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Results of a phase I pilot clinical trial examining the effect of plant-derived resveratrol and grape powder on Wnt pathway target gene expression in colonic mucosa and colon cancer  [cached]
Anthony V Nguyen,Micaela Martinez,Michael J Stamos,Mary P Moyer
Cancer Management and Research , 2009,
Abstract: Anthony V Nguyen1, Micaela Martinez1, Michael J Stamos2, Mary P Moyer3, Kestutis Planutis1, Christopher Hope1 Randall F Holcombe11Division of Hematology/Oncology and Chao Family Comprehensive Cancer Center, 2Department of Surgery, University of California, Irvine CA, USA; 3Incell Corporation, San Antonio, TX USAContext: Resveratrol exhibits colon cancer prevention activity in animal models; it is purported to have this activity in humans and inhibit a key signaling pathway involved in colon cancer initiation, the Wnt pathway, in vitro.Design: A phase I pilot study in patients with colon cancer was performed to evaluate the effects of a low dose of plant-derived resveratrol formulation and resveratrol-containing freeze-dried grape powder (GP) on Wnt signaling in the colon. Eight patients were enrolled and normal colonic mucosa and colon cancer tissue were evaluated by Wnt pathway-specific microarray and quantitative real-time polymerase chain reaction (qRT-PCR) pre- and post-exposure to resveratrol/GP.Results: Based on the expression of a panel of Wnt target genes, resveratrol/GP did not inhibit the Wnt pathway in colon cancer but had significant (p < 0.03) activity in inhibiting Wnt target gene expression in normal colonic mucosa. The greatest effect on Wnt target gene expression was seen following ingestion of 80 g of GP per day (p < 0.001). These results were confirmed with qRT-PCR of cyclinD1 and axinII. The inhibitory effect of GP on Wnt signal throughput was confirmed in vitro with a normal colonic mucosa-derived cell line.Conclusions: These data suggest that GP, which contains low dosages of resveratrol in combination with other bioactive components, can inhibit the Wnt pathway in vivo and that this effect is confined to the normal colonic mucosa. Further study of dietary supplementation with resveratrol-containing foods such as whole grapes or GP as a potential colon cancer preventive strategy is warranted.Trial registration: NCT00256334.Keywords: resveratrol, clinical trial, colon cancer, Wnt signaling, grapes, cancer prevention
Influence of Maternal Bifidobacteria on the Development of Gut Bifidobacteria in Infants  [PDF]
Katsunaka Mikami,Moto Kimura,Hidenori Takahashi
Pharmaceuticals , 2012, DOI: 10.3390/ph5060629
Abstract: Intestinal microbiota plays an important role in human health by influencing metabolic activities that result in the creation of energy and absorbable nutrients, a barrier to the colonization of pathogens, and stimulation of the immune system. The development of fecal microbiota in neonates is crucial because those bacteria are the first to colonize the sterile intestine of the neonates and, thus, have a significant effect on the host. Initial colonization is also relevant to the ?nal composition of the permanent microbiota in adults. Bifidobacteria are predominant in the fecal microbiota of infants, and, therefore, they are important to an understanding of how commensal bifidobacteria is established in the intestine of infants. While the mother’s bifidobacteria are considered to significantly influence the infant’s bifidobacteria, it is not clear whether a specific bifidobacterial strain transmits vertically from mother to infant and what factors of the mother before delivery influence the establishment of intestinal bifidobacteria in infants. This review focuses on the impact of maternal bifidobacteria on the development of gut bifidobacteria in the infant and suggests that there is cumulative evidence regarding bifidobacterial transfer from the maternal gut or breast milk to the infant gut.
Results of a phase I pilot clinical trial examining the effect of plant-derived resveratrol and grape powder on Wnt pathway target gene expression in colonic mucosa and colon cancer
Anthony V Nguyen, Micaela Martinez, Michael J Stamos, Mary P Moyer, Kestutis Planutis, Christopher Hope, Randall F Holcombe
Cancer Management and Research , 2009, DOI: http://dx.doi.org/10.2147/CMAR.S4544
Abstract: ults of a phase I pilot clinical trial examining the effect of plant-derived resveratrol and grape powder on Wnt pathway target gene expression in colonic mucosa and colon cancer Original Research (6236) Total Article Views Authors: Anthony V Nguyen, Micaela Martinez, Michael J Stamos, Mary P Moyer, Kestutis Planutis, Christopher Hope, Randall F Holcombe Published Date April 2009 Volume 2009:1 Pages 25 - 37 DOI: http://dx.doi.org/10.2147/CMAR.S4544 Anthony V Nguyen1, Micaela Martinez1, Michael J Stamos2, Mary P Moyer3, Kestutis Planutis1, Christopher Hope1 Randall F Holcombe1 1Division of Hematology/Oncology and Chao Family Comprehensive Cancer Center, 2Department of Surgery, University of California, Irvine CA, USA; 3Incell Corporation, San Antonio, TX USA Context: Resveratrol exhibits colon cancer prevention activity in animal models; it is purported to have this activity in humans and inhibit a key signaling pathway involved in colon cancer initiation, the Wnt pathway, in vitro. Design: A phase I pilot study in patients with colon cancer was performed to evaluate the effects of a low dose of plant-derived resveratrol formulation and resveratrol-containing freeze-dried grape powder (GP) on Wnt signaling in the colon. Eight patients were enrolled and normal colonic mucosa and colon cancer tissue were evaluated by Wnt pathway-specific microarray and quantitative real-time polymerase chain reaction (qRT-PCR) pre- and post-exposure to resveratrol/GP. Results: Based on the expression of a panel of Wnt target genes, resveratrol/GP did not inhibit the Wnt pathway in colon cancer but had significant (p < 0.03) activity in inhibiting Wnt target gene expression in normal colonic mucosa. The greatest effect on Wnt target gene expression was seen following ingestion of 80 g of GP per day (p < 0.001). These results were confirmed with qRT-PCR of cyclinD1 and axinII. The inhibitory effect of GP on Wnt signal throughput was confirmed in vitro with a normal colonic mucosa-derived cell line. Conclusions: These data suggest that GP, which contains low dosages of resveratrol in combination with other bioactive components, can inhibit the Wnt pathway in vivo and that this effect is confined to the normal colonic mucosa. Further study of dietary supplementation with resveratrol-containing foods such as whole grapes or GP as a potential colon cancer preventive strategy is warranted. Trial registration: NCT00256334.
Pilot programme - detection of colon tumour in subjects living in the district of northern Banat  [PDF]
Naumov Ivana,Fenjve?i Atila
Medicinski Pregled , 2012, DOI: 10.2298/mpns1208285n
Abstract: Introduction. Tumours of the colon are among the leading neoplasms in the world as well as in Europe and our country both in the male and female population. The study was aimed at showing the incidence of colon tumour in a group of 300 subjects who had undergone total colonoscopy as well. Material and Methods. The endoscopic examinations were performed by the Fujinon video endoscopes. The faecal occult blood test was done by the original test ‘ULTI Med Products Deutschland GmbH’. The biopsy specimens were delivered to the Pathomorphological Service to be processed and stained by the method of Hematoksilin-eosin. Results. A group of 300 subjects, consisting of 144 men (48%) and 156 women (52%) were examined. The indication for the lower endoscopy in 52 patients (17.33%) was manifest bleeding. The faecal occult blood test was positive in 79 patients (26.33). The endoscopic examination verified 25 colon polyps (8.33%) and 14 malignant colon tumours (4.60%) in the examined group. The endoscopy was also performed in 48 patients who had been already operated for colon carcinoma (16%) and in 5 patients who had undergone endoscopic polypectomy (1.66%). Specificity, sensitivity and predictivity were calculated to be 55.8%, 63% and for positive finding 9.4% and for negative finding 95.8%, respectively, for the Haemoccult test as compared to the histological finding as a ”gold standard”. Discussion. The obtained results were compared with the findings of other authors. Conclusion. Our opinion, formed according to the obtained results and findings of other authors, is that it is necessary to perform systematic examination of people over 45 years of age for early detection of colon tumour.
Promoting Physical Activity in Patients with Colon Adenomas: A Randomized Pilot Intervention Trial  [PDF]
Kathleen Y. Wolin, Casey Fagin, Aimee S. James, Dayna S. Early
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0039719
Abstract: Background Physical activity decreases risk of colon polyps and colon cancer and might reduce risk of colon cancer recurrence. Focusing on recent calls for translation of epidemiologic evidence into clinical care, our pilot study delivered an evidence-based physical activity intervention in adults with polyps, who are thus at elevated risk of developing colon cancer. The objective was to evaluate change in physical activity, measured by steps per day and minutes of moderate/vigorous physical activity. Methods Sixteen adults with adenomas detected and removed at screening colonoscopy were recruited to a 12-week physical activity intervention. Participants were randomized to receive a standard (30 minutes/day) or high (60 minutes/day) walking program. Physical activity was measured via blinded pedometer and accelerometer at baseline and follow-up. Intervention messages focused on self-monitoring using pedometers and overcoming barriers to engaging in physical activity. Results Participants in both arms significantly increased objectively measured minutes of moderate/vigorous physical activity over the course of the intervention. Both arms exceeded the intervention goal, but there was not a significant difference between arms at follow-up. Results were similar for pedometer measured physical activity, with a significant overall increase in steps/day from baseline to follow-up, but no between arm difference in change. Conclusion Simple interventions of minimal contact time focusing on walking can significantly increase physical activity in individuals at increased risk of developing colon cancer. Trial Registration ClinicalTrials.gov NCT01476631
The capacity of short-chain fructo-oligosaccharides to stimulate faecal bifidobacteria: a dose-response relationship study in healthy humans
Yoram Bouhnik, Laurent Raskine, Guy Simoneau, Damien Paineau, Francis Bornet
Nutrition Journal , 2006, DOI: 10.1186/1475-2891-5-8
Abstract: Forty healthy volunteers (18 males, 22 females) eating their usual diets were randomly divided into 5 groups of 8 subjects and received scFOS at a dose of 2.5, 5.0, 7.5 and 10 g/d or a placebo for 7 d. Stools were collected before (day (d) 8) and at the end (day (d) 15) of sugar consumption, and tolerance was evaluated using a daily chart.Bifidobacteria counts increase was higher in scFOS than in placebo group for all doses tested [2.5 g/d (from 9.15 ± 0.59 to 9.39 ± 0.70; P = 0.02); 5 g/d (from 10.21 ± 0.21 to 10.67 ± 0.22; P = 0.03); 7.5 g/d (from 9.28 ± 0.49 to 9.85 ± 0.35;P = 0.01); 10 g/d (from 9.00 ± 0.81 to 10.18 ± 0.60; P = 0.003)]. A significant correlation between the ingested dose of scFOS and faecal bifidobacteria counts was observed at d15 (r2 = 0.307, P < 0.001). Total anaerobes increased at the dose of 10 g/d. No significant differences were found for Bacteroides, Lactobacillus, enterobacteria or pH in any group. The frequency of digestive symptoms was not different between scFOS at any of the doses tested and placebo. Bloating was significantly more intense during scFOS ingestion at doses of 2.5 and 5 g/d, but not at doses of 7.5 and 10 g/d. Excess flatus, borborygmi and abdominal pain did not differ from the placebo at any of the doses tested.This study showed that scFOS is bifidogenic and well tolerated at doses ranging from 2.5 to 10 g/d, and that there is a dose-response relationship in healthy volunteers.Short chain fructo-oligosaccharides (scFOS) are a mixture of oligosaccharides consisting of glucose linked to fructose units; links between fructose units are β-(1,2) [1]. They are produced commercially from sucrose using an enzymatic process. ScFOS are poorly digested in the human small intestine but are fermented in the colon by the resident microflora [2].In light of the recent interest in "prebiotics", defined as "a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or the activity of
Four-week short chain fructo-oligosaccharides ingestion leads to increasing fecal bifidobacteria and cholesterol excretion in healthy elderly volunteers
Yoram Bouhnik, Lotfi Achour, Damien Paineau, Michel Riottot, Alain Attar, Francis Bornet
Nutrition Journal , 2007, DOI: 10.1186/1475-2891-6-42
Abstract: Stools composition, oro-fecal transit time, and clinical tolerance were evaluated in 12 healthy volunteers, aged 69 ± 2 yrs, in three consecutive periods: basal period (2 weeks), scFOS (Actilight?) ingestion period (8 g/d for 4 weeks) and follow-up period (4 weeks). Two-way ANOVA, with time and treatment as factors, was used to compare the main outcome measures between the three periods.Fecal bifidobacteria counts were significantly increased during the scFOS period (9.17 ± 0.17 log cfu/g vs 8.52 ± 0.26 log cfu/g during the basal period) and returned to their initial values at the end of follow-up (8.37 ± 0.21 log cfu/g; P < 0.05). Fecal cholesterol concentration increased during the scFOS period (8.18 ± 2.37 mg/g dry matter vs 2.81 ± 0.94 mg/g dry matter during the basal period) and returned to the baseline value at the end of follow-up (2.87 ± 0.44 mg/g dry matter; P < 0.05). Fecal pH tended to decrease during scFOS ingestion and follow-up periods compared to the basal period (P = 0.06). Fecal bile acids, stool weight, water percentage, and oro-fecal transit time did not change throughout the study. Excess flatus and bloating were significantly more frequent during scFOS ingestion when compared to the basal period (P < 0.05), but the intensity of these symptoms was very mild.Four-week 8 g/d scFOS ingestion is well tolerated and leads to a significant increase in fecal bifidobacteria in healthy elderly subjects. Whether the change in cholesterol metabolism found in our study could exert a beneficial action warrants further studies.Short-chain fructo-oligosaccharides (scFOS) are a mixture of oligosaccharides consisting of glucose linked to fructose units [1]. They are poorly absorbed in the human small intestine [2], but are fermented in the colon by the resident microflora [3]. It is now well established that scFOS meet criteria to be considered as prebiotic, defined as a non digestible food ingredient that beneficially affects the host by selectively stimulating g
The uptake and effect of a mailed multi-modal colon cancer screening intervention: A pilot controlled trial
Carmen L Lewis, Alison T Brenner, Jennifer M Griffith, Michael P Pignone
Implementation Science , 2008, DOI: 10.1186/1748-5908-3-32
Abstract: We conducted a controlled trial comparing the proportion of intervention patients who received colon cancer screening with wait list controls at one practice site. The intervention was a mailed package that included a letter from their primary care physician, a colon cancer screening decision aid, and instructions for obtaining each screening test without an office visit so that patients could access screening tests directly. Major outcomes were screening test completion and cost per additional patient screened.In the intervention group, 15% (20/137) were screened versus 4% (4/100) in the control group (difference 11%; (95%; CI 3%;18% p = 0.01). The cost per additional patient screened was estimated to be $94.A multi-modal intervention, which included mailing a patient reminder with a colon cancer decision aid to patients and system changes allowing patients direct access to schedule screening tests, increased colon cancer screening test completion in a subset of patients within a single academic practice. Although the uptake of the decision aid was low, the cost was also modest, suggesting that this method could be a viable approach to colon cancer screening.Colon cancer is the second leading cause of cancer-related deaths in the United States, and the third most commonly diagnosed cancer, with over 149,000 new diagnoses and 55,000 deaths expected in 2006 [1]. Colon cancer screening is effective in decreasing colon cancer incidence and mortality [2-4], and there are several recommended screening tests available to patients [5]. Despite its effectiveness, colon cancer screening is underutilized in the United States. Recent data on self-reported screening status from the Behavioral Risk Factor Surveillance System survey shows that only 57% of people in the United States are up to date with recommended screening [6].Barriers at multiple levels of the healthcare system (physician, patient, and system levels) contribute to the underutilization of colon cancer screening,
Dextran Sodium Sulfate (DSS) Induces Colitis in Mice by Forming Nano-Lipocomplexes with Medium-Chain-Length Fatty Acids in the Colon  [PDF]
Hamed Laroui, Sarah A. Ingersoll, Hong Chun Liu, Mark T. Baker, Saravanan Ayyadurai, Moiz A. Charania, Famina Laroui, Yutao Yan, Shanthi V. Sitaraman, Didier Merlin
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0032084
Abstract: Inflammatory bowel diseases (IBDs), primarily ulcerative colitis and Crohn's disease, are inflammatory disorders caused by multiple factors. Research on IBD has often used the dextran sodium sulfate (DSS)-induced colitis mouse model. DSS induces in vivo but not in vitro intestinal inflammation. In addition, no DSS-associated molecule (free glucose, sodium sulfate solution, free dextran) induces in vitro or in vivo intestinal inflammation. We find that DSS but not dextran associated molecules established linkages with medium-chain-length fatty acids (MCFAs), such as dodecanoate, that are present in the colonic lumen. DSS complexed to MCFAs forms nanometer-sized vesicles ~200 nm in diameter that can fuse with colonocyte membranes. The arrival of nanometer-sized DSS/MCFA vesicles in the cytoplasm may activate intestinal inflammatory signaling pathways. We also show that the inflammatory activity of DSS is mediated by the dextran moieties. The deleterious effect of DSS is localized principally in the distal colon, therefore it will be important to chemically modify DSS to develop materials beneficial to the colon without affecting colon-targeting specificity.
Deep Exploration of Bifidobacteria through Metabolomics Study  [PDF]
Juan Li, Yatao Jiang, Yihao Shen, Qingzhi Li, Zhongke Sun
Journal of Biosciences and Medicines (JBM) , 2018, DOI: 10.4236/jbm.2018.65008
Abstract: Bifidobacteria are probiotic bacteria with multiple health-promoting properties for human being. The global market for probiotics, especially for bifidobacteria is booming. However, the entire market is still at an early stage as there is nearly no fine products developed yet except the whole bacterial cells. The maturation of metabolomics technologies make it possible to study complex mixture with high-throughput, comprehensive maps and libraries. Therefore, we prospect that metabolomics studies mainly based on liquid/gas chromatography-mass spectrometry (LC/GC-MS) can deepen our understanding in detail during the study of metabolic mechanisms of bifidobacteria. These studies can be conducted at three phases, including non-targeted, targeted metabolomic analysis of bifidobacteria, and specific metabolites production through metabolic engineering and fermentation. Metabolomic studies of bifidobacteria will allow us to fully explore their metabolic mechanisms and to utilize metabolites that contribute to human health. In particular, bifidobacteria derived conjugated linoleic acids and bacteriocins are two kinds of fined products that may have great potentials in the future and can be used as food additives.
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