A preclinical feasibility study of endoscopic barostat: A possible diagnostic tool for visceral hypersensitivity in functional dyspepsia

Introduction: Diagnosing functional dyspepsia requires excluding organic disease and gastrointestinal function evaluation; however, there are no modalities to evaluate these simultaneously. This preclinical study examined the possibility of an endoscopic barostat. Methods: Ultrathin endoscopy and our newly developed pressure-regulated endoscopic insufflator, which insufflates the gastrointestinal tract until the preset pressure is achieved, were used. The actual intragastric pressure was measured using an optical fiber manometer placed in the stomach. Experiment-1: in an ex vivo experiment, we insufflated the isolated stomach and verified whether the intragastric pressure reached the preset pressure. Experiment-2: we inserted the endoscope orally in a porcine stomach, insufflated the stomach, and verified whether the intragastric pressure reached the preset pressure. Finally, we insufflated the stomach at a random pressure to verify the functional tests for proof-of-concept. Results: Experiment-1: the intragastric pressure reached the preset pressure. After reaching the plateau, the pressure remained stable at the preset pressure (Huber M-value: 1.015, Regression line: 0.988, 95% confidence interval [CI]: 0.994–0.994). Experiment-2: the intragastric pressure reached the preset pressure. After reaching the plateau, the pressure remained stable at the preset pressure (Huber M-value: 1.018, Regression line: 0.971, 95% CI: 0.985–0.986). At randomly preset pressures, the transendoscopic theoretical intragastric pressure detected by the insufflator was correlated with the actual pressure measured by the pressure manometer. Conclusions: This proof-of-concept study shows that a pressure-regulated endoscopic insufflator provides stable intragastric pressure at the preset level, with the potential of an endoscopic barostat to assess visceral the hypersensitivity related to functional dyspepsia.

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64Cu-ATSM/64Cu-Cl2 and their relationship to hypoxia in glioblastoma: a preclinical study

EJNMMI Research ◽

10.1186/s13550-019-0586-6 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Elodie A. Pérès ◽

Jérôme Toutain ◽

Louis-Paul Paty ◽

Didier Divoux ◽

Méziane Ibazizène ◽

...

Keyword(s):

Ex Vivo ◽

In Vitro Study ◽

Tumor Location ◽

Preclinical Study ◽

Significant Rise ◽

Lower Oxygen ◽

Cu Complexes ◽

Ex Vivo Study

Abstract Background Diacetyl-bis(N4-methylthiosemicarbazone), labeled with 64Cu (64Cu-ATSM) has been suggested as a promising tracer for imaging hypoxia. However, various controversial studies highlighted potential pitfalls that may disable its use as a selective hypoxic marker. They also highlighted that the results may be tumor location dependent. Here, we first analyzed uptake of Cu-ATSM and its less lipophilic counterpart Cu-Cl2 in the tumor over time in an orthotopic glioblastoma model. An in vitro study was also conducted to investigate the hypoxia-dependent copper uptake in tumor cells. We then further performed a comprehensive ex vivo study to compare 64Cu uptake to hypoxic markers, specific cellular reactions, and also transporter expression. Methods μPET was performed 14 days (18F-FMISO), 15 days (64Cu-ATSM and 64Cu-Cl2), and 16 days (64Cu-ATSM and 64Cu-Cl2) after C6 cell inoculation. Thereafter, the brains were withdrawn for further autoradiography and immunohistochemistry. C6 cells were also grown in hypoxic workstation to analyze cellular uptake of Cu complexes in different oxygen levels. Results In vivo results showed that Cu-ASTM and Cu-Cl2 accumulated in hypoxic areas of the tumors. Cu-ATSM also stained, to a lesser extent, non-hypoxic regions, such as regions of astrogliosis, with high expression of copper transporters and in particular DMT-1 and CTR1, and also characterized by the expression of elevated astrogliosis. In vitro results show that 64Cu-ATSM showed an increase in the uptake only in severe hypoxia at 0.5 and 0.2% of oxygen while for 64Cu-Cl2, the cell retention was significantly increased at 5% and 1% of oxygen with no significant rise at lower oxygen percentages. Conclusion In the present study, we show that Cu-complexes undoubtedly accumulate in hypoxic areas of the tumors. This uptake may be the reflection of a direct dependency to a redox metabolism and also a reflection of hypoxic-induced overexpression of transporters. We also show that Cu-ATSM also stained non-hypoxic regions such as astrogliosis.

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Ultrasonic microrheology for ex vivo skin explants monitoring: A proof of concept

Biosensors and Bioelectronics ◽

10.1016/j.bios.2021.113831 ◽

2021 ◽

pp. 113831

Author(s):

Vincent Gauthier ◽

Alice Lemarquand ◽

Emmanuel Caplain ◽

Nicolas Wilkie-Chancellier ◽

Stéphane Serfaty

Keyword(s):

Ex Vivo ◽

Proof Of Concept ◽

Skin Explants

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More efficient exchange of sickle red blood cells can be achieved by exchanging the densest red blood cells: An ex vivo proof of concept study

Transfusion and Apheresis Science ◽

10.1016/j.transci.2018.12.005 ◽

2019 ◽

Vol 58 (1) ◽

pp. 100-106

Author(s):

Suzanne R. Thibodeaux ◽

Yvette C. Tanhehco ◽

Leah Irwin ◽

Lita Jamensky ◽

Kevin Schell ◽

...

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Ex Vivo ◽

Proof Of Concept ◽

Concept Study ◽

Sickle Red Blood Cells

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Thermochemical Ablation in an Ex-vivo Porcine Liver Model Using Acetic Acid and Sodium Hydroxide: Proof of Concept

Journal of Vascular and Interventional Radiology ◽

10.1016/j.jvir.2010.06.012 ◽

2010 ◽

Vol 21 (10) ◽

pp. 1573-1578 ◽

Cited By ~ 12

Author(s):

Joseph L. Farnam ◽

Benjamin C. Smith ◽

Brandon R. Johnson ◽

Rodolfo Estrada ◽

Theresa L. Edelman ◽

...

Keyword(s):

Acetic Acid ◽

Sodium Hydroxide ◽

Ex Vivo ◽

Proof Of Concept ◽

Porcine Liver ◽

Liver Model

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Proof of concept of a multimodal intravital molecular imaging system for tumour transpathology investigation

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-021-05574-y ◽

2021 ◽

Author(s):

Zhen Liu ◽

Tao Cheng ◽

Stephan Düwel ◽

Ziying Jian ◽

Geoffrey J. Topping ◽

...

Keyword(s):

Molecular Imaging ◽

Imaging System ◽

Ex Vivo ◽

Fiducial Markers ◽

Proof Of Concept ◽

Registration Accuracy ◽

Microscopic Imaging ◽

Window Chamber

Abstract Background Transpathology highlights the interpretation of the underlying physiology behind molecular imaging. However, it remains challenging due to the discrepancies between in vivo and in vitro measurements and difficulties of precise co-registration between trans-scaled images. This study aims to develop a multimodal intravital molecular imaging (MIMI) system as a tool for in vivo tumour transpathology investigation. Methods The proposed MIMI system integrates high-resolution positron imaging, magnetic resonance imaging (MRI) and microscopic imaging on a dorsal skin window chamber on an athymic nude rat. The window chamber frame was designed to be compatible with multimodal imaging and its fiducial markers were customized for precise physical alignment among modalities. The co-registration accuracy was evaluated based on phantoms with thin catheters. For proof of concept, tumour models of the human colorectal adenocarcinoma cell line HT-29 were imaged. The tissue within the window chamber was sectioned, fixed and haematoxylin–eosin (HE) stained for comparison with multimodal in vivo imaging. Results The final MIMI system had a maximum field of view (FOV) of 18 mm × 18 mm. Using the fiducial markers and the tubing phantom, the co-registration errors are 0.18 ± 0.27 mm between MRI and positron imaging, 0.19 ± 0.22 mm between positron imaging and microscopic imaging and 0.15 ± 0.27 mm between MRI and microscopic imaging. A pilot test demonstrated that the MIMI system provides an integrative visualization of the tumour anatomy, vasculatures and metabolism of the in vivo tumour microenvironment, which was consistent with ex vivo pathology. Conclusions The established multimodal intravital imaging system provided a co-registered in vivo platform for trans-scale and transparent investigation of the underlying pathology behind imaging, which has the potential to enhance the translation of molecular imaging.

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STAT subtype specificity and ischemic preconditioning in mice: is STAT-3 enough?

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00231.2010 ◽

2011 ◽

Vol 300 (2) ◽

pp. H522-H526 ◽

Cited By ~ 10

Author(s):

Michael D. Goodman ◽

Sheryl E. Koch ◽

Muhammad R. Afzal ◽

Karyn L. Butler

Keyword(s):

Ischemic Preconditioning ◽

Ischemia Reperfusion Injury ◽

Contractile Function ◽

Ex Vivo ◽

Ischemia Reperfusion ◽

Cardiac Performance ◽

Subtype Specificity ◽

Developed Pressure ◽

Perfused Hearts

The role of other STAT subtypes in conferring ischemic tolerance is unclear. We hypothesized that in STAT-3 deletion alternative STAT subtypes would protect myocardial function against ischemia-reperfusion injury. Wild-type (WT) male C57BL/6 mice or mice with cardiomyocyte STAT-3 knockout (KO) underwent baseline echocardiography. Langendorff-perfused hearts underwent ischemic preconditioning (IPC) or no IPC before ischemia-reperfusion. Following ex vivo perfusion, hearts were analyzed for STAT-5 and -6 phosphorylation by Western blot analysis of nuclear fractions. Echocardiography and postequilibration cardiac performance revealed no differences in cardiac function between WT and KO hearts. Phosphorylated STAT-5 and -6 expression was similar in WT and KO hearts before perfusion. Contractile function in WT and KO hearts was significantly impaired following ischemia-reperfusion in the absence of IPC. In WT hearts, IPC significantly improved the recovery of the maximum first derivative of developed pressure (+dP/d tmax) compared with that in hearts without IPC. IPC more effectively improved end-reperfusion dP/d tmax in WT hearts compared with KO hearts. Preconditioned and nonpreconditioned KO hearts exhibited increased phosphorylated STAT-5 and -6 expression compared with WT hearts. The increased subtype activation did not improve the efficacy of IPC in KO hearts. In conclusion, baseline cardiac performance is preserved in hearts with cardiac-restricted STAT-3 deletion. STAT-3 deletion attenuates preconditioning and is not associated with a compensatory upregulation of STAT-5 and -6 subtypes. The activation of STAT-5 and -6 in KO hearts following ischemic challenge does not provide functional compensation for the loss of STAT-3. JAK-STAT signaling via STAT-3 is essential for effective IPC.

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Proof of concept comprehensive ex vivo neurological assay

Journal of Pharmacological and Toxicological Methods ◽

10.1016/j.vascn.2019.05.137 ◽

2019 ◽

Vol 99 ◽

pp. 106595

Author(s):

Lois Miraucourt ◽

Michael Accardi ◽

Hai Huang ◽

Simon Authier

Keyword(s):

Ex Vivo ◽

Proof Of Concept

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Gastrointestinal synthetic epithelial linings

Science Translational Medicine ◽

10.1126/scitranslmed.abc0441 ◽

2020 ◽

Vol 12 (558) ◽

pp. eabc0441

Author(s):

Junwei Li ◽

Thomas Wang ◽

Ameya R. Kirtane ◽

Yunhua Shi ◽

Alexis Jones ◽

...

Keyword(s):

Drug Absorption ◽

Ex Vivo ◽

The Body ◽

Proof Of Concept ◽

Barrier Formation ◽

Synthetic Biomaterial ◽

Gastrointestinal Epithelium ◽

Essential Enzyme ◽

Directed Polymerization

Epithelial tissues line the organs of the body, providing an initial protective barrier as well as a surface for nutrient and drug absorption. Here, we identified enzymatic components present in the gastrointestinal epithelium that can serve as selective means for tissue-directed polymerization. We focused on the small intestine, given its role in drug and nutrient absorption and identified catalase as an essential enzyme with the potential to catalyze polymerization and growth of synthetic biomaterial layers. We demonstrated that the polymerization of dopamine by catalase yields strong tissue adhesion. We characterized the mechanism and specificity of the polymerization in segments of the gastrointestinal tracts of pigs and humans ex vivo. Moreover, we demonstrated proof of concept for application of these gastrointestinal synthetic epithelial linings for drug delivery, enzymatic immobilization for digestive supplementation, and nutritional modulation through transient barrier formation in pigs. This catalase-based approach to in situ biomaterial generation may have broad indications for gastrointestinal applications.

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Mitochondrial transplantation for myocardial protection in diabetic hearts

European Journal of Cardio-Thoracic Surgery ◽

10.1093/ejcts/ezz326 ◽

2019 ◽

Vol 57 (5) ◽

pp. 836-845 ◽

Cited By ~ 6

Author(s):

Ilias P Doulamis ◽

Alvise Guariento ◽

Thomas Duignan ◽

Arzoo Orfany ◽

Takashi Kido ◽

...

Keyword(s):

Diastolic Pressure ◽

Ex Vivo ◽

Left Ventricular ◽

Diabetic Rat ◽

Ischaemia Reperfusion Injury ◽

Global Ischaemia ◽

Aortic Cannula ◽

Developed Pressure ◽

Perfused Hearts

Abstract OBJECTIVES Type 2 diabetes causes mitochondrial dysfunction, which increases myocardial susceptibility to ischaemia–reperfusion injury. We investigated the efficacy of transplantation of mitochondria isolated from diabetic or non-diabetic donors in providing cardioprotection from warm global ischaemia and reperfusion in the diabetic rat heart. METHODS Ex vivo perfused hearts from Zucker diabetic fatty (ZDF fa/fa) rats (n = 6 per group) were subjected to 30 min of warm global ischaemia and 120 min reperfusion. Immediately prior to reperfusion, vehicle alone (VEH) or vehicle containing mitochondria isolated from either ZDF (MTZDF) or non-diabetic Zucker lean (ZL +/?) (MTZL) skeletal muscle were delivered to the coronary arteries via the aortic cannula. RESULTS Following 30-min global ischaemia and 120-min reperfusion, left ventricular developed pressure was significantly increased in MTZDF and MTZL groups compared to VEH group (MTZDF: 92.8 ± 5.2 mmHg vs MTZL: 110.7 ± 2.4 mmHg vs VEH: 44.3 ± 5.9 mmHg; P < 0.01 each); and left ventricular end-diastolic pressure was significantly decreased (MTZDF 12.1 ± 1.3 mmHg vs MTZL 8.6 ± 0.8 mmHg vs VEH: 18.6 ± 1.5 mmHg; P = 0.016 for MTZDF vs VEH and P < 0.01 for MTZL vs VEH). Total tissue ATP content was significantly increased in both MT groups compared to VEH group (MTZDF: 18.9 ± 1.5 mmol/mg protein/mg tissue vs MTZL: 28.1 ± 2.3 mmol/mg protein/mg tissue vs VEH: 13.1 ± 0.5 mmol/mg protein/mg tissue; P = 0.018 for MTZDF vs VEH and P < 0.01 for MTZL vs VEH). Infarct size was significantly decreased in the MT groups (MTZDF: 11.8 ± 0.7% vs MTZL: 9.9 ± 0.5% vs VEH: 52.0 ± 1.4%; P < 0.01 each). CONCLUSIONS Mitochondrial transplantation significantly enhances post-ischaemic myocardial functional recovery and significantly decreases myocellular injury in the diabetic heart.

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