Characterization of the Ascending Colon Fluids in Ulcerative Colitis

Vertzoni, Maria; Goumas, Konstantinos; Söderlind, Erik; Abrahamsson, Bertil; Dressman, Jennifer B.; Poulou, Androniki; Reppas, Christos

doi:10.1007/s11095-010-0158-y

Cited by 31 publications

(29 citation statements)

References 23 publications

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“…Procedures for obtaining approval for sample collection, methodology for sample collection and treatment, as well as collection of the liquid phase of colonic samples have been described previously . Upon collection, liquid phases were separated in small vials and stored at −70°C until a specific analysis required for the objectives of this study was performed.…”

Section: Methodsmentioning

confidence: 99%

“…The physicochemical data of the liquid phase with high cholesterol content (HC sample) and the liquid phase with low cholesterol content (LC sample) investigated in this study are presented in Table . The high osmolarity of the HC sample implies that the ascending colon from which this particular sample had been collected may have not been fully recovered from the colon preparation procedure applied before colonoscopy (Table ) . Such possibility, however, does not decrease the usefulness of the HC sample because similar cholesterol levels have been measured in hyposmotic or isosmotic colonic contents .…”

Section: Methodsmentioning

confidence: 99%

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Unravelling the ultrastructure of ascending colon fluids from patients with ulcerative colitis by cryogenic transmission electron microscopy

Müllertz

Fatouros

Vertzoni

et al. 2013

Journal of Pharmacy and Pharmacology

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Unravelling the ultrastructure of ascending colon fluids from patients with ulcerative colitis by cryogenic transmission electron microscopy

Müllertz

Fatouros

Vertzoni

et al. 2013

Journal of Pharmacy and Pharmacology

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“…These results corroborate observations in human patients with IBD, including neonatal necrotizing enterocolitis, Crohn’s disease, and ulcerative colitis, where elevated osmolarity in fecal fluid within the colon is noted (18, 19, 24). Furthermore, the fecal osmolarity elevation in Crohn’s disease patients shows a close correlation with disease severity (18, 19, 129). Under physiological conditions, both pro- and anti-inflammatory cytokines are present within the gastrointestinal tract, with the pro-inflammatory cytokines being kept in check by the anti-inflammatory cytokines.…”

Section: Inflammatory Bowel Diseasementioning

confidence: 97%

“…It is characterized by chronic inflammation of one or more regions of the gastrointestinal tract with reoccurring flare-ups (128, 129). Crohn’s disease and ulcerative colitis comprise the most common forms of IBD.…”

Section: Inflammatory Bowel Diseasementioning

confidence: 99%

The role of hyperosmotic stress in inflammation and disease

Brocker

Thompson²,

Vasiliou

2012

BioMolecular Concepts

230

213

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Hyperosmotic stress is an often overlooked process that potentially contributes to a number of human diseases. Whereas renal hyperosmolarity is a well-studied phenomenon, recent research provides evidence that many non-renal tissues routinely experience hyperosmotic stress that may contribute significantly to disease initiation and progression. Moreover, a growing body of evidence implicates hyperosmotic stress as a potent inflammatory stimulus by triggering proinflammatory cytokine release and inflammation. Under physiological conditions, the urine concentrating mechanism within the inner medullary region of the mammalian kidney exposes cells to high extracellular osmolarity. As such, renal cells have developed many adaptive strategies to compensate for increased osmolarity. Hyperosmotic stress is linked to many maladies, including acute and chronic, as well as local and systemic, inflammatory disorders. Hyperosmolarity triggers cell shrinkage, oxidative stress, protein carbonylation, mitochondrial depolarization, DNA damage, and cell cycle arrest, thus rendering cells susceptible to apoptosis. However, many adaptive mechanisms exist to counter the deleterious effects of hyperosmotic stress, including cytoskeletal rearrangement and up-regulation of antioxidant enzymes, transporters, and heat shock proteins. Osmolyte synthesis is also up-regulated and many of these compounds have been shown to reduce inflammation. The cytoprotective mechanisms and associated regulatory pathways that accompany the renal response to hyperosmolarity are found in many non-renal tissues, suggesting cells are commonly confronted with hyperosmotic conditions. Osmoadaptation allows cells to survive and function under potentially cytotoxic conditions. This review covers the pathological consequences of hyperosmotic stress in relation to disease and emphasizes the importance of considering hyperosmolarity in inflammation and disease progression.

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“…For evaluation of colonic absorption, knowledge of drug solubility and dissolution rates in the region is required but relevant estimations remain problematic because of limited information on the conditions prevailing in the lower intestine . In recent years, our understanding on the environment in the lower intestine has been increased . Solubility of lipophilic APIs in the lumen of the ascending colon seems to be different than in the contents of stomach and/or upper intestine during fasting state .…”

Section: Introductionmentioning

confidence: 99%

Two-Stage Single-Compartment Models to Evaluate Dissolution in the Lower Intestine

Markopoulos

Vertzoni

Symillides

et al. 2015

Journal of Pharmaceutical Sciences

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The purpose was to propose two-stage single-compartment models for evaluating dissolution characteristics in distal ileum and ascending colon, under conditions simulating the bioavailability and bioequivalence studies in fasted and fed state by using the mini-paddle and the compendial flow-through apparatus (closed-loop mode). Immediate release products of two highly dosed active pharmaceutical ingredients (APIs), sulfasalazine and L-870,810, and one mesalamine colon targeting product were used for evaluating their usefulness. Change of medium composition simulating the conditions in distal ileum (SIFileum ) to a medium simulating the conditions in ascending colon in fasted state and in fed state was achieved by adding an appropriate solution in SIFileum . Data with immediate release products suggest that dissolution in lower intestine is substantially different than in upper intestine and is affected by regional pH differences > type/intensity of fluid convection > differences in concentration of other luminal components. Asacol® (400 mg/tab) was more sensitive to type/intensity of fluid convection. In all the cases, data were in line with available human data. Two-stage single-compartment models may be useful for the evaluation of dissolution in lower intestine. The impact of type/intensity of fluid convection and viscosity of media on luminal performance of other APIs and drug products requires further exploration.

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Characterization of the Ascending Colon Fluids in Ulcerative Colitis

Abstract: Variations in fluid composition of the ascending colon with activity and severity of ulcerative colitis may have an impact on the performance of orally administered products that are targeted to release the therapeutic agent in the colon.

Cited by 31 publications

References 23 publications

Unravelling the ultrastructure of ascending colon fluids from patients with ulcerative colitis by cryogenic transmission electron microscopy

Unravelling the ultrastructure of ascending colon fluids from patients with ulcerative colitis by cryogenic transmission electron microscopy

The role of hyperosmotic stress in inflammation and disease

Two-Stage Single-Compartment Models to Evaluate Dissolution in the Lower Intestine

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