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Horasan Sagbasan B, Williams CM, Bell L, Barfoot KL, Poveda C, Walton GE. Inulin and Freeze-Dried Blueberry Intervention Lead to Changes in the Microbiota and Metabolites within In Vitro Studies and in Cognitive Function within a Small Pilot Trial on Healthy Children. Microorganisms 2024; 12:1501. [PMID: 39065269 PMCID: PMC11279127 DOI: 10.3390/microorganisms12071501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 07/15/2024] [Accepted: 07/17/2024] [Indexed: 07/28/2024] Open
Abstract
The relationship between the gut microbiota and cognitive health is complex and bidirectional, being significantly impacted by our diet. Evidence indicates that polyphenols and inulin can impact cognitive function via various mechanisms, one of which is the gut microbiota. In this study, effects of a wild blueberry treatment (WBB) and enriched chicory inulin powder were investigated both in vitro and in vivo. Gut microbiota composition and metabolites, including neurotransmitters, were assessed upon faecal microbial fermentation of WBB and inulin in a gut model system. Secondly, microbiota changes and cognitive function were assessed in children within a small pilot (n = 13) trial comparing WBB, inulin, and a maltodextrin placebo, via a series of tests measuring executive function and memory function, with faecal sampling at baseline, 4 weeks post-intervention and after a 4 week washout period. Both WBB and inulin led to microbial changes and increases in levels of short chain fatty acids in vitro. In vivo significant improvements in executive function and memory were observed following inulin and WBB consumption as compared to placebo. Cognitive benefits were accompanied by significant increases in Faecalibacterium prausnitzii in the inulin group, while in the WBB group, Bacteroidetes significantly increased and Firmicutes significantly decreased (p < 0.05). As such, WBB and inulin both impact the microbiota and may impact cognitive function via different gut-related or other mechanisms. This study highlights the important influence of diet on cognitive function that could, in part, be mediated by the gut microbiota.
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Affiliation(s)
- Buket Horasan Sagbasan
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading RG6 6AP, UK
| | - Claire M Williams
- Department of Psychology, University of Reading, Earley Gate, Whiteknights, Reading RG6 6AL, UK
| | - Lynne Bell
- Department of Psychology, University of Reading, Earley Gate, Whiteknights, Reading RG6 6AL, UK
| | - Katie L Barfoot
- Department of Psychology, University of Reading, Earley Gate, Whiteknights, Reading RG6 6AL, UK
| | - Carlos Poveda
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading RG6 6AP, UK
| | - Gemma E Walton
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading RG6 6AP, UK
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2
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Wollmer E, Ungell AL, Nicolas JM, Klein S. Review of paediatric gastrointestinal physiology relevant to the absorption of orally administered medicines. Adv Drug Deliv Rev 2022; 181:114084. [PMID: 34929252 DOI: 10.1016/j.addr.2021.114084] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 11/13/2021] [Accepted: 12/13/2021] [Indexed: 12/11/2022]
Abstract
Despite much progress in regulations to improve paediatric drug development, there remains a significant need to develop better medications for children. For the design of oral dosage forms, a detailed understanding of the specific gastrointestinal (GI) conditions in children of different age categories and how they differ from GI conditions in adults is essential. Several review articles have been published addressing the ontogeny of GI characteristics, including luminal conditions in the GI tract of children. However, the data reported in most of these reviews are of limited quality because (1) information was cited from very old publications and sometimes low quality sources, (2) data gaps in the original data were filled with textbook knowledge, (3) data obtained on healthy and sick children were mixed, (4) average data obtained on groups of patients were mixed with data obtained on individual patients, and (5) results obtained using investigative techniques that may have altered the outcome of the respective studies were considered. Consequently, many of these reviews draw conclusions that may be incorrect. The aim of the present review was to provide a comprehensive and updated overview of the available original data on the ontogeny of GI luminal conditions relevant to oral drug absorption in the paediatric population. To this end, the PubMed and Web of Science metadatabases were searched for appropriate studies that examined age-related conditions in the oral cavity, esophagus, stomach, small intestine, and colon. Maturation was observed for several GI parameters, and corresponding data sets were identified for each paediatric age group. However, it also became clear that the ontogeny of several GI traits in the paediatric population is not yet known. The review article provides a robust and valuable data set for the development of paediatric in vitro and in silico biopharmaceutical tools to support the development of age-appropriate dosage forms. In addition, it provides important information on existing data gaps and should provide impetus for further systematic and well-designed in vivo studies on GI physiology in children of specific age groups in order to close existing knowledge gaps and to sustainably improve oral drug therapy in children.
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3
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Regional Gastrointestinal Motility in Healthy Children. J Pediatr Gastroenterol Nutr 2021; 73:306-313. [PMID: 34091540 DOI: 10.1097/mpg.0000000000003198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE The aim of the study was to evaluate the safety and use of the 3D-Transit system (Motilis SA, Lausanne, Switzerland) and to describe regional gastrointestinal transit times, segmental colonic transit times, and colonic movement patterns in healthy children. METHODS Twenty-one healthy children (11 girls, median age 10.5 years, range 7-15 years) were included. For evaluation of gastrointestinal transit times and colonic movement patterns, we used the minimally invasive electromagnetic 3D-Transit system. A small electromagnetic capsule (21.5 mm × 8.3 mm) was ingested and tracked through the gastrointestinal tract by a body-worn detector. Regional gastrointestinal transit times were assessed as time between capsule passage of anatomical landmarks. Colonic movement patterns were described and classified based on capsule movement velocity, direction, and distance. RESULTS One child could not swallow the capsule and 20 children completed the study without any discomfort or side-effects. Median whole gut transit time was 33.6 (range 10.7-80.5) hours, median gastric emptying time was 1.9 (range 0.1-22.1) hours, median small intestinal transit time was 4.9 (range 1.1-15.1) hours, and median colonic transit time was 26.4 (range 6.8-74.5) hours. Median ascending colon/cecum transit time was 9.7 (range 0.3-48.1) hours, median transverse colon transit time was 5.6 (range 0.0-11.6) hours, median descending colon transit time was 2.6 (range 0.01-22.3) hours, and median sigmoid colon/rectum transit time was 7.5 (range 0.1-31.6) hours. Colonic movement patterns among children corresponded to those previously described in healthy adults. CONCLUSIONS The 3D-Transit system is a well-tolerated and minimally invasive method for assessment of gastrointestinal motility in children.
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Brinck CE, Mark EB, Klinge MW, Ejerskov C, Sutter N, Schlageter V, Scott SM, Drewes AM, Krogh K. Magnetic tracking of gastrointestinal motility. Physiol Meas 2020; 41:12TR01. [DOI: 10.1088/1361-6579/abcd1e] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Kalsi GK, Grønlund D, Martin J, Drewes AM, Scott SM, Birch MJ. Technical report: Inter- and intra-rater reliability of regional gastrointestinal transit times measured using the 3D-Transit electromagnet tracking system. Neurogastroenterol Motil 2018; 30:e13396. [PMID: 29971879 DOI: 10.1111/nmo.13396] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Accepted: 05/23/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND The 3D-Transit electromagnet tracking system is an emerging tool for the ambulatory assessment of gastrointestinal (GI) transit times and motility patterns, based on the anatomical localization of ingestible electromagnetic capsules. Currently, 3D-Transit recordings are manually analyzed to extract GI transit times. As this is a subjective method, there is some inherent variability in the measurements, which may be experience-dependent. We therefore assessed inter- and intra-rater reliability of GI transit times from 3D-Transit recordings. METHODS Thirty-six 3D-Transit recordings (17 female; median age: 34 years [range: 21-80]) were analyzed twice by 3 raters with varying experience. Each rater manually identified the timestamps when a capsule progressed from antrum to duodenum, and from ileum to right colon. These timestamps, along with the ingestion and expulsion times, were used to determine whole gut (WGTT), gastric emptying (GET), small intestinal (SITT) and colonic (CTT) transit times. Reliability was determined using interclass correlation coefficients (ICCs). KEY RESULTS For capsule progression timestamps, the most and mid-experienced raters had fair to good inter- and excellent intra-rater reliability (ICCmin-max = 0.61-1.00), whereas the inexperienced rater had poor to fair inter- and poor intra-rater reliability (ICCmin-max = 0.28-0.55). GET and SITT reliability between the most and mid-experienced raters was fair (ICCmin-max = 0.61-0.73), while reliability between these raters and the inexperienced rater was poor to fair (ICCmin-max = 0.28-0.55). CTT reliability was excellent between and within all raters (ICCmin-max = 0.92-0.99). CONCLUSIONS & INFERENCES Inexperienced raters provide the least reliable measurements from 3D-Transit recordings, which confirms requirement for adequate training. Automation may improve the reliability of measurements.
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Affiliation(s)
- G K Kalsi
- GI Physiology Unit, The Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.,Clinical Physics, Barts Health NHS Trust, The Royal London Hospital, London, UK
| | - D Grønlund
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - J Martin
- Clinical Physics, Barts Health NHS Trust, The Royal London Hospital, London, UK
| | - A M Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - S M Scott
- GI Physiology Unit, The Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - M J Birch
- GI Physiology Unit, The Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.,Clinical Physics, Barts Health NHS Trust, The Royal London Hospital, London, UK
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6
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Frias B, Phillips AA, Squair JW, Lee AHX, Laher I, Krassioukov AV. Reduced colonic smooth muscle cholinergic responsiveness is associated with impaired bowel motility after chronic experimental high-level spinal cord injury. Auton Neurosci 2018; 216:33-38. [PMID: 30196037 DOI: 10.1016/j.autneu.2018.08.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Revised: 08/29/2018] [Accepted: 08/31/2018] [Indexed: 02/07/2023]
Abstract
The mechanisms underlying bowel dysfunction after high-level spinal cord injury (SCI) are poorly understood. However, impaired supraspinal sympathetic and parasympathetic control is likely a major contributing factor. Disruption of the descending autonomic pathways traversing the spinal cord was achieved by a T3 complete spinal cord transection, and colonic function was examined in vivo and ex vivo four weeks post-injury. Total gastrointestinal transit time (TGTT) was reduced and contractility of the proximal and distal colon was impaired due to reduced M3 receptor sensitivity. These data describe a clinically relevant model of bowel dysfunction after SCI.
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Affiliation(s)
- B Frias
- International Collaboration on Repair Discoveries, University of British Columbia, Canada.
| | - A A Phillips
- International Collaboration on Repair Discoveries, University of British Columbia, Canada; Experimental Medicine Program, University of British Columbia, Canada; Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Canada.
| | - J W Squair
- International Collaboration on Repair Discoveries, University of British Columbia, Canada
| | - A H X Lee
- International Collaboration on Repair Discoveries, University of British Columbia, Canada; Experimental Medicine Program, University of British Columbia, Canada.
| | - I Laher
- Department of Anaesthesiology, Pharmacology and Therapeutics, University of British Columbia, Canada.
| | - A V Krassioukov
- International Collaboration on Repair Discoveries, University of British Columbia, Canada; Experimental Medicine Program, University of British Columbia, Canada; Division of Physical Medicine and Rehabilitation, Department of Medicine, University of British Columbia, Canada; GF Strong Rehabilitation Center, Vancouver Coastal Health, Vancouver, BC, Canada.
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7
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Shamsudhin N, Zverev VI, Keller H, Pane S, Egolf PW, Nelson BJ, Tishin AM. Magnetically guided capsule endoscopy. Med Phys 2017; 44:e91-e111. [PMID: 28437000 DOI: 10.1002/mp.12299] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Revised: 02/22/2017] [Accepted: 04/13/2017] [Indexed: 12/18/2022] Open
Abstract
Wireless capsule endoscopy (WCE) is a powerful tool for medical screening and diagnosis, where a small capsule is swallowed and moved by means of natural peristalsis and gravity through the human gastrointestinal (GI) tract. The camera-integrated capsule allows for visualization of the small intestine, a region which was previously inaccessible to classical flexible endoscopy. As a diagnostic tool, it allows to localize the sources of bleedings in the middle part of the gastrointestinal tract and to identify diseases, such as inflammatory bowel disease (Crohn's disease), polyposis syndrome, and tumors. The screening and diagnostic efficacy of the WCE, especially in the stomach region, is hampered by a variety of technical challenges like the lack of active capsular position and orientation control. Therapeutic functionality is absent in most commercial capsules, due to constraints in capsular volume and energy storage. The possibility of using body-exogenous magnetic fields to guide, orient, power, and operate the capsule and its mechanisms has led to increasing research in Magnetically Guided Capsule Endoscopy (MGCE). This work shortly reviews the history and state-of-art in WCE technology. It highlights the magnetic technologies for advancing diagnostic and therapeutic functionalities of WCE. Not restricting itself to the GI tract, the review further investigates the technological developments in magnetically guided microrobots that can navigate through the various air- and fluid-filled lumina and cavities in the body for minimally invasive medicine.
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Affiliation(s)
- Naveen Shamsudhin
- Multi-Scale Robotics Lab, Institute of Robotics and Intelligent Systems, ETH Zurich, Zurich, CH 8092, Switzerland
| | - Vladimir I Zverev
- Faculty of Physics, M.V. Lomonosov Moscow State University, Moscow, 119991, Russia
| | - Henrik Keller
- KUKA Roboter GmbH, Zugspitzstrasse 140, Augsburg, 86165, Germany
| | - Salvador Pane
- Multi-Scale Robotics Lab, Institute of Robotics and Intelligent Systems, ETH Zurich, Zurich, CH 8092, Switzerland
| | - Peter W Egolf
- Institute of Thermal Sciences and Engineering, University of Applied Sciences of Western Switzerland, Yverdon-les-Bains, CH 1401, Switzerland
| | - Bradley J Nelson
- Multi-Scale Robotics Lab, Institute of Robotics and Intelligent Systems, ETH Zurich, Zurich, CH 8092, Switzerland
| | - Alexander M Tishin
- Faculty of Physics, M.V. Lomonosov Moscow State University, Moscow, 119991, Russia.,Pharmag LLC, Promyshlennaya st 4, Troitsk, Moscow, 142190, Russia
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8
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Brüssow H. How stable is the human gut microbiota? And why this question matters. Environ Microbiol 2016; 18:2779-83. [PMID: 27459371 DOI: 10.1111/1462-2920.13473] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2016] [Accepted: 07/24/2015] [Indexed: 12/29/2022]
Affiliation(s)
- Harald Brüssow
- Nestlé Research Center, Nutrition and Health Research, Host-Microbe Interaction, CH-1000 Lausanne 26, Switzerland.
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9
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Maharaj AR, Edginton AN. Examining Small Intestinal Transit Time as a Function of Age: Is There Evidence to Support Age-Dependent Differences among Children? Drug Metab Dispos 2016; 44:1080-9. [PMID: 26977099 DOI: 10.1124/dmd.115.068700] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Accepted: 03/10/2016] [Indexed: 02/13/2025] Open
Abstract
The small intestine represents the region where the majority of drug and nutrient absorption transpires. Among adults, small intestinal transit kinetics is well delineated; however, the applicability of these values toward children remains unclear. This article serves to examine the relationship between age and mean small intestinal transit time (SITT) based on the available literature. In addition, the influence of alterations in intestinal transit time was explored among children using a model-based approach. Primary literature sources depicting SITT from children to adults were ascertained via the PubMed database. Data were limited to subjects without pathologies that could influence intestinal motility. Random-effect meta-regression models with between-study variability were employed to assess the influence of age on SITT. Three separate models with age as a linear or higher-order (i.e., second- and third-order polynomial) regressor were implemented to assess for the potential of both linear and curvilinear relationships. Examination of the influence of altered intestinal transit kinetics on the absorption of a sustained release theophylline preparation was explored among children between 8 and 14 years using physiologically based pharmacokinetic (PBPK) modeling. Age was not found to be a significant modulator of small intestinal transit within either the linear or higher-order polynomial meta-regression models. PBPK simulations indicated a lack of influence of variations in SITT on the absorption of theophylline from the examined sustained release formulation in older children. Based on the current literature, there is no evidence to suggest that mean SITT differs between children and adults.
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Affiliation(s)
- Anil R Maharaj
- School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada
| | - Andrea N Edginton
- School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada
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10
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Poulsen JL, Nilsson M, Brock C, Sandberg TH, Krogh K, Drewes AM. The Impact of Opioid Treatment on Regional Gastrointestinal Transit. J Neurogastroenterol Motil 2016; 22:282-91. [PMID: 26811503 PMCID: PMC4819867 DOI: 10.5056/jnm15175] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Revised: 12/22/2015] [Accepted: 12/31/2015] [Indexed: 12/28/2022] Open
Abstract
Background/Aims To employ an experimental model of opioid-induced bowel dysfunction in healthy human volunteers, and evaluate the impact of opioid treatment compared to placebo on gastrointestinal (GI) symptoms and motility assessed by questionnaires and regional GI transit times using the 3-dimensional (3D)-Transit system. Methods Twenty-five healthy males were randomly assigned to oxycodone or placebo for 5 days in a double blind, crossover design. Adverse GI effects were measured with the bowel function index, gastrointestinal symptom rating scale, patient assessment of constipation symptom questionnaire, and Bristol stool form scale. Regional GI transit times were determined using the 3D-Transit system, and segmental transit times in the colon were determined using a custom Matlab® graphical user interface. Results GI symptom scores increased significantly across all applied GI questionnaires during opioid treatment. Oxycodone increased median total GI transit time from 22.2 to 43.9 hours (P < 0.001), segmental transit times in the cecum and ascending colon from 5.7 to 9.9 hours (P = 0.012), rectosigmoid colon transit from 2.7 to 9.0 hours (P = 0.044), and colorectal transit time from 18.6 to 38.6 hours (P = 0.001). No associations between questionnaire scores and segmental transit times were detected. Conclusions Self-assessed GI adverse effects and increased GI transit times in different segments were induced during oxycodone treatment. This detailed information about segmental changes in motility has great potential for future interventional head-to-head trials of different laxative regimes for prevention and treatment of constipation.
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Affiliation(s)
- Jakob L Poulsen
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Matias Nilsson
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
| | - Thomas H Sandberg
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Klaus Krogh
- Neurogastroenterology Unit, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Asbjørn M Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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Guerra A, Denis S, le Goff O, Sicardi V, François O, Yao AF, Garrait G, Manzi AP, Beyssac E, Alric M, Blanquet-Diot S. Development and validation of a new dynamic computer-controlled model of the human stomach and small intestine. Biotechnol Bioeng 2015; 113:1325-35. [DOI: 10.1002/bit.25890] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Revised: 11/09/2015] [Accepted: 11/15/2015] [Indexed: 11/12/2022]
Affiliation(s)
- Aurélie Guerra
- EA 4678 Conception; Ingénierie et Développement de l'Aliment et du Médicament Clermont Université; Université d'Auvergne; Centre de Recherche en Nutrition Humaine Auvergne; Faculté de Pharmacie; 28 Place H. Dunant F-63001 Clermont-Ferrand France
| | - Sylvain Denis
- EA 4678 Conception; Ingénierie et Développement de l'Aliment et du Médicament Clermont Université; Université d'Auvergne; Centre de Recherche en Nutrition Humaine Auvergne; Faculté de Pharmacie; 28 Place H. Dunant F-63001 Clermont-Ferrand France
| | - Olivier le Goff
- EA 4678 Conception; Ingénierie et Développement de l'Aliment et du Médicament Clermont Université; Université d'Auvergne; Centre de Recherche en Nutrition Humaine Auvergne; Faculté de Pharmacie; 28 Place H. Dunant F-63001 Clermont-Ferrand France
| | - Vincent Sicardi
- EA 4678 Conception; Ingénierie et Développement de l'Aliment et du Médicament Clermont Université; Université d'Auvergne; Centre de Recherche en Nutrition Humaine Auvergne; Faculté de Pharmacie; 28 Place H. Dunant F-63001 Clermont-Ferrand France
| | | | - Anne-Françoise Yao
- UMR 6620 Laboratoire de Mathématiques; Clermont Université; Université Blaise Pascal; Clermont-Ferrand France
| | - Ghislain Garrait
- EA 4678 Conception; Ingénierie et Développement de l'Aliment et du Médicament Clermont Université; Université d'Auvergne; Centre de Recherche en Nutrition Humaine Auvergne; Faculté de Pharmacie; 28 Place H. Dunant F-63001 Clermont-Ferrand France
| | - Aimé Pacifique Manzi
- EA 4678 Conception; Ingénierie et Développement de l'Aliment et du Médicament Clermont Université; Université d'Auvergne; Centre de Recherche en Nutrition Humaine Auvergne; Faculté de Pharmacie; 28 Place H. Dunant F-63001 Clermont-Ferrand France
| | - Eric Beyssac
- EA 4678 Conception; Ingénierie et Développement de l'Aliment et du Médicament Clermont Université; Université d'Auvergne; Centre de Recherche en Nutrition Humaine Auvergne; Faculté de Pharmacie; 28 Place H. Dunant F-63001 Clermont-Ferrand France
| | - Monique Alric
- EA 4678 Conception; Ingénierie et Développement de l'Aliment et du Médicament Clermont Université; Université d'Auvergne; Centre de Recherche en Nutrition Humaine Auvergne; Faculté de Pharmacie; 28 Place H. Dunant F-63001 Clermont-Ferrand France
| | - Stéphanie Blanquet-Diot
- EA 4678 Conception; Ingénierie et Développement de l'Aliment et du Médicament Clermont Université; Université d'Auvergne; Centre de Recherche en Nutrition Humaine Auvergne; Faculté de Pharmacie; 28 Place H. Dunant F-63001 Clermont-Ferrand France
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12
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Nemiroski A, Ryou M, Thompson CC, Westervelt RM. Swallowable fluorometric capsule for wireless triage of gastrointestinal bleeding. LAB ON A CHIP 2015; 15:4479-4487. [PMID: 26490455 DOI: 10.1039/c5lc00770d] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
Real-time detection of gastrointestinal bleeding remains a major challenge because there does not yet exist a minimally invasive technology that can both i) monitor for blood from an active hemorrhage and ii) uniquely distinguish it from blood left over from an inactive hemorrhage. Such a device would be an important tool for clinical triage. One promising solution, which we have proposed previously, is to inject a fluorescent dye into the blood stream and to use it as a distinctive marker of active bleeding by monitoring leakage into the gastrointestinal tract with a wireless fluorometer. This paper reports, for the first time to our knowledge, the development of a swallowable, wireless capsule with a built-in fluorometer capable of detecting fluorescein in blood, and intended for monitoring gastrointestinal bleeding in the stomach. The embedded, compact fluorometer uses pinholes to define a microliter sensing volume and to eliminate bulky optical components. The proof-of-concept capsule integrates optics, low-noise analog sensing electronics, a microcontroller, battery, and low power Zigbee radio, all into a cylindrical package measuring 11 mm × 27 mm and weighing 10 g. Bench-top experiments demonstrate wireless fluorometry with a limit-of-detection of 20 nM aqueous fluorescein. This device represents a major step towards a technology that would enable simple, rapid detection of active gastrointestinal bleeding, a capability that would save precious time and resources and, ultimately, reduce complications in patients.
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Affiliation(s)
- A Nemiroski
- Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford St., Cambridge, MA 02138, USA.
| | - M Ryou
- Division of Gastroenterology, Brigham & Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
| | - C C Thompson
- Division of Gastroenterology, Brigham & Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
| | - R M Westervelt
- John A. Paulson School of Engineering and Applied Sciences, Harvard University, 9 Oxford St., Cambridge, MA 02138, USA and Department of Physics, Harvard University, 9 Oxford St., Cambridge, MA 02138, USA.
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13
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Kearns GL, Chumpitazi BP, Abdel-Rahman SM, Garg U, Shulman RJ. Systemic exposure to menthol following administration of peppermint oil to paediatric patients. BMJ Open 2015; 5:e008375. [PMID: 26270949 PMCID: PMC4538270 DOI: 10.1136/bmjopen-2015-008375] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVE Peppermint oil (PMO) has been used to treat abdominal ailments dating to ancient Egypt, Greece and Rome. Despite its increasing paediatric use, as in irritable bowel syndrome (IBS) treatment, the pharmacokinetics (PK) of menthol in children given PMO has not been explored. DESIGN AND SETTING Single-site, exploratory pilot study of menthol PK following a single 187 mg dose of PMO. Subjects with paediatric Rome II defined (IBS; n=6, male and female, 7-15 years of age) were enrolled. Blood samples were obtained before PMO administration and at 10 discrete time points over a 12 h postdose period. Menthol was quantitated from plasma using a validated gas chromatography mass spectrometry technique. Menthol PK parameters were determined using a standard non-compartmental approach. RESULTS Following a dose of PMO, a substantial lag time (range 1-4 h) was seen in all subjects for the appearance of menthol which in turn, produced a delayed time of peak (Tmax=5.3 ± 2.4 h) plasma concentration (Cmax=698.2 ± 245.4 ng/mL). Tmax and Tlag were significantly more variable than the two exposure parameters; Cmax, mean residence time and total area under the curve (AUC=4039.7 ± 583.8 ng/mL × h) which had a coefficient of variation of <20%. CONCLUSIONS Delayed appearance of menthol in plasma after oral PMO administration in children is likely a formulation-specific event which, in IBS, could increase intestinal residence time of the active ingredient. Our data also demonstrate the feasibility of using menthol PK in children with IBS to support definitive studies of PMO dose-effect relationships.
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Affiliation(s)
- Gregory L Kearns
- Departments of Pediatrics, University of Missouri—Kansas City, Kansas City, Missouri, USA
- Departments of Pharmacology, University of Missouri—Kansas City, Kansas City, Missouri, USA
- Divisions of Pediatric Pharmacology, Medical Toxicology &Therapeutic Innovation, Children's Mercy Hospitals and Clinics, Kansas City, Missouri, USA
| | - Bruno Pedro Chumpitazi
- Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
- Division of Pediatric Gastroenterology, Texas Children's Hospital, Houston, Texas, USA
| | - Susan M Abdel-Rahman
- Departments of Pediatrics, University of Missouri—Kansas City, Kansas City, Missouri, USA
- Divisions of Pediatric Pharmacology, Medical Toxicology &Therapeutic Innovation, Children's Mercy Hospitals and Clinics, Kansas City, Missouri, USA
| | - Uttam Garg
- Departments of Pathology, University of Missouri—Kansas City, Kansas City, Missouri, USA
- Clinical Laboratory Medicine, Children's Mercy Hospitals and Clinics, Kansas City, Missouri, USA
| | - Robert J Shulman
- Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
- Division of Pediatric Gastroenterology, Texas Children's Hospital, Houston, Texas, USA
- Children's Nutrition Research Center, Houston, Texas, USA
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Keuchel M, Kurniawan N, Baltes P, Bandorski D, Koulaouzidis A. Quantitative measurements in capsule endoscopy. Comput Biol Med 2015; 65:333-47. [PMID: 26299419 DOI: 10.1016/j.compbiomed.2015.07.016] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Revised: 07/16/2015] [Accepted: 07/17/2015] [Indexed: 12/14/2022]
Abstract
This review summarizes several approaches for quantitative measurement in capsule endoscopy. Video capsule endoscopy (VCE) typically provides wireless imaging of small bowel. Currently, a variety of quantitative measurements are implemented in commercially available hardware/software. The majority is proprietary and hence undisclosed algorithms. Measurement of amount of luminal contamination allows calculating scores from whole VCE studies. Other scores express the severity of small bowel lesions in Crohn׳s disease or the degree of villous atrophy in celiac disease. Image processing with numerous algorithms of textural and color feature extraction is further in the research focuses for automated image analysis. These tools aim to select single images with relevant lesions as blood, ulcers, polyps and tumors or to omit images showing only luminal contamination. Analysis of motility pattern, size measurement and determination of capsule localization are additional topics. Non-visual wireless capsules transmitting data acquired with specific sensors from the gastrointestinal (GI) tract are available for clinical routine. This includes pH measurement in the esophagus for the diagnosis of acid gastro-esophageal reflux. A wireless motility capsule provides GI motility analysis on the basis of pH, pressure, and temperature measurement. Electromagnetically tracking of another motility capsule allows visualization of motility. However, measurement of substances by GI capsules is of great interest but still at an early stage of development.
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Affiliation(s)
- M Keuchel
- Clinic for Internal Medicine, Bethesda Krankenhaus Bergedorf, Glindersweg 80, 21029 Hamburg, Germany.
| | - N Kurniawan
- Clinic for Internal Medicine, Bethesda Krankenhaus Bergedorf, Glindersweg 80, 21029 Hamburg, Germany
| | - P Baltes
- Clinic for Internal Medicine, Bethesda Krankenhaus Bergedorf, Glindersweg 80, 21029 Hamburg, Germany
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15
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Gregersen T, Haase AM, Schlageter V, Gronbaek H, Krogh K. Regional Gastrointestinal Transit Times in Patients With Carcinoid Diarrhea: Assessment With the Novel 3D-Transit System. J Neurogastroenterol Motil 2015; 21:423-32. [PMID: 26130638 PMCID: PMC4496908 DOI: 10.5056/jnm15035] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2015] [Revised: 04/04/2015] [Accepted: 04/05/2015] [Indexed: 12/13/2022] Open
Abstract
Background/Aims The paucity of knowledge regarding gastrointestinal motility in patients with neuroendocrine tumors and carcinoid diarrhea restricts targeted treatment. 3D-Transit is a novel, minimally invasive, ambulatory method for description of gastrointestinal motility. The system has not yet been evaluated in any group of patients. We aimed to test the performance of 3D-Transit in patients with carcinoid diarrhea and to compare the patients’ regional gastrointestinal transit times (GITT) and colonic motility patterns with those of healthy subjects. Methods Fifteen healthy volunteers and seven patients with neuroendocrine tumor and at least 3 bowel movements per day were investigated with 3D-Transit and standard radiopaque markers. Results Total GITT assessed with 3D-Transit and radiopaque markers were well correlated (Spearman’s rho = 0.64, P = 0.002). Median total GITT was 12.5 (range: 8.5–47.2) hours in patients versus 25.1 (range: 13.1–142.3) hours in healthy (P = 0.007). There was no difference in gastric emptying (P = 0.778). Median small intestinal transit time was 3.8 (range: 1.4–5.5) hours in patients versus 4.4 (range: 1.8–7.2) hours in healthy subjects (P = 0.044). Median colorectal transit time was 5.2 (range: 2.9–40.1) hours in patients versus 18.1 (range: 5.0–134.0) hours in healthy subjects (P = 0.012). Median frequency of pansegmental colonic movements was 0.45 (range: 0.03–1.02) per hour in patients and 0.07 (range: 0–0.61) per hour in healthy subjects (P = 0.045). Conclusions Three-dimensional Transit allows assessment of regional GITT in patients with diarrhea. Patients with carcinoid diarrhea have faster than normal gastrointestinal transit due to faster small intestinal and colorectal transit times. The latter is caused by an increased frequency of pansegmental colonic movements.
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Affiliation(s)
- Tine Gregersen
- Neurogastroenterology Unit, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Anne-Mette Haase
- Neurogastroenterology Unit, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Henning Gronbaek
- Neurogastroenterology Unit, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Klaus Krogh
- Neurogastroenterology Unit, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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16
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Koulaouzidis A, Iakovidis DK, Karargyris A, Rondonotti E. Wireless endoscopy in 2020: Will it still be a capsule? World J Gastroenterol 2015; 21:5119-5130. [PMID: 25954085 PMCID: PMC4419052 DOI: 10.3748/wjg.v21.i17.5119] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2014] [Revised: 01/26/2015] [Accepted: 03/19/2015] [Indexed: 02/06/2023] Open
Abstract
Currently, the major problem of all existing commercial capsule devices is the lack of control of movement. In the future, with an interface application, the clinician will be able to stop and direct the device into points of interest for detailed inspection/diagnosis, and therapy delivery. This editorial presents current commercially-available new designs, European projects and delivery capsule and gives an overview of the progress required and progress that will be achieved -according to the opinion of the authors- in the next 5 year leading to 2020.
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