Transparent antifouling material for improved operative field visibility in endoscopy

Camera-guided instruments, such as endoscopes, have become an essential component of contemporary medicine. The 15–20 million endoscopies performed every year in the United States alone demonstrate the tremendous impact of this technology. However, doctors heavily rely on the visual feedback provided by the endoscope camera, which is routinely compromised when body fluids and fogging occlude the lens, requiring lengthy cleaning procedures that include irrigation, tissue rubbing, suction, and even temporary removal of the endoscope for external cleaning. Bronchoscopies are especially affected because they are performed on delicate tissue, in high-humidity environments with exposure to extremely adhesive biological fluids such as mucus and blood. Here, we present a repellent, liquid-infused coating on an endoscope lens capable of preventing vision loss after repeated submersions in blood and mucus. The material properties of the coating, including conformability, mechanical adhesion, transparency, oil type, and biocompatibility, were optimized in comprehensive in vitro and ex vivo studies. Extensive bronchoscopy procedures performed in vivo on porcine lungs showed significantly reduced fouling, resulting in either unnecessary or ∼10–15 times shorter and less intensive lens clearing procedures compared with an untreated endoscope. We believe that the material developed in this study opens up opportunities in the design of next-generation endoscopes that will improve visual field, display unprecedented antibacterial and antifouling properties, reduce the duration of the procedure, and enable visualization of currently unreachable parts of the body, thus offering enormous potential for disease diagnosis and treatment.

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The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000116 ◽

2012 ◽

Vol 82 (3) ◽

pp. 228-232 ◽

Cited By ~ 7

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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Repurposing N,N-Dimethylacetamide (DMA), a Pharmaceutical Excipient, as a Prototype Novel Anti-inflammatory Agent for the Prevention and/or Treatment of Preterm Birth

Current Pharmaceutical Design ◽

10.2174/1381612824666180130121706 ◽

2018 ◽

Vol 24 (9) ◽

pp. 989-992 ◽

Cited By ~ 4

Author(s):

Samir Gorasiya ◽

Juliet Mushi ◽

Ryan Pekson ◽

Sabesan Yoganathan ◽

Sandra E. Reznik

Keyword(s):

Preterm Birth ◽

Ex Vivo ◽

The United States ◽

Occurrence Rate ◽

Pharmaceutical Excipient ◽

Ongoing Work ◽

Exciting Line ◽

Pregnant Mice

Background: Preterm birth (PTB), or birth that occurs before 37 weeks of gestation, accounts for the majority of perinatal morbidity and mortality. As of 2016, PTB has an occurrence rate of 9.6% in the United States and accounts for up to 18 percent of births worldwide. Inflammation has been identified as the most common cause of PTB, but effective pharmacotherapy has yet to be developed to prevent inflammation driven PTB. Our group has discovered that N,N-dimethylacetamide (DMA), a readily available solvent commonly used as a pharmaceutical excipient, rescues lipopolysaccharide (LPS)-induced timed pregnant mice from PTB. Methods: We have used in vivo, ex vivo and in vitro approaches to investigate this compound further. Results: Interestingly, we found that DMA suppresses cytokine secretion by inhibiting nuclear factor-kappa B (NF-κB). In ongoing work in this exciting line of investigation, we are currently investigating structural analogs of DMA, some of them novel, to optimize this approach focused on the inflammation associated with PTB. Conclusion: Successful development of pharmacotherapy for the prevention of PTB rests upon the pursuit of multiple strategies to solve this important clinical challenge.

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Iodine-124 PET quantification of organ-specific delivery and expression of NIS-encoding RNA

EJNMMI Research ◽

10.1186/s13550-021-00753-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Matthias Miederer ◽

Stefanie Pektor ◽

Isabelle Miederer ◽

Nicole Bausbacher ◽

Isabell Sofia Keil ◽

...

Keyword(s):

Cell Lines ◽

Ex Vivo ◽

Small Animal ◽

Protein Translation ◽

The Body ◽

Small Animal Pet ◽

Animal Pet ◽

Organ Specific

Abstract Background RNA-based vaccination strategies tailoring immune response to specific reactions have become an important pillar for a broad range of applications. Recently, the use of lipid-based nanoparticles opened the possibility to deliver RNA to specific sites within the body, overcoming the limitation of rapid degradation in the bloodstream. Here, we have investigated whether small animal PET/MRI can be employed to image the biodistribution of RNA-encoded protein. For this purpose, a reporter RNA coding for the sodium-iodide-symporter (NIS) was in vitro transcribed in cell lines and evaluated for expression. RNA-lipoplex nanoparticles were then assembled by complexing RNA with liposomes at different charge ratios, and functional NIS protein translation was imaged and quantified in vivo and ex vivo by Iodine-124 PET upon intravenous administration in mice. Results NIS expression was detected on the membrane of two cell lines as early as 6 h after transfection and gradually decreased over 48 h. In vivo and ex vivo PET/MRI of anionic spleen-targeting or cationic lung-targeting NIS-RNA lipoplexes revealed a visually detectable rapid increase of Iodine-124 uptake in the spleen or lung compared to control-RNA-lipoplexes, respectively, with minimal background in other organs except from thyroid, stomach and salivary gland. Conclusions The strong organ selectivity and high target-to-background acquisition of NIS-RNA lipoplexes indicate the feasibility of small animal PET/MRI to quantify organ-specific delivery of RNA.

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Gold-Polymer Nanocomposites for Future Therapeutic and Tissue Engineering Applications

Pharmaceutics ◽

10.3390/pharmaceutics14010070 ◽

2021 ◽

Vol 14 (1) ◽

pp. 70

Author(s):

Panangattukara Prabhakaran Praveen Kumar ◽

Dong-Kwon Lim

Keyword(s):

Tissue Engineering ◽

Polymer Nanocomposites ◽

Disease Diagnosis ◽

The Body ◽

Hybrid Nanocomposites ◽

Surface Charges ◽

Engineering Applications ◽

Therapeutic Applications

Gold nanoparticles (AuNPs) have been extensively investigated for their use in various biomedical applications. Owing to their biocompatibility, simple surface modifications, and electrical and unique optical properties, AuNPs are considered promising nanomaterials for use in in vitro disease diagnosis, in vivo imaging, drug delivery, and tissue engineering applications. The functionality of AuNPs may be further expanded by producing hybrid nanocomposites with polymers that provide additional functions, responsiveness, and improved biocompatibility. Polymers may deliver large quantities of drugs or genes in therapeutic applications. A polymer alters the surface charges of AuNPs to improve or modulate cellular uptake efficiency and their biodistribution in the body. Furthermore, designing the functionality of nanocomposites to respond to an endo- or exogenous stimulus, such as pH, enzymes, or light, may facilitate the development of novel therapeutic applications. In this review, we focus on the recent progress in the use of AuNPs and Au-polymer nanocomposites in therapeutic applications such as drug or gene delivery, photothermal therapy, and tissue engineering.

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The fate of methylmercury through the formation of bismethylmercury sulfide as an intermediate in mice

Scientific Reports ◽

10.1038/s41598-021-96579-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yumi Abiko ◽

Yusuke Katayama ◽

Wenyang Zhao ◽

Sawako Horai ◽

Kenji Sakurai ◽

...

Keyword(s):

Ex Vivo ◽

Intraperitoneal Administration ◽

Distal Colon ◽

The Body ◽

Gas Chromatography Mass Spectrometry ◽

Dependent Manner ◽

Free System ◽

A Cell

AbstractA previous study by our group indicated that methylmercury (MeHg) is biotransformed to bismethylmercury sulfide [(MeHg)2S)] by interaction with reactive sulfur species (RSS) produced in the body. In the present study, we explored the transformation of MeHg to (MeHg)2S in the gut and the subsequent fate of (MeHg)2S in vitro and in vivo. An ex vivo experiment suggested the possibility of the extracellular transformation of MeHg to (MeHg)2S in the distal colon, and accordingly, the MeHg sulfur adduct was detected in the intestinal contents and feces of mice administered MeHg, suggesting that (MeHg)2S is formed through reactions between MeHg and RSS in the gut. In a cell-free system, we found that (MeHg)2S undergoes degradation in a time-dependent manner, resulting in the formation of mercury sulfide and dimethylmercury (DMeHg), as determined by X-ray diffraction and gas chromatography/mass spectrometry, respectively. We also identified DMeHg in the expiration after the intraperitoneal administration of (MeHg)2S to mice. Thus, our present study identified a new fate of MeHg through (MeHg)2S as an intermediate, which leads to conversion of volatile DMeHg in the body.

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Artificial Super Para Magnetic Nano APC for Active and Adoptive Immunotherapy.

Blood ◽

10.1182/blood.v108.11.3888.3888 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3888-3888

Author(s):

Hugo De La Pena ◽

J. Alejandro Madrigal ◽

M. Bencsik ◽

Gareth W.V. Cave ◽

A. Selman ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Adoptive Immunotherapy ◽

Ex Vivo ◽

The Body ◽

Cell Manipulation ◽

Active Immunotherapy ◽

Immune Gene

Abstract T cells are probably one of the most pivotal cell types in the human adaptive immune system. They have the capability to eradicate primary, metastatic, relapsed tumours and can ameliorate otherwise fatal viral infections. Not surprisingly therefore, activation and expansion of T cells has become one of the main focuses for immunotherapy and immune gene therapy. Sufficient T cells numbers however, are required to deliver a significant clinical impact to patients, and rapid reproducible expansion of viable T cells still remains one of the main challenges for significant improvement. One of the main concerns with adoptive immunotherapy is that it relies on one critical factor: ex-vivo cell manipulation; the problem with this is that the longer the in-vitro T cell culture, the shorter the in-vivo T cell survival after infusion. In-vivo artificial expansion systems for active immunotherapy would clearly circumvent this problem. Therefore ideally a flexible system should be constructed in order to performed both adoptive and/or active immunotherapy depending on the patients requirements. Currently there is no comprehensive artificial Antigen Presenting Cell system (aAPC) for both effective ex-vivo and in-vivo antigen specific T cell expansion. In order to address this, using nanotechnology, we have constructed a nano sized super-para-magnetic artificial targeted and traceable in-vivo APC system by coating liposomes (approved for human use) with an optimised number of MHC Class I / peptide complexes and a specific selected range of ligands for adhesion (anti LFA1), early activation (anti CD28, anti CD27), late activation (anti 4-1BB) and survival (anti CD40L) T cell receptors in the form of Fab antibody regions. We have constructed targeted liposomes (immuno-liposomes), which are also traceable in-vivo via fluorescent and Magnetic Resonance Imaging (MRI). Ex-vivo (human) and in-vivo (animal) models have been investigated showing firstly that these super-para-magnetic immuno-liposomes circulate the body safely and facilitate their own focusing to specific organs, tumour sites or body areas by applying external magnetic attraction. Secondly, in a viral (CMV) antigen specific model and measured by relevant and irrelevant tetramers, the system is capable of activating and expanding antigen specific T cells at greater levels (200 fold) than standard methods from CMV positive (memory) individuals. The system has also been able to accomplish a small successful level of T cell priming from naive CMV negative individuals. The T cells are phenotypicaly relevant and fully functional in terms of degranulation and cytokine production when specifically challenged. As mechanisms of action, we have demonstrated that the system functions directly on T cells as micro APCs and also semi-directly on the surface of natural APCs following a similar exosomes kinetics. The system is generated in less that 48 hr. Once the aAPC is created and it remains viable and stable for 7 days minimum. We have established optimal conditions for an efficient artificial APC, which embodies a superior and controllable approach and platform with enormous potential for cancer nanotechnology and T cell mediated immunotherapy.

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CT Visualization of Cryoablation in Pulmonary Veins

Journal of Medical Devices ◽

10.1115/1.3135157 ◽

2009 ◽

Vol 3 (2) ◽

Author(s):

M. Shenoi ◽

X. Zhang ◽

J. Bischof ◽

L. George

Keyword(s):

The United States ◽

Ct Imaging ◽

The Body ◽

Esophageal Injury ◽

Invasive Technique ◽

Freezing Process ◽

Agarose Gel ◽

Metal Artifacts

Over 2 million adults in the United States are affected by atrial fibrillation (AF), a common cardiac arrhythmia that is associated with decreased survival, increased cardiovascular morbidities, and a decrease in quality of life. AF can be initiated by ectopic beats originating in the myocardial sleeves surrounding the pulmonary viens. Pulmonary vein (PV) isolation via radio frequency ablation is the current gold standard for treating patients with drug-refractory AF. However, cryoablation is emerging as a new minimally-invasive technique to achieve PV isolation. Cryoablation is fast gaining acceptance due to its minimal tissue disruption, decreased thrombogenicity, and reduced complications (RF can lead to low rate of stenosis). One important question in regard to this technology is whether the PV lesion is transmural and circumferential and to what extent adjacent tissues are involved in the freezing process. As ice formation lends itself to image contrast in the body, we hypothesized that intraprocedural CT visualization of the iceball formation would allow us to predict the extent of the cryolesion and provide us with a measure of the adjacent tissue damage. Cryoablation was performed using a prototype balloon catheter cryoablation system (Boston Scientific Corporation). CT visualization of iceball formation was assessed both in vitro and in vivo. Initial in vitro studies were performed in agarose gel phantoms immersed in a 37°C water bath. Subsequently, in vivo cryoablations were performed in 5 PV ostia in 3 crossbred farm swine. The catheters were positioned in the ostia under fluoroscopic guidance. CT scans of the thoracic region were obtained every 2.5 minutes. Animals were sacrified 6 days after the procedures. Gross pathology and histology of tissues in the region of interest were evaluated. Significant metal artifacts from the catheter and edge artifacts from the tissues surrounding the cryoballoon were observed under CT imaging both in vitro and in vivo. In vitro, it was found that the size of the iceball was comparable to that observed visually during freezing of agarose gel phantoms. In vivo, contrast change consistent with iceball formation was observed during the ablation in two out of five veins. The most clearly delineated iceball also yielded the clearest morbidity. In this case, esophageal injury on the anterior side proximal to the cryoablation site was noticed during necropsy of the animal in which the iceball was visualized. Transmural and circumferential lesions were obtained in all PVs ablated. We have shown that CT can be used to visualize iceball formation in vitro and in vivo (with limitations) using our cryoablation system. While the iceball in vitro is easily visualized, iceball growth in vivo is most evident once the iceball has grown beyond the PV into the adjacent tissues. This suggests that while CT cannot easily visualize iceball growth in the PV wall itself, it may still be an important tool to guide clinicians and reduce potential morbidities in adjacent tissues. The authors acknowledge Dan Busian (Fairview University Medical Center, Minneapolis, MN) and Dr. Erik Cressman for assistance with CT imaging.

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The Intestinal Barrier and Current Techniques for the Assessment of Gut Permeability

Cells ◽

10.3390/cells9081909 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1909 ◽

Cited By ~ 2

Author(s):

Ida Schoultz ◽

Åsa V. Keita

Keyword(s):

Intestinal Permeability ◽

Barrier Function ◽

Ex Vivo ◽

Intestinal Barrier ◽

The Body ◽

Functional Studies ◽

Gut Barrier Function ◽

Diverse Backgrounds

The intestinal barrier is essential in human health and constitutes the interface between the outside and the internal milieu of the body. A functional intestinal barrier allows absorption of nutrients and fluids but simultaneously prevents harmful substances like toxins and bacteria from crossing the intestinal epithelium and reaching the body. An altered intestinal permeability, a sign of a perturbed barrier function, has during the last decade been associated with several chronic conditions, including diseases originating in the gastrointestinal tract but also diseases such as Alzheimer and Parkinson disease. This has led to an intensified interest from researchers with diverse backgrounds to perform functional studies of the intestinal barrier in different conditions. Intestinal permeability is defined as the passage of a solute through a simple membrane and can be measured by recording the passage of permeability markers over the epithelium via the paracellular or the transcellular route. The methodological tools to investigate the gut barrier function are rapidly expanding and new methodological approaches are being developed. Here we outline and discuss, in vivo, in vitro and ex vivo techniques and how these methods can be utilized for thorough investigation of the intestinal barrier.

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Biomedical applications of copper-free click chemistry: in vitro, in vivo, and ex vivo

Chemical Science ◽

10.1039/c9sc03368h ◽

2019 ◽

Vol 10 (34) ◽

pp. 7835-7851 ◽

Cited By ~ 55

Author(s):

Eunha Kim ◽

Heebeom Koo

Keyword(s):

Click Chemistry ◽

Chemical Reactions ◽

Biomedical Applications ◽

Ex Vivo ◽

The Body ◽

Cell Surfaces ◽

Cell Cytosol ◽

Biomedical Fields

Copper-free click chemistry has resulted in a change of paradigm, showing that artificial chemical reactions can occur on cell surfaces, in cell cytosol, or within the body. It has emerged as a valuable tool in biomedical fields.

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The Fate of Methylmercury Through Formation of Bismethylmercury Sulfide as an Intermediate in Mice

10.21203/rs.3.rs-454570/v1 ◽

2021 ◽

Author(s):

Yumi Abiko ◽

Yusuke Katayama ◽

Wenyang Zhao ◽

Sawako Horai ◽

Kenji Sakurai ◽

...

Keyword(s):

Ex Vivo ◽

Intraperitoneal Administration ◽

Distal Colon ◽

Intestinal Content ◽

The Body ◽

Gas Chromatography Mass Spectrometry ◽

Free System ◽

A Cell

Abstract A previous study of ours indicated that methylmercury (MeHg) is biotransformed to bismethylmercury sulfide [(MeHg)2S)] by interaction with reactive sulfur species (RSS) produced in the body. In the present study, we explored the transformation of MeHg to (MeHg)2S in the gut and the subsequent fate of (MeHg)2S in vitro and in vivo. An ex vivo experiment suggested the possibility of extracellular transformation of MeHg to (MeHg)2S in the distal colon, and accordingly, the sulfur adduct MeHg was detected in the intestinal content and feces of mice given MeHg, suggesting that (MeHg)2S is formed from reactions of MeHg with RSS in the gut. In a cell-free system, we found that (MeHg)2S spontaneously undergoes degradation in a time-dependent fashion, resulting in formation of mercury sulfide, as determined by X-ray diffraction, and dimethylmercury (DMeHg), as evaluated by gas chromatography/mass spectrometry. We also identified DMeHg in expiration after intraperitoneal administration of (MeHg)2S to mice. Our present study therefore identifies a new fate of MeHg through (MeHg)2S as an intermediate, which leads to conversion of volatile DMeHg in the body.

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