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

An in vitro assessment of tissue compression damage during circular stapler approximation tests, measuring expulsion of intracellular fluid and force

2001 ◽  
Vol 215 (6) ◽  
pp. 589-597 ◽  
Author(s):  
J McGuire ◽  
I C Wright ◽  
J N Leverment
Keyword(s):  
Large Bowel ◽  
Strain Range ◽  
Materials Testing ◽  
Force Measurements ◽  
Intestinal Tissue ◽  
Tissue Samples ◽  
Intracellular Fluid ◽  
In Vitro Assessment ◽  
Small Intestinal

Circular staplers are among the many instruments used during minimally invasive or open surgery that should approximate soft tissue within safe compression limits. Previous in vivo sutureline blood flow measurement has suggested a safe thickness reduction limit of 25 per cent during circular stapling procedures. The present work investigates in vitro assessment of the maximum safe compression of large and small porcine intestines, measuring the required compressive force and the expelled intracellular fluid (measured as a potassium solution). A test-rig mounted on a materials testing machine allowed staplers of three sizes to compress tissue samples to thicknesses ranging from 90 to 45 per cent of original thickness. The expelled fluid was collected in 40 ml of 0.9 per cent NaCl and analysed in a flame photometer. The force measurements indicated that the small intestinal tissue samples underwent a sharp increase in stiffness over a strain range of 0.19-0.34. The large bowel tissue underwent a similar increase in stiffness over a planar compressive strain range of 0.19-0.40. The regularity of the potassium output results was limited, making it difficult to draw firm conclusions, although there was some indication that the potassium output from small intestinal tissue may change from erratic to approximately linear at a strain of approximately 0.19, while that of the large bowel tissue appeared to be approximately linear over the entire strain range tested. From the force measurements, it is concluded that strain-induced structural change may help provide a useful definition of safe tissue approximation. The possible implications for reduced dehiscence (wound disintegration) and stricture incidence in stapled anastomoses are discussed.

3D-human small intestinal tissue model as an alternate to animal testing to predict drug toxicity, permeability, and metabolism

2017 ◽  
Vol 280 ◽  
pp. S271 ◽  
Author(s):  
Seyoum Ayehunie ◽  
Zachary Stevens ◽  
Timothy Landry ◽  
Alex Armento ◽  
Mitchell Klausner ◽  
...  
Keyword(s):  
Drug Toxicity ◽  
Animal Testing ◽  
Intestinal Tissue ◽  
Tissue Model ◽  
Small Intestinal

Release of prostaglandins by small intestinal tissue of man and rat in vitro and the effect of endotoxin in the rat in vivo

1981 ◽  
Vol 21 ◽  
pp. 9-14 ◽  
Author(s):  
B.M. Peskar ◽  
H. Weiler ◽  
E.E. Kröner ◽  
B.A. Peskar
Keyword(s):  
Intestinal Tissue ◽  
Small Intestinal

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

scholarly journals Role of Intimin and Bundle-Forming Pili in Enteropathogenic Escherichia coli Adhesion to Pediatric Intestinal Tissue In Vitro

1998 ◽  
Vol 66 (4) ◽  
pp. 1570-1578 ◽  
Author(s):  
Susan Hicks ◽  
Gad Frankel ◽  
James B. Kaper ◽  
Gordon Dougan ◽  
Alan D. Phillips
Keyword(s):  
Escherichia Coli ◽  
Organ Culture ◽  
Single Amino Acid ◽  
Intestinal Biopsy ◽  
Virulence Plasmid ◽  
Lesion Formation ◽  
Intestinal Tissue ◽  
Small Intestinal

ABSTRACT Attaching and effacing (A/E) lesion formation is central to enteropathogenic Escherichia coli (EPEC) pathogenesis. In vitro experiments with human epithelial cell lines have implicated virulence plasmid-encoded bundle-forming pili (BFP) in initial binding and intimin in intimate attachment and A/E lesion formation. This study investigated the role of BFP and intimin in EPEC interactions with pediatric small intestinal biopsy tissue in in vitro organ culture. Organ culture infections (2 to 8 h) were performed with E2348/69 (a wild-type EPEC O127:H6 clinical isolate) and E2348/69 derivatives including CVD206 (eae deficient), CVD206(pCVD438) (eae-complemented CVD206), CVD206(pCVD438/01) (expressing intimin, which is nonfunctional due to a single amino acid substitution), JPN15 (spontaneous EPEC adherence factor virulence plasmid-cured E2348/69), and 31-6-1(1) (E2348/69 with a TnphoA insertion inactivation mutation in the virulence plasmid-encoded bfpA gene). Scanning and transmission electron microscopy revealed that after 8 h E2348/69 and CVD206(pCVD438) (both Int+ BFP+) adhered to all specimens, causing A/E lesions with surrounding microvillous elongation. JPN15 and 31-6-1(1) (both Int+BFP−) adhered and caused A/E lesions although bacteria adhered in “flat,” two-dimensional groups. CVD206 and CVD206(pCVD438/01) (both Int− BFP+) did not adhere to any sample, and no pathological tissue changes were seen. Thus, in human intestinal organ culture, BFP do not appear to be involved in the initial stages of EPEC nonintimate adhesion but are implicated in the formation of complex, three-dimensional colonies via bacterium-bacterium interactions. Intimin appears to play an essential role in establishing colonization of EPEC on pediatric small intestinal tissue.

Effects of Transport Medium Composition on in vitro Drug Permeation across Excised Pig Intestinal Tissue

2020 ◽  
Vol 10 ◽  
Author(s):  
Bianca Peterson ◽  
Henrico Heystek ◽  
Josias H. Hamman ◽  
Johan D. Steyn
Keyword(s):  
Medium Composition ◽  
Screening Tests ◽  
Intestinal Tissue ◽  
Predictive Values ◽  
Transport Medium ◽  
Intestinal Fluids ◽  
Lower Permeability ◽  
The Impact ◽  
Simulated Intestinal Fluids

Background:: Knowledge of the permeation characteristics of new chemical entities across biological membranes is essential to drug research and development. Transport medium composition may affect the absorption of compounds during in vitro drug transport testing. To preserve the predictive values of screening tests, the possible influence of transport media on the solubility of model drugs, and on the activities of tight junctions and efflux transporter proteins (e.g. P-glycoprotein) must be known. Objective:: The aim of this study was to compare the impact of different transport media on the bi-directional transport of standard compounds, selected from the four classes of the Biopharmaceutical Classification System (BCS), across excised pig intestinal tissue. Methods:: The Sweetana-Grass diffusion apparatus was used for the transport studies. Krebs-Ringer bicarbonate (KRB) buffer and simulated intestinal fluids in the fed (FeSSIF) and fasted (FaSSIF) states were used as the three transport media, while the chosen compounds were abacavir (BCS class 1), dapsone (BCS class 2), lamivudine (BCS class 3) and furosemide (BCS class 4). Results:: Abacavir exhibited lower permeability in both the simulated intestinal fluids than in the KRB buffer. Dapsone showed similar permeability in all media. Lamivudine exhibited lower permeability in FaSSIF than in the other two media. Furosemide exhibited improved transport with pronounced efflux in FaSSIF. Conclusion:: Different permeation behaviors were observed for the selected drugs in the respective media, which may have resulted from their different physico-chemical properties, as well as from the effects that dissimilar transport media components had on excised pig intestinal tissue.

In vitro digestion of polysaccharides: InfoGest protocol and use of small intestinal extract from rat

2021 ◽  
Vol 140 ◽  
pp. 110054
Author(s):  
Pablo Gallego-Lobillo ◽  
Alvaro Ferreira-Lazarte ◽  
Oswaldo Hernández-Hernández ◽  
Mar Villamiel
Keyword(s):  
In Vitro Digestion ◽  
Small Intestinal

scholarly journals 695 Oral delivery of a microbial extracellular vesicle induces potent anti-tumor immunity in mice

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A737-A737
Author(s):  
Loise Francisco-Anderson ◽  
Loise Francisco-Anderson ◽  
Mary Abdou ◽  
Michael Goldberg ◽  
Erin Troy ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Extracellular Vesicles ◽  
Tumor Immunity ◽  
Extracellular Vesicle ◽  
The Body ◽  
Checkpoint Inhibition ◽  
Small Intestinal ◽  
The Impact

BackgroundThe small intestinal axis (SINTAX) is a network of anatomic and functional connections between the small intestine and the rest of the body. It acts as an immunosurveillance system, integrating signals from the environment that affect physiological processes throughout the body. The impact of events in the gut in the control of tumor immunity is beginning to be appreciated. We have previously shown that an orally delivered single strain of commensal bacteria induces anti-tumor immunity preclinically via pattern recognition receptor-mediated activation of innate and adaptive immunity. Some bacteria produce extracellular vesicles (EVs) that share molecular content with the parent bacterium in a particle that is roughly 1/1000th the volume in a non-replicating form. We report here an orally-delivered and gut-restricted bacterial EV which potently attenuates tumor growth to a greater extent than whole bacteria or checkpoint inhibition.MethodsEDP1908 is a preparation of extracellular vesicles produced by a gram-stain negative strain of bacterium of the Oscillospiraceae family isolated from a human donor. EDP1908 was selected for its immunostimulatory profile in a screen of EVs from a range of distinct microbial strains. Its mechanism of action was determined by ex vivo analysis of the tumor microenvironment (TME) and by in vitro functional studies with murine and human cells.ResultsOral treatment of tumor-bearing mice with EDP1908 shows superior control of tumor growth compared to checkpoint inhibition (anti-PD-1) or an intact microbe. EDP1908 significantly increased the percentage of IFNγ and TNF producing CD8+ CTLs, NK cells, NKT cells and CD4+ cells in the tumor microenvironment (TME). EDP1908 also increased tumor-infiltrating dendritic cells (DC1 and DC2). Analysis of cytokines in the TME showed significant increases in IP-10 and IFNg production in mice treated with EDP1908, creating an environment conducive to the recruitment and activation of anti-tumor lymphocytes.ConclusionsThis is the first report of striking anti-tumor effects of an orally delivered microbial extracellular vesicle. These data point to oral EVs as a new class of immunotherapeutic drugs. They are particularly effective at harnessing the biology of the small intestinal axis, acting locally on host cells in the gut to control distal immune responses within the TME. EDP1908 is in preclinical development for the treatment of cancer.Ethics ApprovalPreclinical murine studies were conducted under the approval of the Avastus Preclinical Services’ Ethics Board. Human in vitro samples were attained by approval of the IntegReview Ethics Board; informed consent was obtained from all subjects.

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