaction between Salmonella Pullorum and developing embryos, and it will also contribute to the development of more rational vaccines to protect laying hens and embryos.

Synchronous isolated splenic metastasis from colon carcinoma and concomitant splenic abscess: A case report and review of the literature

PubMed Central

Pisanu, Adolfo; Ravarino, Alberto; Nieddu, Riccardo; Uccheddu, Alessandro

2007-01-01

This study aimed to describe a case in which an isolated splenic metastasis was synchronous with the colonic primary and a concomitant splenic abscess was associated. A wide review of the literature was also performed. A 54-year-old woman with abdominal pain and fever was admitted to our department. Abdominal CT revealed two low-density areas in the spleen and wall-thickening of the left colonic flexure, which was indistinguishable from the spleen parenchyma. The patient underwent emergency celiotomy, with the presumptive diagnosis of obstructing colon carcinoma of the splenic flexure, and concomitant splenic abscess. Subtotal colectomy and splenectomy were performed. Pathological findings were consistent with mucinous colonic carcinoma, synchronous isolated splenic metastasis and concomitant splenic abscess. This paper is also a review of the existing literature on the association between colorectal cancer and splenic metastasis. Only 41 cases of isolated splenic metastasis from colon carcinoma have been reported in the literature. This report is the third described case of synchronous isolated splenic metastasis from colon carcinoma. Only one case with concomitant splenic abscess has been previously reported. When obstructing left-sided colorectal cancer is suspected, careful CT examination can allow early diagnosis of splenic involvement by the tumor. The literature review suggests that there might be a significant improvement in survival following splenectomy for a metachronous isolated splenic metastasis from colon carcinoma. Prognosis for synchronous splenic metastasis seems to be related to the advanced stage of the disease. Nevertheless, no definitive conclusions can be drawn because of the small number of cases. PMID:17907299

Functional genome analysis of Bifidobacterium breve UCC2003 reveals type IVb tight adherence (Tad) pili as an essential and conserved host-colonization factor

PubMed Central

O'Connell Motherway, Mary; Zomer, Aldert; Leahy, Sinead C.; Reunanen, Justus; Bottacini, Francesca; Claesson, Marcus J.; O'Brien, Frances; Flynn, Kiera; Casey, Patrick G.; Moreno Munoz, Jose Antonio; Kearney, Breda; Houston, Aileen M.; O'Mahony, Caitlin; Higgins, Des G.; Shanahan, Fergus; Palva, Airi; de Vos, Willem M.; Fitzgerald, Gerald F.; Ventura, Marco; O'Toole, Paul W.; van Sinderen, Douwe

2011-01-01

Development of the human gut microbiota commences at birth, with bifidobacteria being among the first colonizers of the sterile newborn gastrointestinal tract. To date, the genetic basis of Bifidobacterium colonization and persistence remains poorly understood. Transcriptome analysis of the Bifidobacterium breve UCC2003 2.42-Mb genome in a murine colonization model revealed differential expression of a type IVb tight adherence (Tad) pilus-encoding gene cluster designated “tad2003.” Mutational analysis demonstrated that the tad2003 gene cluster is essential for efficient in vivo murine gut colonization, and immunogold transmission electron microscopy confirmed the presence of Tad pili at the poles of B. breve UCC2003 cells. Conservation of the Tad pilus-encoding locus among other B. breve strains and among sequenced Bifidobacterium genomes supports the notion of a ubiquitous pili-mediated host colonization and persistence mechanism for bifidobacteria. PMID:21690406

Functional genome analysis of Bifidobacterium breve UCC2003 reveals type IVb tight adherence (Tad) pili as an essential and conserved host-colonization factor.

PubMed

O'Connell Motherway, Mary; Zomer, Aldert; Leahy, Sinead C; Reunanen, Justus; Bottacini, Francesca; Claesson, Marcus J; O'Brien, Frances; Flynn, Kiera; Casey, Patrick G; Munoz, Jose Antonio Moreno; Kearney, Breda; Houston, Aileen M; O'Mahony, Caitlin; Higgins, Des G; Shanahan, Fergus; Palva, Airi; de Vos, Willem M; Fitzgerald, Gerald F; Ventura, Marco; O'Toole, Paul W; van Sinderen, Douwe

2011-07-05

Development of the human gut microbiota commences at birth, with bifidobacteria being among the first colonizers of the sterile newborn gastrointestinal tract. To date, the genetic basis of Bifidobacterium colonization and persistence remains poorly understood. Transcriptome analysis of the Bifidobacterium breve UCC2003 2.42-Mb genome in a murine colonization model revealed differential expression of a type IVb tight adherence (Tad) pilus-encoding gene cluster designated "tad(2003)." Mutational analysis demonstrated that the tad(2003) gene cluster is essential for efficient in vivo murine gut colonization, and immunogold transmission electron microscopy confirmed the presence of Tad pili at the poles of B. breve UCC2003 cells. Conservation of the Tad pilus-encoding locus among other B. breve strains and among sequenced Bifidobacterium genomes supports the notion of a ubiquitous pili-mediated host colonization and persistence mechanism for bifidobacteria.

15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis.

PubMed

Myung, Seung-Jae; Rerko, Ronald M; Yan, Min; Platzer, Petra; Guda, Kishore; Dotson, Angela; Lawrence, Earl; Dannenberg, Andrew J; Lovgren, Alysia Kern; Luo, Guangbin; Pretlow, Theresa P; Newman, Robert A; Willis, Joseph; Dawson, Dawn; Markowitz, Sanford D

2006-08-08

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is a prostaglandin-degrading enzyme that is highly expressed in normal colon mucosa but is ubiquitously lost in human colon cancers. Herein, we demonstrate that 15-PGDH is active in vivo as a highly potent suppressor of colon neoplasia development and acts in the colon as a required physiologic antagonist of the prostaglandin-synthesizing activity of the cyclooxygenase 2 (COX-2) oncogene. We first show that 15-PGDH gene knockout induces a marked 7.6-fold increase in colon tumors arising in the Min (multiple intestinal neoplasia) mouse model. Furthermore, 15-PGDH gene knockout abrogates the normal resistance of C57BL/6J mice to colon tumor induction by the carcinogen azoxymethane (AOM), conferring susceptibility to AOM-induced adenomas and carcinomas in situ. Susceptibility to AOM-induced tumorigenesis is mediated by a marked induction of dysplasia, proliferation, and cyclin D1 expression throughout microscopic aberrant crypt foci arising in 15-PGDH null colons and is concomitant with a doubling of prostaglandin E(2) in 15-PGDH null colonic mucosa. A parallel role for 15-PGDH loss in promoting the earliest steps of colon neoplasia in humans is supported by our finding of a universal loss of 15-PGDH expression in microscopic colon adenomas recovered from patients with familial adenomatous polyposis, including adenomas as small as a single crypt. These models thus delineate the in vivo significance of 15-PGDH-mediated negative regulation of the COX-2 pathway and moreover reveal the particular importance of 15-PGDH in opposing the neoplastic progression of colonic aberrant crypt foci.

Goat whey ameliorates intestinal inflammation on acetic acid-induced colitis in rats.

PubMed

Araújo, Daline Fernandes de Souza; Guerra, Gerlane Coelho Bernardo; Júnior, Raimundo Fernandes de Araújo; Antunes de Araújo, Aurigena; Antonino de Assis, Paloma Oliveira; Nunes de Medeiros, Ariosvaldo; Formiga de Sousa, Yasmim Regis; Pintado, Maria Manuela Estevez; Gálvez, Julio; Queiroga, Rita de Cássia Ramos do Egypto

2016-12-01

Complementary or alternative medicine is of great interest for the treatment of inflammatory bowel disease, with the aim of ameliorating the side effects of the drugs commonly used or improving their efficacy. In this study, we evaluated the ability of goat whey to prevent intestinal inflammation in the experimental model of acetic acid-induced rats and compared it to sulfasalazine. Pretreatment with goat whey (1, 2, and 4g/kg) and sulfasalazine (250mg/kg) on colitic rats improved colonic inflammatory markers, including myeloperoxidase activity, leukotriene B 4 levels, as well as the production of proinflammatory cytokines IL-1β and tumor necrosis factor-α. Furthermore, the administration of goat whey significantly reduced the colonic oxidative stress by reducing malondialdehyde levels and increased total glutathione content, a potent antioxidant peptide. The histological evaluation of the colonic specimens from colitic rats confirmed these beneficial effects, as goat whey preserved the colonic tissue, especially in those rats treated with the highest dose of goat whey or with sulfasalazine. The immunohistochemistry analysis of the colonic tissue evaluation also revealed a reduction in the expression of cyclooxygenase-2, inducible nitric oxide synthase, and matrix metalloproteinase-9, together with an increased expression of suppressor of cytokine signaling-1. These results suggest that goat whey exerted a preventive effect against the intestinal damage induced by acetic acid, showing a similar efficacy to that shown by sulfasalazine, therefore making it a potential treatment for human inflammatory bowel disease. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Oncological outcomes of complete versus conventional mesocolic excision in laparoscopic right hemicolectomy.

PubMed

An, Min Sung; Baik, HyungJoo; Oh, Se Hui; Park, Yo-Han; Seo, Sang Hyuk; Kim, Kwang Hee; Hong, Kwan Hee; Bae, Ki Beom

2018-06-12

Complete mesocolic excision (CME) has been proposed for colon cancer to improve oncological outcomes. The risks and benefits of laparoscopic CME have not been examined fully. We compared short- and long-term outcomes of CME with a conventional mesocolic excision (non-CME) in laparoscopic right hemicolectomy (RHC) for right-sided colon cancer. In total, 115 patients who underwent laparoscopic RHC with stage I-III right-sided colon cancer at Busan Paik Hospital from August 2007 to October 2011 were enrolled in this case-control study. Three trained colorectal surgeons reviewed videos of the surgeries; patients were divided into two groups: those who underwent a CME (CME group, n = 34) and those who underwent a conventional mesocolic excision (non-CME group, n = 81). There was no significant difference between the CME and non-CME groups in operative time, post-operative complications, or hospital stay. However, the CME group had more lymph nodes harvested (P < 0.001) and lower blood loss (P = 0.016) versus the non-CME group. There was no difference in 5-year disease-free survival rate between the groups, but 5-year overall survival rate was 100% in the CME group and 89.49% in the non-CME group (P < 0.05). Laparoscopic RHC with CME is safe and associated with better 5-year overall survival rate than non-CME for patients with stage I-III right-sided colon cancer. Implementation of CME surgery might improve oncological outcomes for patients with right-sided colon cancer. © 2018 Royal Australasian College of Surgeons.

Dynamic changes in the initial colonization of Actinomyces naeslundii and Streptococcus gordonii using a new animal model.

PubMed

Zhang, Xi; Senpuku, Hidenobu

2013-01-01

Actinomyces naeslundii and Streptococcus gordonii are the predominant bacteria and initial colonizers of oral microflora. The binding of A. naeslundii and S. gordonii and the interaction between them on the salivary pellicle-coated tooth surface play an important role in the biofilm development. Recently, we reported that NOD/SCID.e2f1(-) mice are a useful model for studying oral biofilm formation by Streptococcus mutans on the tooth surface. In this study, we aimed to determine whether NOD/SCID.e2f1(-) mice can be used for studying oral colonization of A. naeslundii and S. gordonii. Colonization of A. naeslundii in mice fed with 1% sucrose water for 24 h before inoculation was higher than that among mice fed with sucrose water for 1 h. A. naeslundii colonization using mixed species-inoculation was lower than that using single-species inoculation 30-90 min after inoculation; however, the colonization was higher 120-180 min after inoculation. The mixed inoculation induced better colonization of S. gordonii than single-species inoculation 60-180 min after inoculation. Polyclonal and fluorescein isothiocyanate-labeled antibody stained bacteria showed better colonization of S. gordonii when a mixed culture is used in vivo. NOD/SCID.e2f1(-) mice were useful for studying the initial colonization of A. naeslundii and S. gordonii. Long-term supply of sucrose water creates a favorable environment for the initial colonization of A. naeslundii that, in turn, supports the colonization of S. gordonii.

Purple rice extract supplemented diet reduces DMH- induced aberrant crypt foci in the rat colon by inhibition of bacterial β-glucuronidase.

PubMed

Summart, Ratasark; Chewonarin, Teera

2014-01-01

Purple rice has become a natural product of interest which is widely used for health promotion. This study investigated the preventive effect of purple rice extract (PRE) mixed diet on DMH initiation of colon carcinogenesis. Rats were fed with PRE mixed diet one week before injection of DMH (40 mg/kg of body weight once a week for 2 weeks). They were killed 12 hrs after a second DMH injection to measure the level of O6-methylguanine and xenobiotic metabolizing enzyme activities. In rats that received PRE, guanine methylation was reduced in the colonic mucosa, but not in the liver, whereas PRE did not affect xenobiotic conjugation, with reference to glutathione-S-transferase or UDP-glucuronyl transferase. After 5 weeks, rats that received PRE with DMH injection had fewer ACF in the colon than those treated with DMH alone. Interestingly, a PRE mixed diet inhibited the activity of bacterial β-glucuronidase in rat feces, a critical enzyme for free methylazoxymethanol (MAM) release in the rat colon. These results indicated that purple rice extract inhibited β-glucuronidase activity in the colonic lumen, causing a reduction of MAM-induced colonic mucosa DNA methylation, leaded to decelerated formation of aberrant crypt foci in the rat colon. The supplemented purple rice extract might thus prevent colon carcinogenesis by the alteration of the colonic environment, and thus could be further developed for neutraceutical products for colon cancer prevention.

Asian and Hispanic Americans' cancer fatalism and colon cancer screening.

PubMed

Jun, Jungmi; Oh, Kyeung Mi

2013-03-01

To explore fatalistic attributions of colon cancer development among Asian and Hispanic Americans in comparison with non-Hispanic whites; also to examine the impacts of fatalism on adherence to the colon cancer screening guideline. For the analysis, the 2005 Health Information National Trends Survey data were employed. Both Asian and Hispanic Americans were more likely to make fatalistic attribution and were less likely to follow the guideline than whites. Particularly for Asians, fatalism was a significant predictor for not adhering to the guideline. These findings emphasize the need for cultural interventions to disrupt fatalistic attitudes towards colon cancer preventions.

Endotracheal tube biofilm translocation in the lateral Trendelenburg position.

PubMed

Li Bassi, Gianluigi; Fernandez-Barat, Laia; Saucedo, Lina; Giunta, Valeria; Marti, Joan Daniel; Tavares Ranzani, Otavio; Aguilera Xiol, Eli; Rigol, Montserrat; Roca, Ignasi; Muñoz, Laura; Luque, Nestor; Esperatti, Mariano; Saco, Maria Adela; Ramirez, Jose; Vila, Jordi; Ferrer, Miguel; Torres, Antoni

2015-02-27

Laboratory studies demonstrated that the lateral Trendelenburg position (LTP) is superior to the semirecumbent position (SRP) in the prevention of ventilator-associated pulmonary infections. We assessed whether the LTP could also prevent pulmonary colonization and infections caused by an endotracheal tube (ETT) biofilm. Eighteen pigs were intubated with ETTs colonized by Pseudomonas aeruginosa biofilm. Pigs were positioned in LTP and randomized to be on mechanical ventilatin (MV) up to 24 hour, 48 hour, 48 hour with acute lung injury (ALI) by oleic acid and 72 hour. Bacteriologic and microscopy studies confirmed presence of biofilm within the ETT. Upon autopsy, samples from the proximal and distal airways were excised for P.aeruginosa quantification. Ventilator-associated tracheobronchitis (VAT) was confirmed by bronchial tissue culture ≥3 log colony forming units per gram (cfu/g). In pulmonary lobes with gross findings of pneumonia, ventilator-associated pneumonia (VAP) was confirmed by lung tissue culture ≥3 log cfu/g. P.aeruginosa colonized the internal lumen of 16 out of 18 ETTs (88.89%), and a mature biofilm was consistently present. P.aeruginosa colonization did not differ among groups, and was found in 23.6% of samples from the proximal airways, and in 7.1% from the distal bronchi (P = 0.001). Animals of the 24 hour group never developed respiratory infections, whereas 20%, 60% and 25% of the animals in group 48 hour, 48 hour-ALI and 72 hour developed P.aeruginosa VAT, respectively (P = 0.327). Nevertheless, VAP never developed. Our findings imply that during the course of invasive MV up to 72 hour, an ETT P.aeruginosa biofilm hastily colonizes the respiratory tract. Yet, the LTP compartmentalizes colonization and infection within the proximal airways and VAP never develops.

Influence of Long-Term Fertilization on Spore Density and Colonization of Arbuscular Mycorrhizal Fungi in a Brown Soil

NASA Astrophysics Data System (ADS)

Li, Dongdong; Luo, Peiyu; Yang, Jinfeng

2017-12-01

This study aims to explore changes of long-term fertilization on spore density and colonization of AMF (Arbuscular mycorrhizal fungi) under a 38-y long-term fertilization in a brown soil. Soil samples (0-20 cm,20-40cm,40-60cm)were taken from the six treatments of the long-term fertilization trial in October 2016:no fertilizer (CK), N1(mineral nitrogen fertilizer), N1P (mineral nitrogen and phosphate fertilizer), N1PK (mineral nitrogen, phosphate and potassic fertilizer), pig manure (M2), M2N1P (pig manure, mineral nitrogen andphosphate fertilizer).Spores were isolated from soils by wet sieving and sucrose density gradient centrifugation; mycorrhizal colonization levels were determined by the gridline intersect. The spore density was highest in the topsoils (0-20 cm), and was decreased with increasing of soil depth in each treatment. The spores density of M2N1P treatment was significantly higher than that of other treatments in each soil layer. Application of inorganic fertilizer (especially inorganic with organic fertilizer) can greatly improve the level of colonization. Our results suggested that long-term fertilization significantly affects spore density and colonization of AMF, however, spore density is not related to colonization rate.

Ursolic acid protects against ulcerative colitis via anti-inflammatory and antioxidant effects in mice.

PubMed

Liu, Baohai; Piao, Xuehua; Guo, Lianyi; Liu, Shanshan; Chai, Fang; Gao, Leming

2016-06-01

Ursolic acid (UA) has been reported to have a protective effect in colitis. However, the underlying mechanisms remain to be elucidated. In the present study, experimental ulcerative colitis was induced in male BALB/c mice by the administration of 5% dextran sulfate sodium (DSS) for 7 days, followed by treatment with UA for another 7 days. Hematoxylin & eosin staining was performed to evaluate colon tissue damage, and enzyme assays were used to measure malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in colon homogenate. In addition, serum levels of interleukin (IL)‑1β and tumor necrosis factor (TNF)‑α were measured using an ELISA, and the level of nuclear factor (NF)‑κB p65 in the colonic tissues was assessed by western blotting. The 7‑day DSS administration induced marked colon damage, increased the serum levels of IL‑1β and TNF‑α, increased MDA content and decreased SOD activity in the colon homogenate. These changes were significantly improved by treatment with UA. UA also reduced the DSS‑stimulated high nuclear level of NF‑κB p65 in the colon tissues. These results demonstrate a protective role of UA in ulcerative colitis, and suggest that anti-inflammatory and antioxidant activities are involved in the underlying mechanisms.

Daikenchuto stimulates colonic motility after laparoscopic-assisted colectomy.

PubMed

Yaegashi, Mizunori; Otsuka, Koki; Itabashi, Tetsuya; Kimura, Toshimoto; Kato, Kuniyuki; Fujii, Hitoshi; Koeda, Keisuke; Sasaki, Akira; Wakabayashi, Go

2014-01-01

Paralytic ileus after laparoscopic-assisted surgery often occurs. We investigated whether daikenchuto (DKT), a traditional Japanese herbal medicine, improves intestinal motility in patients undergoing laparoscopic-assisted colectomy for colon cancer. Fifty-four patients who underwent colectomy at Iwate Medical University Hospital between October 2010 and March 2012 were randomized to either the DKT group (7.5 g/day, p.o.) or the control group (lactobacillus preparation, 3g/day, p.o.). Primary endpoints included time to first flatus, bowel movement, and tolerance of diet after extubation. Secondary endpoints were WBC count, C-reactive protein (CRP) level, length of hospital stay, and postoperative ileus. Colonic transit time was measured using radiopaque markers and abdominal radiographs. Fifty-one patients (DKT, 26 vs. control, 25) were included in the per-protocol analysis. The DKT group had significantly faster time until first flatus (67.5 +/- 13.6h vs. 77.9 +/- 11.8h, P < 0.01) and bowel movement (82.9 +/- 17.8h vs. 99.5 +/- 18.9h, P < 0.01) and colonic transit time (91.9 +/- 19.8h vs. 115.2 +/- 12.8 h, P < 0.05). There were no significant intergroup differences in secondary endpoints and adverse events. DKT accelerates colonic motility in patients undergoing laparoscopic-assisted colectomy for colon cancer.

Clinical outcome of using gastric remnant or jejunum or colon conduit in surgery for esophageal carcinoma with previous gastrectomy.

PubMed

Jun, Wang; Wei, Wen; Weibing, Wu; Jing, Xu; Fuxi, Zhen; Xiaoxiang, Xi; Bihong, Lu; Tong, Zhou; Liang, Chen; Jinhua, Luo

2017-05-01

For esophageal carcinoma patients with early gastrectomy, individualized surgical plans-including selection of replacement conduit and operation route based on patient's new lesion and surgical history-can achieve the desired therapeutic effect and improve postoperative life quality. We investigated the outcomes at our institution. The clinical data of 42 esophageal carcinoma patients with early gastrectomy were analyzed retrospectively. Esophagectomy was performed combining replacement with remnant stomach in 16 patients, jejunum in 17, and colon in 9. Esophagectomy combining replacement with gastric remnant got advantages of shorter operation time and less bleeding over that of replacement with jejunum or colon. Gastric remnant group scored higher on the QLQ-C30 questionnaire than jejunum or colon group with respect to overall quality of life, physical function, and social relationships. In QLQ-OES18 questionnaire, the scores of appetite recovery and reflux mitigation were more favorable in remnant stomach group than those in jejunum or colon group. Survival analysis showed no significant difference in survival rate among the patients undergoing replacement with gastric remnant, jejunum, or colon. For esophageal carcinoma patients with early gastrectomy, esophagus-gastric remnant anastomosis possesses advantages of shorter operation time, less surgical trauma, and greater life quality after surgery. © 2017 Wiley Periodicals, Inc.

An autoantibody in narcolepsy disrupts colonic migrating motor complexes.

PubMed

Jackson, Michael W; Reed, Joanne H; Smith, Anthony J F; Gordon, Tom P

2008-12-03

Despite strong circumstantial evidence for the autoimmune hypothesis of narcolepsy, conventional immunological methods have failed to detect an autoantibody. This study investigated the real-time effects of narcoleptic immunoglobulins on a spontaneous colonic migrating motor complex (CMMC) preparation. IgG from patients with narcolepsy with cataplexy or healthy controls was added directly to isolated mouse colons undergoing CMMC activity to test for autoantibodies that disrupt colonic motility. The effect of immunoglobulins prepared for clinical intravenous treatment (IVIg) on autoantibody-mediated colonic disruption was also assessed. Narcoleptic IgGs markedly reduced the frequency of CMMCs or irreversibly abolished them. Abrogation of CMMCs was followed by an increase in the resting tension of the colon preparation and appearance of atropine-sensitive phasic smooth muscle contractions. IVIg partially neutralized the inhibitory effect of narcoleptic IgG on the CMMCs. The dramatic effect of narcoleptic IgG on CMMC generation is consistent with an autoantibody-mediated disruption of enteric neural pathways. The ex vivo whole-organ approach allows real-time examination of the physiological effects of the narcoleptic autoantibody and offers a new avenue for exploring the autoimmune basis of narcolepsy. The neutralizing effect of IVIg on the autoantibody provides a rationale for the reported clinical improvement in cataplexy when IVIg are given at disease onset.

Experts reviews of the multidisciplinary consensus conference colon and rectal cancer 2012: science, opinions and experiences from the experts of surgery.

PubMed

van de Velde, C J H; Boelens, P G; Tanis, P J; Espin, E; Mroczkowski, P; Naredi, P; Pahlman, L; Ortiz, H; Rutten, H J; Breugom, A J; Smith, J J; Wibe, A; Wiggers, T; Valentini, V

2014-04-01

The first multidisciplinary consensus conference on colon and rectal cancer was held in December 2012, achieving a majority of consensus for diagnostic and treatment decisions using the Delphi Method. This article will give a critical appraisal of the topics discussed during the meeting and in the consensus document by well-known leaders in surgery that were involved in this multidisciplinary consensus process. Scientific evidence, experience and opinions are collected to support multidisciplinary teams (MDT) with arguments for medical decision-making in diagnosis, staging and treatment strategies for patients with colon or rectal cancer. Surgery is the cornerstone of curative treatment for colon and rectal cancer. Standardizing treatment is an effective instrument to improve outcome of multidisciplinary cancer care for patients with colon and rectal cancer. In this article, a review of the following focuses; Perioperative care, age and colorectal surgery, obstructive colorectal cancer, stenting, surgical anatomical considerations, total mesorectal excision (TME) surgery and training, surgical considerations for locally advanced rectal cancer (LARC) and local recurrent rectal cancer (LRRC), surgery in stage IV colorectal cancer, definitions of quality of surgery, transanal endoscopic microsurgery (TEM), laparoscopic colon and rectal surgery, preoperative radiotherapy and chemoradiotherapy, and how about functional outcome after surgery? Copyright © 2013 Elsevier Ltd. All rights reserved.

Application of three-dimensional printing for colon targeted drug delivery systems

PubMed Central

Charbe, Nitin B.; McCarron, Paul A.; Lane, Majella E.; Tambuwala, Murtaza M.

2017-01-01

Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems. PMID:28929046

Application of three-dimensional printing for colon targeted drug delivery systems.

PubMed

Charbe, Nitin B; McCarron, Paul A; Lane, Majella E; Tambuwala, Murtaza M

2017-01-01

Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems.

Operative factors associated with short-term outcome in horses with large colon volvulus: 47 cases from 2006 to 2013

PubMed Central

Gonzalez, L. M.; Fogle, C. A.; Baker, W. T.; Hughes, F. E.; Law, J. M.; Motsinger-Reif, A. A.; Blikslager, A. T.

2014-01-01

Summary Reasons for performing the study There is an important need for objective parameters that accurately predict the outcome of horses with large colon volvulus. Objectives To evaluate the predictive value of a series of histomorphometric parameters on short-term outcome, as well as the impact of colonic resection on horses with large colon volvulus. Study Design Retrospective cohort study Methods Adult horses admitted to the Equine and Farm Animal Veterinary Center at North Carolina State University, Peterson & Smith and Chino Valley Equine Hospitals between 2006–2013 undergoing an exploratory celiotomy, diagnosed with large colon volvulus of ≥360 degrees, where a pelvic flexure biopsy was obtained, and that recovered from general anaesthesia, were selected for inclusion in the study. Logistic regression was used to determine associations between signalment, histomorphometric measurements of interstitial: crypt ratio, degree of haemorrhage, percentage loss of luminal and glandular epithelium, as well as colonic resection with short-term outcome (discharge from the hospital). Results Pelvic flexure biopsies from 47 horses with large colon volvulus were evaluated. Factors that were significantly associated with short-term outcome on univariate logistic regression were Thoroughbred breed (P = 0.04), interstitial: crypt ratio >1 (P = 0.02) and haemorrhage score ≥3 (P = 0.005). Resection (P = 0.92) was not found to be significantly associated with short-term outcome. No combined factors increased the likelihood of death in forward stepwise logistic regression modelling. A digitally quantified haemorrhage area measurement strengthened the association of haemorrhage with non-survival in cases of large colon volvulus. Conclusions Histomorphometric measurements of interstitial: crypt ratio and degree of haemorrhage predict short-term outcome in cases of large colon volvulus. Resection was not associated with short-term outcome in horses selected for this study. Accurate quantification of mucosal haemorrhage at the time of surgery may improve veterinary surgeons’ prognostic capabilities in horses with large colon volvulus. PMID:24735170

Operative factors associated with short-term outcome in horses with large colon volvulus: 47 cases from 2006 to 2013.

PubMed

Gonzalez, L M; Fogle, C A; Baker, W T; Hughes, F E; Law, J M; Motsinger-Reif, A A; Blikslager, A T

2015-05-01

There is an important need for objective parameters that accurately predict the outcome of horses with large colon volvulus. To evaluate the predictive value of a series of histomorphometric parameters on short-term outcome, as well as the impact of colonic resection on horses with large colon volvulus. Retrospective cohort study. Adult horses admitted to the Equine and Farm Animal Veterinary Center at North Carolina State University, Peterson and Smith and Chino Valley Equine Hospitals between 2006 and 2013 that underwent an exploratory coeliotomy, diagnosed with large colon volvulus of ≥360 degrees, where a pelvic flexure biopsy was obtained, and that recovered from general anaesthesia, were selected for inclusion in the study. Logistic regression was used to determine associations between signalment, histomorphometric measurements of interstitium-to-crypt ratio, degree of haemorrhage, percentage loss of luminal and glandular epithelium, as well as colonic resection with short-term outcome (discharge from the hospital). Pelvic flexure biopsies from 47 horses with large colon volvulus were evaluated. Factors that were significantly associated with short-term outcome on univariate logistic regression were Thoroughbred breed (P = 0.04), interstitium-to-crypt ratio >1 (P = 0.02) and haemorrhage score ≥3 (P = 0.005). Resection (P = 0.92) was not found to be associated significantly with short-term outcome. No combined factors increased the likelihood of death in forward stepwise logistic regression modelling. A digitally quantified measurement of haemorrhage area strengthened the association of haemorrhage with nonsurvival in cases of large colon volvulus. Histomorphometric measurements of interstitium-to-crypt ratio and degree of haemorrhage predict short-term outcome in cases of large colon volvulus. Resection was not associated with short-term outcome in horses selected for this study. Accurate quantification of mucosal haemorrhage at the time of surgery may improve veterinary surgeons' prognostic capabilities in horses with large colon volvulus. © 2014 EVJ Ltd.

Fluorescent diagnostics of epithelial neoplasms of different colon parts.

PubMed

Korneva, Yulia S; Dorosevich, Alexander E; Maryakhina, Valeriya S

2017-10-01

Changes in the biochemical composition of the tissue during colon cancer progression usually precede morphological changes registered by light microscopy. These changes are very sensitive and may be used for diagnostics in difficult cases, when it is impossible to obtain sufficient amount of material during colonoscopy. The aim of the study is analysis of spectral characteristics of sporadic adenomas and tumors in different parts of colon for improving tumors diagnostics in disputable cases. The spectra of fluorescence excitation of histological sections from 78 patients with colon cancer (adenocarcinoma) and colonic adenomas of different localizations were measured. The spectra of fluorescence excitation of all types of adenomas as well as adenocarcinoma have two maxima at 260/270 nm and at 330/340 nm. The first maximum is primarily defined by tryptophan and phenylalanin containing peptides, one of them is glucagon. The second maximum is mainly defined by collagen in stroma. Progression of precancer lesions to advanced cancer leads to increase of NADH concentration impacting on the second maximum of spectra. However, spectra of all types of the investigated lesions have peculiarities depending on localization. At odds to the previous data about similarities between distal colon and rectum, our results demonstrate similar spectra for proximal colon and rectum due to some similarities in morphological and, as a consequence, biochemical composition. Tumor can be detected by spectral techniques on histological slides even if the specimen contains very few tumorous cells in stroma. Biochemical changes and their similarities for precancer lesions and advanced colon cancer have described. Peculiarities of spectral data for different parts of colon may change the previous opinion about similar mechanisms of cancerogenesis for distal colon and rectum. Moreover, investigation of tissue specimen obtained for histological examination and containing lack of malignant epithelial cells in massive stroma does not interfere with analysis due to specific disproportion of spectrum maxima. Lasers Surg. Med. 49:763-766, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Suture marker lesion detection in the colon by self-stabilizing and unmodified capsule endoscopes: pilot study in acute canine models.

PubMed

Filip, Dobromir; Yadid-Pecht, Orly; Muench, Gregory; Mintchev, Martin P; Andrews, Christopher N

2013-02-01

Capsule endoscopy is a noninvasive method for examining the small intestine. Recently, this method has been used to visualize the colon. However, the capsule often tumbles in the wider colon lumen, resulting in potentially missed pathology. In addition, the capsule does not have the ability to distend collapsed segments of the organ. Self-stabilizing capsule endoscopy is a new method of visualizing the colon without tumbling and with the ability to passively distend colon walls. To quantitatively compare the detection rate of intraluminal suture marker lesions for colonoscopy by using a custom-modified, self-stabilizing capsule endoscope (SCE); an unmodified capsule endoscope (CE) of the same brand; and a standard colonoscope. Four mongrel dogs underwent laparotomy and the implantation of 5 to 8 suture markers to approximate colon lesions. Each dog had both capsule endoscopy and self-stabilizing capsule endoscopy, administered consecutively in random order. In each case, the capsule was inserted endoscopically into the proximal lumen of the colon followed by pharmacologically induced colon peristalsis to propel it distally through the colon. Blinded standard colonoscopy was performed by an experienced gastroenterologist after the capsule endoscopies. Experimental study in a live canine model. Four dogs. Laparotomy, capsule endoscopy, colonoscopy. Comparison of the marker detection rate of the SCE to that of the unmodified MiroCam CE and a colonoscope. The average percentages of the marker detection rate for unmodified capsule endoscopy, self-stabilizing capsule endoscopy, and colonoscopy, respectively, were 31.1%, 86%, and 100% (P < .01), with both self-stabilizing capsule endoscopy and colonoscopy performing significantly better than the unmodified capsule endoscopy. Acute canine model, suture markings poorly representative of epithelial polyps, limited number of animals. The proposed self-stabilizing capsule endoscope delivered a significant improvement in detection rates of colon suture markings when compared with the unmodified capsule endoscope. Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Development of an Anti-HER2 Monoclonal Antibody H2Mab-139 Against Colon Cancer.

PubMed

Kaneko, Mika K; Yamada, Shinji; Itai, Shunsuke; Kato, Yukinari

2018-02-01

Human epidermal growth factor receptor 2 (HER2) expression has been reported in several cancers, such as breast, gastric, lung, pancreatic, and colorectal cancers. HER2 is overexpressed in those cancers and is associated with poor clinical outcomes. Trastuzumab, a humanized anti-HER2 antibody, provides significant survival benefits for patients with HER2-overexpressing breast cancers and gastric cancers. In this study, we developed a novel anti-HER2 monoclonal antibody (mAb), H 2 Mab-139 (IgG 1 , kappa) and investigated it against colon cancers using flow cytometry, western blot, and immunohistochemical analyses. Flow cytometry analysis revealed that H 2 Mab-139 reacted with colon cancer cell lines, such as Caco-2, HCT-116, HCT-15, HT-29, LS 174T, COLO 201, COLO 205, HCT-8, SW1116, and DLD-1. Although H 2 Mab-139 strongly reacted with LN229/HER2 cells on the western blot, we did not observe a specific signal for HER2 in colon cancer cell lines. Immunohistochemical analyses revealed sensitive and specific reactions of H 2 Mab-139 against colon cancers, indicating that H 2 Mab-139 is useful in detecting HER2 overexpression in colon cancers using flow cytometry and immunohistochemical analyses.

AMPK/p53 Axis Is Essential for α-Lipoic Acid-Regulated Metastasis in Human and Mouse Colon Cancer Cells.

PubMed

Park, Sunmi; Choi, Seung Kug; Choi, Yura; Moon, Hyun-Seuk

2015-10-01

α-Lipoic acid (ALA) has an anticancer property of lung, cervix, and prostate cancer cells. However, direct evidence that ALA contributes to the development of colon cancer has not been fully elucidated. In addition, no previous studies have evaluated whether ALA may regulate malignant potential, such as adhesion, invasion, and colony formation of colon cancer cells. To address the aforementioned questions, we conducted in vitro ALA signaling studies using human (HT29) and mouse (MCA38) colon cancer cell lines. We observed that cell proliferation is reduced by ALA administration in a dose-dependent manner in human and mouse colon cancer cell lines. Specifically, 0.5 to 1 mM concentration of ALA significantly decreased cell proliferation when compared with control. Similarly, we found that ALA downregulates adhesion, invasion, and colony formation. Finally, we observed that ALA activates p53 and AMPK signaling pathways in human and mouse colon cancer cells. We found for the first time that ALA suppresses cell proliferation and malignant potential via p53 and AMPK signaling pathways in human and mouse colon cancer cells. These new and early mechanistic studies provide a causal role of ALA in colon cancer, suggesting that ALA might be a useful agent in the management or chemoprevention of colon cancer.

Association of bacterial colonization at the time of presentation to a combat support hospital in a combat zone with subsequent 30-day colonization or infection.

PubMed

Kaspar, Robert L; Griffith, Matthew E; Mann, Paul B; Lehman, Devon J; Conger, Nicholas G; Hospenthal, Duane R; Murray, Clinton K

2009-09-01

U.S. casualties have developed multidrug-resistant (MDR) bacterial infections. A surveillance project to evaluate U.S. military patients for the presence of MDR pathogens from wounding through the first 30 days of care in the military healthcare system (MHS) was performed. U.S. military patients admitted to a single combat support hospital in Iraq during June-July of 2007 had screening swabs obtained for the detection of MDR bacteria and a subsequent retrospective electronic medical records review for presence of colonization or infection in the subsequent 30 days. Screening of 74 U.S. military patients in Iraq found one colonized with methicillin-resistant Staphylococcus aureus. Fifty-six patients of these were screened for Acinetobacter in Germany and one found colonized. Of patients evacuated to the U.S., 9 developed infections. Carefully obtained screening cultures immediately after injury combined with look-back monitoring supports the role of nosocomial transmission. Consistent infection control strategies are needed for the entire MHS.

Low prevalence of Pneumocystis jirovecii lung colonization in Ugandan HIV-infected patients hospitalized with non-Pneumocystis pneumonia.

PubMed

Taylor, Steve M; Meshnick, Steven R; Worodria, William; Andama, Alfred; Davis, J Lucian; Cattamanchi, Adithya; den Boon, Saskia; Yoo, Samuel D; Goodman, Carol D; Huang, Laurence

2012-02-01

Pneumocystis jirovecii is an important opportunistic infection in human immunodeficiency virus (HIV)-infected patients. In the developed world, P. jirovecii epidemiology is marked by frequent colonization in immunosuppressed patients, but data on the prevalence of colonization are very limited in sub-Saharan Africa, where the majority of persons living with HIV reside. Our objective was to describe the epidemiology of P. jirovecii colonization among HIV-positive patients in a cross-sectional, hospital-based study of patients admitted with suspected pneumonia in Kampala, Uganda. P. jirovecii was detectable in bronchoalveolar lavage fluid from 7 (6%) of 124 consecutive patients with non-Pneumocystis pneumonia. Colonization was not associated with patient demographic or clinical information. This prevalence is substantially lower than in published studies in the developed world and suggests that there is a limited reservoir of organisms for clinical infections in this Ugandan population. These findings may partially explain the low incidence of Pneumocystis pneumonia in Uganda and other sub-Saharan African countries. Copyright © 2012 Elsevier Inc. All rights reserved.

A central venous catheter coated with benzalkonium chloride for the prevention of catheter-related microbial colonization.

PubMed

Moss, H A; Tebbs, S E; Faroqui, M H; Herbst, T; Isaac, J L; Brown, J; Elliott, T S

2000-11-01

In an attempt to overcome infections associated with central venous catheters, a new antiseptic central venous catheter coated with benzalkonium chloride on the internal and external surfaces has been developed and evaluated in a clinical trial. Patients (235) randomly received either a triple-lumen central venous catheter coated with benzalkonium chloride (117) or a polyurethane non-antiseptic catheter (118). The incidence of microbial colonization of both catheters and retained antiseptic activity of the benzalkonium chloride device following removal were determined. The benzalkonium chloride resulted in a significant reduction of the incidence of microbial colonization on both the internal and external catheter surfaces. The reduction in colonization was detected at both the intradermal (21 benzalkonium chloride catheters vs. 38 controls, P = 0.0016) and distal segments of the antiseptic-coated catheters. Following catheter removal retained activity was demonstrated in benzalkonium chloride catheters which had been in place for up to 12 days. No patients developed adverse reactions to the benzalkonium chloride catheters. The findings demonstrate that the benzalkonium chloride catheter significantly reduced the incidence of catheter-associated colonization.

Colonic irrigation for defecation disorders after dynamic graciloplasty.

PubMed

Koch, Sacha M; Uludağ, Ozenç; El Naggar, Kadri; van Gemert, Wim G; Baeten, Cor G

2008-02-01

Dynamic graciloplasty (DGP) improves anal continence and quality of life for most patients. However, in some patients, DGP fails and fecal incontinence is unsolved or only partially improved. Constipation is also a significant problem after DGP, occurring in 13-90%. Colonic irrigation can be considered as an additional or salvage treatment for defecation disorders after unsuccessful or partially successful DGP. In this study, the effectiveness of colonic irrigation for the treatment of persistent fecal incontinence and/or constipation after DGP is investigated. Patients with defecation disorders after DGP visiting the outpatient clinic of the University Hospital Maastricht were selected for colonic irrigation as additional therapy or salvage therapy in the period between January 1999 and June 2003. The Biotrol(R) Irrimatic pump or the irrigation bag was used for colonic irrigation. Relevant physical and medical history was collected. The patients were asked to fill out a detailed questionnaire about colonic irrigation. Forty-six patients were included in the study with a mean age of 59.3 +/- 12.4 years (80% female). On average, the patients started the irrigation 21.39 +/- 38.77 months after the DGP. Eight patients started irrigation before the DGP. Fifty-two percent of the patients used the irrigation as additional therapy for fecal incontinence, 24% for constipation, and 24% for both. Irrigation was usually performed in the morning. The mean frequency of irrigation was 0.90 +/- 0.40 times per day. The mean amount of water used for the irrigation was 2.27 +/- 1.75 l with a mean duration of 39 +/- 23 min. Four patients performed antegrade irrigation through a colostomy or appendicostomy, with good results. Overall, 81% of the patients were satisfied with the irrigation. Thirty-seven percent of the patients with fecal incontinence reached (pseudo-)continence, and in 30% of the patients, the constipation completely resolved. Side effects of the irrigation were reported in 61% of the patients: leakage of water after irrigation, abdominal cramps, and distended abdomen. Seven (16%) patients stopped the rectal irrigation. Colonic irrigation is an effective alternative for the treatment of persistent fecal incontinence after DGP and/or recurrent or onset constipation additional to unsuccessful or (partially) successful DGP.

Regulation of Plant Growth, Photosynthesis, Antioxidation and Osmosis by an Arbuscular Mycorrhizal Fungus in Watermelon Seedlings under Well-Watered and Drought Conditions.

PubMed

Mo, Yanling; Wang, Yongqi; Yang, Ruiping; Zheng, Junxian; Liu, Changming; Li, Hao; Ma, Jianxiang; Zhang, Yong; Wei, Chunhua; Zhang, Xian

2016-01-01

Drought stress has become an increasingly serious environmental issue that influences the growth and production of watermelon. Previous studies found that arbuscular mycorrhizal (AM) colonization improved the fruit yield and water use efficiency (WUE) of watermelon grown under water stress; however, the exact mechanisms remain unknown. In this study, the effects of Glomus versiforme symbiosis on the growth, physio-biochemical attributes, and stress-responsive gene expressions of watermelon seedlings grown under well-watered and drought conditions were investigated. The results showed that AM colonization did not significantly influence the shoot growth of watermelon seedlings under well-watered conditions but did promote root development irrespective of water treatment. Drought stress decreased the leaf relative water content and chlorophyll concentration, but to a lesser extent in the AM plants. Compared with the non-mycorrhizal seedlings, mycorrhizal plants had higher non-photochemical quenching values, which reduced the chloroplast ultrastructural damage in the mesophyll cells and thus maintained higher photosynthetic efficiency. Moreover, AM inoculation led to significant enhancements in the enzyme activities and gene expressions of superoxide dismutase, catalase, ascorbate peroxidase, glutathione reductase, and monodehydroascorbate reductase in watermelon leaves upon drought imposition. Consequently, AM plants exhibited lower accumulation of MDA, H2O2 and [Formula: see text] compared with non-mycorrhizal plants. Under drought stress, the soluble sugar and proline contents were significantly increased, and further enhancements were observed by pre-treating the drought-stressed plants with AM. Taken together, our findings indicate that mycorrhizal colonization enhances watermelon drought tolerance through a stronger root system, greater protection of photosynthetic apparatus, a more efficient antioxidant system and improved osmoregulation. This study contributes to advances in the knowledge of AM-induced drought tolerance.

Regulation of Plant Growth, Photosynthesis, Antioxidation and Osmosis by an Arbuscular Mycorrhizal Fungus in Watermelon Seedlings under Well-Watered and Drought Conditions

PubMed Central

Mo, Yanling; Wang, Yongqi; Yang, Ruiping; Zheng, Junxian; Liu, Changming; Li, Hao; Ma, Jianxiang; Zhang, Yong; Wei, Chunhua; Zhang, Xian

2016-01-01

Drought stress has become an increasingly serious environmental issue that influences the growth and production of watermelon. Previous studies found that arbuscular mycorrhizal (AM) colonization improved the fruit yield and water use efficiency (WUE) of watermelon grown under water stress; however, the exact mechanisms remain unknown. In this study, the effects of Glomus versiforme symbiosis on the growth, physio-biochemical attributes, and stress-responsive gene expressions of watermelon seedlings grown under well-watered and drought conditions were investigated. The results showed that AM colonization did not significantly influence the shoot growth of watermelon seedlings under well-watered conditions but did promote root development irrespective of water treatment. Drought stress decreased the leaf relative water content and chlorophyll concentration, but to a lesser extent in the AM plants. Compared with the non-mycorrhizal seedlings, mycorrhizal plants had higher non-photochemical quenching values, which reduced the chloroplast ultrastructural damage in the mesophyll cells and thus maintained higher photosynthetic efficiency. Moreover, AM inoculation led to significant enhancements in the enzyme activities and gene expressions of superoxide dismutase, catalase, ascorbate peroxidase, glutathione reductase, and monodehydroascorbate reductase in watermelon leaves upon drought imposition. Consequently, AM plants exhibited lower accumulation of MDA, H2O2 and O2− compared with non-mycorrhizal plants. Under drought stress, the soluble sugar and proline contents were significantly increased, and further enhancements were observed by pre-treating the drought-stressed plants with AM. Taken together, our findings indicate that mycorrhizal colonization enhances watermelon drought tolerance through a stronger root system, greater protection of photosynthetic apparatus, a more efficient antioxidant system and improved osmoregulation. This study contributes to advances in the knowledge of AM-induced drought tolerance. PMID:27242845

Cell surface fucosylation does not affect development of colon tumors in mice with germline Smad3 mutation

PubMed Central

Domino, Steven E.; Karnak, David M.; Hurd, Elizabeth A.

2006-01-01

Background/Aims: Neoplasia-related alterations in cell surface α(1,2)fucosylated glycans have been reported in multiple tumors including colon, pancreas, endometrium, cervix, bladder, lung, and choriocarcinoma. Spontaneous colorectal tumors from mice with a germline null mutation of transforming growth factor-β signaling gene Smad3 (Madh3) were tested for α(1,2)fucosylated glycan expression. Methods: Ulex Europaeus Agglutinin-I lectin staining, fucosyltransferase gene northern blot analysis, and a cross of mutant mice with Fut2 and Smad3 germline mutations were performed. Results: Spontaneous colorectal tumors from Smad3 (-/-) homozygous null mice were found to express α(1,2)fucosylated glycans in an abnormal pattern compared to adjacent nonneoplastic colon. Northern blot analysis of α(1,2)fucosyltransferase genes Fut1 and Fut2 revealed that Fut2, but not Fut1, steady-state mRNA levels were significantly increased in tumors relative to adjacent normal colonic mucosa. Mutant mice with a Fut2-inactivating germline mutation were crossed with Smad3 targeted mice. In Smad3 (-/-)/Fut2 (-/-) double knock-out mice, UEA-I lectin staining was eliminated from colon and colon tumors, however, the number and size of tumors present by 24 weeks of age did not vary regardless of the Fut2 genotype. Conclusions: In this model of colorectal cancer, cell surface α(1,2)fucosylation does not affect development of colon tumors. PMID:17264540

Splitting a colon geometry with multiplanar clipping

NASA Astrophysics Data System (ADS)

Ahn, David K.; Vining, David J.; Ge, Yaorong; Stelts, David R.

1998-06-01

Virtual colonoscopy, a recent three-dimensional (3D) visualization technique, has provided radiologists with a unique diagnostic tool. Using this technique, a radiologist can examine the internal morphology of a patient's colon by navigating through a surface-rendered model that is constructed from helical computed tomography image data. Virtual colonoscopy can be used to detect early forms of colon cancer in a way that is less invasive and expensive compared to conventional endoscopy. However, the common approach of 'flying' through the colon lumen to visually search for polyps is tedious and time-consuming, especially when a radiologist loses his or her orientation within the colon. Furthermore, a radiologist's field of view is often limited by the 3D camera position located inside the colon lumen. We have developed a new technique, called multi-planar geometry clipping, that addresses these problems. Our algorithm divides a complex colon anatomy into several smaller segments, and then splits each of these segments in half for display on a static medium. Multi-planar geometry clipping eliminates virtual colonoscopy's dependence upon expensive, real-time graphics workstations by enabling radiologists to globally inspect the entire internal surface of the colon from a single viewpoint.

Pneumolysin plays a key role at the initial step of establishing pneumococcal nasal colonization.

PubMed

Hotomi, Muneki; Yuasa, Jun; Briles, David E; Yamanaka, Noboru

2016-09-01

Nasopharyngeal colonization by Streptococcus pneumoniae is an important initial step for the subsequent development of pneumococcal infections. Pneumococci have many virulence factors that play a role in colonization. Pneumolysin (PLY), a pivotal pneumococcal virulence factor for invasive disease, causes severe tissue damage and inflammation with disruption of epithelial tight junctions. In this study, we evaluated the role of PLY in nasal colonization of S. pneumoniae using a mouse colonization model. A reduction of numbers of PLY-deficient pneumococci recovered from nasal tissue, as well as nasal wash, was observed at days 1 and 2 post-intranasal challenges, but not later. The findings strongly support an important role for PLY in the initial establishment nasal colonization. PLY-dependent invasion of local nasal mucosa may be required to establish nasal colonization with S. pneumoniae. The data help provide a rationale to explain why an organism that exists as an asymptomatic colonizer has evolved virulence factors that enable it to occasionally invade and kill its hosts. Thus, the same pneumococcal virulence factor, PLY that can contribute to killing the host, may also play a role early in the establishment of nasopharynx carriage.

Advances in Lymphatic Imaging and Drug Delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nune, Satish K.; Gunda, Padmaja; Majeti, Bharat K.

2011-09-10

Cancer remains the second leading cause of death after heart disease in the US. While metastasized cancers such as breast, prostate, and colon are incurable, before their distant spread, these diseases will have invaded the lymphatic system as a first step in their progression. Hence, proper evaluation of the disease state of the lymphatics which drain a tumor site is crucial to staging and the formation of a treatment plan. Current lymphatic imaging modalities with visible dyes and radionucleotide tracers offer limited sensitivity and poor resolution; however, newer tools using nanocarriers, quantum dots, and magnetic resonance imaging promise to vastlymore » improve the staging of lymphatic spread without needless biopsies. Concurrent with the improvement of lymphatic imaging agents, has been the development of drug carriers that can localize chemotherapy to the lymphatic system, thus improving the treatment of localized disease while minimizing the exposure of healthy organs to cytotoxic drugs. This review will focus on polymeric systems that have been developed for imaging and drug delivery to the lymph system, how these new devices improve upon current technologies, and where further improvement is needed.« less

The effect of improved compliance with hygiene guidelines on transmission of Staphylococcus aureus to newborn infants: the Swedish Hygiene Intervention and Transmission of S aureus study.

PubMed

Mernelius, Sara; Löfgren, Sture; Lindgren, Per-Eric; Blomberg, Marie; Olhager, Elisabeth; Gunnervik, Christina; Lenrick, Raymond; Thrane, Malena Tiefenthal; Isaksson, Barbro; Matussek, Andreas

2013-07-01

Newborn infants are often colonized with Staphylococcus aureus originating from health care workers (HCWs). We therefore use colonization with S aureus of newborn infants to determine the effect of an improved compliance with hygiene guidelines on bacterial transmission. Compliance with hygiene guidelines was monitored prior to (baseline) and after (follow-up) a multimodal hygiene intervention in 4 departments of obstetrics and gynecology. spa typing was used to elucidate transmission routes of S aureus collected from newborn infants, mothers, fathers, staff members, and environment. The compliance with hygiene guidelines increased significantly from baseline to follow-up. The transmission of S aureus from HCWs to infants was however not affected. Fathers had the highest colonization rates. Persistent carriage was indicated in 18% of the HCWs. The most commonly isolated spa type was t084, which was not detected in a previous study from the same geographic area. It is possible to substantially improve the compliance with hygiene guidelines, by using multimodal hygiene intervention. The improved compliance did not decrease the transmission of S aureus from sources outside the own family to newborn infants. Furthermore, we show the establishment of a new spa type (t084), which now is very common in our region. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Rebamipide alleviates radiation-induced colitis through improvement of goblet cell differentiation in mice.

PubMed

Jang, Hyosun; Park, Sunhoo; Lee, Janet; Myung, Jae Kyung; Jang, Won-Suk; Lee, Sun-Joo; Myung, Hyunwook; Lee, Changsun; Kim, Hyewon; Lee, Seung-Sook; Jin, Young-Woo; Shim, Sehwan

2018-04-01

Radiation-induced colitis is a common clinical problem associated with radiotherapy and accidental exposure to ionizing radiation. Goblet cells play a pivotal role in the intestinal barrier against pathogenic bacteria. Rebamipide, an anti-gastric ulcer drug, has the effects to promote goblet cell proliferation. The aim of this study was to investigate whether radiation-induced colonic injury could be alleviated by rebamipide. This study orally administered rebamipide for 6 days to mice, which were subjected to 13 Gy abdominal irradiation, to evaluate the therapeutic effects of rebamipide against radiation-induced colitis. To confirm the effects of rebamipide on irradiated colonic epithelial cells, this study used the HT29 cell line. Rebamipide clearly alleviated the acute radiation-induced colitis, as reflected by the histopathological data, and significantly increased the number of goblet cells. The drug also inhibited intestinal inflammation and protected from bacterial translocation during acute radiation-induced colitis. Furthermore, rebamipide significantly increased mucin 2 expression in both the irradiated mouse colon and human colonic epithelial cells. Additionally, rebamipide accelerated not only the recovery of defective tight junctions but also the differentiation of impaired goblet cells in an irradiated colonic epithelium, which indicates that rebamipide has beneficial effects on the colon. Rebamipide is a therapeutic candidate for radiation-induced colitis, owing to its ability to inhibit inflammation and protect the colonic epithelial barrier. © 2017 The Authors Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

A novel high-throughput assay to quantify the vaccine-induced inhibition of Bordetella pertussis adhesion to airway epithelia.

PubMed

Zanaboni, Elisa; Arato, Vanessa; Pizza, Mariagrazia; Seubert, Anja; Leuzzi, Rosanna

2016-09-15

Pertussis or whooping cough is an acute respiratory illness caused by the Gram-negative pathogen Bordetella pertussis. Despite high vaccination coverage whooping cough is currently re-emerging in many developed countries. Although the causes of pertussis resurgence are matter of debate, emerging evidences suggest that acellular vaccines efficiently protect against the hallmark symptoms of pertussis disease but fail to prevent colonization. This presumably impacts on increased risk of bacterial transmission and consequent spread throughout the population. These evidences suggest that improved vaccines may be required for efficient bacterial clearance in the upper respiratory tract. Consequently, there is a need for novel bioassays to evaluate at pre-clinical or clinical level the impact of different vaccines on B. pertussis colonization. We developed a high-throughput bacterial adhesion inhibition (BAI) assay based on human respiratory cell lines and on live bacteria chemically conjugated to a fluorescent dye. Employing A549 cells as model, we evaluated the impact of antibodies elicited by acellular (aP) and whole cell (wP) vaccines on B. pertussis adhesion in vitro. Moreover, we settled the method also on polarized Calu-3 cells grown at air-liquid interface (ALI), showing that this assay can be extended to more complex cell models mimicking the airway epithelium. We proved that this method is a sensitive, rapid and reproducible system to evaluate the anti-adhesive properties of vaccine-induced antibodies and can be employed to assess improved pertussis vaccines.

Staphylococcal biofilm growth on smooth and porous titanium coatings for biomedical applications.

PubMed

Braem, Annabel; Van Mellaert, Lieve; Mattheys, Tina; Hofmans, Dorien; De Waelheyns, Evelien; Geris, Liesbet; Anné, Jozef; Schrooten, Jan; Vleugels, Jef

2014-01-01

Implant-related infections are a serious complication in prosthetic surgery, substantially jeopardizing implant fixation. As porous coatings for improved osseointegration typically present an increased surface roughness, their resulting large surface area (sometimes increasing with over 700% compared to an ideal plane) renders the implant extremely susceptible to bacterial colonization and subsequent biofilm formation. Therefore, there is particular interest in orthopaedic implantology to engineer surfaces that combine both the ability to improve osseointegration and at the same time reduce the infection risk. As part of this orthopaedic coating development, the interest of in vitro studies on the interaction between implant surfaces and bacteria/biofilms is growing. In this study, the in vitro staphylococcal adhesion and biofilm formation on newly developed porous pure Ti coatings with 50% porosity and pore sizes up to 50 μm is compared to various dense and porous Ti or Ti-6Al-4V reference surfaces. Multiple linear regression analysis indicates that surface roughness and hydrophobicity are the main determinants for bacterial adherence. Accordingly, the novel coatings display a significant reduction of up to five times less bacterial surface colonization when compared to a commercial state-of-the-art vacuum plasma sprayed coating. However, the results also show that a further expansion of the porosity with over 15% and/or the pore size up to 150 μm is correlated to a significant increase in the roughness parameters resulting in an ascent of bacterial attachment. Chemically modifying the Ti surface in order to improve its hydrophilicity, while preserving the average roughness, is found to strongly decrease bacteria quantities, indicating the importance of surface functionalization to reduce the infection risk of porous coatings. Copyright © 2013 Wiley Periodicals, Inc.

Toward decolonizing nursing: the colonization of nursing and strategies for increasing the counter-narrative.

PubMed

McGibbon, Elizabeth; Mulaudzi, Fhumulani M; Didham, Paula; Barton, Sylvia; Sochan, Ann

2014-09-01

Although there are notable exceptions, examination of nursing's participation in colonizing processes and practices has not taken hold in nursing's consciousness or political agenda. Critical analyses, based on the examination of politics and power of the structural determinants of health, continue to be marginalized in the profession. The goals of this discussion article are to underscore the urgent need to further articulate postcolonial theory in nursing and to contribute to nursing knowledge about paths to work toward decolonizing the profession. The authors begin with a description of unifying themes in postcolonial theory, with an emphasis on colonized subjectivities and imperialism; the application of a critical social science perspective, including postcolonial feminist theory; and the project of working toward decolonization. Processes involved in the colonization of nursing are described in detail, including colonization of nursing's intellectual development and the white privilege and racism that sustain colonizing thinking and action in nursing. The authors conclude with strategies to increase the counter-narrative to continued colonization, with a focus on critical social justice, human rights and the structural determinants of health. © 2013 John Wiley & Sons Ltd.

Natural mycorrhizal colonization of pines on reclaimed surface mines in Virginia. [Pinus strobus; Pinus taeda; Pinus virginiana

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schoenholtz, S.H.; Burger, J.A.; Torbert, J.L.

The effects of spoil type, slow-release fertilization, and weed control using glyphosate on the degree of ectomycorrhizal colonization of container-grown white (Pinus strobus L.), loblolly (P. taeda L.), and Virginia (P. virginiana Mill.) pines were studied on two strip mined sites (sandstone vs. siltstone overburden material) in southwestern Virginia. Although some seedlings were successfully colonized at both sites, the number of seedlings colonized and the proportion of short-root colonization per seedling were consistently higher on the sandstone spoil. On both sites, loblolly and Virginia pines had more ectomycorrhizal formation than white pine. Foliar P levels of all three species onmore » the sandstone spoil and of loblolly pine on the siltstone spoil were significantly correlated with ectomycorrhizal development. The degree of ectomycorrhizal formation for any of the species on either spoil was not decreased by slow-release fertilization or glyphosate applications. These results indicate that natural mycorrhizal colonization is compatible with these cultural treatments, and that colonization from indigenous fungal species may be adequate, eliminating the need for artificial inoculation.« less

Epidemiology and Characteristics of Escherichia coli Sequence Type 131 (ST131) from Long-Term Care Facility Residents Colonized Intestinally with Fluoroquinolone-Resistant Escherichia coli

PubMed Central

Han, Jennifer H.; Garrigan, Charles; Johnston, Brian; Nachamkin, Irving; Clabots, Connie; Bilker, Warren B.; Santana, Evelyn; Tolomeo, Pam; Maslow, Joel; Myers, Janice; Carson, Lesley; Lautenbach, Ebbing; Johnson, James R.

2016-01-01

The objective of this study was to evaluate molecular and epidemiologic factors associated with Escherichia coli sequence type 131 (ST131) among long-term care facility (LTCF) residents who acquired gastrointestinal tract colonization with fluoroquinolone-resistant E. coli (FQREC). Colonizing isolates from 37 residents who newly developed FQREC colonization at three LTCFs from 2006–2008 were evaluated. Twenty-nine (78%) of 37 total FQREC colonizing isolates were ST131. Most ST131 isolates had a distinctive combination of gyrA and parC replacement mutations. The ST131 and non-ST131 isolates differed significantly for the prevalence of many individual virulence factors but not for the proportion that qualified molecularly as extraintestinal pathogenic E. coli (ExPEC) or aggregate virulence factor scores. E. coli ST131 was highly prevalent among LTCF residents with FQREC colonization. Future studies should determine the risk factors for infection among ST131-colonized residents, and assess the potential for increased transmissibility of ST131 in the long-term care setting. PMID:27939288

Effect of chronic hypokalemia on H(+)-K(+)-ATPase expression in rat colon.

PubMed

Codina, J; Pressley, T A; DuBose, T D

1997-01-01

Although the kidney plays the major role in the regulation of systemic K+ homeostasis, the colon also participates substantively in K+ balance. The colon is capable of both K+ absorption and secretion, the magnitude of which can be modulated in response to dietary K+ intake. The H(+)-K(+)-adenosinetriphosphatase (H(+)-K(+)-ATPase) has been proposed as a possible mediator of K+ absorption in distal colon, but inhibitor profiles obtained in recent studies suggest that two, and perhaps more, distinct H(+)-K(+)-ATPase activities may be present in mammalian distal colon. We have developed highly specific probes for the catalytic alpha-subunits of colonic and gastric H(+)-K(+)-ATPase, alpha 1-Na(+)-K(+)-ATPase, and beta-actin, which were used in Northern analysis of total RNA from whole distal colon and stomach obtained from one of three experimental groups of rats: 1) controls, 2) chronic dietary K+ depletion, and 3) chronic metabolic acidosis. The probe for the colonic but not the gastric H(+)-K(+)-ATPase alpha-isoform hybridized to distal colon total RNA in all groups. A significant increase in colonic H(+)-K(+)-ATPase mRNA abundance was observed in response to chronic dietary K+ depletion but not to chronic metabolic acidosis. The alpha 1-isoform of Na(+)-K(+)-ATPase, which is also expressed in distal colon, did not respond consistently to either chronic dietary K+ depletion or chronic metabolic acidosis. The gastric probe did not hybridize to total RNA from distal colon but, as expected, hybridized to total stomach RNA. However, the abundance of gastric H(+)-K(+)-ATPase or Na(+)-K(+)-ATPase in stomach was not altered consistently by either chronic dietary K+ depletion or metabolic acidosis. Under the conditions of this study, it appears that the mRNA encoding the colonic alpha-isoform is upregulated by chronic dietary K+ restriction, a condition shown previously to increase K+ absorption in the distal colon.

Assessment of the probiotic potential of a dairy product fermented by Propionibacterium freudenreichii in piglets.

PubMed

Cousin, Fabien J; Foligné, Benoît; Deutsch, Stéphanie-Marie; Massart, Sébastien; Parayre, Sandrine; Le Loir, Yves; Boudry, Gaëlle; Jan, Gwénaël

2012-08-15

Dairy propionibacteria, including Propionibacterium freudenreichii , display promising probiotic properties, including immunomodulation. These properties are highly strain-dependent and rarely studied in a fermented dairy product. We screened 10 strains, grown in a newly developed fermented milk ultrafiltrate, for immunomodulatory properties in vitro. The most anti-inflammatory strain, P. freudenreichii BIA129, was further tested on piglets. P. freudenreichii -fermented product improved food intake and growth of piglets. Colonic mucosa explants of treated pigs secreted less interleukin 8 (-25%, P < 0.05) and tumor necrosis factor α (-20%, P < 0.05), either in basal conditions or after a lipopolysaccharide challenge. By contrast, the gut structure, barrier function (measured ex vivo in Ussing chambers), microbial diversity (assessed by 16S rRNA pyrosequencing), and colonic short-chain fatty acid content were unchanged, assuming maintenance of normal intestinal physiology. In conclusion, this work confirms in vivo probiotic properties of dairy propionibacteria-fermented products, which are promising for the prevention or healing of inflammatory bowel diseases.

Severe delayed complication after percutaneous endoscopic colostomy for chronic intestinal pseudo-obstruction: A case report and review of the literature

PubMed Central

Bertolini, David; De Saussure, Philippe; Chilcott, Michael; Girardin, Marc; Dumonceau, Jean-Marc

2007-01-01

Percutaneous endoscopic colostomy (PEC) is increasingly proposed as an alternative to surgery to treat various disorders, including acute colonic pseudo-obstruction, chronic intestinal pseudo-obstruction and relapsing sigmoid volvulus. We report on a severe complication that occurred two months after PEC placement. A 74-year-old man with a history of chronic intestinal pseudo-obstruction evolving since 8 years was readmitted to our hospital and received PEC to provide long-standing relief. The procedure was uneventful and greatly improved the patient’s quality of life. Two months later, the patient developed acute stercoral peritonitis. At laparotomy, the colostomy flange was embedded in the abdominal wall but no pressure necrosis was found at the level of the colonic wall. This complication was likely related to inadvertent traction of the colostomy tube. Subtotal colectomy with terminal ileostomy was performed. We review the major features of 60 cases of PEC reported to date, including indications and complications. PMID:17465514

Severe delayed complication after percutaneous endoscopic colostomy for chronic intestinal pseudo-obstruction: a case report and review of the literature.

PubMed

Bertolini, David; De Saussure, Philippe; Chilcott, Michael; Girardin, Marc; Dumonceau, Jean-Marc

2007-04-21

Percutaneous endoscopic colostomy (PEC) is increasingly proposed as an alternative to surgery to treat various disorders, including acute colonic pseudo-obstruction, chronic intestinal pseudo-obstruction and relapsing sigmoid volvulus. We report on a severe complication that occurred two months after PEC placement. A 74-year-old man with a history of chronic intestinal pseudo-obstruction evolving since 8 years was readmitted to our hospital and received PEC to provide long-standing relief. The procedure was uneventful and greatly improved the patient's quality of life. Two months later, the patient developed acute stercoral peritonitis. At laparotomy, the colostomy flange was embedded in the abdominal wall but no pressure necrosis was found at the level of the colonic wall. This complication was likely related to inadvertent traction of the colostomy tube. Subtotal colectomy with terminal ileostomy was performed. We review the major features of 60 cases of PEC reported to date, including indications and complications.

Using discrete multi-physics for detailed exploration of hydrodynamics in an in vitro colon system.

PubMed

Alexiadis, A; Stamatopoulos, K; Wen, W; Batchelor, H K; Bakalis, S; Barigou, M; Simmons, M J H

2017-02-01

We developed a mathematical model that describes the motion of viscous fluids in the partially-filled colon caused by the periodic contractions of flexible walls (peristalsis). In-vitro data are used to validate the model. The model is then used to identify two fundamental mechanisms of mass transport: the surfing mode and the pouring mode. The first mechanism is faster, but only involves the surface of the liquid. The second mechanism causes deeper mixing, and appears to be the main transport mechanism. Based on the gained understanding, we propose a series of measures that can improve the reliability of in-vitro models. The tracer in PET-like experiments, in particular, should not be injected in the first pocket, and its viscosity should be as close as possible to that of the fluid. If these conditions are not met, the dynamics of the tracer and the fluid diverge, compromising the accuracy of the in-vitro data. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diagnosis of pediatric gastric, small-bowel and colonic volvulus.

PubMed

Garel, Charles; Blouet, Marie; Belloy, Frederique; Petit, Thierry; Pelage, Jean-Pierre

2016-01-01

Digestive volvulus affects the stomach, small bowel and mobile segments of the colon and often has a developmental cause. Reference radiologic examinations include upper gastrointestinal contrast series for gastric volvulus, possibly with ultrasonography for small-bowel volvulus, and contrast enema for colonic volvulus. Treatment is usually surgical. This pictorial essay describes the embryological development and discusses the clinical and radiologic presentation of volvulus, depending on location, and details the appropriate radiologic examinations.

Hypothesis: Induction of biomarkers for detection of colonic neoplasms

PubMed Central

Bordonaro, Michael; Lazarova, Darina

2018-01-01

The signing of the National Cancer Act of 1971 by President Nixon marked the beginning of our war on cancer. More than 45 years later, the war is still going steady, with the enemy being almost as strong as in 1971. Furthermore, the increasing rates of obesity not only among adults, but among children and adolescents, are the likely cause for the 30-year trend of colon cancer (CC) becoming a disease of the younger population in the U.S. These trends, however, have not spurred the development of novel screening approaches for CC. Considering the need for a sensitive and non-invasive detection of early stage neoplastic lesions in the colon, we propose the development of a test based on a novel concept - the concept of induced biomarkers. The proposal is based upon our findings that the food additives propolis and gamma-cyclodextrin (gCD) (a) decrease the neoplastic burden in normal weight and obese ApcMin mice, a model of early stage intestinal neoplasia, and (b) elicit significant changes in the serum proteome in ApcMin mice. We posit that gCD and propolis induce the release of neoplasm-associated biomarkers in systemic circulation (e.g., metabolites, neoplastic, apoptotic, and immune response proteins), and these markers could be used to detect early stage intestinal neoplasms. Additional dietary bioactives may also elicit a complement of induced markers. The hypothesis could be ascertained by utilizing a mouse model, the Apc+/1638Nmice, as well as through human subject studies that integrate proteomics and metabolomics analyses. The concept of detecting inducible markers of colonic neoplasms is novel, and is substantiated by the significant physiological effects of gCD and propolis on neoplastic colonic cells in culture and on early neoplastic development in ApcMinmice. The long-term objective is to develop a minimally invasive method that detects early stage neoplastic development in the human colon. PMID:29290782

Characterization of colonic dendritic cells in normal and colitic mice.

PubMed

Cruickshank, Sheena M; English, Nicholas R; Felsburg, Peter J; Carding, Simon R

2005-10-28

Recent studies demonstrating the direct involvement of dendritic cells (DC) in the activation of pathogenic T cells in animal models of inflammatory bowel disease identify DC as important antigen presenting cells in the colon. However, very little is known about the properties of colonic DC. Using immunohistochemistry, electron microscopy and flow cytometry we have characterized and compared colonic DC in the colon of healthy animals and interleukin-2-deficient (IL2(-/-)) mice that develop colitis. In the healthy colon, DC resided within the lamina propria and in close association with the basement membrane of colonic villi. Type 1 myeloid (CD11c(+), CD11b(+), B220(-), CD8alpha(-)) DC made up the largest (40-45%) population and all DC expressed low levels of CD80, CD86, and CD40, and had high endocytic activity consistent with an immature phenotype. In colitic IL2(-/-) mice, colonic DC numbers increased four- to five-fold and were localized within the epithelial layer and within aggregates of T and B cells. They were also many more DC in mesenteric lymph nodes (MLN). The majority (>85%) of DC in the colon and MLN of IL2(-/-) mice were type 1 myeloid, and expressed high levels of MHC class II, CD80, CD86, CD40, DEC 205, and CCR5 molecules and were of low endocytic activity consistent with mature DC. These findings demonstrate striking changes in the number, distribution and phenotype of DC in the inflamed colon. Their intimate association with lymphocytes in the colon and draining lymph nodes suggest that they may contribute directly to the ongoing inflammation in the colon.

Characterization of colonic dendritic cells in normal and colitic mice

PubMed Central

Cruickshank, Sheena M; English, Nicholas R; Felsburg, Peter J; Carding, Simon R

2005-01-01

AIM: Recent studies demonstrating the direct involvement of dendritic cells (DC) in the activation of pathogenic T cells in animal models of inflammatory bowel disease identify DC as important antigen presenting cells in the colon. However, very little is known about the properties of colonic DC. METHODS: Using immunohistochemistry, electron microscopy and flow cytometry we have characterized and compared colonic DC in the colon of healthy animals and interleukin-2-deficient (IL2-/-) mice that develop colitis. RESULTS: In the healthy colon, DC resided within the lamina propria and in close association with the basement membrane of colonic villi. Type 1 myeloid (CD11c+, CD11b+, B220-, CD8α-) DC made up the largest (40-45%) population and all DC expressed low levels of CD80, CD86, and CD40, and had high endocytic activity consistent with an immature phenotype. In colitic IL2-/- mice, colonic DC numbers increased four- to five-fold and were localized within the epithelial layer and within aggregates of T and B cells. They were also many more DC in mesenteric lymph nodes (MLN). The majority (>85%) of DC in the colon and MLN of IL2-/- mice were type 1 myeloid, and expressed high levels of MHC class II, CD80, CD86, CD40, DEC 205, and CCR5 molecules and were of low endocytic activity consistent with mature DC. CONCLUSION: These findings demonstrate striking changes in the number, distribution and phenotype of DC in the inflamed colon. Their intimate association with lymphocytes in the colon and draining lymph nodes suggest that they may contribute directly to the ongoing inflammation in the colon. PMID:16419163

Colitis and Colon Cancer in WASP-Deficient Mice Require Helicobacter Spp.

PubMed Central

Nguyen, Deanna D.; Muthupalani, Suresh; Goettel, Jeremy A.; Eston, Michelle A.; Mobley, Melissa; Taylor, Nancy S.; McCabe, Amanda; Marin, Romela; Snapper, Scott B.; Fox, James G.

2014-01-01

Background Wiskott-Aldrich Syndrome protein (WASP)-deficient patients and mice are immunodeficient and can develop inflammatory bowel disease. The intestinal microbiome is critical to the development of colitis in most animal models, in which, Helicobacter spp. have been implicated in disease pathogenesis. We sought to determine the role of Helicobacter spp. in colitis development in WASP-deficient (WKO) mice. Methods Feces from WKO mice raised under specific pathogen free conditions were evaluated for the presence of Helicobacter spp., after which, a subset of mice were rederived in Helicobacter spp.-free conditions. Helicobacter spp.-free WKO animals were subsequently infected with Helicobacter bilis. Results Helicobacter spp. were detected in feces from WKO mice. After re-derivation in Helicobacter spp.-free conditions, WKO mice did not develop spontaneous colitis but were susceptible to radiation-induced colitis. Moreover, a T-cell transfer model of colitis dependent on WASP-deficient innate immune cells also required Helicobacter spp. colonization. Helicobacter bilis infection of rederived WKO mice led to typhlitis and colitis. Most notably, several H. bilis-infected animals developed dysplasia with 10% demonstrating colon carcinoma, which was not observed in uninfected controls. Conclusions Spontaneous and T-cell transfer, but not radiation-induced, colitis in WKO mice is dependent on the presence of Helicobacter spp. Furthermore, H. bilis infection is sufficient to induce typhlocolitis and colon cancer in Helicobacter spp.-free WKO mice. This animal model of a human immunodeficiency with chronic colitis and increased risk of colon cancer parallels what is seen in human colitis and implicates specific microbial constituents in promoting immune dysregulation in the intestinal mucosa. PMID:23820270

When is Helicobacter pylori acquired in populations in developing countries? A birth-cohort study in Bangladeshi children.

PubMed

Kienesberger, Sabine; Perez-Perez, Guillermo I; Olivares, Asalia Z; Bardhan, Pradip; Sarker, Shafiqul A; Hasan, Kh Zahid; Sack, R Bradley; Blaser, Martin J

2018-03-01

Helicobacter pylori colonization is prevalent throughout the world, and is predominantly acquired during childhood. In developing countries, >70% of adult populations are colonized with H. pylori and >50% of children become colonized before the age of 10 years. However, the exact timing of acquisition is unknown. We assessed detection of H. pylori acquisition among a birth cohort of 105 children in Mirzapur, Bangladesh. Blood samples collected at time 0 (cord blood), and at 6, 12, 18, and 24 months of life were examined for the presence of IgG and IgA antibodies to whole cell H. pylori antigen and for IgG antibodies to the CagA antigen using specific ELISAs and immunoblotting. Breast milk samples were analyzed for H. pylori-specific IgA antibodies. Cord blood was used to establish maternal colonization status. H. pylori seroprevalence in the mothers was 92.8%. At the end of the two-year follow-up period, 50 (47.6%) of the 105 children were positive for H. pylori in more than one assay. Among the colonized children, CagA prevalence was 78.0%. A total of 58 children seroconverted: 50 children showed persistent colonization and 8 (7.6%) children showed transient seroconversion, but immunoblot analysis suggested that the transient seroconversion observed by ELISA may represent falsely positive results. Acquisition of H. pylori was not influenced by the mother H. pylori status in serum or breastmilk. In this population with high H. pylori prevalence, we confirmed that H. pylori in developing countries is detectable mainly after the first year of life.

Metastatic colonic and gastric polyps from breast cancer resembling hyperplastic polyps.

PubMed

Horimoto, Yoshiya; Hirashima, Tetsuro; Arakawa, Atsushi; Miura, Hiroyoshi; Saito, Mitsue

2018-03-23

Breast cancer metastasis to the gastrointestinal tract is relatively rare and is generally found when patients complain of symptoms such as gastrointestinal obstruction. Herein, we report a case with metastatic colonic and gastric lesions from breast cancer, with the formation of mucosal polyps which resembled typical hyperplastic polyps.A 47-year-old woman underwent curable surgery for breast cancer and received standard systemic treatments. Her primary tumor was composed of a mix of invasive lobular and ductal carcinomas. During adjuvant endocrine therapy, she developed multiple colonic metastases, identified by colonoscopy performed as part of a general health check-up. She had no symptoms. Small elevated sessile polyps in the transverse colon and rectum showed histological features of signet-ring cell type adenocarcinoma, similar to the invasive lobular component of the primary breast cancer. During treatments for recurrent disease, she also developed multiple gastric metastases, with the same endoscopic and pathological features as the colonic lesions. Her treatment regimen was switched to oral chemotherapy, and she has since maintained stable disease for nearly 3 years. Multiple bone metastases eventually developed, and she was again switched to another systemic treatment but, to date, has remained free of symptoms.We emphasize that the endoscopic findings of the metastatic lesions in the colon and stomach in this case highly resembled hyperplastic polyps. Since biopsy is not always performed for hyperplastic polyps in the gastrointestinal tract, we believe that this case report may encourage endoscopists to offer biopsies to the patient who has a history of breast cancer.

Use of Granada Medium To Detect Group B Streptococcal Colonization in Pregnant Women

PubMed Central

Rosa-Fraile, Manuel; Rodriguez-Granger, Javier; Cueto-Lopez, Marina; Sampedro, Antonio; Gaye, Enrique Biel; Haro, José Manuel; Andreu, Antonia

1999-01-01

Direct inoculation onto Granada medium (GM) in plates and tubes was compared to inoculation into a selective Todd-Hewitt broth (with 8 μg of gentamicin per ml and 15 μg of nalidixic acid per ml) for detection of group B streptococci (GBS) in pregnant women with 800 vaginal and 450 vaginoanorectal samples. Comparatively, GM was found to be as sensitive as the selective broth for the detection of GBS in vaginal specimens and more sensitive than selective broth for the detection of GBS in vaginoanorectal samples (96 versus 82%). The use of GM improved the time to reporting of a GBS-positive result by at least 24 h and reduced the direct cost of screening. We have also found that the inconvenience of anaerobic incubation of GM plates can be avoided when a cover slide is placed upon the inoculum, because aerobic incubation in GM plates with cover slides causes GBS to develop the same pigmentation that it develops with incubation under anaerobic conditions. These data support the routine use of GM plates or tubes as a more accurate, easier, and cheaper method of identification of GBS-colonized women compared to the enrichment broth technique. PMID:10405420

Voriconazole Exposure and Risk of Cutaneous Squamous Cell Carcinoma, Aspergillus Colonization, Invasive Aspergillosis and Death in Lung Transplant Recipients

PubMed Central

Mansh, M.; Binstock, M.; Williams, K.; Hafeez, F.; Kim, J.; Glidden, D.; Boettger, R.; Hays, S.; Kukreja, J.; Golden, J.; Asgari, M.M.; Chin-Hong, P.; Singer, J.P.; Arron, S.

2015-01-01

Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but has been associated with an increased risk for developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance its competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco transplanted between October 1991 and December 2012 (n=455) to investigate whether voriconazole exposure impacted development of SCC, Aspergillus colonization, invasive aspergillosis, and all-cause mortality. Voriconazole exposure was associated with a 73% increased risk for developing SCC (HR=1.73; 95% CI: 1.04–2.88; p=0.03), with each additional 30-day exposure at the standard dose increasing the risk by 3.0% (HR=1.03; 95% CI: 1.02–1.04; p<0.001). Voriconazole exposure reduced risk of Aspergillus colonization by 50% (HR=0.50; 95% CI: 0.34–0.72; p<0.001), but we were underpowered to detect risk reduction for invasive aspergillosis. Voriconazole exposure significantly reduced all-cause mortality among subjects who developed Aspergillus colonization (HR=0.34; 95% CI: 0.13–0.91; p=0.03), but had no significant impact on those without colonization. Physicians should consider patient-specific factors that modify the potential risks and benefits of voriconazole in the care of lung transplant recipients. PMID:26372838

Human Immune Response to Outer Membrane Protein CD of Moraxella catarrhalis in Adults with Chronic Obstructive Pulmonary Disease

PubMed Central

Murphy, Timothy F.; Kirkham, Charmaine; Liu, Dai-Fang; Sethi, Sanjay

2003-01-01

Moraxella catarrhalis is a common cause of lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). The antibody response to outer membrane protein (OMP) CD, a highly conserved surface protein of M. catarrhalis under consideration as a vaccine antigen, was studied in adults with COPD following 40 episodes of infection or colonization. Following infection or colonization, 9 of 40 patients developed new serum immunoglobulin G (IgG) to OMP CD, as measured by enzyme-linked immunosorbent assay. Adsorption assays revealed that a proportion of the serum IgG was directed toward surface-exposed epitopes on OMP CD in six of the nine patients who developed new IgG to OMP CD. Immunoblot assays with fusion peptide constructs indicated that the new antibodies that developed after infection or colonization recognized conformational epitopes, particularly in the carboxy region of the protein. Three of 28 patients developed new mucosal IgA to OMP CD in sputum supernatants. This study establishes that OMP CD is a target of a systemic and mucosal immune response following infection and colonization in some patients with COPD. PMID:12595444

Bone marrow dendritic cells from mice with an altered microbiota provide interleukin 17A-dependent protection against Entamoeba histolytica colitis.

PubMed

Burgess, Stacey L; Buonomo, Erica; Carey, Maureen; Cowardin, Carrie; Naylor, Caitlin; Noor, Zannatun; Wills-Karp, Marsha; Petri, William A

2014-11-04

There is an emerging paradigm that the human microbiome is central to many aspects of health and may have a role in preventing enteric infection. Entamoeba histolytica is a major cause of amebic diarrhea in developing countries. It colonizes the colon lumen in close proximity to the gut microbiota. Interestingly, not all individuals are equally susceptible to E. histolytica infection. Therefore, as the microbiota is highly variable within individuals, we sought to determine if a component of the microbiota could regulate susceptibility to infection. In studies utilizing a murine model, we demonstrated that colonization of the gut with the commensal Clostridia-related bacteria known as segmented filamentous bacteria (SFB) is protective during E. histolytica infection. SFB colonization in this model was associated with elevated cecal levels of interleukin 17A (IL-17A), dendritic cells, and neutrophils. Bone marrow-derived dendritic cells (BMDCs) from SFB-colonized mice had higher levels of IL-23 production in response to stimulation with trophozoites. Adoptive transfer of BMDCs from an SFB(+) to an SFB(-) mouse was sufficient to provide protection against E. histolytica. IL-17A induction during BMDC transfer was necessary for this protection. This work demonstrates that intestinal colonization with a specific commensal bacterium can provide protection during amebiasis in a murine model. Most importantly, this work demonstrates that the microbiome can mediate protection against an enteric infection via extraintestinal effects on bone marrow-derived dendritic cells. Entamoeba histolytica is the causative agent of amebiasis, an infectious disease that contributes significantly to morbidity and mortality due to diarrhea in the developing world. We showed in a murine model that colonization with the commensal members of the Clostridia known as SFB provides protection against E. histolytica and that dendritic cells from SFB-colonized mice alone can recapitulate protection. Understanding interactions between enteropathogens, commensal intestinal bacteria, and the mucosal immune response, including dendritic cells, will help in the development of effective treatments for this disease and other infectious and inflammatory diseases. The demonstration of immune-mediated protection due to communication from the microbiome to the bone marrow represents an emerging field of study that will yield unique approaches to the development of these treatments. Copyright © 2014 Burgess et al.

The effect of vagotomy and drainage on the small bowel flora

PubMed Central

Browning, G. G.; Buchan, K. A.; Mackay, C.

1974-01-01

The incidence of small intestinal colonization in unoperated duodenal ulcer patients was low and similar to that in the normal population. The majority of patients seven to 10 days following truncal vagotomy and drainage were colonized whereas none of a control group of patients following simple closure of a perforated duodenal ulcer was colonized. In patients with pyloroplasty, this high incidence fell to control levels on average 18 months postoperatively, but in patients with a gastro-jejunostomy, the incidence remained raised probably due to the presence of the afferent loop. Only two patients developed episodic diarrhoea and there was no obvious association with small bowel colonization. PMID:4820640

Gated Mesoporous Silica Nanocarriers for a "Two-Step" Targeted System to Colonic Tissue.

PubMed

González-Alvarez, Marta; Coll, Carmen; Gonzalez-Alvarez, Isabel; Giménez, Cristina; Aznar, Elena; Martínez-Bisbal, M Carmen; Lozoya-Agulló, Isabel; Bermejo, Marival; Martínez-Máñez, Ramón; Sancenón, Félix

2017-12-04

Colon targeted drug delivery is highly relevant not only to treat colonic local diseases but also for systemic therapies. Mesoporous silica nanoparticles (MSNs) have been demonstrated as useful systems for controlled drug release given their biocompatibility and the possibility of designing gated systems able to release cargo only upon the presence of certain stimuli. We report herein the preparation of three gated MSNs able to deliver their cargo triggered by different stimuli (redox ambient (S1), enzymatic hydrolysis (S2), and a surfactant or being in contact with cell membrane (S3)) and their performance in solution and in vitro with Caco-2 cells. Safranin O dye was used as a model drug to track cargo fate. Studies of cargo permeability in Caco-2 monolayers demonstrated that intracellular safranin O levels were significantly higher in Caco-2 monolayers when using MSNs compared to those of free dye. Internalization assays indicated that S2 nanoparticles were taken up by cells via endocytosis. S2 nanoparticles were selected for in vivo tests in rats. For in vivo assays, capsules were filled with S2 nanoparticles and coated with Eudragit FS 30 D to target colon. The enteric coated capsule containing the MSNs was able to deliver S2 nanoparticles in colon tissue (first step), and then nanoparticles were able to deliver safranin O inside the colonic cells after the enzymatic stimuli (second step). This resulted in high levels of safranin O in colonic tissue combined with low dye levels in plasma and body tissues. The results suggested that this combination of enzyme-responsive gated MSNs and enteric coated capsules may improve the absorption of drugs in colon to treat local diseases with a reduction of systemic effects.

Endothelin-1 stimulates colon cancer adjacent fibroblasts.

PubMed

Knowles, Jonathan P; Shi-Wen, Xu; Haque, Samer-ul; Bhalla, Ashish; Dashwood, Michael R; Yang, Shiyu; Taylor, Irving; Winslet, Marc C; Abraham, David J; Loizidou, Marilena

2012-03-15

Endothelin-1 (ET-1) is produced by and stimulates colorectal cancer cells. Fibroblasts produce tumour stroma required for cancer development. We investigated whether ET-1 stimulated processes involved in tumour stroma production by colonic fibroblasts. Primary human fibroblasts, isolated from normal tissues adjacent to colon cancers, were cultured with or without ET-1 and its antagonists. Cellular proliferation, migration and contraction were measured. Expression of enzymes involved in tumour stroma development and alterations in gene transcription were determined by Western blotting and genome microarrays. ET-1 stimulated proliferation, contraction and migration (p < 0.01 v control) and the expression of matrix degrading enzymes TIMP-1 and MMP-2, but not MMP-3. ET-1 upregulated genes for profibrotic growth factors and receptors, signalling molecules, actin modulators and extracellular matrix components. ET-1 stimulated colonic fibroblast cellular processes in vitro that are involved in developing tumour stroma. Upregulated genes were consistent with these processes. By acting as a strong stimulus for tumour stroma creation, ET-1 is proposed as a target for adjuvant cancer therapy. Copyright © 2011 UICC.

Transabdominal electrical stimulation (TES) for the treatment of slow-transit constipation (STC).

PubMed

Hutson, John M; Dughetti, Lauren; Stathopoulos, Lefteris; Southwell, Bridget R

2015-05-01

Slow-transit constipation (STC) is a newly described subtype of intractable constipation in children which we originally identified with deficiency of substance P in axons supplying the proximal colonic muscle. When nuclear transit studies became available, the patients were found to have slow proximal colonic transit, and responded to antegrade enemas. Using the appendicostomy, we found that there was reduced frequency in propagating sequences throughout the colon. We began testing whether transcutaneous electrical stimulation (TES) could improve motility and symptoms, and over several trials have now shown that TES is remarkably effective in treating children with STC, with long-lasting effects. TES holds promise for treating STC, as well as a range of gastrointestinal motility disorders.

Severe eosinophilic colitis caused by neuropathic agents in a patient with chronic fatigue syndrome and functional abdominal pain: case report and review of the literature.

PubMed

Fragkos, Konstantinos C; Barragry, John; Fernando, Charisma Shahi; Novelli, Marco; Begent, Joanna; Zárate-Lopez, Natalia

2018-06-01

Eosinophilic colitis is a rare clinical condition that belongs to the group of eosinophilic gastrointestinal disorders. Its occurrence can be primary or secondary to infection, medications, or autoimmune/hematological conditions. We present a case of a young female adult with severe chronic fatigue syndrome, widespread chronic pain, including functional abdominal pain, who developed severe eosinophilic colitis following successive treatments with gabapentin and pregabalin. On both occasions, symptoms manifested as abdominal pain, diarrhea, and eosinophilia and improved upon discontinuation of the medications. Magnetic resonance imaging of the small bowel demonstrated an ascending colon colitis, and endoscopic investigations confirmed florid colitis mainly in the ascending colon with biopsies demonstrating a dense eosinophilic infiltrate with micro-abscesses. Serum eosinophil counts correlated well with the timing of the agents' administration. There was no other organ involvement. Symptoms improved upon discontinuation of the drugs and steroid administration. Eosinophilic colitis is an exceptionally rare entity and its mechanism of action is still unclear. Suspicion of eosinophilic colitis should be raised if a patient presents with abdominal pain, diarrhea, and peripheral eosinophilia following treatment with pregabalin or gabapentin. © Georg Thieme Verlag KG Stuttgart · New York.

Lubiprostone plus PEG electrolytes versus placebo plus PEG electrolytes for outpatient colonoscopy preparation: a randomized, double-blind placebo-controlled trial.

PubMed

Sofi, Aijaz A; Nawras, Ali T; Pai, Chetan; Samuels, Qiana; Silverman, Ann L

2015-01-01

Bowel preparation using large volume of polyethylene glycol (PEG) solutions is often poorly tolerated. Therefore, there are ongoing efforts to develop an alternative bowel cleansing regimen that should be equally effective and better tolerated. The aim of this study was to assess the efficacy of lubiprostone (versus placebo) plus PEG as a bowel cleansing preparation for colonoscopy. Our study was a randomized, double-blind placebo-controlled design. Patients scheduled for screening colonoscopy were randomized 1:1 to lubiprostone (group 1) or placebo (group 2) plus 1 gallon of PEG. The primary endpoints were patient's tolerability and endoscopist's evaluation of the preparation quality. The secondary endpoint was to determine any reduction in the amount of PEG consumed in the lubiprostone group compared with the placebo group. One hundred twenty-three patients completed the study and were included in the analysis. There was no difference in overall cleanliness. The volume of PEG was similar in both the groups. The volume of PEG approached significance as a predictor of improved score for both the groups (P = 0.054). Lubiprostone plus PEG was similar to placebo plus PEG in colon cleansing and volume of PEG consumed. The volume of PEG consumed showed a trend toward improving the quality of the colon cleansing.

A Novel In Situ Simulation Intervention Used to Mitigate an Outbreak of Methicillin-Resistant Staphylococcus aureus in a Neonatal Intensive Care Unit.

PubMed

Gibbs, Kathleen; DeMaria, Samuel; McKinsey, Scarlett; Fede, Andrea; Harrington, Anne; Hutchison, Deborah; Torchen, Carol; Levine, Adam; Goldberg, Andrew

2018-03-01

To describe the successful implementation of an in situ simulation program to diagnose and correct latent safety threats in a level 4 neonatal intensive care unit (NICU) to mitigate a methicillin-resistant Staphylococcus aureus (MRSA) outbreak. An investigational report describes a simulation intervention that occurred during a 4-month MRSA outbreak in a single-center, 46-bed, newly renovated level 4 NICU. The simulation program was developed for all NICU providers in which they were exposed to a 30-minute in situ human simulation intervention that included education, evaluation, and debriefing to resolve perceived or observed latent safety threats. The primary study outcome was improved hand hygiene compliance and an enhanced estimate of the culture of safety during a 6-month period. A total of 99 healthcare providers including physicians, nurses, respiratory therapists, and environmental service workers completed the course. Before the simulation intervention, there were 18 patients colonized or infected with a single MRSA clone; after the intervention, there were no new episodes of colonization or infection. An in situ, simulation-based intervention can counter threats to patient safety related to workflow and lapses in infection control practices and improve patient outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

A case of gastrojejunocolic fistula with steatohepatitis.

PubMed

Omori, Teppei; Tokushige, Katsutoshi; Kinoshita, Fukiko; Ito, Ayumi; Taniai, Makiko; Taneichi, Mikiko; Iizuka, Bunei; Itabashi, Michio; Nagashima, Yoji; Yamamoto, Masakazu; Nakamura, Shinichi; Hashimoto, Etsuko

2017-02-01

A man in his 30s, who had undergone retrocolic Billroth II reconstruction for perforated duodenal ulcer, presented with watery diarrhea for 2 years and suspected fatty liver. He was referred to our hospital for management of chronic diarrhea, weight loss, hepatopathy and hypoalbuminemia. Initial upper and lower gastrointestinal endoscopies were negative. Since a small bowel lesion was suspected, peroral single-balloon enteroscopy was performed, which identified feces-like residue near the Billroth II anastomotic site and a connection to the colon separate from the afferent and efferent loops. Transanal single-balloon enteroscopy identified a fistula between the gastrojejunal anastomosis and transverse colon, with the scope reaching the stomach transanally. Barium enema confirmed flow of contrast medium from the transverse colon through the fistula to the anastomotic site, allowing the diagnosis of gastrojejunocolic fistula. Liver biopsy showed relatively severe steatohepatitis (Brunt's classification: stage 2-3, grade 3). Resection of the anastomotic site and partial transverse colectomy were performed to remove the fistula, followed by Roux-en-Y reconstruction. Postoperatively, watery diarrhea resolved and the stools became normal. Hepatopathy and hypoproteinemia improved. One year later, liver biopsy showed marked improvement of steatosis. This case demonstrated marked improvement of both diarrhea/nutritional status and steatohepatitis after treatment of gastrojejunocolic fistula, suggesting that the fistula caused non-alcoholic steatohepatitis.

Curcumin Conjugated with PLGA Potentiates Sustainability, Anti-Proliferative Activity and Apoptosis in Human Colon Carcinoma Cells

PubMed Central

Waghela, Bhargav N.; Sharma, Anupama; Dhumale, Suhashini; Pandey, Shashibahl M.; Pathak, Chandramani

2015-01-01

Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid) and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116). The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy. PMID:25692854

A Systems Biology Approach Reveals Differences in the Dynamics of Colonization and Degradation of Grass vs. Hay by Rumen Microbes with Minor Effects of Vitamin E Supplementation

PubMed Central

Belanche, Alejandro; Newbold, Charles J.; Lin, Wanchang; Rees Stevens, Pauline; Kingston-Smith, Alison H.

2017-01-01

Increasing the efficiency of utilization of fresh and preserved forage is a key target for ruminant science. Vitamin E is often used as additive to improve product quality but its impact of the rumen function is unknown. This study investigated the successional microbial colonization of ryegrass (GRA) vs. ryegrass hay (HAY) in presence of zero or 50 IU/d supplementary vitamin E, using a rumen simulation technique. A holistic approach was used to link the dynamics of feed degradation with the structure of the liquid-associated (LAB) and solid-associated bacteria (SAB). Results showed that forage colonization by SAB was a tri-phasic process highly affected by the forage conservation method: Early colonization (0–2 h after feeding) by rumen microbes was 2× faster for GRA than HAY diets and dominated by Lactobacillus and Prevotella which promoted increased levels of lactate (+56%) and ammonia (+18%). HAY diets had lower DM degradation (-72%) during this interval being Streptococcus particularly abundant. During secondary colonization (4–8 h) the SAB community increased in size and decreased in diversity as the secondary colonizers took over (Pseudobutyrivibrio) promoting the biggest differences in the metabolomics profile between diets. Secondary colonization was 3× slower for HAY vs. GRA diets, but this delay was compensated by a greater bacterial diversity (+197 OTUs) and network complexity resulting in similar feed degradations. Tertiary colonization (>8 h) consisted of a slowdown in the colonization process and simplification of the bacterial network. This slowdown was less evident for HAY diets which had higher levels of tertiary colonizers (Butyrivibrio and Ruminococcus) and may explain the higher DM degradation (+52%) during this interval. The LAB community was particularly active during the early fermentation of GRA and during the late fermentation for HAY diets indicating that the availability of nutrients in the liquid phase reflects the dynamics of feed degradation. Vitamin E supplementation had minor effects but promoted a simplification of the LAB community and a slight acceleration in the SAB colonization sequence which could explain the higher DM degradation during the secondary colonization. Our findings suggest that when possible, grass should be fed instead of hay, in order to accelerate feed utilization by rumen microbes. PMID:28824585

Methyl-orvinol-Dual activity opioid receptor ligand inhibits gastrointestinal transit and alleviates abdominal pain in the mouse models mimicking diarrhea-predominant irritable bowel syndrome.

PubMed

Zielińska, Marta; Jarmuż, Agata; Wasilewski, Andrzej; Cami-Kobeci, Gerta; Husbands, Stephen; Fichna, Jakub

2017-04-01

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional disorder of the gastrointestinal (GI) tract. The major IBS-D symptoms include diarrhea, abdominal pain and discomfort. High density of opioid receptors (ORs) in the GI tract and their participation in the maintenance of GI homeostasis make ORs ligands an attractive option for developing new anti-IBS-D treatments. The aim of this study was to characterize the effect of methyl-orvinol on the GI motility and secretion and in mouse models mimicking symptoms of IBS-D. In vitro, the effects of methyl-orvinol on electrical field stimulated smooth muscle contractility and epithelial ion transport were characterized in the mouse colon. In vivo, the following tests were used to determine methyl-orvinol effect on mouse GI motility: colonic bead expulsion, whole GI transit and fecal pellet output. An antinociceptive action of methyl-orvinol was assessed in the mouse model of visceral pain induced by mustard oil. Methyl-orvinol (10 -10 to 10 -6 M) inhibited colonic smooth muscle contractions in a concentration-dependent manner. This effect was reversed by naloxone (non-selective opioid antagonist) and β-funaltrexamine (selective MOP antagonist). Experiments with a selective KOP receptor agonist, U50488 revealed that methyl-orvinol is a KOP receptor antagonist in the GI tract. Methyl-orvinol enhanced epithelial ion transport. In vivo, methyl-orvinol inhibited colonic bead expulsion and prolonged GI transit. Methyl-orvinol improved hypermotility and reduced abdominal pain in the mouse models mimicking IBS-D symptoms. Methyl-orvinol could become a promising drug candidate in chronic therapy of functional GI diseases such as IBS-D. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Orally administered sodium 4-phenylbutyrate suppresses the development of dextran sulfate sodium-induced colitis in mice.

PubMed

Ono, Kazuhiko; Nimura, Satoshi; Hideshima, Yuko; Nabeshima, Kazuki; Nakashima, Manabu

2017-12-01

Sodium 4-phenylbutyrate (PBA) exerts therapeutic effects in a wide range of pathologies. A previous study by the present authors revealed that intraperitoneal administration of PBA suppresses the onset of dextran sulfate sodium (DSS)-induced colitis in mice. In the present study, the effects of orally administered PBA are investigated, as this route of administration is more clinically relevant. The therapeutic efficacy of PBA (10 mg/12 h) in mice with experimental colitis was assessed based on the disease activity index, production of inflammatory cytokines, colon length and histopathological investigations. The results of the present study demonstrated a significantly higher survival rate in the PBA-treated group compared with the PBA-untreated (DSS control) group (P=0.0156). PBA treatment improved pathological indices of experimental colitis (P<0.05). Furthermore, the oral administration of PBA significantly inhibited the DSS-induced shortening of the colon (P<0.05) and overproduction of interleukin (IL)-1β and IL-6 (both P<0.05) as measured in colonic lavage fluids. A marked attenuation of the DSS-induced overproduction of tumor necrosis factor was also observed. For histopathological analysis, a marked decrease in mature goblet cells and increase in enlarged nuclei of the absorptive cells was observed in colon lesions of DSS control mice as compared with normal untreated mice. However, in the PBA-treated mice, no such lesions were observed and the mucosa resembled that of DSS-untreated mice. The results of the present study, combined with those results of a previous study, suggest that oral and intraperitoneal administration of PBA have similar preventative effects on DSS-induced colitis, achieved by suppressing its pathogenesis.

Radioprotection of 1,2-dimethylhydrazine-initiated colon cancer in rats using low-dose γ rays by modulating multidrug resistance-1, cytokeratin 20, and β-catenin expression.

PubMed

Nabil, H M; Hassan, B N; Tohamy, A A; Waaer, H F; Abdel Moneim, A E

2016-03-01

Ionizing radiation is a widely used therapy for solid tumors. However, high-dose ionizing radiation causes apoptosis, transforms normal cells into tumor cells, and impairs immune functions, leading to the defects in the removal of damaged or tumor cells. In contrast, low-dose radiation has been reported to exert various beneficial effects in cells. This experimental study investigated the effect of γ rays at low dose on the development of colorectal tumor in a 1,2-dimethylhydrazine (DMH)-induced colon cancer. Colorectal tumor model was induced in Wistar rats by subcutaneous injection of DMH (20 mg/kg) once a week for 15 weeks. Starting from zero day of DMH injection, a single low dose of whole-body γ irradiation of 0.5 Gy/week was applied to the rats. A significant reduction in lipid peroxidation, nitric oxide, and elevation in the glutathione content and antioxidant enzyme activity (superoxide dismutase and catalase) were observed after γ irradiation comparing with DMH group. Moreover, γ ray reduced the expressions of multidrug resistance 1 (MDR1), β-catenin, and cytokeratin 20 (CK20) those increased in DMH-treated rats. However, survivin did not change with γ ray treatment. A histopathological examination of the DMH-injected rats revealed ulcerative colitis, dysplasia, anaplasia, and hyperchromasia. An improvement in the histopathological picture was seen in the colon of rats exposed to γ rays. In conclusion, the present results showed that low-dose γ ray significantly inhibited DMH-induced colon carcinogenesis in rats by modulating CK20, MDR1, and β-catenin expression but not survivin expression. © The Author(s) 2015.

Continuous blood pressure monitoring via non-invasive radial artery applanation tonometry and invasive arterial catheter demonstrates good agreement in patients undergoing colon carcinoma surgery.

PubMed

Sun, Jing; Chen, Hanjian; Zheng, Jun; Mao, Bin; Zhu, Shengmei; Feng, Jingyi

2017-12-01

Radial artery applanation tonometry (RAAT) has been developed and utilized for continuous arterial pressure monitoring. However, evidence is lacking to clinically verify the RAAT technology and identify appropriate patient groups before routine clinical use. This study aims to evaluate the RAAT technology by comparing systolic blood pressure (SBP), mean blood pressure (MBP) and diastolic blood pressure (DBP) values in patients undergoing colon carcinoma surgery. Blood Pressure (BP) values obtained via RAAT (TL-300, Tensys Medical Inc., San Diego, CA, USA) and conventional arterial catheterization from 30 colon carcinoma surgical patients were collected and compared via Bland-Atman method, linear regression and 4-quadrant plot concordance analysis. For SBPs, MBPs and DBPs, means of the differences (±standard deviation; 95% limits of agreement) were -0.9 (±7.6; -15.7 to 13.9) mmHg, 3.1 (±6.5; -9.6 to 15.8) mmHg and 4.3 (±7.4; -10.3 to 18.8) mmHg, respectively. Linear regression coefficients of determination were 0.8706 for SBPs, 0.8353 for MBPs and 0.6858 for DBPs. Four-quadrant concordance correlation coefficients were 0.8740, 0.8522 and 0.7108 for SBPs, MBPs and DBPs, respectively. A highly selected patient collective undergoing colon carcinoma surgery was studied. BP measurements obtained via the TL-300 had clinically acceptable agreement with that acquired invasively using an arterial catheter. For use in clinical routine, it is necessary to take measures for improvement regarding movement artifacts and dilution of noise. A large sample size of patients under various conditions is also needed to further evaluate the RAAT technology before clinically routine use.

Improvement of absorption enhancing effects of n-dodecyl-beta-D-maltopyranoside by its colon-specific delivery using chitosan capsules.

PubMed

Fetih, Gihan; Lindberg, Sara; Itoh, Katsuhito; Okada, Naoki; Fujita, Takuya; Habib, Fawsia; Artersson, Per; Attia, Mohammed; Yamamoto, Akira

2005-04-11

In general, absorption enhancing effects of various absorption enhancers were greater in the large intestine than those in the small intestinal regions. Therefore, the effectiveness of absorption enhancers is expected to be remarkably observed, if these enhancers can be delivered to the large intestine with some poorly absorbable drugs after oral administration. In this study, therefore, we examined whether chitosan capsules were effective for the colon-specific delivery of a certain absorption enhancer and can improve the absorption enhancing action of the absorption enhancer after oral administration. 5(6)-Carboxyfluorescein (CF) was used as a model drug to investigate the site-dependent effectiveness of various absorption enhancers by an in situ closed loop method. Sodium glycocholate (NaGC), n-dodecyl-beta-d-maltopyranoside (LM), sodium salicylate (NaSal) and sodium caprate (NaCap) were used as models of absorption enhancers in this study. Overall, the absorption enhancing effects of these enhancers for intestinal absorption of CF were greater in the colon than those in the jejunum and the ileum. Especially, among these enhancers tested in this study, LM showed much greater absorption enhancing effect in the colon than in the jejunum and the ileum. Therefore, LM was selected as a model absorption enhancer to examine the effect of chitosan capsules on the absorption enhancing effect of LM. When CF and LM were orally administered to rats using chitosan capsules, the plasma concentration of CF was much higher than those in other dosage forms including solution and gelatin capsules. Therefore, chitosan capsules may be useful carriers for colon-specific delivery of LM, thereby increasing its absorption enhancing effect from the intestinal membranes.

Newly identified helper bacteria stimulate ectomycorrhizal formation in Populus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Labbe, Jessy L.; Weston, David J.; Dunkirk, Nora

Mycorrhiza helper bacteria (MHB) are known to increase host root colonization by mycorrhizal fungi but the molecular mechanisms and potential tripartite trophic interactions are poorly understood. Through an effort to study Populus microbiome, we isolated 21 Pseudomonas strains from native Populus deltoides roots. These bacterial isolates were characterized and screened for MHB effectiveness on the Populus-Laccaria system. Two other Pseudomonas strains (i.e., Pf-5 and BBc6R8) from existing collections were also included as reference in the screening process. We analyzed Laccaria bicolor S238N growth rate, mycelial architecture and transcriptional changes induced by the contrasting Pseudomonas strains (i.e., inhibitory, neutral and beneficial).more » We characterized 17 out of the 21 Pseudomonas strains from the Populus rhizosphere with positive effects on L. bicolor S238N growth, as well as on Populus root architecture and colonization by L. bicolor S238N across three Populus species. Four of seven reporter genes, Tra1, Tectonin2, Gcn5 and Cipc1, thought to be specific to the interaction with strain BBc6R8, were induced or repressed while interacting with six (i.e., GM17, GM33, GM41, GM48, Pf-5 and BBc6R8) of the tested Pseudomonas strains. GM41 promoted the highest roots colonization across three Populus species but most notably in P. deltoides, which is otherwise, poorly colonized by L. bicolor. Here we report novel MHB strains isolated from native Populus that improve roots colonization. This tripartite relationship could be exploited in nursery production for target Populus species/genotypes as a means of improving establishment and survival in marginal lands.« less

Newly identified helper bacteria stimulate ectomycorrhizal formation in Populus

DOE PAGES

Labbe, Jessy L.; Weston, David J.; Dunkirk, Nora; ...

2014-10-24

Mycorrhiza helper bacteria (MHB) are known to increase host root colonization by mycorrhizal fungi but the molecular mechanisms and potential tripartite trophic interactions are poorly understood. Through an effort to study Populus microbiome, we isolated 21 Pseudomonas strains from native Populus deltoides roots. These bacterial isolates were characterized and screened for MHB effectiveness on the Populus-Laccaria system. Two other Pseudomonas strains (i.e., Pf-5 and BBc6R8) from existing collections were also included as reference in the screening process. We analyzed Laccaria bicolor S238N growth rate, mycelial architecture and transcriptional changes induced by the contrasting Pseudomonas strains (i.e., inhibitory, neutral and beneficial).more » We characterized 17 out of the 21 Pseudomonas strains from the Populus rhizosphere with positive effects on L. bicolor S238N growth, as well as on Populus root architecture and colonization by L. bicolor S238N across three Populus species. Four of seven reporter genes, Tra1, Tectonin2, Gcn5 and Cipc1, thought to be specific to the interaction with strain BBc6R8, were induced or repressed while interacting with six (i.e., GM17, GM33, GM41, GM48, Pf-5 and BBc6R8) of the tested Pseudomonas strains. GM41 promoted the highest roots colonization across three Populus species but most notably in P. deltoides, which is otherwise, poorly colonized by L. bicolor. Here we report novel MHB strains isolated from native Populus that improve roots colonization. This tripartite relationship could be exploited in nursery production for target Populus species/genotypes as a means of improving establishment and survival in marginal lands.« less

Combining heterogeneous features for colonic polyp detection in CTC based on semi-definite programming

NASA Astrophysics Data System (ADS)

Wang, Shijun; Yao, Jianhua; Petrick, Nicholas A.; Summers, Ronald M.

2009-02-01

Colon cancer is the second leading cause of cancer-related deaths in the United States. Computed tomographic colonography (CTC) combined with a computer aided detection system provides a feasible combination for improving colonic polyps detection and increasing the use of CTC for colon cancer screening. To distinguish true polyps from false positives, various features extracted from polyp candidates have been proposed. Most of these features try to capture the shape information of polyp candidates or neighborhood knowledge about the surrounding structures (fold, colon wall, etc.). In this paper, we propose a new set of shape descriptors for polyp candidates based on statistical curvature information. These features, called histogram of curvature features, are rotation, translation and scale invariant and can be treated as complementing our existing feature set. Then in order to make full use of the traditional features (defined as group A) and the new features (group B) which are highly heterogeneous, we employed a multiple kernel learning method based on semi-definite programming to identify an optimized classification kernel based on the combined set of features. We did leave-one-patient-out test on a CTC dataset which contained scans from 50 patients (with 90 6-9mm polyp detections). Experimental results show that a support vector machine (SVM) based on the combined feature set and the semi-definite optimization kernel achieved higher FROC performance compared to SVMs using the two groups of features separately. At a false positive per patient rate of 7, the sensitivity on 6-9mm polyps using the combined features improved from 0.78 (Group A) and 0.73 (Group B) to 0.82 (p<=0.01).

Survival ability of Mexican fruit fly males from different strains in presence of the predatory orb-weaving spider Argiope argentata (Araneae: Araneidae).

PubMed

Dor, A; Liedo, P

2018-04-18

The sterile insect technique (SIT) is a key element for the integrated management of pest populations of the Mexican fruit fly, Anastrepha ludens, in Mexico. Its success depends on the survival of mass-reared sterile males and their ability to mate with wild females. However, colonization and mass-rearing conditions can adversely affect their ability to avoid predators. To test if colony management strategies could contribute to improve field survival abilities of mass-reared flies, we compared the survival of males exposed to the orb-weaver spider Argiope argentata. Males compared originated from three strains with different colonization strategies: (a) a colony started from field-collected wild flies (replacement), (b) a colony started by hybridizing wild males with mass-reared adapted females (hybrid) and (c) a colony started with mass-reared males selected on the basis of their survival ability and mating competitiveness in field cages (selected). Mass-reared males and wild males were used as controls. Males were exposed to spiders under laboratory cage conditions. Overall, wild males showed better survival ability than mass-reared males. Regarding the colonization approach, wild males survived better than a hybrid, replaced and selected males. We conclude that mass-rearing conditions have a strong negative effect on the ability of males to escape spiders. The colonization systems evaluated did not counter this effect. The lower survival of males from the selected colony suggests that the selection over one generation did not contribute to improve males' predator avoidance and escape abilities and probably needs to be modified. Possible explanations for this and implications on colonization and colony management for SIT purpose are discussed.

Combining Statistical and Geometric Features for Colonic Polyp Detection in CTC Based on Multiple Kernel Learning

PubMed Central

Wang, Shijun; Yao, Jianhua; Petrick, Nicholas; Summers, Ronald M.

2010-01-01

Colon cancer is the second leading cause of cancer-related deaths in the United States. Computed tomographic colonography (CTC) combined with a computer aided detection system provides a feasible approach for improving colonic polyps detection and increasing the use of CTC for colon cancer screening. To distinguish true polyps from false positives, various features extracted from polyp candidates have been proposed. Most of these traditional features try to capture the shape information of polyp candidates or neighborhood knowledge about the surrounding structures (fold, colon wall, etc.). In this paper, we propose a new set of shape descriptors for polyp candidates based on statistical curvature information. These features called histograms of curvature features are rotation, translation and scale invariant and can be treated as complementing existing feature set. Then in order to make full use of the traditional geometric features (defined as group A) and the new statistical features (group B) which are highly heterogeneous, we employed a multiple kernel learning method based on semi-definite programming to learn an optimized classification kernel from the two groups of features. We conducted leave-one-patient-out test on a CTC dataset which contained scans from 66 patients. Experimental results show that a support vector machine (SVM) based on the combined feature set and the semi-definite optimization kernel achieved higher FROC performance compared to SVMs using the two groups of features separately. At a false positive per scan rate of 5, the sensitivity of the SVM using the combined features improved from 0.77 (Group A) and 0.73 (Group B) to 0.83 (p ≤ 0.01). PMID:20953299

Combined Treatment with Hyaluronic Acid and Mesalamine Protects Rats from Inflammatory Bowel Disease Induced by Intracolonic Administration of Trinitrobenzenesulfonic Acid.

PubMed

Chiu, Chih-Tung; Kuo, Sheng-Nan; Hung, Shao-Wen; Yang, Cheng-Yao

2017-05-30

Drugs such as mesalamine (5-ASA) are currently recommended for the treatment of inflammatory bowel disease (IBD). To reduce the frequency of their administration and improve their therapeutic effect, this study investigated the adhesion efficacy, wound healing promotion, and decrease in inflammation in ulcers in the colonic tissue of rats with colitis after combined treatment with hyaluronic acid (HA) and 5-ASA (IBD98-M). HA-fluoresceinamine (FL) conjugates successfully adhered to the mucosal layer and were conjugated in the vascular tissue. In addition, macroscopic and microscopic observations indicated that colonic injuries reduced significantly after treatment with IBD98-M. Compared with PBS and 5-ASA treatment alone, treatment with IBD98-M more effectively reduced bowel inflammation and promoted colonic mucosal healing in TNBS-induced colitis. IBD98-M treatment also reduced myeloperoxidase activity and the expression levels of cyclooxygenase 2 and tumor necrosis factor-αin the colitis tissue. In conclusion, IBD98-M treatment strongly promoted wound healing in colonic injuries and significantly inhibited MPO activity in the inflamed colon tissue of rats. Combined treatment with HA and 5-ASA can accelerate wound healing and reduce inflammatory reaction in rat colitis.

Transmission of Staphylococcus aureus from maternity unit staff members to newborns disclosed through spa typing.

PubMed

Matussek, Andreas; Taipalensuu, Jan; Einemo, Ing-Marie; Tiefenthal, Malena; Löfgren, Sture

2007-03-01

We observed previously that newborn infants are colonized with Staphylococcus aureus, even if their mothers do not carry S aureus. This observation indicated a cross colonization, and, thus, a risk for nosocomial infection, although the infants are roomed in with their mothers. The S aureus colonization of infants, their parents, and staff members was measured at 3 maternity units. Possible transmission routes were determined using spa typing of S aureus isolates. Infants had the highest S aureus carriage (45%) compared with fathers (39%), mothers (27%), and staff members (27%). In 13 out of 44 colonized infants, transmission from staff members was indicated. This transmission was more frequent than was transmission from their own parents (11 cases), and occurred even in cases when parents were colonized with S aureus of other spa types. We confirm a high level of transmission of S aureus from staff members to infants, indicating a risk for patient safety, which necessitates continuing work with implementing scientific evidence for infection control. The spa typing is a rapid and valuable epidemiological tool, and it can be used in improving hospital hygiene control programs.

[Applied anatomy of laparoscopic-assisted right hemicolectomy for colon cancer].

PubMed

Lin, Guole; Xiao, Yi; Qiu, Huizhong

2015-06-01

Laparoscopic-assisted colon surgery is an alternative to open surgery. Furthermore, complete mesocolic excision (CME) as a new concept in colon cancer surgery was first proposed by Hohenberger from Germany, which follows the oncological principle of the tumor and is based on the embryology and anatomy. Some researches about CME showed that this procedure could improve the prognosis, decrease the local recurrence of the tumor without increased complications. Although a laparoscopic approach for right colon cancer is performed frequently, identifying an adequate dissection plane is not always easy. The surgeons need to know well about local anatomy of laparoscopic-assisted radical right hemicolectomy, and to master the right surgical plane in operation process, then to reduce the incidence of conversion to laparotomy and side injury. The superior mesenteric vein (SMV) is the key landmark. The fusion fascia space is the right surgical plane, as well as a series of peripheral peritoneal attachments are important fixations in laparoscopic right hemicolectomy by medial access. Identifying the anatomical location of the SMV and performing meticulous dissection along the SMV is an essential procedure to dissect all potential lymphatic drainage during laparoscopic CME for right colon cancer.

Transverse colon volvulus in neurologicaly imparied patient as an emergency surgical condition: A case report.

PubMed

Miličković, Maja; Savić, Đorđe; Stanković, Nikola; Vukadin, Miroslav; Božić, Dejana

2017-01-01

Transverse colon volvulus is an uncommon cause of bowel obstruction in general. Predisposing factors are mental retardation, dysmotility disorders, chronic constipation and congenital megacolon. We presented transverse colon volvulus in a 16-year-old boy with cerebral palsy. Chronic constipation in neurologicaly impaired patient was a risk factor predisposing to volvulus. The patient was admitted to the hospital with enormous abdominal distension and acute respiratory insufficiency. A boy was emergently taken to the operating room for exploratory laparotomy. During the surgery, a 360º clockwise volvulus of the transverse colon was found. After reduction of volvulus, an enormous transverse colon was resected and colostomy was formed. In the postoperative period, despite the good functioning of stoma and intraabdominal normotension, numerous and long lasting respiratory problems developed. The patient was discharged from our institution after 8 months. Though very rare in pediatric group, the possibility of a transverse colon volvulus must be considered in the differential diagnosis of acute large bowel obstruction.

[Surgical correction of the intraabdominal hypertension in patients with colon cancer].

PubMed

Aliev, S A

2012-01-01

The experience of treatment of 48 patients with colon cancer, complicated with bowe obstruction, colon perforation, abdominal sepsis and intraabdominal hypertension was analyzed. Men were 18, women - 30. Patients' age ranged 24-85 years. 31 patients (64.6%) had the 3rd stage (T4N2M0) of the disease by the time of the diagnosis. Tumor perforation was registered in 35 patients, the rest 13 had suprastenotic perforation. 39 patients developed SIRS and abdominal sepsis. The method of intraoperative "closed" colon decompression and intraluminar colon irrigation with the original modification of vacuum aspiration-irrigation device was introduced, as well as the modified method of end colostomy. Radical treatment was performed in 36 (78.3%) patients, 10 patients received palliative treatment and 2 patients could not be operated on. The postoperative lethality rate was 45.6%, the overall - 47.9%. The suggested method of colon decompression allowed to decrease the postoperative lethality rate from 47.7 to 45.6%, and the overall lethality rate from 50 to 47.9%.

Metabolome progression during early gut microbial colonization of gnotobiotic mice

PubMed Central

Marcobal, Angela; Yusufaly, Tahir; Higginbottom, Steven; Snyder, Michael; Sonnenburg, Justin L.; Mias, George I.

2015-01-01

The microbiome has been implicated directly in host health, especially host metabolic processes and development of immune responses. These are particularly important in infants where the gut first begins being colonized, and such processes may be modeled in mice. In this investigation we follow longitudinally the urine metabolome of ex-germ-free mice, which are colonized with two bacterial species, Bacteroides thetaiotaomicron and Bifidobacterium longum. High-throughput mass spectrometry profiling of urine samples revealed dynamic changes in the metabolome makeup, associated with the gut bacterial colonization, enabled by our adaptation of non-linear time-series analysis to urine metabolomics data. Results demonstrate both gradual and punctuated changes in metabolite production and that early colonization events profoundly impact the nature of small molecules circulating in the host. The identified small molecules are implicated in amino acid and carbohydrate metabolic processes, and offer insights into the dynamic changes occurring during the colonization process, using high-throughput longitudinal methodology. PMID:26118551

Metastatic Male Ductal Breast Cancer Mimicking Obstructing Primary Colon Cancer

PubMed Central

Koleilat, Issam; Syal, Anil; Hena, Muhammad

2010-01-01

Male breast cancer comprises only about 1% of all breast cancers. Commonly, sites of metastases include the central nervous system, lungs, bones, and even liver. In females, extrahepatic gastrointestinal metastases are unusual but have been reported with various clinical presentations. We are reporting the first case of a male patient with a history of ductal breast carcinoma that developed colonic metastasis and presented with mechanical large bowel obstruction masquerading as primary colon cancer. PMID:23675178

Development, evaluation and pharmacokinetics of time-dependent ketorolac tromethamine tablets.

PubMed

Vemula, Sateesh Kumar; Veerareddy, Prabhakar Reddy

2013-01-01

The present study was intended to develop a time-dependent colon-targeted compression-coated tablets of ketorolac tromethamine (KTM) using hydroxypropyl methylcellulose (HPMC) that release the drug slowly but completely in the colonic region by retarding the drug releases in stomach and small intestine. KTM core tablets were prepared by direct compression method and were compression coated with HPMC. The formulation is optimized based on the in vitro drug release studies and further evaluated by X-ray imaging technique in healthy humans to ensure the colonic delivery. To prove these results, in vivo pharmacokinetic studies in human volunteers were designed to study the in vitro-in vivo correlation. From the in vitro dissolution study, optimized formulation F3 showed negligible drug release (6.75 ± 0.49%) in the initial lag period followed by slow release (97.47 ± 0.93%) for 24 h which clearly indicates that the drug is delivered to the colon. The X-ray imaging studies showed that the tablets reached the colon without disintegrating in upper gastrointestinal system. From the pharmacokinetic evaluation, the immediate-release tablets producing peak plasma concentration (C(max)) was 4482.74 ng/ml at 2 h T(max) and colon-targeted tablets showed C(max) = 3562.67 ng/ml at 10 h T(max). The area under the curve for the immediate-release and compression-coated tablets was 10595.14 and 18796.70 ng h/ml and the mean resident time was 3.82 and 10.75 h, respectively. Thus, the compression-coated tablets based on time-dependent approach were preferred for colon-targeted delivery of ketorolac.

Ability of a Generalist Seed Beetle to Colonize an Exotic Host: Effects of Host Plant Origin and Oviposition Host.

PubMed

Amarillo-Suárez, A; Repizo, A; Robles, J; Diaz, J; Bustamante, S

2017-08-01

The colonization of an exotic species by native herbivores is more likely to occur if that herbivore is a generalist. There is little information on the life-history mechanisms used by native generalist insects to colonize exotic hosts and how these mechanisms are affected by host properties. We examined the ability of the generalist seed beetle Stator limbatus Horn to colonize an exotic species. We compared its host preference, acceptability, performance, and egg size when ovipositing and developing on two native (Pithecellobium dulce (Roxb.) Benth and Senegalia riparia (Kunth)) and one exotic legume species (Leucaena leucocephala (Lam.)). We also analyzed the seed chemistry. We found that females recognize the exotic species as an unfavorable host for larval development and that they delayed oviposition and laid fewer and larger eggs on the exotic species than on the native species. Survivorship on the exotic host was 0%. Additionally, seeds of the native species contain five chemical compounds that are absent in the exotic species, and the exotic species contains three sterols, which are absent in the native legumes. Genetically based differences between beetles adapted to different hosts, plastic responses toward new hosts, and chemical differences among seeds are important in host colonization and recognition of the exotic host. In conclusion, the generalist nature of S. limbatus does not influence its ability to colonize L. leucocephala. Explanations for the colonization of exotic hosts by generalist native species and for the success of invasive species must be complemented with studies measuring local adaptation and plasticity.

Intraoperative colonic pulse oximetry in left-sided colorectal surgery: can it predict anastomotic leak?

PubMed

Salusjärvi, Johannes M; Carpelan-Holmström, Monika A; Louhimo, Johanna M; Kruuna, Olli; Scheinin, Tom M

2018-03-01

An anastomotic leak is a fairly common and a potentially lethal complication in colorectal surgery. Objective methods to assess the viability and blood circulation of the anastomosis could help in preventing leaks. Intraoperative pulse oximetry is a cheap, easy to use, fast, and readily available method to assess tissue viability. Our aim was to study whether intraoperative pulse oximetry can predict the development of an anastomotic leak. The study was a prospective single-arm study conducted between the years 2005 and 2011 in Helsinki University Hospital. Patient material consisted of 422 patients undergoing elective left-sided colorectal surgery. The patients were operated by one of the three surgeons. All of the operations were partial or total resections of the left side of the colon with a colorectal anastomosis. The intraoperative colonic oxygen saturation was measured with pulse oximetry from the colonic wall, and the values were analyzed with respect to post-operative complications. 2.3 times more operated anastomotic leaks occurred when the colonic StO 2 was ≤ 90% (11/129 vs 11/293). The mean colonic StO 2 was 91.1 in patients who developed an operated anastomotic leak and 93.0 in patients who did not. With logistic regression analysis, the risk of operated anastomotic leak was 4.2 times higher with StO 2 values ≤ 90%. Low intraoperative colonic StO 2 values are associated with the occurrence of anastomotic leak. Despite its handicaps, the method seems to be useful in assessing anastomotic viability.

Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults

PubMed Central

Chambers, Edward S; Viardot, Alexander; Psichas, Arianna; Morrison, Douglas J; Murphy, Kevin G; Zac-Varghese, Sagen E K; MacDougall, Kenneth; Preston, Tom; Tedford, Catriona; Finlayson, Graham S; Blundell, John E; Bell, Jimmy D; Thomas, E Louise; Mt-Isa, Shahrul; Ashby, Deborah; Gibson, Glen R; Kolida, Sofia; Dhillo, Waljit S; Bloom, Stephen R; Morley, Wayne; Clegg, Stuart; Frost, Gary

2015-01-01

Objective The colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults. Design To investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults. Results Propionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group. Conclusions These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans. Trial registration number NCT00750438. PMID:25500202

Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts

PubMed Central

2014-01-01

Background Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats; the cytotoxicity of AOM is considered to mediate oxidative stress. This study investigated the chemopreventive effect of three natural extracts [pomegranate peel extract (PomPE), papaya peel extract (PapPE) and seaweed extract (SE)] against AOM-induced oxidative stress and carcinogenesis in rat colon. Methods Eighty Sprague–Dawley rats (aged 4 weeks) were randomly divided into 8 groups (10 rats/group). Control group was fed a basal diet; AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of PomPE, PapPE or SE, in the presence or absence of AOM injection. All animals were continuously fed ad-libitum until aged 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, genotoxicity (induced micronuclei (MN) cells enumeration), and glutathione and lipid peroxidation. Results Our results showed that AOM-induced ACF development and pathological changes in the colonic mucosal tissues, increased bone marrow MN cells and oxidative stress (glutathione depletion, lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with PomPE, PapPE or SE significantly ameliorated the cytotoxic effects of AOM. Conclusions The results of this study provide in-vivo evidence that PomPE, PapPE and SE reduced the AOM-induced colon cancer in rats, through their potent anti-oxidant activities. PMID:24533833

Parallels between Global Transcriptional Programs of Polarizing Caco-2 Intestinal Epithelial Cells In Vitro and Gene Expression Programs in Normal Colon and Colon Cancer

PubMed Central

Sääf, Annika M.; Halbleib, Jennifer M.; Chen, Xin; Yuen, Siu Tsan; Leung, Suet Yi

2007-01-01

Posttranslational mechanisms are implicated in the development of epithelial cell polarity, but little is known about the patterns of gene expression and transcriptional regulation during this process. We characterized temporal patterns of gene expression during cell–cell adhesion-initiated polarization of cultured human Caco-2 cells, which develop structural and functional polarity resembling enterocytes in vivo. A distinctive switch in gene expression patterns occurred upon formation of cell–cell contacts. Comparison to gene expression patterns in normal human colon and colon tumors revealed that the pattern in proliferating, nonpolarized Caco-2 cells paralleled patterns seen in human colon cancer in vivo, including expression of genes involved in cell proliferation. The pattern switched in polarized Caco-2 cells to one more closely resembling that in normal colon tissue, indicating that regulation of transcription underlying Caco-2 cell polarization is similar to that during enterocyte differentiation in vivo. Surprisingly, the temporal program of gene expression in polarizing Caco-2 cells involved changes in signaling pathways (e.g., Wnt, Hh, BMP, FGF) in patterns similar to those during migration and differentiation of intestinal epithelial cells in vivo, despite the absence of morphogen gradients and interactions with stromal cells characteristic of enterocyte differentiation in situ. The full data set is available at http://microarray-pubs.stanford.edu/CACO2. PMID:17699589

Colonization of Vitis vinifera by a Green Fluorescence Protein-Labeled, gfp-Marked Strain of Xylophilus ampelinus, the Causal Agent of Bacterial Necrosis of Grapevine

PubMed Central

Grall, Sophie; Manceau, Charles

2003-01-01

The dynamics of Xylophilus ampelinus were studied in Vitis vinifera cv. Ugni blanc using gfp-marked bacterial strains to evaluate the relative importance of epiphytic and endophytic phases of plant colonization in disease development. Currently, bacterial necrosis of grapevine is of economic importance in vineyards in three regions in France: the Cognac, Armagnac, and Die areas. This disease is responsible for progressive destruction of vine shoots, leading to their death. We constructed gfp-marked strains of the CFBP2098 strain of X. ampelinus for histological studies. We studied the colonization of young plants of V. vinifera cv. Ugni blanc by X. ampelinus after three types of artificial contamination in a growth chamber and in a greenhouse. (i) After wounding of the stem and inoculation, the bacteria progressed down to the crown through the xylem vessels, where they organized into biofilms. (ii) When the bacteria were forced into woody cuttings, they rarely colonized the emerging plantlets. Xylem vessels could play a key role in the multiplication and conservation of the bacteria, rather than being a route for plant colonization. (iii) When bacterial suspensions were sprayed onto the plants, bacteria progressed in two directions: both in emerging organs and down to the crown, thus displaying the importance of epiphytic colonization in disease development. PMID:12676663

Colonization of Vitis vinifera by a green fluorescence protein-labeled, gfp-marked strain of Xylophilus ampelinus, the causal agent of bacterial necrosis of grapevine.

PubMed

Grall, Sophie; Manceau, Charles

2003-04-01

The dynamics of Xylophilus ampelinus were studied in Vitis vinifera cv. Ugni blanc using gfp-marked bacterial strains to evaluate the relative importance of epiphytic and endophytic phases of plant colonization in disease development. Currently, bacterial necrosis of grapevine is of economic importance in vineyards in three regions in France: the Cognac, Armagnac, and Die areas. This disease is responsible for progressive destruction of vine shoots, leading to their death. We constructed gfp-marked strains of the CFBP2098 strain of X. ampelinus for histological studies. We studied the colonization of young plants of V. vinifera cv. Ugni blanc by X. ampelinus after three types of artificial contamination in a growth chamber and in a greenhouse. (i) After wounding of the stem and inoculation, the bacteria progressed down to the crown through the xylem vessels, where they organized into biofilms. (ii) When the bacteria were forced into woody cuttings, they rarely colonized the emerging plantlets. Xylem vessels could play a key role in the multiplication and conservation of the bacteria, rather than being a route for plant colonization. (iii) When bacterial suspensions were sprayed onto the plants, bacteria progressed in two directions: both in emerging organs and down to the crown, thus displaying the importance of epiphytic colonization in disease development.

Fetal sigmoid colon mesentery - In relevance in fetal ultrasound application. A pilot study.

PubMed

Wozniak, Slawomir; Florjanski, Jerzy; Kordecki, Henryk; Podhorska-Okolow, Marzena; Domagala, Zygmunt

2018-03-01

Ultrasound examinations during pregnancy are routine procedures used to detect fetal congenital malformations. Ultrasound monitoring of sigmoid colon mesenterial development could be useful for early detection of subjects at risk of sigmoid colon volvulus. The aim of our paper was to assess the sigmoid colon length, and sigmoid colon mesentery width and height in the late fetal period, and, using the results, to estimate the surface area of the mesocolon (in mm 2 ) in living fetuses. Moreover, we attempted to repeat some of these measurements in living fetuses using ultrasound imaging. The study was carried out on 209 formalin fixed human fetuses (100 female and 109 male) aged from 4th to 7th gestational months (102-203 days), with a crown-rump length of 132-342mm. The length of the sigmoid colon, as well as the height and width of its mesentery were measured. The surface area of the mesocolon was estimated. Correction for formalin induced shrinkage was applied. Pilot ultrasound examinations of live fetuses were performed. Mean values of sigmoid colon length, mesenteric width and height (formalin fixed fetuses) for respective gestational ages were: month 4: 21.46±6.7mm, 6.80±2.1mm, 5.5±1.49mm; month 5: 27.32±1.2mm, 7.62±2.01mm, 7.33±2.17mm; month 6: 47.56±9.57mm, 11.68±3.8mm, 10.3±3.05mm; month 7: 56.92±17.48mm. 15.32±8 mm, 12.81±3.16mm. The surface area ranges of the sigmoid colon mesentery found for respective gestational months (intrauterine fetuses) were as follows: month 4: 33.24-51.95mm 2 ; month 5: 49.63-77.6mm 2 ; month 6: 106.89-167.15mm 2 and month 7: 145.69-272.53mm 2 . The surface area of the sigmoid colon mesentery can be used as a simple parameter applied in fetal ultrasonographic evaluation. The development of the sigmoid colon accelerates in the 6th gestational month, and decelerates in the 7th gestational month. The sigmoid colon mesentery width was larger than its height between the 4th and 7th gestational months. Copyright © 2017 Elsevier GmbH. All rights reserved.

Affinity-based strategies to fast track development of colon cancer biomarkers — EDRN Public Portal

Cancer.gov

Our goal is to discover plasma and tissue-based tumor biomarkers that work well enough together to identity colon cancer at early stages, lead to accurate diagnosis and could ultimately allow for individualized treatment.

Bacterial colonization patterns in mechanically ventilated patients with traumatic and medical head injury. Incidence, risk factors, and association with ventilator-associated pneumonia.

PubMed

Ewig, S; Torres, A; El-Ebiary, M; Fábregas, N; Hernández, C; González, J; Nicolás, J M; Soto, L

1999-01-01

We prospectively evaluated the relation of upper airway, lower airway, and gastric colonization patterns with the development of pneumonia and its etiology in 48 patients with surgical (n = 25) and medical (n = 23) head injury. Initial colonization was assessed by cultures of nasal and pharyngeal swabs, tracheobronchial aspirates, gastric juice, and bronchoscopically retrieved protected specimen brush. Follow-up colonization was determined until the end points extubation, suspected ventilator-associated pneumonia (VAP), or death. The initial colonization rate at any site at ICU admission was 39/47 (83%). It mainly accounted for Group I pathogens (Streptococcus pneumoniae, Staphylococcus aureus, Hemophilus influenzae) of the upper and lower airways. At follow-up, colonization rates with Group II pathogens (Gram-negative enteric bacilli and Pseudomonas spp.) increased significantly. The high initial bacterial load with Group I pathogens of the upper airways and trachea decreased during Days 2 to 4, whereas that of Group II pathogens increased. Upper airway colonization was an independent predictor of follow-up tracheobronchial colonization (odds ratio [OR], 9.9; 95% confidence interval [CI], 1.8 to 56.3 for initial colonization with Group I pathogens; OR, 23.9; 95% CI, 3.8 to 153.3 for follow-up colonization with Group II pathogens). Previous (short-term) antibiotics had a protective effect against colonization with Group I pathogens of the lower respiratory tract (OR, 0.2; 95% CI, 0.05 to 0.86), but they were a risk factor for colonization with Group II pathogens (OR, 6.1; 95% CI, 1.3 to 29). Initial tracheobronchial colonization with Group I pathogens was associated with a higher probability of early onset pneumonia (OR, 4. 1; 95% CI, 0.7 to 23.3), whereas prolonged antibiotic treatment (> 24 h) independently predicted late-onset pneumonia (OR, 9.2; 95% CI, 1.7 to 51.3). We conclude that patients with head injury are colonized in the airways mainly by Group I pathogens early in the evolution of illness. The upper airways represent the main reservoir for subsequent lower airway colonization with Group I pathogens. Previous (short-term) antibiotic treatment is protective against initial tracheobronchial colonization with Group I pathogens, but it represents a risk factor for subsequent lower airway colonization by Group II pathogens.

Colon Cancer Tumorigenesis Initiated by the H1047R Mutant PI3K.

PubMed

Yueh, Alexander E; Payne, Susan N; Leystra, Alyssa A; Van De Hey, Dana R; Foley, Tyler M; Pasch, Cheri A; Clipson, Linda; Matkowskyj, Kristina A; Deming, Dustin A

2016-01-01

The phosphoinositide 3-kinase (PI3K) signaling pathway is critical for multiple important cellular functions, and is one of the most commonly altered pathways in human cancers. We previously developed a mouse model in which colon cancers were initiated by a dominant active PI3K p110-p85 fusion protein. In that model, well-differentiated mucinous adenocarcinomas developed within the colon and initiated through a non-canonical mechanism that is not dependent on WNT signaling. To assess the potential relevance of PI3K mutations in human cancers, we sought to determine if one of the common mutations in the human disease could also initiate similar colon cancers. Mice were generated expressing the Pik3caH1047R mutation, the analog of one of three human hotspot mutations in this gene. Mice expressing a constitutively active PI3K, as a result of this mutation, develop invasive adenocarcinomas strikingly similar to invasive adenocarcinomas found in human colon cancers. These tumors form without a polypoid intermediary and also lack nuclear CTNNB1 (β-catenin), indicating a non-canonical mechanism of tumor initiation mediated by the PI3K pathway. These cancers are sensitive to dual PI3K/mTOR inhibition indicating dependence on the PI3K pathway. The tumor tissue remaining after treatment demonstrated reduction in cellular proliferation and inhibition of PI3K signaling.

Expression of accessory colonization factor subunit A (ACFA) of Vibrio cholerae and ACFA fused to cholera toxin B subunit in transgenic tomato (Solanum lycopersicum).

PubMed

Sharma, Manoj Kumar; Jani, Dewal; Thungapathra, M; Gautam, J K; Meena, L S; Singh, Yogendra; Ghosh, Amit; Tyagi, Akhilesh Kumar; Sharma, Arun Kumar

2008-05-20

In earlier study from our group, cholera toxin B subunit had been expressed in tomato for developing a plant-based vaccine against cholera. In the present investigation, gene for accessory colonization factor (acf) subunit A, earlier reported to be essential for efficient colonization in the intestine, has been expressed in Escherichia coli as well as tomato plants. Gene encoding for a chimeric protein having a fusion of cholera toxin B subunit and accessory colonization factor A was also expressed in tomato to generate more potent combinatorial antigen. CaMV35S promoter with a duplicated enhancer sequence was used for expression of these genes in tomato. Integration of transgenes into tomato genome was confirmed by PCR and Southern hybridization. Expression of the genes was confirmed at transcript and protein levels. Accessory colonization factor A and cholera toxin B subunit fused to this protein accumulated up to 0.25% and 0.08% of total soluble protein, respectively, in the fruits of transgenic plants. Whereas protein purified from E. coli, in combination with cholera toxin B subunit can be used for development of conventional subunit vaccine, tomato fruits expressing these proteins can be used together with tomato plants expressing cholera toxin B subunit for development of oral vaccine against cholera.

Microbial Surface Colonization and Biofilm Development in Marine Environments

PubMed Central

2015-01-01

SUMMARY Biotic and abiotic surfaces in marine waters are rapidly colonized by microorganisms. Surface colonization and subsequent biofilm formation and development provide numerous advantages to these organisms and support critical ecological and biogeochemical functions in the changing marine environment. Microbial surface association also contributes to deleterious effects such as biofouling, biocorrosion, and the persistence and transmission of harmful or pathogenic microorganisms and their genetic determinants. The processes and mechanisms of colonization as well as key players among the surface-associated microbiota have been studied for several decades. Accumulating evidence indicates that specific cell-surface, cell-cell, and interpopulation interactions shape the composition, structure, spatiotemporal dynamics, and functions of surface-associated microbial communities. Several key microbial processes and mechanisms, including (i) surface, population, and community sensing and signaling, (ii) intraspecies and interspecies communication and interaction, and (iii) the regulatory balance between cooperation and competition, have been identified as critical for the microbial surface association lifestyle. In this review, recent progress in the study of marine microbial surface colonization and biofilm development is synthesized and discussed. Major gaps in our knowledge remain. We pose questions for targeted investigation of surface-specific community-level microbial features, answers to which would advance our understanding of surface-associated microbial community ecology and the biogeochemical functions of these communities at levels from molecular mechanistic details through systems biological integration. PMID:26700108

Microbial Surface Colonization and Biofilm Development in Marine Environments.

PubMed

Dang, Hongyue; Lovell, Charles R

2016-03-01

Biotic and abiotic surfaces in marine waters are rapidly colonized by microorganisms. Surface colonization and subsequent biofilm formation and development provide numerous advantages to these organisms and support critical ecological and biogeochemical functions in the changing marine environment. Microbial surface association also contributes to deleterious effects such as biofouling, biocorrosion, and the persistence and transmission of harmful or pathogenic microorganisms and their genetic determinants. The processes and mechanisms of colonization as well as key players among the surface-associated microbiota have been studied for several decades. Accumulating evidence indicates that specific cell-surface, cell-cell, and interpopulation interactions shape the composition, structure, spatiotemporal dynamics, and functions of surface-associated microbial communities. Several key microbial processes and mechanisms, including (i) surface, population, and community sensing and signaling, (ii) intraspecies and interspecies communication and interaction, and (iii) the regulatory balance between cooperation and competition, have been identified as critical for the microbial surface association lifestyle. In this review, recent progress in the study of marine microbial surface colonization and biofilm development is synthesized and discussed. Major gaps in our knowledge remain. We pose questions for targeted investigation of surface-specific community-level microbial features, answers to which would advance our understanding of surface-associated microbial community ecology and the biogeochemical functions of these communities at levels from molecular mechanistic details through systems biological integration. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Utilizing Depth of Colonization of Seagrasses to Develop ...

EPA Pesticide Factsheets

US EPA is working with state and local partners in Florida to develop numeric water quality criteria to protect estuaries from nutrient pollution. Similar to other nutrient management programs in Florida, EPA is considering status of seagrass habitats as an indicator of biological integrity, with depth of colonization of seagrasses used to relate potential seagrass extent to water quality requirements (especially water clarity). We developed and validated an automated methodology for evaluating depth of colonization and applied it to generate 228 estimates of seagrass colonization depth for coverage years spanning 67 years (1940-2007) in a total of 100 segments within 19 estuarine and coastal areas in Florida. A validation test showed that two parameters that were computed, Zc50 and ZcMax, approximated the average and 95th percentile depth at the deep-water margin of seagrass beds. Zc50 was estimated separately for continuous seagrass vs. all seagrass. Average values for Zc50 as well as long-term trends were evaluated for the entire state, illustrating a decline on average from early years (e.g., 1940-1953) to a middle period (1982-1999) and a variable degree of recovery since 2000. The largest decrease in Zc50 occurred in Florida panhandle estuaries. Extensive water quality data compiled in the Florida DEP’s Impaired Waters Rule database was evaluated to characterize Secchi depth, CDOM, TSS, and chlorophyll-a in relation to depth of colonization estima

Butyrate and bioactive proteolytic form of Wnt-5a regulate colonic epithelial proliferation and spatial development

PubMed Central

Uchiyama, Kazuhiko; Sakiyama, Toshio; Hasebe, Takumu; Musch, Mark W.; Miyoshi, Hiroyuki; Nakagawa, Yasushi; He, Tong-Chuan; Lichtenstein, Lev; Naito, Yuji; Itoh, Yoshito; Yoshikawa, Toshikazu; Jabri, Bana; Stappenbeck, Thaddeus; Chang, Eugene B.

2016-01-01

Proliferation and spatial development of colonic epithelial cells are highly regulated along the crypt vertical axis, which, when perturbed, can result in aberrant growth and carcinogenesis. In this study, two key factors were identified that have important and counterbalancing roles regulating these processes: pericrypt myofibroblast-derived Wnt-5a and the microbial metabolite butyrate. Cultured YAMC cell proliferation and heat shock protein induction were analzyed after butryate, conditioned medium with Wnt5a activity, and FrzB containing conditioned medium. In vivo studies to modulate Hsp25 employed intra-colonic wall Hsp25 encoding lentivirus. To silence Wnt-5a in vivo, intra-colonic wall Wnt-5a silencing RNA was used. Wnt-5a, secreted by stromal myofibroblasts of the lower crypt, promotes proliferation through canonical β-catenin activation. Essential to this are two key requirements: (1) proteolytic conversion of the highly insoluble ~40 kD Wnt-5a protein to a soluble 36 mer amino acid peptide that activates epithelial β-catenin and cellular proliferation, and (2) the simultaneous inhibition of butyrate-induced Hsp25 by Wnt-5a which is necessary to arrest the proliferative process in the upper colonic crypt. The interplay and spatial gradients of these factors insures that crypt epithelial cell proliferation and development proceed in an orderly fashion, but with sufficient plasticity to adapt to physiological perturbations including inflammation. PMID:27561676

Colon Cancer Tumorigenesis Initiated by the H1047R Mutant PI3K

PubMed Central

Yueh, Alexander E.; Payne, Susan N.; Leystra, Alyssa A.; Van De Hey, Dana R.; Foley, Tyler M.; Pasch, Cheri A.; Clipson, Linda; Matkowskyj, Kristina A.; Deming, Dustin A.

2016-01-01

The phosphoinositide 3-kinase (PI3K) signaling pathway is critical for multiple important cellular functions, and is one of the most commonly altered pathways in human cancers. We previously developed a mouse model in which colon cancers were initiated by a dominant active PI3K p110-p85 fusion protein. In that model, well-differentiated mucinous adenocarcinomas developed within the colon and initiated through a non-canonical mechanism that is not dependent on WNT signaling. To assess the potential relevance of PI3K mutations in human cancers, we sought to determine if one of the common mutations in the human disease could also initiate similar colon cancers. Mice were generated expressing the Pik3caH1047R mutation, the analog of one of three human hotspot mutations in this gene. Mice expressing a constitutively active PI3K, as a result of this mutation, develop invasive adenocarcinomas strikingly similar to invasive adenocarcinomas found in human colon cancers. These tumors form without a polypoid intermediary and also lack nuclear CTNNB1 (β-catenin), indicating a non-canonical mechanism of tumor initiation mediated by the PI3K pathway. These cancers are sensitive to dual PI3K/mTOR inhibition indicating dependence on the PI3K pathway. The tumor tissue remaining after treatment demonstrated reduction in cellular proliferation and inhibition of PI3K signaling. PMID:26863299

Right hemicolectomy for mesenteric phlebosclerosis potentially caused by long-term use of herbal medicine: A case report and literature review.

PubMed

Hoshino, Nobuaki; Hasegawa, Suguru; Hida, Koya; Kawada, Kenji; Sakai, Yoshiharu

2016-01-01

Mesenteric phlebosclerosis is a rare ischemic disease affecting the colon. Systemic disease and herbal medicine have been pointed out as possible causes, and the disease is characterized by calcifications involved the mesocolic veins. Patients who do not respond to conservative therapy require surgical treatment. In surgical intervention, an adequate extent of colonic resection is important. We present a case of an 87-year-old woman with mesenteric phlebosclerosis who had consumed herbal medicine for 40 years. She suffered from ileus caused by mesenteric phlebosclerosis, and the symptoms did not improve with conservative therapy. Right hemicolectomy was performed since the disease was localized in the right colon. Long-term use of herbal medicine was considered the potential cause of mesenteric phlebosclerosis. The postoperative course was mostly uneventful. The patient stopped using herbal medicine and had no signs of recurrence 2 years after surgery. The greatest concern in surgery for mesenteric phleboscrerosis is to detect the affected area, which should be removed. Characteristic findings in computed tomography and intraoperative findings can help to determine the optimal extent of colonic resection. Mesenteric phlebosclerosis caused by herbal medicines occurs as localized disease in the right colon compared with mesenteric phlebosclerosis caused by other pathogenesis. Limited colonic resection is usually indicated for mesenteric phlebosclerosis caused by herbal medicine. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Ischemic colitis in five points: an update 2013.

PubMed

Rania, Hefaiedh; Mériam, Sabbah; Rym, Ennaifer; Hyafa, Romdhane; Amine, Attaoui; Najet, Bel Hadj; Lassad, Gharbi; Mohamed, Taher Khalfallah

2014-05-01

Ischemic colitis is the most common form of intestinal ischemia. The presence of diarrhea and mild lower gastrointestinal bleeding should guide the diagnosis. Although many laboratory tests and radiographic images may suggest the diagnosis, colonic endoscopic with histological analysis of biopsies is the gold standard for identification of colonic ischemia. aim : The aim of this study was to resume in 5 points: the epidemiology, the clinical features, the diagnostic approach and the management of ischemic colitis in five points. methods: Review of literature. results: Incidence of ischemic colitis was between 3 and 10%. The clinical presentation is predominated by the non gangrenous form associating abdominal pain, tenderness, diarrhea and lower gastrointestinal bleeding. The most frequent causes are represented by systemic hypoperfusion. Laboratory tests can orientate the diagnosis but are unspecific. Radiographic images based on computed tomography or more recently magnetic resonance imaging may suggest the diagnosis, but the confirmation will be given by endoscopic visualization of colonic mucosa with histological analysis of biopsies. Conservative treatment is the most often sufficient to improve colonic lesions. Surgical treatment is reserved for perforations and strictures. The incidence of colonic ischemia is difficult to ascertain. The diagnosis is usually made by medical history, examination, and endoscopy which have become the diagnostic procedure of choice. A high index of suspicion and prompt management are essential for optimum outcomes in patients with colonic ischemia.

Lactobacillus salivarius Ren prevent the early colorectal carcinogenesis in 1, 2-dimethylhydrazine-induced rat model.

PubMed

Zhu, J; Zhu, C; Ge, S; Zhang, M; Jiang, L; Cui, J; Ren, F

2014-07-01

The objective of this study was to investigate the impact of Lactobacillus salivarius Ren (LS) on modulating colonic micro flora structure and influencing host colonic health in a rat model with colorectal precancerous lesions. Male F344 rats were injected with 1, 2-dimethylhydrazine (DMH) and treated with LS of two doses (5 × 10(8) and 1 × 10(10) CFU kg(-1) body weight) for 15 weeks. The colonic microflora profiles, luminal metabolites, epithelial proliferation and precancerous lesions [aberrant crypt foci (ACF)] were determined. A distinct segregation of colonic microflora structures was observed in LS-treated group. The abundance of one Prevotella-related strain was increased, and the abundance of one Bacillus-related strain was decreased by LS treatment. These changes were accompanied by increased short-chain fatty acid levels and decreased azoreductase activity. LS treatment also reduced the number of ACF by c. 40% and suppressed epithelial proliferation. Lactobacillus salivarius Ren improved the colonic microflora structures and the luminal metabolisms in addition preventing the early colorectal carcinogenesis in DMH-induced rat model. Colonic microflora is an important factor in colorectal carcinogenesis. Modulating the structural shifts of microflora may provide a novel option for preventing colorectal carcinogenesis. This study suggested a potential probiotic-based approach to modulate the intestinal microflora in the prevention of colorectal carcinogenesis. © 2014 The Society for Applied Microbiology.

Ursodeoxycholic acid in patients with ulcerative colitis and primary sclerosing cholangitis for prevention of colon cancer: a meta-analysis.

PubMed

Ashraf, Imran; Choudhary, Abhishek; Arif, Murtaza; Matteson, Michelle L; Hammad, Hazem T; Puli, Srinivas R; Bechtold, Matthew L

2012-04-01

Colon cancer risk is high in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). Ursodeoxycholic acid has been shown to have some promise as a chemopreventive agent. A meta-analysis was performed to compare the efficacy of ursodeoxycholic acid in the prevention of colonic neoplasia in patients with UC and PSC. Multiple databases were searched (January 2011). Studies examining the use of ursodeoxycholic acid vs. no ursodeoxycholic acid or placebo in adult patients with UC and PSC were included. Data were extracted in standard forms by two independent reviewers. Meta-analysis for the effect of ursodeoxycholic acid was performed by calculating pooled estimates of adenoma or colon cancer formation by odds ratio (OR) with random effects model. Heterogeneity was assessed by calculating the I (2) measure of inconsistency. RevMan 5 was utilized for statistical analysis. Four studies (n = 281) met the inclusion criteria. The studies were of adequate quality. Ursodeoxycholic acid demonstrated no overall improvement in adenoma (OR 0.53; 95 % CI: 0.19-1.48, p = 0.23) or colon cancer occurrence (OR 0.50; 95 % CI: 0.18-1.43, p = 0.20) as compared to no ursodeoxycholic acid or placebo in patients with UC and PSC. Ursodeoxycholic acid use in patients with UC and PSC does not appear to decrease the risk of adenomas or colon cancer.

Accurate motion parameter estimation for colonoscopy tracking using a regression method

NASA Astrophysics Data System (ADS)

Liu, Jianfei; Subramanian, Kalpathi R.; Yoo, Terry S.

2010-03-01

Co-located optical and virtual colonoscopy images have the potential to provide important clinical information during routine colonoscopy procedures. In our earlier work, we presented an optical flow based algorithm to compute egomotion from live colonoscopy video, permitting navigation and visualization of the corresponding patient anatomy. In the original algorithm, motion parameters were estimated using the traditional Least Sum of squares(LS) procedure which can be unstable in the context of optical flow vectors with large errors. In the improved algorithm, we use the Least Median of Squares (LMS) method, a robust regression method for motion parameter estimation. Using the LMS method, we iteratively analyze and converge toward the main distribution of the flow vectors, while disregarding outliers. We show through three experiments the improvement in tracking results obtained using the LMS method, in comparison to the LS estimator. The first experiment demonstrates better spatial accuracy in positioning the virtual camera in the sigmoid colon. The second and third experiments demonstrate the robustness of this estimator, resulting in longer tracked sequences: from 300 to 1310 in the ascending colon, and 410 to 1316 in the transverse colon.

The history of the North African mitochondrial DNA haplogroup U6 gene flow into the African, Eurasian and American continents

PubMed Central

2014-01-01

Background Complete mitochondrial DNA (mtDNA) genome analyses have greatly improved the phylogeny and phylogeography of human mtDNA. Human mitochondrial DNA haplogroup U6 has been considered as a molecular signal of a Paleolithic return to North Africa of modern humans from southwestern Asia. Results Using 230 complete sequences we have refined the U6 phylogeny, and improved the phylogeographic information by the analysis of 761 partial sequences. This approach provides chronological limits for its arrival to Africa, followed by its spreads there according to climatic fluctuations, and its secondary prehistoric and historic migrations out of Africa colonizing Europe, the Canary Islands and the American Continent. Conclusions The U6 expansions and contractions inside Africa faithfully reflect the climatic fluctuations that occurred in this Continent affecting also the Canary Islands. Mediterranean contacts drove these lineages to Europe, at least since the Neolithic. In turn, the European colonization brought different U6 lineages throughout the American Continent leaving the specific sign of the colonizers origin. PMID:24885141

A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility.

PubMed

Desai, Mahesh S; Seekatz, Anna M; Koropatkin, Nicole M; Kamada, Nobuhiko; Hickey, Christina A; Wolter, Mathis; Pudlo, Nicholas A; Kitamoto, Sho; Terrapon, Nicolas; Muller, Arnaud; Young, Vincent B; Henrissat, Bernard; Wilmes, Paul; Stappenbeck, Thaddeus S; Núñez, Gabriel; Martens, Eric C

2016-11-17

Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota, and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome, and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics. Copyright © 2016 Elsevier Inc. All rights reserved.

New optical method for enhanced detection of colon cancer by capsule endoscopy

NASA Astrophysics Data System (ADS)

AnkriEqually Contributed, Rinat; Peretz, Dolev; Motiei, Menachem; Sella-Tavor, Osnat; Popovtzer, Rachela

2013-09-01

PillCam®COLON capsule endoscopy (CE), a non-invasive diagnostic tool of the digestive tract, has dramatically changed the diagnostic approach and has become an attractive alternative to the conventional colonoscopy for early detection of colorectal cancer. However, despite the significant progress and non-invasive detection capability, studies have shown that its sensitivity and specificity is lower than that of conventional colonoscopy. This work presents a new optical detection method, specifically tailored to colon cancer detection and based on the well-known optical properties of immune-conjugated gold nanorods (GNRs). We show, on a colon cancer model implanted in a chick chorioallantoic membrane (CAM), that this detection method enables conclusive differentiation between cancerous and normal tissues, where neither the distance between the light source and the intestinal wall, nor the background signal, affects the monitored signal. This optical method, which can easily be integrated in CE, is expected to reduce false positive and false negative results and improve identification of tumors and micro metastases.

Mechanism of aqueous fructus aurantii immaturus extracts in neuroplexus of cathartic colons

PubMed Central

Wang, Shi-Yi; Liu, Yan-Ping; Fan, Yi-Hong; Zhang, Lu; Cai, Li-Jun; Lv, Bin

2015-01-01

AIM: To examine the effect of aqueous fructus aurantii immaturus (FAI) extracts on the intestinal plexus of cathartic colons. METHODS: Cathartic colons were induced in rats with dahuang, a laxative used in traditional Chinese medicine. Once the model was established (after approximately 12 wk), rats were administered mosapride (1.54 mg/kg) or various doses of aqueous FAI extracts (1-4 g/kg) for 14 d. Transit function was assessed using an ink propulsion test. Rats were then sacrificed, and the ultramicrostructure of colonic tissue was examined using transmission electron microscopy. The expression of the 5-hydroxytryptamine receptor 4 (5-HTR4) and neurofilament-H was assessed in colon tissues using real-time PCR, Western blot, and immunohistochemistry. RESULTS: Mosapride and high dose (4 g/kg) of aqueous FAI extracts significantly improved the bowel movement in cathartic colons compared to untreated model colons as measured by the intestinal transit rate (70.06 ± 7.25 and 72.02 ± 8.74, respectively, vs 64.12 ± 5.19; P < 0.05 for both). Compared to controls, the ultramicrostructure of cathartic colons showed signs of neural degeneration. Treatment with mosapride and aqueous FAI extracts resulted in recovery of ultrastructural pathology. Treatment with mosapride alone upregulated the gene and protein expression of 5-HTR4 compared to untreated controls (P < 0.05 for both). Treatment with aqueous FAI extracts (≥ 2 g/kg) increased 5-HTR4 mRNA levels (P < 0.05), but no change in protein level was observed by Western blot or immunohistochemistry. The mRNA and protein levels of neurofilament-H were significantly increased with mosapride and ≥ 2 g/kg aqueous FAI extracts compared to controls (P < 0.05 for all). CONCLUSION: Aqueous FAI extracts and mosapride strengthen bowel movement in cathartic colons via increasing the expression of 5-HTR4 and neurofilament-H. PMID:26309361

The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery.

PubMed

Ma, Yiming; Fuchs, Adrian V; Boase, Nathan R B; Rolfe, Barbara E; Coombes, Allan G A; Thurecht, Kristofer J

2015-08-01

Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan-hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8h to 24h post-administration compared to the free NPs, due to a NP 'guarding' effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Knockdown of Immature Colon Carcinoma Transcript 1 Inhibits Proliferation and Promotes Apoptosis of Non–Small Cell Lung Cancer Cells

PubMed Central

He, Jiantao; Zhang, Shenghui; Yang, Qingbo; Wang, Bo; Liu, Zhiyu; Wu, Xintian

2016-01-01

Non–small cell lung cancer, as the most frequent type lung cancer, has lower survival rate of 5 years, despite improvements in surgery and chemotherapy. Previous studies showed immature colon carcinoma transcript 1 is closely related to tumorigenesis of human cancer cells. In the present study, we found immature colon carcinoma transcript 1 was overexpressed in lung cancer tissues using Oncomine database mining, and the biological effect of immature colon carcinoma transcript 1 was investigated in non–small cell lung cancer cell lines 95D and A549. Lentivirus-mediated RNA interference was used to knock down immature colon carcinoma transcript 1 expression in 95D and A549 cells in vitro, and the knockdown efficiency was determined using quantitative real-time polymerase chain reaction and Western blot assay. Knockdown of immature colon carcinoma transcript 1 significantly suppressed non–small cell lung cancer cell proliferation and colony formation ability confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assay. Flow cytometry was applied to measure cell cycle arrest, and the result showed the cell cycle arrested in G2/M phase in 95D cells and arrested in G0/G1 phase in A549 cells. Furthermore, we measured the levels of cell cycle–associated proteins by Western blot analysis and found immature colon carcinoma transcript 1–mediated cell proliferation inhibition appeared due to downregulation of cell cycle activator cyclin D1 and upregulation of cell cycle inhibitor p21. In addition, immature colon carcinoma transcript 1 silencing significantly induced non–small cell lung cancer cell apoptosis by annexin V/7-amino-actinomycin D double-staining assay. All our data suggest that immature colon carcinoma transcript 1 may play an important role for non–small cell lung cancer cell proliferation and could be a potential molecular target for diagnosing and treating human non–small cell lung cancer. PMID:27413166

Molecular characterization of total and metabolically active bacterial communities of "white colonizations" in the Altamira Cave, Spain.

PubMed

Portillo, M Carmen; Saiz-Jimenez, Cesareo; Gonzalez, Juan M

2009-01-01

Caves with paleolithic paintings are influenced by bacterial development. Altamira Cave (Spain) contains some of the most famous paintings from the Paleolithic era. An assessment of the composition of bacterial communities that have colonized this cave represents a first step in understanding and potentially controlling their proliferation. In this study, areas showing colonization with uncolored microorganisms, referred to as "white colonizations", were analyzed. Microorganisms present in these colonizations were studied using DNA analysis, and those showing significant metabolic activity were detected in RNA-based RNA analysis. Bacterial community fingerprints were obtained both from DNA and RNA analyses, indicating differences between the microorganisms present and metabolically active in these white colonizations. Metabolically active microorganisms represented only a fraction of the total bacterial community present in the colonizations. 16S rRNA gene libraries were used to identify the major representative members of the studied communities. Proteobacteria constituted the most frequently found division both among metabolically active microorganisms (from RNA-based analysis) and those present in the community (from DNA analysis). Results suggest the existence of a huge variety of taxa in white colonizations of the Altamira Cave which represent a potential risk for the conservation of the cave and its paintings.

Experimental Feeding of Hydrilla verticillata Colonized by Stigonematales Cyanobacteria Induces Vacuolar Myelinopathy in Painted Turtles (Chrysemys picta)

PubMed Central

Mercurio, Albert D.; Hernandez, Sonia M.; Maerz, John C.; Yabsley, Michael J.; Ellis, Angela E.; Coleman, Amanda L.; Shelnutt, Leslie M.; Fischer, John R.; Wilde, Susan B.

2014-01-01

Vacuolar myelinopathy (VM) is a neurologic disease primarily found in birds that occurs when wildlife ingest submerged aquatic vegetation colonized by an uncharacterized toxin-producing cyanobacterium (hereafter “UCB” for “uncharacterized cyanobacterium”). Turtles are among the closest extant relatives of birds and many species directly and/or indirectly consume aquatic vegetation. However, it is unknown whether turtles can develop VM. We conducted a feeding trial to determine whether painted turtles (Chrysemys picta) would develop VM after feeding on Hydrilla (Hydrilla verticillata), colonized by the UCB (Hydrilla is the most common “host” of UCB). We hypothesized turtles fed Hydrilla colonized by the UCB would exhibit neurologic impairment and vacuolation of nervous tissues, whereas turtles fed Hydrilla free of the UCB would not. The ability of Hydrilla colonized by the UCB to cause VM (hereafter, “toxicity”) was verified by feeding it to domestic chickens (Gallus gallus domesticus) or necropsy of field collected American coots (Fulica americana) captured at the site of Hydrilla collections. We randomly assigned ten wild-caught turtles into toxic or non-toxic Hydrilla feeding groups and delivered the diets for up to 97 days. Between days 82 and 89, all turtles fed toxic Hydrilla displayed physical and/or neurologic impairment. Histologic examination of the brain and spinal cord revealed vacuolations in all treatment turtles. None of the control turtles exhibited neurologic impairment or had detectable brain or spinal cord vacuolations. This is the first evidence that freshwater turtles can become neurologically impaired and develop vacuolations after consuming toxic Hydrilla colonized with the UCB. The southeastern United States, where outbreaks of VM occur regularly and where vegetation colonized by the UCB is common, is also a global hotspot of freshwater turtle diversity. Our results suggest that further investigations into the effect of the putative UCB toxin on wild turtles in situ are warranted. PMID:24695109

Effect of dietary monensin on the bacterial population structure of dairy cattle colonic contents

USDA-ARS?s Scientific Manuscript database

Monensin is a carboxylic polyether ionophore antibiotic that is routinely used to improve the performance of beef cattle and was recently approved by the U.S. Food and Drug Administration for the use in dairy cattle to improve milk yields. Previous studies have suggested that monensin improves anima...

Therapeutic efficacy of osthole against dinitrobenzene sulphonic acid induced-colitis in rats.

PubMed

Khairy, Hanan; Saleh, Hanan; Badr, Abeer M; Marie, Mohamed-Assem S

2018-04-01

Several mediators were associated with the pathogenesis of inflammatory bowel disease such as oxidative stress through the production of reactive oxygen metabolites, neutrophils infiltration and release of pro-inflammatory cytokines. This study was designed to investigate the therapeutic efficacy of osthole against dinitrobenzene sulfonic acid (DNBS) induced-colitis in rats through its anti-oxidant and anti-inflammatory properties. Colitis was induced in rats by single intracolonic instillation of (250 μl DNBS-25 mg/rat). Then 4 days later, rats were received oral administration of either (osthole 50 mg/kg), (sulfasalazine 500 mg/kg) or both in combination for 7 consecutive days. Body weight, some hematological parameters, colonic malondialdehyde (MDA) and myeloperoxidase activity (MPO), antioxidant parameters, colon injury and mucosa architectures were assessed. T helper (Th1)-related cytokines [Tumor necrosis factor alpha (TNF-α) and interferon-gamma (INF-γ)], Th2-relarted cytokines (interleukin-4 [IL-4 and IL-10], and Th-17 related cytokines [IL-17] were determined by ELISA. Osthole significantly improved the loss in body weight. That was accompanied with a remarkable amelioration of the disruption of the colonic architecture as well as a significant improvement in the antioxidant defense system. A reduction in MPO and MDA was observed in flamed colon. Treatment with either osthole or combination therapy showed suppressive activities on pro-inflammatory Th2-related cytokines and upregulation of anti-inflammatory Th2-related cytokines The results of this study suggest that osthole exert beneficial therapeutic effect in experimental colitis and improved the efficacy of the synthetized drugs such as sulfasalazine. Therefore, osthole may have a valuable sound in the treatment of inflammatory bowel disease. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Pseudomonas fluorescens F113 Mutant with Enhanced Competitive Colonization Ability and Improved Biocontrol Activity against Fungal Root Pathogens ▿

PubMed Central

Barahona, Emma; Navazo, Ana; Martínez-Granero, Francisco; Zea-Bonilla, Teresa; Pérez-Jiménez, Rosa María; Martín, Marta; Rivilla, Rafael

2011-01-01

Motility is one of the most important traits for efficient rhizosphere colonization by Pseudomonas fluorescens F113rif (F113). In this bacterium, motility is a polygenic trait that is repressed by at least three independent pathways, including the Gac posttranscriptional system, the Wsp chemotaxis-like pathway, and the SadB pathway. Here we show that the kinB gene, which encodes a signal transduction protein that together with AlgB has been implicated in alginate production, participates in swimming motility repression through the Gac pathway, acting downstream of the GacAS two-component system. Gac mutants are impaired in secondary metabolite production and are unsuitable as biocontrol agents. However, the kinB mutant and a triple mutant affected in kinB, sadB, and wspR (KSW) possess a wild-type phenotype for secondary metabolism. The KSW strain is hypermotile and more competitive for rhizosphere colonization than the wild-type strain. We have compared the biocontrol activity of KSW with those of the wild-type strain and a phenotypic variant (F113v35 [V35]) which is hypermotile and hypercompetitive but is affected in secondary metabolism since it harbors a gacS mutation. Biocontrol experiments in the Fusarium oxysporum f. sp. radicis-lycopersici/Lycopersicum esculentum (tomato) and Phytophthora cactorum/Fragaria vesca (strawberry) pathosystems have shown that the three strains possess biocontrol activity. Biocontrol activity was consistently lower for V35, indicating that the production of secondary metabolites was the most important trait for biocontrol. Strain KSW showed improved biocontrol compared with the wild-type strain, indicating that an increase in competitive colonization ability resulted in improved biocontrol and that the rational design of biocontrol agents by mutation is feasible. PMID:21685161

Pseudomonas fluorescens F113 mutant with enhanced competitive colonization ability and improved biocontrol activity against fungal root pathogens.

PubMed

Barahona, Emma; Navazo, Ana; Martínez-Granero, Francisco; Zea-Bonilla, Teresa; Pérez-Jiménez, Rosa María; Martín, Marta; Rivilla, Rafael

2011-08-01

Motility is one of the most important traits for efficient rhizosphere colonization by Pseudomonas fluorescens F113rif (F113). In this bacterium, motility is a polygenic trait that is repressed by at least three independent pathways, including the Gac posttranscriptional system, the Wsp chemotaxis-like pathway, and the SadB pathway. Here we show that the kinB gene, which encodes a signal transduction protein that together with AlgB has been implicated in alginate production, participates in swimming motility repression through the Gac pathway, acting downstream of the GacAS two-component system. Gac mutants are impaired in secondary metabolite production and are unsuitable as biocontrol agents. However, the kinB mutant and a triple mutant affected in kinB, sadB, and wspR (KSW) possess a wild-type phenotype for secondary metabolism. The KSW strain is hypermotile and more competitive for rhizosphere colonization than the wild-type strain. We have compared the biocontrol activity of KSW with those of the wild-type strain and a phenotypic variant (F113v35 [V35]) which is hypermotile and hypercompetitive but is affected in secondary metabolism since it harbors a gacS mutation. Biocontrol experiments in the Fusarium oxysporum f. sp. radicis-lycopersici/Lycopersicum esculentum (tomato) and Phytophthora cactorum/Fragaria vesca (strawberry) pathosystems have shown that the three strains possess biocontrol activity. Biocontrol activity was consistently lower for V35, indicating that the production of secondary metabolites was the most important trait for biocontrol. Strain KSW showed improved biocontrol compared with the wild-type strain, indicating that an increase in competitive colonization ability resulted in improved biocontrol and that the rational design of biocontrol agents by mutation is feasible.

A De Novo Germline APC Mutation (3927del5) in a Patient with Familial Adenomatous Polyposis: Case Report and Literature Review

PubMed Central

Zeichner, Simon B.; Raj, Naveen; Cusnir, Mike; Francavilla, Michael; Hirzel, Alicia

2012-01-01

Introduction Characterized by the development of hundreds to thousands of colonic adenomas, classic familial adenomatous polyposis (FAP) is one of the most common hereditary syndromes associated with an increased risk of colorectal cancer. Several studies have attempted to correlate specific APC mutations with clinical phenotype.6 However, there is considerable variability in the expression of specific phenotypes within families and among individuals with identical mutations.7 Case presentation A 30 year-old Hispanic female presented to the emergency department with a 2-week history of persistent, worsening, left lower quadrant abdominal pain. She had no family history of malignancy. Sigmoidoscopy revealed innumerable polyps in the rectum and sigmoid colon and a large mass in the sigmoid colon. Biopsy of the mass revealed a moderately differentiated adenocarcinoma invading the subserosa. Endoscopy revealed innumerable polyps. Genetic testing of the patient via southern blot revealed a germline APC mutation 3927del5, resulting in a premature truncation of the APC protein at amino acid position 1312. Conclusion Genetic information has only recently started being incorporated into clinical care. More research and randomized clinical trials need to be conducted to definitively characterize random mutations. Once these mutations are further understood, FAP patients may be able to be risk stratified and this may ultimately improve the screening, diagnosis, and treatment of this rare condition. PMID:23115482

An Interaction of LPS and RSV Infection in Augmenting the AHR and Airway Inflammation in Mice.

PubMed

Zhou, Na; Li, Wei; Ren, Luo; Xie, Xiaohong; Liu, Enmei

2017-10-01

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection (LRTI) in children under 5 years of age, especially infants with severe bronchiolitis. Our preliminary clinical experiments showed that bacterial colonization was commonly observed in children with virus-induced wheezing, particularly in those with recurrent wheezing, suggesting that bacterial colonization with an accompanying viral infection may contribute to disease severity. In most cases, RSV-infected infants were colonized with pathogenic bacteria (mainly Gram-negative bacteria). LPS is the main component of Gram-negative bacteria and acts as a ligand for Toll-like receptor 4 (TLR4). Relevant studies have reported that the TLR family is crucial in mediating the link between viral components and immunologic responses to infection. Of note, TLR4 activation has been associated with disease severity during RSV infection. In the present study, we identified that LPS aggravated RSV-induced AHR and airway inflammation in BALB/c mice using an RSV coinfection model. We found that the airway inflammatory cells and cytokines present in BALF and TRIF in lung tissue play a role in inducing AHR and airway inflammation upon RSV and bacteria coinfection, which might occur through the TRIF-MMP-9-neutrophil-MMP-9 signalling pathway. These results may aid in the development of novel treatments and improve vaccine design.

Enhanced Ghrelin Levels and Hypothalamic Orexigenic AgRP and NPY Neuropeptide Expression in Models of Jejuno-Colonic Short Bowel Syndrome

PubMed Central

Gillard, Laura; Billiauws, Lore; Stan-Iuga, Bogdan; Ribeiro-Parenti, Lara; Jarry, Anne-Charlotte; Cavin, Jean-Baptiste; Cluzeaud, Françoise; Mayeur, Camille; Thomas, Muriel; Freund, Jean-Noël; Lacorte, Jean-Marc; Le Gall, Maude; Bado, André; Joly, Francisca; Le Beyec, Johanne

2016-01-01

Short bowel syndrome (SBS) patients developing hyperphagia have a better outcome. Gastrointestinal endocrine adaptations help to improve intestinal functions and food behaviour. We investigated neuroendocrine adaptations in SBS patients and rat models with jejuno-ileal (IR-JI) or jejuno-colonic (IR-JC) anastomosis with and without parenteral nutrition. Circulating levels of ghrelin, PYY, GLP-1, and GLP-2 were determined in SBS rat models and patients. Levels of mRNA for proglucagon, PYY and for hypothalamic neuropeptides were quantified by qRT-PCR in SBS rat models. Histology and immunostaining for Ki67, GLP-1 and PYY were performed in SBS rats. IR-JC rats, but not IR-JI, exhibited significantly higher crypt depths and number of Ki67-positive cells than sham. Fasting and/or postprandial plasma ghrelin and PYY concentrations were higher, or tend to be higher, in IR-JC rats and SBS-JC patients than in controls. Proglucagon and Pyy mRNA levels were significantly enhanced in IR-JC rats. Levels of mRNA coding hypothalamic orexigenic NPY and AgRP peptides were significantly higher in IR-JC than in sham rats. We demonstrate an increase of plasma ghrelin concentrations, major changes in hypothalamic neuropeptides levels and greater induction of PYY in SBS-JC rats and patients suggesting that jejuno-colonic continuity creates a peculiar environment promoting further gut-brain adaptations. PMID:27323884

Enhanced Ghrelin Levels and Hypothalamic Orexigenic AgRP and NPY Neuropeptide Expression in Models of Jejuno-Colonic Short Bowel Syndrome.

PubMed

Gillard, Laura; Billiauws, Lore; Stan-Iuga, Bogdan; Ribeiro-Parenti, Lara; Jarry, Anne-Charlotte; Cavin, Jean-Baptiste; Cluzeaud, Françoise; Mayeur, Camille; Thomas, Muriel; Freund, Jean-Noël; Lacorte, Jean-Marc; Le Gall, Maude; Bado, André; Joly, Francisca; Le Beyec, Johanne

2016-06-21

Short bowel syndrome (SBS) patients developing hyperphagia have a better outcome. Gastrointestinal endocrine adaptations help to improve intestinal functions and food behaviour. We investigated neuroendocrine adaptations in SBS patients and rat models with jejuno-ileal (IR-JI) or jejuno-colonic (IR-JC) anastomosis with and without parenteral nutrition. Circulating levels of ghrelin, PYY, GLP-1, and GLP-2 were determined in SBS rat models and patients. Levels of mRNA for proglucagon, PYY and for hypothalamic neuropeptides were quantified by qRT-PCR in SBS rat models. Histology and immunostaining for Ki67, GLP-1 and PYY were performed in SBS rats. IR-JC rats, but not IR-JI, exhibited significantly higher crypt depths and number of Ki67-positive cells than sham. Fasting and/or postprandial plasma ghrelin and PYY concentrations were higher, or tend to be higher, in IR-JC rats and SBS-JC patients than in controls. Proglucagon and Pyy mRNA levels were significantly enhanced in IR-JC rats. Levels of mRNA coding hypothalamic orexigenic NPY and AgRP peptides were significantly higher in IR-JC than in sham rats. We demonstrate an increase of plasma ghrelin concentrations, major changes in hypothalamic neuropeptides levels and greater induction of PYY in SBS-JC rats and patients suggesting that jejuno-colonic continuity creates a peculiar environment promoting further gut-brain adaptations.

Staphylococcal Enterotoxin P Predicts Bacteremia in Hospitalized Patients Colonized With Methicillin-Resistant Staphylococcus aureus

PubMed Central

Calderwood, Michael S.; Desjardins, Christopher A.; Sakoulas, George; Nicol, Robert; DuBois, Andrea; Delaney, Mary L.; Kleinman, Ken; Cosimi, Lisa A.; Feldgarden, Michael; Onderdonk, Andrew B.; Birren, Bruce W.; Platt, Richard; Huang, Susan S.

2014-01-01

Background. Methicillin-resistant Staphylococcus aureus (MRSA) colonization predicts later infection, with both host and pathogen determinants of invasive disease. Methods. This nested case-control study evaluates predictors of MRSA bacteremia in an 8–intensive care unit (ICU) prospective adult cohort from 1 September 2003 through 30 April 2005 with active MRSA surveillance and collection of ICU, post-ICU, and readmission MRSA isolates. We selected MRSA carriers who did (cases) and those who did not (controls) develop MRSA bacteremia. Generating assembled genome sequences, we evaluated 30 MRSA genes potentially associated with virulence and invasion. Using multivariable Cox proportional hazards regression, we assessed the association of these genes with MRSA bacteremia, controlling for host risk factors. Results. We collected 1578 MRSA isolates from 520 patients. We analyzed host and pathogen factors for 33 cases and 121 controls. Predictors of MRSA bacteremia included a diagnosis of cancer, presence of a central venous catheter, hyperglycemia (glucose level, >200 mg/dL), and infection with a MRSA strain carrying the gene for staphylococcal enterotoxin P (sep). Receipt of an anti-MRSA medication had a significant protective effect. Conclusions. In an analysis controlling for host factors, colonization with MRSA carrying sep increased the risk of MRSA bacteremia. Identification of risk-adjusted genetic determinants of virulence may help to improve prediction of invasive disease and suggest new targets for therapeutic intervention. PMID:24041793

Cold atmospheric plasma treatment inhibits growth in colorectal cancer cells.

PubMed

Schneider, Christin; Arndt, Stephanie; Zimmermann, Julia L; Li, Yangfang; Karrer, Sigrid; Bosserhoff, Anja-Katrin

2018-06-01

Plasma oncology is a relatively new field of research. Recent developments have indicated that cold atmospheric plasma (CAP) technology is an interesting new therapeutic approach to cancer treatment. In this study, p53 wildtype (LoVo) and human p53 mutated (HT29 and SW480) colorectal cancer cells were treated with the miniFlatPlaSter - a device particularly developed for the treatment of tumor cells - that uses the Surface Micro Discharge (SMD) technology for plasma production in air. The present study analyzed the effects of plasma on colorectal cancer cells in vitro and on normal colon tissue ex vivo. Plasma treatment had strong effects on colon cancer cells, such as inhibition of cell proliferation, induction of cell death, and modulation of p21 expression. In contrast, CAP treatment of murine colon tissue ex vivo for up to 2 min did not show any toxic effect on normal colon cells compared to H2O2 positive control. In summary, these results suggest that the miniFlatPlaSter plasma device is able to kill colorectal cancer cells independent of their p53 mutation status. Thus, this device presents a promising new approach in colon cancer therapy.