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Ala I Sharara - One of the best experts on this subject based on the ideXlab platform.
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a randomized single blind trial of split dose peg electrolyte solution without Dietary Restriction compared with whole dose peg electrolyte solution with Dietary Restriction for colonoscopy preparation
Gastrointestinal Endoscopy, 2005Co-Authors: Elie Aoun, Heitham Abdulbaki, Cecilio Azar, Fadi H Mourad, Kassem Barada, Zeina Berro, Mohsen Tarchichi, Ala I ShararaAbstract:Background Colonoscopy preparation regimens are poorly tolerated, requiring the use of a large volume of an unpalatable solution and Diet Restriction for adequate cleansing. The aim of this study was to compare the efficacy of two regimens of bowel preparation before colonoscopy: a whole dose of polyethylene glycol electrolyte solution (PEG-E), with Diet Restriction vs. a split dose with no Diet Restriction. Methods A total of 141 patients (ages 20-84 years, 81 men) were randomly assigned to receive either 4 L PEG-E, along with a liquid Diet the day before colonoscopy (Group A) or 2 L PEG-E with a regular Diet the day before colonoscopy followed by another 2 L PEG-E on the day of the procedure (Group B). The quality of the preparation was graded by the endoscopist (poor to excellent), who was blinded to the type of preparation. Tolerability of the assigned preparation and adverse effects were recorded by an independent investigator by using a questionnaire administered before colonoscopy. Intra- and interobserver variability was studied by using randomly chosen videotapes of colonoscopies performed as part of the study. Results There were 73 patients in Group A and 68 patients in Group B. The quality of the preparation was significantly better in Group B ( p =0.011). The tolerability of the preparation regimen was not different overall between study groups in terms of side effects (except for bloating, which was more frequent in Group B, p =0.039) or willingness to repeat the preparation. There was a nonsignificant trend toward improved adherence to the assigned preparation in favor of Group B ( p =0.062). Inter- and intraobserver variability analysis showed good to excellent correlation among endoscopists. Conclusions Colonic preparation with split-dose PEG-E and no Dietary Restriction provides better quality colon cleansing than whole-dose preparation, with no significant impact on patient tolerability and side effects.
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a randomized single blind trial of split dose peg electrolyte solution without Dietary Restriction compared with whole dose peg electrolyte solution with Dietary Restriction for colonoscopy preparation
Gastrointestinal Endoscopy, 2005Co-Authors: Elie Aoun, Heitham Abdulbaki, Cecilio Azar, Fadi H Mourad, Kassem Barada, Zeina Berro, Mohsen Tarchichi, Ala I ShararaAbstract:Background Colonoscopy preparation regimens are poorly tolerated, requiring the use of a large volume of an unpalatable solution and Diet Restriction for adequate cleansing. The aim of this study was to compare the efficacy of two regimens of bowel preparation before colonoscopy: a whole dose of polyethylene glycol electrolyte solution (PEG-E), with Diet Restriction vs. a split dose with no Diet Restriction. Methods A total of 141 patients (ages 20-84 years, 81 men) were randomly assigned to receive either 4 L PEG-E, along with a liquid Diet the day before colonoscopy (Group A) or 2 L PEG-E with a regular Diet the day before colonoscopy followed by another 2 L PEG-E on the day of the procedure (Group B). The quality of the preparation was graded by the endoscopist (poor to excellent), who was blinded to the type of preparation. Tolerability of the assigned preparation and adverse effects were recorded by an independent investigator by using a questionnaire administered before colonoscopy. Intra- and interobserver variability was studied by using randomly chosen videotapes of colonoscopies performed as part of the study. Results There were 73 patients in Group A and 68 patients in Group B. The quality of the preparation was significantly better in Group B ( p =0.011). The tolerability of the preparation regimen was not different overall between study groups in terms of side effects (except for bloating, which was more frequent in Group B, p =0.039) or willingness to repeat the preparation. There was a nonsignificant trend toward improved adherence to the assigned preparation in favor of Group B ( p =0.062). Inter- and intraobserver variability analysis showed good to excellent correlation among endoscopists. Conclusions Colonic preparation with split-dose PEG-E and no Dietary Restriction provides better quality colon cleansing than whole-dose preparation, with no significant impact on patient tolerability and side effects.
Andrew Dillin - One of the best experts on this subject based on the ideXlab platform.
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a kruppel like factor downstream of the e3 ligase wwp 1 mediates Dietary Restriction induced longevity in caenorhabditis elegans
Nature Communications, 2014Co-Authors: Andrea C Carrano, Andrew Dillin, Tony HunterAbstract:The HECT ubiquitin E3 ligase WWP-1 is a positive regulator of lifespan in response to Dietary Restriction (DR) in Caenorhabditis elegans. However, substrates of WWP-1 for ubiquitylation in the DR pathway have not yet been identified. Here we identify the C. elegans Kruppel-like factor, KLF-1, as an essential and specific regulator of DR-induced longevity and a substrate for ubiquitylation by WWP-1. Knockdown of klf-1 suppresses the extended lifespan of both DR animals and wwp-1-overexpressing animals, indicating that KLF-1 functions within the same pathway as WWP-1. In addition, overexpression of klf-1 in the intestine is sufficient to extend the lifespan of WT animals on an ad libitum Diet, and requires wwp-1 or pha-4/FoxA. We demonstrate that WWP-1 directly interacts with KLF-1 and mediates multiple monoubiquitylation of KLF-1 in vitro and in cellulo. Our data support a model in which modulation of KLF-1 by WWP-1 regulates Diet-Restriction-induced longevity.
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a conserved ubiquitination pathway determines longevity in response to Diet Restriction
Nature, 2009Co-Authors: Andrea C Carrano, Andrew Dillin, Zheng Liu, Tony HunterAbstract:Dietary Restriction extends longevity in diverse species, suggesting that there is a conserved mechanism for nutrient regulation and prosurvival responses. Here we show a role for the HECT (homologous to E6AP carboxy terminus) E3 ubiquitin ligase WWP-1 as a positive regulator of lifespan in Caenorhabditis elegans in response to Dietary Restriction. We find that overexpression of wwp-1 in worms extends lifespan by up to 20% under conditions of ad libitum feeding. This extension is dependent on the FOXA transcription factor pha-4, and independent of the FOXO transcription factor daf-16. Reduction of wwp-1 completely suppresses the extended longevity of Diet-restricted animals. However, the loss of wwp-1 does not affect the long lifespan of animals with compromised mitochondrial function or reduced insulin/IGF-1 signalling. Overexpression of a mutant form of WWP-1 lacking catalytic activity suppresses the increased lifespan of Diet-restricted animals, indicating that WWP-1 ubiquitin ligase activity is essential for longevity. Furthermore, we find that the E2 ubiquitin conjugating enzyme, UBC-18, is essential and specific for Diet-Restriction-induced longevity. UBC-18 interacts with WWP-1 and is required for the ubiquitin ligase activity of WWP-1 and the extended longevity of worms overexpressing wwp-1. Taken together, our results indicate that WWP-1 and UBC-18 function to ubiquitinate substrates that regulate Diet-Restriction-induced longevity.
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pha 4 foxa mediates Diet Restriction induced longevity of c elegans
Nature, 2007Co-Authors: Siler H Panowski, Suzanne Wolff, Hugo Aguilaniu, Jenni Durieux, Andrew DillinAbstract:Reduced food intake as a result of Dietary Restriction increases the lifespan of a wide variety of metazoans and delays the onset of multiple age-related pathologies. Dietary Restriction elicits a genetically programmed response to nutrient availability that cannot be explained by a simple reduction in metabolism or slower growth of the organism. In the nematode worm Caenorhabditis elegans, the transcription factor PHA-4 has an essential role in the embryonic development of the foregut and is orthologous to genes encoding the mammalian family of Foxa transcription factors, Foxa1, Foxa2 and Foxa3. Foxa family members have important roles during development, but also act later in life to regulate glucagon production and glucose homeostasis, particularly in response to fasting. Here we describe a newly discovered, adult-specific function for PHA-4 in the regulation of Diet-Restriction-mediated longevity in C. elegans. The role of PHA-4 in lifespan determination is specific for Dietary Restriction, because it is not required for the increased longevity caused by other genetic pathways that regulate ageing.
Elie Aoun - One of the best experts on this subject based on the ideXlab platform.
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a randomized single blind trial of split dose peg electrolyte solution without Dietary Restriction compared with whole dose peg electrolyte solution with Dietary Restriction for colonoscopy preparation
Gastrointestinal Endoscopy, 2005Co-Authors: Elie Aoun, Heitham Abdulbaki, Cecilio Azar, Fadi H Mourad, Kassem Barada, Zeina Berro, Mohsen Tarchichi, Ala I ShararaAbstract:Background Colonoscopy preparation regimens are poorly tolerated, requiring the use of a large volume of an unpalatable solution and Diet Restriction for adequate cleansing. The aim of this study was to compare the efficacy of two regimens of bowel preparation before colonoscopy: a whole dose of polyethylene glycol electrolyte solution (PEG-E), with Diet Restriction vs. a split dose with no Diet Restriction. Methods A total of 141 patients (ages 20-84 years, 81 men) were randomly assigned to receive either 4 L PEG-E, along with a liquid Diet the day before colonoscopy (Group A) or 2 L PEG-E with a regular Diet the day before colonoscopy followed by another 2 L PEG-E on the day of the procedure (Group B). The quality of the preparation was graded by the endoscopist (poor to excellent), who was blinded to the type of preparation. Tolerability of the assigned preparation and adverse effects were recorded by an independent investigator by using a questionnaire administered before colonoscopy. Intra- and interobserver variability was studied by using randomly chosen videotapes of colonoscopies performed as part of the study. Results There were 73 patients in Group A and 68 patients in Group B. The quality of the preparation was significantly better in Group B ( p =0.011). The tolerability of the preparation regimen was not different overall between study groups in terms of side effects (except for bloating, which was more frequent in Group B, p =0.039) or willingness to repeat the preparation. There was a nonsignificant trend toward improved adherence to the assigned preparation in favor of Group B ( p =0.062). Inter- and intraobserver variability analysis showed good to excellent correlation among endoscopists. Conclusions Colonic preparation with split-dose PEG-E and no Dietary Restriction provides better quality colon cleansing than whole-dose preparation, with no significant impact on patient tolerability and side effects.
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a randomized single blind trial of split dose peg electrolyte solution without Dietary Restriction compared with whole dose peg electrolyte solution with Dietary Restriction for colonoscopy preparation
Gastrointestinal Endoscopy, 2005Co-Authors: Elie Aoun, Heitham Abdulbaki, Cecilio Azar, Fadi H Mourad, Kassem Barada, Zeina Berro, Mohsen Tarchichi, Ala I ShararaAbstract:Background Colonoscopy preparation regimens are poorly tolerated, requiring the use of a large volume of an unpalatable solution and Diet Restriction for adequate cleansing. The aim of this study was to compare the efficacy of two regimens of bowel preparation before colonoscopy: a whole dose of polyethylene glycol electrolyte solution (PEG-E), with Diet Restriction vs. a split dose with no Diet Restriction. Methods A total of 141 patients (ages 20-84 years, 81 men) were randomly assigned to receive either 4 L PEG-E, along with a liquid Diet the day before colonoscopy (Group A) or 2 L PEG-E with a regular Diet the day before colonoscopy followed by another 2 L PEG-E on the day of the procedure (Group B). The quality of the preparation was graded by the endoscopist (poor to excellent), who was blinded to the type of preparation. Tolerability of the assigned preparation and adverse effects were recorded by an independent investigator by using a questionnaire administered before colonoscopy. Intra- and interobserver variability was studied by using randomly chosen videotapes of colonoscopies performed as part of the study. Results There were 73 patients in Group A and 68 patients in Group B. The quality of the preparation was significantly better in Group B ( p =0.011). The tolerability of the preparation regimen was not different overall between study groups in terms of side effects (except for bloating, which was more frequent in Group B, p =0.039) or willingness to repeat the preparation. There was a nonsignificant trend toward improved adherence to the assigned preparation in favor of Group B ( p =0.062). Inter- and intraobserver variability analysis showed good to excellent correlation among endoscopists. Conclusions Colonic preparation with split-dose PEG-E and no Dietary Restriction provides better quality colon cleansing than whole-dose preparation, with no significant impact on patient tolerability and side effects.
Marc Tatar - One of the best experts on this subject based on the ideXlab platform.
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counting calories in drosophila Diet Restriction
Experimental Gerontology, 2007Co-Authors: Kyungjin Min, Thomas Flatt, Indrek Kulaots, Marc TatarAbstract:The extension of life span by Diet Restriction in Drosophila has been argued to occur without limiting calories. Here we directly measure the calories assimilated by flies when maintained on full- and restricted-Diets. We find that caloric intake is reduced on all Diets that extend life span. Flies on low-yeast Diet are long-lived and consume about half the calories of flies on high-yeast Diets, regardless of the energetic content of the Diet itself. Since caloric intake correlates with yeast concentration and thus with the intake of every metabolite in this Dietary component, it is premature to conclude for Drosophila that calories do not explain extension of life span.
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Diet Restriction in drosophila melanogaster design and analysis
Mechanisms of dietary restriction in aging and disease, 2007Co-Authors: Marc TatarAbstract:Diet Restriction (DR) was first shown to extend adult survival in Drosophila only a bit longer than a dozen years ago. Limiting the amount of Dietary yeast was sufficient to increase life span. In the short time since this initial observation, work with Drosophila has revealed several insights into the mechanisms of DR. It has also uncovered many unanticipated technical issues. This paper describes how resolving the way we study DR in Drosophila is a prerequisite to discover the way nutrition modulates aging. Key empirical problems include the necessity of measuring the impact of DR upon life span with multiple levels of Diet, analysis of the demographic response to Diet with mortality data and, in the context of reaction norms, methods of Diet modification, and uncertainty as to how Diet dilution translates to changes in actual nutrient uptake. We review the accumulated literature of DR in Drosophila from this methodological lens to distill four important results: yeast Restriction alone is sufficient to increase survival; Diet affects survival through two distinct physiological responses, starvation and longevity assurance; mortality has no memory of its past with respect to nutrition; the molecular operation of DR may involve processes of deacetylation via Sir-2 and Rpd-3. Finally, it remains unknown whether or not DR functions through insulin-related signaling.
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drosophila Diet Restriction in practice do flies consume fewer nutrients
Mechanisms of Ageing and Development, 2006Co-Authors: Kyungjin Min, Marc TatarAbstract:Although many studies of Drosophila melanogaster report an effect of Diet upon lifespan, it is assumed rather than know that adults maintained on restricted Diet acquire fewer nutrients. Diet is restricted in practice by feeding flies a medium where nutrients are diluted and some early reports suggest that flies on diluted medium compensate with increased food intake to consume equal calories on all Diets. Here we measure the feeding rate of adult Drosophila upon a yeast-restricted Diet that increases survival and reduces fecundity. We directly assessed food intake from the volume of consumed dye-marked medium and from the quantity of marked fecal pellets. Females were longest lived on Diet with intermediate yeast concentration but food intake was greatest on Diet with abundant yeast. Rather than compensatory feeding upon diluted Diet, females increased food intake on the Diet with elevated nutrient concentration. Consequently, females on diluted yeast-limited media will consume fewer calories as well as less yeast. To understand the importance of specific nutrients relative to calories as mediators of Drosophila aging, we must directly measure food intake and control for the feeding stimulation of nutrients.
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juvenile Diet Restriction and the aging and reproduction of adult drosophila melanogaster
Aging Cell, 2003Co-Authors: Marc TatarAbstract:Mutations of the insulin signal pathway in Drosophila melanogaster produce long-lived adults with many correlated phenotypes. Homozygotes of insulin-like receptor (InR) and insulin-like receptor substrate (chico) delay time to eclosion, reduce body size, decrease reproduction and increase life span. Because these mutations are expressed through all life stages it is unclear when insulin signals must be reduced to increase life span. As a first analysis of this problem in D. melanogaster we have manipulated the larval Diet to determine if changes in metabolic regulation at this stage are sufficient to slow aging. We controlled the Dietary yeast fed to third instar larvae and studied the size, mortality, fecundity and hormones of the resulting adults, which were fed a normal, yeast-replete Diet. Adults from yeast-deprived larvae phenocopied many traits of InR and chico mutants: small body size, delayed eclosion, reduced ovariole number and reduced age-specific fecundity. But unlike constitutive mutants of the insulin/IGF system, adults from yeast-deprived larvae had normal patterns of demographic senescence, and this was accompanied by normal insulin-like peptide and juvenile hormone syntheses. Surprisingly, the normal aging in these adults was also associated with greatly reduced fecundity. Although nutritional conditions of the larvae can affect the subsequent body size and fecundity of adults, these are not sufficient to slow aging.
Roberto Pili - One of the best experts on this subject based on the ideXlab platform.
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Dietary protein Restriction inhibits tumor growth in human xenograft models of prostate and breast cancer
Oncotarget, 2013Co-Authors: Luigi Fontana, Remi Adelaiye, Kiersten Marie Miles, Eric Ciamporcero, Holly M Nguyen, Robert L Vessella, Antonella Rastelli, Valter D Longo, Roberto PiliAbstract:Purpose: Data from epidemiological and experimental studies suggest that Dietary protein intake may play a role in inhibiting prostate and breast cancer by modulating the IGF/AKT/mTOR pathway. In this study we investigated the effects of Diets with different protein content or quality on prostate and breast cancer. Experimental Design: To test our hypothesis we assessed the inhibitory effect of protein Diet Restriction on prostate and breast cancer growth, serum PSA and IGF1 concentrations, mTOR activity and epigenetic markers, by using human xenograft cancer models. Results: Our results showed a 70% inhibition of tumor growth in the castrateresistant LuCaP23.1 prostate cancer model and a 56% inhibition in the WHIM16 breast cancer model fed with a 7% protein Diet when compared to an isocaloric 21% protein Diet. Inhibition of tumor growth correlated, in the LuCaP23.1 model, with decreased serum PSA and IGF-1 levels, down-regulation of mTORC1 activity, decreased cell proliferation as indicated by Ki67 staining, and reduction in epigenetic markers of prostate cancer progression, including the histone methyltransferase EZH2 and the associated histone mark H3K27me3. In addition, we observed that modifications of Dietary protein quality, independently of protein quantity, decreased tumor growth. A Diet containing 20% plant protein inhibited tumor weight by 37% as compared to a 20% animal dairy protein Diet. Conclusions: Our findings suggest that a reduction in Dietary protein intake is highly effective in inhibiting tumor growth in human xenograft prostate and breast cancer models, possibly through the inhibition of the IGF/AKT/mTOR pathway and epigenetic modifications.
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abstract 4859 tumor growth inhibition and epigenetic changes following protein Diet Restriction in a human prostate cancer model
Cancer Research, 2013Co-Authors: Remi Adelaiye, Kiersten Marie Miles, Eric Ciamporcero, Holly M Nguyen, Robert L Vessella, Luigi Fontana, Roberto PiliAbstract:Background: Environmental factors such as a Western Diet may be associated with the risk of developing prostate cancer (PCa). Diet modifications such as calorie and fat Restriction have been shown to have an impact on PCa development and progression. Protein Diet Restriction has been associated with epigenetic changes in embrional development. The aim of this study was to assess the effect of protein Restriction on prostate tumor progression. Methods: A human xenograft LuCaP 23.1 castrate resistant (AI) model, which resembles the pathological features of human prostate cancer including prostate specific antigen (PSA) expression, was utilized. SCID mice were randomly grouped and placed on either regular (21%) or low (7%) protein isocaloric Diet. LuCaP 23.1 AI tumor tissue was implanted 4 weeks either before or after Diet modifications. To investigate whether the source of protein Diet had an impact on tumor growth, we randomly grouped mice and placed them prior to tumor implantation on either normal plant protein Diet (20%), low plant based protein Diet (10%), normal dairy protein Diet (20%) or low diary protein Diet (10%). We assessed tumor growth two times a week and body weight once a week. Endpoint tumor weights were assessed and tumor samples were collected for immunohistochemistry (IHC) studies. Body fluids were collected for IGF-1 and glucose level analysis. Results: Our preliminary results showed a >70% inhibition of tumor growth in LuCaP23.1 AI model with 7% low protein Diet when compared to 21% normal protein Diet (p >0.01). Tumor inhibition correlated with a decrease in PSA values. Tumor growth assessment also indicated that 20% and 10% plant protein, and 10% dairy protein Diet decreased tumor weight by 37% (20% and 10% plant protein) and 35% (10% dairy protein) as compared to 20% animal protein Diet (p >0.05). Serum glucose levels were higher in mice on low protein Diet (150.3mg/dL+22.4) as compared to those on normal Diet (136.6mg/dL+17.6). IHC analysis showed a decrease in proliferation as suggested by Ki67 staining (21% Diet = 47%+4.4 vs. 7% Diet = 22%+3.4), inhibition of mTORC1 activity as demonstrated by a reduction in phosphor-mTOR (21% Diet = 54%+2.7 vs. 7% Diet = 21%+2.7) and its downstream enzyme phosphor-S6 (21% Diet = 52%+4.0 vs. 7% Diet = 5.4%+0.5). In addition, low protein Diet decreased the level of the histone methyltransferase EZH2 (21% Diet = 97.3% +1.69 vs. 7% Diet = 55.1%+3.46) and the associated repressive histone mark H3K27me3 (21% Diet = 82.3%+5.1 vs. 7% Diet = 54.9%+3.8). Additional animal models for PCa are being tested. Conclusions: Our findings suggest that a reduction in animal protein Diet is effective in inhibiting tumor growth in a human xenograft PCa model. Tumor inhibition following protein Restriction was associated with modifications of mTOR signaling pathway and epigenetic marks. These data provide a rationale for protein Diet modifications in patients with PCa. Citation Format: Remi M. Adelaiye, Kiersten Marie Miles, Eric Ciamporcero, Holly Nguyen, Robert Vessella, Luigi Fontana, Roberto Pili. Tumor growth inhibition and epigenetic changes following protein Diet Restriction in a human prostate cancer model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4859. doi:10.1158/1538-7445.AM2013-4859