Endoworm: A new semi-autonomous enteroscopy device

Using enteroscopes with therapeutic capacity to explore the small intestine entails certain limitations, including long exploration times, patient discomfort, the need for sedation, a high percentage of incomplete explorations and a long learning curve. This article describes the advances and setbacks encountered in designing the new Endoworm enteroscopy system, a semi-autonomous device consisting of a control unit and three cavities that inflate and deflate in such a way that the bowel retracts over the endoscope. The system can be adapted to any commercial enteroscope. Endoworm was tested in different intestine models: a polymethyl methacrylate rigid tube, an in vitro polyester urethane model, an ex vivo pig model and an in vivo animal model. The general behavior of the prototype was evaluated by experienced medical personnel. The mean distance covered through the lumen was measured in each cycle. The system was found to have excellent performance in the rigid tube and in the in vitro model. The ex vivo tests showed that the behavior depended largely on the mechanical properties of the lumen, while the in vivo experiments suggest that the device will require further modifications to improve its performance.

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Development of a gel dedicated to gel immersion endoscopy

Endoscopy International Open ◽

10.1055/a-1396-4236 ◽

2021 ◽

Vol 09 (06) ◽

pp. E918-E924

Author(s):

Tomonori Yano ◽

Atsushi Ohata ◽

Yuji Hiraki ◽

Makoto Tanaka ◽

Satoshi Shinozaki ◽

...

Keyword(s):

Electrical Conductivity ◽

Porcine Model ◽

Ex Vivo ◽

In Vitro Experiments ◽

Efficacy And Safety ◽

Coagulative Necrosis ◽

Novel Technique ◽

In Vivo Experiments

Abstract Backgrounds and study aims Gel immersion endoscopy is a novel technique to secure the visual field during endoscopy. The aim of this study was to develop a dedicated gel for this technique. Methods To identify appropriate viscoelasticity and electrical conductivity, various gels were examined. Based on these results, the dedicated gel “OPF-203” was developed. Efficacy and safety of OPF-203 were evaluated in a porcine model. Results In vitro experiments showed that a viscosity of 230 to 1900 mPa·s, loss tangent (tanδ) ≤ 0.6, and hardness of 240 to 540 N/cm2 were suitable. Ex vivo experiments showed electrical conductivity ≤ 220 μS/cm is appropriate. In vivo experiments using gastrointestinal bleeding showed that OPF-203 provided clear visualization compared to water. After electrocoagulation of gastric mucosa in OPF-203, severe coagulative necrosis was not observed in the muscularis but limited to the mucosa. Conclusions OPF-203 is useful for gel immersion endoscopy.

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Effect of the proinflammatory cytokine TNF-α on intestinal riboflavin uptake: inhibition mediated via transcriptional mechanism(s)

AJP Cell Physiology ◽

10.1152/ajpcell.00295.2018 ◽

2018 ◽

Vol 315 (5) ◽

pp. C653-C663 ◽

Cited By ~ 5

Author(s):

Kasin Yadunandam Anandam ◽

Omar A. Alwan ◽

Veedamali S. Subramanian ◽

Padmanabhan Srinivasan ◽

Rubina Kapadia ◽

...

Keyword(s):

Ex Vivo ◽

Significant Inhibition ◽

Mrna Levels ◽

In Vivo Models ◽

Uptake Inhibition ◽

Tnf Α ◽

Vitro Model ◽

Factor Α

Riboflavin (RF), is essential for normal cellular metabolism/function. Intestinal RF absorption occurs via a specific carrier-mediated process that involves the apical transporter RFVT-3 ( SLC52A3) and the basolateral RFVT-1 (SLC52A1). Previously, we characterized different cellular/molecular aspects of the intestinal RF uptake process, but nothing is known about the effect of proinflammatory cytokines on the uptake event. We addressed this issue using in vitro, ex vivo, and in vivo models. First, we determined the level of mRNA expression of the human (h)RFVT-3 and hRFVT-1 in intestinal tissue of patients with inflammatory bowel disease (IBD) and observed a markedly lower level compared with controls. In the in vitro model, exposing Caco-2 cells to tumor necrosis factor-α (TNF-α) led to a significant inhibition in RF uptake, an effect that was abrogated upon knocking down TNF receptor 1 (TNFR1). The inhibition in RF uptake was associated with a significant reduction in the expression of hRFVT-3 and -1 protein and mRNA levels, as well as in the activity of the SLC52A3 and SLC52A1 promoters. The latter effects appear to involve Sp1 and NF-κB sites in these promoters. Similarly, exposure of mouse small intestinal enteroids and wild-type mice to TNF-α led to a significant inhibition in physiological and molecular parameters of intestinal RF uptake. Collectively, these findings demonstrate that exposure of intestinal epithelial cells to TNF-α leads to inhibition in RF uptake and that this effect is mediated, at least in part, via transcriptional mechanism(s). These findings may explain the significantly low RF levels observed in patients with IBD.

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Entrectinib, a TRK/ROS1 inhibitor with anti-CNS tumor activity: differentiation from other inhibitors in its class due to weak interaction with P-glycoprotein

Neuro-Oncology ◽

10.1093/neuonc/noaa052 ◽

2020 ◽

Vol 22 (6) ◽

pp. 819-829 ◽

Cited By ~ 3

Author(s):

Holger Fischer ◽

Mohammed Ullah ◽

Cecile C de la Cruz ◽

Thomas Hunsaker ◽

Claudia Senn ◽

...

Keyword(s):

Steady State ◽

Lipid Membrane ◽

Kinase Inhibitor ◽

Ex Vivo ◽

Intracranial Tumor ◽

Brain Penetration ◽

In Vivo Experiments ◽

P Glycoprotein

Abstract Background Studies evaluating the CNS penetration of a novel tyrosine kinase inhibitor, entrectinib, proved challenging, particularly due to discrepancies across earlier experiments regarding P-glycoprotein (P-gp) interaction and brain distribution. To address this question, we used a novel “apical efflux ratio” (AP-ER) model to assess P-gp interaction with entrectinib, crizotinib, and larotrectinib, and compared their brain-penetration properties. Methods AP-ER was designed to calculate P-gp interaction with the 3 drugs in vitro using P-gp–overexpressing cells. Brain penetration was studied in rat plasma, brain, and cerebrospinal fluid (CSF) samples after intravenous drug infusion. Unbound brain concentrations were estimated through kinetic lipid membrane binding assays and ex vivo experiments, while the antitumor activity of entrectinib was evaluated in a clinically relevant setting using an intracranial tumor mouse model. Results Entrectinib showed lower AP-ER (1.1–1.15) than crizotinib and larotrectinib (≥2.8). Despite not reaching steady-state brain exposures in rats after 6 hours, entrectinib presented a more favorable CSF-to-unbound concentration in plasma (CSF/Cu,p) ratio (>0.2) than crizotinib and larotrectinib at steady state (both: CSF/Cu,p ~0.03). In vivo experiments validated the AP-ER approach. Entrectinib treatment resulted in strong tumor inhibition and full survival benefit in the intracranial tumor model at clinically relevant systemic exposures. Conclusions Entrectinib, unlike crizotinib and larotrectinib, is a weak P-gp substrate that can sustain CNS exposure based on our novel in vitro and in vivo experiments. This is consistent with the observed preclinical and clinical efficacy of entrectinib in neurotrophic tropomyosin receptor kinase (NTRK) and ROS1 fusion-positive CNS tumors and secondary CNS metastases.

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The Source Of Thromboxane Formation Associated With Complement-Mediated Pulmonary Leukostasis In Sheep

10.1055/s-0038-1652125 ◽

1981 ◽

Author(s):

J W D McDonald ◽

M Ali ◽

J D Cooper ◽

E R Townsend

Keyword(s):

Pulmonary Artery ◽

Blood Clotting ◽

Ex Vivo ◽

Lung Parenchyma ◽

Mechanical Obstruction ◽

Vascular Response ◽

In Vivo Experiments ◽

Pulmonary Arterial

The infusion of plasma containing Zymosan-activated complement (ZAC) into sheep produces leukopenia with pulmonary leukostasis and transient pulmonary arterial hypertension (PAH). Previous work has related PAH to elevations of plasma thromboxane B2 (TXB2) rather than to mechanical obstruction by sequestered leukocytes (WBC). We have investigated the source of the TXB2 formation in this model. Incubation of platelet-poor WBC preparations with arachi- donate resulted in negligible TXB2 formation. WBC-poor platelet preparations on the other hand formed significant amounts of TXB2 (approximately 6-18 ng/108 platelets). Incubation of whole sheep blood or plasma with ZAC failed to generate significant amounts of TXB2. Thus, WBC agglutination in vitro did not induce platelet TXB2 formation.Pretreatment of sheep with aspirin (ASA)(10 mg/kg IV) completely blocked TXB2 formation and PAH in response to infusion of plasma containing ZAC. The infusion of 10-50% nonnal platelets into sheep 4 hours after ASA pretreatment failed to restore TXB2 formation and pulmonary vascular response to subsequent challenge with ZAC. TXB2 formation during blood clotting ex vivo was restored by the platelet infusions. These experiments make it appear unlikely that platelets are the source of the TXB2. It is possible that the transfused platelets respond to thrombin but are unable to interact with sequestered leukocytes. Sheep lung and pulmonary artery were incubated in vitro with arachidonate. Lung formed 630 ng TXB2 and 39 ng 6-keto-PGF1α/g of wet tissue. Pulmonary artery formed 9 ng TXB2 and 180 ng 6-keto-PGF1α/g of wet tissue. The relative proportions of TXB2 and 6-keto-PGF1α formed by lung parenchyma but not pulmonary artery resemble the proportions observed in previous in vivo experiments with ZAC. It appears that lung tissue is the most likely source of TXB2 formation causing PAH in response to ZAC-mediated pulmonary leukostasis.

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Removal of obturation material in endodontic retreatment: a literature review

RSBO ◽

10.21726/rsbo.v16i2.934 ◽

2019 ◽

Vol 16 (2) ◽

pp. 109

Author(s):

Carina Do Nascimento Menezes ◽

Verydianna Frota Carneiro ◽

Mônica Sampaio do Vale

Keyword(s):

Literature Review ◽

Latin American ◽

Root Canal ◽

Ex Vivo ◽

Filling Material ◽

Advantages And Disadvantages ◽

In Vivo Experiments ◽

Automated Method

Introduction: Removal of filling material from the root canal system is required when a previous endodontic treatment fails, what may result in the permanence of an unfavorable periapical condition. The intent is to completely remove the filling material inside of the root canal to achieve sufficient cleaning and shaping for successful retreatment. Objective: The aims of this article were to provide asystematic review of the different techniques of endodontic filling material associated or not with organic solvents and to analyze them critically in terms of advantages and disadvantages of each technique. Literature review: The descriptors used were “guttapercha”, “obturation,” and “retreatment” in the following databases: PubMed, MEDLINE, Latin American and Caribbean Center on Health Sciences Information (Bireme), Latin-American and CaribbeanHealth Sciences (Lilacs), Brazilian Dentistry Bibliography (BBO), and Scientific Electronic Library Online (SciELO). Publications of in vitro/ ex vivo and in vivo experiments without language restriction between the years 2010 and 2018 were selected. Conclusion: None of the techniques were capable of performing complete root canal cleaning, and the manual method was so effective as the automated method, although it requires longer working time. Furthermore, although this review confirmed that the solvent action did not allow a significantimprovement in the removal of the filling material, ultrasoundactivated irrigation proved to be an efficient adjunctive device as it could significantly reduce the volume of intracanal residuals.

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Bioavailability and Speciation of Mineral Micronutrients: The Enzymolysis Approach

Journal of AOAC International ◽

10.1093/jaoac/80.4.920 ◽

1997 ◽

Vol 80 (4) ◽

pp. 920-927 ◽

Cited By ~ 15

Author(s):

Pierre Hocquellet ◽

Marie-Dominique L'Hotellier

Keyword(s):

Gastrointestinal Tract ◽

Absorption Spectrometry ◽

Insoluble Residue ◽

In Vivo Experiments ◽

Treatment Data ◽

Dietary Components ◽

Vitro Model ◽

Good Agreement

Abstract Speciation analyses are essential to investigate the effects of dietary components on bioavailability of mineral micronutrients. Enzymolysis was used. An in vitro model simulating enzymatic activity in the gastrointestinal tract of monogastric species was developed and used to assess availability of Fe, Cu, Mn, and Zn in some foodstuffs. The solubility of each element in samples was measured by atomic absorption spectrometry after enzymatic treatment. Data are in good agreement with information obtained from earlier, more expensive nutritional surveys or in vivo experiments and, therefore, allow prediction of the tendency of a particular food to induce mineral deficiency. In addition, ligands responsible for inhibiting intestinal absorption were identified by determining the amount of metal released after treatment of the insoluble residue with an appropriate enzyme such as cellulase and phytase, used respectively to study fiber and phytate interactions. Enzymolysis may be useful for optimizing mineral supplementations though its nutritional significance is somewhat limited by the fact that it does not take into account the dynamic changes in the gastrointestinal tract. Enzymolysis is a prerequisite for further speciation studies of complex systems and in some instances is the only way for specifying physicochemical forms of elements.

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BMP activity controlled by BMPER regulates the proinflammatory phenotype of endothelium

Blood ◽

10.1182/blood-2011-03-339762 ◽

2011 ◽

Vol 118 (18) ◽

pp. 5040-5049 ◽

Cited By ~ 47

Author(s):

Thomas Helbing ◽

René Rothweiler ◽

Elena Ketterer ◽

Lena Goetz ◽

Jennifer Heinke ◽

...

Keyword(s):

Vascular Endothelial Cells ◽

Ex Vivo ◽

Leukocyte Adhesion ◽

Vascular Inflammation ◽

Bmp Signaling ◽

In Vivo Models ◽

In Vivo Experiments ◽

And Migration

Abstract The endothelium plays a pivotal role in vascular inflammation. Here we study bone morphogenetic protein (BMP) signaling in endothelial inflammation and in particular the role of BMPER, an extracellular BMP modulator that is important in vascular development and angiogenesis. Using the BMP antagonist dorsomorphin or BMP2 as an agonist we show that BMP signaling is essential for the inflammatory response of vascular endothelial cells as demonstrated by intravital microscopy. We found that BMPER is decreased in inflammation similar to vascular protective genes like KLF2 and eNOS. Using in vitro and in vivo models we show that BMPER is down-regulated through the TNFα-NFκB-KLF2 signaling pathway. Functionally, lack of BMPER induced by siRNA or in BMPER+/− mice confers a proinflammatory endothelial phenotype with reduced eNOS levels and enhanced expression of adhesion molecules leading to increased leukocyte adhesion and extravasation in ex vivo and in vivo experiments. Vice versa, addition of BMPER exerts endothelium protective functions and antagonizes TNFα induced inflammation. Mechanistically, we demonstrate that these effects of BMPER are dependent on BMP signaling because of enhanced NFκB activity. In conclusion, the BMP modulator BMPER is a new protective regulator of vascular inflammation that modulates leukocyte adhesion and migration in vitro and in vivo.

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Rapid ratiometric biomarker detection with topically applied SERS nanoparticles

TECHNOLOGY ◽

10.1142/s2339547814500125 ◽

2014 ◽

Vol 02 (02) ◽

pp. 118-132 ◽

Cited By ~ 38

Author(s):

Yu "Winston" Wang ◽

Altaz Khan ◽

Madhura Som ◽

Danni Wang ◽

Ye Chen ◽

...

Keyword(s):

Ex Vivo ◽

Clinical Success ◽

Simultaneous Detection ◽

Integration Time ◽

In Vivo Experiments ◽

Surface Enhanced Raman ◽

Detection Probe ◽

Multiple Cell

Multiplexed surface-enhanced Raman scattering (SERS) nanoparticles (NPs) offer the potential for rapid molecular phenotyping of tissues, thereby enabling accurate disease detection as well as patient stratification to guide personalized therapies or to monitor treatment outcomes. The clinical success of molecular diagnostics based on SERS NPs would be facilitated by the ability to accurately identify tissue biomarkers under time-constrained staining and detection conditions with a portable device. In vitro, ex vivo and in vivo experiments were performed to optimize the technology and protocols for the rapid detection (0.1-s integration time) of multiple cell-surface biomarkers with a miniature fiber-optic spectral-detection probe following a brief (5 min) topical application of SERS NPs on tissues. Furthermore, we demonstrate that the simultaneous detection and ratiometric quantification of targeted and nontargeted NPs allows for an unambiguous assessment of molecular expression that is insensitive to nonspecific variations in NP concentrations.

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Antibacterial properties of thioridazine

Farmatsevtychnyi zhurnal ◽

10.32352/0367-3057.4.19.11 ◽

2019 ◽

pp. 96-104

Author(s):

N. Hrynchuk ◽

N. Vrynchanu

Keyword(s):

Antibacterial Activity ◽

Ex Vivo ◽

Antibacterial Properties ◽

Antimicrobial Properties ◽

Antibiotic Resistant ◽

In Vivo Experiments ◽

Antistaphylococcal Activity ◽

The Impact

The emergence and spread of antibiotic-resistant strains of microorganisms reduces the effectiveness of antibiotic therapy and requires finding solutions to problems, one of which is the study of antimicrobial properties in drugs of various pharmacological groups. The purpose of the work was to summarize the data on the antibacterial activity of thioridazine and its derivatives to determine the feasibility and prospects of creating new antibacterial drugs on their basis. The paper presents literature data on the effects of thioridazine on the causative agent of tuberculosis, antistaphylococcal activity, susceptibility of plasmodium and trypanosoma. The antibacterial activity of the drug was established within in vitro studies with the determination of MIC towards gram-positive and gram-negative microorganisms, ex vivo using macrophage lines, as well as within in vivo experiments on mice. It is established that the neuroleptic thioridazine is characterized by pronounced anti-tuberculosis activity, the mechanism of action is associated with the impact on the cell membrane of M. tuberculosis, inactivation by calmodulin and inhibition of specific NADH-dehydrogenase type II. The literature data indicate that thioridazine is able to increase the activity of isoniazid against the strains of mycobacteria that are susceptible and resistant to its action. It has been established that resistance to thioridazine in antibiotic-resistant M. tuberculosis strains is not formed. The drug is characterized by its ability to inhibit the growth and reproduction of both methicylin-sensitive (MSSA) and methicilin-resistant (MRSA) strains of Staphylococcus aureus, which has been proven within in vitro experiments. The effectiveness of thioridazine has been proven within in vivo experiments in case of skin infection and sepsis caused by S. aureus. Antimicrobial effect of the drug is also observed towards to plasmodium (P. falciparum) and trypanosomes (Trypanosoma spp.). Currently, the synthesis of thioridazine derivatives is carried out to identify compounds with a pronounced antibacterial effect. Some of the first synthesized compounds are not inferior or superior to thioridazine by the inhibitory effect. Thus, these data suggest that drugs of different pharmacological groups, including drugs that affect the nervous system - thioridazine and its derivatives, can be a source of replenishment of the arsenal of antimicrobial drugs to control such threatening infections as tuberculosis and diseases caused by polyresistant strains of microorganisms.

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