Pharmacodynamic Evaluation of Stool Output Following Oral Administration of Various Low Volume PEG3350-based Gut Cleansing Solutions Using the Split Dose Intake in Healthy Subjects
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer,Colorectal Neoplasms
PROVIDER: 2143369 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:The l-galactose (Smirnoff-Wheeler) pathway represents the major route to l-ascorbic acid (vitamin C) biosynthesis in plants. Arabidopsis thaliana VTC2 and its paralogue VTC5 function as GDP-l-galactose phosphorylases converting GDP-l-galactose to l-galactose-1-P, thus catalyzing the first committed step in the biosynthesis of l-ascorbate. Here we report that the l-galactose pathway of ascorbate biosynthesis described in higher plants is conserved in green algae. The Chlamydomonas reinhardtii genome encodes all the enzymes required for vitamin C biosynthesis via the Smirnoff-Wheeler pathway. We have characterized recombinant C. reinhardtii VTC2 as an active GDP-l-galactose phosphorylase. C. reinhardtii cells exposed to oxidative stress show increased VTC2 mRNA and l-ascorbate levels. We have also shown that enzymatic components of the ascorbate-glutathione system (e.g. ascorbate peroxidase, Mn superoxide dismutase, dehydroascorbate reductase) are up-regulated in response to increased oxidative stress. These results indicate that C. reinhardtii VTC2, like its plant homologs, is a key enzyme in ascorbate biosynthesis in green algae and together with components of the ascorbate recycling system represents the major route in providing protective levels of ascorbate in oxidatively stressed algal cells. Our results suggest that C. reinhardtii cells exposed to oxidative stress conditions produce more ascorbate both by de novo synthesis (Smirnoff-Wheeler pathway) and by recycling via the ascorbate-glutathione cycle.
2012-05-03 | GSE34826 | GEO
Project description:The l-galactose (Smirnoff-Wheeler) pathway represents the major route to l-ascorbic acid (vitamin C) biosynthesis in plants. Arabidopsis thaliana VTC2 and its paralogue VTC5 function as GDP-l-galactose phosphorylases converting GDP-l-galactose to l-galactose-1-P, thus catalyzing the first committed step in the biosynthesis of l-ascorbate. Here we report that the l-galactose pathway of ascorbate biosynthesis described in higher plants is conserved in green algae. The Chlamydomonas reinhardtii genome encodes all the enzymes required for vitamin C biosynthesis via the Smirnoff-Wheeler pathway. We have characterized recombinant C. reinhardtii VTC2 as an active GDP-l-galactose phosphorylase. C. reinhardtii cells exposed to oxidative stress show increased VTC2 mRNA and l-ascorbate levels. We have also shown that enzymatic components of the ascorbate-glutathione system (e.g. ascorbate peroxidase, Mn superoxide dismutase, dehydroascorbate reductase) are up-regulated in response to increased oxidative stress. These results indicate that C. reinhardtii VTC2, like its plant homologs, is a key enzyme in ascorbate biosynthesis in green algae and together with components of the ascorbate recycling system represents the major route in providing protective levels of ascorbate in oxidatively stressed algal cells. Our results suggest that C. reinhardtii cells exposed to oxidative stress conditions produce more ascorbate both by de novo synthesis (Smirnoff-Wheeler pathway) and by recycling via the ascorbate-glutathione cycle. Sampling of Chlamydomonas 2137 exposed to hydrogen peroxide
2012-05-02 | E-GEOD-34826 | biostudies-arrayexpress
Project description:Ascorbic acid (AA) is known to play a vital role in plant growth and detoxification of reactive oxygen species, however little is known about the significance of AA oxidation in plant defence against pathogens. • The role of ascorbate oxidation in rice defence against root-knot nematodes, Meloidogyne graminicola, was tested with application of AA, ascorbate oxidase (AO), dehydroascorbic acid (DHA), biosynthesis inhibitors and use of mutants. Transcriptome analysis was done on AO treated plants, and hormone measurements were executed to confirm the results. Biochemical analyses were used to study oxidative stress markers, including accumulation of H2O2, , malondialdehyde and AA/DHA.
2020-01-22 | GSE125427 | GEO
Project description:D1 multipotent mesenchymal stromal cells (D1‐MSCs,ATCC® CRL 12424TM) and genetically modified with the lentiviral vector pSIN‐EF2‐Epo‐Pur to express erythropoietin (EPO). D1‐MSCs genetically modified to release EPO were immobilized into 3D alginatepoly‐ L‐lysine‐alginate (APA) microcapsules. Since different formulations of alginate 1.5%, poly‐L‐lysine 0.05%, alginate 0.1% and washings were designed, two types of APA microcapsules were obtained: Biological microcapsules (made of Biological formulations) and Technological microcapsules (made of Technological formulations). The expression of the cells under different conditions of these two types of microcapsules have been analyzed. The present analysis proved that the mechanical properties of the matrix in which cells are enclosed influences drastically gene expression
2017-10-30 | E-MTAB-5786 | biostudies-arrayexpress
Project description:The gold standard of colorectal examination is colonoscopy. One of the main purposes of colonoscopy is detecting bowel neoplasms. Right now there are several methods the bowel preparation for the colonoscopy.
Several factors can affect the quality of the bowel preparation, such as the kind of oral laxative, the time after its intake and the diet followed in the days before colonoscopy. In this randomized clinical trial the investigators aimed to compare the safety and efficiency of two low-volume laxatives for bowel preparation: potassium, magnesium and sodium sulphates-based laxative Eziclen (IPSEN, France) and Macrogol-3350 + Sodium Sulfate + Potassium Chloride+ Sodium Chloride + Ascorbic Acid-based and Sodium Ascorbate-based Moviprep (Nordgine B.V., The Netherlands)
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Project description:Endoplasmic reticulum (ER) thiol oxidases initiate a disulfide relay to oxidatively-fold secreted proteins. We found that combined loss-of-function mutations in genes encoding the ER thiol oxidases ERO1alpha, ERO1beta and PRDX4, compromised the extracellular matrix in mice and interfered with the intracellular maturation of procollagen. These severe abnormalities were associated with an unexpectedly-modest delay in disulfide bond formation in secreted proteins but a profound, five-fold lower procollagen 4 hydroxyproline content and enhanced cysteinyl sulfenic acid modification of ER proteins. Tissue ascorbic acid content was lower in mutant mice and ascorbic acid supplementation improved procollagen maturation and lowered sulfenic acid content, in vivo. In vitro, the presence of a sulfenic acid donor accelerated the oxidative inactivation of ascorbate by an H2O2 generating system. Compromised ER disulfide relay thus exposes protein thiols to competing oxidation to sulfenic acid, resulting in depletion of ascorbic acid, impaired procollagen proline 4-hydroxylation and a non-canonical form of scurvy. double and triple mutants and wild type
2012-09-15 | E-GEOD-39492 | biostudies-arrayexpress
Project description:Endoplasmic reticulum (ER) thiol oxidases initiate a disulfide relay to oxidatively-fold secreted proteins. We found that combined loss-of-function mutations in genes encoding the ER thiol oxidases ERO1alpha, ERO1beta and PRDX4, compromised the extracellular matrix in mice and interfered with the intracellular maturation of procollagen. These severe abnormalities were associated with an unexpectedly-modest delay in disulfide bond formation in secreted proteins but a profound, five-fold lower procollagen 4 hydroxyproline content and enhanced cysteinyl sulfenic acid modification of ER proteins. Tissue ascorbic acid content was lower in mutant mice and ascorbic acid supplementation improved procollagen maturation and lowered sulfenic acid content, in vivo. In vitro, the presence of a sulfenic acid donor accelerated the oxidative inactivation of ascorbate by an H2O2 generating system. Compromised ER disulfide relay thus exposes protein thiols to competing oxidation to sulfenic acid, resulting in depletion of ascorbic acid, impaired procollagen proline 4-hydroxylation and a non-canonical form of scurvy.
2012-09-15 | GSE39492 | GEO
Project description:Interventions: split-dose PEG-ELS combination with Lubiprostone 3 times by specifying as follows; 2 days before colonoscopy 1 capsule of Lubiprostone at 6.00 a.m. then took 1 capsule of Lubiprostone at 6 p.m. Day before colonoscopy - 1 capsule of Lubiprostone at 6.00 a.m. The subjects would receive 1 sachet of PEG-ELS mixed with 2 liters of water, which the patients had to take all within 2 hours at 6:00 p.m. Lastly, on the colonoscopy day, the subjects received 1 sachet of PEG-ELS mixed with 2 liters of water and took it all in 2 hours at 4.00 a.m. on the day of the colonoscopy.,split-dose PEG-ELS before colonoscopy day, patients had to take 1 sachet of PEG-ELS with 2 Liter of water at 6 p.m. and 1 sachet of PEG-ELS with 2 Liter of water at 4 a.m. on the day of the colonoscopy.;Active Comparator Drug,Placebo Comparator Drug;split-dose PEG-ELS combination with Lubiprostone 3 times ,split-dose PEG-ELS combination
Primary outcome(s): the Ottawa bowel preparation score Colonoscopy day proportion of adequate bowel cleansing
Study Design: Randomized
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Project description:Tetrahexyldecyl Ascorbate (THDC) is an L-ascorbic acid precursor with improved stability and ability to penetrate the epidermis. The stability and transdermal penetration of THDC, however, may be compromised by the oxidant-rich environment of human skin. In this study, we show that THDC is a poor antioxidant that degrades rapidly when exposed to singlet oxygen. This degrada-tion, however, was prevented by combination with acetyl zingerone (AZ) as a stabilizing antiox-idant. As a standalone ingredient, THDC led to unexpected activation of type I interferon signaling, but this pro-inflammatory effect was blunted in the presence of AZ. Moreover, the combination of THDC and AZ increased expression of genes associated with phospholipid homeostasis and keratinocyte differentiation, along with repression of MMP1 and MMP7 expression, inhibition of MMP enzyme activity, and increased production of collagen proteins by dermal fibroblasts. Lastly, whereas THDC alone reduced viability of keratinocytes exposed to oxidative stress, this effect was completely abrogated by the addition of AZ to THDC. These results show that AZ is an effective antioxidant stabilizer of THDC and that combination of these products may improve ascorbic acid delivery. This provides a step towards reaching the full potential of ascorbate as an active ingredient in topical preparations.
2021-08-17 | GSE182177 | GEO
Project description:Recently, a novel operation method for synchrotron light sources with transversely split beams has been explored to fulfill the rising demand for flexible and high-throughput X-ray sources required in such diverse fields as time-resolved X-ray spectroscopy, molecular chemistry in organic cells, high-resolution medical imaging, quantum materials science or sustainable energy research. Within that novel operation mode, additional stable regions are produced in the horizontal phase space by operating an electron storage ring on a resonance that is driven by the nonlinear sextupole or octupole magnets. In the longitudinal phase space, a similar split can be produced by introducing an oscillation of the synchrotron phase via a modulation of the phase of the radiofrequency resonator. Strong radiation damping in electron storage rings, however, has to be overcome before additional regions in phase space can become populated by particles and form stable islands. This damping mechanism changes the dynamics of the system and causes diffusion between the different islands in phase space, raising the question what kind of equilibrium state exists in the asymptotic temporal limit. In this paper, a finite-differences approximation in rotating action-angle coordinates is used to solve the Vlasov-Fokker-Planck equation and to study the obtained equilibrium states for the longitudinal as well as the transverse case. The number of solution vectors and the magnitude of the corresponding singular values of the matrix of the underlying finite-differences equation are used as abstract indicators to define the required parameter set that provides stable additional beamlets. As a consequence, the beamlets have a stability that is close to that of the main beam in terms of diffusion caused by the radiation damping and quantum excitation.
| S-EPMC9626505 | biostudies-literature