scholarly journals Radiologic-pathologic analysis of increased ethanol localization and ablative extent achieved by ethyl cellulose

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Erika Chelales ◽  
Robert Morhard ◽  
Corrine Nief ◽  
Brian Crouch ◽  
Jeffrey I. Everitt ◽  
...  
Keyword(s):  
Ethyl Cellulose ◽  
Time Course ◽  
Ethanol Concentration ◽  
Ex Vivo ◽  
Ct Imaging ◽  
Distribution Volume ◽  
Ablation Zone ◽  
Pure Ethanol ◽  
The Relationship

AbstractEthanol provides a rapid, low-cost ablative solution for liver tumors with a small technological footprint but suffers from uncontrolled diffusion in target tissue, limiting treatment precision and accuracy. Incorporating the gel-forming polymer ethyl cellulose to ethanol localizes the distribution. The purpose of this study was to establish a non-invasive methodology based on CT imaging to quantitatively determine the relationship between the delivery parameters of the EC-ethanol formulation, its distribution, and the corresponding necrotic volume. The relationship of radiodensity to ethanol concentration was characterized with water–ethanol surrogates. Ex vivo EC-ethanol ablations were performed to optimize the formulation (n = 6). In vivo ablations were performed to compare the optimal EC-ethanol formulation to pure ethanol (n = 6). Ablations were monitored with CT and ethanol distribution volume was quantified. Livers were removed, sectioned and stained with NADH-diaphorase to determine the ablative extent, and a detailed time-course histological study was performed to assess the wound healing process. CT imaging of ethanol–water surrogates demonstrated the ethanol concentration-radiodensity relationship is approximately linear. A concentration of 12% EC in ethanol created the largest distribution volume, more than eight-fold that of pure ethanol, ex vivo. In vivo, 12% EC-ethanol was superior to pure ethanol, yielding a distribution volume three-fold greater and an ablation zone six-fold greater than pure ethanol. Finally, a time course histological evaluation of the liver post-ablation with 12% EC-ethanol and pure ethanol revealed that while both induce coagulative necrosis and similar tissue responses at 1–4 weeks post-ablation, 12% EC-ethanol yielded a larger ablation zone. The current study demonstrates the suitability of CT imaging to determine distribution volume and concentration of ethanol in tissue. The distribution volume of EC-ethanol is nearly equivalent to the resultant necrotic volume and increases distribution and necrosis compared to pure ethanol.

scholarly journals Radiologic-Pathologic Analysis of Increased Ethanol Localization and Ablative Extent Achieved by Ethyl Cellulose

2020 ◽  
Author(s):  
Erika Chelales ◽  
Robert Morhard ◽  
Corrine Nief ◽  
Brian Crouch ◽  
Alan Sag ◽  
...  
Keyword(s):  
Ethyl Cellulose ◽  
Ethanol Concentration ◽  
Liver Tumors ◽  
Ex Vivo ◽  
Low Cost ◽  
Distribution Volume ◽  
Target Tissue ◽  
Pure Ethanol ◽  
Middle Income

Abstract PurposeEthanol provides a rapid, low-cost ablative solution for liver tumors with a small technological footprint but suffers from uncontrolled diffusion in target tissue, limiting treatment precision and accuracy. The authors demonstrate that incorporating the gel-forming polymer ethyl cellulose to ethanol localizes the distribution. This therapy may have a low barrier of entry for cancer care in low- and middle- income countries.Materials and MethodsThe relationship of radiodensity to ethanol concentration was characterized with water-ethanol surrogates. Ex vivo EC-ethanol ablations were performed to optimize the formulation (n=6). In vivo ablations were performed to compare the optimal EC-ethanol formulation to pure ethanol (n=6). Ablations were monitored with CT and ethanol distribution volume was quantified. Livers were explanted, sectioned and stained with NADH-diaphorase to determine the ablative extent.ResultsCT imaging of ethanol-water surrogates demonstrated the ethanol concentration-radiodensity relationship is approximately linear. A concentration of 12% EC in ethanol created the largest distribution volume, more than 8-fold that of pure ethanol, ex vivo. In vivo, 12% EC-ethanol was superior to pure ethanol, yielding a distribution volume 3 times greater and an ablation zone 6 times greater than pure ethanol.Conclusions EC-ethanol, a novel gel formulation injectable ablative injectate, safely increases distribution and necrosis compared to pure ethanol.

scholarly journals Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 730
Author(s):  
Biji Mathew ◽  
Leianne A. Torres ◽  
Lorea Gamboa Gamboa Acha ◽  
Sophie Tran ◽  
Alice Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Time Course ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Dependent Manner ◽  
Paracrine Effects

Cell replacement therapy using mesenchymal (MSC) and other stem cells has been evaluated for diabetic retinopathy and glaucoma. This approach has significant limitations, including few cells integrated, aberrant growth, and surgical complications. Mesenchymal Stem Cell Exosomes/Extracellular Vesicles (MSC EVs), which include exosomes and microvesicles, are an emerging alternative, promoting immunomodulation, repair, and regeneration by mediating MSC’s paracrine effects. For the clinical translation of EV therapy, it is important to determine the cellular destination and time course of EV uptake in the retina following administration. Here, we tested the cellular fate of EVs using in vivo rat retinas, ex vivo retinal explant, and primary retinal cells. Intravitreally administered fluorescent EVs were rapidly cleared from the vitreous. Retinal ganglion cells (RGCs) had maximal EV fluorescence at 14 days post administration, and microglia at 7 days. Both in vivo and in the explant model, most EVs were no deeper than the inner nuclear layer. Retinal astrocytes, microglia, and mixed neurons in vitro endocytosed EVs in a dose-dependent manner. Thus, our results indicate that intravitreal EVs are suited for the treatment of retinal diseases affecting the inner retina. Modification of the EV surface should be considered for maintaining EVs in the vitreous for prolonged delivery.

scholarly journals Monitoring the Early Response of Fulvestrant Plus Tanshinone IIA Combination Therapy to Estrogen Receptor-Positive Breast Cancer by Longitudinal 18F-FES PET/CT

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
SiMin He ◽  
MingWei Wang ◽  
YongPing Zhang ◽  
JianMin Luo ◽  
YingJian Zhang
Keyword(s):  
Combination Therapy ◽  
Ex Vivo ◽  
Early Response ◽  
Ct Imaging ◽  
Tanshinone Iia ◽  
Breast Cancers ◽  
Antitumor Effects ◽  
Pet Ct ◽  
Er Positive

Endocrine monotherapy of breast cancers is generally hampered by the primary/acquired resistance and adverse sides in clinical settings. Herein, advantaging the multitargeting antitumor effects and normal organ-protecting roles of Chinese herbal medicine, the aim of this study was to investigate the enhanced synergistic efficacy of fulvestrant plus Tan IIA combination therapy in ER-positive breast cancers and to monitor the early response by longitudinal 18F-FES PET/CT imaging. The experimental results showed FUL + Tan IIA combination therapy significantly inhibited tumor growth of ER-positive ZR-75-1 tumor xenografts and exhibited distinct antitumor effects at an earlier time point after treatment than did the monotherapy of FUL or Tan IIA. Moreover, 18F-FES PET/CT imaging competently monitored the early response of FUL + Tan IIA combination therapy. The quantitative 18F-FES %ID/gmax in vivo was further confirmed by and correlated well with ERα expression ex vivo. In conclusion, the synergic effect of FUL + Tan IIA combination therapy to ER-positive breast cancers was verified in the preclinical tumor models and the early treatment response could be monitored by 18F-FES PET/CT.

scholarly journals Progestin increases the expression of gonadotropins in pituitaries of male zebrafish

2016 ◽  
Vol 230 (1) ◽  
pp. 143-156 ◽  
Author(s):  
Cuili Wang ◽  
Dongteng Liu ◽  
Weiting Chen ◽  
Wei Ge ◽  
Wanshu Hong ◽  
...  
Keyword(s):  
Time Course ◽  
Ex Vivo ◽  
Mrna Levels ◽  
Adult Zebrafish ◽  
Male Adult ◽  
Positive Effects ◽  
Time Course Experiment ◽  
Nuclear Progesterone Receptor

Our previous study showed that the in vivo positive effects of 17α,20β-dihydroxy-4-pregnen-3-one (DHP), the major progestin in zebrafish, on early spermatogenesis was much stronger than the ex vivo ones, which may suggest an effect of DHP on the expression of gonadotropins. In our present study, we first observed that fshb and lhb mRNA levels in the pituitary of male adult zebrafish were greatly inhibited by 3 weeks exposure to 10nM estradiol (E2). However, an additional 24h 100nM DHP exposure not only reversed the E2-induced inhibition, but also significantly increased the expression of fshb and lhb mRNA. These stimulatory effects were also observed in male adult fish without E2 pretreatment, and a time course experiment showed that it took 24h for fshb and 12h for lhb to respond significantly. Because these stimulatory activities were partially antagonized by a nuclear progesterone receptor (Pgr) antagonist mifepristone, we generated a Pgr-knockout (pgr–/–) model using the TALEN technique. With and without DHP in vivo treatment, fshb and lhb mRNA levels of pgr–/– were significantly lower than those of pgr+/+. Furthermore, ex vivo treatment of pituitary fragments of pgr–/– with DHP stimulated lhb, but not fshb mRNA expression. Results from double-colored fluorescent in situ hybridization showed that pgr mRNA was expressed only in fshb-expressing cells. Taken together, our results indicated that DHP participated in the regulation of neuroendocrine control of reproduction in male zebrafish, and exerted a Pgr-mediated direct stimulatory effect on fshb mRNA at pituitary level.

scholarly journals Multimodality Approach to Characterizing the Distinctive Hallmarks of Lung Fibrosis: A Mouse Model with Bleomycin and Indocyanine Green

2021 ◽  
Author(s):  
Andrea Grandi ◽  
Erica Ferrini ◽  
Roberta Ciccimarra ◽  
Martina Mambrini ◽  
Laura Mecozzi ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Time Course ◽  
Ex Vivo ◽  
Imaging Techniques ◽  
Lavage Fluid ◽  
Pharmacological Therapy ◽  
Micro Ct ◽  
Oropharyngeal Aspiration ◽  
Multimodality Approach

Abstract Background.Idiopathic Pulmonary Fibrosis is a progressive disease with short life expectancy and no disease-modifying pharmacological therapy. The continuous refinement of animal models and the integration of in-vivo imaging techniques is fundamental for the selection of new antifibrotic drugs.Indocyanine Green (ICG), a fluorescent dye, was administered by oropharyngeal aspiration (OA) to mice with Bleomycin (BLM) to map the lung exposure.Methods.Female mice C57bl/6 were treated via OA with BLM+ICG or ICG. Animals were imaged at 7, 14 and 21 days either with the fluorescent system or Micro-CT. At each time point subsets of mice were sampled for ex-vivo assessment. Histological assessment of fibrosis by Ashcroft score, airspace enlargements and mean linear intercept (MLI) were evaluated at 7, 14 and 21 days. Leukocytes and cytokines were measured in bronchoalveolar lavage fluid. Results.Fluorescence imaging revealed a persistent lung signal in both groups until 21 days. In BLM+ICG group, Micro-CT detected a marked increase in hypo- and non-aerated tissues throughout the study. At later time points hyper-inflated tissue was detected. Histology revealed high Ashcroft score throughout the time-course with a prominent increase in airspace size and MLI at day 21. ICG mice had healthy lungs.Conclusions.We showed that ICG can be used as a tracer to map the distribution of BLM in lungs. However, BLM+ICG produced unexpected severe lung changes different from pure BLM model, such as emphysema-like features which progressively worsened. The multimodalities approach warranted characterization of the distinctive features of this new pulmonary fibrosis model and provided fundamentals for in-vivo translation.

scholarly journals Extrapolating In Vitro Screening Assay Data for Thyroperoxidase Inhibition to Predict Serum Thyroid Hormones in the Rat

2019 ◽  
Vol 173 (2) ◽  
pp. 280-292 ◽  
Author(s):  
Iman Hassan ◽  
Hisham El-Masri ◽  
Jermaine Ford ◽  
Amanda Brennan ◽  
Sakshi Handa ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Time Course ◽  
Ex Vivo ◽  
Response Analysis ◽  
In Vitro Screening ◽  
Screening Assay ◽  
High Throughput Screening Assay ◽  
Serum T4

Abstract Thyroperoxidase (TPO) is an enzyme essential for thyroid hormone (TH) synthesis and a target site for a number of xenobiotics that disrupt TH homeostasis. An in vitro high-throughput screening assay for TPO inhibition, the Amplex UltraRed-TPO (AUR-TPO), has been used to screen the ToxCast chemical libraries for this action. Output from this assay would be most useful if it could be readily translated into an in vivo response, namely a reduction of TH in serum. To this end, the relationship between TPO inhibition in vitro and serum TH decreases was examined in rats exposed to 2 classic TPO inhibitors, propylthiouracil (PTU) and methimazole (MMI). Serum and gland PTU, MMI, and TH levels were quantified using tandem liquid chromatography mass spectrometry. Thyroperoxidase activity was determined in thyroid gland microsomes treated with PTU or MMI in vitro and ex vivo from thyroid gland microsomes prepared from exposed animals. A quantitative model was constructed by contrasting in vitro and ex vivo AUR-TPO results and the in vivo time-course and dose-response analysis. In vitro:ex vivo correlations of AUR-TPO outputs indicated that less than 30% inhibition of TPO in vitro was sufficient to reduce serum T4 by 20%, a degree of regulatory significance. Although further testing of model estimates using other TPO inhibitors is essential for verification of these initial findings, the results of this study provide a means to translate in vitro screening assay results into predictions of in vivo serum T4 changes to inform risk assessment.

scholarly journals Relationship Between Ex Vivo Tissue Diffusion Tensor Indexes and Material Properties in Posterior Tibialis Tendon

2019 ◽  
Vol 4 (4) ◽  
pp. 2473011419S0045
Author(s):  
Jennifer A. Zellers ◽  
Masoud Edalati ◽  
Jeremy Eekhoff ◽  
Spencer P. Lake ◽  
Jie Zheng ◽  
...  
Keyword(s):  
Diffusion Tensor ◽  
Ex Vivo ◽  
Water Displacement ◽  
Tendon Tissue ◽  
Tract Length ◽  
Tissue Organization ◽  
Scan Time ◽  
Relationship Of ◽  
The Relationship

Category: Ankle, tendon imaging Introduction/Purpose: Posterior tibialis tendon is of clinical importance in the development and progression of acquired flatfoot and other midfoot deformity. The ability to quantitatively evaluate tendon tissue non-invasively would enable assessment of tendon health status and tracking of recovery from injury. Magnetic resonance diffusion tensor imaging (DTI) has been used to examine tendon tissue organization in healing tendon tissue. However, the relationship of DTI-based measures to tendon mechanical function has not been established. The purpose of this pilot study was to quantitatively evaluate posterior tibialis tendon using DTI and determine the relationship of these parameters to tendon function assessed via ex vivo mechanical testing. Methods: Posterior tibialis tendons from individuals undergoing amputation were positioned vertically in an agarose mold filled with saline for imaging. High resolution diffusion imaging parameters were optimized for tendon on a 3 T MRI to acquire 13 6-mm transverse slices covering the length: 1mm2 isotropic resolution, 2 signal averaging, repetition/echo times of 5000/58 ms, diffusion strength of 500s/mm2 with 30 gradient directions, scan time 5 min. Diffusion images had sufficient quality and were corrected for motion and image distortion. DTI parametric maps including fractional anisotropy (FA), mean, axial, and radial diffusivities (MD, AD, and RD; mm2/s) were calculated along with fiber tracking indexes of fiber length (mm) and density. After imaging, specimens were preloaded to 10 Newtons, preconditioned 10 cycles at 6% strain, subjected to stress-relaxation at 6% strain (10 minutes), then loaded to a maximum of 10% strain. Relationships between DTI indexes and mechanical properties (stiffness and hysteresis) were evaluated using Spearman correlation. Results: Six individuals (4 male, mean(SD) age: 56(5)years, body mass index: 30(6) kg/m2) were included. Reason for amputation was diabetes-related complications in 5 participants and failed orthopaedic surgery in 1 participant. In DTI (Figure 1A), tendons had a tract length of 11.5(11.3)mm and tract density of 23.9(2.4) per ROI. FA, MD, AD, and RD quantify how freely a water molecule is able to move within the tissue, and the directionality of that movement. Tendons had an FA of 0.26(0.25), MD of 1.25(1.28), AD of 1.54(1.57), and RD of 1.11(1.14). Tract length was positively related to linear stiffness (rho=0.829, p=0.04) and hysteresis at 10% strain (rho=0.886, p=0.019) (Figure 1B-D). AD was positively related to hysteresis at 10% strain (rho=0.812, p=0.05). Conclusion: This is the first study to describe posterior tibialis tendon appearance on DTI. Tract length and AD are both related to tendon mechanics. Tract length is based on quantity and directionality of water displacement and may indicate degree of collagen organization given its relationship to stiffness. Tract length and AD related positively to hysteresis, which will require additional research to identify the mechanisms behind this relationship. This study is limited by sample size and specimens that likely do not represent healthy tissue. Regardless, these findings support continued investigation into in vivo imaging of tendon with DTI for quantitative tendon assessment.

The effects of repeated allergen challenge on airway smooth muscle structural and molecular remodeling in a rat model of allergic asthma

2009 ◽  
Vol 297 (4) ◽  
pp. L698-L705 ◽  
Author(s):  
Isabelle Labonté ◽  
Muhannad Hassan ◽  
Paul-André Risse ◽  
Kimitake Tsuchiya ◽  
Michel Laviolette ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Ex Vivo ◽  
Mrna Level ◽  
Allergen Challenge ◽  
Airway Responsiveness ◽  
Brown Norway ◽  
Contractile Phenotype ◽  
The Relationship

The effects of remodeling of airway smooth muscle (SM) by hyperplasia on airway SM contractility in vivo are poorly explored. The aim of this study was to investigate the relationship between allergen-induced airway SM hyperplasia and its contractile phenotype. Brown Norway rats were sensitized with ovalbumin (OVA) or saline on day 0 and then either OVA-challenged once on day 14 and killed 24 h later or OVA-challenged 3 times (on days 14, 19, and 24) and killed 2 or 7 days later. Changes in SM mass, expression of total myosin, SM myosin heavy chain fast isoform (SM-B) and myosin light chain kinase (MLCK), tracheal contractions ex vivo, and airway responsiveness to methacholine (MCh) in vivo were assessed. One day after a single OVA challenge, the number of SM cells positive for PCNA was greater than for control animals, whereas the SM mass, contractile phenotype, and tracheal contractility were unchanged. Two days after three challenges, SM mass and PCNA immunoreactive cells were increased (3- and 10-fold, respectively; P < 0.05), but airway responsiveness to MCh was unaffected. Lower expression in total myosin, SM-B, and MLCK was observed at the mRNA level ( P < 0.05), and total myosin and MLCK expression were lower at the protein level ( P < 0.05) after normalization for SM mass. Normalized tracheal SM force generation was also significantly lower 2 days after repeated challenges ( P < 0.05). Seven days after repeated challenges, features of remodeling were restored toward control levels. Allergen-induced hyperplasia of SM cells was associated with a loss of contractile phenotype, which was offset by the increase in mass.

scholarly journals Frictional internal work of damped limbs oscillation in human locomotion

2020 ◽  
Vol 287 (1931) ◽  
pp. 20201410 ◽  
Author(s):  
Alberto E. Minetti ◽  
Alex P. Moorhead ◽  
Gaspare Pavei
Keyword(s):  
Energy Balance ◽  
Time Course ◽  
Ex Vivo ◽  
Biological Tissues ◽  
The Body ◽  
Lower Limbs ◽  
Metabolic Energy ◽  
External Work ◽  
Internal Work

Joint friction has never previously been considered in the computation of mechanical and metabolic energy balance of human and animal (loco)motion, which heretofore included just muscle work to move the body centre of mass (external work) and body segments with respect to it. This happened mainly because, having been previously measured ex vivo , friction was considered to be almost negligible. Present evidences of in vivo damping of limb oscillations, motion captured and processed by a suited mathematical model, show that: (a) the time course is exponential, suggesting a viscous friction operated by the all biological tissues involved; (b) during the swing phase, upper limbs report a friction close to one-sixth of the lower limbs; (c) when lower limbs are loaded, in an upside-down body posture allowing to investigate the hip joint subjected to compressive forces as during the stance phase, friction is much higher and load dependent; and (d) the friction of the four limbs during locomotion leads to an additional internal work that is a remarkable fraction of the mechanical external work. These unprecedented results redefine the partitioning of the energy balance of locomotion, the internal work components, muscle and transmission efficiency, and potentially readjust the mechanical paradigm of the different gaits.

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