scholarly journals Ingestible transiently anchoring electronics for microstimulation and conductive signaling

2020 ◽  
Vol 6 (35) ◽  
pp. eaaz0127 ◽  
Author(s):  
Alex Abramson ◽  
David Dellal ◽  
Yong Lin Kong ◽  
Jianlin Zhou ◽  
Yuan Gao ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Ex Vivo ◽  
Electronic Devices ◽  
Noninvasive Evaluation ◽  
Stomach Muscle ◽  
Gi Tract ◽  
Electrically Conductive ◽  
Electrical Pulses ◽  
Gastric Motility Disorders

Ingestible electronic devices enable noninvasive evaluation and diagnosis of pathologies in the gastrointestinal (GI) tract but generally cannot therapeutically interact with the tissue wall. Here, we report the development of an orally administered electrical stimulation device characterized in ex vivo human tissue and in in vivo swine models, which transiently anchored itself to the stomach by autonomously inserting electrically conductive, hooked probes. The probes provided stimulation to the tissue via timed electrical pulses that could be used as a treatment for gastric motility disorders. To demonstrate interaction with stomach muscle tissue, we used the electrical stimulation to induce acute muscular contractions. Pulses conductively signaled the probes’ successful anchoring and detachment events to a parenterally placed device. The ability to anchor into and electrically interact with targeted GI tissues controlled by the enteric nervous system introduces opportunities to treat a multitude of associated pathologies.

scholarly journals Light-degradable hydrogels as dynamic triggers for gastrointestinal applications

2020 ◽  
Vol 6 (3) ◽  
pp. eaay0065 ◽  
Author(s):  
Ritu Raman ◽  
Tiffany Hua ◽  
Declan Gwynne ◽  
Joy Collins ◽  
Siddartha Tamang ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Implantable Devices ◽  
Large Animal Model ◽  
Large Animal ◽  
Gi Tract ◽  
Biomedical Device ◽  
Precise Tool ◽  
And Performance

Triggerable materials capable of being degraded by selective stimuli stand to transform our capacity to precisely control biomedical device activity and performance while reducing the need for invasive interventions. Here, we describe the development of a modular and tunable light-triggerable hydrogel system capable of interfacing with implantable devices. We apply these materials to two applications in the gastrointestinal (GI) tract: a bariatric balloon and an esophageal stent. We demonstrate biocompatibility and on-demand triggering of the material in vitro, ex vivo, and in vivo. Moreover, we characterize performance of the system in a porcine large animal model with an accompanying ingestible LED. Light-triggerable hydrogels have the potential to be applied broadly throughout the GI tract and other anatomic areas. By demonstrating the first use of light-degradable hydrogels in vivo, we provide biomedical engineers and clinicians with a previously unavailable, safe, dynamically deliverable, and precise tool to design dynamically actuated implantable devices.

scholarly journals Magnetic Interference on Cardiac Implantable Electronic Devices From Apple iPhone MagSafe Technology

2021 ◽  
Author(s):  
Fahd Nadeem ◽  
Arismendy Nunez Garcia ◽  
Cao Thach Tran ◽  
Michael Wu
Keyword(s):  
Ex Vivo ◽  
Electronic Devices ◽  
Wireless Charging ◽  
Current Generation ◽  
Cardiac Implantable Electronic Devices ◽  
Clinically Significant

Background Magnet wireless charging is being utilized increasingly in current generation smartphones. Apple's MagSafe is a proprietary wireless charging technology with an array of magnets that has the capacity to generate magnet fieldstrength >50 gauss (G). We hypothesize that there is clinically significant magnet interference caused by Apple's MagSafe technology on cardiac implantable electronic devices (CIED). Methods and Results This study has an in vivo and an ex vivo component. The in vivo component consists of consecutive patients who presented to the electrophysiology laboratory with previously implanted CIEDs. The iPhone 12 Pro Max was directly placed on the skin over the pocket of these patients and the effect was studied by device interrogation. For the ex vivo component of the study, CIEDs from major device companies were tested for magnetic interference caused by iPhone 12 Pro Max through unopened packages. We found that iPhone 12 Pro Max resulted in clinically identifiable magnet interference in 3/3 (100%) participants in vivo and in 8/11 (72.7%) devices ex vivo. Conclusions Apple's iPhone 12 Pro Max MagSafe technology can cause magnet interference on CIEDs and has the potential to inhibit lifesaving therapy.

scholarly journals Ex Vivo and In Vivo Imaging Study of Ultrasound Capsule Endoscopy

2020 ◽  
Vol 14 (2) ◽  
Author(s):  
John H. Lee ◽  
Giovanni Traverso ◽  
David Ibarra-Zarate ◽  
Duane S. Boning ◽  
Brian W. Anthony
Keyword(s):  
Capsule Endoscopy ◽  
In Vivo Imaging ◽  
Clinical Utility ◽  
Ex Vivo ◽  
Imaging Study ◽  
Mucosal Surface ◽  
Swine Model ◽  
Gi Tract ◽  
Acoustic Coupling

Abstract Wireless capsule endoscopy (WCE) has revolutionized the capacity for evaluation of the gastrointestinal (GI) tract, but its evaluation is limited to the mucosal surface. To overcome this, ultrasound capsule endoscopy (UCE) that can evaluate the deeper structures beyond the mucosal surface has been proposed and several studies focusing on technology development have demonstrated promising results. However, investigations of the potential for clinical utility of this technology are lacking. This work had two main goals: perform ex vivo and in vivo imaging studies in a swine model to (1) evaluate if acoustic coupling between a capsule with a specific size and GI tract can be achieved only through peristalsis autonomously without any human control and (2) identify key issues and challenges to help guide further research. The images acquired in these studies were able to visualize the wall of the GI tract as well as the structures within demonstrating that achieving adequate acoustic coupling through peristalsis is possible. Critical challenges were identified including level of visualization and area of coverage; these require further in-depth investigation before potential clinical utility of UCE technology can be concluded.

scholarly journals Electrophysiological investigation of intact retina with soft printed organic neural interface

2021 ◽  
Author(s):  
Ieva Vebraite-Adereth ◽  
Moshe David-Pur ◽  
David Rand ◽  
Eric Glowacki ◽  
Yael Hanein
Keyword(s):  
Electrical Stimulation ◽  
Ex Vivo ◽  
Electrode Array ◽  
Carbon Electrodes ◽  
Natural Image ◽  
Neural Firing ◽  
Electrode Arrays ◽  
Electrical Recording ◽  
Research Activities

Abstract Objective. Understanding how the retina converts a natural image or an electrically stimulated one into neural firing patterns is the focus of on-going research activities. Ex vivo, the retina can be readily investigated using multi electrode arrays. However, multi electrode array recording and stimulation from an intact retina (in the eye) has been so far insufficient. Approach. In the present study, we report new soft carbon electrode arrays suitable for recording and stimulating neural activity in an intact retina. Screen-printing of carbon ink on 20 µm polyurethane (PU) film was used to realize electrode arrays with electrodes as small as 40 µm in diameter. Passivation was achieved with a holey membrane, realized using laser drilling in a thin (50 µm) PU film. Plasma polymerized EDOT was used to coat the electrode array to improve the electrode specific capacitance. Chick retinas, embryonic stage day 13, both ex-planted and intact inside an enucleated eye, were used. Main results. A novel fabrication process based on printed carbon electrodes was developed and yielded high capacitance electrodes on a soft substrate. Ex vivo electrical recording of retina activity with carbon electrodes is demonstrated. With the addition of organic photo-capacitors, simultaneous photo-electrical stimulation and electrical recording was achieved. Finally, electrical activity recordings from an intact chick retina (inside enucleated eyes) were demonstrated. Both photosensitive retinal ganglion cell responses and spontaneous retina waves were recorded and their features analyzed. Significance. Results of this study demonstrated soft electrode arrays with unique properties, suitable for simultaneous recording and photo-electrical stimulation of the retina at high fidelity. This novel electrode technology opens up new frontiers in the study of neural tissue in vivo.

Electrical signals affect the cardiomyocyte transcriptome independently of contraction

2010 ◽  
Vol 42A (4) ◽  
pp. 283-289 ◽  
Author(s):  
Ruben S. R. M. Martherus ◽  
Sabina J. V. Vanherle ◽  
Erika D. J. Timmer ◽  
Volkert A. Zeijlemaker ◽  
Jos L. Broers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Electrical Stimulation ◽  
Primary Cultures ◽  
Calcium Handling ◽  
Specific Gene ◽  
Electrical Signals ◽  
Electrical Pulses ◽  
And Function ◽  
Evoked Contractions

Cardiomyocytes in vivo are continuously subjected to electrical signals that evoke contractions and instigate drastic changes in the cells' morphology and function. Studies on how electrical stimulation affects the cardiac transcriptome have remained limited to a small number of heart-specific genes. Furthermore, these studies have ignored the interplay between the electrical excitation and the subsequent contractions. We carried out a genomewide assessment of the effects of electrical signaling on gene expression, while distinguishing between the effects deriving from the electrical pulses themselves and the effects instigated by the evoked contractions. Changes in gene expression in primary cultures of neonatal ventricular cardiomyocytes from Lewis Rattus norvegicus were investigated with microarrays and RT-quantitative PCR (QPCR). A series of experiments was included in which the culture medium was supplemented with the contraction inhibitor blebbistatin to allow for electrical stimulation in the absence of contraction. Electrical stimulation was shown to directly enhance calcium handling and induce cardiomyocyte differentiation by arresting cell division and activating key cardiac transcription factors as well as additional differentiation mechanisms such as wnt signaling. Several genes involved in metabolism were also directly activated by electrical stimulation. Furthermore, our data suggest that contraction exerts negative feedback on the transcription of various genes. Together, these observations indicate that intercellular electric currents between adjacent cardiomyocytes have an important role in cardiomyocyte development. They act at least partially through a pulse-specific gene expression program that is activated independently from the evoked contractions.

scholarly journals 3293 Region Specific Dysregulation of Dopaminergic Signaling in Mice Displaying Excessive Over-Grooming

2019 ◽  
Vol 3 (s1) ◽  
pp. 19-20
Author(s):  
Daniel Foster ◽  
Samantha Yohn ◽  
Muhammad Mahmood ◽  
Madigan Lavery ◽  
Daniel O’Brien ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Repetitive Behaviors ◽  
Optical Stimulation ◽  
Fast Scan Cyclic Voltammetry ◽  
Postsynaptic Protein ◽  
Electrical Pulses ◽  
Dopamine Signaling ◽  
And Control ◽  
Excessive Grooming

OBJECTIVES/SPECIFIC AIMS: The objective of this study was to determine if dopamine signaling is altered in a mouse model displaying excessive self-grooming and further elucidate the potential utility of compounds targeting the striatal DA system in modulating repetitive behaviors. METHODS/STUDY POPULATION: Here, we report studies using fast-scan cyclic voltammetry (FSCV) in mice lacking the postsynaptic protein SAP90/PSD95-associated protein (SAPAP3 KO mice) as well as control littermates. Rodent self-grooming provides a behavioral output with which one can monitor repetitive, self-directed, patterned behavior that has great translational value to OCD-like disorders. Total time spent grooming was monitored in SAPAP3KO mice and control littermates. To further examine the role of DA in regulating repetitive grooming behaviors the magnitude and kinetics of DA transients were assessed using FSCV in ex vivo slice preparations as well as in anesthetized mice in vivo. DA transients were elicited in the dorsolateral striatum (DLS), dorsomedial striatum (DMS); and nucelus accumbens core (NAcc). In some experiments mice were crossed with DAT-Cre animals and channelrhodopsin 2 (ChR2) was virally expressed in DA neurons to allow optical stimulation of DA transients. RESULTS/ANTICIPATED RESULTS: As previously reported, SAPAP3 KO mice showed excessive grooming compared to control littermates at the age assessed (4-5 months). DA transients evoked by a single electrical pulse in slices from SAPAP3 KO mice were not significantly different from those observed in slices from control littermates in any of the regions tested including the DLS, DMS and NAcc. However, when four electrical pulses were applied at a frequency of 10Hz to mimic DA neuron bursting, the magnitude of DA transients observed in the DMS and NAcc of SAPAP3 mice were greater than those evoked in control littermates.Interestingly, phasic stimulation produced similar DA transients in the DLS of both genotypes suggesting that phasic DA signaling was not globally altered. To confirm this finding we crossed SAPAP3 KO mice with DAT-Cre mice and injected ChR2 containing virus into the midbrain to selectively express ChR2 in DA neurons. Transients were then optically evoked resulting in selective activation of DA neurons. Optical stimulation produced a pronounced enhancement of DA release in SAPAP3 KO mice specifically in the DMS and only following phasic-like stimulation. DISCUSSION/SIGNIFICANCE OF IMPACT: These exciting findings suggest that DA signaling in SAPAP3KO mice is dysregulated in a very precise manner that is sub-region specific as well as dependent on the pattern of stimulation. These results suggest that targeted therapies that can modulate these specific modes of dopaminergic signaling in these distinct striatal subregions could provide improved efficacy in OCD patients that are resistant to SSRI treatment.

scholarly journals Ex Vivo Evaluation of Egg Yolk IgY Degradation in Chicken Gastrointestinal Tract

2021 ◽  
Vol 12 ◽  
Author(s):  
Huiwen Wang ◽  
Ximin Zeng ◽  
Jun Lin
Keyword(s):  
Small Intestine ◽  
Ex Vivo ◽  
Egg Yolk ◽  
Critical Issue ◽  
Saline Control ◽  
Gi Tract ◽  
Convenient Route ◽  
Egg Yolk Antibody ◽  
Short Time

Egg yolk antibody (immunoglobulin Y, IgY), due to its unique features (e.g., cost-effectiveness for mass production), is emerging as a promising passive immune agent and alternative to antibiotics to combat infectious diseases, particularly in livestock. Oral administration of egg yolk IgY is the most common and convenient route that has been extensively investigated for controlling enteric pathogens. However, the in vivo stability of egg yolk IgY in the gastrointestinal (GI) tract, a critical issue for the success of this approach, still has not been clearly elucidated. Our recent study showed instability of orally administered egg yolk IgY in chicken GI tract, as demonstrated by both in vivo and ex vivo evidence. To better understand the magnitude and dynamics of instability of egg yolk IgY in vivo, in this study, we conducted comprehensive ex vivo analyses by spiking hyperimmune egg yolk IgY in fresh GI contents collected from five broilers at each sampling age (2, 4, or 6 weeks). The pH in gizzard slightly increased with age from 2.4 to 3.0, while the pH in the small intestine was around 5.8. ELISA analysis indicated that a short time of treatment (30 or 60 min) of IgY with the gizzard contents from the chickens at 2, 4, and 6 weeks of age greatly reduced specific IgY titer by over 8, 6, and 5 log2 units, respectively, when compared with saline control. However, small intestine content only had a mild effect on egg yolk IgY, leading to 1 log2 unit of reduction in IgY titer upon 30 min of treatment. Consistent with these findings, SDS-PAGE and immunoblotting analyses provided direct evidence demonstrating that egg yolk IgY could be drastically degraded to undetectable level in gizzard content upon as short as 5 min of treatment; however, the IgY was only slightly degraded in small intestine content. Immunoblotting also showed that treatment of IgY with HCl (pH 3.0) for 60 min did not affect its integrity at all, further supporting the enzymatic degradation of IgY in gizzard. Collectively, egg yolk IgY could be substantially degraded in chicken gizzard, highly warranting the development of effective approaches, such as encapsulation, for the controlled release and protection of orally administered egg yolk IgY in livestock.

scholarly journals In VivoandEx VivoImaging Reveals a Long-Lasting Chlamydial Infection in the Mouse Gastrointestinal Tract following Genital Tract Inoculation

2015 ◽  
Vol 83 (9) ◽  
pp. 3568-3577 ◽  
Author(s):  
Qi Zhang ◽  
Yumeng Huang ◽  
Siqi Gong ◽  
Zhangsheng Yang ◽  
Xin Sun ◽  
...  
Keyword(s):  
Genital Tract ◽  
Chlamydial Infection ◽  
Ex Vivo ◽  
Mouse Strains ◽  
Gi Tract ◽  
Tubal Infertility ◽  
Content Type ◽  
Chlamydia Muridarum ◽  
Rapid Ascent

Intravaginal infection withChlamydia muridarumin mice can ascend to the upper genital tract, resulting in hydrosalpinx, a pathological hallmark for tubal infertility in women infected withC. trachomatis. Here, we utilizedin vivoimaging ofC. muridaruminfection in mice following an intravaginal inoculation and confirmed the rapid ascent of the chlamydial organisms from the lower to upper genital tracts. Unexpectedly, theC. muridarum-derived signal was still detectable in the abdominal area 100 days after inoculation.Ex vivoimaging of the mouse organs revealed that the long-lasting presence of the chlamydial signal was restricted to the gastrointestinal (GI) tract, which was validated by directly measuring the chlamydial live organisms and genomes in the same organs. TheC. muridarumorganisms spreading from the genital to the GI tracts were detected in different mouse strains and appeared to be independent of oral or rectal routes. Mice prevented from orally taking up excretions also developed the long-lasting GI tract infection. Inoculation ofC. muridarumdirectly into the upper genital tract, which resulted in a delayed vaginal shedding of live organisms, accelerated the chlamydial spreading to the GI tract. Thus, we have demonstrated that the genital tract chlamydial organisms may use a systemic route to spread to and establish a long-lasting infection in the GI tract. The significance of the chlamydial spreading from the genital to GI tracts is discussed.

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.

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