In Vitro and ex Vivo Intestinal Tissue Models to Measure Mucoadhesion of Poly (Methacrylate) and N-Trimethylated Chitosan Polymers

2005 ◽  
Vol 22 (1) ◽  
pp. 38-49 ◽  
Author(s):  
Simon Keely ◽  
Atvinder Rullay ◽  
Carolyn Wilson ◽  
Adrian Carmichael ◽  
Steve Carrington ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Intestinal Tissue ◽  
Tissue Models

ACTIVATED INTESTINAL MUSCLE CELLS PROMOTE PREADIPOCYTE MIGRATION: A NOVEL MECHANISM OF CREEPING FAT FORMATION IN CROHN’S DISEASE

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S34-S34
Author(s):  
Ren Mao ◽  
Genevieve Doyon ◽  
Ilyssa Gordon ◽  
Jiannan Li ◽  
Sinan Lin ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Ex Vivo ◽  
Muscularis Propria ◽  
Dominant Factor ◽  
Stricture Formation ◽  
Intestinal Tissue ◽  
Mesenteric Fat

Abstract Background and Aims Creeping fat, the wrapping of mesenteric fat around the bowel wall, is a typical feature of Crohn’s disease, and is associated with stricture formation and bowel obstruction. How creeping fat forms is unknown, and we interrogated potential mechanisms using novel intestinal tissue and cell interaction systems. Methods Tissues from normal, ulcerative colitis, non-strictured and strictured Crohn’s disease intestinal specimens were obtained. Fresh and decellularized tissue, mesenteric fat explants, primary human adipocytes, pre-adipocytes, muscularis propria cells, and native extracellular matrix were used in multiple ex vivo and in vitro systems involving cell growth, differentiation and migration, proteomics, and integrin expression. Results Crohn’s disease muscularis propria cells produced an extracellular matrix scaffold which is in direct spatial and functional contact with the immediately overlaid creeping fat. The scaffold contained multiple proteins, but only fibronectin production was singularly upregulated by TGF-b1. The muscle cell-derived matrix triggered migration of pre-adipocytes out of mesenteric fat, fibronectin being the dominant factor responsible for their migration. Blockade of α5β1 on the pre-adipocyte surface inhibited their migration out of mesenteric fat and on 3D decellularized intestinal tissue extracellular matrix. Conclusion Crohn’s disease creeping fat appears to result from the migration of pre-adipocytes out of mesenteric fat and differentiation into adipocytes in response to an increased production of fibronectin by activated muscularis propria cells. These new mechanistic insights may lead to novel approaches for prevention of creeping fat-associated stricture formation.

scholarly journals Feruloyl esterase activity is influenced by bile, probiotic intestinal adhesion and milk fat

2016 ◽  
Vol 7 (4) ◽  
pp. 597-607 ◽  
Author(s):  
M.C. Abeijón Mukdsi ◽  
E. Argañaraz Martínez ◽  
A. Perez Chaia ◽  
R.B. Medina
Keyword(s):  
Intestinal Epithelium ◽  
Esterase Activity ◽  
Milk Fat ◽  
Ex Vivo ◽  
Positive Control ◽  
Feruloyl Esterase ◽  
Intestinal Tissue ◽  
Whole Cells ◽  
Methyl Ferulate

Cinnamoyl esterases (CE) are microbial and mammalian intestinal enzymes able to release antioxidant hydroxycinnamic acids from their non-digestible ester-linked forms naturally present in vegetable foods. Previous findings showed that oral administration of Lactobacillus fermentum CRL1446 increased intestinal CE activity and improved oxidative status in mice. The aim of this work was to evaluate the in vitro CE activity of L. fermentum CRL1446 and the effect of bile on this activity, as well as strain resistance to simulated gastrointestinal tract (GIT) conditions and its ability to adhere to intestinal epithelium and influence its basal CE activity. L. fermentum CRL1446 and L. fermentum ATCC14932 (positive control for CE activity) were able to hydrolyse different synthetic hydroxycinnamates, with higher specificity toward methyl ferulate (3,853.73 and 899.19 U/g, respectively). Feruloyl esterase (FE) activity was mainly intracellular in L. fermentum CRL1446 and cell-surface associated in L. fermentum ATCC14932. Both strains tolerated simulated GIT conditions and were able to adhere ex vivo to intestinal epithelium. Pre-incubation of L. fermentum strains with bile increased FE activity in both whole cells and supernatants (~2-fold), compared to controls, suggesting that cells were permeabilised by bile, allowing more substrate to enter the cell and/or leakage of FE enzymes. Three-fold higher FE activities were detected in intestinal tissue fragments with adhered L. fermentum CRL1446 cells compared to control fragments (without bacteria), indicating that this strain provides exogenous FE activity and could stimulate esterase activity in the intestinal mucosa. Finally, we found that milk fat had a negative effect on FE activity of intestinal tissue, in absence or presence of adhered L. fermentum. These results help explaining the increase in intestinal FE activity previously observed in mice fed with L. fermentum CRL1446, and support the potential use of this strain for the development of new functional foods directed to oxidative stress-related ailments.

scholarly journals Efficient Aflatoxin B1 Sequestration by Yeast Cell Wall Extract and Hydrated Sodium Calcium Aluminosilicate Evaluated Using a Multimodal In-Vitro and Ex-Vivo Methodology

Toxins ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 24
Author(s):  
Alexandros Yiannikouris ◽  
Juha Apajalahti ◽  
Hannele Kettunen ◽  
Suvi Ojanperä ◽  
Andrew N. W. Bell ◽  
...  
Keyword(s):  
Cell Wall ◽  
Yeast Cell ◽  
Aflatoxin B1 ◽  
In Vitro Model ◽  
Ex Vivo ◽  
Intestinal Tissue ◽  
Sodium Calcium ◽  
Calcium Aluminosilicate ◽  
Vitro Model

In this work, adsorption of the carcinogenic mycotoxin aflatoxin B1 (AFB1) by two sequestrants—a yeast cell wall-based adsorbent (YCW) and a hydrated sodium calcium aluminosilicate (HSCAS)—was studied across four laboratory models: (1) an in vitro model from a reference method was employed to quantify the sorption capabilities of both sequestrants under buffer conditions at two pH values using liquid chromatography with fluorescence detection (LC-FLD); (2) in a second in vitro model, the influence of the upper gastrointestinal environment on the mycotoxin sorption capacity of the same two sequestrants was studied using a chronic AFB1 level commonly encountered in the field (10 µg/L and in the presence of feed); (3) the third model used a novel ex vivo approach to measure the absorption of 3H-labelled AFB1 in the intestinal tissue and the ability of the sequestrants to offset this process; and (4) a second previously developed ex vivo model readapted to AFB1 was used to measure the transfer of 3H-labelled AFB1 through live intestinal tissue, and the influence of sequestrants on its bioavailability by means of an Ussing chamber system. Despite some sorption effects caused by the feed itself studied in the second model, both in vitro models established that the adsorption capacity of both YCW and HSCAS is promoted at a low acidic pH. Ex vivo Models 3 and 4 showed that the same tested material formed a protective barrier on the epithelial mucosa and that they significantly reduced the transfer of AFB1 through live intestinal tissue. The results indicate that, by reducing the transmembrane transfer rate and reducing over 60% of the concentration of free AFB1, both products are able to significantly limit the bioavailability of AFB1. Moreover, there were limited differences between YCW and HSCAS in their sorption capacities. The inclusion of YCW in the dietary ration could have a positive influence in reducing AFB1′s physiological bioavailability.

Organotypic in vitro human small intestinal tissue models to assess drug toxicity and permeation

2015 ◽  
Vol 238 (2) ◽  
pp. S193-S194 ◽  
Author(s):  
S. Ayehunie ◽  
Z. Stevens ◽  
T. Landry ◽  
M. Tami ◽  
M. Klausner ◽  
...  
Keyword(s):  
Drug Toxicity ◽  
Intestinal Tissue ◽  
Small Intestinal ◽  
Tissue Models

scholarly journals Investigation of Mucoadhesion and Degradation of PCL and PLGA Microcontainers for Oral Drug Delivery

Polymers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1828 ◽  
Author(s):  
Zarmeena Abid ◽  
Mette Dalskov Mosgaard ◽  
Giorgio Manfroni ◽  
Ritika Singh Petersen ◽  
Line Hagner Nielsen ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Glycolic Acid ◽  
Oral Drug Delivery ◽  
Ex Vivo ◽  
The Other ◽  
Oral Drug ◽  
Intestinal Tissue ◽  
Retention Model ◽  
In Vitro Degradation

Microfabricated devices have been introduced as a promising approach to overcome some of the challenges related to oral administration of drugs and, thereby, improve their oral bioavailability. In this study, we fabricate biodegradable microcontainers with different polymers, namely poly-ɛ-caprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) 50:50 and PLGA 75:25 by hot punching. The mucoadhesion of the microcontainers is assessed with an ex vivo retention model on porcine intestinal tissue. Finally, in vitro degradation studies of the biodegradable microcontainers are completed for six weeks in simulated intestinal medium with the addition of pancreatic enzymes. Through SEM inspection, the PLGA 50:50 microcontainers show the first signs of degradation already after two weeks and complete degradation within four weeks, while the other polymers slowly degrade in the medium over several weeks.

Effects of the Tibetan herbal preparation PADMA 28 on blood lipids and lipid oxidisability in subjects with mild hypercholesterolaemia

VASA ◽  
2005 ◽  
Vol 34 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Brunner-La Rocca ◽  
Schindler ◽  
Schlumpf ◽  
Saller ◽  
Suter
Keyword(s):  
Endothelial Dysfunction ◽  
Blood Lipids ◽  
Ex Vivo ◽  
Hdl Cholesterol ◽  
Blood Lipid ◽  
Tibetan Medicine ◽  
Double Blind ◽  
Intraarterial Infusion ◽  
Padma 28

Background: Previous studies showed an anti-atherosclerotic effect of PADMA 28, an herbal formula based on Tibetan medicine. As the mechanisms of action are not fully understood, we investigated whether PADMA 28 may lower blood lipids and lipid oxidisability, and affect early endothelial dysfunction. Patients and methods: Sixty otherwise healthy subjects with total cholesterol ≥5.2 mmol/l and < 8.0 mmol/l were randomly assigned to placebo or PADMA 28, 3 x 2 capsules daily, for 4 weeks (double-blind). Blood lipids (total, LDL-, and HDL-cholesterol, triglycerides, Apo-lipoprotein A1 and B) and ex vivo lipid oxidisability were measured before and after treatment. In a subset of 24 subjects, endothelial function was assessed using venous occlusion plethysmography with intraarterial infusion of acetylcholine. Isolated LDL and plasma both untreated and pre-treated with PADMA 28 extract were oxidised by the radical generator AAPH. Conjugated diene formation was measured at 245 nm. Results: Blood lipids did not change during the study in both groups. In contrast to previous reports in mild hypercholesterolaemia, no endothelial dysfunction was seen and, consequently, was not influenced by therapy. Ex vivo blood lipid oxidisability was significantly reduced with PADMA 28 (area under curve: 5.29 ± 1.62 to 4.99 ± 1.46, p = 0.01), and remained unchanged in the placebo group (5.33 ± 1.88 to 5.18 ± 1.78, p > 0.1). This effect persisted one week after cessation of medication. In vitro experiments confirmed the prevention of lipid peroxidation in the presence of PADMA 28 extracts. Persistent protection was also seen for LDL isolated from PADMA 28-pretreated blood after being subjected to rigorous purification. Conclusions: This study suggests that the inhibition of blood lipid oxidisability by PADMA 28 may play a role in its anti-atherosclerotic effect.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Kutane antioxidative Wirkung von Johanniskrautextrakt (Hypericum perforatum): In-vitro-, Ex-vivo- und In-vivo-Untersuchungen

2012 ◽  
Vol 33 (S 01) ◽  
Author(s):  
MC Meinke ◽  
S Schanzer ◽  
S Arndt ◽  
A Kleemann ◽  
J Lademann
Keyword(s):  
Hypericum Perforatum ◽  
Ex Vivo ◽  
Antioxidative Wirkung
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