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1

Lifetime-based photoacoustic oxygen sensing in vivo  

PubMed Central

Abstract. The determination of oxygen levels in blood and other tissues in vivo is critical for ensuring proper body functioning, for monitoring the status of many diseases, such as cancer, and for predicting the efficacy of therapy. Here we demonstrate, for the first time, a lifetime-based photoacoustic technique for the measurement of oxygen in vivo, using an oxygen sensitive dye, enabling real time quantification of blood oxygenation. The results from the main artery in the rat tail indicated that the lifetime of the dye, quantified by the photoacoustic technique, showed a linear relationship with the blood oxygenation levels in the targeted artery. PMID:22612143

Ray, Aniruddha; Rajian, Justin Rajesh; Lee, Yong-Eun Koo; Wang, Xueding; Kopelman, Raoul

2012-01-01

2

Solid MRI contrast agents for long-term, quantitative in vivo oxygen sensing  

PubMed Central

Targeted MRI contrast agents have proven useful in research and clinical studies for highlighting specific metabolites and biomarkers [Davies GL, et al. (2013) Chem Commun (Camb) 49(84):9704–9721] but their applicability in serial imaging is limited owing to a changing concentration postinjection. Solid enclosures have previously been used to keep the local concentration of contrast agent constant, but the need to surgically implant these devices limits their use [Daniel K, et al. (2009) Biosens Bioelectron 24(11):3252–3257]. This paper describes a novel class of contrast agent that comprises a responsive material for contrast generation and an injectable polymeric matrix for structural support. Using this principle, we have designed a contrast agent sensitive to oxygen, which is composed of dodecamethylpentasiloxane as the responsive material and polydimethylsiloxane as the matrix material. A rodent inspired-gas model demonstrated that these materials are functionally stable in vivo for at least 1 mo, which represents an order of magnitude improvement over an injection of liquid siloxane [Kodibagkar VD, et al. (2006) Magn Reson Med 55(4):743–748]. We also observed minimal adverse tissue reactions or migration of contrast agents from the initial injection site. This class of contrast agents, thus, represented a new and complementary method to monitor chronic diseases by MRI. PMID:24753603

Liu, Vincent H.; Vassiliou, Christophoros C.; Imaad, Syed M.; Cima, Michael J.

2014-01-01

3

Optical oxygen sensing systems for drug discovery applications: Respirometric Screening Technology (RST)  

NASA Astrophysics Data System (ADS)

Quenched-fluorescence oxygen sensing allows non-chemical, reversible, real-time monitoring of molecular oxygen and rates of oxygen consumption in biological samples. Using this approach we have developed Respirometric Screening Technology (RST); a platform which facilitates the convenient analysis of cellular oxygen uptake. This in turn allows the investigation of compounds and processes which affect respiratory activity. The RST platform employs soluble phosphorescent oxygen-sensitive probes, which may be assessed in standard microtitter plates on a fluorescence plate reader. New formats of RST assays and time-resolved fluorescence detection instrumentation developed by Luxcel provide improvements in assay sensitivity, miniaturization and overall performance. RST has a diverse range of applications in drug discovery area including high throughput analysis of mitochondrial function; studies of mechanisms of toxicity and apoptosis; cell and animal based screening of compound libraries and environmental samples; and, sterility testing. RST has been successfully validated with a range of practical targets and adopted by several leading pharmaceutical companies.

Papkovsky, Dmitri B.; Hynes, James; Fernandes, Richard

2005-11-01

4

Significance of KATP channels, L-type Ca2+ channels and CYP450-4A enzymes in oxygen sensing in mouse cremaster muscle arterioles In vivo  

PubMed Central

Background ATP-sensitive K+ channels (KATP channels), NO, prostaglandins, 20-HETE and L-type Ca2+ channels have all been suggested to be involved in oxygen sensing in skeletal muscle arterioles, but the role of the individual mechanisms remain controversial. We aimed to establish the importance of these mechanisms for oxygen sensing in arterioles in an in vivo model of metabolically active skeletal muscle. For this purpose we utilized the exteriorized cremaster muscle of anesthetized mice, in which the cremaster muscle was exposed to controlled perturbation of tissue PO2. Results Change from “high” oxygen tension (PO2?=?153.4?±?3.4?mmHg) to “low” oxygen tension (PO2?=?13.8?±?1.3?mmHg) dilated cremaster muscle arterioles from 11.0?±?0.4??m to 32.9?±?0.9??m (n?=?28, P?oxygen sensing, 2) KATP channels are permissive for the arteriolar response to oxygen, but are not directly involved in the oxygen sensing mechanism and 3) CYP450-4A mediated 20-HETE production is involved in vasoconstriction to high PO2. PMID:23663730

2013-01-01

5

Oxygen sensing in the body  

Microsoft Academic Search

This review is divided into three parts: (a) The primary site of oxygen sensing is the carotid body which instantaneously respond to hypoxia without involving new protein synthesis, and is historically known as the first oxygen sensor and is therefore placed in the first section (Lahiri, Roy, Baby and Hoshi). The carotid body senses oxygen in acute hypoxia, and produces

S. Lahiri; A. Roy; S. M. Baby; T. Hoshi; G. L. Semenza; N. R. Prabhakar

2006-01-01

6

Injectable polymer for in vivo oxygen sensing  

E-print Network

This thesis documents the synthesis and characterization of an elastomeric polymer that is oxygen sensitive and can be interrogated using Magnetic Resonance Imaging (MRI) or Magnetic Resonance (MR) technology to report the ...

Imaad, Syed M. (Syed Muhammad)

2013-01-01

7

Ratiometric optical oxygen sensing: a review in respect of material design.  

PubMed

The quantitative determination of oxygen concentration is essential for a variety of applications ranging from life sciences to environmental sciences. Optical oxygen sensing allows non-invasive measurements with biological objects, parallel monitoring of multiple samples, and imaging. In general, ratiometric optical oxygen sensing is more desirable, due to its advantages of selectivity, insensitivity to ambient or scattered light, and elimination of instrumental fluctuation. Moreover, it can provide the perceived colour change, which would be useful not only for the ratiometric method of detection but also for rapid visual sensing. Mainly focusing on material design for ratiometric measurement, this review describes the overall progress made in the past ten years on ratiometric optical ground-state triplet oxygen sensing and offers a critical comparison of various methods reported in the literature. It also provides a development blueprint for ratiometric optical oxygen sensing. PMID:22943050

Feng, Yan; Cheng, Jinghui; Zhou, Li; Zhou, Xiangge; Xiang, Haifeng

2012-11-01

8

Characterization of ormosil film for dissolved oxygen-sensing  

Microsoft Academic Search

An organically modified silicate (ormosil) as a matrix for the fabrication of dissolved oxygen-sensing film was produced. The process included taking tetramethoxysilane (TMOS) and dimethyldimethoxysilane (DiMe-DMOS) as precursor and running a reaction at 60°C in an open vial, which accelerates hydrolysis and condensation and results in the formation of emulsion. The film doped with tris-(4,7-diphenyl-1,10-phenanthroline) ruthenium(II) ([Ru(dpp)3]2+) as an oxygen

Xi Chen; Zhenming Zhong; Zhen Li; Yaqi Jiang; Xiaoru Wang; Kwokyin Wong

2002-01-01

9

Ceramide Mediates Acute Oxygen Sensing in Vascular Tissues  

PubMed Central

Abstract Aims: A variety of vessels, such as resistance pulmonary arteries (PA) and fetoplacental arteries and the ductus arteriosus (DA) are specialized in sensing and responding to changes in oxygen tension. Despite opposite stimuli, normoxic DA contraction and hypoxic fetoplacental and PA vasoconstriction share some mechanistic features. Activation of neutral sphingomyelinase (nSMase) and subsequent ceramide production has been involved in hypoxic pulmonary vasoconstriction (HPV). Herein we aimed to study the possible role of nSMase-derived ceramide as a common factor in the acute oxygen-sensing function of specialized vascular tissues. Results: The nSMase inhibitor GW4869 and an anticeramide antibody reduced the hypoxic vasoconstriction in chicken PA and chorioallantoic arteries (CA) and the normoxic contraction of chicken DA. Incubation with interference RNA targeted to SMPD3 also inhibited HPV. Moreover, ceramide and reactive oxygen species production were increased by hypoxia in PA and by normoxia in DA. Either bacterial sphingomyelinase or ceramide mimicked the contractile responses of hypoxia in PA and CA and those of normoxia in the DA. Furthermore, ceramide inhibited voltage-gated potassium currents present in smooth muscle cells from PA and DA. Finally, the role of nSMase in acute oxygen sensing was also observed in human PA and DA. Innovation: These data provide evidence for the proposal that nSMase-derived ceramide is a critical player in acute oxygen-sensing in specialized vascular tissues. Conclusion: Our results indicate that an increase in ceramide generation is involved in the vasoconstrictor responses induced by two opposite stimuli, such as hypoxia (in PA and CA) and normoxia (in DA). Antioxid. Redox Signal. 20, 1–14. PMID:23725018

Moreno, Laura; Moral-Sanz, Javier; Morales-Cano, Daniel; Barreira, Bianca; Moreno, Enrique; Ferrarini, Alessia; Pandolfi, Rachele; Ruperez, Francisco J.; Cortijo, Julio; Sanchez-Luna, Manuel; Villamor, Eduardo; Perez-Vizcaino, Francisco

2014-01-01

10

Two-Photon Oxygen Sensing with Quantum Dot-Porphyrin Conjugates  

PubMed Central

Supramolecular assemblies of a quantum dot (QD) associated to palladium(II) porphyrins have been developed to detect oxygen (pO2) in organic solvents. Palladium porphyrins are sensitive in the 0–160 torr range, making them ideal phosphors for in vivo biological oxygen quantification. Porphyrins with meso pyridyl substituents bind to the surface of the QD to produce self–assembled nanosensors. Appreciable overlap between QD emission and porphyrin absorption features results in efficient Förster resonance energy transfer (FRET) for signal transduction in these sensors. The QD serves as a photon antenna, enhancing porphyrin emission under both one– and two–photon excitation, demonstrating that QD–palladium porphyrin conjugates may be used for oxygen sensing over physiological oxygen ranges. PMID:23978247

Lemon, Christopher M.; Karnas, Elizabeth; Bawendi, Moungi G.; Nocera, Daniel G.

2013-01-01

11

The Role of Redox Changes in Oxygen Sensing  

PubMed Central

The specialized oxygen-sensing tissues include the carotid body and arterial smooth muscle cells in the pulmonary artery (PA) and ductus arteriosus (DA). We discuss the evidence that changes in oxygen tension are sensed through changes in redox status. “Redox” changes imply the giving or accepting of electrons. This might occur through the direct tunneling of electrons from mitochondria or redox couples to an effector protein (eg. ion channel). Alternatively, the electron might be transferred through reactive oxygen species from mitochondria or an NADPH oxidase isoform. The PA's response to hypoxia and DA's response to normoxia result from reduction or oxidation, respectively. These opposing redox stimuli lead to K+ channel inhibition, membrane depolarization and an increase in cytosolic calcium and/or calcium sensitization that causes contraction. In the neuroendocrine cells (the type 1 cell of the carotid body, neuroepithelial body and adrenomedullary cells), the response is secretion. We examine the roles played by superoxide anion, hydrogen peroxide and the anti-oxidant enzymes in the signaling of oxygen tensions. PMID:20801237

Weir, E. Kenneth; Archer, Stephen L.

2010-01-01

12

Oxygen sensing neurons and neuropeptides regulate survival after anoxia in developing C. elegans.  

PubMed

Hypoxic brain injury remains a major source of neurodevelopmental impairment for both term and preterm infants. The perinatal period is a time of rapid transition in oxygen environments and developmental resetting of oxygen sensing. The relationship between neural oxygen sensing ability and hypoxic injury has not been studied. The oxygen sensing circuitry in the model organism C. elegans is well understood. We leveraged this information to investigate the effects of impairments in oxygen sensing on survival after anoxia. There was a significant survival advantage in developing worms specifically unable to sense oxygen shifts below their preferred physiologic range via genetic ablation of BAG neurons, which appear important for conferring sensitivity to anoxia. Oxygen sensing that is mediated through guanylate cyclases (gcy-31, 33, 35) is unlikely to be involved in conferring this sensitivity. Additionally, animals unable to process or elaborate neuropeptides displayed a survival advantage after anoxia. Based on these data, we hypothesized that elaboration of neuropeptides by BAG neurons sensitized animals to anoxia, but further experiments indicate that this is unlikely to be true. Instead, it seems that neuropeptides and signaling from oxygen sensing neurons operate through independent mechanisms, each conferring sensitivity to anoxia in wild type animals. PMID:24967811

Flibotte, John J; Jablonski, Angela M; Kalb, Robert G

2014-01-01

13

Pharmaceutical applications of in vivo EPR  

NASA Astrophysics Data System (ADS)

The aim of this article is to discuss the applications of in vivo EPR in the field of pharmacy. In addition to direct detection of free radical metabolites and measurement of oxygen, EPR can be used to characterize the mechanisms of drug release from biodegradable polymers. Unique information about drug concentration, the microenvironment (viscosity, polarity, pH) and biodistribution (by localized measurement or EPR Imaging) can be obtained.

Mäder, Karsten

1998-07-01

14

Biomedical Applications of Sodium MRI In Vivo  

PubMed Central

In this article, we present an up-to-date overview of the potential biomedical applications of sodium MRI in vivo. Sodium MRI is a subject of increasing interest in translational imaging research as it can give some direct and quantitative biochemical information on the tissue viability, cell integrity and function, and therefore not only help the diagnosis but also the prognosis of diseases and treatment outcomes. It has already been applied in vivo in most of human tissues, such as brain for stroke or tumor detection and therapeutic response, in breast cancer, in articular cartilage, in muscle and in kidney, and it was shown in some studies that it could provide very useful new information not available through standard proton MRI. However, this technique is still very challenging due to the low detectable sodium signal in biological tissue with MRI and hardware/software limitations of the clinical scanners. The article is divided in three parts: (1) the role of sodium in biological tissues, (2) a short review on sodium magnetic resonance, and (3) a review of some studies on sodium MRI on different organs/diseases to date. PMID:23722972

Madelin, Guillaume; Regatte, Ravinder R.

2013-01-01

15

Sensors and Actuators B 113 (2006) 162168 Dependence of potentiometric oxygen sensing  

E-print Network

Sensors and Actuators B 113 (2006) 162­168 Dependence of potentiometric oxygen sensing-based oxygen sensor is presented. Platinum (Pt), lanthanum strontium iron cobalt oxide (La0.6Sr0.4Fe0.8Co0.2O3. But, the measured response times for oxygen sensors using these electrodes showed values of the order

Dutta, Prabir K.

16

Dissolved Oxygen Sensing in a Flow Stream using Molybdenum Chloride Optical Indicators  

E-print Network

Dissolved Oxygen Sensing in a Flow Stream using Molybdenum Chloride Optical Indicators Reza Loloee1@msu.edu Abstract--Dissolved oxygen concentration is considered the most important water quality variable in fish culture. Reliable and continuous (24/7) oxygen monitoring of dissolved oxygen (DO) in the 1 ­ 11 mg

Ghosh, Ruby N.

17

Spatially monitoring oxygen level in 3D microfabricated cell culture systems using optical oxygen sensing beads  

PubMed Central

Capability of measuring and monitoring local oxygen concentration at the single cell level (tens of microns scale) is often desirable but difficult to achieve in cell culture. In this study, biocompatible oxygen sensing beads were prepared and tested for their potential for real-time monitoring and mapping of local oxygen concentration in 3D micro-patterned cell culture systems. Each oxygen sensing bead is composed of a silica core loaded with both an oxygen sensitive Ru(Ph2phen3)Cl2 dye and oxygen insensitive Nile blue reference dye, and a poly-dimethylsiloxane (PDMS) shell rendering biocompatibility. Human intestinal epithelial Caco-2 cells were cultivated on a series of PDMS and type I collagen based substrates patterned with micro-well arrays for 3 or 7 days, and then brought into contact with oxygen sensing beads. Using an image analysis algorithm to convert florescence intensity of beads to partial oxygen pressure in the culture system, tens of microns-size oxygen sensing beads enabled the spatial measurement of local oxygen concentration in the microfabricated system. Results generally indicated lower oxygen level inside wells than on top of wells, and local oxygen level dependence on structural features of cell culture surfaces. Interestingly, chemical composition of cell culture substrates also appeared to affect oxygen level, with type-I collagen based cell culture systems having lower oxygen concentration compared to PDMS based cell culture systems. In general, results suggest that oxygen sensing beads can be utilized to achieve real-time and local monitoring of micro-environment oxygen level in 3D microfabricated cell culture systems. PMID:23443975

Wang, Lin; Acosta, Miguel A.; Leach, Jennie B.; Carrier, Rebecca L.

2013-01-01

18

Oxygen Sensing for Industrial Safety -- Evolution and New Approaches  

PubMed Central

The requirement for the detection of oxygen in industrial safety applications has historically been met by electrochemical technologies based on the consumption of metal anodes. Products using this approach have been technically and commercially successful for more than three decades. However, a combination of new requirements is driving the development of alternative approaches offering fresh opportunities and challenges. This paper reviews some key aspects in the evolution of consumable anode products and highlights recent developments in alternative technologies aimed at meeting current and anticipated future needs in this important application. PMID:24681673

Willett, Martin

2014-01-01

19

The hypoxia-inducible transcription factor pathway regulates oxygen sensing in the simplest animal, Trichoplax adhaerens.  

PubMed

The hypoxic response in humans is mediated by the hypoxia-inducible transcription factor (HIF), for which prolyl hydroxylases (PHDs) act as oxygen-sensing components. The evolutionary origins of the HIF system have been previously unclear. We demonstrate a functional HIF system in the simplest animal, Trichoplax adhaerens: HIF targets in T. adhaerens include glycolytic and metabolic enzymes, suggesting a role for HIF in the adaptation of basal multicellular animals to fluctuating oxygen levels. Characterization of the T. adhaerens PHDs and cross-species complementation assays reveal a conserved oxygen-sensing mechanism. Cross-genomic analyses rationalize the relative importance of HIF system components, and imply that the HIF system is likely to be present in all animals, but is unique to this kingdom. PMID:21109780

Loenarz, Christoph; Coleman, Mathew L; Boleininger, Anna; Schierwater, Bernd; Holland, Peter W H; Ratcliffe, Peter J; Schofield, Christopher J

2011-01-01

20

Oxygen Sensing and the Activation of the Hypoxia Inducible Factor 1 (HIF-1)– Invited Article  

Microsoft Academic Search

For mammals, oxygen sensing is fundamental to survive. An adequate response to reduced oxygen tension, herein termed hypoxia,\\u000a requires an instantaneous adaptation of the respiratory and the circulatory systems. While the glomus caroticum as well as\\u000a the pulmonary and systemic vasculature and potentially also the airway chemoreceptors enable a corresponding response within\\u000a seconds, changes in gene expression require minutes to

Joachim Fandrey; Max Gassmann

21

Study on an oxygen sensing rhenium(I) complex with enlarged sensing/active area: fabrication, photophysical parameters and molecular oxygen sensing performance.  

PubMed

In this paper, we synthesize a novel 1,10-phenanthroline-derived (Phen-derived) diamine ligand of benzo[f][1,10]phenanthroline-6,7-dicarbonitrile (Phen-CN) with enlarged conjugation planar and its corresponding Re(I) complex of Re(CO)3Cl(Phen-CN), hoping to achieve an optical sensor owing large sensing/active area. Its geometric and electronic structures are investigated, which suggests that the effective sensing/active area of Re(CO)3Cl(Phen-CN) is enlarged by the successful formation of conjugation planar. The promising photophysical parameters of Re(CO)3Cl(Phen-CN), including large sensing/active area and long excited state lifetime, make it a potential probe for oxygen detection. By doping Re(CO)3Cl(Phen-CN) into a polymer matrix of poly(vinylpyrrolidone), oxygen sensing performances of the resulted composite materials are investigated. Finally, a high sensitivity of 17.1 is realized, with short response/recovery time of 9s/32s. PMID:24412790

Xu, Guiying; Lu, Mang; Huang, Can; Wang, Yaoqiong; Ge, Shuping

2014-04-01

22

Silicon-on-glass pore network micromodels with oxygen-sensing fluorophore films for chemical imaging and defined spatial structure  

SciTech Connect

Pore network microfluidic models were fabricated by a silicon-on-glass technique that provides the precision advantage of dry etched silicon while creating a structure that is transparent across all microfluidic channels and pores, and can be imaged from either side. A silicon layer is bonded to an underlying borosilicate glass substrate and thinned to the desired height of the microfluidic channels and pores. The silicon is then patterned and through-etched by deep reactive ion etching (DRIE), with the underlying glass serving as an etch stop. After bonding on a transparent glass cover plate, one obtains a micromodel in oxygen impermeable materials with water wet surfaces where the microfluidic channels are transparent and structural elements such as the pillars creating the pore network are opaque. The micromodel can be imaged from either side. The advantageous features of this approach in a chemical imaging application are demonstrated by incorporating a Pt porphyrin fluorophore in a PDMS film serving as the oxygen sensing layer and a bonding surface, or in a polystyrene film coated with a PDMS layer for bonding. The sensing of a dissolved oxygen gradient was demonstrated using fluorescence lifetime imaging, and it is shown that different matrix polymers lead to optimal use in different ranges dissolved oxygen concentration. Imaging with the opaque pillars in between the observation direction and the continuous fluorophore film yields images that retain spatial information in the sensor image.

Grate, Jay W.; Kelly, Ryan T.; Suter, Jonathan D.; Anheier, Norman C.

2012-11-21

23

Silicon-on-glass pore network micromodels with oxygen-sensing fluorophore films for chemical imaging and defined spatial structure.  

PubMed

Pore network microfluidic models were fabricated by a silicon-on-glass technique that provides the precision advantage of dry etched silicon while creating a structure that is transparent across all microfluidic channels and pores, and can be imaged from either side. A silicon layer is bonded to an underlying borosilicate glass substrate and thinned to the desired height of the microfluidic channels and pores. The silicon is then patterned and through-etched by deep reactive ion etching (DRIE), with the underlying glass serving as an etch stop. After bonding on a transparent glass cover plate, one obtains a micromodel in oxygen impermeable materials with water-wet surfaces where the microfluidic channels are transparent and structural elements such as the pillars creating the pore network are opaque. The advantageous features of this approach in a chemical imaging application are demonstrated by incorporating a Pt porphyrin fluorophore in a PDMS film serving as the oxygen-sensing layer and a bonding surface, or in a polystyrene film coated with a PDMS layer for bonding. The sensing of a dissolved oxygen gradient was demonstrated using fluorescence lifetime imaging, and it is shown that different matrix polymers lead to optimal use in different ranges of oxygen concentration. Imaging with the opaque pillars in between the observation direction and the continuous fluorophore film yields images that retain defined spatial structure in the sensor image. PMID:22995983

Grate, Jay W; Kelly, Ryan T; Suter, Jonathan; Anheier, Norm C

2012-11-21

24

Handheld multispectral fluorescence lifetime imaging system for in vivo applications  

PubMed Central

There is an increasing interest in the application of fluorescence lifetime imaging (FLIM) for medical diagnosis. Central to the clinical translation of FLIM technology is the development of compact and high-speed clinically compatible systems. We present a handheld probe design consisting of a small maneuverable box fitted with a rigid endoscope, capable of continuous lifetime imaging at multiple emission bands simultaneously. The system was characterized using standard fluorescent dyes. The performance was then further demonstrated by imaging a hamster cheek pouch in vivo, and oral mucosa tissue both ex vivo and in vivo, all using safe and permissible exposure levels. Such a design can greatly facilitate the evaluation of FLIM for oral cancer imaging in vivo. PMID:24688824

Cheng, Shuna; Cuenca, Rodrigo M.; Liu, Boang; Malik, Bilal H.; Jabbour, Joey M.; Maitland, Kristen C.; Wright, John; Cheng, Yi-Shing Lisa; Jo, Javier A.

2014-01-01

25

From spin-labeled proteins to in vivo EPR applications  

Microsoft Academic Search

This is a historical overview of the advent of applications of spin labeling to biological systems and the subsequent developments\\u000a from the perspective of a scientist who was working as a Ph.D. student when the technique was conceived and was fortunate\\u000a enough to participate in its development. In addition, the historical development of in vivo applications of EPR on animals

Lawrence J. Berliner

2010-01-01

26

Are rare-Earth nanoparticles suitable for in vivo applications?  

PubMed

Rare earth (RE) nanoparticles have attracted considerable attention due to their unique optical and magnetic properties associated with f-electrons. The recent accomplishments in RE nanoparticle synthesis have aroused great interest of scientists to further explore their biomedical applications. This Research News summarizes recent achievements in controlled synthesis of magnetic and luminescent RE nanoparticles, surface modification, and toxicity studies of RE nanomaterials, and highlights state-of-the-art in in vivo applications of RE nanoparticles. PMID:24616057

Liu, Chunyan; Hou, Yi; Gao, Mingyuan

2014-10-01

27

Thiosulfate: a readily accessible source of hydrogen sulfide in oxygen sensing.  

PubMed

H2S derived from organic thiol metabolism has been proposed serve as an oxygen sensor in a variety of systems because of its susceptibility to oxidation and its ability to mimic hypoxic responses in numerous oxygen-sensing tissues. Thiosulfate, an intermediate in oxidative H2S metabolism can alternatively be reduced and regenerate H2S. We propose that this contributes to the H2S-mediated oxygen-sensing mechanism. H2S formation from thiosulfate in buffers and in a variety of mammalian tissues and in lamprey dorsal aorta was examined in real time using a polarographic H2S sensor. Inferences of intracellular H2S production were made by examining hypoxic pulmonary vasoconstriction (HPV) in bovine pulmonary arteries under conditions in which increased H2S production would be expected and in mouse and rat aortas, where reducing conditions should mediate vasorelaxation. In Krebs-Henseleit (mammalian) and Cortland (lamprey) buffers, H2S was generated from thiosulfate in the presence of the exogenous reducing agent, DTT, or the endogenous reductant dihydrolipoic acid (DHLA). Both the magnitude and rate of H2S production were greatly increased by these reductants in the presence of tissue, with the most notable effects occurring in the liver. H2S production was only observed when tissues were hypoxic; exposure to room air, or injecting oxygen inhibited H2S production and resulted in net H2S consumption. Both DTT and DHLA augmented HPV, and DHLA dose-dependently relaxed precontracted mouse and rat aortas. These results indicate that thiosulfate can contribute to H2S signaling under hypoxic conditions and that this is not only a ready source of H2S production but also serves as a means of recycling sulfur and thereby conserving biologically relevant thiols. PMID:23804280

Olson, Kenneth R; Deleon, Eric R; Gao, Yan; Hurley, Kevin; Sadauskas, Victor; Batz, Catherine; Stoy, Gilbrian F

2013-09-15

28

Application of in vivo laser scanning microscope in dermatology  

NASA Astrophysics Data System (ADS)

The state of the art of in-vivo and in-vitro penetration measurements of topically applied substances is described. Only optical techniques represent online measuring methods based on the absorption or scattering properties of the topically applied substances. Laser scanning microscopy (LSM) has become a promising method for investigations in dermatology and skin physiology, after it was possible to analyze the skin surface on any body side in-vivo. In the present paper the application of a dermatological laser scanning microscope for penetration and distribution measurements of topically applied substances is described. The intercellular and follicular penetration pathways were studied.

Lademann, Juergen; Richter, H.; Otberg, N.; Lawrenz, F.; Blume-Peytavi, U.; Sterry, W.

2003-10-01

29

21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.  

Code of Federal Regulations, 2010 CFR

...culture media for human ex vivo tissue and cell culture processing applications. 876...culture media for human ex vivo tissue and cell culture processing applications. (a...culture media for human ex vivo tissue and cell culture processing applications...

2010-04-01

30

Thickness Dependency of Thin Film Samaria Doped Ceria for Oxygen Sensing  

SciTech Connect

High temperature oxygen sensors are widely used for exhaust gas monitoring in automobiles. This particular study explores the use of thin film single crystalline samaria doped ceria as the oxygen sensing material. Desired signal to noise ratio can be achieved in a material system with high conductivity. From previous studies it is established that 6 atomic percent samarium doping is the optimum concentration for thin film samaria doped ceria to achieve high ionic conductivity. In this study, the conductivity of the 6 atomic percent samaria doped ceria thin film is measured as a function of the sensing film thickness. Hysteresis and dynamic response of this sensing platform is tested for a range of oxygen pressures from 0.001 Torr to 100 Torr for temperatures above 673 K. An attempt has been made to understand the physics behind the thickness dependent conductivity behavior of this sensing platform by developing a hypothetical operating model and through COMSOL simulations. This study can be used to identify the parameters required to construct a fast, reliable and compact high temperature oxygen sensor.

Sanghavi, Rahul P.; Nandasiri, Manjula I.; Kuchibhatla, Satyanarayana V N T; Jiang, Weilin; Varga, Tamas; Nachimuthu, Ponnusamy; Engelhard, Mark H.; Shutthanandan, V.; Thevuthasan, Suntharampillai; Kayani, Asghar N.; Prasad, Shalini

2011-01-01

31

A phosphorescent copper(I) complex: Synthesis, characterization, photophysical property, and oxygen-sensing behavior  

NASA Astrophysics Data System (ADS)

In this paper, we report the synthesis, crystal structure, photophysical properties, and electronic nature of a phosphorescent Cu(I) complex of [Cu(Phen-Np)(POP)]BF 4, where Phen-Np and POP stand for 2-(naphthalen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline and bis(2-(diphenylphosphanyl)phenyl) ether, respectively. [Cu(Phen-Np)(POP)]BF 4 renders a yellow phosphorescence peaking at 545 nm, with a long excited state lifetime of 4.69 ?s. Density functional calculation reveals that the emission comes from a triplet metal-to-ligand-charge-transfer excited state. We electrospun composite nanofibers of [Cu(Phen-Np)(POP)]BF 4 and polystyrene (PS), hoping to explore the possibility of using the composite nanofibers as an oxygen sensing material. The finally obtained samples with average diameter of ˜300 nm exhibit a maximum sensitivity of 7.2 towards molecular oxygen with short response time of 7 s due to the large surface-area-to-volume ratio of nanofibrous membranes. No photobleaching is detected in these samples.

Wen, Caihong; Tao, Guoquan; Xu, Xinhua; Feng, Xiaoqing; Luo, Rongcheng

2011-09-01

32

Synthesis, characterization and theoretical analysis on a oxygen-sensing phosphorescent copper(I) complex  

NASA Astrophysics Data System (ADS)

In this paper, we report the synthesis, crystal structure, photophysical properties, and electronic nature of a phosphorescent Cu(I) complex of [Cu(Phen-Ph)(PPh 3) 2]BF 4, where Phen-Ph and PPh 3 stand for 2-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline and triphenylphosphine, respectively. [Cu(Phen-Ph)(PPh 3) 2]BF 4 renders a yellow phosphorescence peaking at 553 nm, with a long excited state lifetime of 13.2 ?s under N 2 atmosphere. Density functional calculation reveals that the emission comes from a triplet metal-to-ligand-charge-transfer excited state. We electrospun composite nanofibers of [Cu(Phen-Ph)(PPh 3) 2]BF 4 and polystyrene (PS), hoping to explore the possibility of using the composite nanofibers as an oxygen sensing material. The finally obtained samples with average diameter of ˜400 nm exhibit a maximum sensitivity of 6.52 towards molecular oxygen with short response time of 15 s due to the large surface-area-to-volume ratio of nanofibrous membranes. No photobleaching is detected in these samples.

Li, Zheng

2011-10-01

33

Engineering the oxygen sensing regulation results in an enhanced recombinant human hemoglobin production by Saccharomyces cerevisiae.  

PubMed

Efficient production of appropriate oxygen carriers for transfusions (blood substitutes or artificial blood) has been pursued for many decades, and to date several strategies have been used, from synthetic polymers to cell-free hemoglobin carriers. The recent advances in the field of metabolic engineering also allowed the generation of different genetically modified organisms for the production of recombinant human hemoglobin. Several studies have showed very promising results using the bacterium Escherichia coli as a production platform, reporting hemoglobin titers above 5% of the total cell protein content. However, there are still certain limitations regarding the protein stability and functionality of the recombinant hemoglobin produced in bacterial systems. In order to overcome these limitations, yeast systems have been proposed as the eukaryal alternative. We recently reported the generation of a set of plasmids to produce functional human hemoglobin in Saccharomyces cerevisiae, with final titers of active hemoglobin exceeding 4% of the total cell protein. In this study, we propose a strategy for further engineering S. cerevisiae by altering the oxygen sensing pathway by deleting the transcription factor HAP1, which resulted in an increase of the final recombinant active hemoglobin titer exceeding 7% of the total cellular protein. Biotechnol. Bioeng. 2015;112: 181-188. © 2014 Wiley Periodicals, Inc. PMID:25082441

Martínez, José L; Liu, Lifang; Petranovic, Dina; Nielsen, Jens

2015-01-01

34

A series of phosphorescent Cu(I) complexes and their oxygen sensing performance in SBA-15 silica matrix  

NASA Astrophysics Data System (ADS)

A series of [Cu(N-N)(PPh3)2]BF4 complexes were synthesized and characterized in this paper, where N-N and PPh3 suggest a diamine ligand and triphenylphosphane, respectively. Their structures were revealed by single crystal analysis and density functional theory calculation. The photophysical feature comparison between those Cu(I) complexes revealed the correlation between emission performance and diamine ligand structure. In addition, it was found that the emissive states were vulnerable to O2 attack, making them potential oxygen sensing probes. They were thus doped into a silica molecular sieve SBA-15 to systematically explore their oxygen sensing performance. High sensitivity and good photostability were observed from the composite sensing systems.

Xu, Xiao-yong; Xiao, Han-ning; Deng, Ai-ping

2014-07-01

35

Vertically integrated human P450 and oxygen sensing film for the assays of P450 metabolic activities.  

PubMed

An assaying method of cytochrome P450 (P450 or CYP) monooxygenase activities for toxicological evaluation of drugs and environmental pollutants was developed by immobilizing P450 on an oxygen sensoring layer. Membrane fractions from E. coli expressing human P450 were entrapped in agarose or silica-based gels and immobilized on 96-well microarrays having an oxygen sensing film at the bottom. The oxygen sensing film was made of an organically modified silica film (ORMOSIL) doped with Tris(4,7-diphenyl-1,10-phenanthroline) ruthenium dichloride (Ru(dpp)(3)Cl(2)). P450 activity toward the substrates was monitored through the fluorescence intensity enhancement due to the oxygen consumption by the metabolic reactions. For the metabolism of chlortoluron, a selective herbicide used to control grass weeds, CYP1A1 immobilized in agarose gel showed a higher activity and stability compared with those in silica gels and free suspensions. The luminescence changing rate evaluated by the dynamic transient method (DTM) could be correlated with the substrate concentration. We also compared the metabolic responses of human P450s (CYP1A1,CYP2C8, CYP2E1, CYP3A4) toward various substances. The use of immobilized P450 on an oxygen sensing layer provides a versatile assaying platform owing to the following features. First, the oxygen sensor can detect metabolic reactions of any P450 species, in contrast with assays using fluorogenic substrates. Second, vertical integration of the oxygen sensor and immobilized P450 enhanced the sensitivity because of the effective depletion of oxygen in the vicinity of the oxygen sensing layer. Third, immobilization enables repeated use of P450 by replacing the substrate solutions using a flow cell. Furthermore, the activity of immobilized P450 was retained at least for 3 weeks at 4 °C, suggesting its long-term stability, which is an additional attractive feature. PMID:21434664

Chang, Gang; Morigaki, Kenichi; Tatsu, Yoshiro; Hikawa, Takashi; Goto, Tatsushi; Imaishi, Hiromasa

2011-04-15

36

Transesophageal ultrasound applicator for sector-based thermal ablation: First in vivo experiments  

E-print Network

: Ultrasound, thermal ablation, coagulation necrosis, intraductal therapy, sector- based, plane transducerTransesophageal ultrasound applicator for sector-based thermal ablation: First in vivo experiments-based thermal surgery: First in vivo experiments Abstract New curative and palliative treatments must

Paris-Sud XI, Université de

37

Synthesis, processing and characterization of calcia-stabilized zirconia solid electrolytes for oxygen sensing applications  

SciTech Connect

Precursor powders of calcia-stabilized zirconia (CSZ) solid electrolytes have been synthesized by a sol-gel method. The phase evolution of the precursor powders after thermal treatments at different temperatures were analysized by X-ray diffraction technique. Disc-shaped sensor elements were fabricated via uniaxial pressing of the calcined powders and subsequently sintered at 1650 deg. C. Scanning electron microscopy (SEM) was used to analyze the microstructure of the sintered pellets. Platinum electrodes were applied to the sintered elements to produce potentiometric/electrochemical gas sensors. The electrical response of the gas sensors to oxygen and the complex impedance of the sensors in air were measured at various temperatures. Impedance analyses indicate that the sensor cell with 15 mol% CaO has much lower resistance (the sum of bulk and grain-boundary resistance) than the sensor cell with 22 mol% CaO. This is also reflected by the EMF responses of both sensor cells to various oxygen concentrations in the testing gas. The EMF deviation from the theoretical value of the CSZ sensor cell with 22 mol% CaO was larger than that of the CSZ sensor cell with 15 mol% CaO. The corrrelations between material compositions, microstructures of the sintered pellets and the electrical properties of the sensors are discussed.

Zhou Minghua [Materials Technology Laboratory, Natural Resources Canada, 3484 Limebank Road, Ottawa, Ont., K1A 0E4 (Canada)]. E-mail: mzhou@nrcan.gc.ca; Ahmad, Aftab [Materials Technology Laboratory, Natural Resources Canada, 3484 Limebank Road, Ottawa, Ont., K1A 0E4 (Canada)

2006-04-13

38

Relationship between the microscopic and macroscopic world in optical oxygen sensing: a luminescence lifetime microscopy study.  

PubMed

An investigation based on confocal fluorescence lifetime imaging microscopy (FLIM) of silica-loaded silicone films doped with a molecular oxygen-sensitive ruthenium(II) polyazaheterocyclic complex is presented. The effect of the silica type (hydrophilic/hydrophobic), particle size and amount of silica filler on the luminescence decay of the immobilized indicator dye has thoroughly been studied. A higher amount of hydrophilic silica leads to both a higher solubility of molecular oxygen into the silicone film and to higher levels of the metal indicator dye. Thus, incorporation of 10% (by wt) pyrogenic silica into silicone shortens the mean luminescence lifetime from 1.4 to 0.9 micros. However, an excess of filler may lead to overloading of the dye into the film producing new phenomena such as triplet-triplet annihilation and excitation energy homotransfer, as observed from their influence on the emission lifetime of the metal complex. Those phenomena do not take place when trimethylated silica (hydrophobic filler) is used. In this case, no increase on the oxygen or dye concentration is observed after addition of the filler and no significant reduction of the luminescence lifetime is measured. Both the addition of silica and the possible precipitation of dye crystals lead to the appearance of microdomains where the molecular probe exhibits widely different excited state lifetimes. For the first time, such microdomains within the oxygen sensing layer are visualized and analyzed by means of FLIM, showing the potential of this technique and the usefulness of our conclusions to the future design and development of novel luminescent oxygen sensor films for environmental and process analysis. PMID:20099927

López-Gejo, Juan; Haigh, David; Orellana, Guillermo

2010-02-01

39

Permeation peptide conjugates for in vivo molecular imaging applications.  

PubMed

Rapid and efficient delivery of imaging probes to the cell interior using permeation peptides has enabled novel applications in molecular imaging. Membrane permeant peptides based on the HIV-1 Tat basic domain sequence, GRKKRRQRRR, labeled with fluorophores and fluorescent proteins for optical imaging or with appropriate peptide-based motifs or macrocycles to chelate metals, such as technetium for nuclear scintigraphy and gadolinium for magnetic resonance imaging, have been synthesized. In addition, iron oxide complexes have been functionalized with the Tat basic domain peptides for magnetic resonance imaging applications. Herein we review current applications of permeation peptides in molecular imaging and factors influencing permeation peptide internalization. These diagnostic agents show concentrative cell accumulation and rapid kinetics and display cytosolic and focal nuclear accumulation in human cells. Combining methods, dual-labeled permeation peptides incorporating fluorescein maleimide and chelated technetium have allowed for both qualitative and quantitative analysis of cellular uptake. Imaging studies in mice following intravenous administration of prototypic diagnostic permeation peptides show rapid whole-body distribution allowing for various molecular imaging applications. Strategies to develop permeation peptides into molecular imaging probes have included incorporation of targeting motifs such as molecular beacons or protease cleavable domains that enable selective retention, activatable fluorescence, or targeted transduction. These novel permeation peptide conjugates maintain rapid translocation across cell membranes into intracellular compartments and have the potential for targeted in vivo applications in molecular imaging and combination therapy. PMID:16779965

Bullok, Kristin E; Gammon, Seth T; Violini, Stefania; Prantner, Andrew M; Villalobos, Victor M; Sharma, Vijay; Piwnica-Worms, David

2006-01-01

40

DNMT3a epigenetic program regulates the HIF-2? oxygen-sensing pathway and the cellular response to hypoxia  

PubMed Central

Epigenetic regulation of gene expression by DNA methylation plays a central role in the maintenance of cellular homeostasis. Here we present evidence implicating the DNA methylation program in the regulation of hypoxia-inducible factor (HIF) oxygen-sensing machinery and hypoxic cell metabolism. We show that DNA methyltransferase 3a (DNMT3a) methylates and silences the HIF-2? gene (EPAS1) in differentiated cells. Epigenetic silencing of EPAS1 prevents activation of the HIF-2? gene program associated with hypoxic cell growth, thereby limiting the proliferative capacity of adult cells under low oxygen tension. Naturally occurring defects in DNMT3a, observed in primary tumors and malignant cells, cause the unscheduled activation of EPAS1 in early dysplastic foci. This enables incipient cancer cells to exploit the HIF-2? pathway in the hypoxic tumor microenvironment necessary for the formation of cellular masses larger than the oxygen diffusion limit. Reintroduction of DNMT3a in DNMT3a-defective cells restores EPAS1 epigenetic silencing, prevents hypoxic cell growth, and suppresses tumorigenesis. These data support a tumor-suppressive role for DNMT3a as an epigenetic regulator of the HIF-2? oxygen-sensing pathway and the cellular response to hypoxia. PMID:24817692

Lachance, Gabriel; Uniacke, James; Audas, Timothy E.; Holterman, Chet E.; Franovic, Aleksandra; Payette, Josianne; Lee, Stephen

2014-01-01

41

Sol-gel-Derived highly sensitive optical oxygen sensing materials using Ru(II) complex via covalent grafting strategy.  

PubMed

The preparation and oxygen sensing properties of Ru(ll) covalently-grafted and physically-incorporated silica based hybrid materials by sol-gel technique are described in this article. The Ru(II) complexes are successfully grafted onto the backbone of the silica via the condensation reaction of the tetraethoxysilane and the functionalized Ru(II) complex 2-[4'-{3-(Triethoxysilyl)propyl}phenyl]imidazo [4,5-f]-1,10-phenanthroline that contains the hydrolysable tri-alkoxylsilyl group. The luminescence quenching of Ru(II) complex by oxygen within the silica matrix is efficient. The oxygen quenching sensitivity of the covalently-grafted sample is higher than that of the physically-incorporated one due to the strong Si-CH2 bond that is useful to prolong the excited state lifetimes and enhance the photobleaching of the luminophore. The downward oxygen sensing Stern-Volmer plots can be well fitted using the Demas two-site model and the Lehrer model due to the heterogeneous distribution of the Ru(ll) complex within the sol-gel derived silica. PMID:24738438

Zhang, Haoran; Lei, Bingfu; Liu, Yingliang; Liu, Xiaotang; Zheng, Mingtao; Dong, Hanwu; Xiao, Yong; Zhang, Jianying

2014-06-01

42

DNMT3a epigenetic program regulates the HIF-2? oxygen-sensing pathway and the cellular response to hypoxia.  

PubMed

Epigenetic regulation of gene expression by DNA methylation plays a central role in the maintenance of cellular homeostasis. Here we present evidence implicating the DNA methylation program in the regulation of hypoxia-inducible factor (HIF) oxygen-sensing machinery and hypoxic cell metabolism. We show that DNA methyltransferase 3a (DNMT3a) methylates and silences the HIF-2? gene (EPAS1) in differentiated cells. Epigenetic silencing of EPAS1 prevents activation of the HIF-2? gene program associated with hypoxic cell growth, thereby limiting the proliferative capacity of adult cells under low oxygen tension. Naturally occurring defects in DNMT3a, observed in primary tumors and malignant cells, cause the unscheduled activation of EPAS1 in early dysplastic foci. This enables incipient cancer cells to exploit the HIF-2? pathway in the hypoxic tumor microenvironment necessary for the formation of cellular masses larger than the oxygen diffusion limit. Reintroduction of DNMT3a in DNMT3a-defective cells restores EPAS1 epigenetic silencing, prevents hypoxic cell growth, and suppresses tumorigenesis. These data support a tumor-suppressive role for DNMT3a as an epigenetic regulator of the HIF-2? oxygen-sensing pathway and the cellular response to hypoxia. PMID:24817692

Lachance, Gabriel; Uniacke, James; Audas, Timothy E; Holterman, Chet E; Franovic, Aleksandra; Payette, Josianne; Lee, Stephen

2014-05-27

43

Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensing.  

PubMed

Hypoxia-inducible factor1 (HIF-1) is an essential transcription factor for cellular adaptation to decreased oxygen availability. In normoxia the oxygen-sensitive alpha-subunit of HIF-1 is hydroxylated on Pro564 and Pro402 and thus targeted for proteasomal degradation. Three human oxygen-dependent HIF-1 alpha prolyl hydroxylases (PHD1, PHD2, and PHD3) function as oxygen sensors in vivo. Furthermore, the asparagine hydroxylase FIH-1 (factor inhibiting HIF) has been found to hydroxylate Asp803 of the HIF-1 C-terminal transactivation domain, which results in the decreased ability of HIF-1 to bind to the transcriptional coactivator p300/CBP. We have fused these enzymes to the N-terminus of fluorescent proteins and transiently transfected the fusion proteins into human osteosarcoma cells (U2OS). Three-dimensional 2-photon confocal fluorescence microscopy showed that PHD1 was exclusively present in the nucleus, PHD2 and FIH-1 were mainly located in the cytoplasm and PHD3 was homogeneously distributed in cytoplasm and nucleus. Hypoxia did not influence the localisation of any enzyme under investigation. In contrast to FIH-1, each PHD inhibited nuclear HIF-1 alpha accumulation in hypoxia. All hydroxylases suppressed activation of a cotransfected hypoxia-responsive luciferase reporter gene. Endogenous PHD2mRNA and PHD3mRNA were hypoxia-inducible, whereas expression of PHD1mRNA and FIH-1mRNA was oxygen independent. We propose that PHDs and FIH-1 form an oxygen sensor cascade of distinct subcellular localisation. PMID:12615973

Metzen, Eric; Berchner-Pfannschmidt, Utta; Stengel, Petra; Marxsen, Jan H; Stolze, Ineke; Klinger, Matthias; Huang, Wei Qi; Wotzlaw, Christoph; Hellwig-Bürgel, Thomas; Jelkmann, Wolfgang; Acker, Helmut; Fandrey, Joachim

2003-04-01

44

FIBER OPTICAL MICRO-DETECTORS FOR OXYGEN SENSING IN POWER PLANTS  

SciTech Connect

A reflection mode fiber optic oxygen sensor that can operate at high temperatures for power plant applications is being developed. The sensor is based on the {sup 3}O{sub 2} quenching of the red emission from hexanuclear molybdenum chloride clusters. High temperature measurements of the emission of clusters in sol gel films show that the luminescence intensity from the films follow a 1/T relationship from room temperature to 150 C, and then declines at a slower rate at higher temperatures. The large number of photons available at 230 C is consistent with simple low cost optics for fiber optic probes based on the emission from clusters in sol gel films.

Gregory L. Baker; Ruby N. Ghosh; D.J. Osborn III

2004-10-01

45

In Vivo Application of Optogenetics for Neural Circuit Analysis  

PubMed Central

Optogenetics combines optical and genetic methods to rapidly and reversibly control neural activities or other cellular functions. Using genetic methods, specific cells or anatomical pathways can be sensitized to light through exogenous expression of microbial light activated opsin proteins. Using optical methods, opsin expressing cells can be rapidly and reversibly controlled by pulses of light of specific wavelength. With the high spatial temporal precision, optogenetic tools have enabled new ways to probe the causal role of specific cells in neural computation and behavior. Here, we overview the current state of the technology, and provide a brief introduction to the practical considerations in applying optogenetics in vivo to analyze neural circuit functions. PMID:22896801

2012-01-01

46

ZnO nanowire field-effect transistor and oxygen sensing property  

NASA Astrophysics Data System (ADS)

Single-crystal ZnO nanowires are synthesized using a vapor trapping chemical vapor deposition method and configured as field-effect transistors. Electrical transport studies show n-type semiconducting behavior with a carrier concentration of ˜107cm-1 and an electron mobility of ˜17cm2/Vs. The contact Schottky barrier between the Au/Ni electrode and nanowire is determined from the temperature dependence of the conductance. Thermionic emission is found to dominate the transport mechanism. The effect of oxygen adsorption on electron transport through the nanowires is investigated. The sensitivity to oxygen is demonstrated to be higher with smaller radii nanowires. Moreover, the oxygen detection sensitivity can be modulated by the gate voltage. These results indicate that ZnO holds high potential for nanoscale sensing applications.

Fan, Zhiyong; Wang, Dawei; Chang, Pai-Chun; Tseng, Wei-Yu; Lu, Jia G.

2004-12-01

47

FIBER OPTICAL MICRO-DETECTORS FOR OXYGEN SENSING IN POWER PLANTS  

SciTech Connect

A reflection mode fiber optic oxygen sensor that can operate at high temperatures for power plant applications is being developed. The sensor is based on the {sup 3}O{sub 2} quenching of the red emission from hexanuclear molybdenum chloride clusters. Alkali salts of Mo{sub 6}Cl{sub 12} were synthesized and heated to 280 C for one hour in air. Optical measurements of the thermally treated material confirm the potential of the salts as lumophores in high temperature fiber optic sensors. In addition sol-gel films containing Mo{sub 6}Cl{sub 12} were dip coated on quartz substrates and heated at 200 C for one hour. Conditions were developed for successfully immobilizing monomeric complexes that are compatible with sol-gel processing.

Gregory L. Baker; Ruby N. Ghosh; D.J. Osborn III

2004-07-01

48

Fiber Optical Micro-detectors for Oxygen Sensing in Power Plants  

SciTech Connect

A reflection mode fiber optic oxygen sensor that can operate at high temperatures for power plant applications is being developed. The sensor is based on the {sup 3}O{sub 2} quenching of the red emission from hexanuclear molybdenum chloride clusters. Our approach towards immobilizing the potassium salt of the molybdenum cluster, K{sub 2}Mo{sub 6}Cl{sub 14}, at the far end of an optical fiber is to embed the cluster in a thermally cured sol-gel matrix particle. This particle-in-binder approach affords fibers with greatly improved mechanical properties, as compared to previous approaches. The sensor was characterized in 2-21% gas phase oxygen at 40, 70 and 100 C. These are promising results for a high temperature fiber optical oxygen sensor based on molybdenum chloride clusters.

Gregory L. Baker; Ruby N. Ghosh; D.J. Osborn; Po Zhang

2006-06-30

49

Fiber Optical Micro-detectors for Oxygen Sensing in Power Plants  

SciTech Connect

A reflection mode fiber optic oxygen sensor that can operate at high temperatures for power plant applications is being developed. The sensor is based on the {sup 3}O{sub 2} quenching of the red emission from hexanuclear molybdenum chloride clusters. Our approach towards immobilizing the potassium salt of the molybdenum cluster, K{sub 2}Mo{sub 6}Cl{sub 14}, at the far end of an optical fiber is to embed the cluster in a thermally cured sol-gel matrix particle. Due to the improved mechanical properties of this approach high temperature sensor measurements were performed up to 100 C. These are promising results for a high temperature fiber optical oxygen sensor based on molybdenum chloride clusters.

Gregory L. Baker; Ruby N. Ghosh; D. J. Osborn; Po Zhang

2006-09-30

50

Fiber Optical Micro-detectors for Oxygen Sensing in Power Plants  

SciTech Connect

A reflection mode fiber optic oxygen sensor that can operate at high temperatures for power plant applications is being developed. The sensor is based on the {sup 3}O{sub 2} quenching of the red emission from hexanuclear molybdenum chloride clusters. Previously we described a particle-in-binder approach to immobilizing the potassium salt of the molybdenum cluster, K{sub 2}Mo{sub 6}Cl{sub 14}, at the tips of optical fibers. Compared to previous methods, the particle-in-binder approach affords fibers with greatly improved mechanical properties. The response of the sensor to oxygen at 40, 70 and 100 C was measured in 2-21% gas phase oxygen. The normalized sensor signal is linear with molar oxygen concentration and fits the theoretical Stern-Volmer relationship. Although the sensitivity decreases with temperature, at 100 C the sensitivity is 160 [O{sub 2}]{sup -1}. These are promising results for a high temperature fiber optical oxygen sensor based on molybdenum chloride clusters.

Gregory L. Baker; Ruby N. Ghosh; D.J. Osborn III; Po Zhang

2006-05-01

51

FIBER OPTICAL MICRO-DETECTORS FOR OXYGEN SENSING IN POWER PLANTS  

SciTech Connect

A reflection mode fiber optic oxygen sensor that can operate at high temperatures for power plant applications is being developed. The sensor is based on the {sup 3}O{sub 2} quenching of the red emission from hexanuclear molybdenum chloride clusters. One of the critical materials issues is to demonstrate that the luminescent cluster immobilized in the sol-gel porous support can withstand high temperature. At the same time the sol-gel matrix must have a high permeability to oxygen. Using a potassium salt of the molybdenum clusters, K{sub 2}Mo{sub 6}Cl{sub 14}, we have established the conditions necessary for deposition of optical quality sol-gel films. From spectroscopic measurements of the film we have shown that the cluster luminescence is stable following heat cycling of 1 hour at 250 C. Quenching of a factor of 4X between pure nitrogen and 21% oxygen was observed for films cured directly at 200 C. These are promising results for a high temperature fiber optical oxygen sensor based on molybdenum chloride clusters.

Gregory L. Baker; Ruby N. Ghosh; D.J. Osborn III; Po Zhang

2005-01-01

52

Fiber Optical Micro-detectors for Oxygen Sensing in Power Plants  

SciTech Connect

A reflection mode fiber optic oxygen sensor that can operate at high temperatures for power plant applications is being developed. The sensor is based on the {sup 3}O{sub 2} quenching of the red emission from hexanuclear molybdenum chloride clusters. Previously we described a particle-in-binder approach to immobilizing the potassium salt of a molybdenum cluster, K{sub 2}Mo{sub 6}Cl{sub 14}, at the tips of optical fibers. Compared to previous methods, the particle-in-binder approach affords fibers with greatly improved mechanical properties. We have extensively characterized two fiber sensors at high temperature. We obtain quenching ratios between pure nitrogen and 21% oxygen as high as 3.9 x at 70 C. For the first sensor at 60 C we obtained a {+-} 1% variation in the quenching ratio over 6 cycles of measurement, and monitored the device performance over 23 days. We were able to operate the second sensor continuously for 14 hours at 70 C, and the sensor quenching ratio was stable to 5% over that time period. These are promising results for a high temperature fiber optical oxygen sensor based on molybdenum chloride clusters.

Gregory L. Baker; Ruby N. Ghosh; D.J. Osborn III; Po Zhang

2006-01-01

53

FIBER OPTICAL MICRO-DETECTORS FOR OXYGEN SENSING IN POWER PLANTS  

SciTech Connect

A reflection mode fiber optic oxygen sensor that can operate at high temperatures for power plant applications is being developed. The sensor is based on the {sup 3}O{sub 2} quenching of the red emission from hexanuclear molybdenum chloride clusters. The luminescence of Mo{sub 6}Cl{sub 12} immobilized in a sol-gel matrix was measured as a function of heater temperature up to 200 C, in an inert environment. While the luminescence decreased with temperature, the integrated intensity at 200 C should be sufficient to enable detection of the luminescence in a fiber geometry. Previously we found that aging Mo{sub 6}Cl{sub 12} at temperatures above 250 C converts the canary yellow Mo{sub 6}Cl{sub 12} to a non-luminescent gray solid. Optical and thermal aging experiments show that the alkali metal salts of Mo{sub 6}Cl{sub 12} have higher thermal stabilities and remain luminescent after aging at 280 C.

Gregory L. Baker; Ruby N. Ghosh; D.J. Osborn III

2004-04-01

54

FIBER OPTICAL MICRO-DETECTORS FOR OXYGEN SENSING IN POWER PLANTS  

SciTech Connect

A reflection mode fiber optic oxygen sensor is being developed that can operate at high temperatures for power plant applications. The sensor is based on the {sup 3}O{sub 2} quenching of the red emission from hexanuclear molybdenum chloride clusters. Two critical materials issues are the cluster's ability to withstand high temperatures when immobilized in a porous the sol-gel support, and whether after heating to high temperatures, the sol-gel matrix maintains a high and constant permeability to oxygen to support rapid quenching of luminescence. We used a composite materials approach to prepare stable sensing layers on optical fibers. We dispersed 60 w/w% of a pre-cured sol-gel composite containing the potassium salt of molybdenum clusters (K{sub 2}Mo{sub 6}Cl{sub 14}) into a sol-gel binder solution, and established the conditions necessary for deposition of sol-gel films on optical fibers and planar substrates. The fiber sensor has an output signal of 5 nW when pumped with an inexpensive commercial 365 nm ultraviolet light emitting diode (LED). Quenching of the sensor signal by oxygen was observed up to a gas temperature of 175 C with no degradation of the oxygen permeability of the composite after high temperature cycling. On planar substrates the cluster containing composite responds within <1 second to a gas exchange from nitrogen to oxygen, indicating the feasibility of real-time oxygen detection.

Gregory L. Baker; Ruby N. Ghosh; D.J. Osborn III; Po Zhang

2005-07-01

55

FIBER OPTICAL MICRO-DETECTORS FOR OXYGEN SENSING IN POWER PLANTS  

SciTech Connect

A reflection mode fiber optic oxygen sensor that can operate at high temperatures for power plant applications is being developed. The sensor is based on the {sup 3}O{sub 2} quenching of the red emission from hexanuclear molybdenum chloride clusters. One of the critical materials issues is to demonstrate that the luminescent cluster immobilized in the sol-gel porous support can withstand high temperature. At the same time the sol-gel matrix must have a high permeability to oxygen. Using a potassium salt of the molybdenum clusters, K{sub 2}Mo{sub 6}Cl{sub 14}, we have established the conditions necessary for deposition of optical quality sol-gel films. From spectroscopic measurements of the film we have shown that the cluster luminescence is stable following heat cycling of 54 hours at 200 C. Quenching of a factor of 1.5X between pure nitrogen and 21% oxygen was observed from in-situ measurements of films heated directly at 200 C. An automated system for characterizing fiber optic oxygen sensors up to 220 C with a temporal resolution better than 10 s is under construction. We estimate a signal of 6 x 10{sup 8} photons/s after complete quenching in 21% oxygen. These are promising results for a high temperature fiber optical oxygen sensor based on molybdenum chloride clusters.

Gregory L. Baker; Ruby N. Ghosh; D.J. Osborn III; Po Zhang

2005-04-01

56

Fiber Optical Micro-detectors for Oxygen Sensing in Power Plants  

SciTech Connect

A reflection mode fiber optic oxygen sensor that can operate at high temperatures for power plant applications is being developed. The sensor is based on the {sup 3}O{sub 2} quenching of the red emission from hexanuclear molybdenum chloride clusters. Previously we immobilized the potassium salt of a molybdenum cluster, K{sub 2}M{sub 6}Cl{sub 14}, in a sol-gel matrix and showed that the luminescence is stable after 54 hours at 200 C, but the quenching ratios were low and the films delaminated after thermal cycling due to densification of the matrix. Three new approaches to solve decreased quenching over time and delamination of films off fiber tips were investigated. In the first approach K{sub 2}Mo{sub 6}Cl{sub 14} embedded in cured sol-gel particles were incorporated into a TEOS based sol-gel. These gave enhanced quenching (6x), but delaminated. Our second approach was to use a commercial cyanoacrylate glue to immobilize the particles onto the tip of an optical fiber. This gave better adhesion and good quenching initially, but eventually the glue degraded upon heating. Our third approach was to use a 55% OtMOS/ TEOS sol-gel binder. Films based on this new sol-gel binder show high quenching ({approx}6x) and superior mechanical stability even after thermal cycling. Sensor measurements on an optical fiber containing K{sub 2}Mo{sub 6}Cl{sub 14} embedded in cured sol-gel particles were obtained from 100 to 25 C. The signal intensity in nitrogen was stable at 2.8 {+-} 0.2 nW, and the quenching ratio (ratio of signal in N{sub 2} vs. 21 % O{sub 2}) varied from 4.4 to 6.9X. These are promising results for a high temperature fiber optical oxygen sensor based on molybdenum chloride clusters.

Gregory L. Baker; Ruby N. Ghosh; D.J. Osborn III; Po Zhang

2005-10-01

57

A Telemedicine Application to Schedule Temperature in an In Vivo Sensor Network for Cancer Treatment  

PubMed Central

Abstract Wireless communication has played a significant role in modern healthcare systems. However, the death toll from chronic diseases, such as cancer, continues to increase. Hyperthermia combined with radiotherapy and/or chemotherapy is a promising strategy for cancer treatment, and temperature control is critical for the success of this intervention. In vivo sensors are an emerging technology in healthcare. Thermal awareness has also received attention in in vivo sensor research. In this context, we have been motivated to use in vivo sensors to regulate the temperature changes in cancer cells during combined treatment. Limitations in existing in vivo thermal-aware routing algorithms motivated us to use the in vivo “lightweight rendezvous routing” approach. However, smartphone-driven telemedicine applications are proliferating to provide remote healthcare and collaborative consultation, required in combined therapies. In this context, we have proposed a telemedicine application where a smartphone not only regulates temperature scheduling in in vivo sensors, but also communicates with local or remote clinicians to maintain collaborative efforts for combined therapies against cancer. PMID:23234425

Kamal, Rossi; Lee, Seok-Geun

2012-01-01

58

Comparison of in vivo and ex vivo laser scanning microscopy and multiphoton tomography application for human and porcine skin imaging  

NASA Astrophysics Data System (ADS)

Two state-of-the-art microscopic optical methods, namely, confocal laser scanning microscopy in the fluorescence and reflectance regimes and multiphoton tomography in the autofluorescence and second harmonic generation regimes, are compared for porcine skin ex vivo and healthy human skin in vivo. All skin layers such as stratum corneum (SC), stratum spinosum (SS), stratum basale (SB), papillary dermis (PD) and reticular dermis (RD) as well as transition zones between these skin layers are measured noninvasively at a high resolution, using the above mentioned microscopic methods. In the case of confocal laser scanning microscopy (CLSM), measurements in the fluorescence regime were performed by using a fluorescent dye whose topical application on the surface is well suited for the investigation of superficial SC and characterisation of the skin barrier function. For investigations of deeply located skin layers, such as SS, SB and PD, the fluorescent dye must be injected into the skin, which markedly limits fluorescence measurements using CLSM. In the case of reflection CLSM measurements, the obtained results can be compared to the results of multiphoton tomography (MPT) for all skin layers excluding RD. CLSM cannot distinguish between dermal collagen and elastin measuring their superposition in the RD. By using MPT, it is possible to analyse the collagen and elastin structures separately, which is important for the investigation of anti-aging processes. The resolution of MPT is superior to CLSM. The advantages and limitations of both methods are discussed and the differences and similarities between human and porcine skin are highlighted.

Darvin, M. E.; Richter, H.; Zhu, Y. J.; Meinke, M. C.; Knorr, F.; Gonchukov, S. A.; Koenig, K.; Lademann, J.

2014-07-01

59

Histotripsy for Pediatric Cardiac Applications: In Vivo Neonatal Pig Model  

NASA Astrophysics Data System (ADS)

This study investigated the in vivo feasibility of using histotripsy to non-invasively create a flow channel between the ventricles by generating a perforation of the ventricular septum, clinically referred to as a ventricular septum defect (VSD). The overall goal is to develop a non-invasive procedure to aid in the treatment of neonatal patients with complex congenital heart diseases such as Hypoplastic Left Heart Syndrome (HLHS). Histotripsy is a therapeutic ultrasound technique that produces mechanical fractionation of soft tissue through controlled cavitation. The study was conducted in a live and intact neonatal pig model. The ventricular septum in the neonatal pig heart was treated with histotripsy delivered by a spherically focused 1 MHz transducer positioned outside the chest wall. Histotripsy treatment was applied using 5-cycle ultrasound pulses at 1 kHz pulse repetition frequency with 12-18 MPa peak negative pressure. The treatment was guided and monitored with ultrasound imaging. In all nine subjects treated, a bubble cloud was generated on the ventricular septum using histotripsy, and visualized with ultrasound imaging. Within 20 seconds to 4 minutes following the initiation of a bubble cloud, a VSD was created in all nine pigs and confirmed by the detection of blood flow through the ventricular septum with color Doppler ultrasound. Gross morphology and histology on all hearts showed a demarcated perforation in the ventricular septum. This study shows that a VSD can be created in an intact neonatal animal using extracorporeal histotripsy under real-time ultrasound guidance.

Miller, Ryan M.; Owens, Gabe; Ensing, Gregory; Ludomirsky, Achiau; Cain, Charles; Xu, Zhen

2010-03-01

60

Stimuli-responsive photoacoustic nanoswitch for in vivo sensing applications.  

PubMed

Photoacoustic imaging provides high-resolution images at depths beyond the optical diffusion limit. To broaden its utility, there is need for molecular sensors capable of detecting environmental stimuli through alterations in photoacoustic signal. Photosynthetic organisms have evolved ingenious strategies to optimize light absorption through nanoscale ordered dye aggregation. Here, we use this concept to synthesize a stimuli-responsive nanoswitch with a large optical absorbance and sensing capabilities. Ordered dye aggregation between light-harvesting porphyrins was achieved through intercalation within thermoresponsive nanovesicles. This causes an absorbance red-shift of 74 nm and a 2.7-fold increase in absorptivity of the Qy-band, with concomitant changes in its photoacoustic spectrum. This spectral feature can be reversibly switched by exceeding a temperature threshold. Using this thermochromic property, we noninvasively determined a localized temperature change in vivo, relevant for monitoring thermal therapies of solid tumors. Similar strategies may be applied alongside photoacoustic imaging, to detect other stimuli such as pH and enzymatic activity. PMID:25046406

Ng, Kenneth K; Shakiba, Mojdeh; Huynh, Elizabeth; Weersink, Robert A; Roxin, Áron; Wilson, Brian C; Zheng, Gang

2014-08-26

61

Biodegradable luminescent porous silicon nanoparticles for in vivo applications  

Microsoft Academic Search

Nanomaterials that can circulate in the body hold great potential to diagnose and treat disease. For such applications, it is important that the nanomaterials be harmlessly eliminated from the body in a reasonable period of time after they carry out their diagnostic or therapeutic function. Despite efforts to improve their targeting efficiency, significant quantities of systemically administered nanomaterials are cleared

Ji-Ho Park; Luo Gu; Geoffrey von Maltzahn; Erkki Ruoslahti; Sangeeta N. Bhatia; Michael J. Sailor

2009-01-01

62

In vivo confocal microscopy in dermatology: from research to clinical application  

NASA Astrophysics Data System (ADS)

Confocal laser scanning microscopy (CLSM) represents an emerging technique for the noninvasive histomorphological analysis of skin in vivo and has shown its applicability for dermatological research as well as its value as an adjunct tool in the clinical management of skin cancer patients. Herein, we aim to give an overview on the current clinical indications for CLSM in dermatology and also highlight the diverse applications of CLSM in dermatological research.

Ulrich, Martina; Lange-Asschenfeldt, Susanne

2013-06-01

63

Nanoparticles: are rare-Earth nanoparticles suitable for in vivo applications? (Adv. Mater. 40/2014).  

PubMed

Rare earth (RE) nanoparticles attract considerable attention in biomedical applications due to their unique optical and magnetic properties associated with f-electrons. On page 6922, M. Y. Gao and co-workers summarize the recent achievements in controlled synthesis of magnetic and luminescent RE nanoparticles, surface modification, and toxicity studies of RE nanomaterials, and highlight state-of-the-art in vivo applications of RE nanoparticles. PMID:25339278

Liu, Chunyan; Hou, Yi; Gao, Mingyuan

2014-10-01

64

Tracking of stem cells in vivo for cardiovascular applications  

PubMed Central

In the past ten years, the concept of injecting stem and progenitor cells to assist with rebuilding damaged blood vessels and myocardial tissue after injury in the heart and peripheral vasculature has moved from bench to bedside. Non-invasive imaging can not only provide a means to assess cardiac repair and, thereby, cellular therapy efficacy but also a means to confirm cell delivery and engraftment after administration. In this first of a two-part review, we will review the different types of cellular labeling techniques and the application of these techniques in cardiovascular magnetic resonance and ultrasound. In addition, we provide a synopsis of the cardiac cellular clinical trials that have been performed to-date. PMID:24406054

2014-01-01

65

Nanoparticle-based delivery system for application of siRNA in vivo.  

PubMed

Small interfering RNAs (siRNAs) silence the expression of specific target genes by mediating RNA interference (RNAi) in mammalian cells. siRNAs have not only been widely used as a valuable tool for functional genomics research, but they also have demonstrated great potential in biomedical therapeutic applications for diseases caused by abnormal gene overexpression or mutation. One of the most important issues to overcome before full clinical application is the development of effective administration methods for siRNAs to the target tissue or cells in vivo, which is highly dependent on the delivery system. Currently, there are two major kinds of in vivo delivery systems: viral or nonviral. As one of the nonviral carrier systems, nanoparticles, combinations of liposomes and cationic polymer complexes, have exhibited improved in vivo stability, target specificity, and cell/tissue uptake and internalization of the encapsulated RNAi oligos, which result in more effective silencing with less cellular toxicity and immune stimulation. This review will discuss the latest advancements in nanoparticle-mediated RNAi delivery systems, including nano-materials, preparation, and characteristics. In conjunction, the clinical trial cases related to the nanoparticle-siRNA complexes will be highlighted. The safety issues of nanoparticles used in vivo will also be mentioned. Finally, this review will summarize the perspectives for future applications of nanoparticle-mediated RNAi delivery systems. PMID:20359287

Wang, Yan; Li, Zhiguo; Han, Yee; Liang, Leo Hwa; Ji, Aimin

2010-02-01

66

Application of in vivo measurements for the management of cyanobacteria breakthrough into drinking water treatment plants.  

PubMed

The increasing presence of potentially toxic cyanobacterial blooms in drinking water sources and within drinking water treatment plants (DWTPs) has been reported worldwide. The objectives of this study are to validate the application of in vivo probes for the detection and management of cyanobacteria breakthrough inside DWTPs, and to verify the possibility of treatment adjustment based on intensive real-time monitoring. In vivo phycocyanin YSI probes were used to monitor the fate of cyanobacteria in raw water, clarified water, filtered water, and chlorinated water in a full scale DWTP. Simultaneous samples were also taken for microscopic enumeration. The in vivo probe was successfully used to detect the incoming densities of high cyanobacterial cell number into the clarification process and their breakthrough into the filtered water. In vivo probes were used to trace the increase in floating cells over the clarifier, a robust sign of malfunction of the coagulation-sedimentation process. Pre-emptive treatment adjustments, based on in vivo probe monitoring, resulted in successful removal of cyanobacterial cells. The field results on validation of the probes with cyanobacterial bloom samples showed that the probe responses are highly linear and can be used to trigger alerts to take action. PMID:24429778

Zamyadi, Arash; Dorner, Sarah; Ndong, Mouhamed; Ellis, Donald; Bolduc, Anouka; Bastien, Christian; Prévost, Michèle

2014-02-01

67

Applications of the direct photon absorption technique for measuring bone mineral content in vivo. Determination of body composition in vivo  

NASA Technical Reports Server (NTRS)

The bone mineral content, BMC, determined by monoenergetic photon absorption technique, of 29 different locations on the long bones and vertebral columns of 24 skeletons was measured. Compressive tests were made on bone from these locations in which the maximum load and maximum stress were measured. Also the ultimate strain, modulus of elasticity and energy absorbed to failure were determined for compact bone from the femoral diaphysis and cancellous bone from the eighth through eleventh thoracic vertebrae. Correlations and predictive relationships between these parameters were examined to investigate the applicability of using the BMC at sites normally measured in vivo, i.e. radius and ulna in estimating the BMC and/or strength of the spine or femoral neck. It was found that the BMC at sites on the same bone were highly correlated r = 0.95 or better; the BMC at sites on different bones were also highly interrelated, r = 0.85. The BMC at various sites on the long bones could be estimated to between 10 and 15 per cent from the BMC of sites on the radius or ulna.

Cameron, J. R.

1972-01-01

68

A New Crosslinkable Oxygen Sensor Covalently Bonded into Poly(2-hydroxyethyl methacrylate)-CO-Polyacrylamide Thin Film for Dissolved Oxygen Sensing  

PubMed Central

A new oxygen sensor, compound 2, was synthesized through a chemical modification of a popularly used oxygen sensor of platinum(II)-5,10,15,20-tetrakis-(2,3,4,5,6-pentafluorophenyl)-porphyrin (PtTFPP). The new sensor compound 2 possesses four crosslinkable methacrylate functional moieties, enabling it to be polymerized and crosslinked with other monomers for polymer sensing film (also called membrane) preparation. Using this characteristic, compound 2 was covalently bonded to hydrophilic poly(2-hydroxyethyl methacrylate)-co-polyacrylamide (referred to as PHEMA to simplify) and hydrophobic polystyrene (PS) films. To better understand the advantages and disadvantages of chemical crosslinking approaches and the influence of polymer matrices on sensing performance, PtTFPP was physically incorporated into the same PHEMA and PS matrices to compare. Response to dissolved oxygen (DO), leaching of the sensor molecules from their matrices, photostability of the sensors, and response time to DO changes were studied. It was concluded that the chemical crosslinking of the sensor compound 2 in polymer matrices: (i) alleviated the leaching problem of sensor molecules which usually occurred in the physically doped sensing systems and (ii) significantly improved sensors’ photostability. The PHEMA matrix was demonstrated to be more suitable for oxygen sensing than PS, because for the same sensor molecule, the oxygen sensitivity in PHEMA film was higher than that in PS and response time to DO change in the PHEMA film was faster than that in PS. It was the first time oxygen sensing films were successfully prepared using biocompatible hydrophilic PHEMA as a matrix, which does not allow leaching of the sensor molecules from the polymer matrix, has a faster response to DO changes than that of PS, and does not present cytotoxicity to human lung adenocarcinoma epithelial cells (A549). It is expected that the new sensor compound 2 and its similar compounds with chemically crosslinking characteristics can be widely applied to generate many interesting oxygen sensing materials for studying biological phenomena. PMID:20352057

Tian, Yanqing; Shumway, Bradley R.; Meldrum, Deirdre R.

2010-01-01

69

Ex vivo assessment of cellular immune function - applications in patient care and clinical studies.  

PubMed

Cellular ex vivo assays have a broad range of applications in patient care and clinical studies, especially when they are standardized and highly sensitive. As compared to analyses by molecular genetics such as the single nucleotide polymorphism (SNP) testing, they are usually more global. These assays partly mimic the in vivo situation, relying on a complex interaction of various immune cells. For example, they can be used to determine modulation of alloresponses by treatment or underlying disease, diagnose and quantify primary and secondary cellular immunodeficiency, follow-up vaccination responses, measure adoptive transfer of virus-specific immunity via hematopoietic stem cell or liver transplantation, assess allergy, antimicrobial immunity and also rare effector/memory cells directed against tumor antigens. This review will first shortly describe various cellular in vitro methods and then present applications, summarizing some own studies performed within the last 18?years. PMID:25329632

Lindemann, M

2014-11-01

70

The application of dermal papillary rings in dermatology by in vivo confocal laser scanning microscopy  

NASA Astrophysics Data System (ADS)

Confocal laser scanning microscopy (CLSM) allows noninvasive visualization of human skin in vivo, without needing to fix or section the tissue. Melanocytes and pigmented keratinocytes at the level of the basal layer form bright dermal papillary rings which are readily amenable to identify in confocal images. Our purpose was to explore the role of dermal papillary rings in assessment of lesion location, the diagnosis, differential diagnosis of lesions and assessment of therapeutic efficacy by in vivo CLSM. Seventy-one patients were imaged with the VivaScope 1500 reflectance confocal microscope provided by Lucid, Inc. The results indicate that dermal papillary rings can assess the location of lesion; the application of dermal papillary rings can provide diagnostic support and differential diagnosis for vitiligo, nevus depigmentosus, tinea versicolor, halo nevus, common nevi, and assess the therapeutic efficacy of NBUVB phototherapy plus topical 0.1 percent tacrolimus ointment for vitiligo. In conclusion, our findings indicate that the dermal papillary rings play an important role in the assessment the location of lesion, diagnosis, differential diagnosis of lesions and assessment of therapeutic efficacy by in vivo CLSM. CLSM may be a promising tool for noninvasive examination in dermatology. However, larger studies are needed to expand the application of dermal papillary rings in dermatology.

Xiang, W. Z.; Xu, A. E.; Xu, J.; Bi, Z. G.; Shang, Y. B.; Ren, Q. S.

2010-08-01

71

In vivo evaluation of drug delivery after ultrasound application: A new use for the photoacoustic technique  

NASA Astrophysics Data System (ADS)

Ultrasound application is a therapeutical resource widely employed in physiotherapy. One of its applications is the phonophoresis, a technique in which the ultrasound radiation is utilized to deliver drugs through the skin to soft tissues. The proposal of our study was to employ the Photoacoustic Technique to evaluate the efficacy of such treatment, analyzing if phonophoresis could enhance drug delivery through skin when compared to the more traditional method of manual massage. The configuration of the system employed was such that it was possible to perform in vivo measurements, which is a pre-requisite for this kind of study. The changes observed in the photoacoustic signal amplitude after each form of drug application were attributed to changes in the thermal effusivity of the system, due to penetration of the drug. The technique was able to detect differences in drug delivery between the specified physiotherapy treatments, indicating that phonophoresis enhances drug absorption by tissue.

Barja, P. R.; Acosta-Avalos, D.; Rompe, P. C. B.; Dos Anjos, F. H.; Marciano, F. R.; da Silva, M. D.

2005-06-01

72

In vivo imaging of free radicals: applications from mouse to man.  

PubMed

Free radicals and other paramagnetic species, play an important role in cellular injury and pathophysiology. EPR spectroscopy and imaging has emerged as an important tool for non-invasive in vivo measurement and spatial mapping of free radicals in biological tissues. Extensive applications have been performed in small animals such as mice and recently applications in humans have been performed. Spatial EPR imaging enables 3D mapping of the distribution of a given free radical while spectral-spa-tial EPR imaging enables mapping of the spectral information at each spatial position, and, from the observed line width, the localized tissue oxygenation can be determined. A variety of spatial, and spectral-spatial EPR imaging applications have been performed. These techniques, along with the use of biocompatible paramagnetic probes including particulate suspensions and soluble nitroxide radicals, enable spatial imaging of the redox state and oxygenation in a variety of biomedical applications. With spectral-spatial EPR imaging, oxygenation was mapped within the gastrointestinal (GI) tract of living mice, enabling measurement of the oxygen gradient from the proximal to the distal GI tract. Using spatial EPR imaging, the distribution and metabolism of nitroxide radicals within the major organs of the body of living mice was visualized and anatomically co-registered by proton MRI enabling in vivo mapping of the redox state and radical clearance. EPR imaging techniques have also been applied to non-invasively measure the distribution and metabolism of topically applied nitroxide redox probes in humans, providing information regarding the penetration of the label through the skin and measurement of its redox clearance. Thus, EPR spectroscopy and imaging has provided important information in a variety of applications ranging from small animal models of disease to topical measurement of redox state in humans. PMID:12162454

He, Guanglong; Samouilov, Alexandre; Kuppusamy, Periannan; Zweier, Jay L

2002-01-01

73

Phosphorescent nanoparticles for quantitative measurements of oxygen profiles in vitro and in vivo  

PubMed Central

We present the development and characterization of nanoparticles loaded with a custom phosphor; we exploit these nanoparticles to perform quantitative measurements of the concentration of oxygen within three-dimensional (3-D) tissue cultures in vitro and blood vessels in vivo. We synthesized a customized ruthenium (Ru)-phosphor and incorporated it into polymeric nanoparticles via self-assembly. We demonstrate that the encapsulated phosphor is non-toxic with and without illumination. We evaluated two distinct modes of employing the phosphorescent nanoparticles for the measurement of concentrations of oxygen: 1) in vitro, in a 3-D microfluidic tumor model via ratiometric measurements of intensity with an oxygen-insensitive fluorophore as a reference, and 2) in vivo, in mouse vasculature using measurements of phosphorescence lifetime. With both methods, we demonstrated micrometer-scale resolution and absolute calibration to the dissolved oxygen concentration. Based on the ease and customizability of the synthesis of the nanoparticles and the flexibility of their application, these oxygen-sensing polymeric nanoparticles will find a natural home in a range of biological applications, benefiting studies of physiological as well as pathological processes in which oxygen availability and concentration play a critical role. PMID:22240511

Choi, Nak Won; Verbridge, Scott S.; Williams, Rebecca M.; Chen, Jin; Kim, Ju-Young; Schmehl, Russel; Farnum, Cornelia E.; Zipfel, Warren R.; Fischbach, Claudia; Stroock, Abraham D.

2012-01-01

74

Non invasive in vivo investigation of hepatobiliary structure and function in STII medaka (Oryzias latipes): methodology and applications  

PubMed Central

Background A novel transparent stock of medaka (Oryzias latipes; STII), recessive for all pigments found in chromatophores, permits transcutaneous imaging of internal organs and tissues in living individuals. Findings presented describe the development of methodologies for non invasive in vivo investigation in STII medaka, and the successful application of these methodologies to in vivo study of hepatobiliary structure, function, and xenobiotic response, in both 2 and 3 dimensions. Results Using brightfield, and widefield and confocal fluorescence microscopy, coupled with the in vivo application of fluorescent probes, structural and functional features of the hepatobiliary system, and xenobiotic induced toxicity, were imaged at the cellular level, with high resolution (< 1 ?m), in living individuals. The findings presented demonstrate; (1) phenotypic response to xenobiotic exposure can be investigated/imaged in vivo with high resolution (< 1 ?m), (2) hepatobiliary transport of solutes from blood to bile can be qualitatively and quantitatively studied/imaged in vivo, (3) hepatobiliary architecture in this lower vertebrate liver can be studied in 3 dimensions, and (4) non invasive in vivo imaging/description of hepatobiliary development in this model can be investigated. Conclusion The non-invasive in vivo methodologies described are a unique means by which to investigate biological structure, function and xenobiotic response with high resolution in STII medaka. In vivo methodologies also provide the future opportunity to integrate molecular mechanisms (e.g., genomic, proteomic) of disease and toxicity with phenotypic changes at the cellular and system levels of biological organization. While our focus has been the hepatobiliary system, other organ systems are equally amenable to in vivo study, and we consider the potential for discovery, within the context of in vivo investigation in STII medaka, as significant. PMID:18838008

Hardman, Ron C; Kullman, Seth W; Hinton, David E

2008-01-01

75

Live Cell in Vitro and in Vivo Imaging Applications: Accelerating Drug Discovery  

PubMed Central

Dynamic regulation of specific molecular processes and cellular phenotypes in live cell systems reveal unique insights into cell fate and drug pharmacology that are not gained from traditional fixed endpoint assays. Recent advances in microscopic imaging platform technology combined with the development of novel optical biosensors and sophisticated image analysis solutions have increased the scope of live cell imaging applications in drug discovery. We highlight recent literature examples where live cell imaging has uncovered novel insight into biological mechanism or drug mode-of-action. We survey distinct types of optical biosensors and associated analytical methods for monitoring molecular dynamics, in vitro and in vivo. We describe the recent expansion of live cell imaging into automated target validation and drug screening activities through the development of dedicated brightfield and fluorescence kinetic imaging platforms. We provide specific examples of how temporal profiling of phenotypic response signatures using such kinetic imaging platforms can increase the value of in vitro high-content screening. Finally, we offer a prospective view of how further application and development of live cell imaging technology and reagents can accelerate preclinical lead optimization cycles and enhance the in vitro to in vivo translation of drug candidates. PMID:24310493

Isherwood, Beverley; Timpson, Paul; McGhee, Ewan J; Anderson, Kurt I; Canel, Marta; Serrels, Alan; Brunton, Valerie G; Carragher, Neil O

2011-01-01

76

In vivo Raman spectroscopy of biochemical changes in human skin by cosmetic application  

NASA Astrophysics Data System (ADS)

The skin aging process is mainly accelerated by external agents such as sunlight, air humidity and surfactants action. Changes in protein structures and hydration during the aging process are responsible for skin morphological variations. In this work the human skin was investigated by in vivo Raman spectroscopy before and after the topical applications of a cosmetic on 17 healthy volunteers (age 60 to 75). In vivo Raman spectra of the skin were obtained with a Spectrometer SpectraPro- 2500i (Pi-Acton), CCD detector and a 785 nm laser excitation source, collected at the beginning of experiment without cream (T0), after 30 (T30) and 60 (T60) days using the product. The primary changes occurred in the following spectral regions: 935 cm-1 (?CC), 1060 cm-1 (lipids), 1174 to 1201 cm-1 (tryptofan, phenylalanine and tyrosine), 1302 cm-1 (phospholipids), 1520 to 1580 cm-1 (C=C) and 1650 cm-1 (amide I). These findings indicate that skin positive effects were enhanced by a continuous cream application.

Tosato, Maira Gaspar; dos Santos, Edson Pereira; Alves, Rani de Souza; Raniero, Leandro; Menezes, Priscila Fernanda C.; Kruger, Odivânia; Praes, Carlos Eduardo O.; Martin, Airton Abrahão

2010-02-01

77

In vivo electroporation of gene sequences for therapeutic and vaccination applications.  

PubMed

Many recent studies have addressed the impact of gene patents and methods of gene delivery on downstream research and innovation. The field of gene therapy has progressed over the last 10 years due to the rapid advancement in delivery technology. Efficient delivery of genes into target cells depends on the absence of cell injury, oncogenic mutation or inflammation. Gene transfer technology saw a significant boost by the applications of in vivo electroporation. This approach is versatile and safe and can be used to deliver nucleic acid fragments, oligonucleotides, siRNA, and plasmids to a wide variety of tissues, such as skeletal muscle, skin and liver. Many have applied this approach in autoimmune or inflammatory diseases, for the intratumoral delivery of therapeutic vectors, or for systemic delivery of endocrine hormones, hematopoietic factors, antibodies, enzymes, or numerous other protein drugs. This technique has been found to strongly boost DNA vaccination against infectious agents or tumor antigens. in vivo Electroporation has been performed in humans. This review will focus on the intellectual property revolving around recent developments in the area of electroporation, including devices and methodology for various applications. PMID:19075935

Draghia-Akli, Ruxandra; Khan, Amir S

2007-01-01

78

Qualichem In Vivo: A Tool for Assessing the Quality of In Vivo Studies and Its Application for Bisphenol A  

PubMed Central

In regulatory toxicology, quality assessment of in vivo studies is a critical step for assessing chemical risks. It is crucial for preserving public health studies that are considered suitable for regulating chemicals are robust. Current procedures for conducting quality assessments in safety agencies are not structured, clear or consistent. This leaves room for criticism about lack of transparency, subjective influence and the potential for insufficient protection provided by resulting safety standards. We propose a tool called “Qualichem in vivo” that is designed to systematically and transparently assess the quality of in vivo studies used in chemical health risk assessment. We demonstrate its use here with 12 experts, using two controversial studies on Bisphenol A (BPA) that played an important role in BPA regulation in Europe. The results obtained with Qualichem contradict the quality assessments conducted by expert committees in safety agencies for both of these studies. Furthermore, they show that reliance on standardized guidelines to ensure scientific quality is only partially justified. Qualichem allows experts with different disciplinary backgrounds and professional experiences to express their individual and sometimes divergent views—an improvement over the current way of dealing with minority opinions. It provides a transparent framework for expressing an aggregated, multi-expert level of confidence in a study, and allows a simple graphical representation of how well the study integrates the best available scientific knowledge. Qualichem can be used to compare assessments of the same study by different health agencies, increasing transparency and trust in the work of expert committees. In addition, it may be used in systematic evaluation of in vivo studies submitted by industry in the dossiers that are required for compliance with the REACH Regulation. Qualichem provides a balanced, common framework for assessing the quality of studies that may or may not be following standardized guidelines. PMID:24489958

Maxim, Laura; van der Sluijs, Jeroen P.

2014-01-01

79

An Ex Vivo Toe Model Used to Assess Applicators for the Iontophoretic Ungual Delivery of Terbinafine  

Microsoft Academic Search

Purpose  An ex vivo intact toe model was developed to assess two different applicator designs for iontophoretic delivery of terbinafine into\\u000a the nail only or the nail and surrounding skin.\\u000a \\u000a \\u000a \\u000a Methods  Iontophoretic permeation studies were carried out on intact cadaver toes using nail-only and nail\\/skin applicators with a\\u000a current dose of 10 mA*min (0.5 mA for 20 min).\\u000a \\u000a \\u000a \\u000a Results  Iontophoresis enhanced drug permeation and tissue loading

Anroop B. Nair; Hyun D. Kim; Shawn P. Davis; Robert Etheredge; Michael Barsness; Phillip M. Friden; S. Narasimha Murthy

2009-01-01

80

Development and Applications of Laminar Optical Tomography for In Vivo Imaging  

NASA Astrophysics Data System (ADS)

Laminar optical tomography (LOT) is an optical imaging technique capable of making depth-resolved measurements of absorption and fluorescence contrast in scattering tissue. LOT was first demonstrated in 2004 by Hillman et al [1]. The technique combines a non-contact laser scanning geometry, similar to a low magnification confocal microscope, with the imaging principles of diffuse optical tomography (DOT). This thesis describes the development and application of a second generation LOT system, which acquires both fluorescence and multi-wavelength measurements simultaneously and is better suited for in vivo measurements. Chapter 1 begins by reviewing the interactions of light with tissue that form the foundation of optical imaging. A range of related optical imaging techniques and the basic principles of LOT imaging are then described. In Chapter 2, the development of the new LOT imaging system is described including the implementation of a series of interfaces to allow clinical imaging. System performance is then evaluated on a range of imaging phantoms. Chapter 3 describes two in vivo imaging applications explored using the second generation LOT system, first in a clinical setting where skin lesions were imaged, and then in a laboratory setting where LOT imaging was performed on exposed rat cortex. The final chapter provides a brief summary and describes future directions for LOT. LOT has the potential to find applications in medical diagnostics, surgical guidance, and in-situ monitoring owing to its sensitivity to absorption and fluorescence contrast as well as its ability to provide depth sensitive measures. Optical techniques can characterize blood volume and oxygenation, two important biological parameters, through measurements at different wavelengths. Fluorescence measurements, either from autofluorescence or fluorescent dyes, have shown promise for identifying and analyzing lesions in various epithelial tissues including skin [2, 3], colon [4], esophagus [5, 6], oral mucosa [7, 8], and cervix [9]. The desire to capture these types of measurements with LOT motivated much of the work presented here.

Burgess, Sean A.

81

Highly purified mussel adhesive protein to secure biosafety for in vivo applications  

PubMed Central

Background Unique adhesive and biocompatibility properties of mussel adhesive proteins (MAPs) are known for their great potential in many tissue engineering and biomedical applications. Previously, it was successfully demonstrated that redesigned hybrid type MAP, fp-151, mass-produced in Gram-negative bacterium Escherichia coli, could be utilized as a promising adhesive biomaterial. However, purification of recombinant fp-151 has been unsatisfactory due to its adhesive nature and polarity which make separation of contaminants (especially, lipopolysaccharide, a toxic Gram-negative cell membrane component) very difficult. Results In the present work, we devised a high resolution purification approach to secure safety standards of recombinant fp-151 for the successful use in in vivo applications. Undesirable impurities were remarkably eliminated as going through sequential steps including treatment with multivalent ion and chelating agent for cell membrane washing, mechanical cell disruption, non-ionic surfactant treatment for isolated inclusion body washing, acid extraction of washed inclusion body, and ion exchange chromatography purification of acid extracted sample. Through various analyses, such as high performance liquid chromatographic purity assay, limulus amoebocyte lysate endotoxin assay, and in vitro mouse macrophage cell tests on inflammation, viability, cytotoxicity, and apoptosis, we confirmed the biological safety of bacterial-derived purified recombinant fp-151. Conclusions Through this purification design, recombinant fp-151 achieved 99.90% protein purity and 99.91% endotoxin reduction that nearly no inflammation response was observed in in vitro experiments. Thus, the highly purified recombinant MAP would be successfully used as a safety-secured in vivo bioadhesive for tissue engineering and biomedical applications. PMID:24725543

2014-01-01

82

The application of quantum dots for the melanoma tumor in vivo imaging  

NASA Astrophysics Data System (ADS)

Objective: Over the past decade, fluorescent semiconductor nanocrystals, also known as quantum dots (QDs), have been applied in biomedical imaging in vitro and in vivo because of their fascinating optical properties. In this work, we investigated the application of CdTe QDs for tumor fluorescence in vivo imaging. Methods: The transparent dorsal skin fold window chamber (DSFC) was constructed on the 4~6 week-old BALB/c mice. The melanoma cells stably expressing green fluorescent protein ---ZsGreen were transplanted into the chamber and the melanoma DSFC model was established successfully. The water soluble CdTe QDs were synthesized and then administrated in the model through the tail intravenous injection. The fluorescent expression of B16 cells were assayed by fluorescent microscopy, the tumor growth, the blood capillaries distributions and its dynamic changes were observed by stereomicroscopy and laser scanning confocal microscopy. Results: The results demonstrated that the expression efficiency of ZsGreen was 41%, which met the experimental requirement. The tumors was visible inside the chamber after implantation of melanoma cells for 5~6 days, while no obvious changes in mice behaviors were found. After injection of the QDs, CdTe QDs accumulated at the invading edge of a range of solid tumor. We could also observe the tumor cells growth near the blood vessels, the angiogenesis occurred inside the tumor and the local blood capillaries increased. Conclusions: This work provided a new strategy for the tumor in vivo imaging and the development of targeted antineoplastic drugs.

Feng, Yayi; Zhai, Peng; Wang, Xiaomei; Ying, Ming; Wu, Jinbo; Zhu, Xiaomei; Lin, Guimiao; Chen, Qiang; Xu, Gaixia

2014-09-01

83

A feasibility study of in vivo applications of single beam acoustic tweezers  

NASA Astrophysics Data System (ADS)

Tools that are capable of manipulating micro-sized objects have been widely used in such fields as physics, chemistry, biology, and medicine. Several devices, including optical tweezers, atomic force microscope, micro-pipette aspirator, and standing surface wave type acoustic tweezers have been studied to satisfy this need. However, none of them has been demonstrated to be suitable for in vivo and clinical studies. Single beam acoustic tweezers (SBAT) is a technology that uses highly focused acoustic beam to trap particles toward the beam focus. Its feasibility was first theoretically and experimentally demonstrated by Lee and Shung several years ago. Since then, much effort has been devoted to improving this technology. At present, the tool is capable of trapping a microparticle as small as 1 ?m, as well as a single red blood cell. Although in comparing to other microparticles manipulating technologies, SBAT has advantages of providing stronger trapping force and deeper penetration depth in tissues, and producing less tissue damage, its potential for in vivo applications has yet been explored. It is worth noting that ultrasound has been used as a diagnostic tool for over 50 years and no known major adverse effects have been observed at the diagnostic energy level. This paper reports the results of an initial attempt to assess the feasibility of single beam acoustic tweezers to trap microparticles in vivo inside of a blood vessel. The acoustic intensity of SBAT under the trapping conditions that were utilized was measured. The mechanical index and thermal index at the focus of acoustic beam were found to be 0.48 and 0.044, respectively, which meet the standard of commercial diagnostic ultrasound system.

Li, Ying; Lee, Changyang; Chen, Ruimin; Zhou, Qifa; Shung, K. Kirk

2014-10-01

84

Please cite this article in press as: L. Shen, et al., A CMOS optical detection system for point-of-use luminescent oxygen sensing, Sens. Actuators B: Chem. (2011), doi:10.1016/j.snb.2011.01.001  

E-print Network

optical detection system for point-of-use luminescent oxygen sensing Li Shena , Michael Rattermana , David of the CMOS image sensor, an oxygen insensitive reference can be integrated to improve the reliability when powered by a battery. The low-cost and high sensitivity of the demonstrated optical sensing approach make

Papautsky, Ian

85

Adapting MRI acoustic radiation force imaging for in vivo human brain focused ultrasound applications.  

PubMed

A variety of magnetic resonance imaging acoustic radiation force imaging (MR-ARFI) pulse sequences as the means for image guidance of focused ultrasound therapy have been recently developed and tested ex vivo and in animal models. To successfully translate MR-ARFI guidance into human applications, ensuring that MR-ARFI provides satisfactory image quality in the presence of patient motion and deposits safe amount of ultrasound energy during image acquisition is necessary. The first aim of this work was to study the effect of motion on in vivo displacement images of the brain obtained with 2D Fourier transform spin echo MR-ARFI. Repeated bipolar displacement encoding configuration was shown less sensitive to organ motion. The optimal signal-to-noise ratio of displacement images was found for the duration of encoding gradients of 12 ms. The second aim was to further optimize the displacement signal-to-noise ratio for a particular tissue type by setting the time offset between the ultrasound emission and encoding based on the tissue response to acoustic radiation force. A method for measuring tissue response noninvasively was demonstrated. Finally, a new method for simultaneous monitoring of tissue heating during MR-ARFI acquisition was presented to enable timely adjustment of the ultrasound energy aimed at ensuring the safety of the MR-ARFI acquisition. PMID:22555751

Kaye, Elena A; Pauly, Kim Butts

2013-03-01

86

Improved Model of Fluorescence Recovery Expands the Application of Multiphoton Fluorescence Recovery after Photobleaching in Vivo  

PubMed Central

Abstract Multiphoton fluorescence recovery after photobleaching is a well-established microscopy technique used to measure the diffusion of macromolecules in biological systems. We have developed an improved model of the fluorescence recovery that includes the effects of convective flows within a system. We demonstrate the validity of this two-component diffusion-convection model through in vitro experimentation in systems with known diffusion coefficients and known flow speeds, and show that the diffusion-convection model broadens the applicability of the multiphoton fluorescence recovery after photobleaching technique by enabling accurate determination of the diffusion coefficient, even when significant flows are present. Additionally, we find that this model allows for simultaneous measurement of the flow speed in certain regimes. Finally, we demonstrate the effectiveness of the diffusion-convection model in vivo by measuring the diffusion coefficient and flow speed within tumor vessels of 4T1 murine mammary adenocarcinomas implanted in the dorsal skinfold chamber. PMID:19527668

Sullivan, Kelley D.; Sipprell, William H.; Brown, Edward B.; Brown, Edward B.

2009-01-01

87

Application of FRET Technology to the In Vivo Evaluation of Therapeutic Nucleic Acids (ANTs)  

NASA Astrophysics Data System (ADS)

Developing applications for therapeutic nucleic acids (TNAs) (i.e. ribozymes, antisense oligodeoxynucleotides (AS-ODNs), siRNA and aptamers) requires a reporter system designed to rapidly evaluate their in vivo effect. To this end we designed a reporter system based on the fluorescence resonance energy transfer (FRET) engineered to release the FRET effect produced by two green fluorescent protein (GFP) variants linked by a TNA target site. Because the FRET effect occurs instantaneously when two fluorophores are very close to each other (>100nm) stimulating emission of the acceptor fluorophore by the excitation of the donor fluorophore it has been widely use to reveal interactions between molecules. The present system (FRET2) correlates the FRET effect with the in vivo activity of distinct types of TNAs based on a model consisting of RNA from human papillomavirus type 16 (HPV-16) previously shown accessible to TNAs. HPV-16 is the most common papillomavirus associated with cervical cancer, the leading cause of death by cancer in México. The FRET2 system was first tested in vitro and then used in bacteria in which transcription is linked to translation allowing controlled expression and rapid evaluation of the FRET2 protein. To assure accessibility of the target mRNA to TNAs, the FRET2 mRNA was probed by RNaseH assays prior FRET testing. The fluorescence features of the FRET2 system was tested with different FRET-producing GFP donor-acceptor pairs leading to selection of green (donor) and yellow (acceptor) variants of GFP as the most efficient. Modifications in aminoacid composition and linker length of the target sequence did not affect FRET efficiency. In vivo AS-ODN-mediated destruction of the chimerical FRET2 reporter mRNA resulted in the recovery of GFP fluorescent spectrum in a concentration and time dependent manner. Reported anti-HPV ribozymes were also tested with similar results. Therefore, we conclude that the FRET effect can be a useful tool in the development of TNAs.

Benítez-Hess, María Luisa; Alvarez-Salas, Luis Marat

2007-02-01

88

Direct optic nerve sheath (DONS) application of Schwann cells prolongs retinal ganglion cell survival in vivo  

PubMed Central

Cell-based therapies are increasingly recognized as a potential strategy to treat retinal neurodegenerative disease. Their administration, however, is normally indirect and complex, often with an inability to assess in real time their effects on cell death and their migration/integration into the host retina. In the present study, using a partial optic nerve transection (pONT) rat model, we describe a new method of Schwann cell (SC) delivery (direct application to injured optic nerve sheath, SC/DONS), which was compared with intravitreal SC delivery (SC/IVT). Both SC/DONS and SC/IVT were able to be assessed in vivo using imaging to visualize retinal ganglion cell (RGC) apoptosis and SC retinal integration. RGC death in the pONT model was best fitted to the one-phase exponential decay model. Although both SC/DONS and SC/IVT altered the temporal course of RGC degeneration in pONT, SC/DONS resulted in delayed but long-lasting effects on RGC protection, compared with SC/IVT treatment. In addition, their effects on primary and secondary degeneration, and axonal regeneration, were also investigated, by histology, whole retinal counting, and modelling of RGC loss. SC/DONS was found to significantly reduce RGC apoptosis in vivo and significantly increase RGC survival by targeting secondary rather than primary degeneration. Both SC/DONS and SC/IVT were found to promote RGC axonal regrowth after optic nerve injury, with evidence of GAP-43 expression in RGC somas and axons. SC/DONS may have the potential in the treatment of optic neuropathies, such as glaucoma. We show that SC transplantation can be monitored in real time and that the protective effects of SCs are associated with targeting secondary degeneration, with implications for translating cell-based therapies to the clinic. PMID:25321467

Guo, L; Davis, B; Nizari, S; Normando, E M; Shi, H; Galvao, J; Turner, L; Shi, J; Clements, M; Parrinello, S; Cordeiro, M F

2014-01-01

89

Novel biomaterial for transdermal application: in vitro and in vivo characterization.  

PubMed

The objective of the present study was to evaluate a novel film forming biomaterial for its potential application in the preparation of unilaminate transdermal adhesive matrix systems. The biomaterial, Damar Batu (DB), was tried alone and in combination with Eudragit RL100 as a matrixing agent in the preparation of transdermal patches. Developed transdermal patches of Diltiazem hydrochloride (DH) were evaluated for thickness uniformity, weight uniformity, folding endurance and drug content. USP dissolution apparatus V was used for in vitro drug release studies. Modified Franz diffusion cell used for permeation study using excised human cadaver skin. Total 6 formulations were developed and on the basis of in vitro drug release and in vitro skin permeation profile F5 composed of DB: Eudragit RL100 (60:40) and carrying 20 %w/w DH was selected as an optimized formulation for in vivo study. The in vivo study results showed that F5 achieved the Cmax of about 269.76 ± 1.52 ng/mL in 6 h and sustained the release of the drug till 24 h. The skin irritation study results proved that the novel biomaterial is non-sensitizing and non-irritating. Drug-polymer interaction study carried out to check the compatibility of drug and polymer showed the intactness of the drug in the formulation proving the compatibility of the polymer. It can be proposed from the outcome of the present study that by applying suitable adhesive layer and backing membrane, DB: Eudragit RL100 (60:40) transdermal patches can be of potential therapeutic use. PMID:21554152

Mundada, A S; Avari, J G

2011-08-01

90

Direct optic nerve sheath (DONS) application of Schwann cells prolongs retinal ganglion cell survival in vivo.  

PubMed

Cell-based therapies are increasingly recognized as a potential strategy to treat retinal neurodegenerative disease. Their administration, however, is normally indirect and complex, often with an inability to assess in real time their effects on cell death and their migration/integration into the host retina. In the present study, using a partial optic nerve transection (pONT) rat model, we describe a new method of Schwann cell (SC) delivery (direct application to injured optic nerve sheath, SC/DONS), which was compared with intravitreal SC delivery (SC/IVT). Both SC/DONS and SC/IVT were able to be assessed in vivo using imaging to visualize retinal ganglion cell (RGC) apoptosis and SC retinal integration. RGC death in the pONT model was best fitted to the one-phase exponential decay model. Although both SC/DONS and SC/IVT altered the temporal course of RGC degeneration in pONT, SC/DONS resulted in delayed but long-lasting effects on RGC protection, compared with SC/IVT treatment. In addition, their effects on primary and secondary degeneration, and axonal regeneration, were also investigated, by histology, whole retinal counting, and modelling of RGC loss. SC/DONS was found to significantly reduce RGC apoptosis in vivo and significantly increase RGC survival by targeting secondary rather than primary degeneration. Both SC/DONS and SC/IVT were found to promote RGC axonal regrowth after optic nerve injury, with evidence of GAP-43 expression in RGC somas and axons. SC/DONS may have the potential in the treatment of optic neuropathies, such as glaucoma. We show that SC transplantation can be monitored in real time and that the protective effects of SCs are associated with targeting secondary degeneration, with implications for translating cell-based therapies to the clinic. PMID:25321467

Guo, L; Davis, B; Nizari, S; Normando, E M; Shi, H; Galvao, J; Turner, L; Shi, J; Clements, M; Parrinello, S; Cordeiro, M F

2014-01-01

91

Laccase-catalysed oxidations of naturally occurring phenols: from in vivo biosynthetic pathways to green synthetic applications  

PubMed Central

Summary Laccases are oxidases that contain several copper atoms, and catalyse single?electron oxidations of phenolic compounds with concomitant reduction of oxygen to water. The enzymes are particularly widespread in ligninolytic basidiomycetes, but also occur in certain prokaryotes, insects and plants. Depending on the species, laccases are involved in various biosynthetic processes contributing to carbon recycling in land ecosystems and the morphogenesis of biomatrices, wherein low?molecular?weight naturally occurring phenols serve as key enzyme substrates. Studies of these in vivo synthetic pathways have afforded new insights into fungal laccase applicability in green synthetic chemistry. Thus, we here review fungal laccase?catalysed oxidations of naturally occurring phenols that are particularly relevant to the synthesis of fine organic chemicals, and we discuss how the discovered synthetic strategies mimic laccase?involved in vivo pathways, thus enhancing the green nature of such reactions. Laccase?catalysed in vivo processes yield several types of biopolymers, including those of cuticles, lignin, polyflavonoids, humus and the melanin pigments, using natural mono? or poly?phenols as building blocks. The in vivo synthetic pathways involve either phenoxyl radical?mediated coupling or cross?linking reactions, and can be adapted to the design of in vitro oxidative processes involving fungal laccases in organic synthesis; the laccase substrates and the synthetic mechanisms reflect in vivo processes. Notably, such in vitro synthetic pathways can also reproduce physicochemical properties (e.g. those of chromophores, and radical?scavenging, hydration and antimicrobial activities) found in natural biomaterials. Careful study of laccase?associated in vivo metabolic pathways has been rewarded by the discovery of novel green applications for fungal laccases. This review comprehensively summarizes the available data on laccase?catalysed biosynthetic pathways and associated applications in fine chemical syntheses. PMID:21791030

Jeon, Jong-Rok; Baldrian, Petr; Murugesan, Kumarasamy; Chang, Yoon-Seok

2012-01-01

92

An electrochemically driven poly(dimethylsiloxane) microfluidic actuator: oxygen sensing and programmable flows and pH gradients.  

PubMed

We describe the fabrication and performance of an integrated microelectrochemical reactor-a design possessing utility for multiple applications that include electrochemical sensing, the generation and manipulation of in-channel microfluidic pH gradients, and fluid actuation and flow. The device architecture is based on a three-electrode electrochemical cell design that incorporates a Pt interdigitated array (IDA) working (WE), a Pt counter (CE), and Ag pseudo-reference (RE) electrodes within a microfluidic network in which the WE is fully immersed in a liquid electrolyte confined in the channels. The microchannels are made from a conventional poly(dimethylsiloxane)(PDMS) elastomer, which serves also as a thin gas-permeable membrane through which gaseous reactants in the external ambient environment are supplied to the working electrode by diffusion. Due to the high permeability of oxygen through PDMS, the microfluidic cell supports significantly (>order of magnitude) higher current densities in the oxygen reduction reaction (ORR) than those measured in conventional (quiescent) electrochemical cells for the same electrode areas. We demonstrate in this work that, when operated at constant potential under mass transport control, the device can be utilized as a membrane-covered oxygen sensor, the response of which can be tuned by varying the thickness of the PDMS membrane. Depending on the experimental conditions under which the electrochemical ORR is performed, the data establish that the device can be operated as both a programmable pH gradient generator and a microfluidic pump. PMID:15915256

Mitrovski, Svetlana M; Nuzzo, Ralph G

2005-06-01

93

In vitro and in vivo characterization of novel biomaterial for transdermal application.  

PubMed

Polymers have become an indispensable part in the design of a conventional as well as novel drug delivery system. Gum Copal (GC), a novel biomaterial obtained from Agathis species, is evaluated in the present study for its potential application as a matrix former in transdermal drug delivery systems. GC was initially characterized for various physicochemical properties and then mechanical characterization of the Plasticized films of GC was investigated. Verapamil hydrochloride (VH), owing to its pharmacokinetic properties, was selected as the model drug for the present work. Matrix type transdermal films of VH with GC, alone and in combination with polyvinyl pyrrolidone (PVP K-30), were developed and evaluated for various physicochemical properties. In-vitro drug release study was carried out using paddle over disk method and in-vitro skin permeation study was performed using human cadaver skin. On the basis of physicochemical properties, in-vitro drug release study and permeation performance, formulation F5 containing GC: PVP K-30 (60:40) was selected as an optimized formulation for in vivo study. Animal studies were carried out using Dawley rats and the data obtained from the plasma drug analysis showed that peak drug concentration of about 244.94 ± 1.25 ng/mL was achieved in 6 h after the application of the patch and plasma drug concentration was maintained till 24 h. Skin irritancy test results proved the suitability of the biomaterial for transdermal application. The drug polymer interaction studies carried out using UV, FTIR and TLC analysis indicated that drug and polymer were compatible. Due to reasonably good mechanical properties, low water vapor transmission and sustained release capability, GC seems to be a promising film former for transdermal drug delivery. PMID:21696352

Mundada, Atish S; Avari, Jasmine G

2011-09-01

94

In vivo pH monitoring using boron doped diamond microelectrode and silver needles: Application to stomach disorder diagnosis  

NASA Astrophysics Data System (ADS)

This study presents the in vivo electrochemical monitoring of pH using boron doped diamond (BDD) microelectrode and silver needles for potential application in medical diagnosis. Accurate calibration curve for pH determination were obtained through in vitro electrochemical measurements. The increase induced in stomach pH by treatment with pantoprazole was used to demonstrate that it is possible to monitor the pH in vivo using the simple and noninvasive system proposed herein. Using the results of the in vivo and in vitro experiments, a quantitative analysis of the increase in stomach pH is also presented. It is proposed that the catheter-free pH monitoring system presented in this study could be potentially employed in any biological environment.

Fierro, Stéphane; Seishima, Ryo; Nagano, Osamu; Saya, Hideyuki; Einaga, Yasuaki

2013-11-01

95

In vivo pH monitoring using boron doped diamond microelectrode and silver needles: application to stomach disorder diagnosis.  

PubMed

This study presents the in vivo electrochemical monitoring of pH using boron doped diamond (BDD) microelectrode and silver needles for potential application in medical diagnosis. Accurate calibration curve for pH determination were obtained through in vitro electrochemical measurements. The increase induced in stomach pH by treatment with pantoprazole was used to demonstrate that it is possible to monitor the pH in vivo using the simple and noninvasive system proposed herein. Using the results of the in vivo and in vitro experiments, a quantitative analysis of the increase in stomach pH is also presented. It is proposed that the catheter-free pH monitoring system presented in this study could be potentially employed in any biological environment. PMID:24247214

Fierro, Stéphane; Seishima, Ryo; Nagano, Osamu; Saya, Hideyuki; Einaga, Yasuaki

2013-01-01

96

Retinal electrophysiology for toxicology studies: applications and limits of ERG in animals and ex vivo recordings.  

PubMed

Assessing retinal drug toxicity is becoming increasingly important as different molecules are now developed for the treatment of neurodegenerative diseases and vascular disorders. In pharmacology and toxicology, the electroretinogram (ERG) and the multielectrode array (MEA) recording techniques can be used to quantify the possible side effects of retino-active xenobiotics. Toxicity testing requires the use of rodent as well as non-rodent models for extrapolation to the human model when determining risk and safety. Animal species differ in their retinal anatomo-physiology: most rodents used in toxicology studies are essentially nocturnal species, whereas the non-rodent laboratory species normally used (e.g. dogs, pigs and monkeys) are diurnal. The ratio between the photoreceptor populations which varies from species to species, should be considered when designing the experiment protocol and the interpretation. The described ERG procedures are designed to comply with all applicable good laboratory practice standards. Use of these procedures should yield an acceptable level of intra- and inter-subject variability for compiling a historical database, and for detecting possible retinal toxicity in animal studies. They could therefore be used as specific and standardized tools for screening of potential retinotoxic molecules in drug discovery and development in order to compare methods and results with those obtained in human electrophysiological assessments. Recording of ganglion cell light responses on ex vivo retina with the MEA technique can further demonstrate how retino-active xenobiotics affect retinal visual information processing by eliminating potential obstacles related to bioavailability and blood barrier permeability. PMID:18294830

Rosolen, Serge Georges; Kolomiets, Bogdan; Varela, Oscar; Picaud, Serge

2008-06-01

97

Combining whispering gallery mode lasers and microstructured optical fibers for in-vivo biosensing applications  

NASA Astrophysics Data System (ADS)

Whispering Gallery Modes (WGMs) have been widely studied for the past 20 years for various applications, including biological sensing. While the different WGM-based sensing approaches reported in the literature enable useful sensor characteristics, at present this technology is not yet mature, mainly for practical reasons. Our work has been focused on developing a simple, yet efficient, WGM-based sensing platform capable of being used as a dip sensor for in-vivo biosensing applications. We recently demonstrated that a dye-doped polymer microresonator, supporting WGMs, positioned onto the tip of a suspended core Microstructured Optical Fiber can be used as a dip sensor. In this architecture, the resonator is located on an air hole next to the fiber core at the fiber's tip, enabling a significant portion of the sphere to overlap with the guided light emerging from the fiber tip. This architecture offers significant benefits that have never been reported in the literature in terms of radiation efficiency, compared to the standard freestanding resonators, which arise from breaking the symmetry of the resonator. In addition to providing the remote excitation and collection of the WGMs' signal, the fiber also allows easy manipulation of the microresonator and the use this sensor in a dip sensing architecture, alleviating the need for a complex microfluidic interface. Here, we present our recent results on the microstructured fiber tip WGM-based sensor, including its lasing behavior and enhancement of the radiation efficiency as a function of the position of the resonator on the fiber tip. We also show that this platform can be used for clinical diagnostics and applying this technology to the detection of Troponin T, an acute myocardial infarction biomarker, down to a concentration of 7.4 pg/mL.

François, A.; Rowland, K. J.; Reynolds, T.; Nicholls, S. J.; Monro, T. M.

2013-10-01

98

Development of HiLo Microscope and its use in In-Vivo Applications  

NASA Astrophysics Data System (ADS)

The functionality of achieving optical sectioning in biomedical research is invaluable as it allows for visualization of a biological sample at different depths while being free of background scattering. Most current microscopy techniques that offer optical sectioning, unfortunately, require complex instrumentation and thus are generally costly. HiLo microscopy, on the other hand, offers the same functionality and advantage at a relatively low cost. Hence, the work described in this thesis involves the design, build, and application of a HiLo microscope. More specifically, a standalone HiLo microscope was built in addition to implementing HiLo microscopy on a standard fluorescence microscope. In HiLo microscopy, optical sectioning is achieved by acquiring two different types of images per focal plane. One image is acquired under uniform illumination and the other is acquired under speckle illumination. These images are processed using an algorithm that extracts in-focus information and removes features and glare that occur as a result of background fluorescence. To show the benefits of the HiLo microscopy, several imaging experiments on various samples were performed under a HiLo microscope and compared against a traditional fluorescence microscope and a confocal microscope, which is considered the gold standard in optical imaging. In-vitro and ex-vivo imaging was performed on a set of pollen grains, and optically cleared mouse brain and heart slices. Each of these experiments showed great reduction in background scattering at different depths under HiLo microscopy. More importantly, HiLo imaging of optically cleared heart slice demonstrated emergence of different vasculature at different depths. Reduction of out-of-focus light increased the spatial resolution and allowed better visualization of capillary vessels. Furthermore, HiLo imaging was tested in an in-vivo model of a rodent dorsal window chamber model. When imaging the same sample under confocal microscope, the results were comparable between the two modalities. Additionally, a method of achieving blood flow maps at different depth using a combination of HiLo and LSI imaging is also discussed. The significance of this combined technique could help categorize blood flow to particular depths; this can help improve outcomes of medical treatments such pulse dye laser and photodynamic therapy treatments.

Patel, Shreyas J.

99

Oxygen sensing by HIF hydroxylases  

Microsoft Academic Search

The transcription factor HIF (hypoxia-inducible factor) has a central role in oxygen homeostasis in animals ranging from nematode worms to man. Recent studies have shown that this factor is regulated by an unprecedented signalling mechanism that involves post-translational hydroxylation. This hydroxylation is catalysed by a set of non-haem, Fe2+-dependent enzymes that belong to the 2-oxoglutarate-dependent-oxygenase superfamily. The absolute requirement of

Christopher J. Schofield; Peter J. Ratcliffe

2004-01-01

100

A Multimode Optical Imaging System for Preclinical Applications In Vivo: Technology Development, Multiscale Imaging, and Chemotherapy Assessment  

PubMed Central

Purpose Several established optical imaging approaches have been applied, usually in isolation, to preclinical studies; however, truly useful in vivo imaging may require a simultaneous combination of imaging modalities to examine dynamic characteristics of cells and tissues. We developed a new multimode optical imaging system designed to be application-versatile, yielding high sensitivity, and specificity molecular imaging. Procedures We integrated several optical imaging technologies, including fluorescence intensity, spectral, lifetime, intravital confocal, two-photon excitation, and bioluminescence, into a single system that enables functional multiscale imaging in animal models. Results The approach offers a comprehensive imaging platform for kinetic, quantitative, and environmental analysis of highly relevant information, with micro-to-macroscopic resolution. Applied to small animals in vivo, this provides superior monitoring of processes of interest, represented here by chemo-/nanoconstruct therapy assessment. Conclusions This new system is versatile and can be optimized for various applications, of which cancer detection and targeted treatment are emphasized here. PMID:21874388

Hwang, Jae Youn; Wachsmann-Hogiu, Sebastian; Ramanujan, V. Krishnan; Ljubimova, Julia; Gross, Zeev; Gray, Harry B.; Medina-Kauwe, Lali K.; Farkas, Daniel L.

2012-01-01

101

Novel nanocomposite coating for dental implant applications in vitro and in vivo evaluation.  

PubMed

This study aimed at preparation and in vitro and in vivo evaluation of novel bioactive, biodegradable, and antibacterial nanocomposite coating for the improvement of stem cells attachment and antibacterial activity as a candidate for dental implant applications. Poly (lactide-co-glycolide)/bioactive glass/hydroxyapatite (PBGHA) nanocomposite coating was prepared via solvent casting process. The nanoparticle amounts of 10, 15, and 20 weight percent (wt%) were chosen in order to determine the optimum amount of nanoparticles suitable for preparing an uniform coating. Bioactivity and degradation of the coating with an optimum amount of nanoparticles were evaluated by immersing the prepared samples in simulated body fluid and phosphate buffer saline (PBS), respectively. The effect of nanocomposite coating on the attachment and viability of human adipose-derived stem cells (hASCs) was investigated. Kirschner wires (K-wires) of stainless steel were coated with the PBGHA nanocomposite coating, and mechanical stability of the coating was studied during intramedullary implantation into rabbit tibiae. The results showed that using 10 wt% nanoparticles (5 wt% HA and 5 wt% BG) in the nanocomposite could provide the desired uniform coating. The study of in vitro bioactivity showed rapid formation of bone-like apatite on the PBGHA coating. It was degraded considerably after about 60 days of immersion in PBS. The hASCs showed excellent attachment and viability on the coating. PBGHA coating remained stable on the K-wires with a minimum of 96% of the original coating mass. It was concluded that PBGHA nanocomposite coating provides an ideal surface for the stem cells attachment and viability. In addition, it could induce antibacterial activity, simultaneously. PMID:22127403

Mehdikhani-Nahrkhalaji, M; Fathi, M H; Mortazavi, V; Mousavi, S B; Hashemi-Beni, B; Razavi, S M

2012-02-01

102

Sustained Growth of the Ex Vivo Ablation Zones' Critical Short Axis Using Gas-cooled Radiofrequency Applicators  

SciTech Connect

Purpose: To evaluate the ablation zones created with a gas-cooled bipolar radiofrequency applicator performed on ex vivo bovine liver tissue. Materials and Methods: A total of 320 ablations with an internally gas-cooled bipolar radiofrequency applicator were performed on fresh ex vivo bovine liver tissue, varying the ablation time (5, 10, 15, and 20 min), power (20, 30, 40, and 50 W), and gas pressure of the CO{sub 2} used for cooling (585, 600, 615, 630, 645 psi), leading to a total of 80 different parameter combinations. Size and shape of the white coagulation zone were assessed. Results: The largest complete ablation zone was achieved after 20 min of implementing 50 W and 645 psi, resulting in a short axis of mean 46 {+-} 1 mm and a long axis of 56 {+-} 2 mm (mean {+-} standard deviation). Short-axis diameters increased between 5 and 20 min of ablation time at 585 psi (increase of the short axis was 45% at 30 W, 29% at 40 W, and 39% at 50 W). This increase was larger at 645 psi (113% at 30 W, 67% at 40 W, and 70% at 50 W). Macroscopic assessment and NADH (nicotinamide adenine dinucleotide) staining revealed incompletely ablated tissue along the needle track in 18 parameter combinations including low-power settings (20 and 30 W) and different cooling levels and ablation times. Conclusion: Gas-cooled radiofrequency applicators increase the short-axis diameter of coagulation in an ex vivo setting if appropriate parameters are selected.

Rempp, Hansjoerg, E-mail: hansjoerg.rempp@med.uni-tuebingen.de [Eberhard Karls University of Tuebingen, Department of Diagnostic and Interventional Radiology (Germany); Scharpf, Marcus [Insitute of Pathology, Eberhard Karls University of Tuebingen, Department of General Pathology and Pathological Anatomy (Germany); Voigtlaender, Matthias [ERBE Elektromedizin GmbH (Germany); Schraml, Christina; Schmidt, Diethard [Eberhard Karls University of Tuebingen, Department of Diagnostic and Interventional Radiology (Germany); Fend, Falko [Insitute of Pathology, Eberhard Karls University of Tuebingen, Department of General Pathology and Pathological Anatomy (Germany); Claussen, Claus D. [Eberhard Karls University of Tuebingen, Department of Diagnostic and Interventional Radiology (Germany); Enderle, Markus D. [ERBE Elektromedizin GmbH (Germany); Pereira, Philippe L. [Klinik fuer Radiologie, Minimalinvasive Therapien und Nuklearmedizin (Germany); Clasen, Stephan [Eberhard Karls University of Tuebingen, Department of Diagnostic and Interventional Radiology (Germany)

2011-02-15

103

Informatics approach using metabolic reactivity classifiers to link in vitro to in vivo data in application to the ToxCast Phase I dataset  

EPA Science Inventory

Strategic combinations and tiered application of alternative testing methods to replace or minimize the use of animal models is attracting much attention. With the advancement of high throughput screening (HTS) assays and legacy databases providing in vivo testing results, suffic...

104

A sparse-projection computed tomography reconstruction method for in vivo application of in-line phase-contrast imaging  

PubMed Central

Background In recent years, X-ray phase-contrast imaging techniques have been extensively studied to visualize weakly absorbing objects. One of the most popular methods for phase-contrast imaging is in-line phase-contrast imaging (ILPCI). Combined with computed tomography (CT), phase-contrast CT can produce 3D volumetric images of samples. To date, the most common reconstruction method for phase-contrast X-ray CT imaging has been filtered back projection (FBP). However, because of the impact of respiration, lung slices cannot be reconstructed in vivo for a mouse using this method. Methods for reducing the radiation dose and the sampling time must also be considered. Methods This paper proposes a novel method of in vivo mouse lung in-line phase-contrast imaging that has two primary improvements compared with recent methods: 1) using a compressed sensing (CS) theory-based CT reconstruction method for the in vivo in-line phase-contrast imaging application and 2) using the breathing phase extraction method to address the lung and rib cage movement caused by a live mouse’s breathing. Results Experiments were performed to test the breathing phase extraction method as applied to the lung and rib cage movement of a live mouse. Results with a live mouse specimen demonstrate that our method can reconstruct images of in vivo mouse lung. Conclusions The results demonstrate that our method could deal with vivo mouse’s breathing and movements, meanwhile, using less sampling data than FBP while maintaining the same high quality. PMID:23898866

2013-01-01

105

Application of electrical stimulation for functional tissue engineering in vitro and in vivo  

NASA Technical Reports Server (NTRS)

The present invention provides new methods for the in vitro preparation of bioartificial tissue equivalents and their enhanced integration after implantation in vivo. These methods include submitting a tissue construct to a biomimetic electrical stimulation during cultivation in vitro to improve its structural and functional properties, and/or in vivo, after implantation of the construct, to enhance its integration with host tissue and increase cell survival and functionality. The inventive methods are particularly useful for the production of bioartificial equivalents and/or the repair and replacement of native tissues that contain electrically excitable cells and are subject to electrical stimulation in vivo, such as, for example, cardiac muscle tissue, striated skeletal muscle tissue, smooth muscle tissue, bone, vasculature, and nerve tissue.

Radisic, Milica (Inventor); Park, Hyoungshin (Inventor); Langer, Robert (Inventor); Freed, Lisa (Inventor); Vunjak-Novakovic, Gordana (Inventor)

2013-01-01

106

Advanced in vivo applications of blue light photoreceptors as alternative fluorescent proteins.  

PubMed

The ultimate ambition in cell biology, microbiology and biomedicine is to unravel complex physiological and pathophysiological processes within living organisms. To conquer this challenge, fluorescent proteins (FPs) are used as versatile in vivo reporters and biosensors to study gene regulation as well as the synthesis, localization and function of proteins in living cells. The most widely used FPs are the green fluorescent protein (GFP) and its derivatives and relatives. Their use as in vivo reporter proteins, however, is sometimes restricted by different environmental and cellular factors. Consequently, a whole range of alternative, cofactor-dependent reporter proteins have been developed recently. In this perspective, we summarize the advantages and limitations of the novel class of cyan-green fluorescent flavoproteins in comparison to members of the GFP family and discuss some correlated consequences for the use of FPs as in vivo reporters. PMID:23660639

Drepper, Thomas; Gensch, Thomas; Pohl, Martina

2013-07-01

107

In vivo application of an inhibitory RNA aptamer against T7 RNA polymerase  

E-print Network

to quickly assess the feasibility of aptamer functions in vivo, a cell-free expression system was used variants in the cell-free expression system, verifying the aptamer functionality in the cell-free testbed Correspondence: jongmin@dna.caltech.edu Abstract Synthetic biology involves the design of complex artificial

Murray, Richard M.

108

Preparation of 2 nm gold nanoparticles for in vitro and in vivo applications  

PubMed Central

Summary Gold nanoparticles have been a versatile tool in recent years for the exploration of biological systems. However, challenges with purification and adequate surface coverage limit the biocompatibility of gold nanoparticles. Here, we describe a detailed procedure for the synthesis, purification, and functionalization of biologically compatible gold nanoparticles for in vitro and in vivo studies. PMID:23918325

Moyano, Daniel F.; Duncan, Bradley; Rotello, Vincent M.

2014-01-01

109

Application of mass spectrometry to characterize localization and efficacy of nanoceria in vivo.  

PubMed

In vivo study of nanomaterials is complicated by the physical and chemical changes induced in the nanomaterial by exposure to biological compartments. A diverse array of proteins can bind to the nanomaterial, forming a protein corona which may alter the dispersion, surface charge, distribution, and biological activity of the material. Evidence suggests that unique synthesis and stabilization strategies can greatly affect the composition of the corona, and thus, the in vivo properties of the nanomaterial. Protein and elemental analyses techniques are critical to characterizing the nature of the protein corona in order to best predict the in vivo behavior of the nanomaterial. Further, as described here, inductively coupled mass spectroscopy (ICP-MS) can also be used to quantify nanomaterial deposition in tissues harvested from exposed animals. Elemental analysis of ceria content demonstrated deposition of cerium oxide nanoparticles (CeNPs) in various tissues of healthy mice and in the brains of mice with a model of multiple sclerosis. Thus, ICP-MS analysis of nanomaterial tissue distribution can complement data illustrating the biological, and in this case, therapeutic efficacy of nanoparticles delivered in vivo. PMID:24952203

Heckman, Karin L; Erlichman, Joseph; Reed, Ken; Skeels, Matthew

2014-01-01

110

Experimental model to measure the increase of dental pulp temperature in vivo during laser application  

Microsoft Academic Search

Carbon dioxide laser has been used in dental surgery. The existence of healthy teeth, which have pulp vitality needing to be preserved, is observed in a great number of cases. In this work we describe an experimental model which provides the measurement of temperature in pulp chamber `in vivo,' during oral surgeries in which the CO2 laser beam is applied

Ester M. Nicola; Silvio L. Junqueira; Mara S. Busato

1994-01-01

111

A new strategy for in vivo spectral editing. Application to GABA editing using selective homonuclear polarization transfer spectroscopy  

NASA Astrophysics Data System (ADS)

A novel single-shot in vivo spectral editing method is proposed in which the signal to be detected, is regenerated anew from the thermal equilibrium magnetization of a source to which it is J-coupled. The thermal equilibrium magnetization of the signal to be detected together with those of overlapping signals are suppressed by single-shot gradient dephasing prior to the signal regeneration process. Application of this new strategy to in vivo GABA editing using selective homonuclear polarization transfer allows complete suppression of overlapping creatine and glutathione while detecting the GABA-4 methylene resonance at 3.02 ppm with an editing yield similar to that of conventional editing methods. The NAA methyl group at 2.02 ppm was simultaneously detected and can be used as an internal navigator echo for correcting the zero order phase and frequency shifts and as an internal reference for concentration. This new method has been demonstrated for robust in vivo GABA editing in the rat brain and for study of GABA synthesis after acute vigabatrin administration.

Shen, Jun; Yang, Jehoon; Choi, In-Young; Li, Shizhe Steve; Chen, Zhengguang

2004-10-01

112

Application of XRF to measure strontium in human bone in vivo  

SciTech Connect

As a basis for better understanding the role that Sr fulfills in human body, it is desirable to measure directly the main Sr store in human body. Although strontium is omnipresent in human tissues, 99% is stored inthe mineral portion of the bone. In the present study x-ray fluorescence (XRF) was applied to measure the strontium content of the tibial shaft in vivo. The feasibility studies showed that normal levels of stable strontium in the bone can be measured successfully.

Wielopolski, L.; Vartsky, D.; Yasumura, S.; Cohn, S.H.

1982-01-01

113

Applications of RNA interference: current state and prospects for siRNA-based strategies in vivo  

Microsoft Academic Search

Within the recent years, RNA interference (RNAi) has become an almost-standard method for in vitro knockdown of any target\\u000a gene of interest. Now, one major focus is to further explore its potential in vivo, including the development of novel therapeutic\\u000a strategies. From the mechanism, it becomes clear that small interfering RNAs (siRNAs) play a pivotal role in triggering RNAi.\\u000a Thus,

Achim Aigner

2007-01-01

114

HPLC determination of novel dithiolethione containing drugs and its application for in vivo studies in rats  

Microsoft Academic Search

A panel of new drugs obtained by grafting a sulfurated moiety, i.e. 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADTOH) onto existing drugs have been synthesized and their in vivo action is under preclinical evaluation. In the present paper we describe rapid HPLC methods to detect ADTOH derivatives of valproic acid (ACS2), sildenafil (ACS6), aspirin (ACS14) and diclofenac (ACS15) in plasma. These methods allow the simultaneous

Daniela Giustarini; Elena Perrino; Valerio Tazzari; Ranieri Rossi

2010-01-01

115

Miniature Uncooled Infrared Sensitive Detectors for in Vivo Biomedical Imaging Applications  

SciTech Connect

Broadband infrared (OR) radiation detectors have been developed using miniature, inexpensive, mass produced microcantilevers capable of detecting temperature differences as small as lea(-6) K. Microcantilevers made out of semiconductor materials can be used either as uncurled photon or thermal detectors. Mounted on a probe mm in diameter a number of microcantilevers can be accommodated in the working channel of existing endoscopes for in vivo proximity focus measurements inside the human body.

Datskos, P. G.; Demos, S. G.; Rajic, S.

1998-06-01

116

In vivo measurement of human rectus femoris architecture by ultrasonography: validity and applicability.  

PubMed

The architectural feature of the rectus femoris (RF) has been scarcely investigated despite its substantial contribution to knee extension torque and large plasticity in the muscularity. This study aimed to examine the reproducibility and validity of ultrasound measurements of RF architecture and interrelationships among the architectural parameters. After confirming the measurement accuracy of an examiner (measurement errors <1%), in vivo and cadaveric measurements of fascicle lengths and pennation angles of RF were performed. Day-to-day reproducibility of measurements was investigated in vivo including muscle thickness measurement. Validity of measurements was investigated by comparing the values between direct and ultrasound measurements for the cadaver. The intraclass correlation coefficients were 0·984, 0·960 and 0·932, and root mean square difference between measured values on 2 days was 0·8 mm, 3·1 mm and 1·4° for muscle thickness, fascicle length and pennation angle, respectively. The validity of measurements was similar or better than those of previous reports on other muscles. We also confirmed a positive correlation between the muscle thickness and the pennation angle as has been shown in other muscles. The current results warrant the use of B-mode ultrasonography for examining the architectural characteristics of RF in vivo. PMID:23692615

Ema, Ryoichi; Wakahara, Taku; Mogi, Yasuyoshi; Miyamoto, Naokazu; Komatsu, Toshihiko; Kanehisa, Hiroaki; Kawakami, Yasuo

2013-07-01

117

Parametric spectrum analysis of 2D NMR signals. Application to in Vivo J spectroscopy  

NASA Astrophysics Data System (ADS)

Parametric modeling techniques for spectrum analysis, based on the linear prediction principle, have previously been proposed to process NMR data. In this paper, they are tested on different practical NMR signals, and especially on in vivo 2D NMR spectroscopy data. The linear prediction version of the maximum entropy method, using AR modeling, and the Prony method are outlined with some considerations about the choice of the AR algorithm. Then simulation and experimental results obtained with the Prony method are presented and compared with those obtained with classical 2D Fourier transform processing. The data processed here result from homonuclear 2D J-resolved spectroscopy experiments performed to measure the spin-spin coupling constants between the three phosphorus nuclei of ATP in the rat brain. The parametric techniques (especially the Prony method) applied in both dimensions yield increased resolution and sensitivity and their ability to process limited data allows the total acquisition time to be reduced without loss of resolution. Although the noise may damage the performances, the results obtained here, on in vivo 2D data, are quite encouraging.

Luthon, F.; Blanpain, R.; Decorps, M.; Albrand, J. P.

118

Monoclonal antibodies reactive with human breast or ovarian carcinoma: In vivo applications  

SciTech Connect

Monoclonal antibodies (MoAbs) are unique and useful bioprobes that allow in vivo targeting of membrane-associated or circulating antigens. Most of the clinical trials to date have used low dosages of radiolabeled MoAb given in a single dose. Newer studies have included antibody fragments, repeated injections, intraperitoneal (IP) administration, and other labels such as 90Y. Clinical MoAb trials are often arduous, expensive, and time-consuming to perform. Before human use, animal studies and extensive MoAb characterization are required. The production of pharmaceutical grade, radiolabeled MoAb is technically difficult and costly. Clinical trials require administrative and patient consent as well as extensive written protocols. These studies necessitate interdepartmental and intradepartmental cooperation and coordination. Furthermore, the use of in vivo radiolabeled probes impacts many levels of health care providers from janitorial, nursing, and technical staff to laboratories and physicians. Simple blood tests or disposal of body excretions may concern nursing or technical staff with the possibility of radiation exposure. The responsibility for study design, personnel involvement, and prospective use in patients without a definitive cancer diagnosis ultimately rests with the physician. While many issues have been addressed, additional clinical trials, consideration of safety issues, and standardization between institutions will be necessary before the use of radiolabeled MoAb for diagnosis, management, or therapy of human tumors becomes routine. Continued cooperation and funding should ensure its achievement. 136 references.

Thor, A.D.; Edgerton, S.M. (Harvard Medical School, Boston, MA (USA))

1989-10-01

119

In vivo application of poly-3-hydroxyoctanoate as peripheral nerve graft  

PubMed Central

Objective: This study aims to investigate the degree of biocompatibility and neuroregeneration of a polymer tube, poly-3-hydroxyoctanoate (PHO) in nerve gap repair. Methods: Forty Wistar Albino male rats were randomized into two groups: autologous nerve gap repair group and PHO tube repair group. In each group, a 10-mm right sciatic nerve defect was created and reconstructed accordingly. Neuroregeneration was studied by sciatic function index (SFI), electromyography, and immunohistochemical studies on Days 7, 21, 45 and 60 of implantation. Biocompatibility was analyzed by the capsule formation around the conduit. Biodegradation was analyzed by the molecular weight loss in vivo. Results: Electrophysiological and histomorphometric assessments demonstrated neuroregeneration in both groups over time. In the experimental group, a straight alignment of the Schwann cells parallel to the axons was detected. However, autologous nerve graft seems to have a superior neuroregeneration compared to PHO grafts. Minor biodegradation was observed in PHO conduit at the end of 60 d. Conclusions: Although neuroregeneration is detected in PHO grafts with minor degradation in 60 d, autologous nerve graft is found to be superior in axonal regeneration compared to PHO nerve tube grafts. PHO conduits were found to create minor inflammatory reaction in vivo, resulting in good soft tissue response. PMID:24190445

Hazer, D. Burcu; Bal, Ercan; Nurlu, Gulay; Benli, Kemal; Balci, Serdar; Ozturk, Feral; Hazer, Baki

2013-01-01

120

Synthesis, cellular delivery and in vivo application of dendrimer-based pH sensors.  

PubMed

The development of fluorescent indicators represented a revolution for life sciences. Genetically encoded and synthetic fluorophores with sensing abilities allowed the visualization of biologically relevant species with high spatial and temporal resolution. Synthetic dyes are of particular interest thanks to their high tunability and the wide range of measureable analytes. However, these molecules suffer several limitations related to small molecule behavior (poor solubility, difficulties in targeting, often no ratiometric imaging allowed). In this work we introduce the development of dendrimer-based sensors and present a procedure for pH measurement in vitro, in living cells and in vivo. We choose dendrimers as ideal platform for our sensors for their many desirable properties (monodispersity, tunable properties, multivalency) that made them a widely used scaffold for several biomedical devices. The conjugation of fluorescent pH indicators to the dendrimer scaffold led to an enhancement of their sensing performances. In particular dendrimers exhibit reduced cell leakage, improved intracellular targeting and allow ratiometric measurements. These novel sensors were successfully employed to measure pH in living HeLa cells and in vivo in mouse brain. PMID:24056638

Albertazzi, Lorenzo; Storti, Barbara; Brondi, Marco; Sulis Sato, Sebastian; Ratto, Gian Michele; Signore, Giovanni; Beltram, Fabio

2013-01-01

121

Application of a new high-speed magnetic deformable mirror for in-vivo retinal imaging  

NASA Astrophysics Data System (ADS)

Nowadays in ophthalmologic practice several commercial instruments are available to image patient retinas in vivo. Many modern fundus cameras and confocal scanning laser ophthalmoscopes allow acquisition of two dimensional en face images of the retina with both back reflected as well as fluorescent light. Additionally, optical coherence tomography systems allow non-invasive probing of three-dimensional retinal morphology. For all of these instruments the available lateral resolution is limited by optical quality of the human eye used as the imaging objective. To improve lateral resolution and achieve diffraction-limited imaging, adaptive optics (AO) can be implemented with any of these imaging systems to correct both static and dynamic aberrations inherent in human eyes. Most of the wavefront correctors used previously in AO systems have limited dynamic range and an insufficient number of actuators to achieve diffraction-limited correction of most human eyes. Thus, additional corrections were necessary, either by trial lenses or additional deformable mirrors (DMs). The UC Davis AO flood-illuminated fundus camera system described in this paper has been previously used to acquire in vivo images of the photoreceptor mosaic and for psychophysical studies on normal and diseased retinas. These results were acquired using a DM manufactured by Litton ITEK (DM109), which has 109 actuators arranged in a hexagonal array below a continuous front-surface mirror. It has an approximate surface actuator stroke of +/-2?m. Here we present results with a new hi-speed magnetic DM manufactured by ALPAO (DM97, voice coil technology), which has 97 actuators and similar inter-actuator stroke (>3?m, mirror surface) but much higher low-order aberration correction (defocus stroke of at least +/-30?m) than the previous one. In this paper we report results of testing performance of the ALPAO DM for the correction of human eye aberrations. Additionally changes made to our AO flood illuminated system are presented along with images of the model eye retina and in-vivo human retina acquired with this system.

Balderas-Mata, Sandra E.; Jones, Steven M.; Zawadzki, Robert J.; Werner, John S.

2011-08-01

122

Intelligent spectral signature bio-imaging in vivo for surgical applications  

NASA Astrophysics Data System (ADS)

Multi-spectral imaging provides digital images of a scene or object at a large, usually sequential number of wavelengths, generating precise optical spectra at every pixel. We use the term "spectral signature" for a quantitative plot of optical property variations as a function of wavelengths. We present here intelligent spectral signature bio-imaging methods we developed, including automatic signature selection based on machine learning algorithms and database search-based automatic color allocations, and selected visualization schemes matching these approaches. Using this intelligent spectral signature bio-imaging method, we could discriminate normal and aganglionic colon tissue of the Hirschsprung's disease mouse model with over 95% sensitivity and specificity in various similarity measure methods and various anatomic organs such as parathyroid gland, thyroid gland and pre-tracheal fat in dissected neck of the rat in vivo.

Jeong, Jihoon; Frykman, Philip K.; Gaon, Mark; Chung, Alice P.; Lindsley, Erik H.; Hwang, Jae Y.; Farkas, Daniel L.

2007-02-01

123

Delivery Systems for the Direct Application of siRNAs to Induce RNA Interference (RNAi) In Vivo  

PubMed Central

RNA interference (RNAi) is a powerful method for specific gene silencing which may also lead to promising novel therapeutic strategies. It is mediated through small interfering RNAs (siRNAs) which sequence-specifically trigger the cleavage and subsequent degradation of their target mRNA. One critical factor is the ability to deliver intact siRNAs into target cells/organs in vivo. This review highlights the mechanism of RNAi and the guidelines for the design of optimal siRNAs. It gives an overview of studies based on the systemic or local application of naked siRNAs or the use of various nonviral siRNA delivery systems. One promising avenue is the the complexation of siRNAs with the polyethylenimine (PEI), which efficiently stabilizes siRNAs and, upon systemic administration, leads to the delivery of the intact siRNAs into different organs. The antitumorigenic effects of PEI/siRNA-mediated in vivo gene-targeting of tumor-relevant proteins like in mouse tumor xenograft models are described. PMID:17057369

Aigner, Achim

2006-01-01

124

Topical application of ex vivo expanded endothelial progenitor cells promotes vascularisation and wound healing in diabetic mice.  

PubMed

Impaired wound healing leading to skin ulceration is a serious complication of diabetes and may be caused by defective angiogenesis. Endothelial progenitor cells (EPCs) can augment neovascularisation in the ischaemic tissue. Experiments were performed to test the hypothesis that locally administered EPCs can promote wound healing in diabetes. Full-thickness skin wounds were created on the dorsum of diabetic mice. EPCs were obtained from bone marrow mononuclear cells (BMMNCs) and applied topically to the wound immediately after surgery. Vehicle and non-selective BMMNCs were used as controls. Wound size was measured on days 5, 10 and 14 after treatment, followed by resection, histological analysis and quantification of vascularity. Topical application of EPCs significantly promoted wound healing, as assessed by closure rate and wound vascularity. Immunostaining revealed that transplanted EPCs induced increased expression of vascular endothelial growth factor and basic fibroblast growth factor. Few EPCs were observed in the neovasculature based on in vivo staining of the functional vasculature. Ex vivo expanded EPCs promote wound healing in diabetic mice via mechanisms involving increased local cytokine expression and enhanced neovascularisation of the wound. This strategy exploiting the therapeutic capacity of autologously derived EPCs may be a novel approach to skin repair in diabetes. PMID:22738265

Asai, Jun; Takenaka, Hideya; Ii, Masaaki; Asahi, Michio; Kishimoto, Saburo; Katoh, Norito; Losordo, Douglas W

2013-10-01

125

Ketorolac tromethamine floating beads for oral application: Characterization and in vitro/in vivo evaluation.  

PubMed

The floating beads have been employed to make a sustained release of the drug in the stomach and to decrease the dose of the drug and hence overcome its side effects. The common benefits of the floating beads were it is easy preparation, without the need of a high temperature, and high percentage of the drug entrapment. In the present work, the Ketorolac tromethamine (KT) floating beads were prepared by extrusion congealing method utilizing calcium carbonate as a gas forming agent. The physical characters of the produced beads were investigated such as KT yield, KT loading, and entrapment efficiency of the drug. In addition, floating behavior, swelling, particle size, morphology and KT stability were also evaluated. In vitro drug release study was carried out, and the kinetics of the release was evaluated using the linear regression method. Furthermore, the in vivo analgesic effect of KT after oral administration of the selected formula of floating beads (F10) was carried out using hot plate and tail flick methods. Oral commercial KT tablets and KT solution were used for the comparison. The prepared beads remained floated for more than 8 h. The optimized formulation (F10) exhibited prolonged drug release (more than 8 h) and the drug release follows the Higuchi kinetic model, with a Fickian diffusion mechanism according to Korsmeyer-Peppas (n = 0.466). Moreover, F10 showed a sustained analgesic effect as compared to the commercial tablet. PMID:25161380

Abou El Ela, Amal El Sayeh F; Hassan, Maha A; El-Maraghy, Dalia A

2014-09-01

126

TOPICAL APPLICATION OF BLEACHING PHENOLS; IN VIVO STUDIES AND MECHANISM OF ACTION RELEVANT TO MELANOMA TREATMENT  

PubMed Central

Skin depigmentation represents a well established treatment for extensive vitiligo and may likewise be suited to prevent tumor recurrences and as a prophylactic treatment of familial melanoma, as common bleaching agents are cytotoxic to melanocytes. Effective melanoma prevention requires a bleaching agent-induced loss of exposed melanocytes supported by an immune response to distant pigment cells. Studies on human explant cultures treated with depigmenting agents, 4-tertiary butyl phenol (4-TBP) or monobenzyl ether of hydroquinone (MBEH) revealed a significant increase in the migration of Langerhans cells towards the dermis only upon MBEH treatment thus suggesting selective elicitation of an immune response. To assess the depigmenting potential of bleaching agents in vivo, 4-TBP and MBEH were topically applied to C57BL/6 wild type as well as k14-SCF transgenic, epidermally pigmented mice. MBEH induced significant skin depigmentation in both strains, not observed upon 4-TBP treatment. Cytokine expression patterns in MBEH treated skin support activation of a Th1 mediated immune response corresponding to an influx of T cells and macrophages. Importantly, despite insensitivity of tumor cells to MBEH induced cytotoxicity, significantly retarded tumor growth was observed in B16 challenged k14-SCF mice pretreated with MBEH, likely due to an abundance of cytotoxic T cells accompanied by an increased expression of Th1 and Th17 cytokines. These data support the use of MBEH as a prophylactic treatment for melanoma. PMID:21317816

Hariharan, Vidhya; Toole, Timothy; Klarquist, Jared; Longley, Jack B; Mosenson, Jeffrey; Le Poole1, I. Caroline

2012-01-01

127

Ketorolac tromethamine floating beads for oral application: Characterization and in vitro/in vivo evaluation  

PubMed Central

The floating beads have been employed to make a sustained release of the drug in the stomach and to decrease the dose of the drug and hence overcome its side effects. The common benefits of the floating beads were it is easy preparation, without the need of a high temperature, and high percentage of the drug entrapment. In the present work, the Ketorolac tromethamine (KT) floating beads were prepared by extrusion congealing method utilizing calcium carbonate as a gas forming agent. The physical characters of the produced beads were investigated such as KT yield, KT loading, and entrapment efficiency of the drug. In addition, floating behavior, swelling, particle size, morphology and KT stability were also evaluated. In vitro drug release study was carried out, and the kinetics of the release was evaluated using the linear regression method. Furthermore, the in vivo analgesic effect of KT after oral administration of the selected formula of floating beads (F10) was carried out using hot plate and tail flick methods. Oral commercial KT tablets and KT solution were used for the comparison. The prepared beads remained floated for more than 8 h. The optimized formulation (F10) exhibited prolonged drug release (more than 8 h) and the drug release follows the Higuchi kinetic model, with a Fickian diffusion mechanism according to Korsmeyer-Peppas (n = 0.466). Moreover, F10 showed a sustained analgesic effect as compared to the commercial tablet. PMID:25161380

Abou el Ela, Amal El Sayeh F.; Hassan, Maha A.; El- Maraghy, Dalia A.

2013-01-01

128

Application of a Bioinformatics-Based Approach to Identify Novel Putative in vivo BACE1 Substrates  

PubMed Central

BACE1, a membrane-bound aspartyl protease that is implicated in Alzheimer’s disease, is the first protease to cut the amyloid precursor protein resulting in the generation of amyloid-? and its aggregation to form senile plaques, a hallmark feature of the disease. Few other native BACE1 substrates have been identified despite its relatively loose substrate specificity. We report a bioinformatics approach identifying several putative BACE1 substrates. Using our algorithm, we successfully predicted the cleavage sites for 70% of known BACE1 substrates and further validated our algorithm output against substrates identified in a recent BACE1 proteomics study that also showed a 70% success rate. Having validated our approach with known substrates, we report putative cleavage recognition sequences within 962 proteins, which can be explored using in vivo methods. Approximately 900 of these proteins have not been identified or implicated as BACE1 substrates. Gene ontology cluster analysis of the putative substrates identified enrichment in proteins involved in immune system processes and in cell surface protein-protein interactions.

Johnson, Joseph L; Chambers, Emily; Jayasundera, Keerthi

2013-01-01

129

HPLC determination of novel dithiolethione containing drugs and its application for in vivo studies in rats.  

PubMed

A panel of new drugs obtained by grafting a sulfurated moiety, i.e. 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADTOH) onto existing drugs have been synthesized and their in vivo action is under preclinical evaluation. In the present paper we describe rapid HPLC methods to detect ADTOH derivatives of valproic acid (ACS2), sildenafil (ACS6), aspirin (ACS14) and diclofenac (ACS15) in plasma. These methods allow the simultaneous detection of the potential drugs and of ADTOH moiety. In the case of ACS14 the de-acetylated metabolite (ACS21) can also be concomitantly measured. The chromatographic separation was performed on a C18 column, applying a mobile phase consisting of a mixture of trifluoroacetic acid and acetonitrile. ADTOH, ACS6, ACS14, ACS21 were separated isocratically whereas ACS2 and ACS15 were separated applying gradient elution. The methods are precise and accurate, with a low quantification limit of 200 nM for ACS2, ACS15 and ACS21 or 100 nM for ADTOH, ACS6 and ACS14. The mean absolute recovery for all tested molecules was always found to be close to 100%. The methods are shown to be selective and linear in the range 0.2-50 microM and thus appear suitable for pharmacokinetic studies with ADTOH containing compounds, as indicated by exemplificative experiments performed with intravenous administration of the drugs to rats. PMID:20006565

Giustarini, Daniela; Perrino, Elena; Tazzari, Valerio; Rossi, Ranieri

2010-02-01

130

In vivo application of an RNAi strategy for the selective suppression of a mutant allele.  

PubMed

Gene therapy for dominantly inherited diseases with small interfering RNA (siRNA) requires mutant allele-specific suppression when genes in which mutation causes disease normally have an important role. We previously proposed a strategy for selective suppression of mutant alleles; both mutant and wild-type alleles are inhibited by most effective siRNA, and wild-type protein is restored using mRNA mutated to be resistant to the siRNA. Here, to prove the principle of this strategy in vivo, we applied it to our previously reported anti-copper/zinc superoxide dismutase (SOD1) short hairpin RNA (shRNA) transgenic (Tg) mice, in which the expression of the endogenous wild-type SOD1 gene was inhibited by more than 80%. These shRNA Tg mice showed hepatic lipid accumulation with mild liver dysfunction due to downregulation of endogenous wild-type SOD1. To rescue this side effect, we generated siRNA-resistant SOD1 Tg mice and crossed them with anti-SOD1 shRNA Tg mice, resulting in the disappearance of lipid accumulation in the liver. Furthermore, we also succeeded in mutant SOD1-specific gene suppression in the liver of SOD1(G93A) Tg mice, a model for amyotrophic lateral sclerosis, using intravenously administered viral vectors. Our method may prove useful for siRNA-based gene therapy for dominantly inherited diseases. PMID:20649474

Kubodera, Takayuki; Yamada, Hiromi; Anzai, Masayuki; Ohira, Shinga; Yokota, Shigefumi; Hirai, Yukihiko; Mochizuki, Hideki; Shimada, Takashi; Mitani, Tasuku; Mizusawa, Hidehiro; Yokota, Takanori

2011-01-01

131

Clinical Application of in-room PET for in vivo Treatment Monitoring in Proton Radiotherapy  

PubMed Central

Purpose/Objective(s) The purpose of this study is to evaluate the potential of using an in-room PET for treatment verification in proton therapy and to derive suitable PET scan times. Materials/Methods Nine patients undergoing passive scattering proton therapy were scanned immediately after treatment with an in-room PET scanner. The scanner was positioned next to the treatment head after treatment. The Monte Carlo (MC) method was employed to reproduce PET activities for each patient. To assess the proton beam range uncertainty we designed a novel concept where the measured PET activity surface distal to the target at the end of range was compared with MC predictions. The repositioning of patients for the PET scan took on average about 2 minutes. The PET images were reconstructed considering varying scan times to test the scan time dependency of the method. Results The measured PET images show overall good spatial correlations with MC predictions. Some discrepancies could be attributed to uncertainties in the local elemental composition and biological washout. For 8 patients treated with a single field, the average range differences between PET measurements and CT-image-based MC results were less than 5 mm (< 3 mm for 6 of 8 patients) and root-mean-square deviations (RMSD) were 4-11 mm with PET-CT image co-registration errors of about 2 mm. Our results also show that a short-length PET scan of 5 minutes can yield similar results compared to a 20 minutes PET scan. Conclusions Our first clinical trials of 9 patients using an in-room PET system demonstrated its potential for in vivo treatment monitoring in proton therapy. For a quantitative range prediction with arbitrary shape of target volume, we suggest employing the distal PET activity surface. PMID:23391817

Min, Chul Hee; Zhu, Xuping; Winey, Brian A.; Grogg, Kira; Testa, Mauro; Fakhri, Georges El; Bortfeld, Thomas R.; Paganetti, Harald; Shih, Helen A.

2013-01-01

132

In vivo sustained dermal delivery and pharmacokinetics of interferon alpha in biphasic vesicles after topical application.  

PubMed

Biphasic vesicles, a novel nanostructured lipid-based delivery system show potential for topical application of interferon alpha (IFN ?) for the treatment of human papillomavirus (HPV) infections (anogenital warts). Dermal delivery of IFN ? encapsulated in biphasic vesicles (BPV-IFN ?), applied topically to the skin, was characterized in a guinea pig model. BPV-IFN ? (1g, 2 MIU/g) was topically applied either as a single or multiple treatments on the skin of guinea pigs. As a comparison with currently used regimens, IFN ? solution was administered intravenously or intradermally. Skin and serum samples were collected over 96 h, IFN ? levels were determined by an antiviral assay, and half-life (t?/?) and elimination (k) rates were calculated. Topical BPV-IFN ? treatment resulted in maximum skin levels (about 100,000 U/100 cm(2)) of IFN ? within 6h and maintained for 72-96 h. Clearance from the skin after intradermal injections was initially fast (t?/? 0.62 h, k 1.1179 h(-1)), followed by a slower steady decrease after 6h. After intravenous and intradermal administration, IFN ? was rapidly cleared from the serum, t?/? 0.75 h, k 0.9271 h(-1) and t?/? 1.28 h, k 0.5421 h(-1), respectively, whereas after topical application, IFN ? levels remained below 100 U/mL. Topical application of BPV- IFN ? resulted in sustained delivery of biologically active IFN ? locally into skin with minimal systemic exposure. PMID:23500117

King, Martin; Kumar, Praveen; Michel, Deborah; Batta, Ravinderjit; Foldvari, Marianna

2013-08-01

133

Robust 3-D reconstruction of surfaces from image focus by local cross-sectional multivariate statistical analyses: application to human ex-vivo corneal endotheliums  

E-print Network

statistical analyses: application to human ex-vivo corneal endotheliums Mathieu Fernandes , Yann Gavet, Jean in computationally and passively recovering both topography and texture of a scene surface observed by optical-depth-of-field respectively involve recovering both topography (depth map) and texture image of the surface by researching in

Paris-Sud XI, Université de

134

Transurethral ultrasound applicators with dynamic multi-sector control for prostate thermal therapy: In vivo evaluation under MR guidance  

SciTech Connect

The purpose of this study was to explore the feasibility and performance of a multi-sectored tubular array transurethral ultrasound applicator for prostate thermal therapy, with potential to provide dynamic angular and length control of heating under MR guidance without mechanical movement of the applicator. Test configurations were fabricated, incorporating a linear array of two multi-sectored tubular transducers (7.8-8.4 MHz, 3 mm OD, 6 mm length), with three 120 deg. independent active sectors per tube. A flexible delivery catheter facilitated water cooling (100 ml min{sup -1}) within an expandable urethral balloon (35 mm longx10 mm diameter). An integrated positioning hub allows for rotating and translating the transducer assembly within the urethral balloon for final targeting prior to therapy delivery. Rotational beam plots indicate {approx}90 deg. - 100 deg. acoustic output patterns from each 120 deg. transducer sector, negligible coupling between sectors, and acoustic efficiencies between 41% and 53%. Experiments were performed within in vivo canine prostate (n=3), with real-time MR temperature monitoring in either the axial or coronal planes to facilitate control of the heating profiles and provide thermal dosimetry for performance assessment. Gross inspection of serial sections of treated prostate, exposed to TTC (triphenyl tetrazolium chloride) tissue viability stain, allowed for direct assessment of the extent of thermal coagulation. These devices created large contiguous thermal lesions (defined by 52 deg. C maximum temperature, t{sub 43}=240 min thermal dose contours, and TTC tissue sections) that extended radially from the applicator toward the border of the prostate ({approx}15 mm) during a short power application ({approx}8-16 W per active sector, 8-15 min), with {approx}200 deg. or 360 deg. sector coagulation demonstrated depending upon the activation scheme. Analysis of transient temperature profiles indicated progression of lethal temperature and thermal dose contours initially centered on each sector that coalesced within {approx}5 min to produce uniform and contiguous zones of thermal destruction between sectors, with smooth outer boundaries and continued radial propagation in time. The dimension of the coagulation zone along the applicator was well-defined by positioning and active array length. Although not as precise as rotating planar and curvilinear devices currently under development for MR-guided procedures, advantages of these multi-sectored transurethral applicators include a flexible delivery catheter and that mechanical manipulation of the device using rotational motors is not required during therapy. This multi-sectored tubular array transurethral ultrasound technology has demonstrated potential for relatively fast and reasonably conformal targeting of prostate volumes suitable for the minimally invasive treatment of BPH and cancer under MR guidance, with further development warranted.

Kinsey, Adam M.; Diederich, Chris J.; Rieke, Viola; Nau, William H.; Pauly, Kim Butts; Bouley, Donna; Sommer, Graham [Thermal Therapy Research Group, Department of Radiation Oncology, University of California, San Francisco, California 94143 (United States) and Joint Graduate Group in Bioengineering, University of California, Berkeley and San Francisco, California 94158 (United States); Department of Radiology, Stanford University Medical Center, Stanford, California 94305 (United States); Thermal Therapy Research Group, Department of Radiation Oncology, University of California, San Francisco, California 94143 (United States); Department of Radiology, Stanford University Medical Center, Stanford, California 94305 (United States); Department of Comparative Medicine, Stanford University, Stanford, California 94305 (United States); Department of Radiology, Stanford University Medical Center, Stanford, California 94305 (United States)

2008-05-15

135

In vitro and in vivo degradation evaluation of novel iron-bioceramic composites for bone implant applications.  

PubMed

Biodegradable metals such as magnesium, iron and their alloys have been known as potential materials for temporary medical implants. However, most of the studies on biodegradable metals have been focusing on optimizing their mechanical properties and degradation behavior with no emphasis on improving their bioactivity behavior. We therefore investigated the possibility of improving iron biodegradation rate and bioactivity by incorporating various bioactive bioceramics. The iron-based bioceramic (hydroxyapatite, tricalcium phosphate and biphasic calcium phosphate) composites were prepared by mechanical mixing and sintering process. Degradation studies indicated that the addition of bioceramics lowered the corrosion potential of the composites and slightly increased their corrosion rate compared to that of pure iron. In vitro cytotoxicity results showed an increase of cellular activity when rat smooth muscle cells interacted with the degrading composites compared to pure iron. X-ray radiogram analysis showed a consistent degradation progress with that found in vivo and positive tissue response up to 70 days implantation in sheep animal model. Therefore, the iron-based bioceramic composites have the potential to be used for biodegradable bone implant applications. PMID:24433920

Ulum, M F; Arafat, A; Noviana, D; Yusop, A H; Nasution, A K; Abdul Kadir, M R; Hermawan, H

2014-03-01

136

Spatially Localized, One- and Two-Dimensional NMR Spectroscopy and in VivoApplication to Human Muscle  

NASA Astrophysics Data System (ADS)

The localized 1H MR spectrum of human muscle has recently been reported to feature unassigned, orientation-dependent resonance lines. For their characterization in vivo,various NMR techniques were combined with 3D spatial localization: 2D-J spectroscopy, zero-quantum- and Zeeman-order-filtering, double-quantum-filtering, 2D-constant-time COSY, dipolar-order filtering, and 2D-longitudinal-order separated spectroscopy. The successful implementation of these methods on a whole-body MR system and their application to study human subjects is described. 1H MR spectra of human muscle were found to feature residual dipolar couplings and anisotropic susceptibilities which render resonance frequencies, phases, and—with some sequences—signal intensities orientation dependent. Two of the unidentified resonances unequivocally form a dipolar doublet of two equivalent protons, centered at 3.93 ppm. All unknown as well as previously assigned peaks in the range between 2.7 and 3.6 ppm are either subject to dipolar coupling themselves or overlap with spectral contributions of metabolites involved in dipolar coupling. The methyl protons of creatine are likely to be subject to residual dipolar coupling and do therefore form a dipolar triplet and not a singlet as previously assumed. Finally, X3, a further unidentified peak at 3.5 ppm, appears to be part of a multiplet with its center at 3.3 ppm and overlapping the trimethylammonium resonance.

Kreis, Roland; Boesch, Chris

137

Portable semiconductor disk laser for in vivo tissue monitoring: a platform for the development of clinical applications  

NASA Astrophysics Data System (ADS)

Long term in vivo observations at large penetration depths and minimum sample disturbance are some of the key factors that have enabled the study of different cellular and tissue mechanisms. The continuous optimization of these aspects is the main driving force for the development of advanced microscopy techniques such as those based on nonlinear effects. Its wide implementation for general biomedical applications is however, limited as the currently used nonlinear microscopes are based on bulky, maintenance-intensive and expensive excitation sources such as Ti:sapphire ultrafast lasers. We present the suitability of a portable (140x240x70 mm) ultrafast semiconductor disk laser (SDL) source, to be used in nonlinear microscopy. The SDL is modelocked by a quantum-dot semiconductor saturable absorber mirror (SESAM). This enables the source to deliver an average output power of 287 mW with 1.5 ps pulses at 500 MHz, corresponding to a peak power of 0.4 kW. The laser center wavelength (965 nm) virtually matches the two-photon absorption cross-section of the widely used Green Fluorescent Protein (GFP). This property greatly relaxes the required peak powers, thus maximizing sample viability. This is demonstrated by presenting two-photon excited fluorescence images of GFP labeled neurons and second-harmonic generation images of pharyngeal muscles in living C. elegans nematodes. Our results also demonstrate that this compact laser is well suited for efficiently exciting different biological dyes. Importantly this non expensive, turn-key, compact laser system could be used as a platform to develop portable nonlinear bio-imaging devices, facilitating its widespread adoption in biomedical applications.

Aviles-Espinosa, Rodrigo; Filippidis, George; Hamilton, Craig; Malcolm, Graeme; Weingarten, Kurt J.; Südmeyer, Thomas; Barbarin, Yohan; Keller, Ursula; Artigas, David; Loza-Alvarez, Pablo

2011-07-01

138

In vivo skin irritation potential of a Castanea sativa (Chestnut) leaf extract, a putative natural antioxidant for topical application.  

PubMed

Topical application of natural antioxidants has proven to be effective in protecting the skin against ultraviolet-mediated oxidative damage and provides a straightforward way to strengthen the endogenous protection system. However, natural products can provoke skin adverse effects, such as allergic and irritant contact dermatitis. Skin irritation potential of Castanea sativa leaf ethanol:water (7:3) extract was investigated by performing an in vivo patch test in 20 volunteers. Before performing the irritation test, the selection of the solvent and extraction method was guided by the 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging test and polyphenols extraction (measured by the Folin Ciocalteu assay). Iron-chelating activity and the phenolic composition (high performance liquid chromatography/diode array detection) were evaluated for the extract obtained under optimized conditions. The extraction method adopted consisted in 5 short extractions (10 min.) with ethanol:water (7:3), performed at 40 degrees. The IC(50) found for the iron chelation and DPPH scavenging assays were 132.94 +/- 9.72 and 12.58 +/- 0.54 microg/ml (mean +/- S.E.M.), respectively. The total phenolic content was found to be 283.8 +/- 8.74 mg GAE/g extract (mean +/- S.E.M.). Five phenolic compounds were identified in the extract, namely, chlorogenic acid, ellagic acid, rutin, isoquercitrin and hyperoside. The patch test carried out showed that, with respect to irritant effects, this extract can be regarded as safe for topical application. PMID:18793273

Almeida, Isabel F; Valentão, Patrícia; Andrade, Paula B; Seabra, Rosa M; Pereira, Teresa M; Amaral, M Helena; Costa, Paulo C; Bahia, M Fernanda

2008-11-01

139

21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.  

Code of Federal Regulations, 2011 CFR

...FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell culture processing...

2011-04-01

140

21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.  

Code of Federal Regulations, 2012 CFR

...FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell culture processing...

2012-04-01

141

21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.  

...FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell culture processing...

2014-04-01

142

21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.  

Code of Federal Regulations, 2013 CFR

...FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell culture processing...

2013-04-01

143

Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions  

NASA Astrophysics Data System (ADS)

We report the application of the Laguerre deconvolution technique (LDT) to the analysis of in-vivo time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data and the diagnosis of atherosclerotic plaques. TR-LIFS measurements were obtained in vivo from normal and atherosclerotic aortas (eight rabbits, 73 areas), and subsequently analyzed using LDT. Spectral and time-resolved features were used to develop four classification algorithms: linear discriminant analysis (LDA), stepwise LDA (SLDA), principal component analysis (PCA), and artificial neural network (ANN). Accurate deconvolution of TR-LIFS in-vivo measurements from normal and atherosclerotic arteries was provided by LDT. The derived Laguerre expansion coefficients reflected changes in the arterial biochemical composition, and provided a means to discriminate lesions rich in macrophages with high sensitivity (>85%) and specificity (>95%). Classification algorithms (SLDA and PCA) using a selected number of features with maximum discriminating power provided the best performance. This study demonstrates the potential of the LDT for in-vivo tissue diagnosis, and specifically for the detection of macrophages infiltration in atherosclerotic lesions, a key marker of plaque vulnerability.

Jo, Javier A.; Fang, Qiyin; Papaioannou, Thanassis; Baker, J. Dennis; Dorafshar, Amir; Reil, Todd; Qiao, Jianhua; Fishbein, Michael C.; Freischlag, Julie A.; Marcu, Laura

2006-03-01

144

Manufacture of IRDye800CW-coupled Fe3O4 nanoparticles and their applications in cell labeling and in vivo imaging  

PubMed Central

Background In recent years, near-infrared fluorescence (NIRF)-labeled iron nanoparticles have been synthesized and applied in a number of applications, including the labeling of human cells for monitoring the engraftment process, imaging tumors, sensoring the in vivo molecular environment surrounding nanoparticles and tracing their in vivo biodistribution. These studies demonstrate that NIRF-labeled iron nanoparticles provide an efficient probe for cell labeling. Furthermore, the in vivo imaging studies show excellent performance of the NIR fluorophores. However, there is a limited selection of NIRF-labeled iron nanoparticles with an optimal wavelength for imaging around 800 nm, where tissue autofluorescence is minimal. Therefore, it is necessary to develop additional alternative NIRF-labeled iron nanoparticles for application in this area. Results This study manufactured 12-nm DMSA-coated Fe3O4 nanoparticles labeled with a near-infrared fluorophore, IRDye800CW (excitation/emission, 774/789 nm), to investigate their applicability in cell labeling and in vivo imaging. The mouse macrophage RAW264.7 was labeled with IRDye800CW-labeled Fe3O4 nanoparticles at concentrations of 20, 30, 40, 50, 60, 80 and 100 ?g/ml for 24 h. The results revealed that the cells were efficiently labeled by the nanoparticles, without any significant effect on cell viability. The nanoparticles were injected into the mouse via the tail vein, at dosages of 2 or 5 mg/kg body weight, and the mouse was discontinuously imaged for 24 h. The results demonstrated that the nanoparticles gradually accumulated in liver and kidney regions following injection, reaching maximum concentrations at 6 h post-injection, following which they were gradually removed from these regions. After tracing the nanoparticles throughout the body it was revealed that they mainly distributed in three organs, the liver, spleen and kidney. Real-time live-body imaging effectively reported the dynamic process of the biodistribution and clearance of the nanoparticles in vivo. Conclusion IRDye800CW-labeled Fe3O4 nanoparticles provide an effective probe for cell-labeling and in vivo imaging. PMID:21034487

2010-01-01

145

Synthesis and in vivo evaluation of the biodistribution of a 18F-labeled conjugate gold-nanoparticle-peptide with potential biomedical application.  

PubMed

Gold nanoparticles (AuNPs) have been extensively used in biological applications because of their biocompatibility, size, and ease of characterization, as well as an extensive knowledge of their surface chemistry. These features make AuNPs readily exploitable for biomedical applications, including drug delivery and novel diagnostic and therapeutic approaches. In a previous work, we studied ex vivo distribution of the conjugate C(AuNP)-LPFFD for its potential uses in the treatment of Alzheimer's disease. In this study, we covalently labeled the conjugate with [(18)F]-fluorobenzoate to study the in vivo distribution of the AuNP by positron emission tomography (PET). After intravenous administration in rat, the highest concentration of the radiolabeled conjugate was found in the bladder and urine with a lower proportion in the intestine, demonstrating progressive accumulation compatible with biliary excretion of the conjugate. The conjugate also accumulated in the liver and spleen. PET imaging allowed us to study the in vivo biodistribution of the AuNPs in a noninvasive and sensitive way using a reduced number of animals. Our results show that AuNPs can be covalently and radioactively labeled for PET biodistribution studies. PMID:22284226

Guerrero, Simon; Herance, José Raul; Rojas, Santiago; Mena, Juan F; Gispert, Juan Domingo; Acosta, Gerardo A; Albericio, Fernando; Kogan, Marcelo J

2012-03-21

146

A volume birdcage coil with an adjustable sliding tuner ring for neuroimaging in high field vertical magnets: ex and in vivo applications at 21.1T.  

PubMed

A tunable 900 MHz transmit/receive volume coil was constructed for ¹H MR imaging of biological samples in a 21.1 T vertical bore magnet. To accommodate a diverse range of specimen and RF loads at such a high frequency, a sliding-ring adaptation of a low-pass birdcage was implemented through simultaneous alteration of distributed capacitance. To make efficient use of the constrained space inside the vertical bore, a modular probe design was implemented with a bottom-adjustable tuning and matching apparatus. The sliding ring coil displays good homogeneity and sufficient tuning range for different samples of various dimensions representing large span of RF loads. High resolution in vivo and ex vivo images of large rats (up to 350 g), mice and human postmortem tissues were obtained to demonstrate coil functionality and to provide examples of potential applications at 21.1 T. PMID:22750638

Qian, Chunqi; Masad, Ihssan S; Rosenberg, Jens T; Elumalai, Malathy; Brey, William W; Grant, Samuel C; Gor'kov, Peter L

2012-08-01

147

In vivo determination of subject-specific musculotendon parameters: applications to the prime elbow flexors in normal and hemiparetic subjects  

Microsoft Academic Search

Objective. This study aimed at estimating the musculotendon parameters of the prime elbow flexors in vivo for both normal and hemiparetic subjects.Design. A neuromusculoskeletal model of the elbow joint was developed incorporating detailed musculotendon modeling and geometrical modeling.Background. Neuromusculoskeletal modeling is a valuable tool in orthopedic biomechanics and motor control research. However, its reliability depends on reasonable estimation of the

Terry K. K Koo; Arthur F. T Mak; L. K Hung

2002-01-01

148

Characteristics and Applications of the ToxRefDB In Vivo Datasets from Chronic, Reproductive and Developmental Assays  

EPA Science Inventory

ToxRefDB was developed to store data from in vivo animal toxicity studies. The initial focus was populating ToxRefDB with pesticide registration toxicity data that has been historically stored as hard-copy and scanned documents by the Office of Pesticide Programs. A significant p...

149

Rapid response oxygen-sensing nanofibers.  

PubMed

Molecular oxygen has profound effects on cell and tissue viability. Relevant sensor forms that can rapidly determine dissolved oxygen levels under biologically relevant conditions provide critical metabolic information. Using 0.5 ?m diameter electrospun polycaprolactone (PCL) fiber containing an oxygen-sensitive probe, tris (4,7-diphenyl-1,10-phenanthroline) ruthenium(II) dichloride, we observed a response time of 0.9±0.12 s while the t95 for the corresponding film was more than two orders of magnitude greater. Interestingly, the response and recovery times of slightly larger diameter PCL fibers were 1.79±0.23 s and 2.29±0.13 s, respectively, while the recovery time was not statistically different likely due to the more limited interactions of nitrogen with the polymer matrix. A more than 10-fold increase in PCL fiber diameter reduces oxygen sensitivity while having minor effects on response time; conversely, decreases in fiber diameter to less than 0.5 ?m would likely decrease response times even further. In addition, a 50°C heat treatment of the electrospun fiber resulted in both increased Stern-Volmer slope and linearity likely due to secondary recrystallization that further homogenized the probe microenvironment. At exposure times up to 3600 s in length, photobleaching was observed but was largely eliminated by the use of either polyethersulfone (PES) or a PES-PCL core-shell composition. However, this resulted in 2- and 3-fold slower response times. Finally, even the non-core shell compositions containing the Ru oxygen probe result in no apparent cytotoxicity in representative glioblastoma cell populations. PMID:23706233

Xue, Ruipeng; Behera, Prajna; Viapiano, Mariano S; Lannutti, John J

2013-08-01

150

Porous Phosphorescent Coordination Polymers for Oxygen Sensing  

SciTech Connect

Phosphorescent cyclometalated iridium tris(2-phenylpyridine) derivatives were designed and incorporated into coordination polymers as tricarboxylate bridging ligands. Three different crystalline coordination polymers were synthesized using a solvothermal technique and were characterized using a variety of methods, including single-crystal X-ray diffraction, PXRD, TGA, IR spectroscopy, gas adsorption measurements, and luminescence measurements. The coordination polymer built from Ir[3-(2-pyridyl)benzoate]{sub 3}, 1, was found to be highly porous with a nitrogen BET surface area of 764 m{sup 2}/g, whereas the coordination polymers built from Ir[4-(2-pyridyl)benzoate]{sub 3}, 2 and 3, were nonporous. The {sup 3}MLCT phosphorescence of each of the three coordination polymers was quenched in the presence of O{sub 2}. However, only 1 showed quick and reversible luminescence quenching by oxygen, whereas 2 and 3 exhibited gradual and irreversible luminescence quenching by oxygen. The high permanent porosity of 1 allows for rapid diffusion of oxygen through the open channels, leading to efficient and reversible quenching of the {sup 3}MLCT phosphorescence. This work highlights the opportunity of designing highly porous and luminescent coordination polymers for sensing other important analytes.

Xie, Zhigang; Ma, Liqing; deKrafft, Kathryn E.; Jin, Athena; Lin, Wenbin

2010-01-01

151

Chemistry, Properties, and in Vitro and in Vivo Applications of 2'-O-Methoxyethyl-4'-thioRNA, a Novel Hybrid Type of Chemically Modified RNA.  

PubMed

We report the synthesis, properties, and in vitro and in vivo applications of 2'-O-methoxyethyl-4'-thioRNA (MOE-SRNA), a novel type of hybrid chemically modified RNA. In its hybridization with complementary RNA, MOE-SRNA showed a moderate improvement of Tm value (+3.4?°C relative to an RNA:RNA duplex). However, the results of a comprehensive comparison of the nuclease stability of MOE-SRNA relative to 2'-O-methoxyethylRNA (MOERNA), 2'-O-methyl-4'-thioRNA (Me-SRNA), 2'-O-methylRNA (MeRNA), 4'-thioRNA (SRNA), and natural RNA revealed that MOE-SRNA had the highest stability (t1/2 >48 h in human plasma). Because of the favorable properties of MOE-SRNA, we evaluated its in vitro and in vivo potencies as an anti-microRNA oligonucleotide against miR-21. Although the in vitro potency of MOE-SRNA was moderate, its in vivo potency was significant for the suppression of tumor growth (similar to that of MOERNA). PMID:25314258

Saito, Yota; Hashimoto, Yosuke; Arai, Mai; Tarashima, Noriko; Miyazawa, Tadashi; Miki, Kazuya; Takahashi, Mayumi; Furukawa, Kazuhiro; Yamazaki, Naoshi; Matsuda, Akira; Ishida, Tatsuhiro; Minakawa, Noriaki

2014-11-24

152

In Vivo Imaging of Brain Development: Technologies, Models, Applications, and Impact on Understanding the Etiology of Mental Retardation  

Microsoft Academic Search

\\u000a Development of the mammalian brain proceeds in a precisely controlled sequence of cell divisions, migration, differentiation,\\u000a and synaptogenesis. It is a process of precise dynamic assembly, and time lapse in vivo imaging of these processes is fundamental\\u000a for the multidisciplinary endeavor to merge and understand the morphological, physiological, and regulatory processes of neurogenesis.\\u000a \\u000a \\u000a Modern optical and non-optical imaging technologies enable

Vicko Gluncic

153

A Clinically Applicable Method for the ex vivo Generation of Antigen–Presenting Cells from CD34+ Progenitors  

Microsoft Academic Search

Background and Objectives: Dendritic cells (DCs), the most potent of antigen–presenting cells, can be generated in vitro from bone marrow or blood progenitor cells. We have developed a method for producing such cells from mobilised peripheral blood CD34+ cells in the absence of bovine products. Methods: The culture system developed used X–Vivo 10 culture medium with 10% autologous serum, rhGM–CSF,

K. M. Ardeshna; C. P. Corney; S. J. Ings; M. J. Watts; D. C. Linch; S. Devereux

2000-01-01

154

In vivo application of biodegradable controlled antibiotic release systems for the treatment of implant-related osteomyelitis  

Microsoft Academic Search

In this study the construction and in vivo testing of antibiotic-loaded polyhydroxyalkanoate rods were planned for use in the treatment of implant-related osteomyelitis. The rods were constructed of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and poly(3-hydroxybutyrate-co-4-hydroxybutyrate), carrying 50% (w\\/w) Sulperazone® or Duocid®. They were implanted in rabbit tibia in which implant-related osteomyelitis (IRO) had been induced with Staphylococcus aureus. The effectiveness of the antibiotics in

?hsan Gürsel; Feza Korkusuz; Füsun Türesin; N. Gürdal Alaeddino?lu; Vas?f Has?rc?

2000-01-01

155

Application of wide-field optical coherence tomography to monitoring of viability of rat brain in vivo  

NASA Astrophysics Data System (ADS)

We investigated the feasibility of OCT in monitoring the viability of the brain. It was confirmed that after an overdose of pentobarbital sodium salt for an euthanasia, the OCT signal intensity increased before cardiac arrest and finally became 2.7 times, and by periodically changing the tissue temperature from 20 to 32 °C in vivo, average correlation coefficients between the ratio of signal intensity (RSI) and temperature were determined to be -0:42 to -0:50. RSI reversibly changed with subsequent variations of temperatures and finally increased rapidly just before cardiac arrest. These results indicate that RSI could correspond to decreases in viability.

Sato, Manabu; Nishidate, Izumi

2014-05-01

156

In vivo fluence rate measurements during Foscan®-mediated photodynamic therapy of persistent and recurrent nasopharyngeal carcinomas using a dedicated light applicator  

NASA Astrophysics Data System (ADS)

The objective of this study was to evaluate the performance of a dedicated light applicator for light delivery and fluence rate monitoring during Foscan®-mediated photodynamic therapy of nasopharyngeal carcinoma in a clinical phase I/II study. We have developed a flexible silicone applicator that can be inserted through the mouth and fixed in the nasopharyngeal cavity. Three isotropic fibers, for measuring of the fluence (rate) during therapy, were located within the nasopharyngeal tumor target area and one was manually positioned to monitor structures at risk in the shielded area. A flexible black silicon patch tailored to the patient's anatomy is attached to the applicator to shield the soft palate and oral cavity from the 652-nm laser light. Fourteen patients were included in the study, resulting in 26 fluence rate measurements in the risk volume (two failures). We observed a systematic reduction in fluence rate during therapy in 20 out of 26 illuminations, which may be related to photodynamic therapy-induced increased blood content, decreased oxygenation, or reduced scattering. Our findings demonstrate that the applicator was easily inserted into the nasopharynx. The average light distribution in the target area was reasonably uniform over the length of the applicator, thus giving an acceptably homogeneous illumination throughout the cavity. Shielding of the risk area was adequate. Large interpatient variations in fluence rate stress the need for in vivo dosimetry. This enables corrections to be made for differences in optical properties and geometry resulting in comparable amounts of light available for Foscan® absorption.

van Veen, R. L. P.; Nyst, H.; Indrasari, S. R.; Yudharto, M. A.; Robinson, D. J.; Tan, I. B.; Meewis, C.; Peters, R.; Spaniol, Stefan B.; Stewart, Fiona A.; Levendag, P. C.; Sterenborg, Henricus J. C. M.

2006-07-01

157

Application of "in vivo cryotechnique" to detect erythrocyte oxygen saturation in frozen mouse tissues with confocal Raman cryomicroscopy.  

PubMed

To measure oxygen saturation (SO2) of flowing erythrocytes in blood vessels of living animals, our "in vivo cryotechnique" (IVCT) was combined with confocal Raman microscopy at low temperature (-150 degrees C), referred to as cryomicroscopy. We evaluated two resonance Raman (RR) shifts around 1355 and 1378 cm(-1), reflecting de-oxygenated and oxygenated hemoglobin molecular structures, respectively. Judging from the calibration analyses of quickly frozen human whole blood for the control experiment in vitro, the two RR shifts were well retained at the low temperature, and their calculated ratios mostly reflected the relative SO2 measured with a blood-gas analyzer. In blood vessels of living mouse organs prepared with the IVCT, their RR spectral peaks were also detected at the same RR shifts obtained in human blood. In the blood vessels of living mouse small intestines, some arterioles and venules were clearly distinguishable by monitoring different peak patterns of their RR shifts. The different ratios of the RR shift-areas were calculated even in the arterial vessels. In blood vessels of mouse livers, the Raman spectra showed a lower peak shift of 1378 cm(-1) compared to that of 1355 cm(-1), indicating an SO2 decrease in hepatic blood circulation. Thus, the new cryopreparation technique will enable us to directly analyze the in vivo SO2 in various tissues of a whole animal body prepared with the IVCT, reflecting their living states. PMID:18571433

Terada, Nobuo; Ohno, Nobuhiko; Saitoh, Sei; Ohno, Shinichi

2008-08-01

158

Development of a Small D-Enantiomeric Alzheimer's Amyloid-? Binding Peptide Ligand for Future In Vivo Imaging Applications  

PubMed Central

Alzheimer’s disease (AD) is a devastating disease affecting predominantly the aging population. One of the characteristic pathological hallmarks of AD are neuritic plaques, consisting of amyloid-? peptide (A?). While there has been some advancement in diagnostic classification of AD patients according to their clinical severity, no fully reliable method for pre-symptomatic diagnosis of AD is available. To enable such early diagnosis, which will allow the initiation of treatments early in the disease progress, neuroimaging tools are under development, making use of A?-binding ligands that can visualize amyloid plaques in the living brain. Here we investigate the properties of a newly designed series of D-enantiomeric peptides which are derivatives of ACI-80, formerly called D1, which was developed to specifically bind aggregated A?1–42. We describe ACI-80 derivatives with increased stability and A? binding properties, which were characterized using surface plasmon resonance and enzyme-linked immunosorbent assays. The specific interactions of the lead compounds with amyloid plaques were validated by ex vivo immunochemistry in transgenic mouse models of AD. The novel compounds showed increased binding affinity and are promising candidates for further development into in vivo imaging compounds. PMID:22848501

Funke, Susanne Aileen; Bartnik, Dirk; Gluck, Julian Marius; Piorkowska, Kasia; Wiesehan, Katja; Weber, Urs; Gulyas, Balazs; Halldin, Christer; Pfeifer, Andrea; Spenger, Christian; Muhs, Andreas; Willbold, Dieter

2012-01-01

159

Photophysics and ex vivo biodistribution of ?-cyclodextrin-meso-tetra(m-hydroxyphenyl)porphyrin conjugate for biomedical applications.  

PubMed

Low aqueous solubility of porphyrin-based photosensitizers hampers their clinical use in photodynamic therapy because of complex delivery. In this study, we explore meso-tetra(m-hydroxyphenyl)-21,23H-porphyrin (mTHPP), a potent photosensitizer, covalently attached to ?-cyclodextrin (CD-mTHPP) with a focus on topical delivery and cellular uptake. The photophysical properties of CD-mTHPP were examined using steady-state fluorescence and lifetime measurements verifying increased aqueous solubility. Confocal and fluorescence lifetime imaging microscopy on human squamous carcinoma cells (A431) evidenced a cytoplasmic uptake of CD-mTHPP in predominantly monomeric form. CD-mTHPP was also delivered to human skin ex vivo and the skin penetration was assessed using two-photon fluorescence microscopy. The results indicated that CD-mTHPP exhibits improved skin distribution compared to mTHPP alone using aqueous vehicles. Thus the CD-mTHPP conjugate demonstrates improved biodistribution ex vivo compared to mTHPP and is a promising multimodal system for photodynamic therapy. PMID:24943653

Kirejev, V; Gonçalves, A R; Aggelidou, C; Manet, I; Mårtensson, J; Yannakopoulou, K; Ericson, M B

2014-08-01

160

Application of an ex vivo cellular model of circadian variation for bipolar disorder research: a proof of concept study  

PubMed Central

Objectives Disruption of circadian function has been observed in several human disorders, including bipolar disorder (BD). Research into these disorders can be facilitated by human cellular models that evaluate external factors (zeitgebers) that impact circadian pacemaker activity. Incorporating a firefly luciferase reporter system into human fibroblasts provides a facile, bioluminescent readout that estimates circadian phase, while leaving the cells intact. We evaluated whether this system can be adapted to clinical BD research and whether it can incorporate zeitgeber challenge paradigms. Methods Fibroblasts from patients with bipolar I disorder (BD-I) (n = 13) and controls (n = 12) were infected ex vivo with a lentiviral reporter incorporating the promoter sequences for Bmal1, a circadian gene to drive expression of the firefly Luciferase gene. Following synchronization, the bioluminescence was used to estimate period length. Phase response curves (PRC) were also generated following forskolin challenge and the phase response patterns characterized. Results Period length and PRCs could be estimated reliably from the constructs. There were no significant case–control differences in period length, with a nonsignificant trend for differences in PRCs following the phase setting experiments. Conclusions An ex vivo cellular fibroblast-based model can be used to investigate circadian function in BD-I. It can be generated from specific individuals and this could usefully complement ongoing circadian clinical research. PMID:23782472

Bamne, Mikhil N; Ponder, Christine A; Wood, Joel A; Mansour, Hader; Frank, Ellen; Kupfer, David J; Young, Michael W; Nimgaonkar, Vishwajit L

2013-01-01

161

Carotid artery wall motion analysis from B-mode ultrasound using adaptive block matching: in silico evaluation and in vivo application  

NASA Astrophysics Data System (ADS)

Valid risk stratification for carotid atherosclerotic plaques represents a crucial public health issue toward preventing fatal cerebrovascular events. Although motion analysis (MA) provides useful information about arterial wall dynamics, the identification of motion-based risk markers remains a significant challenge. Considering that the ability of a motion estimator (ME) to handle changes in the appearance of motion targets has a major effect on accuracy in MA, we investigated the potential of adaptive block matching (ABM) MEs, which consider changes in image intensities over time. To assure the validity in MA, we optimized and evaluated the ABM MEs in the context of a specially designed in silico framework. ABMFIRF2, which takes advantage of the periodicity characterizing the arterial wall motion, was the most effective ABM algorithm, yielding a 47% accuracy increase with respect to the conventional block matching. The in vivo application of ABMFIRF2 revealed five potential risk markers: low movement amplitude of the normal part of the wall adjacent to the plaques in the radial (RMAPWL) and longitudinal (LMAPWL) directions, high radial motion amplitude of the plaque top surface (RMAPTS), and high relative movement, expressed in terms of radial strain (RSIPL) and longitudinal shear strain (LSSIPL), between plaque top and bottom surfaces. The in vivo results were reproduced by OFLK(WLS) and ABMKF-K2, MEs previously proposed by the authors and with remarkable in silico performances, thereby reinforcing the clinical values of the markers and the potential of those MEs. Future in vivo studies will elucidate with confidence the full potential of the markers.

Gastounioti, A.; Golemati, S.; Stoitsis, J. S.; Nikita, K. S.

2013-12-01

162

Potential application of in vivo imaging of impaired lymphatic duct to evaluate the severity of pressure ulcer in mouse model  

PubMed Central

Ischemia-reperfusion (IR) injury is a cause of pressure ulcer. However, a mechanism underlying the IR injury-induced lymphatic vessel damage remains unclear. We investigated the alterations of structure and function of lymphatic ducts in a mouse cutaneous IR model. And we suggested a new method for evaluating the severity of pressure ulcer. Immunohistochemistry showed that lymphatic ducts were totally vanished by IR injury, while blood vessels were relatively preserved. The production of harmful reactive oxygen species (ROS) was increased in injured tissue. In vitro study showed a high vulnerability of lymphatic endothelial cells to ROS. Then we evaluated the impaired lymphatic drainage using an in vivo imaging system for intradermally injected indocyanine green (ICG). The dysfunction of ICG drainage positively correlated with the severity of subsequent cutaneous changes. Quantification of the lymphatic duct dysfunction by this imaging system could be a useful strategy to estimate the severity of pressure ulcer. PMID:24566895

Kasuya, Akira; Sakabe, Jun-ichi; Tokura, Yoshiki

2014-01-01

163

In Vivo Noninvasive Analysis of Human Forearm Muscle Function and Fatigue: Applications to EVA Operations and Training Maneuvers  

NASA Technical Reports Server (NTRS)

Forearm muscle fatigue is one of the major limiting factors affecting endurance during performance of deep-space extravehicular activity (EVA) by crew members. Magnetic resonance (MR) provides in vivo noninvasive analysis of tissue level metabolism and fluid exchange dynamics in exercised forearm muscles through the monitoring of proton magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (P-31-MRS) parameter variations. Using a space glove box and EVA simulation protocols, we conducted a preliminary MRS/MRI study in a small group of human test subjects during submaximal exercise and recovery and following exhaustive exercise. In assessing simulated EVA-related muscle fatigue and function, this pilot study revealed substantial changes in the MR image longitudinal relaxation times (T2) as an indicator of specific muscle activation and proton flux as well as changes in spectral phosphocreatine-to-phosphate (PCr/Pi) levels as a function of tissue bioenergetic potential.

Fotedar, L. K.; Marshburn, T.; Quast, M. J.; Feeback, D. L.

1999-01-01

164

Potential application of in vivo imaging of impaired lymphatic duct to evaluate the severity of pressure ulcer in mouse model  

NASA Astrophysics Data System (ADS)

Ischemia-reperfusion (IR) injury is a cause of pressure ulcer. However, a mechanism underlying the IR injury-induced lymphatic vessel damage remains unclear. We investigated the alterations of structure and function of lymphatic ducts in a mouse cutaneous IR model. And we suggested a new method for evaluating the severity of pressure ulcer. Immunohistochemistry showed that lymphatic ducts were totally vanished by IR injury, while blood vessels were relatively preserved. The production of harmful reactive oxygen species (ROS) was increased in injured tissue. In vitro study showed a high vulnerability of lymphatic endothelial cells to ROS. Then we evaluated the impaired lymphatic drainage using an in vivo imaging system for intradermally injected indocyanine green (ICG). The dysfunction of ICG drainage positively correlated with the severity of subsequent cutaneous changes. Quantification of the lymphatic duct dysfunction by this imaging system could be a useful strategy to estimate the severity of pressure ulcer.

Kasuya, Akira; Sakabe, Jun-Ichi; Tokura, Yoshiki

2014-02-01

165

Dynamic in vivo imaging of dual-triggered microspheres for sustained release applications: synthesis, characterization and cytotoxicity study.  

PubMed

This paper deals with the synthesis, characterization and property evaluation of drug-loaded magnetic microspheres with pH-responsive cross-linked polymer shell. The synthetic procedure consists of 3 steps, of which the first two comprise the synthesis of a poly methyl methacrylate (PMMA) template and the synthesis of a shell by using acrylic acid (AA) and methyl methacrylate (MMA) as monomers, and divinyl benzene (DVB) as cross-linker. The third step of the procedure refers to the formation of magnetic nanoparticles on the microsphere's surface. AA that attaches pH-sensitivity in the microspheres and magnetic nanoparticles in the inner and the outer surface of the microspheres, enhance the efficacy of this intelligent drug delivery system (DDS), which constitutes a promising approach toward cancer therapy. A number of experimental techniques were used to characterize the resulting microspheres. In order to investigate the in vitro controlled release behavior of the synthesized microspheres, we studied the Dox release percentage under different pH conditions and under external magnetic field. Hyperthermia caused by an alternating magnetic field (AFM) is used in order to study the doxorubicin (Dox) release behavior from microspheres with pH functionality. The in vivo fate of these hybrid-microspheres was tracked by labeling them with the ?-emitting radioisotope (99m)Tc after being intravenously injected in normal mice. According to our results, microsphere present a pH depending and a magnetic heating, release behavior. As expected, labeled microspheres were mainly found in the mononuclear phagocyte system (MPS). The highlights of the current research are: (i) to illustrate the advantages of controlled release by combining hyperthermia and pH-sensitivity and (ii) to provide noninvasive, in vivo information on the spatiotemporal biodistribution of these microsphere by dynamic ?-imaging. PMID:24286923

Efthimiadou, Eleni K; Tapeinos, Christos; Chatzipavlidis, Alexandros; Boukos, Nikos; Fragogeorgi, Eirini; Palamaris, Lazaros; Loudos, George; Kordas, George

2014-01-30

166

Non-contact respiration monitoring for in-vivo murine micro computed tomography: characterization and imaging applications  

PubMed Central

A cone beam micro-CT has previously been utilized along with a pressure-tracking respiration sensor to acquire prospectively gated images of both wild-type mice and various adult murine disease models. While the pressure applied to the abdomen of the subject by this sensor is small and is generally without physiological effect, certain disease models of interest, as well as very young animals, are prone to atelectasis with added pressure, or they generate too weak of a respiration signal with this method to achieve optimal prospective gating. In this work we present a new fiber-optic displacement sensor which monitors respiratory motion of a subject without requiring physical contact. The sensor outputs an analog signal which can be used for prospective respiration gating in micro-CT imaging. The device was characterized and compared against a pneumatic air chamber pressure sensor for the imaging of adult wild-type mice. The resulting images were found to be of similar quality with respect to physiological motion blur; the quality of the respiration signal trace obtained using the non-contact sensor was comparable to that of the pressure sensor and was superior for gating purposes due to its better signal-to-noise ratio. The non-contact sensor was then used to acquire in-vivo micro-CT images of a murine model for congenital diaphragmatic hernia and of 11-day-old mouse pups. In both cases, quality CT images were successfully acquired using this new respiration sensor. Despite the presence of beam hardening artifact arising from the presence of a fiber-optic cable in the imaging field, we believe this new technique for respiration monitoring and gating presents an opportunity for in-vivo imaging of disease models which were previously considered too delicate for established animal handling methods. PMID:22948192

Burk, Laurel M; Lee, Yueh Z; Wait, J Matthew; Lu, Jianping; Zhou, Otto Z

2012-01-01

167

Non-contact respiration monitoring for in-vivo murine micro computed tomography: characterization and imaging applications  

NASA Astrophysics Data System (ADS)

A cone beam micro-CT has previously been utilized along with a pressure-tracking respiration sensor to acquire prospectively gated images of both wild-type mice and various adult murine disease models. While the pressure applied to the abdomen of the subject by this sensor is small and is generally without physiological effect, certain disease models of interest, as well as very young animals, are prone to atelectasis with added pressure, or they generate too weak a respiration signal with this method to achieve optimal prospective gating. In this work we present a new fibre-optic displacement sensor which monitors respiratory motion of a subject without requiring physical contact. The sensor outputs an analogue signal which can be used for prospective respiration gating in micro-CT imaging. The device was characterized and compared against a pneumatic air chamber pressure sensor for the imaging of adult wild-type mice. The resulting images were found to be of similar quality with respect to physiological motion blur; the quality of the respiration signal trace obtained using the non-contact sensor was comparable to that of the pressure sensor and was superior for gating purposes due to its better signal-to-noise ratio. The non-contact sensor was then used to acquire in-vivo micro-CT images of a murine model for congenital diaphragmatic hernia and of 11-day-old mouse pups. In both cases, quality CT images were successfully acquired using this new respiration sensor. Despite the presence of beam hardening artefacts arising from the presence of a fibre-optic cable in the imaging field, we believe this new technique for respiration monitoring and gating presents an opportunity for in-vivo imaging of disease models which were previously considered too delicate for established animal handling methods.

Burk, Laurel M.; Lee, Yueh Z.; Wait, J. Matthew; Lu, Jianping; Zhou, Otto Z.

2012-09-01

168

Measured and Modeled Toxicokinetics in Cultured Fish Cells and Application to In Vitro - In Vivo Toxicity Extrapolation  

PubMed Central

Effect concentrations in the toxicity assessment of chemicals with fish and fish cells are generally based on external exposure concentrations. External concentrations as dose metrics, may, however, hamper interpretation and extrapolation of toxicological effects because it is the internal concentration that gives rise to the biological effective dose. Thus, we need to understand the relationship between the external and internal concentrations of chemicals. The objectives of this study were to: (i) elucidate the time-course of the concentration of chemicals with a wide range of physicochemical properties in the compartments of an in vitro test system, (ii) derive a predictive model for toxicokinetics in the in vitro test system, (iii) test the hypothesis that internal effect concentrations in fish (in vivo) and fish cell lines (in vitro) correlate, and (iv) develop a quantitative in vitro to in vivo toxicity extrapolation method for fish acute toxicity. To achieve these goals, time-dependent amounts of organic chemicals were measured in medium, cells (RTgill-W1) and the plastic of exposure wells. Then, the relation between uptake, elimination rate constants, and log KOW was investigated for cells in order to develop a toxicokinetic model. This model was used to predict internal effect concentrations in cells, which were compared with internal effect concentrations in fish gills predicted by a Physiologically Based Toxicokinetic model. Our model could predict concentrations of non-volatile organic chemicals with log KOW between 0.5 and 7 in cells. The correlation of the log ratio of internal effect concentrations in fish gills and the fish gill cell line with the log KOW was significant (r>0.85, p?=?0.0008, F-test). This ratio can be predicted from the log KOW of the chemical (77% of variance explained), comprising a promising model to predict lethal effects on fish based on in vitro data. PMID:24647349

Stadnicka-Michalak, Julita; Tanneberger, Katrin; Schirmer, Kristin; Ashauer, Roman

2014-01-01

169

Comparison of elastic scattering spectroscopy with histology in ex vivo prostate glands: potential application for optically guided biopsy and directed treatment.  

PubMed

The false-negative rate of ultrasound-guided sextant prostate biopsy has been estimated to be as high as 35 %. A significant percentage (10-35 %) of these prostate cancers diagnosed at a second or later attempt are high grade and, therefore, potentially lethal. We discuss the feasibility for performing optically guided biopsy using elastic scattering spectroscopy (ESS) to reduce sampling errors and improve sensitivity. ESS measurements were performed on 42 prostate glands ex vivo and correlated with standard histopathological assessment. Sliced glands were examined with wavelength ranges of 330-760 nm. The ESS portable system used a new fiber-optic probe with integrated cutting tool, designed specifically for ex vivo pathology applications. ESS spectra were grouped by diagnosis from standard histopathological procedure and then classified using linear support vector machine. Preliminary data are encouraging. ESS data showed strong spectral trends correlating with the histopathological assignments. The classification results showed a sensitivity of 0.83 and specificity of 0.87 for distinguishing dysplastic prostatic tissue from benign prostatic tissue. Similar results were obtained for distinguishing dysplastic prostatic tissue from prostatitis with a sensitivity and specificity of 0.80 and 0.88, respectively. The negative predictive values obtained with ESS are better than those obtained with transrectal ultrasound (TRUS)-guided core-needle biopsy. PMID:23247663

A'Amar, O M; Liou, L; Rodriguez-Diaz, E; De las Morenas, A; Bigio, I J

2013-09-01

170

In vivo application of ( sup 111 In-DTPA-D-Phe sup 1 )-octreotide for detection of somatostatin receptor-positive tumors in rats  

SciTech Connect

In this study the authors investigated its in vivo application in the visualization of somatostatin receptor-positive tumors in rats. The distribution of the radiopharmaceutical was investigated after intravenous injection in normal rats and in rats bearing the somatostatin receptor-positive rat pancreatic carcinoma CA 20948. Ex vivo autoradiographic studies showed that specific accumulation of radioactivity occurred in somatostatin receptor-containing tissue (anterior pituitary gland). However, in contrast to the adrenals and pituitary, the tracer accumulation in the kidneys was not mediated by somatostatin receptors. Increasing radioactivity over the somatostatin receptor-positive tumors was measured rapidly after injection and the tumors were clearly visualized by gamma camera scintigraphy. In rats pretreated with 1 mg octreotide accumulation of ({sup 111}In-DPTA-D-Phe{sup 1})-octreotide in the tumors was prevented. Because of its relatively long effective half-life, ({sup 111}In-DTPA-D-Phe{sup 1})-octreotide is a radionuclide-coupled somatostatin analogue which can be used to visualize somatostatin receptor-bearing tumors efficiently after 24 hr, when interfering background radioactivity is minimized by renal clearance.

Bakker, W.H.; Krenning, E.P.; Reubi, J.C.; Breeman, W.A.P.; Setyono-Han, B.; de Jong, M.; Kooij, P.P.M.; Bruns, C.; van Hagen, P.M.; Marbach, P.; Visser, T.J.; Pless, J.; Lamberts, S.W.J. (Erasmus Univ., Rotterdam (Netherlands) Sandoz Research Inst., Berne (Switzerland) Dr. Daniel den Hoed Cancer Centre, Rotterdam (Netherlands) Sandoz Pharma AG, Basel (Switzerland))

1991-01-01

171

Neurofibrillary degeneration can be arrested in an in vivo cellular model of human tauopathy by application of a compound which inhibits tau filament formation in vitro.  

PubMed

Although tau filament formation is a central event in familial tauopathies and Alzheimer's disease (AD), the cellular consequences of neurofibrillary tangle (NFT) formation are poorly understood because of the unavailability of mammalian in vivo cellular models of neurofibrillary degeneration (NFD). We have shown that human tau forms filaments and is associated with cytodegeneration when overexpressed chronically in identified neurons (ABCs) in the lamprey central nervous system (CNS). In this model, degeneration occurs according to a stereotyped sequence that closely resembles the pattern seen in tangle-bearing neurons in AD, with both tau deposition and fragmentation beginning in distal dendrites and progressing proximally over time. This sequence has been divided into four stages ranging from (1) mild beading of terminal dendrites only through (4) extensive dendritic fragmentation and loss. Here, we show that lipid-soluble, low-molecular-weight (approx 300 Da) proprietary compounds that have been demonstrated to block tau filament formation in vitro can significantly retard the progressive degeneration of ABCs that express human tau23. Bath application of one of these compounds for periods of up to 50 d after plasmid injection prevented degeneration beyond stage 2 in 90% of all treated cells, whereas over half of control cells showed severe degeneration by this time. This provides the first in vivo experimental evidence directly supporting a causal role for tau filament formation in the pathogenesis of NFD and suggests that intensive effort toward developing therapeutic agents for AD and other NFDs targeted at blocking tau filament formation is warranted. PMID:12540050

Hall, Garth F; Lee, Sangmook; Yao, Jun

2002-12-01

172

Conditioned medium from horse amniotic membrane-derived multipotent progenitor cells: immunomodulatory activity in vitro and first clinical application in tendon and ligament injuries in vivo.  

PubMed

We have recently demonstrated that heterologous transplantation of horse amniotic membrane-derived mesenchymal cells (AMCs) can be useful for cell therapy applications in tendon diseases, and hypothesized that these cells may promote tendon repair via paracrine-acting molecules targeting inflammatory processes. To test this hypothesis, here we examined the immunomodulatory characteristics of AMCs and of their conditioned medium (AMC-CM) in vitro, and studied the potential therapeutic effect of AMC-CM in thirteen different spontaneous horse tendon and ligament injuries in vivo. Our results demonstrate that AMCs are capable of inhibiting peripheral blood mononuclear cell (PBMC) proliferation after allogenic stimulation either when cocultured in cell-to-cell contact, or when the two cell types are physically separated by a transwell membrane, suggesting that soluble factors are implicated in this phenomenon. Our hypothesis is further supported by the demonstration that PBMC proliferation is inhibited by AMC-CM. In our in vivo studies, no significant adverse effects were observed in treated tendons, and clinical and ultrasonographical evaluation did not reveal evidence of inappropriate tissue or tumor formation. Clinical outcomes were favorable and the significantly lower rate (15.38%) of reinjuries observed compared to untreated animals, suggests that treatment with AMC-CM is very efficacious. In conclusion, this study identifies AMC-CM as a novel therapeutic biological cell-free product for treating horse tendon and ligament diseases. PMID:23795963

Lange-Consiglio, Anna; Rossi, Daniele; Tassan, Stefano; Perego, Roberta; Cremonesi, Fausto; Parolini, Ornella

2013-11-15

173

UNIVERSITY OF CALIFORNIA, SAN DIEGO The Application of a Novel Multispectral Imaging System to the in vivo Study of  

E-print Network

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2. LUMIS: The Low-light-level Underwater Multispectral Imaging SystemUNIVERSITY OF CALIFORNIA, SAN DIEGO The Application of a Novel Multispectral Imaging System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 2.6. Image Format . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Jaffe, Jules

174

Special conference of the American Association for Cancer Research on molecular imaging in cancer: linking biology, function, and clinical applications in vivo.  

PubMed

The AACR Special Conference on Molecular Imaging in Cancer: Linking Biology, Function, and Clinical Applications In Vivo, was held January 23-27, 2002, at the Contemporary Hotel, Walt Disney World, Orlando, FL. Co-Chairs David Piwnica-Worms, Patricia Price and Thomas Meade brought together researchers with diverse expertise in molecular biology, gene therapy, chemistry, engineering, pharmacology, and imaging to accelerate progress in developing and applying technologies for imaging specific cellular and molecular signals in living animals and humans. The format of the conference was the presentation of research that focused on basic and translational biology of cancer and current state-of-the-art techniques for molecular imaging in animal models and humans. This report summarizes the special conference on molecular imaging, highlighting the interfaces of molecular biology with animal models, instrumentation, chemistry, and pharmacology that are essential to convert the dreams and promise of molecular imaging into improved understanding, diagnosis, and management of cancer. PMID:11929844

Luker, Gary D

2002-04-01

175

Folic acid-functionalized up-conversion nanoparticles: toxicity studies in vivo and in vitro and targeted imaging applications  

NASA Astrophysics Data System (ADS)

Folate receptors (FRs) are overexpressed on a variety of human cancer cells and tissues, including cancers of the breast, ovaries, endometrium, and brain. This over-expression of FRs can be used to target folate-linked imaging specifically to FR-expressing tumors. Fluorescence is emerging as a powerful new modality for molecular imaging in both the diagnosis and treatment of disease. Combining innovative molecular biology and chemistry, we prepared three kinds of folate-targeted up-conversion nanoparticles as imaging agents (UCNC-FA: UCNC-Er-FA, UCNC-Tm-FA, and UCNC-Er,Tm-FA). In vivo and in vitro toxicity studies showed that these nanoparticles have both good biocompatibility and low toxicity. Moreover, the up-conversion luminescence imaging indicated that they have good targeting to HeLa cells and can therefore serve as potential fluorescent contrast agents.Folate receptors (FRs) are overexpressed on a variety of human cancer cells and tissues, including cancers of the breast, ovaries, endometrium, and brain. This over-expression of FRs can be used to target folate-linked imaging specifically to FR-expressing tumors. Fluorescence is emerging as a powerful new modality for molecular imaging in both the diagnosis and treatment of disease. Combining innovative molecular biology and chemistry, we prepared three kinds of folate-targeted up-conversion nanoparticles as imaging agents (UCNC-FA: UCNC-Er-FA, UCNC-Tm-FA, and UCNC-Er,Tm-FA). In vivo and in vitro toxicity studies showed that these nanoparticles have both good biocompatibility and low toxicity. Moreover, the up-conversion luminescence imaging indicated that they have good targeting to HeLa cells and can therefore serve as potential fluorescent contrast agents. Electronic supplementary information (ESI) available: Up-conversion luminescence spectra of UCNC-Er and UCNC-Er-FA, UCNC-Tm and UCNC-Tm-FA. Confocal luminescence imaging data collected as a series along the Z optical axis. See DOI: 10.1039/c4nr02312a

Sun, Lining; Wei, Zuwu; Chen, Haige; Liu, Jinliang; Guo, Jianjian; Cao, Ming; Wen, Tieqiao; Shi, Liyi

2014-07-01

176

Automated Segmentation and Object Classification of CT Images: Application to In Vivo Molecular Imaging of Avian Embryos  

PubMed Central

Background. Although chick embryogenesis has been studied extensively, there has been growing interest in the investigation of skeletogenesis. In addition to improved poultry health and minimized economic loss, a greater understanding of skeletal abnormalities can also have implications for human medicine. True in vivo studies require noninvasive imaging techniques such as high-resolution microCT. However, the manual analysis of acquired images is both time consuming and subjective. Methods. We have developed a system for automated image segmentation that entails object-based image analysis followed by the classification of the extracted image objects. For image segmentation, a rule set was developed using Definiens image analysis software. The classification engine was implemented using the WEKA machine learning tool. Results. Our system reduces analysis time and observer bias while maintaining high accuracy. Applying the system to the quantification of long bone growth has allowed us to present the first true in ovo data for bone length growth recorded in the same chick embryos. Conclusions. The procedures developed represent an innovative approach for the automated segmentation, classification, quantification, and visualization of microCT images. MicroCT offers the possibility of performing longitudinal studies and thereby provides unique insights into the morpho- and embryogenesis of live chick embryos. PMID:23997760

Schmidt, Jana; Zimmermann, Johannes; Saluz, Hans Peter

2013-01-01

177

Automated Segmentation and Object Classification of CT Images: Application to In Vivo Molecular Imaging of Avian Embryos.  

PubMed

Background. Although chick embryogenesis has been studied extensively, there has been growing interest in the investigation of skeletogenesis. In addition to improved poultry health and minimized economic loss, a greater understanding of skeletal abnormalities can also have implications for human medicine. True in vivo studies require noninvasive imaging techniques such as high-resolution microCT. However, the manual analysis of acquired images is both time consuming and subjective. Methods. We have developed a system for automated image segmentation that entails object-based image analysis followed by the classification of the extracted image objects. For image segmentation, a rule set was developed using Definiens image analysis software. The classification engine was implemented using the WEKA machine learning tool. Results. Our system reduces analysis time and observer bias while maintaining high accuracy. Applying the system to the quantification of long bone growth has allowed us to present the first true in ovo data for bone length growth recorded in the same chick embryos. Conclusions. The procedures developed represent an innovative approach for the automated segmentation, classification, quantification, and visualization of microCT images. MicroCT offers the possibility of performing longitudinal studies and thereby provides unique insights into the morpho- and embryogenesis of live chick embryos. PMID:23997760

Heidrich, Alexander; Schmidt, Jana; Zimmermann, Johannes; Saluz, Hans Peter

2013-01-01

178

Application of interferometry for in-vivo testing of the stability of the tear film on the contact lens  

NASA Astrophysics Data System (ADS)

The shearing interferometry is presented as an in vivo method for testing the stability of the tear film covering the contact lens. The material and quality of a contact lens and its correct fitting to the surface of cornea influence the stability of the tear film. By observation of the tear film distribution, the precise assessment of the quality of the contact lens surface can be performed. Moreover, the overused or damaged contact lens can be detected by the analysis of interferograms. In this study the following types of soft contact lenses were used: Dura Soft D3 (r equals 8,7 mm, r equals 8,4 mm), Medalist (r equals 8,7 mm) and Johnson and Johnson (r equals 8,8 mm). The contact lenses were placed on the patients' cornea. The 3 mW HeNe laser was used as the light source in shearing interferometer and the CCD camera for recording the interference images. The coherent light reflected from the surface of the contact lens covered with the tear film formed the interference pattern. The sequence of the obtained interferograms were recorded and then analyzed. The accuracy of the contact lens fitting can be estimated by the interferogram analysis. The examples of correct and incorrect fitting of the overused or damaged contact lenses are presented. The proposed method is noncontact, nondestructive and of the high accuracy.

Licznerski, Tomasz J.; Lechna-Marczynska, Monika I.; Kasprzak, Henryk T.

1998-10-01

179

Clinical Application of In-Room Positron Emission Tomography for In Vivo Treatment Monitoring in Proton Radiation Therapy  

SciTech Connect

Purpose: The purpose of this study is to evaluate the potential of using in-room positron emission tomography (PET) for treatment verification in proton therapy and for deriving suitable PET scan times. Methods and Materials: Nine patients undergoing passive scattering proton therapy underwent scanning immediately after treatment with an in-room PET scanner. The scanner was positioned next to the treatment head after treatment. The Monte Carlo (MC) method was used to reproduce PET activities for each patient. To assess the proton beam range uncertainty, we designed a novel concept in which the measured PET activity surface distal to the target at the end of range was compared with MC predictions. The repositioning of patients for the PET scan took, on average, approximately 2 minutes. The PET images were reconstructed considering varying scan times to test the scan time dependency of the method. Results: The measured PET images show overall good spatial correlations with MC predictions. Some discrepancies could be attributed to uncertainties in the local elemental composition and biological washout. For 8 patients treated with a single field, the average range differences between PET measurements and computed tomography (CT) image-based MC results were <5 mm (<3 mm for 6 of 8 patients) and root-mean-square deviations were 4 to 11 mm with PET-CT image co-registration errors of approximately 2 mm. Our results also show that a short-length PET scan of 5 minutes can yield results similar to those of a 20-minute PET scan. Conclusions: Our first clinical trials in 9 patients using an in-room PET system demonstrated its potential for in vivo treatment monitoring in proton therapy. For a quantitative range prediction with arbitrary shape of target volume, we suggest using the distal PET activity surface.

Min, Chul Hee [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States)] [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Zhu, Xuping [Center for Advanced Radiological Sciences, Nuclear Medicine and Molecular Imaging, Radiology Department, Massachusetts General Hospital, Boston, Massachusetts (United States)] [Center for Advanced Radiological Sciences, Nuclear Medicine and Molecular Imaging, Radiology Department, Massachusetts General Hospital, Boston, Massachusetts (United States); Winey, Brian A. [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States)] [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Grogg, Kira [Center for Advanced Radiological Sciences, Nuclear Medicine and Molecular Imaging, Radiology Department, Massachusetts General Hospital, Boston, Massachusetts (United States)] [Center for Advanced Radiological Sciences, Nuclear Medicine and Molecular Imaging, Radiology Department, Massachusetts General Hospital, Boston, Massachusetts (United States); Testa, Mauro [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States)] [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); El Fakhri, Georges [Center for Advanced Radiological Sciences, Nuclear Medicine and Molecular Imaging, Radiology Department, Massachusetts General Hospital, Boston, Massachusetts (United States)] [Center for Advanced Radiological Sciences, Nuclear Medicine and Molecular Imaging, Radiology Department, Massachusetts General Hospital, Boston, Massachusetts (United States); Bortfeld, Thomas R.; Paganetti, Harald [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States)] [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Shih, Helen A., E-mail: hshih@partners.org [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States)

2013-05-01

180

Choice of detectors for in vivo elemental analysis by counting natural and neutron-induced gamma rays for medical applications  

NASA Astrophysics Data System (ADS)

Body fat is measured by detecting C and O in vivo through fast neutron inelastic scattering. A sealed D?T neutron generator is used for the pulsed (4-10 kHz) production of fast neutrons. Carbon and oxygen are detected by counting the 4.44 and 6.13 MeV gamma rays resulting from the inelastic scattering of the fast neutrons from 12C and 16O. Large Bi 4Ge 3O 12 (BGO) crystal detectors (127 × 76 mm) are used for the gamma ray detection during the 10 ?s neutron burst. BGO detectors improved the signal to background ratio for the carbon detection by a factor of six compared to 152 × 152 mm NaI (Tl) detectors. Exposure to scattered neutrons did not affect the gain stability of the BGOs. Thermal neutrons from a moderated 238Pu?Be source are used for the measurement of total body nitrogen (and thus protein). The resulting high energy prompt gamma rays from nitrogen (10.83 MeV) are detected simultaneously with the irradiation. BGO detectors have superior stability operating in an environment of variable neutron exposure and high counting rates. However, the presence of neutrons creates a 10.2 MeV gamma ray peak from 73Ge in the BGO detector which interferes with the nitrogen peak. Whole body gamma ray counters, consisting of NaI(Tl) crystal detectors in a shielded room, are used to measure the natural radioactivity of the body due to 40K. They are also used to measure body Ca, P, Na and Cl, following total body exposure to thermal neutrons.

Kehayias, Joseph J.; Zhuang, Hong; Dowling, Lisa; Ma, Ruimei; Moore, Robert

1994-12-01

181

Temperature monitoring and lesion volume estimation during double-applicator laser-induced thermotherapy in ex vivo swine pancreas: a preliminary study.  

PubMed

Tissue temperature distribution plays a crucial role in the outcome of laser-induced thermotherapy (LITT), a technique employed for neoplasias removal. Since recent studies proposed LITT for pancreatic tumors treatment, assessment of temperature and of its effects around the laser applicator could be useful to define optimal laser settings. The aims of this work are temperature monitoring and measurement of ablated tissue volume in an ex vivo porcine pancreas undergoing double-applicator LITT. A three-dimensional numerical model is implemented to predict temperature rise and volumes of ablated tissue in treated pancreas. Experiments are performed to validate the model, with two modalities: (1) 12-fiber Bragg grating sensors are adopted to monitor the heating and cooling during LITT at several distances from the applicators tip, and (2) 1.5-T MR imaging is used to estimate the ablated volume. Experimental data agree with theoretical ones: at 2 mm from both applicators tips, the maximum temperature increase is approximately 60 °C downward from the tips, while it increases of about 40 °C and 30 °C, respectively, at the level and upward from the tips. This behavior occurs also at other distances, proving that the tissue downward from the tip is mostly heated. Furthermore, the estimated volume with MRI agrees with theoretical one (i.d., 0.91?±?0.09 vs. 0.95 cm(3)). The encouraging results indicate that the model could be a suitable tool to choose the optimal laser settings, in order to control the volume of ablated tissue. PMID:23780709

Saccomandi, Paola; Schena, Emiliano; Giurazza, Francesco; Del Vescovo, Riccardo; Caponero, Michele A; Mortato, Luca; Panzera, Francesco; Cazzato, Roberto L; Grasso, Francesco R; Di Matteo, Francesco M; Silvestri, Sergio; Zobel, Bruno B

2014-03-01

182

The application of micro-CT in monitoring bone alterations in tail-suspended rats in vivo  

NASA Astrophysics Data System (ADS)

Osteopenia is a pathological process that affects human skeletal health not only on earth but also in long-time spaceflight. Micro-computed tomography (micro-CT) is a nondestructive method for assessing both bone quantity and bone quality. To investigate the characteristics of micro-CT on evaluating the microgravity-induced osteopenia (e.g. early detection time and the sensitive parameters), the bone loss process of tail-suspended rats was monitored by micro-CT in this study. 8-Week-old female Sprague Dawley rats were divided into two groups: tail suspension (TS) and control (CON). Volumetric bone mineral density (vBMD) and microstructure of the femur and tibia were evaluated in vivo by micro-CT at 0, 7, 14, 22 days. Biomechanical properties of the femur and tibia were determined by three-point bending test. The ash weight of bone was also investigated. The results showed that (1) bone loss in the proximal tibia appeared earlier than in the distal femur. (2) On day 7, the percent bone volume (BV/TV) of the tibia 15.44% decreased significantly, and the trabecular separation (Tb.Sp) 30.29% increased significantly in TS group, both of which were detected earlier than other parameters. (3) Biomechanical properties (e.g. femur, -22.4% maximum load and -23.75% Young’s modulus vs. CON) and ash weight of the femur and tibia decreased significantly in the TS group in comparison to CON group. (4) vBMD of the femur and tibia were clearly related to bone ash and dry weight (r = 0.75-0.87, p < 0.05). (5) BV/TV of both femur and tibia were clearly related to maximum load and Young’s modulus (r = 0.66-0.87, p < 0.05). Similarly, trabecular vBMD and BV/TV of the femur and tibia were clearly related to Young’s modulus (r = 0.73-0.89, p < 0.05). These indicated that BV/TV and Tb.Sp were more sensitive than other parameters for evaluating bone loss induced by tail suspension, moreover, trabecular vBMD and other parameters might be used to evaluate bone strength. Therefore, micro-CT is a reliable and sensitive method for predicting unloading-induced bone loss in small animals.

Luan, Hui-Qin; Sun, Lian-Wen; Huang, Yun-Fei; Wang, Ying; McClean, Colin J.; Fan, Yu-Bo

2014-06-01

183

AAV2 production with optimized N/P ratio and PEI-mediated transfection results in low toxicity and high titer for in vitro and in vivo applications.  

PubMed

The adeno-associated virus (AAV) is one of the most useful viral vectors for gene delivery for both in vivo and in vitro applications. A variety of methods have been established to produce and characterize recombinant AAV (rAAV) vectors; however most methods are quite cumbersome and obtaining consistently high titer can be problematic. This protocol describes a triple-plasmid co-transfection approach with 25 kDa linear polyethylenimine (PEI) in 293 T cells for the production of AAV serotype 2. Seventy-two hours post-transfection, supernatant and cells were harvested and purified by a discontinuous iodixanol density gradient ultracentrifugation, then dialyzed and concentrated with an Amicon 15 100,000 MWCO concentration unit. To optimize the protocol for AAV2 production using PEI, various N/P ratios and DNA amounts were compared. We found that an N/P ratio of 40 coupled with 1.05 ?g DNA per ml of media (21 ?g DNA/15 cm dish) was found to produce the highest yields for viral replication and assembly measured multiple ways. The infectious units, as determined by serial dilution, were between 1×10(8) and 2×10(9) IU/ml. The genomic titer of the viral stock was determined by qPCR and ranged from 2×10(12) to 6×10(13) VG/ml. These viral vectors showed high expression both in vivo within the brain and in vitro in cell culture. The use of linear 25 kDa polyethylenamine PEI as a transfection reagent is a simple, more cost-effective, and stable means of high-throughput production of high-titer AAV serotype 2. The use of PEI also eliminates the need to change cell medium post-transfection, lowering cost and workload, while producing high-titer, efficacious AAV2 vectors for routine gene transfer. PMID:23791963

Huang, Xinping; Hartley, Antja-Voy; Yin, Yishi; Herskowitz, Jeremy H; Lah, James J; Ressler, Kerry J

2013-11-01

184

In vivo effects of a synthetic 2-kilodalton macrophage-activating lipopeptide of Mycoplasma fermentans after pulmonary application.  

PubMed

Mycoplasmas can cause interstitial pneumonias inducing critical illness in humans and animals. Mycoplasma infections are characterized by an influx of neutrophils, followed by an accumulation of macrophages and lymphocytes. The present study deals with the question of which mycoplasmal components cause this host reaction. The mycoplasma-derived, macrophage-activating lipopeptide 2S-MALP-2 was used to mimic the sequelae of a mycoplasma infection. To this end, 2S-MALP-2 was intratracheally instilled into the lungs of Lewis rats, and the bronchoalveolar lavage cells were examined at different times after different doses of 2S-MALP-2. Application of 2.5 microg induced a pronounced leukocyte accumulation in the bronchoalveolar space. At 24 h after 2S-MALP-2 administration, the majority of leukocytes consisted of neutrophils, followed by macrophages, peaking on days 2 and 3. Lymphocyte numbers, although amounting to only a few percent of the total bronchoalveolar lavage cells, also increased significantly, with maximal lymphocyte accumulation occurring by 72 h after instillation. The leukocyte count of the lung interstitium was increased on day 3 after treatment. After 10 days all investigated cell populations returned to control levels. Transient chemotactic activity for neutrophils was detected in the bronchoalveolar lavage fluid early after 2S-MALP-2 application, followed by monocyte chemoattractant protein-1 activity (MCP-1) in lung homogenates. MCP-1 was produced by bronchoalveolar lavage cells upon stimulation with 2S-MALP-2. Our data indicate that mycoplasmal lipoproteins and lipopeptides are probably the most relevant mycoplasmal components for the early host reaction. The primary target cells are likely to be the alveolar macrophages liberating chemokines, which attract further leukocytes. PMID:12065522

Lührmann, Anke; Deiters, Ursula; Skokowa, Julia; Hanke, Michaela; Gessner, Johannes E; Mühlradt, Peter F; Pabst, Reinhard; Tschernig, Thomas

2002-07-01

185

Theory and application of optimal linear resolution to MRI truncation artifacts, multiexponential decays and in vivo multiple sclerosis pathology  

NASA Astrophysics Data System (ADS)

It is widely believed that one of the best way to proceed when analysing data is to generate estimates which fit the data. However, when the relationship between the unknown model and data is linear for highly underdetermined systems, is it common practice to find estimates with good linear resolution with no regard for fitting the data. For example, windowed Fourier transforms produces estimates that have good linear resolution but do not fit the data. Surprisingly, many researchers do not seem to be explicitly aware of this fact. This thesis presents a theoretical basis for the linear resolution which demonstrates that, for a wide range of problems, algorithms which produce estimates with good linear resolution can be a more powerful and convenient way of presenting the information in the data, than models that fit the data. Linear resolution was also applied to two outstanding problems in linear inverse theory. The first was the problem of truncation artifacts in magnetic resonance imaging (MRI). Truncation artifacts were heavily suppressed or eliminated by the choice of one of two novel Fourier transform windows. Complete elimination of truncation artifacts generally led to unexpectedly blurry images. Heavy suppression seemed to be the best compromise between truncation artifacts and blurriness. The second problem was estimating the relaxation distribution of a multiexponential system from its decay curve. This is an example where hundreds of papers have been written on the subject, yet almost no one has made a substantial effort to apply linear resolution. I found the application to be very successful. As an example, the algorithm was applied to the decay of MRI data from multiple sclerosis patients in an attempt to differentiate between various pathologies.

Cover, Keith S.

186

In Vivo Blood Characterization from Bioimpedance Spectroscopy of Blood  

E-print Network

In Vivo Blood Characterization from Bioimpedance Spectroscopy of Blood Pooling Tao Dai Department indices such as haematocrit, glucose level and hydration. Current in vivo bioimpedance spectroscopy parameters for many biomedical and clinical monitoring applications. #12;Index Terms Bioimpedance

Adler, Andy

187

A Sensitive Method for Detecting in Vivo Formation of \\/V-Nitrosomorpholine and Its Application to Rats Given Low Doses of Morpholine and Sodium Nitrite1  

Microsoft Academic Search

A method was developed to monitor the in vivo formation of W-nitrosomorpholine. A\\/-Nitroso(2-hydroxyethyl)glycine, a major urinary metabolite of A\\/-nitrosomorpholine, was quantified as its methyl ester-trimethylsilyl ether derivative, using gas chromatog- raphy with nitrosamine-specific detection. When the method was applied to rats, the in vivo formation of, or exposure to, as little as 0.6 ut) of \\/V-nitrosomorpholine could be quantified. The

Stephen S. Hecht; J. Bradley Morrison

188

Application of basic and composite thrombelastography parameters in monitoring of the antithrombotic effect of the low molecular weight heparin dalteparin: an in vivo study  

PubMed Central

Background Low molecular weight heparin (LMWH) is in vast usage for treatment of thromboembolic diseases such as deep venous thrombosis and acute coronary syndromes. There are certain clinical situations where a quick point of care testing of the effect of LMWH would be useful. At this point there are no point of care devices available in the market for monitoring the effect of LMWH. Thrombelastography (TEG) evaluates the viscoelastic properties of blood during coagulation. The clinical application of TEG in monitoring LMWH treatment is not yet well defined. The purpose of this in vivo study was to systematically evaluate the most suitable TEG parameters for evaluation of the antithrombotic effect of LMWH. We furthermore evaluated for the first time the usefulness of the composite TEG parameter the Thrombodynamic Ratio (TDR) in monitoring LMWH treatment. Methods Healthy male volunteers (n = 7) were injected subcutaneously with the LMWH dalteparin 120 IU/kg. TEG parameters and antifactor Xa levels were measures at baseline, 2, 4, 5 and 24 hours after the injection. Correlation between TEG parameters and antiXa were calculated. The sensitivity and specificity of the TEG parameters for plasma levels of antiXa in the therapeutic range of 0.5 - 1.0 U/ml were calculated. Results All basic TEG parameters correlated significantly with antiXa levels. Among the basic parameters, the TEG reaction time R had the best correlation with antiXa levels with the most favorable combination of sensitivity and specificity for the therapeutic range of antiXa levels (r = 0.82, p < 0.0001, sensitivity 68%, specificity 100%). The composite TEG parameter TDR demonstrated the best correlation with antiXa levels, and an even more favorable combination of sensitivity and specificity compared to any of the basic parameters (r = - 0.87, p < 0.0001, sensitivity 95%, specificity 79%). Conclusion The TEG reaction time R and TDR are the most suitable TEG parameters for evaluation of the antithrombotic effect of dalteparin with a highly significant correlation with antiXa levels in healthy male volunteers. Measures for uniform clinical use of these parameters are proposed. Larger clinical trials are needed to correlate R and TDR with clinical outcomes. PMID:19903343

Artang, Ramin; Frandsen, Niels J; Nielsen, J?rn Dalsgaard

2009-01-01

189

In vivo methods for drug absorption - comparative physiologies, model selection, correlations with in vitro methods (IVIVC), and applications for formulation/API/excipient characterization including food effects.  

PubMed

This review summarizes the current knowledge on anatomy and physiology of the human gastrointestinal tract in comparison with that of common laboratory animals (dog, pig, rat and mouse) with emphasis on in vivo methods for testing and prediction of oral dosage form performance. A wide range of factors and methods are considered in addition, such as imaging methods, perfusion models, models for predicting segmental/regional absorption, in vitro in vivo correlations as well as models to investigate the effects of excipients and the role of food on drug absorption. One goal of the authors was to clearly identify the gaps in today's knowledge in order to stimulate further work on refining the existing in vivo models and demonstrate their usefulness in drug formulation and product performance testing. PMID:24637348

Sjögren, Erik; Abrahamsson, Bertil; Augustijns, Patrick; Becker, Dieter; Bolger, Michael B; Brewster, Marcus; Brouwers, Joachim; Flanagan, Talia; Harwood, Matthew; Heinen, Christian; Holm, René; Juretschke, Hans-Paul; Kubbinga, Marlies; Lindahl, Anders; Lukacova, Viera; Münster, Uwe; Neuhoff, Sibylle; Nguyen, Mai Anh; Peer, Achiel van; Reppas, Christos; Hodjegan, Amin Rostami; Tannergren, Christer; Weitschies, Werner; Wilson, Clive; Zane, Patricia; Lennernäs, Hans; Langguth, Peter

2014-06-16

190

Application of second-harmonic generation microscopy for in-vivo observation of structural change in human dermal collagen fiber caused by aging and/or UV exposure  

NASA Astrophysics Data System (ADS)

Second-harmonic-generation (SHG) microscopy is useful to visualize collagen fiber in biological tissues in vivo. In this paper, we applied our SHG microscopy equipped with a Cr:Forsterite laser to visualize human dermal collagen fiber in vivo. The obtained SHG images indicated the structural difference of dermal collagen fiber between different ages, for example, fine collagen fiber is densely distributed in 20's subjects whereas only thick collagen fiber is remained in 60's subjects. These results reflect structural change of collagen fiber caused by natural aging and/or photoaging. The SHG microscopy has a potential to become an in vivo collagen-sensitive microscopy for assessment of skin aging.

Yasui, T.; Yonetsu, M.; Tanaka, R.; Fukushima, S.; Yamashita, T.; Ogura, Y.; Hirao, T.; Araki, T.

2012-03-01

191

Establishment of an Allo-Transplantable Hamster Cholangiocarcinoma Cell Line and Its Application for In Vivo Screening of Anti-Cancer Drugs  

PubMed Central

Opisthorchis viverrini (O. viverrini) is a well-known causative agent of cholangiocarcinoma (CCA) in humans. CCA is very resistant to chemotherapy and is frequently fatal. To understand the pathogenesis of CCA in humans, a rodent model was developed. However, the development of CCA in rodents is time-consuming and the xenograft-transplantation model of human CCA in immunodeficient mice is costly. Therefore, the establishment of an in vivo screening model for O. viverrini-associated CCA treatment was of interest. We developed a hamster CCA cell line, Ham-1, derived from the CCA tissue of O. viverrini-infected and N-nitrosodimethylamine-treated Syrian golden hamsters. Ham-1 has been maintained in Dulbecco's Modified Essential Medium supplemented with 10% fetal bovine serum for more than 30 subcultures. These cells are mostly diploid (2n=44) with some being polyploid. Tumorigenic properties of Ham-1 were demonstrated by allograft transplantation in hamsters. The transplanted tissues were highly proliferative and exhibited a glandular-like structure retaining a bile duct marker, cytokeratin 19. The usefulness of this for in vivo model was demonstrated by berberine treatment, a traditional medicine that is active against various cancers. Growth inhibitory effects of berberine, mainly by an induction of G1 cell cycle arrest, were observed in vitro and in vivo. In summary, we developed the allo-transplantable hamster CCA cell line, which can be used for chemotherapeutic drug testing in vitro and in vivo. PMID:24516278

Puthdee, Nattapong; Seubwai, Wunchana; Wonkchalee, Orasa; Kaewkong, Worasak; Juasook, Amornrat; Pinlaor, Somchai; Pairojkul, Chawalit; Wongkham, Chaisiri; Okada, Seiji; Boonmars, Thidarut; Wongkham, Sopit

2013-01-01

192

Application of the correlation of in vitro dissolution behavior and in vivo plasma concentration profile (IVIVC) for soft-gel capsules--a pointless pursuit?  

PubMed

Plasma concentration profiles of arundic acid ((R)-(-)-2-propyloctanoic acid), an oil-like medicine, administered as soft-gel capsules in human clinical tests were predicted from the dissolution test data of the soft-gel capsules with different storage terms (short- and long-term stored drugs) by applying the in vitro-in vivo correlation (IVIVC). We established two linear-regression IVIVCs, which were characterized by either the in vitro dissolution behaviors against the pH 8.0 dissolution medium or the pH 6.8 dissolution medium containing 2% sodium dodecyl sulfate (SDS), in this study. Also, the prediction accuracies for the in vivo plasma profiles in humans for these two IVIVCs were compared. Regarding dissolution from the long-term stored capsule in pH 8.0 dissolution medium without surfactant, the prediction accuracies of the in vivo plasma profiles in humans were not satisfactory for the obtained IVIVC. The use of pH 6.8 dissolution medium containing 2% SDS, according to the Japanese guideline, improved the dissolution of the long-term stored capsule. Furthermore, the prediction accuracies for the in vivo plasma profiles in humans for these two IVIVCs were compared. The IVIVC established by the in vitro dissolution data obtained with the dissolution medium containing surfactant more effectively predicted the plasma drug concentration profiles following oral administrations of the soft-gel capsules under both storage conditions. PMID:17978506

Nishimura, Hidekatsu; Hayashi, Chiaki; Aiba, Tetsuya; Okamoto, Ichiro; Miyamoto, Yuji; Nakade, Susumu; Takeda, Kazuhisa; Kurosaki, Yuji

2007-11-01

193

Establishment of an allo-transplantable hamster cholangiocarcinoma cell line and its application for in vivo screening of anti-cancer drugs.  

PubMed

Opisthorchis viverrini (O. viverrini) is a well-known causative agent of cholangiocarcinoma (CCA) in humans. CCA is very resistant to chemotherapy and is frequently fatal. To understand the pathogenesis of CCA in humans, a rodent model was developed. However, the development of CCA in rodents is time-consuming and the xenograft-transplantation model of human CCA in immunodeficient mice is costly. Therefore, the establishment of an in vivo screening model for O. viverrini-associated CCA treatment was of interest. We developed a hamster CCA cell line, Ham-1, derived from the CCA tissue of O. viverrini-infected and N-nitrosodimethylamine-treated Syrian golden hamsters. Ham-1 has been maintained in Dulbecco's Modified Essential Medium supplemented with 10% fetal bovine serum for more than 30 subcultures. These cells are mostly diploid (2n=44) with some being polyploid. Tumorigenic properties of Ham-1 were demonstrated by allograft transplantation in hamsters. The transplanted tissues were highly proliferative and exhibited a glandular-like structure retaining a bile duct marker, cytokeratin 19. The usefulness of this for in vivo model was demonstrated by berberine treatment, a traditional medicine that is active against various cancers. Growth inhibitory effects of berberine, mainly by an induction of G1 cell cycle arrest, were observed in vitro and in vivo. In summary, we developed the allo-transplantable hamster CCA cell line, which can be used for chemotherapeutic drug testing in vitro and in vivo. PMID:24516278

Puthdee, Nattapong; Vaeteewoottacharn, Kulthida; Seubwai, Wunchana; Wonkchalee, Orasa; Kaewkong, Worasak; Juasook, Amornrat; Pinlaor, Somchai; Pairojkul, Chawalit; Wongkham, Chaisiri; Okada, Seiji; Boonmars, Thidarut; Wongkham, Sopit

2013-12-01

194

The application of anti-ESAT-6 monoclonal antibody fluorescent probe in ex vivo near-infrared fluorescence imaging in mice with pulmonary tuberculosis.  

PubMed

Here, we aimed to assess the feasibility of anti-ESAT-6 monoclonal antibody (mAb) coupling with IR783 and rhodamine fluorescent probe in the detection of ESAT-6 expression in tuberculosis tissue of mice using near-infrared fluorescence imaging. IR783 and rhodamine were conjugated to the anti-ESAT-6 mAb or IgG. Mice in the experimental group were injected with fluorescence-labeled mAb probe, and mice in the control group were injected with fluorescence-labeled non-specific IgG antibody. Twenty-four hours later, the lung tissue of mice was examined using ex vivo near-infrared fluorescence imaging. In addition, the contrast-to-noise ratio (CNR) was calculated by measuring the signal intensities of the pulmonary lesions, normal lung tissue and background noise. The frozen lung tissue section was examined under fluorescence microscopy and compared with hemoxylin and eosin (HE) staining. The ex vivo near-infrared fluorescence imaging showed that the fluorescence signal in the lung tuberculosis lesions in the experimental group was significantly enhanced, whereas there was only a weak fluorescence signal or even no fluorescence signal in the control group. CNR values were 64.40?±?7.02 (n?=?6) and 8.75?±?3.87 (n?=?6), respectively (t?=?17.01, p?vivo imaging of mice tuberculosis, and may be of further use in tuberculosis in living mice. PMID:24170605

Feng, Feng; Zhang, Haoling; Zhu, Zhaoqin; Li, Cong; Shi, Yuxin; Zhang, Zhiyong

2014-09-01

195

Novel application of human periodontal ligament stem cells and water-soluble chitin for collagen tissue regeneration: in vitro and in vivo investigations.  

PubMed

Human periodontal ligament stem cells (hPDLSCs) have been proposed as an alternative to conventional cosmetic fillers because they display an innate ability to synthesize collagen. The aims of this study were to determine the effects of water-soluble chitin (WSC) on the proliferation and migration of hPDLSCs, and to quantify collagen synthesis in vitro and in vivo compared with human adipose-derived stem cell (hADSC)s. hPDLSCs were isolated from healthy extracted teeth, and the cell proliferation and cell migration capacities of untreated hPDLSCs (control group) and WSC-treated hPDLSCs (test group) were compared. Insoluble/soluble collagen synthesis were also assessed, and collagen related markers were evaluated including lysyl oxidase (LOX), lysyl oxidase like (LOXL)1, LOXL2, and hydroxyproline. In vivo collagen formation was examined by transplanting hyaluronic acid as a cell carrier into the subcutaneous pockets of immunocompromised mice in the control and test groups; histology and immunohistochemistry analyses were performed 4 (n=4) and 8 (n=4) weeks later. There was a dose-dependent enhancement of hPDLSCs proliferation in the test group, and a concomitant reduction in cell migration. The amount of insoluble collagen formed was greater in the test group than in the control group (p<0.05), whereas soluble collagen formation was significantly reduced in the test group (p<0.05). The histology and immunohistochemistry results revealed that the amount of collagen formed in vivo was greater in WSC-treated hPDLSCs than in the control cells at 4 and 8 weeks (p<0.05), and histometric analysis at 8 weeks revealed that enhancement of collagen formation by hPDLSCs was greater than by hADSCs. These results indicate that WSC modulates the properties of hPDLSCs, rendering them more suitable for cosmetic soft-tissue augmentation. PMID:21981356

Jung, Im Hee; Park, Jung Chul; Kim, Jane C; Jeon, Dong Won; Choi, Seong Ho; Cho, Kyoo Sung; Im, Gun Il; Kim, Byung Soo; Kim, Chang Sung

2012-03-01

196

/sup 31/P in-vivo spectroscopic study by high-field whole-body MR system--an application to a case with arteriosclerosis obliterans  

SciTech Connect

/sup 31/P in-vivo spectroscopy was performed by a 1.5-tesla whole-body MR system. The /sup 31/P spectrum for the calf muscle in a patient with arteriosclerosis obliterans having intermittent claudication was obtained every two minutes. When the spectrum after the workload was compared with that at rest, an increase in inorganic phosphate (Pi) and a decrease in phosphocreatine (PCr) were observed, resulting in a strong decrease in the PCr/Pi ratio. This method can measure the ischemic and recovery stages of energy metabolism in skeletal muscle noninvasively and continuously in addition to magnetic resonance imaging.

Nishimura, T.; Imakita, S.; Naito, H.; Takamiya, M.; Matsuo, H.; Nakayama, R.

1987-08-01

197

Biocompatible Nanogenerators through High Piezoelectric Coefficient 0.5Ba(Zr0.2 Ti0.8 )O3 -0.5(Ba0.7 Ca0.3 )TiO3 Nanowires for In-Vivo Applications.  

PubMed

Lead-free BZT-BCT (0.5Ba(Zr0.2 Ti0.8 )O3 -0.5(Ba0.7 Ca0.3 )TiO3 ) nanowires with a high piezoelectric coefficient are synthesized and nanogenerators (NGs) composed of them are successfully developed. The studied in vitro and in vivo biocompatibility of the NGs shows great potential for their application as in vivo power sources. PMID:25257019

Yuan, Miaomiao; Cheng, Li; Xu, Qi; Wu, Weiwei; Bai, Suo; Gu, Long; Wang, Zhe; Lu, Jun; Li, Huanping; Qin, Yong; Jing, Tao; Wang, Zhong Lin

2014-11-01

198

Development of a disposable maglev centrifugal blood pump intended for one-month support in bridge-to-bridge applications: in vitro and initial in vivo evaluation.  

PubMed

MedTech Dispo, a disposable maglev centrifugal blood pump with two degrees of freedom magnetic suspension and radial magnetic coupling rotation, has been developed for 1-month extracorporeal circulatory support. As the first stage of a two-stage in vivo evaluation, 2-week evaluation of a prototype MedTech Dispo was conducted. In in vitro study, the pump could produce 5 L/min against 800 mm Hg and the normalized index of hemolysis was 0.0054 +/- 0.0008 g/100 L. In in vivo study, the pump, with its blood-contacting surface coated with biocompatible 2-methacryloyloxyethyl phosphorylcholine polymer, was implanted in seven calves in left heart bypass. Pump performance was stable with a mean flow of 4.49 +/- 0.38 L/min at a mean speed of 2072.1 +/- 64.5 rpm. The maglev control revealed its stability in rotor position during normal activity by the calves. During 2 weeks of operation in two calves which survived the intended study period, no thrombus formation was seen inside the pump and levels of plasma free hemoglobin were maintained below 4 mg/dL. Although further experiments are required, the pump demonstrated the potential for sufficient and reliable performance and biocompatibility in meeting the requirements for cardiopulmonary bypass and 1-week circulatory support. PMID:19775262

Someya, Takeshi; Kobayashi, Mariko; Waguri, Satoshi; Ushiyama, Tomohiro; Nagaoka, Eiki; Hijikata, Wataru; Shinshi, Tadahiko; Arai, Hirokuni; Takatani, Setsuo

2009-09-01

199

EDITORIAL: Nanotechnology in vivo Nanotechnology in vivo  

NASA Astrophysics Data System (ADS)

Since the development of x-rays the ability to image inside our bodies has provided medicine with a potent diagnostic tool, as well as fascinating us with the eerie evidence of our mechanistic mortality. In December 2008 Osamu Shimomura, Martin Chalfie and Roger Y Tsien received a Nobel Prize for the discovery and development of the green fluorescent protein. The award recognised a new discovery that further facilitated our abilities to follow cellular activities and delve deeper into the workings of living organisms. Since the first observation of green fluorescent protein in jelly fish over thirty years ago, quantum dots have emerged as a potential alternative tool for imaging [1]. The advantages of quantum dots over organic dyes and fluorescent proteins include intense luminescence, high molar extinction coefficient, resistance to photobleaching, and broad excitation with narrow emission bands. However, one drawback for biological applications has been the layer of hydrophobic organic ligands often present at the surface as a result of the synthesis procedures. One solution to improve the solubility of quantum dots has been to conjugate them with a hydrophilic substance, as reported by Nie et al [2]. Chitosan is a hydrophilic, non-toxic, biocompatible and biodegradable substance and has been conjugated with quantum dots such as CdSe-ZnS [2] for bioassays and intracellular labelling. As well as luminescence, different nanoparticles present a variety of exceptional properties that render them useful in a range of bio applications, including MRI, drug delivery and cancer hyperthermia therapy. The ability to harness these various attributes in one system was reported by researchers in China, who incorporated magnetic nanoparticles, fluorescent quantum dots and pharmaceutical drugs into chitosan nanoparticles for multifunctional smart drug delivery systems [3]. More recently silicon quantum dots have emerged as a less cytotoxic alternative to CdSe for bio-imaging labels [4]. A surface hydroxyl group renders silicon quantum dots soluble in water and the photoluminescence can be made stable with oxygen-passivation. In addition, researchers in Japan have demonstrated how the initially modest yield in the preparation of silicon quantum dots can be improved to tens of milligrams per batch, thus further promoting their application in bio-imaging [5]. In the search for non-toxic quantum dots, researchers at the Amrita Centre for Nanoscience in India have prepared heavy metal-free quantum dot bio-probes based on single phase ZnS [6]. The quantum dots are selectively doped with metals, transition metals and halides to provide tuneable luminescence properties, and they are surface conjugated with folic acid for cancer targeting. The quantum dots were demonstrated to be water-soluble, non-toxic in normal and cancer cell lines, and have bright, tuneable luminescence. So far most of the quantum dots developed for bio-imaging have had excitation and emission wavelengths in the visible spectrum, which is highly absorbed by tissue. This limits imaging with these quantum dots to superficial tissues. This week, researchers in China and the US reported work developing functionalized dots for in vivo tumour vasculature in the infrared part of the spectrum [7]. In addition the quantum dots were functionalised with glycine-aspartic acid (RGD) peptides, which target the vasculature of almost all types of growing tumours, unlike antibody- or aptamer-mediated targeting strategies that are specific to a particular cancer type. In this issue, researchers in China and the US demonstrate a novel type of contrast agent for ultrasonic tumour imaging [8]. Contrast-enhanced ultrasonic tumour imaging extends the diagnostic and imaging capabilities of traditional techniques. The use of nanoparticles as ultrasound contrast agents exploits the presence of open pores in the range of 380 to 780 nm in tumour blood vessels, which enhance the permeability and retention of nanoparticles in the tumour vasculature. However, previous reports on techniques to generate

Demming, Anna

2010-04-01

200

Clinical application of in vivo treatment delivery verification based on PET/CT imaging of positron activity induced at high energy photon therapy  

NASA Astrophysics Data System (ADS)

The purpose of this study was to investigate in vivo verification of radiation treatment with high energy photon beams using PET/CT to image the induced positron activity. The measurements of the positron activation induced in a preoperative rectal cancer patient and a prostate cancer patient following 50 MV photon treatments are presented. A total dose of 5 and 8 Gy, respectively, were delivered to the tumors. Imaging was performed with a 64-slice PET/CT scanner for 30 min, starting 7 min after the end of the treatment. The CT volume from the PET/CT and the treatment planning CT were coregistered by matching anatomical reference points in the patient. The treatment delivery was imaged in vivo based on the distribution of the induced positron emitters produced by photonuclear reactions in tissue mapped on to the associated dose distribution of the treatment plan. The results showed that spatial distribution of induced activity in both patients agreed well with the delivered beam portals of the treatment plans in the entrance subcutaneous fat regions but less so in blood and oxygen rich soft tissues. For the preoperative rectal cancer patient however, a 2 ± (0.5) cm misalignment was observed in the cranial-caudal direction of the patient between the induced activity distribution and treatment plan, indicating a beam patient setup error. No misalignment of this kind was seen in the prostate cancer patient. However, due to a fast patient setup error in the PET/CT scanner a slight mis-position of the patient in the PET/CT was observed in all three planes, resulting in a deformed activity distribution compared to the treatment plan. The present study indicates that the induced positron emitters by high energy photon beams can be measured quite accurately using PET imaging of subcutaneous fat to allow portal verification of the delivered treatment beams. Measurement of the induced activity in the patient 7 min after receiving 5 Gy involved count rates which were about 20 times lower than that of a patient undergoing standard 18F-FDG treatment. When using a combination of short lived nuclides such as 15O (half-life: 2 min) and 11C (half-life: 20 min) with low activity it is not optimal to use clinical reconstruction protocols. Thus, it might be desirable to further optimize reconstruction parameters as well as to address hardware improvements in realizing in vivo treatment verification with PET/CT in the future. A significant improvement with regard to 15O imaging could also be expected by having the PET/CT unit located close to the radiation treatment room.

Janek Strååt, Sara; Andreassen, Björn; Jonsson, Cathrine; Noz, Marilyn E.; Maguire, Gerald Q., Jr.; Näfstadius, Peder; Näslund, Ingemar; Schoenahl, Frederic; Brahme, Anders

2013-08-01

201

A new graphical user interface for fast construction of computation phantoms and MCNP calculations: application to calibration of in vivo measurement systems.  

PubMed

The paper reports on a new utility for development of computational phantoms for Monte Carlo calculations and data analysis for in vivo measurements of radionuclides deposited in tissues. The individual properties of each worker can be acquired for a rather precise geometric representation of his (her) anatomy, which is particularly important for low energy gamma ray emitting sources such as thorium, uranium, plutonium and other actinides. The software discussed here enables automatic creation of an MCNP input data file based on scanning data. The utility includes segmentation of images obtained with either computed tomography or magnetic resonance imaging by distinguishing tissues according to their signal (brightness) and specification of the source and detector. In addition, a coupling of individual voxels within the tissue is used to reduce the memory demand and to increase the calculational speed. The utility was tested for low energy emitters in plastic and biological tissues as well as for computed tomography and magnetic resonance imaging scanning information. PMID:12132715

Borisov, N; Franck, D; de Carlan, L; Laval, L

2002-08-01

202

Development of a liquid chromatographic method for the quantification of paromomycin. Application to in vitro release and ex vivo permeation studies.  

PubMed

We have developed a reversed phase high performance liquid chromatography pulsed amperometric detection (RPHPLC-PAD) method for the determination of paromomycin. It is sensitive, repeatable, and selective without the pretreatment step. Trifluoroacetic acid-water was utilized as the eluent and detected by PAD under NaOH alkaline conditions. The paromomycin detection limit (S/N=3.3) was 2?gmL(-1) and the quantification limit (S/N=10) was 6?gmL(-1). Coefficients of linear regression were higher than 0.99 for concentrations between 6.25 and 200?gmL(-1). The intra and inter-day precision (RSD) was less than 6.5%. The average recoveries were 97.53-102.01%. The proposed HPLC-PAD method presented advantageous performance characteristics and it can be considered suitable for the evaluation of paromomycin loaded nanogel formulation in ex vivo permeation and in vitro release studies. PMID:24992924

Pujol-Brugués, A; Calpena-Campmany, A C; Riera-Lizandra, C; Halbaut-Bellowa, L; Clares-Naveros, B

2014-12-10

203

High-field MRI of single histological slices using an inductively coupled, self-resonant microcoil: application to ex vivo samples of patients with Alzheimer's disease.  

PubMed

A simple inductively coupled microcoil has been designed to image tissue samples placed on a microscope slide, samples which can subsequently be stained histologically. As the exact same tissue is used for MRI and histology, the two data sets can be compared without the need for complicated image registration techniques. The design can be integrated into any MRI system using existing commercial hardware. Compared with a commercial 25-mm-diameter birdcage, the signal-to-noise ratio was increased by a factor of 3.8, corresponding to an approximate 15-fold reduction in the data acquisition time. An example is shown of ex vivo samples from patients with Alzheimer's disease, in which the coregistration of highly sensitive iron staining and amyloid-? deposits is confirmed. PMID:20960578

Nabuurs, Rob J A; Hegeman, Ingrid; Natté, Remco; van Duinen, Sjoerd G; van Buchem, Mark A; van der Weerd, Louise; Webb, Andrew G

2011-05-01

204

Design, synthesis and binding properties of a fluorescent ????/???? integrin antagonist and its application as an in vivo probe for bone marrow haemopoietic stem cells.  

PubMed

The ?9?1 and ?4?1 integrin subtypes are expressed on bone marrow haemopoietic stem cells and have important roles in stem cell regulation and trafficking. Although the roles of ?4?1 integrin have been thoroughly investigated with respect to HSC function, the role of ?9?1 integrin remains poorly characterised. Small molecule fluorescent probes are useful tools for monitoring biological processes in vivo, to determine cell-associated protein localisation and activation, and to elucidate the mechanism of small molecule mediated protein interactions. Herein, we report the design, synthesis and integrin-dependent cell binding properties of a new fluorescent ?9?1 integrin antagonist (R-BC154), which was based on a series of N-phenylsulfonyl proline dipeptides and assembled using the Cu(I)-catalyzed azide alkyne cycloaddition (CuAAC) reaction. Using transfected human glioblastoma LN18 cells, we show that R-BC154 exhibits high nanomolar binding affinities to ?9?1 integrin with potent cross-reactivity against ?4?1 integrin under physiological mimicking conditions. On-rate and off-rate measurements revealed distinct differences in the binding kinetics between ?9?1 and ?4?1 integrins, which showed faster binding to ?4?1 integrin relative to ?9?1, but more prolonged binding to the latter. Finally, we show that R-BC154 was capable of binding rare populations of bone marrow haemopoietic stem and progenitor cells when administered to mice. Thus, R-BC154 represents a useful multi-purpose fluorescent integrin probe that can be used for (1) screening small molecule inhibitors of ?9?1 and ?4?1 integrins; (2) investigating the biochemical properties of ?9?1 and ?4?1 integrin binding and (3) investigating integrin expression and activation on defined cell phenotypes in vivo. PMID:24363056

Cao, Benjamin; Hutt, Oliver E; Zhang, Zhen; Li, Songhui; Heazlewood, Shen Y; Williams, Brenda; Smith, Jessica A; Haylock, David N; Savage, G Paul; Nilsson, Susan K

2014-02-14

205

Supramolecular quantum dot-porphyrin assemblies for biological oxygen sensing  

E-print Network

Generating metabolic profiles of tumors provides a spatiotemporal map of the concentration of key species to assess and quantify tumor growth, metabolism, and response to therapy. Because the tumor microenvironment is ...

Lemon, Christopher M. (Christopher Michael)

2013-01-01

206

FRET excited ratiometric oxygen sensing in living tissue  

PubMed Central

Dynamic analysis of oxygen (O2) has been limited by the lack of a real-time, quantitative, and biocompatible sensor. To address these demands, we designed a ratiometric optode matrix consisting of the phosphorescence quenching dye platinum (II) octaethylporphine ketone (PtOEPK) and nanocystal quantum dots (NQDs), which when embedded within an inert polymer matrix allows long-term pre-designed excitation through fluorescence resonance energy transfer (FRET). Depositing this matrix on various glass substrates allowed the development of a series of optical sensors able to measure interstitial oxygen concentration [O2] with several hundred millisecond temporal resolution in varying biological microdomains of active brain tissue. PMID:23333398

Ingram, Justin M.; Zhang, Chunfeng; Xu, Jian; Schiff, Steven J.

2013-01-01

207

Bio-inspired enol-degradation for multipurpose oxygen sensing.  

PubMed

Inspired by the enol-degradation of luciferin, a new oxygen sensor with oppositely changed color and fluorescence has been designed. This new reaction-based dual mode sensor can not only be used as a highly selective instant "fluorescence on" oxygen probe, but also as a freshness indicator of food or food materials by using its property of time-adjustable color fading. PMID:25234330

Zhang, Yu-Mo; Wang, Xiaojun; Li, Wen; Zhang, Weiran; Li, Minjie; Zhang, Sean Xiao-An

2014-10-01

208

Phosphorescent semiconductor nanocrystals and proteins for biological oxygen sensing  

E-print Network

Oxygen is required for cellular respiration by all complex life making it a key metabolic profiling factor in biological systems. Tumors are defined by hypoxia (low pO2), which has been shown to influence response to ...

McLaurin, Emily J. (Emily Jane)

2011-01-01

209

Immobilized Cytochrome P450 2C9 (CYP2C9): Applications for Metabolite Generation, Monitoring Protein-Protein Interactions, and Improving In-vivo Predictions Using Enhanced In-vitro Models  

NASA Astrophysics Data System (ADS)

Cytochrome P450 (P450) enzymes are a family of oxoferroreductase enzymes containing a heme moiety and are well known to be involved in the metabolism of a wide variety of endogenous and xenobiotic materials. It is estimated that roughly 75% of all pharmaceutical compounds are metabolized by these enzymes. Traditional reconstituted in-vitro incubation studies using recombinant P450 enzymes are often used to predict in-vivo kinetic parameters of a drug early in development. However, in many cases, these reconstituted incubations are prone to aggregation which has been shown to affect the catalytic activity of an enzyme. Moreover, the presence of other isoforms of P450 enzymes present in a metabolic incubation, as is the case with microsomal systems, may affect the catalytic activity of an enzyme through isoform-specific protein-protein interactions. Both of these effects may result in inaccurate prediction of in-vivo drug metabolism using in-vitro experiments. Here we described the development of immobilized P450 constructs designed to elucidate the effects of aggregation and protein-protein interactions between P450 isoforms on catalytic activities. The long term objective of this project is to develop a system to control the oligomeric state of Cytochrome P450 enzymes to accurately elucidate discrepancies between in vitro reconstituted systems and actual in vivo drug metabolism for the precise prediction of metabolic activity. This approach will serve as a system to better draw correlations between in-vivo and in-vitro drug metabolism data. The central hypothesis is that Cytochrome P450 enzymes catalytic activity can be altered by protein-protein interactions occurring between Cytochrome P450 enzymes involved in drug metabolism, and is dependent on varying states of protein aggregation. This dissertation explains the details of the construction and characterization of a nanostructure device designed to control the state of aggregation of a P450 enzyme. Moreover, applications of immobilized P450 enzyme constructs will also be used for monitoring protein-protein interaction and metabolite production with the use of immobilized-P450 bioreactor constructs. This work provides insight into the effect on catalytic activity caused by both P450 aggregation as well as isoform-specific protein-protein interactions and provides insight in the production of biosynthetically produced drug metabolites

Wollenberg, Lance A.

210

Tropisms of AAV for Subretinal Delivery to the Neonatal Mouse Retina and Its Application for In Vivo Rescue of Developmental Photoreceptor Disorders  

PubMed Central

Background Adeno-associated virus (AAV) is well established as a vehicle for in vivo gene transfer into the mammalian retina. This virus is promising not only for gene therapy of retinal diseases, but also for in vivo functional analysis of retinal genes. Previous reports have shown that AAV can infect various cell types in the developing mouse retina. However, AAV tropism in the developing retina has not yet been examined in detail. Methodology/Principal Findings We subretinally delivered seven AAV serotypes (AAV2/1, 2/2, 2/5, 2/8, 2/9, 2/10, and 2/11) of AAV-CAG-mCherry into P0 mouse retinas, and quantitatively evaluated the tropisms of each serotype by its infecting degree in retinal cells. After subretinal injection of AAV into postnatal day 0 (P0) mouse retinas, various retinal cell types were efficiently transduced with different AAVs. Photoreceptor cells were efficiently transduced with AAV2/5. Retinal cells, except for bipolar and Müller glial cells, were efficiently transduced with AAV2/9. Horizontal and/or ganglion cells were efficiently transduced with AAV2/1, AAV2/2, AAV2/8, AAV2/9 and AAV2/10. To confirm the usefulness of AAV-mediated gene transfer into the P0 mouse retina, we performed AAV-mediated rescue of the Cone-rod homeobox gene knockout (Crx KO) mouse, which exhibits an outer segment formation defect, flat electroretinogram (ERG) responses, and photoreceptor degeneration. We injected an AAV expressing Crx under the control of the Crx 2kb promoter into the neonatal Crx KO retina. We showed that AAV mediated-Crx expression significantly decreased the abnormalities of the Crx KO retina. Conclusion/Significance In the current study, we report suitable AAV tropisms for delivery into the developing mouse retina. Using AAV2/5 in photoreceptor cells, we demonstrated the possibility of gene replacement for the developmental disorder and subsequent degeneration of retinal photoreceptors caused by the absence of Crx. PMID:23335994

Watanabe, Satoshi; Sanuki, Rikako; Ueno, Shinji; Koyasu, Toshiyuki; Hasegawa, Toshiaki; Furukawa, Takahisa

2013-01-01

211

Multimodal Mn-doped I-III-VI quantum dots for near infrared fluorescence and magnetic resonance imaging: from synthesis to in vivo application  

NASA Astrophysics Data System (ADS)

The development of sensitive multimodal contrast agents is a key issue to provide better global, multi-scale images for diagnostic or therapeutic purposes. Here we present the synthesis of Zn-Cu-In-(S, Se)/Zn1-xMnxS core-shell quantum dots (QDs) that can be used as markers for both near-infrared fluorescence imaging and magnetic resonance imaging (MRI). We first present the synthesis of Zn-Cu-In-(S, Se) cores coated with a thick ZnS shell doped with various proportions of Mn. Their emission wavelengths can be tuned over the NIR optical window suitable for deep tissue imaging. The incorporation of manganese ions (up to a few thousand ions per QD) confers them a paramagnetic character, as demonstrated by structural analysis and electron paramagnetic resonance spectroscopy. These QDs maintain their optical properties after transfer to water using ligand exchange. They exhibit T1-relaxivities up to 1400 mM-1 [QD] s-1 at 7 T and 300 K. We finally show that these QDs are suitable multimodal in vivo probes and demonstrate MRI and NIR fluorescence detection of regional lymph nodes in mice.The development of sensitive multimodal contrast agents is a key issue to provide better global, multi-scale images for diagnostic or therapeutic purposes. Here we present the synthesis of Zn-Cu-In-(S, Se)/Zn1-xMnxS core-shell quantum dots (QDs) that can be used as markers for both near-infrared fluorescence imaging and magnetic resonance imaging (MRI). We first present the synthesis of Zn-Cu-In-(S, Se) cores coated with a thick ZnS shell doped with various proportions of Mn. Their emission wavelengths can be tuned over the NIR optical window suitable for deep tissue imaging. The incorporation of manganese ions (up to a few thousand ions per QD) confers them a paramagnetic character, as demonstrated by structural analysis and electron paramagnetic resonance spectroscopy. These QDs maintain their optical properties after transfer to water using ligand exchange. They exhibit T1-relaxivities up to 1400 mM-1 [QD] s-1 at 7 T and 300 K. We finally show that these QDs are suitable multimodal in vivo probes and demonstrate MRI and NIR fluorescence detection of regional lymph nodes in mice. Electronic supplementary information (ESI) available: Determination of Mn content; magnetization measurements; additional TEM and spectroscopic data; additional NIR fluorescence image; MTT assay results. See DOI: 10.1039/c4nr02239d

Sitbon, Gary; Bouccara, Sophie; Tasso, Mariana; Francois, Aurélie; Bezdetnaya, Lina; Marchal, Frédéric; Beaumont, Marine; Pons, Thomas

2014-07-01

212

The application of hyaluronic acid-derivatized carbon nanotubes in hematoporphyrin monomethyl ether-based photodynamic therapy for in vivo and in vitro cancer treatment.  

PubMed

Carbon nanotubes (CNTs) have shown great potential in both photothermal therapy and drug delivery. In this study, a CNT derivative, hyaluronic acid-derivatized CNTs (HA-CNTs) with high aqueous solubility, neutral pH, and tumor-targeting activity, were synthesized and characterized, and then a new photodynamic therapy agent, hematoporphyrin monomethyl ether (HMME), was adsorbed onto the functionalized CNTs to develop HMME-HA-CNTs. Tumor growth inhibition was investigated both in vivo and in vitro by a combination of photothermal therapy and photodynamic therapy using HMME-HA-CNTs. The ability of HMME-HA-CNT nanoparticles to combine local specific photodynamic therapy with external near-infrared photothermal therapy significantly improved the therapeutic efficacy of cancer treatment. Compared with photodynamic therapy or photothermal therapy alone, the combined treatment demonstrated a synergistic effect, resulting in higher therapeutic efficacy without obvious toxic effects to normal organs. Overall, it was demonstrated that HMME-HA-CNTs could be successfully applied to photodynamic therapy and photothermal therapy simultaneously in future tumor therapy. PMID:23843694

Shi, Jinjin; Ma, Rourou; Wang, Lei; Zhang, Jing; Liu, Ruiyuan; Li, Lulu; Liu, Yan; Hou, Lin; Yu, Xiaoyuan; Gao, Jun; Zhang, Zhenzhong

2013-01-01

213

The application of hyaluronic acid-derivatized carbon nanotubes in hematoporphyrin monomethyl ether-based photodynamic therapy for in vivo and in vitro cancer treatment  

PubMed Central

Carbon nanotubes (CNTs) have shown great potential in both photothermal therapy and drug delivery. In this study, a CNT derivative, hyaluronic acid-derivatized CNTs (HA-CNTs) with high aqueous solubility, neutral pH, and tumor-targeting activity, were synthesized and characterized, and then a new photodynamic therapy agent, hematoporphyrin monomethyl ether (HMME), was adsorbed onto the functionalized CNTs to develop HMME-HA-CNTs. Tumor growth inhibition was investigated both in vivo and in vitro by a combination of photothermal therapy and photodynamic therapy using HMME-HA-CNTs. The ability of HMME-HA-CNT nanoparticles to combine local specific photodynamic therapy with external near-infrared photothermal therapy significantly improved the therapeutic efficacy of cancer treatment. Compared with photodynamic therapy or photothermal therapy alone, the combined treatment demonstrated a synergistic effect, resulting in higher therapeutic efficacy without obvious toxic effects to normal organs. Overall, it was demonstrated that HMME-HA-CNTs could be successfully applied to photodynamic therapy and photothermal therapy simultaneously in future tumor therapy. PMID:23843694

Shi, Jinjin; Ma, Rourou; Wang, Lei; Zhang, Jing; Liu, Ruiyuan; Li, Lulu; Liu, Yan; Hou, Lin; Yu, Xiaoyuan; Gao, Jun; Zhang, Zhenzhong

2013-01-01

214

Extracellularly tumor-activated prodrugs for the selective chemotherapy of cancer: application to doxorubicin and preliminary in vitro and in vivo studies.  

PubMed

Oligopeptidic derivatives of anthracyclines unable to penetrate cells were prepared and screened for their stability in human blood and their reactivation by peptidases secreted by cancer cells. N-beta-alanyl-L-leucyl-L-alanyl-L-leucyl-doxorubicin was selected as a new candidate prodrug. The NH2-terminal beta-alanine allows a very good blood stability. A two-step activation by peptidases found in conditioned media of cancer cells ultimately yields N-L-leucyl-doxorubicin. In vitro, when MCF-7/6 cancer cells are exposed to the prodrug, they accumulate about 14 times more doxorubicin than MRC-5 normal fibroblasts, whereas when exposed to doxorubicin the uptake is slightly higher in fibroblasts than in MCF-7/6 cells. This increased specificity of the prodrug over doxorubicin was confirmed in cytotoxicity assays using the same cell types. In vivo, the prodrug proved about nine times less toxic than doxorubicin in the normal mouse and also much more efficient in two different experimental chemotherapy models of human breast tumors. PMID:11306455

Trouet, A; Passioukov, A; Van derpoorten, K; Fernandez, A M; Abarca-Quinones, J; Baurain, R; Lobl, T J; Oliyai, C; Shochat, D; Dubois, V

2001-04-01

215

Very small embryonic-like stem-cell optimization of isolation protocols: an update of molecular signatures and a review of current in vivo applications  

PubMed Central

As the theory of stem cell plasticity was first proposed, we have explored an alternative hypothesis for this phenomenon: namely that adult bone marrow (BM) and umbilical cord blood (UCB) contain more developmentally primitive cells than hematopoietic stem cells (HSCs). In support of this notion, using multiparameter sorting we were able to isolate small Sca1+Lin?CD45? cells and CD133+Lin?CD45? cells from murine BM and human UCB, respectively, which were further enriched for the detection of various early developmental markers such as the SSEA antigen on the surface and the Oct4 and Nanog transcription factors in the nucleus. Similar populations of cells have been found in various organs by our team and others, including the heart, brain and gonads. Owing to their primitive cellular features, such as the high nuclear/cytoplasm ratio and the presence of euchromatin, they are called very small embryonic-like stem cells (VSELs). In the appropriate in vivo models, VSELs differentiate into long-term repopulating HSCs, mesenchymal stem cells (MSCs), lung epithelial cells, cardiomyocytes and gametes. In this review, we discuss the most recent data from our laboratory and other groups regarding the optimal isolation procedures and describe the updated molecular characteristics of VSELs. PMID:24232255

Shin, Dong-Myung; Suszynska, Malwina; Mierzejewska, Kasia; Ratajczak, Janina; Ratajczak, Mariusz Z

2013-01-01

216

Application of Escherichia coli phage K1E DNA-dependent RNA polymerase for in vitro RNA synthesis and in vivo protein production in Bacillus megaterium.  

PubMed

Gene "7" of Escherichia coli phage K1E was proposed to encode a novel DNA-dependent RNA polymerase (RNAP). The corresponding protein was produced recombinantly, purified to apparent homogeneity via affinity chromatography, and successfully employed for in vitro RNA synthesis. Optimal assay conditions (pH 8, 37 degrees C, 10 mM magnesium chloride and 1.3 mM spermidine) were established. The corresponding promoter regions were identified on the phage genome and summarized in a sequence logo. Surprisingly, next to K1E promoters, the SP6 promoter was also recognized efficiently in vitro by K1E RNAP, while the T7 RNAP promoter was not recognized at all. Based on these results, a system for high-yield in vitro RNA synthesis using K1E RNAP was established. The template plasmid is a pUC18 derivative, which enables blue/white screening for positive cloning of the target DNA. Production of more than 5 microg of purified RNA per microgram plasmid DNA was achieved. Finally, in vivo protein production systems for Bacillus megaterium were established based on K1E and SP6 phage RNAP transcription. Up to 61.4 mg g (CDW) (-1) (K1E RNAP) of the reporter protein Gfp was produced in shaking flask cultures of B. megaterium. PMID:20596705

Stammen, Simon; Schuller, Franziska; Dietrich, Sylvia; Gamer, Martin; Biedendieck, Rebekka; Jahn, Dieter

2010-09-01

217

Determination of Oxycodone, Noroxycodone and Oxymorphone by High-Performance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry in Human Matrices: In vivo and In vitro Applications  

PubMed Central

The opioid analgesic oxycodone is widely abused and increasingly associated with overdose deaths. A sensitive analytical method was developed for oxycodone and its metabolites, noroxycodone and oxymorphone, in human plasma, urine (±enzymatic hydrolysis at 50°C for 16 h) and liver microsomes (HLMs). Liquid–liquid extraction was followed by high-performance liquid chromatography–electrospray ionization-tandem mass spectrometry. The calibration range was 0.2–250 ng/mL for plasma and HLM and 10–5000 ng/mL for urine. Intra- and interrun accuracies were within 13.3% of target; precisions were within 12.8% for all matrices. Recoveries from plasma were: oxycodone, 75.6%; noroxycodone, 37.4% and oxymorphone, 18.2%. Analytes exhibited room temperature stability in plasma and urine up to 24 h, and freeze–thaw stability in plasma up to three cycles. In 24-h hydrolyzed urine from subjects administered intranasal oxycodone (30 mg/70 kg, n = 5), mean concentrations (ng/mL) and % daily doses excreted were: oxycodone, 1150, 6.53%; noroxycodone, 1330, 7.81% and oxymorphone, 3000, 17.1%. Oxycodone incubated with HLM produced more noroxycodone than oxymorphone. With a panel of recombinant human cytochrome P450s (CYPs), CYP2C18 and CYP3A4 produced the most noroxycodone, whereas CYP2D6 produced the most oxymorphone. These results demonstrate a new method suitable for both in vivo and in vitro metabolism and pharmacokinetic studies of oxycodone. PMID:23743505

Fang, Wenfang B.; Lofwall, Michelle R.; Walsh, Sharon L.; Moody, David E.

2013-01-01

218

Multimodal Mn-doped I-III-VI quantum dots for near infrared fluorescence and magnetic resonance imaging: from synthesis to in vivo application.  

PubMed

The development of sensitive multimodal contrast agents is a key issue to provide better global, multi-scale images for diagnostic or therapeutic purposes. Here we present the synthesis of Zn-Cu-In-(S, Se)/Zn(1-x)Mn(x)S core-shell quantum dots (QDs) that can be used as markers for both near-infrared fluorescence imaging and magnetic resonance imaging (MRI). We first present the synthesis of Zn-Cu-In-(S, Se) cores coated with a thick ZnS shell doped with various proportions of Mn. Their emission wavelengths can be tuned over the NIR optical window suitable for deep tissue imaging. The incorporation of manganese ions (up to a few thousand ions per QD) confers them a paramagnetic character, as demonstrated by structural analysis and electron paramagnetic resonance spectroscopy. These QDs maintain their optical properties after transfer to water using ligand exchange. They exhibit T1-relaxivities up to 1400 mM(-1) [QD] s(-1) at 7 T and 300 K. We finally show that these QDs are suitable multimodal in vivo probes and demonstrate MRI and NIR fluorescence detection of regional lymph nodes in mice. PMID:24980473

Sitbon, Gary; Bouccara, Sophie; Tasso, Mariana; Francois, Aurélie; Bezdetnaya, Lina; Marchal, Frédéric; Beaumont, Marine; Pons, Thomas

2014-08-01

219

In Vivo skin hydration and anti-erythema effects of Aloe vera, Aloe ferox and Aloe marlothii gel materials after single and multiple applications  

PubMed Central

Objective: To investigate the skin hydrating and anti-erythema activity of gel materials from Aloe marlothii A. Berger and A. ferox Mill. in comparison to that of Aloe barbadensis Miller (Aloe vera) in healthy human volunteers. Materials and Methods: Aqueous solutions of the polisaccharidic fractions of the selected aloe leaf gel materials were applied to the volar forearm skin of female subjects. The hydration effect of the aloe gel materials were measured with a Corneometer® CM 825, Visioscan® VC 98 and Cutometer® dual MPA 580 after single and multiple applications. The Mexameter® MX 18 was used to determine the anti-erythema effects of the aloe material solutions on irritated skin areas. Results: The A. vera and A. marlothii gel materials hydrated the skin after a single application, whereas the A. ferox gel material showed dehydration effects compared to the placebo. After multiple applications all the aloe materials exhibited dehydration effects on the skin. Mexameter® readings showed that A. vera and A. ferox have anti-erythema activity similar to that of the positive control group (i.e. hydrocortisone gel) after 6 days of treatment. Conclusion: The polysaccharide component of the gel materials from selected aloe species has a dehydrating effect on the skin after multiple applications. Both A. vera and A. ferox gel materials showed potential to reduce erythema on the skin similar to that of hydrocortisone gel. PMID:24991119

Fox, Lizelle T.; du Plessis, Jeanetta; Gerber, Minja; van Zyl, Sterna; Boneschans, Banie; Hamman, Josias H.

2014-01-01

220

Optimization of In Vivo Confocal Autofluorescence Imaging of the Ocular Fundus in Mice and Its Application to Models of Human Retinal Degeneration  

PubMed Central

Purpose. To investigate the feasibility and to identify sources of experimental variability of quantitative and qualitative fundus autofluorescence (AF) assessment in mice. Methods. Blue (488 nm) and near-infrared (790 nm) fundus AF imaging was performed in various mouse strains and disease models (129S2, C57Bl/6, Abca4?/?, C3H-Pde6brd1/rd1, Rho?/?, and BALB/c mice) using a commercially available scanning laser ophthalmoscope. Gray-level analysis was used to explore factors influencing fundus AF measurements. Results. A contact lens avoided cataract development and resulted in consistent fundus AF recordings. Fundus illumination and magnification were sensitive to changes of the camera position. Standardized adjustment of the recorded confocal plane and consideration of the pupil area allowed reproducible recording of fundus AF from the retinal pigment epithelium with an intersession coefficient of repeatability of ±22%. Photopigment bleaching occurred during the first 1.5 seconds of exposure to 488 nm blue light (?10 mW/cm2), resulting in an increase of fundus AF. In addition, there was a slight decrease in fundus AF during prolonged blue light exposure. Fundus AF at 488 nm was low in animals with an absence of a normal visual cycle, and high in BALB/c and Abca4?/? mice. Degenerative alterations in Pde6brd1/rd1 and Rho?/? were reminiscent of findings in human retinal disease. Conclusions. Investigation of retinal phenotypes in mice is possible in vivo using standardized fundus AF imaging. Correlation with postmortem analysis is likely to lead to further understanding of human disease phenotypes and of retinal degenerations in general. Fundus AF imaging may be useful as an outcome measure in preclinical trials, such as for monitoring effects aimed at lowering lipofuscin accumulation in the retinal pigment epithelium. PMID:22169101

Issa, Peter Charbel; Singh, Mandeep S.; Lipinski, Daniel M.; Chong, Ngaihang V.; Delori, Francois C.; Barnard, Alun R.; MacLaren, Robert E.

2012-01-01

221

Radical protection in the visible and infrared by a hyperforin-rich cream--in vivo versus ex vivo methods.  

PubMed

The formation of radicals plays an important role in the development of atopic eczema or barrier-disrupted skin. We evaluated the radical scavenging effect of a cream containing a Hypericum perforatum extract rich in hyperforin in a double-blind placebo-controlled study on 11 healthy volunteers. Electron paramagnetic resonance spectroscopy was applied to determine radical formation during VIS/NIR irradiation of the inner forearm. The results were compared to ex vivo investigations on excised porcine ear skin after a single application of the creams. The non-treated skin was measured as control. The absolute values and the kinetics are not comparable for ex vivo and in vivo radical formation. Whereas in vivo, the radical production decreases with time, it remains stable ex vivo over the investigated timescale. Nevertheless, ex vivo methods could be developed to estimate the protection efficiency of creams. In vivo as well as ex vivo, the radical formation could be reduced by almost 80% when applying the hyperforin-rich cream onto the skin, whereas placebo resulted in about 60%. In vivo, a daylong protection effect could be validated after a 4-week application time of the cream indicating that a regular application is necessary to obtain the full effect. PMID:23614743

Arndt, Sophia; Haag, Stefan F; Kleemann, Anke; Lademann, Juergen; Meinke, Martina C

2013-05-01

222

Fluorescent Multiblock ?-Conjugated Polymer Nanoparticles for In Vivo Tumor Targeting  

PubMed Central

Highly fluorescent multiblock conjugated polymer nanoparticles with folic acid surface ligands are highly effective for bioimaging and in vivo tumor targeting. The targeted nanoparticles were preferentially localized in tumor cells in vivo, thereby illustrating their potential for diagnostic and therapeutic applications. PMID:23794490

Ahmed, Eilaf; Morton, Stephen W.

2014-01-01

223

In-vivo optical investigation of psoriasis  

NASA Astrophysics Data System (ADS)

Psoriasis is an autoimmune disease of the skin characterized by hyperkeratosis, hyperproliferation of the epidermis, inflammatory cell accumulation and increased dilatation of dermal papillary blood vessels. Cases of psoriasis were investigated in vivo with optical means in order to evaluate the potential of in vivo optical biopsy. A Polarization Multispectral Dermoscope was employed for the macroscopic observation. Features such as the 'dotted' blood vessels pattern was observed with high contrast. The average size of dot vessels in Psoriasis was measured to be 974 ?m2 which is much higher compared to healthy skin. High resolution image sections of the epidermis and the dermis were produced with a custom made Multiphoton Microscope. Imaging extended from the surface of the lesion down to the papillary dermis, at a depth of 200 ?m. In the epidermis, a characteristic morphology of the stratum corneum found only in Psoriasis was revealed. Additionally, the cytoplasmic area of the cells in the stratum spinosum layer was found to be smaller than normal. In the dermis the morphological features were more pronounced, where the elongated dermal papillae dominated the papillary layer. Their length exceeds 100?m, which is a far greater value compared to that of healthy skin. These in vivo observations are consistent with the ex vivo histopathological observations, supporting both the applicability and potentiality of multispectral dermoscopy and multiphoton microscopy in the field of in vivo optical investigation and biopsy of skin.

Kapsokalyvas, Dimitrios; Cicchi, Riccardo; Bruscino, Nicola; Alfieri, Domenico; Massi, Daniela; Lotti, Torello; Pavone, Francesco S.

2011-03-01

224

Protein crystallization in vivo  

E-print Network

Protein crystallization in vivo provides some fascinating examples of biological self-assembly. Here, we provide a selective survey to show the diversity of functions for which protein crystals are used, and the physical properties of the crystals thatare exploited. Where known, we emphasize how the nature of the protein-protein interactions leads to control of the crystallization behaviour.

Jonathan P. K. Doye; Wilson C. K. Poon

2005-10-03

225

Ex Vivo and In Vivo Administration of Fluorescent CNA35 Specifically Marks Cardiac Fibrosis.  

PubMed

AbstractCardiac fibrosis is a major hallmark of cardiac diseases. For evaluation of cardiac fibrosis, the development of highly specific and preferably noninvasive methods is desired. Our aim was to evaluate CNA35, a protein known to specifically bind to collagen, as a specific marker of cardiac fibrosis. Fluorescently labeled CNA35 was applied ex vivo on tissue sections of fibrotic rat, mouse, and canine myocardium. After quantification of CNA35, sections were examined with picrosirius red (PSR) and compared to CNA35. Furthermore, fluorescently labeled CNA35 was administered in vivo in mice. Hearts were isolated, and CNA35 labeling was examined in tissue sections. Serial sections were histologically examined with PSR. Ex vivo application of CNA35 showed specific binding to collagen and a high correlation with PSR (Pearson r ?=? .86 for mice/rats and r ?=? .98 for canine; both p < .001). After in vivo administration, CNA35 labeling was observed around individual cardiomyocytes, indicating its ability to penetrate cardiac endothelium. High correlation was observed between CNA35 and PSR (r ?=? .91, p < .001). CNA35 specifically binds to cardiac collagen and can cross the endothelial barrier. Therefore, labeled CNA35 is useful to specifically detect collagen both ex vivo and in vivo and potentially can be converted to a noninvasive method to detect cardiac fibrosis. PMID:25249247

de Jong, Sanne; van Middendorp, Lars B; Hermans, Robin H A; de Bakker, Jacques M T; Bierhuizen, Marti F A; Prinzen, Frits W; van Rijen, Harold V M; Losen, Mario; Vos, Marc A; van Zandvoort, Marc A M J

2014-09-01

226

In Vivo Sound Velocity in Reflection  

Microsoft Academic Search

The measurement accuracy of sound velocity by reflection mode methods is estimated theoretically for the several v ersions of the technique suitable for in vivo application. Focal fields used in versions of the focus adjustment method (FAM) are analyzed b y computer simulation as well as the incoherent crossed-beam method (ICM) and the crossed-transmission-andreception-beam method (CTRM) for the same acoustic

T. Ogawa; S. Umemural; K. Katakura; H. Ikeda; M. Kodama; H. Hayashi

1987-01-01

227

Bi-layer composite dressing of gelatin nanofibrous mat and poly vinyl alcohol hydrogel for drug delivery and wound healing application: in-vitro and in-vivo studies.  

PubMed

Present investigation involves the development of a bi-layer dressing of gelatin nanofibrous mat loaded with epigallocatechin gallate (EGCG)/poly vinyl alcohol (PVA) hydrogel and its in-vivo evaluation on full-thickness excision wounds in experimental Wistar rats. Nanomorphological observation, porosity, effect of crosslinking on tensile strength, physical stability and drug release profile in phosphate buffer and biocompatibility aspects of electrospun nanomat were investigated by various physico-chemical tools. EGCGa release profile was found to increase from 2-4 days with decreasing crosslinking time from 15 to 5 min. PVA hydrogels were prepared by freeze-thaw method and has been utilized as a protective and hydrating outer layer of the bi-layer dressing. Topical application of bi-layer composite dressing loaded with EGCG improve the healing rate in experimental rats as acute wounds model which was evidenced by significant increase in DNA (approximately 42%), total protein (approximately 32%), hydroxyproline (approximately 26%) and hexosamine approximately 24%) contents. A faster wound contraction was observed in wounds treated with composite dressing from approximately 14% to 47%. Histopathological examination revealed significant improvement in angiogenesis, re-epithelialization and less inflammatory response in comparison to control. Van-Gieson's collagen stains revealed matured, compact and parallel deposition of collagen fibrils on day 12. These results were supported by up-regulated expressions of matrix metalloproteinase (MMPs-2 and 9) by gelatin zymography. Control release of EGCG, 3D porous architecture of nanofibrous scaffolds as well as moist microenvironment provides ideal conditions for uninterrupted wound healing. PMID:23980498

Jaiswal, Maneesh; Gupta, Asheesh; Agrawal, Ashwini K; Jassal, Manjeet; Dinda, Amit Kr; Koul, Veena

2013-09-01

228

In vivo dosimetry for IMRT  

SciTech Connect

In vivo dosimetry has a well established role in the quality assurance of 2D radiotherapy and 3D conformal radiotherapy. The role of in vivo dosimetry for IMRT is not as well established. IMRT introduces a range of technical issues that complicate in vivo dosimetry. The first decade or so of IMRT implementation has largely relied upon pre-treatment phantom based dose verification. During that time, several new devices and techniques for in vivo dosimetry have emerged with the promise of providing the ultimate form of IMRT dose verification. Solid state dosimeters continue to dominate the field of in vivo dosimetry in the IMRT era. In this report we review the literature on in vivo dosimetry for IMRT, with an emphasis on clinical evidence for different detector types. We describe the pros and cons of different detectors and techniques in the IMRT setting and the roles that they are likely to play in the future.

Vial, Philip [Department of Medical Physics, Liverpool Cancer Therapy Centre (Australia); Institute of Medical Physics, School of Physics, University of Sydney (Australia)

2011-05-05

229

Electrodeposition of platinum-iridium coatings and nanowires for neurostimulating applications: Fabrication, characterization and in-vivo retinal stimulation/recording. EIS studies of hexavalent and trivalent chromium based military coating systems  

NASA Astrophysics Data System (ADS)

The studies presented in this thesis are composed of two different projects demonstrated in two different parts. The first part of this thesis represents an electrochemical approach to possible improvements of the interface between an implantable device and biological tissue. The second part of this thesis represents electrochemical impedance spectroscopy (EIS) studies on the corrosion resistance behavior of different types of polymer coated Al2024 alloys. In the first part of this thesis, a broad range of investigations on the development of an efficient and reproducible electrochemical deposition method for fabrication of thin-film platinum-iridium alloys were performed. The developed method for production of dense films was then modified to produce very high surface area coatings with ultra-low electrochemical impedance characteristics. The high-surface area platinum-iridium coating was applied on microelectrode arrays for chronic in-vitro stimulation. Using the same method of producing dense films, platinum-iridium nanowires were fabricated using Anodized Aluminum Oxide (AAO) templates for hermetic packaging applications to be used in implantable microelectronics. The implantable microelectronics will be used to perform data reception and transmission management, power recovery, digital processing and analog output of stimulus current. Finally, in-vivo electrical stimulation tests were performed on an animal retina using high surface-area platinum-iridium coated single microelectrodes to verify the charge transfer characteristics of the coatings. In the second part of this thesis, three different sets of samples with different combinations of pretreatments, primers with the same type of topcoat were tested in 0.5 N NaCl for period of 30 days. The surface changes measured by EIS as a function of time were then analyzed. The analysis of the fit parameters of the impedance spectra showed that the different primers had the most effect on the corrosion protection properties of the coatings in which the primers with hexavalent chromium ions (Cr6+) provided better corrosion protection compared to primers with trivalent chromium ions (Cr3+). After 30 days of the exposure of the samples in 0.5 N NaCl, one sample from each set of samples was scribed and exposed to 0.5 N NaCl for 3 days. Analysis of the impedance spectra revealed that the samples with chromium conversion coating pretreatment and hexavalent chromium primer showed "self healing" characteristics and provided better corrosion protection on the scribed areas compared to the scribed samples with trivalent chromium pretreatment and non-hexavalent chromium primer.

Petrossians, Artin

230

Applications  

NASA Astrophysics Data System (ADS)

Economic incentives have spurred numerous applications of genetically engineered organisms in manufacture of pharmaceuticals and industrial chemicals. These successes, involving a variety of methods of genetic manipulation, have dispelled early fears that genetic engineering could not be handled safely, even in the laboratory. Consequently, the potential for applications in the wider environment without physical containment is being considered for agriculture, mining, pollution control, and pest control. These proposed applications range from modest extensions of current plant breeding techniques for new disease-resistant species to radical combinations of organisms (for example, nitrogen-fixing corn plants). These applications raise concerns about potential ecological impacts (see chapter 5), largely because of adverse experiences with both deliberate and inadvertent introductions of nonindigenous species.

Stern, Arthur M.

1986-07-01

231

Imaging schistosomes in vivo  

PubMed Central

Schistosomes are intravascular, parasitic helminths that cause a chronic, often debilitating disease afflicting over 200 million people in over 70 countries. Here we describe novel imaging methods that, for the first time, permit visualization of live schistosomes within their living hosts. The technology centers on fluorescent agent uptake and activation in the parasite’s gut, and subsequent detection and signal quantitation using fluorescence molecular tomography (FMT). There is a strong positive correlation between the signal detected and parasite number. Schistosoma mansoni parasites of both sexes recovered from infected experimental animals exhibit vivid fluorescence throughout their intestines. Likewise, the remaining important human schistosome parasites, S. japonicum and S. hematobium, also exhibit gut fluorescence when recovered from infected animals. Imaging has been used to efficiently document the decline in parasite numbers in infected mice treated with the antischistosome drug praziquantel. This technology will provide a unique opportunity both to help rapidly identify much-needed, novel antischistosome therapies and to gain direct visual insight into the intravascular lives of the major schistosome parasites of humans.—Krautz-Peterson, G., Ndegwa, D., Vasquez, K., Korideck, H., Zhang, J., Peterson, J. D., Skelly, P. J. Imaging schistosomes in vivo. PMID:19346298

Krautz-Peterson, Greice; Ndegwa, David; Vasquez, Kristine; Korideck, Houari; Zhang, Jun; Peterson, Jeffrey D.; Skelly, Patrick J.

2009-01-01

232

Nanocrystal targeting in vivo  

NASA Astrophysics Data System (ADS)

Inorganic nanostructures that interface with biological systems have recently attracted widespread interest in biology and medicine. Nanoparticles are thought to have potential as novel intravascular probes for both diagnostic (e.g., imaging) and therapeutic purposes (e.g., drug delivery). Critical issues for successful nanoparticle delivery include the ability to target specific tissues and cell types and escape from the biological particulate filter known as the reticuloendothelial system. We set out to explore the feasibility of in vivo targeting by using semiconductor quantum dots (qdots). Qdots are small (<10 nm) inorganic nanocrystals that possess unique luminescent properties; their fluorescence emission is stable and tuned by varying the particle size or composition. We show that ZnS-capped CdSe qdots coated with a lung-targeting peptide accumulate in the lungs of mice after i.v. injection, whereas two other peptides specifically direct qdots to blood vessels or lymphatic vessels in tumors. We also show that adding polyethylene glycol to the qdot coating prevents nonselective accumulation of qdots in reticuloendothelial tissues. These results encourage the construction of more complex nanostructures with capabilities such as disease sensing and drug delivery.

Åkerman, Maria E.; Chan, Warren C. W.; Laakkonen, Pirjo; Bhatia, Sangeeta N.; Ruoslahti, Erkki

2002-10-01

233

In vivo hybridization of technetium-99m-labeled peptide nucleic acid (PNA)  

Microsoft Academic Search

Hybridization of a radiolabeled single-stranded DNA oligonucleotide with its single-stranded complement in vivo has not yet been convincingly demonstrated. A contributing factor may be unfavorable in vivo properties of the phosphodiester and phosphorothioate DNAs. Peptide nucleic acid (PNA) oligomers have been reported to possess in vivo properties more suitable for radiopharmaceutical applications. We have radiolabeled an amine-derivatized 15-base PNA oligomer

G. Mardirossian; K. Lei; M. Rusckowski

1997-01-01

234

Programmable nanoparticle functionalization for in vivo targeting  

PubMed Central

The emerging demand for programmable functionalization of existing base nanocarriers necessitates development of an efficient approach for cargo loading that avoids nanoparticle redesign for each individual application. Herein, we demonstrate in vivo a postformulation strategy for lipidic nanocarrier functionalization with the use of a linker peptide, which rapidly and stably integrates cargos into lipidic membranes of nanocarriers after simple mixing through a self-assembling process. We exemplified this strategy by generating a VCAM-1-targeted perfluorocarbon nanoparticle for in vivo targeting in atherosclerosis (ApoE-deficient) and breast cancer (STAT-1-deficient) models. In the atherosclerotic model, a 4.1-fold augmentation in binding to affected aortas was observed for targeted vs. nontargeted nanoparticles (P<0.0298). Likewise, in the breast cancer model, a 4.9-fold increase in the nanoparticle signal from tumor vasculature was observed for targeted vs. nontargeted nanoparticles (P<0.0216). In each case, the nanoparticle was registered with fluorine (19F) magnetic resonance spectroscopy of the nanoparticle perfluorocarbon core, yielding a quantitative estimate of the number of tissue-bound nanoparticles. Because other common nanocarriers with lipid coatings (e.g., liposomes, micelles, etc.) can employ this strategy, this peptide linker postformulation approach is applicable to more than half of the available nanosystems currently in clinical trials or clinical uses.—Pan, H., Myerson, J. W., Hu, L., Marsh, J. N., Hou K., Scott, M. J., Allen, J. S., Hu, G., San Roman, S., Lanza, G. M., Schreiber, R. D., Schlesinger, P. H., Wickline, S. A. Programmable nanoparticle functionalization for in vivo targeting. PMID:23047896

Pan, Hua; Myerson, Jacob W.; Hu, Lingzhi; Marsh, Jon N.; Hou, Kirk; Scott, Michael J.; Allen, John S.; Hu, Grace; San Roman, Susana; Lanza, Gregory M.; Schreiber, Robert D.; Schlesinger, Paul H.; Wickline, Samuel A.

2013-01-01

235

Polycation liposome-mediated gene transfer in vivo  

Microsoft Academic Search

The polycation liposome (PCL), a recently developed gene transfer system, is simply prepared by a modification of liposomes with cetylated polyethylenimine (PEI), and shows remarkable transgene efficiency with low cytotoxicity. In the present study, we investigated the applicability of PCLs for in vivo gene transfer, since the PCL-mediated transgene efficiency was found to be maintained in the presence of serum.

Mitsuo Matsuura; Yukako Yamazaki; Mayu Sugiyama; Masami Kondo; Hidetsugu Ori; Mamoru Nango; Naoto Oku

2003-01-01

236

In Vivo Monitoring of Fluorescently Labeled Cancer Cells  

Microsoft Academic Search

Whole animal in vivo imaging has contributed significantly to the detection of disease progression and drug efficacy for the past several years (1). With the introduction of sensitive imaging instruments, applications in fluorescent imaging have expanded to monitoring tumor cell growth and gene expression. The new fluorescent proteins have improved brightness, photostability and better tissue penetration of signals at a

Eva Barton; Angel Ang; Kevin Francis; Jae-Beom Kim

237

Improving Privacy on Android Smartphones Through In-Vivo Bytecode Instrumentation  

E-print Network

Improving Privacy on Android Smartphones Through In-Vivo Bytecode Instrumentation Alexandre Bartel In this paper we claim that a widely applicable and efficient means to fight against malicious mobile Android- tisement remover. Both prototypes improve the privacy of Android systems thanks to in-vivo bytecode

Paris-Sud XI, Université de

238

Steady-state theory for quantitative microdialysis of solutes and water in vivo and in vitro  

Microsoft Academic Search

A mathematical framework was developed to provide a quantitative basis for either in vivo tissue or in vitro microdialysis. Established physiological and mass transport principles were employed to obtain explicit expressions relating dialysate concentration to tissue extracellular concentration for in vivo applications or external medium concentration in vitro probe characterization. Some of the important generalizations derived from the modeling framework

P. M. Bungay; P. F. Morrison; R. L. Dedrick

1990-01-01

239

Ris-PhD-12(EN) Real-time in vivo luminescence  

E-print Network

Risø-PhD-12(EN) Real-time in vivo luminescence dosimetry in radiotherapy and mammography using Al2O Aznar Title: Real-time in vivo luminescence dosimetry in radiotherapy and mammography using Al2O3:C luminescence (OSL) from carbon-doped aluminium oxide (Al2O3:C), for applications in radiotherapy

240

Survival of thefittest: in vivo selection and stem cell gene therapy  

Microsoft Academic Search

human stem cells has long been the most prominent obstacle to widespread clinical application of stem cell gene therapy. A solution to this problem has been in vivo selection. In vivo selection increases the proportion of circulating gene-corrected cells by conferring a selective growth and\\/or survival advantage to the corrected cell population. While improvements in gene transfer technology did contribute,

Tobias Neff; Brian C. Beard; Hans-Peter Kiem

2006-01-01

241

Tailoring vessel morphology in vivo  

NASA Astrophysics Data System (ADS)

Tissue engineering is a rapidly growing field which seeks to provide alternatives to organ transplantation in order to address the increasing need for transplantable tissues. One huge hurdle in this effort is the provision of thick tissues; this hurdle exists because currently there is no way to provide prevascularized or rapidly vascularizable scaffolds. To design thick, vascularized tissues, scaffolds are needed that can induce vessels which are similar to the microvasculature found in normal tissues. Angiogenic biomaterials are being developed to provide useful scaffolds to address this problem. In this thesis angiogenic and cell signaling and adhesion factors were incorporated into a biomimetic poly(ethylene glycol) (PEG) hydrogel system. The composition of these hydrogels was precisely tuned to induce the formation of differing vessel morphology. To sensitively measure induced microvascular morphology and to compare it to native microvessels in several tissues, this thesis developed an image-based tool for quantification of scale invariant and classical measures of vessel morphology. The tool displayed great utility in the comparison of native vessels and remodeling vessels in normal tissues. To utilize this tool to tune the vessel response in vivo, Flk1::myr-mCherry fluorescently labeled mice were implanted with Platelet Derived Growth Factor-BB (PDGF-BB) and basic Fibroblast Growth Factor (FGF-2) containing PEG-based hydrogels in a modified mouse corneal angiogenesis assay. Resulting vessels were imaged with confocal microscopy, analyzed with the image based tool created in this thesis to compare morphological differences between treatment groups, and used to create a linear relationship between space filling parameters and dose of growth factor release. Morphological parameters of native mouse tissue vessels were then compared to the linear fit to calculate the dose of growth factors needed to induce vessels similar in morphology to native vessels. Resulting induced vessels did match in morphology to the target vessels. Several other covalently bound signals were then analyzed in the assay and resulting morphology of vessels was compared in several studies which further highlighted the utility of the micropocket assay in conjunction with the image based tool for vessel morphological quantification. Finally, an alternative method to provide rapid vasculature to the constructs, which relied on pre-seeded hydrogels encapsulated endothelial cells was also developed and shown to allow anastamosis between induced host vessels and the implanted construct within 48 hours. These results indicate great promise in the rational design of synthetic, bioactive hydrogels, which can be used as a platform to study microvascular induction for regenerative medicine and angiogenesis research. Future applications of this research may help to develop therapeutic strategies to ameliorate human disease by replacing organs or correcting vessel morphology in the case of ischemic diseases and cancer.

Gould, Daniel Joseph

242

In Vivo Histamine Optical Nanosensors  

PubMed Central

In this communication we discuss the development of ionophore based nanosensors for the detection and monitoring of histamine levels in vivo. This approach is based on the use of an amine-reactive, broad spectrum ionophore which is capable of recognizing and binding to histamine. We pair this ionophore with our already established nanosensor platform, and demonstrate in vitro and in vivo monitoring of histamine levels. This approach enables capturing rapid kinetics of histamine after injection, which are more difficult to measure with standard approaches such as blood sampling, especially on small research models. The coupling together of in vivo nanosensors with ionophores such as nonactin provide a way to generate nanosensors for novel targets without the difficult process of designing and synthesizing novel ionophores. PMID:23112690

Cash, Kevin J.; Clark, Heather A.

2012-01-01

243

In vivo Raman spectroscopy of cervix cancers  

NASA Astrophysics Data System (ADS)

Cervix-cancer is the third most common female cancer worldwide. It is the leading cancer among Indian females with more than million new diagnosed cases and 50% mortality, annually. The high mortality rates can be attributed to late diagnosis. Efficacy of Raman spectroscopy in classification of normal and pathological conditions in cervix cancers on diverse populations has already been demonstrated. Our earlier ex vivo studies have shown the feasibility of classifying normal and cancer cervix tissues as well as responders/non-responders to Concurrent chemoradiotherapy (CCRT). The present study was carried out to explore feasibility of in vivo Raman spectroscopic methods in classifying normal and cancerous conditions in Indian population. A total of 182 normal and 132 tumor in vivo Raman spectra, from 63 subjects, were recorded using a fiberoptic probe coupled HE-785 spectrometer, under clinical supervision. Spectra were acquired for 5 s and averaged over 3 times at 80 mW laser power. Spectra of normal conditions suggest strong collagenous features and abundance of non-collagenous proteins and DNA in case of tumors. Preprocessed spectra were subjected to Principal Component-Linear Discrimination Analysis (PCLDA) followed by leave-one-out-cross-validation. Classification efficiency of ~96.7% and 100% for normal and cancerous conditions respectively, were observed. Findings of the study corroborates earlier studies and suggest applicability of Raman spectroscopic methods in combination with appropriate multivariate tool for objective, noninvasive and rapid diagnosis of cervical cancers in Indian population. In view of encouraging results, extensive validation studies will be undertaken to confirm the findings.

Rubina, S.; Sathe, Priyanka; Dora, Tapas Kumar; Chopra, Supriya; Maheshwari, Amita; Krishna, C. Murali

2014-03-01

244

Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo  

Microsoft Academic Search

Mesenchymal stem cells (MSCs) have generated a great deal of interest in clinical application because of their potential use in regenerative medicine and tissue engineering. However, the therapeutic application of MSCs still remain limited unless the favorable effect of MSCs for tumor growth in vivo and the long-term safety of the clinical applications of MSCs are better understood. In this

Wei Zhu; Wenrong Xu; Runqiu Jiang; Hui Qian; Miao Chen; Jiabo Hu; Weike Cao; Chongxu Han; Yongchang Chen

2006-01-01

245

In vivo imaging of microscopic structures in the rat retina  

PubMed Central

Purpose The ability to resolve single retinal cells in rodents in vivo has applications in rodent models of the visual system and retinal disease. We have characterized the performance of a fluorescence adaptive optics scanning laser ophthalmoscope (fAOSLO) that provides cellular and subcellular imaging of rat retina in vivo. Methods Green fluorescent protein (eGFP) was expressed in retinal ganglion cells of normal Sprague Dawley rats via intravitreal injections of adeno-associated viral vectors. Simultaneous reflectance and fluorescence retinal images were acquired using the fAOSLO. fAOSLO resolution was characterized by comparing in vivo images with subsequent imaging of retinal sections from the same eyes using confocal microscopy. Results Retinal capillaries and eGFP-labeled ganglion cell bodies, dendrites, and axons were clearly resolved in vivo with adaptive optics (AO). AO correction reduced the total root mean square wavefront error, on average, from 0.30 ?m to 0.05 ?m (1.7-mm pupil). The full width at half maximum (FWHM) of the average in vivo line-spread function (LSF) was ?1.84 ?m, approximately 82% greater than the FWHM of the diffraction-limited LSF. Conclusions With perfect aberration compensation, the in vivo resolution in the rat eye could be ?2× greater than that in the human eye due to its large numerical aperture (?0.43). While the fAOSLO corrects a substantial fraction of the rat eye's aberrations, direct measurements of retinal image quality reveal some blur beyond that expected from diffraction. Nonetheless, subcellular features can be resolved, offering promise for using AO to investigate the rodent eye in vivo with high resolution. PMID:19578019

Geng, Ying; Greenberg, Kenneth P.; Wolfe, Robert; Gray, Daniel C.; Hunter, Jennifer J.; Dubra, Alfredo; Flannery, John G.; Williams, David R.; Porter, Jason

2010-01-01

246

In-vivo morphologic and spectroscopic investigation of Psoriasis  

NASA Astrophysics Data System (ADS)

Psoriasis is an autoimmune disease of the skin characterized by hyperkeratosis, hyperproliferation of the epidermis, inflammatory cell accumulation and increased dilatation of dermal papillary blood vessels. Cases of psoriasis were investigated in vivo with optical means in order to evaluate the potential of in vivo optical biopsy. A Polarization Multispectral Dermoscope was employed for the macroscopic observation. Features such as the 'dotted' blood vessels pattern was observed with high contrast. High resolution image sections of the epidermis and the dermis were produced with a custom made Multiphoton Microscope. Imaging extended from the surface of the lesion down to the papillary dermis, at a depth of 200 ?m. In the epidermis, a characteristic morphology of the stratum corneum found only in Psoriasis was revealed. Additionally, the cytoplasmic area of the cells in the stratum spinosum layer was found to be smaller than normal. In the dermis the morphological features were more pronounced, where the elongated dermal papillae dominated the papillary layer. Their length exceeds 100?m, which is a far greater value compared to that of healthy skin. These in vivo observations are consistent with the ex vivo histopathological observations, supporting both the applicability and potentiality of multispectral dermoscopy and multiphoton microscopy in the field of in vivo optical investigation and biopsy of skin.

Kapsokalyvas, Dimitrios; Cicchi, Riccardo; Bruscino, Nicola; Alfieri, Domenico; Massi, Daniela; Lotti, Torello; Pavone, Francesco S.

2011-07-01

247

Airway nerves: in vivo electrophysiology  

Microsoft Academic Search

Information about the activity of airway sensory afferent nerves in vivo can be obtained electrophysiologically by extracellular recording of action potentials. Apart from data capture, the basic techniques used for recording sensory nerve activity have not advanced greatly in 50 years. However, clearly they continue to contribute vastly to our understanding of the role of these nerves in the control

John J Adcock

2002-01-01

248

In vivo Lens Fluorescence Photography  

Microsoft Academic Search

We are reporting a new, objective and quantitative method for monitoring age-related molecular changes in the human ocular lens in vivo, as expressed by increases in at least two (nontryptophan) fluorescence wavelengths. These data correlate with previously reported in vitro lens fluorescence changes which are associated with the aging process. This method will also detect alterations in lenticular fluorescence caused

S. L. Lerman; O. Hockwin; V. Dragomirescu

1981-01-01

249

In aqua vivo EPID dosimetry  

SciTech Connect

Purpose: At the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital in vivo dosimetry using an electronic portal imaging device (EPID) has been implemented for almost all high-energy photon treatments of cancer with curative intent. Lung cancer treatments were initially excluded, because the original back-projection dose-reconstruction algorithm uses water-based scatter-correction kernels and therefore does not account for tissue inhomogeneities accurately. The aim of this study was to test a new method, in aqua vivo EPID dosimetry, for fast dose verification of lung cancer irradiations during actual patient treatment. Methods: The key feature of our method is the dose reconstruction in the patient from EPID images, obtained during the actual treatment, whereby the images have been converted to a situation as if the patient consisted entirely of water; hence, the method is termed in aqua vivo. This is done by multiplying the measured in vivo EPID image with the ratio of two digitally reconstructed transmission images for the unit-density and inhomogeneous tissue situation. For dose verification, a comparison is made with the calculated dose distribution with the inhomogeneity correction switched off. IMRT treatment verification is performed for each beam in 2D using a 2D {gamma} evaluation, while for the verification of volumetric-modulated arc therapy (VMAT) treatments in 3D a 3D {gamma} evaluation is applied using the same parameters (3%, 3 mm). The method was tested using two inhomogeneous phantoms simulating a tumor in lung and measuring its sensitivity for patient positioning errors. Subsequently five IMRT and five VMAT clinical lung cancer treatments were investigated, using both the conventional back-projection algorithm and the in aqua vivo method. The verification results of the in aqua vivo method were statistically analyzed for 751 lung cancer patients treated with IMRT and 50 lung cancer patients treated with VMAT. Results: The improvements by applying the in aqua vivo approach are considerable. The percentage of {gamma} values {<=}1 increased on average from 66.2% to 93.1% and from 43.6% to 97.5% for the IMRT and VMAT cases, respectively. The corresponding mean {gamma} value decreased from 0.99 to 0.43 for the IMRT cases and from 1.71 to 0.40 for the VMAT cases, which is similar to the accepted clinical values for the verification of IMRT treatments of prostate, rectum, and head-and-neck cancers. The deviation between the reconstructed and planned dose at the isocenter diminished on average from 5.3% to 0.5% for the VMAT patients and was almost the same, within 1%, for the IMRT cases. The in aqua vivo verification results for IMRT and VMAT treatments of a large group of patients had a mean {gamma} of approximately 0.5, a percentage of {gamma} values {<=}1 larger than 89%, and a difference of the isocenter dose value less than 1%. Conclusions: With the in aqua vivo approach for the verification of lung cancer treatments (IMRT and VMAT), we can achieve results with the same accuracy as obtained during in vivo EPID dosimetry of sites without large inhomogeneities.

Wendling, Markus; McDermott, Leah N.; Mans, Anton; Olaciregui-Ruiz, Igor; Pecharroman-Gallego, Raul; Sonke, Jan-Jakob; Stroom, Joep; Herk, Marcel J.; Mijnheer, Ben van [Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands)

2012-01-15

250

The in vivo activation of persistent nanophosphors for optical imaging of vascularization, tumours and grafted cells  

NASA Astrophysics Data System (ADS)

Optical imaging for biological applications requires more sensitive tools. Near-infrared persistent luminescence nanoparticles enable highly sensitive in vivo optical detection and complete avoidance of tissue autofluorescence. However, the actual generation of persistent luminescence nanoparticles necessitates ex vivo activation before systemic administration, which prevents long-term imaging in living animals. Here, we introduce a new generation of optical nanoprobes, based on chromium-doped zinc gallate, whose persistent luminescence can be activated in vivo through living tissues using highly penetrating low-energy red photons. Surface functionalization of this photonic probe can be adjusted to favour multiple biomedical applications such as tumour targeting. Notably, we show that cells can endocytose these nanoparticles in vitro and that, after intravenous injection, we can track labelled cells in vivo and follow their biodistribution by a simple whole animal optical detection, opening new perspectives for cell therapy research and for a variety of diagnosis applications.

Maldiney, Thomas; Bessière, Aurélie; Seguin, Johanne; Teston, Eliott; Sharma, Suchinder K.; Viana, Bruno; Bos, Adrie J. J.; Dorenbos, Pieter; Bessodes, Michel; Gourier, Didier; Scherman, Daniel; Richard, Cyrille

2014-04-01

251

3D ultrafast ultrasound imaging in vivo  

NASA Astrophysics Data System (ADS)

Very high frame rate ultrasound imaging has recently allowed for the extension of the applications of echography to new fields of study such as the functional imaging of the brain, cardiac electrophysiology, and the quantitative imaging of the intrinsic mechanical properties of tumors, to name a few, non-invasively and in real time. In this study, we present the first implementation of Ultrafast Ultrasound Imaging in 3D based on the use of either diverging or plane waves emanating from a sparse virtual array located behind the probe. It achieves high contrast and resolution while maintaining imaging rates of thousands of volumes per second. A customized portable ultrasound system was developed to sample 1024 independent channels and to drive a 32? × ?32 matrix-array probe. Its ability to track in 3D transient phenomena occurring in the millisecond range within a single ultrafast acquisition was demonstrated for 3D Shear-Wave Imaging, 3D Ultrafast Doppler Imaging, and, finally, 3D Ultrafast combined Tissue and Flow Doppler Imaging. The propagation of shear waves was tracked in a phantom and used to characterize its stiffness. 3D Ultrafast Doppler was used to obtain 3D maps of Pulsed Doppler, Color Doppler, and Power Doppler quantities in a single acquisition and revealed, at thousands of volumes per second, the complex 3D flow patterns occurring in the ventricles of the human heart during an entire cardiac cycle, as well as the 3D in vivo interaction of blood flow and wall motion during the pulse wave in the carotid at the bifurcation. This study demonstrates the potential of 3D Ultrafast Ultrasound Imaging for the 3D mapping of stiffness, tissue motion, and flow in humans in vivo and promises new clinical applications of ultrasound with reduced intra—and inter-observer variability.

Provost, Jean; Papadacci, Clement; Esteban Arango, Juan; Imbault, Marion; Fink, Mathias; Gennisson, Jean-Luc; Tanter, Mickael; Pernot, Mathieu

2014-10-01

252

In vivo nanotoxicity assays in plant models.  

PubMed

Increasing application of silver nanoparticles (SNPs) and zinc oxide nanoparticles (nZnO) in consumer products like textiles, cosmetics, washing machines and other household products increases their chance to reach the environment. Intensive research is required to assess the nanoparticles' toxicity to the environmental system. The toxicological effect of nanoparticles has been studied at the miniscule scale and requires intensive research to be conducted to assess its unknown effects. Plants are the primary target species which need to be included to develop a comprehensive toxicity profile for nanoparticles. So far, the mechanisms of toxicity of nanoparticles to the plant system remains largely unknown and little information on the potential uptake of nanoparticles by plants and their subsequent fate within the food chain is available. The phytoxicological behaviour of silver and zinc oxide nanoparticles on Allium cepa and seeds of Zea mays (maize), Cucumis sativus (cucumber) and Lycopersicum esculentum (tomato) was done. The in vitro studies on A. cepa have been done to check the cytotoxicological effects including mitotic index, chromosomal aberrations, vagrant chromosomes, sticky chromosomes, disturbed metaphase, breaks and formation of micronucleus. In vitro and in vivo studies on seed systems exposed to different concentration of nanoparticles dispersion to check phytotoxicity end point as root length, germination effect, adsorption and accumulation of nanoparticles (uptake studies) into the plant systems. In vivo studies in a seed system was done using phytagel medium. Biochemical studies were done to check effect on protein, DNA and thiobarbituric acid reactive species concentration. FT-IR studies were done to analyze the functional and conformational changes in the treated and untreated samples. The toxicological effects of nanoparticles had to be studied at the miniscule scale to address existing environment problems or prevent future problems. The findings suggest that the engineered nanoparticles, though having significant advantages in research and medical applications, requires a great deal of toxicity database to ascertain the biosafety and risk of using engineered nanoparticles in consumer products. PMID:22975978

Kumari, Mamta; Ernest, Vinita; Mukherjee, Amitava; Chandrasekaran, Natarajan

2012-01-01

253

Ultra-performance liquid chromatography tandem mass spectrometry method for the determination of AZ66, a sigma receptor ligand, in rat plasma and its application to in vivo pharmacokinetics  

PubMed Central

Methamphetamine abuse continues as a major problem in the USA owing to its powerful psychological addictive properties. AZ66, 3-[4-(4-cyclohexylpiperazine-1-yl)pentyl]-6-fluorobenzo[d]thiazole-2(3H)-one, an optimized sigma receptor ligand, is a promising therapeutic agent against methamphetamine. To study the in vivo pharmacokinetics of this novel sigma receptor ligand in rats, a sensitive ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method was developed in rat plasma and validated. The developed method requires a small volume of plasma (100 ?L) and a simple liquid–liquid extraction. The chromatographic separations were achieved in 3.3 min using an Acquity UPLC BEH Shield RP18 column. The mass spectrophotometric detection was carried out using a Waters Micromass Quattro MicroTM triple-quadrupole system. Multiple reaction monitoring was used for the quantitation with transitions m/z 406?m/z 181 for AZ66 and m/z 448?m/z 285 for aripiprazole. The method was validated over a concentration range of 1–3500 ng/mL and the lower limit of quantitation was determined to be 1 ng/mL. Validation of the assay demonstrated that the developed UPLC/MS/MS method was sensitive, accurate and selective for the determination of AZ66 in rat plasma. The present method has been successfully applied to an i.v. pharmacokinetic study in Sprague–Dawley rats. PMID:23558564

Jamalapuram, Seshulatha; Vuppala, Pradeep Kumar; Abdelazeem, Ahmed H.; McCurdy, Christopher R.; Avery, Bonnie A.

2014-01-01

254

Original article Immunomodulatory effects in vivo of  

E-print Network

Original article Immunomodulatory effects in vivo of recombinant porcine interferon gamma cells after in vivo injections of recombinant porcine interferon gamma (rPoIFNy) were studied in pigsPoIFNy modulates leukocyte functions of pigs in vivo. interferon gamma / swine/interleukin / lymphocyte

Paris-Sud XI, Université de

255

Silver Nanoplate Contrast Agents for In Vivo Molecular Photoacoustic Imaging  

PubMed Central

Silver nanoplates are introduced as a new photoacoustic contrast agent that can be easily functionalized for molecular photoacoustic imaging in vivo. Methods are described for synthesis, functionalization, and stabilization of silver nanoplates using biocompatible (“green”) reagents. Directional antibody conjugation to the nanoplate surface is presented along with proof of molecular sensitivity in vitro with pancreatic cancer cells. Cell viability tests show the antibody-conjugated silver nanoplates to be nontoxic at concentrations up to 1 mg/ml. Furthermore, the silver nanoplates' potential for in vivo application as a molecularly sensitive photoacoustic contrast agent is demonstrated using an orthotopic mouse model of pancreatic cancer. Results of these studies suggest that the synthesized silver nanoplates are well suited for a host of biomedical imaging and sensing applications. PMID:22188516

Homan, Kimberly A.; Souza, Michael; Truby, Ryan; Luke, Geoffrey P.; Green, Christopher; Vreeland, Erika; Emelianov, Stanislav

2012-01-01

256

19F MRI for quantitative in vivo cell tracking  

PubMed Central

Cellular therapy, including stem cell transplants and dendritic cell vaccines, is typically monitored for dosage optimization, accurate delivery and localization using non-invasive imaging, of which magnetic resonance imaging (MRI) is a key modality. 19F MRI retains the advantages of MRI as an imaging modality, while allowing direct detection of labelled cells for unambiguous identification and quantification, unlike typical metal-based contrast agents. Recent developments in 19F MRI-based in vivo cell quantification, the existing clinical use of 19F compounds and current explosive interest in cellular therapeutics have brought 19F imaging technology closer to clinical application. We review the application of 19F MRI to cell tracking, discussing intracellular 19F labels, cell labelling and in vivo quantification, as well as the potential clinical use of 19F MRI. PMID:20427096

Srinivas, Mangala; Heerschap, Arend; Ahrens, Eric T.; Figdor, Carl G.; de Vries, I. Jolanda M.

2010-01-01

257

Silver nanoplate contrast agents for in vivo molecular photoacoustic imaging.  

PubMed

Silver nanoplates are introduced as a new photoacoustic contrast agent that can be easily functionalized for molecular photoacoustic imaging in vivo. Methods are described for synthesis, functionalization, and stabilization of silver nanoplates using biocompatible ("green") reagents. Directional antibody conjugation to the nanoplate surface is presented along with proof of molecular sensitivity in vitro with pancreatic cancer cells. Cell viability tests show the antibody-conjugated silver nanoplates to be nontoxic at concentrations up to 1 mg/mL. Furthermore, the silver nanoplates' potential for in vivo application as a molecularly sensitive photoacoustic contrast agent is demonstrated using an orthotopic mouse model of pancreatic cancer. Results of these studies suggest that the synthesized silver nanoplates are well suited for a host of biomedical imaging and sensing applications. PMID:22188516

Homan, Kimberly A; Souza, Michael; Truby, Ryan; Luke, Geoffrey P; Green, Christopher; Vreeland, Erika; Emelianov, Stanislav

2012-01-24

258

Imaging coagulation reactions in vivo  

PubMed Central

Significant gaps remain in the understanding of how blood cells and the vasculature differentially support coagulation enzyme complex function leading to regulated thrombus formation in vivo. While studies employing knock-out or transgenic mice have proved useful many of these scientific gaps partly result from the lack of molecular approaches and analytic tools with appropriate sensitivity for incisive conclusions. Over the past decade, studies employing state of the art videomicroscopy to image hemostasis in vivo following laser injury to the mouse cremaster arteriole have begun to bridge these gaps and provide remarkable insight into the early events of the hemostatic process. Many of these new insights have started to question some of the long-standing concepts that were driven by in vitro approaches. This review provides an overview of this technology, describes insights that have been made using it, and discuses limitations and future directions. PMID:22405051

Ivanciu, Lacramioara; Krishnaswamy, Sriram; Camire, Rodney M.

2012-01-01

259

Multiplexed aberration measurement for deep tissue imaging in vivo.  

PubMed

We describe an adaptive optics method that modulates the intensity or phase of light rays at multiple pupil segments in parallel to determine the sample-induced aberration. Applicable to fluorescent protein-labeled structures of arbitrary complexity, it allowed us to obtain diffraction-limited resolution in various samples in vivo. For the strongly scattering mouse brain, a single aberration correction improved structural and functional imaging of fine neuronal processes over a large imaging volume. PMID:25128976

Wang, Chen; Liu, Rui; Milkie, Daniel E; Sun, Wenzhi; Tan, Zhongchao; Kerlin, Aaron; Chen, Tsai-Wen; Kim, Douglas S; Ji, Na

2014-10-01

260

Advances in fiber optic sensors for in-vivo monitoring  

NASA Astrophysics Data System (ADS)

Biomedical fiber-optic sensors are attractive for the measurement of both physical and chemical parameters as well as for spectral measurements directly performed on the patient. An overview of fiber-optic sensors for in vivo monitoring is given, with particular attention to the advantages that these sensors are able to offer in different fields of application such as cardiovascular and intensive care, angiology, gastroenterology, ophthalmology, oncology, neurology, dermatology, and dentistry.

Baldini, Francesco; Mignani, Anna G.

1995-09-01

261

Positron emitters for {ital in vivo} plant studies  

SciTech Connect

The use of short-lived positron emitter isotopes in studying the dynamics of biological systems provides an indepth understanding of the regulating functions of the system, that is otherwise unattainable. When we coupled such studies with tracer kinetics models, and a system approach of data analysis, {ital in vivo} simultaneous processes and their interactions are understood. The techniques applied, results of their applications and system analysis of data are reported. {copyright} {ital 1997 American Institute of Physics.}

Fares, Y.; Goeschl, J.D.; Magnuson, C.E.; McKinney, C.J.; Musser, R.L.; Strain, B.R. [Phytotron and Botany Department, Duke University, Durham, North Carolina 27706 (United States)

1997-02-01

262

In vivo whole-field blood velocity measurement techniques  

Microsoft Academic Search

In this article a number of whole-field blood velocity measurement techniques are concisely reviewed. We primarily focus on\\u000a optical measurement techniques for in vivo applications, such as laser Doppler velocimetry (including time varying speckle),\\u000a laser speckle contrast imaging and particle image velocimetry (including particle tracking). We also briefly describe nuclear\\u000a magnetic resonance and ultrasound particle image velocimetry, two techniques that

Peter Vennemann; Ralph Lindken; Jerry Westerweel

2007-01-01

263

In Vivo and Ex Vivo Transcutaneous Glucose Detection Using Surface-Enhanced Raman Spectroscopy  

NASA Astrophysics Data System (ADS)

Diabetes mellitus is widely acknowledged as a large and growing health concern. The lack of practical methods for continuously monitoring glucose levels causes significant difficulties in successful diabetes management. Extensive validation work has been carried out using surface-enhanced Raman spectroscopy (SERS) for in vivo glucose sensing. This dissertation details progress made towards a Raman-based glucose sensor for in vivo, transcutaneous glucose detection. The first presented study combines spatially offset Raman spectroscopy (SORS) with SERS (SESORS) to explore the possibility of in vivo, transcutaneous glucose sensing. A SERS-based glucose sensor was implanted subcutaneously in Sprague-Dawley rats. SERS spectra were acquired transcutaneously and analyzed using partial least-squares (PLS). Highly accurate and consistent results were obtained, especially in the hypoglycemic range. Additionally, the sensor demonstrated functionality at least17 days after implantation. A subsequent study further extends the application of SESORS to the possibility of in vivo detection of glucose in brain through skull. Specifically, SERS nanoantennas were buried in an ovine tissue behind a bone with 8 mm thickness and detected by using SESORS. In addition, quantitative detection through bones by using SESORS was also demonstrated. A device that could measure glucose continuously as well as noninvasively would be of great use to patients with diabetes. The inherent limitation of the SESORS approach may prevent this technique from becoming a noninvasive method. Therefore, the prospect of using normal Raman spectroscopy for glucose detection was re-examined. Quantitative detection of glucose and lactate in the clinically relevant range was demonstrated by using normal Raman spectroscopy with low power and short acquisition time. Finally, a nonlinear calibration method called least-squares support vector machine regression (LS-SVR) was investigated for analyzing spectroscopic data sets of glucose detection. Comparison studies were demonstrated between LS-SVR and PLS. LS-SVR demonstrated significant improvements in accuracy over PLS for glucose detection, especially when a global calibration model was required. The improvements imparted by LS-SVR open up the possibility of developing an accurate prediction algorithm for Raman-based glucose sensing applicable to a large human population. Overall, these studies show the high promise held by the Raman-based sensor for the challenge of optimal glycemic control.

Ma, Ke

264

A novel thin-layer amperometric detector based on chemically modified ring-disc electrode and its application for simultaneous measurements of nitric oxide and nitrite in rat brain combined with in vivo microdialysis  

Microsoft Academic Search

A novel thin-layer amperometric detector (TLAD) based on chemically modified ring-disc electrode and its application for simultaneous measurements of nitric oxide (NO) and nitrite (NO2?) in rat brain were demonstrated in this work. The ring-disc electrode was simultaneously sensitive to nitric oxide (NO) and nitrite (NO2?) by modifying its inner disc with electropolymerized film of cobalt(II) tetraaminophthalocyanine (polyCoTAPc)\\/Nafion and its

Lanqun Mao; Guoyue Shi; Yu Tian; Haiying Liu; Litong Jin; Katsunobu Yamamoto; Shuguang Tao; Jiye Jin

1998-01-01

265

An optical device employing multiwavelength photoplethysmography for non-invasive in-vivo monitoring of optically active nanoparticles  

Microsoft Academic Search

Researchers employ increasingly complex sub-micron particles for oncological applications to deliver bioactive therapeutic or imaging compounds to known and unknown in vivo tumor targets. These particles are often manufactured using a vast array of compounds and techniques resulting in a complex architecture, which can be quantified ex vivo by conventional metrology and chemical assays. In practice however, experimental homogeneity using

Gregory J. Michalak; Pratik Adhikari; Jon A. Schwartz; Glenn P. Goodrich; D. Patrick O'Neal

2011-01-01

266

In vivo heterogeneous tomographic bioluminescence imaging via a higher-order approximation forward model  

NASA Astrophysics Data System (ADS)

In vivo bioluminescence imaging (BLI) has played a more and more important role in biomedical research of small animals. Tomographic bioluminescence imaging (TBI) further translates the BLI optical information into three-dimensional bioluminescent source distribution, which could greatly facilitate applications in related studies. Although the diffusion approximation (DA) is one of the most widely-used forward models, higher-order approximations are still needed for in vivo small animal imaging. In this work, as a relatively accurate and higher-order approximation theory, a simplified spherical harmonics approximation (SPN) is applied for heterogeneous tomographic bioluminescence imaging in vivo. Furthermore, coupled with the SPN, a generalized graph cuts optimization approach is utilized, making BLT reconstructions fast and suit for the whole body of small animals. Heterogeneous in vivo experimental reconstructions via the higher-order approximation model demonstrate higher tomographic imaging quality, which is shown the capability for practical biomedical tomographic imaging applications.

Liu, Kai; Tian, Jie, Sr.; Qin, Chenghu; Yang, Xin; Zhu, Shouping; Han, Dong; Wu, Ping; Dai, Xiaoqian

2011-03-01

267

On-chip immobilization of planarians for in vivo imaging.  

PubMed

Planarians are an important model organism for regeneration and stem cell research. A complete understanding of stem cell and regeneration dynamics in these animals requires time-lapse imaging in vivo, which has been difficult to achieve due to a lack of tissue-specific markers and the strong negative phototaxis of planarians. We have developed the Planarian Immobilization Chip (PIC) for rapid, stable immobilization of planarians for in vivo imaging without injury or biochemical alteration. The chip is easy and inexpensive to fabricate, and worms can be mounted for and removed after imaging within minutes. We show that the PIC enables significantly higher-stability immobilization than can be achieved with standard techniques, allowing for imaging of planarians at sub-cellular resolution in vivo using brightfield and fluorescence microscopy. We validate the performance of the PIC by performing time-lapse imaging of planarian wound closure and sequential imaging over days of head regeneration. We further show that the device can be used to immobilize Hydra, another photophobic regenerative model organism. The simple fabrication, low cost, ease of use, and enhanced specimen stability of the PIC should enable its broad application to in vivo studies of stem cell and regeneration dynamics in planarians and Hydra. PMID:25227263

Dexter, Joseph P; Tamme, Mary B; Lind, Christine H; Collins, Eva-Maria S

2014-01-01

268

On-chip immobilization of planarians for in vivo imaging  

PubMed Central

Planarians are an important model organism for regeneration and stem cell research. A complete understanding of stem cell and regeneration dynamics in these animals requires time-lapse imaging in vivo, which has been difficult to achieve due to a lack of tissue-specific markers and the strong negative phototaxis of planarians. We have developed the Planarian Immobilization Chip (PIC) for rapid, stable immobilization of planarians for in vivo imaging without injury or biochemical alteration. The chip is easy and inexpensive to fabricate, and worms can be mounted for and removed after imaging within minutes. We show that the PIC enables significantly higher-stability immobilization than can be achieved with standard techniques, allowing for imaging of planarians at sub-cellular resolution in vivo using brightfield and fluorescence microscopy. We validate the performance of the PIC by performing time-lapse imaging of planarian wound closure and sequential imaging over days of head regeneration. We further show that the device can be used to immobilize Hydra, another photophobic regenerative model organism. The simple fabrication, low cost, ease of use, and enhanced specimen stability of the PIC should enable its broad application to in vivo studies of stem cell and regeneration dynamics in planarians and Hydra. PMID:25227263

Dexter, Joseph P.; Tamme, Mary B.; Lind, Christine H.; Collins, Eva-Maria S.

2014-01-01

269

Gel Encapsulation of Glucose Nanosensors for Prolonged In Vivo Lifetime  

PubMed Central

Background Fluorescent glucose-sensitive nanosensors have previously been used in vivo to track glucose concentration changes in interstitial fluid. However, this technology was limited because of loss of fluorescence intensity due to particle diffusion from the injection site. In this study, we encapsulated the nanosensors into injectable gels to mitigate nanosensor migration in vivo. Methods Glucose-sensitive nanosensors were encapsulated in two different commercially available gelling agents: gel 1 and gel 2. Multiple formulations of each gel were assessed in vitro for their nanosensor encapsulation efficiency, permeability to glucose, and nanosensor retention over time. The optimal formulation for each gel, as determined from the in vitro assessment, was then tested in mice, and the lifetime of the encapsulated nanosensors was compared with controls of nanosensors without gel. Results Five gel formulations had encapsulation efficiencies of the nanosensors greater than 90%. Additionally, they retained up to 20% and 40% of the nanosensors over 24 h for gel 1 and gel 2, respectively. In vivo, both gels prevented diffusion of glucose nanosensors at least three times greater than the controls. Conclusions Encapsulating glucose nanosensors in two injectable gels prolonged nanosensor lifetime in vivo; however, the lifetime must still be increased further to be applicable for diabetes monitoring. PMID:23439160

Balaconis, Mary K.; Clark, Heather A.

2013-01-01

270

In vivo MRI cell tracking using perfluorocarbon probes and fluorine-19 detection  

PubMed Central

This article is a brief survey of preclinical in vivo cell tracking methods and applications using perfluorocarbon (PFC) probes and fluorine-19 (19F) MRI detection. Detection of the 19F signal offers high cell specificity and quantification abilities in spin-density weighted MR images. We discuss the compositions of matter, methods, and applications of PFC-based cell tracking using ex vivo and in situ PFC labeling in preclinical studies of inflammation and cellular therapeutics. We will also address potential applicability of 19F cell tracking to clinical trials. PMID:23606473

Ahrens, Eric T.; Zhong, Jia

2013-01-01

271

Wide-field in vivo background free imaging by selective magnetic modulation of nanodiamond fluorescence  

PubMed Central

The sensitivity and resolution of fluorescence-based imaging in vivo is often limited by autofluorescence and other background noise. To overcome these limitations, we have developed a wide-field background-free imaging technique based on magnetic modulation of fluorescent nanodiamond emission. Fluorescent nanodiamonds are bright, photo-stable, biocompatible nanoparticles that are promising probes for a wide range of in vitro and in vivo imaging applications. Our readily applied background-free imaging technique improves the signal-to-background ratio for in vivo imaging up to 100-fold. This technique has the potential to significantly improve and extend fluorescent nanodiamond imaging capabilities on diverse fluorescence imaging platforms. PMID:24761300

Sarkar, Susanta K.; Bumb, Ambika; Wu, Xufeng; Sochacki, Kem A.; Kellman, Peter; Brechbiel, Martin W.; Neuman, Keir C.

2014-01-01

272

Spatial light modulator based active wide-field illumination for ex vivo and in vivo quantitative NIR FRET imaging  

PubMed Central

Fluorescence lifetime imaging is playing an increasing role in drug development by providing a sensitive method to monitor drug delivery and receptor-ligand interactions. However, the wide dynamic range of fluorescence intensity emitted by ex vivo and in vivo samples presents challenges in retrieving information over the whole subject accurately and quantitatively. To overcome this challenge, we developed an active wide-field illumination (AWFI) strategy based on a spatial light modulator that acquires optimal fluorescence signals by enhancing the dynamic range, signal to noise ratio, and estimation of lifetime-based parameters. We demonstrate the ability of AWFI to estimate Förster resonance energy transfer (FRET) donor fraction from dissected organs with high accuracy (standard deviation <6%) over the whole field of view, in contrast with the homogenous wide-field illumination. We further report its successful application to quantitative FRET imaging in a live mouse. AWFI allows improved detection of weak signals and enhanced quantitative accuracy in ex vivo and in vivo molecular fluorescence quantitative imaging. The technique allows for robust quantitative estimation of the bio-distribution of molecular probes and lifetime-based parameters over an extended imaging field exhibiting a large range of fluorescence intensities and at a high acquisition speed (less than 1 min). PMID:24688826

Zhao, Lingling; Abe, Ken; Rajoria, Shilpi; Pian, Qi; Barroso, Margarida; Intes, Xavier

2014-01-01

273

In Vivo Gene Expression Dynamics of Tumor-Targeted Bacteria  

PubMed Central

The engineering of bacteria to controllably deliver therapeutics is an attractive application for synthetic biology. While most synthetic gene networks have been explored within microbes, there is a need for further characterization of in vivo circuit behavior in the context of applications where the host microbes are actively being investigated for efficacy and safety, such as tumor drug delivery. One major hurdle is that culture-based selective pressures are absent in vivo, leading to strain-dependent instability of plasmid-based networks over time. Here, we experimentally characterize the dynamics of in vivo plasmid instability using attenuated strains of S. typhimurium and real-time monitoring of luminescent reporters. Computational modeling described the effects of growth rate and dosage on live-imaging signals generated by internal bacterial populations. This understanding will allow us to harness the transient nature of plasmid-based networks to create tunable temporal release profiles that reduce dosage requirements and increase the safety of bacterial therapies. PMID:23097750

2012-01-01

274

Biophotonics techniques for structural and functional imaging, in vivo  

PubMed Central

In vivo optical imaging is being conducted in a variety of medical applications, including optical breast cancer imaging, functional brain imaging, endoscopy, exercise medicine, and monitoring the photodynamic therapy and progress of neoadjuvant chemotherapy. In the past three decades, in vivo diffuse optical breast cancer imaging has shown promising results in cancer detection, and monitoring the progress of neoadjuvant chemotherapy. The use of near infrared spectroscopy for functional brain imaging has been growing rapidly. In fluorescence imaging, the difference between autofluorescence of cancer lesions compared to normal tissues were used in endoscopy to distinguish malignant lesions from normal tissue or inflammation and in determining the boarders of cancer lesions in surgery. Recent advances in drugs targeting specific tumor receptors, such as AntiBodies (MAB), has created a new demand for developing non-invasive in vivo imaging techniques for detection of cancer biomarkers, and for monitoring their down regulations during therapy. Targeted treatments, combined with new imaging techniques, are expected to potentially result in new imaging and treatment paradigms in cancer therapy. Similar approaches can potentially be applied for the characterization of other disease-related biomarkers. In this chapter, we provide a review of diffuse optical and fluorescence imaging techniques with their application in functional brain imaging and cancer diagnosis. PMID:22433452

Ardeshirpour, Yasaman; Gandjbakhche, Amir H.; Najafizadeh, Laleh

2014-01-01

275

In vivo pool-based shRNA screens to identify modulators of disease progression in hematopoietic malignancies  

E-print Network

shRNA screens have been very effective in identifying novel cancer genes in mammalian cells, but they have primarily been limited to in vitro applications in tumor cell lines. Whereas in vivo retroviral mutagenesis screens ...

Meacham, Corbin Elizabeth

2012-01-01

276

12 In Vivo Voltammetry with Telemetry  

E-print Network

12 In Vivo Voltammetry with Telemetry Paul A. Garris, Phillip G. Greco, Stefan G. Sandberg, Greg ............................................................................................. 238 Principles of Telemetry ........................................................................................... 240 Digital Telemetry at 2.4 GHz

Casto, Joseph M.

277

Nanoparticle PEBBLE sensors in live cells and in vivo  

PubMed Central

Nanoparticle sensors have been developed for imaging and dynamic monitoring, in live cells and in vivo, of the molecular or ionic components, constructs, forces and dynamics, all in real time, during biological/chemical/physical processes. With their biocompatible small size and inert matrix, nanoparticle sensors have been successfully applied for non-invasive real-time measurements of analytes and fields in cells and rodents, with spatial, temporal, physical and chemical resolution. This review describes the diverse designs of nanoparticle sensors for ions and small molecules, physical fields and biological features, as well as the characterization, properties, and applications of these nanosensors to in vitro and in vivo measurements. Their floating as well as localization ability in biological media is captured by the acronym PEBBLE: photonic explorer for bioanalysis with biologically localized embedding. PMID:20098636

Smith, Ron

2009-01-01

278

In vitro and in vivo evaluation of SU-8 biocompatibility  

PubMed Central

SU-8 negative photoresist is a high tensile strength polymer that has been used for a number of biomedical applications that include cell encapsulation and neuronal probes. Chemically, SU-8 comprises, among other components, an epoxy based monomer and antimony salts, the latter being a potential source of cytotoxicity. We report on the in vitro and in vivo evaluation of SU-8 biocompatibility based on leachates from various solvents, at varying temperature and pH, and upon subcutaneous implantation of SU-8 substrates in mice. MTT cell viability assay did not exhibit any cytotoxic effects from the leachates. The hemolytic activity of SU-8 is comparable to that of FDA approved implant materials such as silicone elastomer, Buna-S and medical steel. In vivo histocompatibility study in mice indicates a muted immune response to subcutaneous SU-8 implants. PMID:23910365

Nemani, Krishnamurthy V.; Moodie, Karen L.; Brennick, Jeoffry B.; Su, Alison; Gimi, Barjor

2013-01-01

279

Development of an integrated microfluidic platform for oxygen sensing and delivery  

E-print Network

Treatment for end stage lung disease has failed to benefit from advances in medical technology that have produced new treatments for cardiovascular disease, certain cancers, and other major illnesses in recent years. As a ...

Vollmer, Adam P

2005-01-01

280

Defective Tibetan PHD2 binding to p23 links high altitude adaption to altered oxygen sensing.  

PubMed

The Tibetan population has adapted to the chronic hypoxia of high altitude. Tibetans bear a genetic signature in the prolyl hydroxylase domain protein 2 (PHD2/EGLN1) gene, which encodes for the central oxygen sensor of the hypoxia-inducible factor (HIF) pathway. Recent studies have focused attention on two nonsynonymous coding region substitutions, D4E and C127S, both of which are markedly enriched in the Tibetan population. These amino acids reside in a region of PHD2 that harbors a zinc finger, which we have previously discovered binds to a Pro-Xaa-Leu-Glu (PXLE) motif in the HSP90 cochaperone p23, thereby recruiting PHD2 to the HSP90 pathway to facilitate HIF-? hydroxylation. We herein report that the Tibetan PHD2 haplotype (D4E/C127S) strikingly diminishes the interaction of PHD2 with p23, resulting in impaired PHD2 down-regulation of the HIF pathway. The defective binding to p23 depends on both the D4E and C127S substitutions. We also identify a PXLE motif in HSP90 itself that can mediate binding to PHD2 but find that this interaction is maintained with the D4E/C127S PHD2 haplotype. We propose that the Tibetan PHD2 variant is a loss of function (hypomorphic) allele, leading to augmented HIF activation to facilitate adaptation to high altitude. PMID:24711448

Song, Daisheng; Li, Lin-sheng; Arsenault, Patrick R; Tan, Qiulin; Bigham, Abigail W; Heaton-Johnson, Katherine J; Master, Stephen R; Lee, Frank S

2014-05-23

281

Fiber Optical Micro-detectors for Oxygen Sensing in Power Plants  

SciTech Connect

Spectroscopy of Mo{sub 6}Cl{sub 12} immobilized in a sol-gel matrix and heated to 200 C has been performed. Oxygen quenching of the luminescence was observed. Aging Mo{sub 6}Cl{sub 12} to temperatures above 250 C converts the canary yellow Mo{sub 6}Cl{sub 12} to a non-luminescent gray solid. Preliminary experiments point to oxidation of the clusters as the likely cause of thermally induced changes in the physical and optical properties of the clusters.

Gregory L. Baker; Ruby N. Ghosh; D. J. Osborn

2003-09-30

282

Fabrication and photoelectric oxygen sensing characteristics of electrospun Co doped ZnO nanofibres  

Microsoft Academic Search

A one-dimensional structure of a Co doped ZnO nanofibre has been successfully fabricated by a relatively simple electrospinning\\u000a technique and characterized by means of SEM, XRD and surface photocurrent spectrum. We found that this fibre exhibits novel\\u000a photoelectric gas sensitivity to oxygen gas under the illumination of a 500 W Xe lamp with a fast response. The microscopic\\u000a process is discussed

Min Yang; Tengfeng Xie; Liang Peng; Yiyang Zhao; Dejun Wang

2007-01-01

283

Regulatory Mechanisms of Low Oxygen Sensing and Response in Arabidopsis thaliana  

E-print Network

plant species of transcriptional and metabolic responses toplant species of transcriptional and metabolic responses tometabolic and developmental acclimation responses to submergence in rice. The Plant

Lee, Seung Cho

2012-01-01

284

High Temperature Oxygen Sensing using K2Mo6Cl14 Luminescence  

E-print Network

technique to realize these objectives. The devel- opment of fiber optic oxygen chemical sensor has been con of quenching decreases with increasing oxygen concentration.[4] The sensor signal is obtained by simply integrating up all the photons in the emission band. In order to develop a fiber based oxygen sensor for high

Ghosh, Ruby N.

285

A UV light enhanced TiO2/graphene device for oxygen sensing at room temperature  

E-print Network

temperature oxygen sensor based on TiO2/graphene device was developed with an enhanced sensing performance the oxygen gas typically use potentiometric1 and amperometric sensors.2 However, their complex structures structures and improve sensing performances. To overcome the common drawbacks of the TiO2-based oxygen sensor

Cao, Wenwu

286

Oxidant and Redox Signaling in Vascular Oxygen Sensing: Implications for Systemic and Pulmonary Hypertension  

PubMed Central

Abstract It has been well known for >100 years that systemic blood vessels dilate in response to decreases in oxygen tension (hypoxia; low Po2), and this response appears to be critical to supply blood to the stressed organ. Conversely, pulmonary vessels constrict to a decrease in alveolar Po2 to maintain a balance in the ventilation-to-perfusion ratio. Currently, although little question exists that the Po2 affects vascular reactivity and vascular smooth muscle cells (VSMCs) act as oxygen sensors, the molecular mechanisms involved in modulating the vascular reactivity are still not clearly understood. Many laboratories, including ours, have suggested that the intracellular calcium concentration ([Ca2+ ]i), which regulates vasomotor function, is controlled by free radicals and redox signaling, including NAD(P)H and glutathione (GSH) redox. In this review article, therefore, we discuss the implications of redox and oxidant alterations seen in pulmonary and systemic hypertension, and how key targets that control [Ca2+ ]i, such as ion channels, Ca2+ release from internal stores and uptake by the sarcoplasmic reticulum, and the Ca2+ sensitivity to the myofilaments, are regulated by changes in intracellular redox and oxidants associated with vascular Po2 sensing in physiologic or pathophysiologic conditions. Antioxid. Redox Signal. 10, 1137–1152. PMID:18315496

Wolin, Michael S.

2008-01-01

287

TOR Signaling Couples Oxygen Sensing to Lifespan in C. elegans.  

PubMed

Metazoans adapt to a low-oxygen environment (hypoxia) through activation of stress-response pathways. Here, we report that transient hypoxia exposure extends lifespan in C. elegans through mitochondrial reactive oxygen species (ROS)-dependent regulation of the nutrient-sensing kinase target of rapamycin (TOR) and its upstream activator, RHEB-1. The increase in lifespan during hypoxia requires the intestinal GATA-type transcription factor ELT-2 downstream of TOR signaling. Using RNA sequencing (RNA-seq), we describe an ELT-2-dependent hypoxia response that includes an intestinal glutathione S-transferase, GSTO-1, and uncover that GSTO-1 is required for lifespan under hypoxia. These results indicate mitochondrial ROS-dependent TOR signaling integrates metabolic adaptations in order to confer survival under hypoxia. PMID:25284791

Schieber, Michael; Chandel, Navdeep S

2014-10-01

288

Oxygen sensing glucose biosensors based on alginate nano-micro systems  

NASA Astrophysics Data System (ADS)

Clinically glucose monitoring in diabetes management is done by point-measurement. However, an accurate, continuous glucose monitoring, and minimally invasive method is desirable. The research aims at developing fluorescence-mediated glucose detecting biosensors based on near-infrared radiation (NIR) oxygen sensitive dyes. Biosensors based on Glucose oxidase (GOx)-Rudpp loaded alginate microspheres (GRAM) and GOx-Platinum-octaethylporphyrin (PtOEP)-PLAalginate microsphere system (GPAM) were developed using air-driven atomization and characterized using optical microscopy, CLSM, fluorescence spectro-photometry etc. Biosensing studies were performed by exposing standard solutions of glucose. Uniform sized GRAM and GPAM with size 50+/-10?m were formed using atomization. CLSM imaging of biosensors suggests that Rudpp and PtOEP nanoparticles are uniformly distributed in alginate microspheres. The GRAM and GPAM showed a good regression constant of 0.974 and of 0.9648 over a range of 0-10 mM of glucose with a high sensitivity of 3.349%/mM (625 nm) and 2.38%/mM (645 nm) at 10 mM of glucose for GRAM and GPAM biosensor. GRAM and GPAM biosensors show great potential in development of an accurate and minimally invasive glucose biosensor. NIR dye based assays can aid sensitive, minimally-invasive and interference-free detection of glucose in diabetic patients.

Chaudhari, Rashmi; Joshi, Abhijeet; Srivastava, Rohit

2014-04-01

289

Enhancement in sensitivity and detection of luminescent quenching based oxygen sensing by gold nanoparticles  

NASA Astrophysics Data System (ADS)

The field of plasmonics has shown a great promise in the enhancement of luminescence detection. Here, a simple method to enhance oxygen detection by quenching of Ru[(4,7-diphenyl-1,10-anthroline)3]2+ (or Ru[dpp]2+) in a sol-gel matrix by localized surface plasmon resonance (LSPR) of gold nanoparticles (AuNP) is presented. In the experiments, AuNP (10 +/- 1.5 nm diameter) were added to a sol that was prepared by hydrolysis of trimethoxysilane, octyltrimethoxysilane and ethanol in the presence of Ru[dpp]2+ luminophore. The resulting sol of the mixture was spincoated on glass and allowed to age in the dark for one week to form the sol-gel film. A control sample was also prepared using the procedure, except that AuNP was not added to the sol. The resulting AuNP embedded sol-gel shows 8.3 times improvement in the baseline (0% O2) intensity (I0) over the control. Moreover, there is a dramatic improvement in the sensitivity from 0.0011 per % O2 in the control to 0.059 per % O2 with AuNP, for O2 level below 15%. Signal to noise ratio also improved, thus leading to a 100-fold improvement in the detection limit. Using phaseluminometry, it was determined that there is a reduction in the luminescence lifetime when AuNP is added to the sol-gel matrix. This reduction in the lifetime can be explained by the near-field interaction between the luminophores and the AuNP.

Cheung, Maurice C.-K.; Roche, Philip J. R.; Yao, Lei; Kirk, Andrew G.; Chodavarapu, Vamsy P.

2010-06-01

290

Novel HIF2A mutations disrupt oxygen sensing, leading to polycythemia, paragangliomas, and somatostatinomas  

PubMed Central

Hypoxia-inducible factors (HIFs) control the cellular response to hypoxia and, when dysregulated, contribute to tumorigenesis. Previously, we identified 2 gain-of-function somatic mutations in patients presenting with multiple paragangliomas or somatostatinomas, and polycythemia. Here, we report 2 additional unique HIF2A mutations, which disrupt the hydroxylation domain recognized by prolyl hydroxylase domain-2 containing protein, leading to stabilization of HIF-2? and increased expression of hypoxia-related genes. PMID:23361906

Yang, Chunzhang; Sun, Michael G.; Matro, Joey; Huynh, Thanh T.; Rahimpour, Shervin; Prchal, Josef T.; Lechan, Ronald; Lonser, Russell

2013-01-01

291

Novel HIF2A mutations disrupt oxygen sensing, leading to polycythemia, paragangliomas, and somatostatinomas.  

PubMed

Hypoxia-inducible factors (HIFs) control the cellular response to hypoxia and, when dysregulated, contribute to tumorigenesis. Previously, we identified 2 gain-of-function somatic mutations in patients presenting with multiple paragangliomas or somatostatinomas, and polycythemia. Here, we report 2 additional unique HIF2A mutations, which disrupt the hydroxylation domain recognized by prolyl hydroxylase domain-2 containing protein, leading to stabilization of HIF-2? and increased expression of hypoxia-related genes. PMID:23361906

Yang, Chunzhang; Sun, Michael G; Matro, Joey; Huynh, Thanh T; Rahimpour, Shervin; Prchal, Josef T; Lechan, Ronald; Lonser, Russell; Pacak, Karel; Zhuang, Zhengping

2013-03-28

292

The effect of high light intensities on luminescence lifetime based oxygen sensing.  

PubMed

This study highlights possible errors in luminescence lifetime measurements when using bright optical oxygen sensors with high excitation light intensities. An analysis of the sensor with a mathematical model shows that high light intensities will cause a depopulation of the ground state of the luminophore, which results in a non-linear behaviour of the luminescence emission light with respect to the excitation light. The effect of this non-linear behaviour on different lifetime determination methods, including phase-fluorometry, is investigated and in good agreement with the output of the model. Furthermore, the consequences of increasingly high light intensities on phase fluorometric lifetime measurements are illustrated for different oxygen sensors based on benzoporphyrin indicators. For the specific case of PdTPTBPF-based sensors an error as high as 50% is possible under high light conditions (0.25 mol m(-2) s(-1) ? 50 mW mm(-2)). A threshold of applied excitation light intensity is derived, thus enabling the point at which errors become significant to be estimated. Strategies to further avoid such errors are presented. The model also predicts a similar depopulation of the ground state of the quencher; however, the effect of this process was not seen in lab measurements. Possible explanations for this deviation are discussed. PMID:25364788

Larndorfer, Christoph; Borisov, Sergey M; Lehner, Philipp; Klimant, Ingo

2014-11-10

293

Measuring the viscosity of whole bovine lens using a fiber optic oxygen sensing system  

PubMed Central

Purpose To obtain a better understanding of oxygen and nutrient transport within the lens, the viscosity of whole lenses was investigated using a fiber optic oxygen sensor (optode). The diffusion coefficient of oxygen was calculated using the Stokes-Einstein equation at the slip boundary condition. Methods The optode was used to measure the oxygen decay signal in samples consisting of different glycerol/water solutions with known viscosities. The oxygen decay signal was fitted to a double exponential decay rate equation, and the lifetimes (tau) were calculated. It was determined that the tau-viscosity relationship is linear, which served as the standard curve. The same procedure was applied to fresh bovine lenses, and the unknown viscosity of the bovine lens was calculated from the tau-viscosity relationship. Results The average viscosity in a whole bovine lens was determined to be 5.74±0.88 cP by our method. Using the Stokes-Einstein equation at the slip boundary condition, the diffusion coefficient for oxygen was calculated to be 8.2 × 10?6 cm2/s. Conclusions These data indicate a higher resistance to flow for oxygen and nutrients in the lens than what is currently assumed in the literature. Overall, this study allows a better understanding of oxygen transport within the lens. PMID:24505211

Thao, Mai T.; Perez, Daniel; Dillon, James

2014-01-01

294

Enhanced performance from a hybrid quenchometric deoxyribonucleic Acid (DNA) silica xerogel gaseous oxygen sensing platform.  

PubMed

A complex of salmon milt deoxyribonucleic acid (DNA) and the cationic surfactant cetyltrimethylammonium (CTMA) forms an organic-soluble biomaterial that can be readily incorporated within an organically modified silane-based xerogel. The photoluminescence (PL) intensity and excited-state luminescence lifetime of tris(4,7'-diphenyl-1,10'-phenanathroline) ruthenium(II) [(Ru(dpp)3](2+), a common O2 responsive luminophore, increases in the presence of DNA-CTMA within the xerogel. The increase in the [Ru(dpp)3](2+)excited-state lifetime in the presence of DNA-CTMA arises from DNA intercalation that attenuates one or more non-radiative processes, leading to an increase in the [Ru(dpp)3](2+) excited-state lifetime. Prospects for the use of these materials in an oxygen sensor are demonstrated. PMID:25280266

Zhou, Bin; Liu, Ke; Liu, Xin; Yung, Ka Yi; Bartsch, Carrie M; Heckman, Emily M; Bright, Frank V; Swihart, Mark T; Cartwright, Alexander N

2014-11-01

295

Determination of the in vivo degradation mechanism of PEGDA hydrogels.  

PubMed

Poly(ethylene glycol) (PEG) hydrogels are one of the most extensively utilized biomaterials systems due to their established biocompatibility and highly tunable properties. It is widely acknowledged that traditional acrylate-derivatized PEG (PEGDA) hydrogels are susceptible to slow degradation in vivo and are therefore unsuitable for long-term implantable applications. However, there is speculation whether the observed degradation is due to hydrolysis of endgroup acrylate esters or oxidation of the ether backbone, both of which are possible in the foreign body response to implanted devices. PEG diacrylamide (PEGDAA) is a polyether-based hydrogel system with similar properties to PEGDA but with amide linkages in place of the acrylate esters. This provides a hydrolytically-stable control that can be used to isolate the relative contributions of hydrolysis and oxidation to the in vivo degradation of PEGDA. Here we show that PEGDAA hydrogels remained stable over 12 weeks of subcutaneous implantation in a rat model while PEGDA hydrogels underwent significant degradation as indicated by both increased swelling ratio and decreased modulus. As PEGDA and PEGDAA have similar susceptibility to oxidation, these results demonstrate for the first time that the primary in vivo degradation mechanism of PEGDA is hydrolysis of the endgroup acrylate esters. Additionally, the maintenance of PEGDAA hydrogel properties in vivo indicates their suitability for long-term implants. These studies serve to elucidate key information about a widely used biomaterial system to allow for better implantable device design and to provide a biostable replacement option for PEGDA in applications that require long-term stability. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 4244-4251, 2014. PMID:24464985

Browning, M B; Cereceres, S N; Luong, P T; Cosgriff-Hernandez, E M

2014-12-01

296

In vivo dosimetry in brachytherapy  

SciTech Connect

In vivo dosimetry (IVD) has been used in brachytherapy (BT) for decades with a number of different detectors and measurement technologies. However, IVD in BT has been subject to certain difficulties and complexities, in particular due to challenges of the high-gradient BT dose distribution and the large range of dose and dose rate. Due to these challenges, the sensitivity and specificity toward error detection has been limited, and IVD has mainly been restricted to detection of gross errors. Given these factors, routine use of IVD is currently limited in many departments. Although the impact of potential errors may be detrimental since treatments are typically administered in large fractions and with high-gradient-dose-distributions, BT is usually delivered without independent verification of the treatment delivery. This Vision 20/20 paper encourages improvements within BT safety by developments of IVD into an effective method of independent treatment verification.

Tanderup, Kari [Department of Oncology, Aarhus University Hospital, Aarhus 8000 (Denmark); Department of Clinical Medicine, Aarhus University, Aarhus 8000 (Denmark); Beddar, Sam [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Andersen, Claus E.; Kertzscher, Gustavo [Center of Nuclear Technologies, Technical University of Denmark, Roskilde 4000 (Denmark); Cygler, Joanna E. [Department of Physics, Ottawa Hospital Cancer Centre, Ottawa, Ontario K1H 8L6 (Canada)

2013-07-15

297

In vivo dosimetry in brachytherapy.  

PubMed

In vivo dosimetry (IVD) has been used in brachytherapy (BT) for decades with a number of different detectors and measurement technologies. However, IVD in BT has been subject to certain difficulties and complexities, in particular due to challenges of the high-gradient BT dose distribution and the large range of dose and dose rate. Due to these challenges, the sensitivity and specificity toward error detection has been limited, and IVD has mainly been restricted to detection of gross errors. Given these factors, routine use of IVD is currently limited in many departments. Although the impact of potential errors may be detrimental since treatments are typically administered in large fractions and with high-gradient-dose-distributions, BT is usually delivered without independent verification of the treatment delivery. This Vision 20/20 paper encourages improvements within BT safety by developments of IVD into an effective method of independent treatment verification. PMID:23822403

Tanderup, Kari; Beddar, Sam; Andersen, Claus E; Kertzscher, Gustavo; Cygler, Joanna E

2013-07-01

298

In Vivo EPR For Dosimetry  

PubMed Central

As a result of terrorism, accident, or war, populations potentially can be exposed to doses of ionizing radiation that could cause direct clinical effects within days or weeks. There is a critical need to determine the magnitude of the exposure to individuals so that those with significant risk have appropriate procedures initiated immediately, while those without a significant probability of acute effects can be reassured and removed from the need for further consideration in the medical/emergency system. In many of the plausible scenarios there is an urgent need to make the determination very soon after the event and while the subject is still present. In vivo EPR measurements of radiation-induced changes in the enamel of teeth is a method, perhaps the only such method, which can differentiate among doses sufficiently for classifying individuals into categories for treatment with sufficient accuracy to facilitate decisions on medical treatment. In its current state, the in vivo EPR dosimeter can provide estimates of absorbed dose with an error approximately ± 50 cGy over the range of interest for acute biological effects of radiation, assuming repeated measurements of the tooth in the mouth of the subject. The time required for acquisition, the lower limit, and the precision are expected to improve, with improvements in the resonator and the algorithm for acquiring and calculating the dose. The magnet system that is currently used, while potentially deployable, is somewhat large and heavy, requiring that it be mounted on a small truck or trailer. Several smaller magnets, including an intraoral magnet are under development, which would extend the ease of use of this technique. PMID:18591988

Swartz, Harold M.; Burke, Greg; Coey, M.; Demidenko, Eugene; Dong, Ruhong; Grinberg, Oleg; Hilton, James; Iwasaki, Akinori; Lesniewski, Piotr; Kmiec, Maciej; Lo, Kai-Ming; Nicolalde, R. Javier; Ruuge, Andres; Sakata, Yasuko; Sucheta, Artur; Walczak, Tadeusz; Williams, Benjamin B.; Mitchell, Chad; Romanyukha, Alex; Schauer, David A.

2007-01-01

299

Optical stimulation of peripheral nerves in vivo  

NASA Astrophysics Data System (ADS)

This dissertation documents the emergence and validation of a new clinical tool that bridges the fields of biomedical optics and neuroscience. The research herein describes an innovative method for direct neurostimulation with pulsed infrared laser light. Safety and effectiveness of this technique are first demonstrated through functional stimulation of the rat sciatic nerve in vivo. The Holmium:YAG laser (lambda = 2.12 mum) is shown to operate at an optimal wavelength for peripheral nerve stimulation with advantages over standard electrical neural stimulation; including contact-free stimulation, high spatial selectivity, and lack of a stimulation artifact. The underlying biophysical mechanism responsible for transient optical nerve stimulation appears to be a small, absorption driven thermal gradient sustained at the axonal layer of nerve. Results explicitly prove that low frequency optical stimulation can reliably stimulate without resulting in tissue thermal damage. Based on the positive results from animal studies, these optimal laser parameters were utilized to move this research into the clinic with a combined safety and efficacy study in human subjects undergoing selective dorsal rhizotomy. The clinical Holmium:YAG laser was used to effectively stimulate human dorsal spinal roots and elicit functional muscle responses recorded during surgery without evidence of nerve damage. Overall these results predict that this technology can be a valuable clinical tool in various neurosurgical applications.

Wells, Jonathon D.

300

Imaging axonal transport of mitochondria in vivo  

E-print Network

Imaging axonal transport of mitochondria in vivo Thomas Misgeld1,2,5, Martin Kerschensteiner1,3,5, Florence M Bareyre1,3, Robert W Burgess4 & Jeff W Lichtman1 Neuronal mitochondria regulate synaptic and sustained changes in anterograde and retrograde transport. In vivo imaging of mitochondria will be a useful

Cai, Long

301

Sentinel lymph node detection ex vivo using  

E-print Network

-vivo methylene-blue-dyed sen- tinel lymph nodes embedded in 3.2-cm-thick chicken breast tissues. The UOT system, as is photoacoustic imaging,6 nonionizing UOT has the potential to detect methylene-blue-dyed SLNs noninva- sively to our knowledge, we report the use of UOT to detect ex-vivo methylene-blue-dyed SLNs buried in chicken

Wang, Lihong

302

Comparison of in vivo normal and malignant  

E-print Network

JermeabiIization (EPN), also termed electro- poration, is a process that results in cell membrane permeability changes]. In vitro cell EPN has been well described [3, 4]. In vivo investigations are more dif- ficult to perform of sophisticated gamma-camera equip- ment. Recently, a new quantitative method of investi- gation of in vivo EPN

Ljubljana, University of

303

Assessing in vivo toxicity of graphene materials: current methods and future outlook.  

PubMed

Graphene, a novel 2D carbon nanomaterial with unique properties, has attracted massive attention. Evaluating its toxicity is of great significance due to its potential applications in many fields, especially in biomedicine. In this review, the toxicity of graphene-based nanomaterials (GNMs) and related mechanisms at the molecular and cellular level, various approaches to evaluation of the in vivo toxicity of GNMs and major factors defining their toxicity will be discussed and summarized. This review will allow better understanding of the in vitro and in vivo toxicity of GNMs, which, we believe, may facilitate design and fabrication of novel, biocompatible and efficient GNM-based systems for biomedical applications. PMID:25253502

Ma, Yufei; Shen, He; Tu, Xiaolong; Zhang, Zhijun

2014-07-01

304

Viral Nanoparticles for In vivo Tumor Imaging  

PubMed Central

The use of nanomaterials has the potential to revolutionize materials science and medicine. Currently, a number of different nanoparticles are being investigated for applications in imaging and therapy. Viral nanoparticles (VNPs) derived from plants can be regarded as self-assembled bionanomaterials with defined sizes and shapes. Plant viruses under investigation in the Steinmetz lab include icosahedral particles formed by Cowpea mosaic virus (CPMV) and Brome mosaic virus (BMV), both of which are 30 nm in diameter. We are also developing rod-shaped and filamentous structures derived from the following plant viruses: Tobacco mosaic virus (TMV), which forms rigid rods with dimensions of 300 nm by 18 nm, and Potato virus X (PVX), which form filamentous particles 515 nm in length and 13 nm in width (the reader is referred to refs. 1 and 2 for further information on VNPs). From a materials scientist's point of view, VNPs are attractive building blocks for several reasons: the particles are monodisperse, can be produced with ease on large scale in planta, are exceptionally stable, and biocompatible. Also, VNPs are "programmable" units, which can be specifically engineered using genetic modification or chemical bioconjugation methods 3. The structure of VNPs is known to atomic resolution, and modifications can be carried out with spatial precision at the atomic level4, a level of control that cannot be achieved using synthetic nanomaterials with current state-of-the-art technologies. In this paper, we describe the propagation of CPMV, PVX, TMV, and BMV in Vigna ungiuculata and Nicotiana benthamiana plants. Extraction and purification protocols for each VNP are given. Methods for characterization of purified and chemically-labeled VNPs are described. In this study, we focus on chemical labeling of VNPs with fluorophores (e.g. Alexa Fluor 647) and polyethylene glycol (PEG). The dyes facilitate tracking and detection of the VNPs 5-10, and PEG reduces immunogenicity of the proteinaceous nanoparticles while enhancing their pharmacokinetics 8,11. We demonstrate tumor homing of PEGylated VNPs using a mouse xenograft tumor model. A combination of fluorescence imaging of tissues ex vivo using Maestro Imaging System, fluorescence quantification in homogenized tissues, and confocal microscopy is used to study biodistribution. VNPs are cleared via the reticuloendothelial system (RES); tumor homing is achieved passively via the enhanced permeability and retention (EPR) effect12. The VNP nanotechnology is a powerful plug-and-play technology to image and treat sites of disease in vivo. We are further developing VNPs to carry drug cargos and clinically-relevant imaging moieties, as well as tissue-specific ligands to target molecular receptors overexpressed in cancer and cardiovascular disease. PMID:23183850

Wen, Amy M.; Lee, Karin L.; Yildiz, Ibrahim; Bruckman, Michael A.; Shukla, Sourabh; Steinmetz, Nicole F.

2012-01-01

305

Optimal ultraviolet wavelength for in vivo photoacoustic imaging of cell nuclei  

NASA Astrophysics Data System (ADS)

In order to image noninvasively cell nuclei in vivo without staining, we have developed ultraviolet photoacoustic microscopy (UV-PAM), in which ultraviolet light excites nucleic acids in cell nuclei to produce photoacoustic waves. Equipped with a tunable laser system, the UV-PAM was applied to in vivo imaging of cell nuclei in small animals. We found that 250 nm was the optimal wavelength for in vivo photoacoustic imaging of cell nuclei. The optimal wavelength enables UV-PAM to image cell nuclei using as little as 2 nJ laser pulse energy. Besides the optimal wavelength, application of a wavelength between 245 and 275 nm can produce in vivo images of cell nuclei with specific, positive, and high optical contrast.

Yao, Da-Kang; Chen, Ruimin; Maslov, Konstantin; Zhou, Qifa; Wang, Lihong V.

2012-05-01

306

Pilot in vivo toxicological investigation of boron nitride nanotubes  

PubMed Central

Boron nitride nanotubes (BNNTs) have attracted huge attention in many different research fields thanks to their outstanding chemical and physical properties. During recent years, our group has pioneered the use of BNNTs for biomedical applications, first of all assessing their in vitro cytocompatibility on many different cell lines. At this point, in vivo investigations are necessary before proceeding toward realistic developments of the proposed applications. In this communication, we report a pilot toxicological study of BNNTs in rabbits. Animals were injected with a 1 mg/kg BNNT solution and blood tests were performed up to 72 hours after injection. The analyses aimed at evaluating any acute alteration of hematic parameters that could represent evidence of functional impairment in blood, liver, and kidneys. Even if preliminary, the data are highly promising, as they showed no adverse effects on all the evaluated parameters, and therefore suggest the possibility of the realistic application of BNNTs in the biomedical field. PMID:22275819

Ciofani, Gianni; Danti, Serena; Genchi, Giada Graziana; D'Alessandro, Delfo; Pellequer, Jean-Luc; Odorico, Michael; Mattoli, Virgilio; Giorgi, Mario

2012-01-01

307

Computer simulation of cardiac cryoablation: comparison with in vivo data.  

PubMed

Simulation of cardiac cryoablation by the finite element method can contribute to optimizing ablation results and understanding the effects of modifications prior to time-consuming and expensive experiments. In this work an intervention scenario using a 9 Fr 8 mm tip applicator applied to ventricular tissue was simulated using the effective heat capacity model based on Pennes' bioheat equation. Using experimentally obtained refrigerant flow rates and temperature profiles recorded by a thermocouple located at the tip of the applicator the cooling performance of the refrigerant was estimated and integrated by time and temperature dependent boundary conditions based on distinct phases of a freeze-thaw cycle. Our simulations exhibited a mean difference of approximately 6°C at the applicator tip compared to temperature profiles obtained during in vivo experiments. The presented model is a useful tool for simulation and validation of new developments in clinical cardiac cryoablation. PMID:23972331

Handler, Michael; Fischer, Gerald; Seger, Michael; Kienast, Roland; Nowak, Claudia-Nike; Pehböck, Daniel; Hintringer, Florian; Baumgartner, Christian

2013-12-01

308

Lessons learned from vivo-morpholinos: How to avoid vivo-morpholino toxicity  

PubMed Central

Vivo-morpholinos are a promising tool for gene silencing. These oligonucleotide analogs transiently silence genes by blocking either translation or pre-mRNA splicing. Little to no toxicity has been reported for vivo-morpholino treatment. However, in a recent study conducted in our lab, treatment of mice with vivo-morpholinos resulted in high mortality rates. We hypothesized that the deaths were the result of oligonucleotide hybridization, causing an increased cationic charge associated with the dendrimer delivery moiety of the vivo-morpholino. The cationic charge increased blood clot formation in whole blood treated with vivo-morpholinos, suggesting that clotting could have caused cardiac arrest in the deceased mice. Therefore, we investigate the mechanism by which some vivo-morpholinos increase mortality rates and propose techniques to alleviate vivo-morpholino toxicity. PMID:24806225

Ferguson, David P.; Dangott, Lawrence J.; Lightfoot, J. Timothy

2014-01-01

309

2D luminescence imaging of pH in vivo  

PubMed Central

Luminescence imaging of biological parameters is an emerging field in biomedical sciences. Tools to study 2D pH distribution are needed to gain new insights into complex disease processes, such as wound healing and tumor metabolism. In recent years, luminescence-based methods for pH measurement have been developed. However, for in vivo applications, especially for studies on humans, biocompatibility and reliability under varying conditions have to be ensured. Here, we present a referenced luminescent sensor for 2D high-resolution imaging of pH in vivo. The ratiometric sensing scheme is based on time-domain luminescence imaging of FITC and ruthenium(II)tris-(4,7-diphenyl-1,10-phenanthroline). To create a biocompatible 2D sensor, these dyes were bound to or incorporated into microparticles (aminocellulose and polyacrylonitrile), and particles were immobilized in polyurethane hydrogel on transparent foils. We show sensor precision and validity by conducting in vitro and in vivo experiments, and we show the versatility in imaging pH during physiological and chronic cutaneous wound healing in humans. Implementation of this technique may open vistas in wound healing, tumor biology, and other biomedical fields. PMID:21262842

Schreml, Stephan; Meier, Robert J.; Wolfbeis, Otto S.; Landthaler, Michael; Szeimies, Rolf-Markus; Babilas, Philipp

2011-01-01

310

In vivo generator for radioimmunotherapy  

DOEpatents

The present invention involves labeling monoclonal antibodies with intermediate half-life radionuclides which decay to much shorter half-life daughters with desirable high energy beta emissions. Since the daughter will be in equilibrium with the parent, it can exert an in-situ tumoricidal effect over a prolonged period in a localized fashion, essentially as an "in-vivo generator". This approach circumvents the inverse relationship between half-life and beta decay energy. Compartmental modeling was used to determine the relative distribution of dose from both parent and daughter nuclei in target and non-target tissues. Actual antibody biodistribution data have been used to fit realistic rate constants for a model containing tumor, blood, and non-tumor compartments. These rate constants were then used in a variety of simulations for two generator systems, Ba-128/Cs-128 (t.sub.1/2 =2.4d/3.6m) and Pd-112/Ag-112 (t.sub.1/2 =0.9d/192m). The results show that higher tumor/background dose ratios may be achievable by virtue of the rapid excretion of a chemically different daughter during the uptake and clearance phases. This modeling also quantitatively demonstrates the favorable impact on activity distribution of a faster monoclonal antibody tumor uptake, especially when the antibody is labeled with a radionuclide with a comparable half-life.

Mausner, Leonard F. (Stony Brook, NY); Srivastava, Suresh G. (Setauket, NY); Straub, Rita F. (Brookhaven, NY)

1988-01-01

311

In Vivo Methods for the Assessment of Topical Drug Bioavailability  

PubMed Central

This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described. PMID:17985216

Herkenne, Christophe; Alberti, Ingo; Naik, Aarti; Kalia, Yogeshvar N.; Mathy, Francois-Xavier; Preat, Veronique

2007-01-01

312

Viscous optical clearing agent for in vivo optical imaging  

NASA Astrophysics Data System (ADS)

By allowing more photons to reach deeper tissue, the optical clearing agent (OCA) has gained increasing attention in various optical imaging modalities. However, commonly used OCAs have high fluidity, limiting their applications in in vivo studies with oblique, uneven, or moving surfaces. In this work, we reported an OCA with high viscosity. We measured the properties of this viscous OCA, and tested its successful performances in the imaging of a living animal's skin with two optical imaging modalities: photoacoustic microscopy and optical coherence tomography. Our results demonstrated that the viscous OCA has a great potential in the study of different turbid tissues using various optical imaging modalities.

Deng, Zijian; Jing, Lijia; Wu, Ning; lv, Pengyu; Jiang, Xiaoyun; Ren, Qiushi; Li, Changhui

2014-07-01

313

Use of an optical clearing agent during noninvasive laser coagulation of the canine vas deferens, ex vivo and in vivo  

NASA Astrophysics Data System (ADS)

Development of a noninvasive vasectomy technique may eliminate male fear of complications and result in a more popular procedure. This study explores application of an optical clearing agent (OCA) to the scrotal skin to reduce both the laser power necessary for successful noninvasive laser vasectomy and the probability of scrotal skin burns. A mixture of DMSO/glycerol was noninvasively delivered into the scrotal skin using a Madajet. Near-infrared laser radiation with a range of average powers (7.0-11.7 W) was delivered in conjunction with a range of cryogen spray cooling rates (0.20-0.33 Hz) to the skin surface in a canine model, ex vivo and in vivo. Burst pressure (BP) measurements were conducted to quantify the strength of vas closure. A 30-min application of the OCA improved skin transparency by 26 +/- 5 %, reducing the average power necessary for successful noninvasive laser vasectomy from 9.2 W without OCA (BP = 291 +/- 31 mmHg) to 7.0 W with OCA (BP = 292 +/- 19 mmHg). Control studies without OCA at 7.0 W failed to coagulate the vas with burst pressures (82 +/- 28 mmHg) significantly below typical ejaculation pressures (136 +/- 29 mmHg). Application of an optical clearing agent reduced the laser power necessary for successful noninvasive thermal coagulation of the vas by approximately 25%. This technique may result in the use of a less expensive laser system and eliminate the formation of scrotal skin burns during the procedure.

Cilip, Christopher M.; Ross, Ashley E.; Jarow, Jonathan P.; Fried, Nathaniel M.

2010-02-01

314

In vivo brain microdialysis: advances in neuropsychopharmacology and drug discovery  

PubMed Central

Introduction Microdialysis is an important in vivo sampling technique, useful in the assay of extracellular tissue fluid. The technique has both pre-clinical and clinical applications but is most widely used in neuroscience. The in vivo microdialysis technique allows measurement of neurotransmitters such as acetycholine (ACh), the biogenic amines including dopamine (DA), norepinephrine (NE) and serotonin (5-HT), amino acids such as glutamate (Glu) and gamma aminobutyric acid (GABA), as well as the metabolites of the aforementioned neurotransmitters, and neuropeptides in neuronal extracellular fluid in discrete brain regions of laboratory animals such as rodents and non-human primates. Areas covered In this review we present a brief overview of the principles and procedures related to in vivo microdialysis and detail the use of this technique in the pre-clinical measurement of drugs designed to be used in the treatment of chemical addiction, neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and as well as psychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD) and schizophrenia. This review offers insight into the tremendous utility and versatility of this technique in pursuing neuropharmacological investigations as well its significant potential in rational drug discovery. Expert opinion In vivo microdialysis is an extremely versatile technique, routinely used in the neuropharmacological investigation of drugs used for the treatment of neurological disorders. This technique has been a boon in the elucidation of the neurochemical profile and mechanism of action of several classes of drugs especially their effects on neurotransmitter systems. The exploitation and development of this technique for drug discovery in the near future will enable investigational new drug candidates to be rapidly moved into the clinical trial stages and to market thus providing new successful therapies for neurological diseases that are currently in demand. PMID:21532928

Darvesh, Altaf S.; Carroll, Richard T.; Geldenhuys, Werner J.; Gudelsky, Gary A.; Klein, Jochen; Meshul, Charles K.; Van der Schyf, Cornelis J.

2010-01-01

315

In vivo soft tissue damage assessment for applications in surgery  

Microsoft Academic Search

In robotic and conventional minimally invasive surgery the risk of complications caused by collateral tissue damage remains high. This paper studies the concept of imposing damage thresholds on surgical instruments to avoid tissue overload. More specifically, the correlation between mechanical loading and damage in case of vascular clamping is investigated.With a computer controlled device, a high and a low clamping

Nele Famaey; Erik Verbeken; Stefan Vinckier; Bert Willaert; Paul Herijgers; Jos Vander Sloten

2010-01-01

316

Gravitational physiology of human immune cells: a review of in vivo, ex vivo and in vitro studies  

NASA Technical Reports Server (NTRS)

The study of the function of immune cells in microgravity has been studied for more than 20 years in several laboratories. It is clear today that the immune system is depressed in more than 50% of the astronauts during and after space flight and that the activation of T lymphocytes by mitogens in vitro changes dramatically. This article gives an overview of the gravitational studies conducted by our laboratory in Spacelab, in MIR station, in sounding rockets and on the ground in the clinostat and the centrifuge. Three experimental approaches are followed in our work: (i) Ex vivo studies are performed with blood samples drawn from astronauts; (ii) in vivo studies are based on the application of seven antigens to the skin of the astronauts; (iii) in vitro studies are carried out with immune cells purified from the blood of healthy donors (not astronauts). The data from our in vivo and ex vivo studies are in agreement with those of other laboratories and show that the immunological function is depressed in the majority of astronauts as a consequence of the stress of space flight rather than by a direct influence of gravity on the cell. Immune depression may become a critical hazard on long duration flights on space stations or to other planets. In vitro experiments show that cultures of free-floating lymphocytes and monocytes undergo a dramatic depression of activation by the mitogen concanavalin A, while activation is more than doubled when the cells are attached to microcarrier beads. Such effects may be attributed to both direct and indirect effects of gravitational unloading on basic biological mechanisms of the cell. While the in vitro data are very important to clarify certain aspects of the biological mechanism of T cells activation, they are not descriptive of the changes of the immunological function of the astronauts.

Cogoli, A.

1996-01-01

317

In vivo [35S]-methionine incorporation.  

PubMed

The purpose of this assay is to measure the incorporation of radiolabeled [(35)S]-methionine into newly synthesized proteins in exponentially growing yeast cells. This allows for a quantitative in vivo measurement of total protein synthesis. PMID:24423266

Esposito, Anthony M; Kinzy, Terri Goss

2014-01-01

318

Development of the in vivo flow cytometer  

E-print Network

An in vivo flow cytometer has been developed that allows the real-time detection and quantification of circulating cells containing fluorescent proteins or labeled with fluorochrome molecules in live animals, without the ...

Novak, John P. (John Peter), 1957-

2004-01-01

319

In vivo radiobiology of heavy ions  

SciTech Connect

The radiobiology of heavy charged particles has been investigated with various animal systems in vivo at the Lawrence Berkeley Laboratory using the helium beam from the 184'' synchrocyclotron and the carbon, neon, and argon beams from the BEVALAC. Tumor experiments were carried out using the R/sub 1/ sarcoma in rats and the EMT6 mouse mammary carcinoma, comparing X rays, carbon ions, neon ions, and argon ions. In vivo normal tissue experiments have been carried out with a wide range of tissues including testis, bone marrow, intestinal crypt cells, lens of the eye, esophagus, lung, and the spinal cord. The induction of dominant lethal mutations after irradiation of the testis was assayed by in vivo embryo culture after in vivo irradiation. Experiments were also done with the Harderian gland tumor induction system.

Phillips, T.L. (Univ. of California, San Francisco); Ross, G.Y.; Goldstein, L.S.; Ainsworth, J.; Alpen, E.

1982-12-01

320

Bone in vivo: Surface mapping technique  

E-print Network

Bone surface mapping technique is proposed on the bases of two kinds of uniqueness of bone in vivo, (i) magnitude of the principal moments of inertia, (ii) the direction cosines of principal axes of inertia relative to inertia reference frame. We choose the principal axes of inertia as the bone coordinate system axes. The geographical marks such as the prime meridian of the bone in vivo are defined and methods such as tomographic reconstruction and boundary development are employed so that the surface of bone in vivo can be mapped. Experimental results show that the surface mapping technique can both reflect the shape and help study the surface changes of bone in vivo. The prospect of such research into the surface shape and changing laws of organ, tissue or cell will be promising.

Fan, Yifang; Lin, Zhiyu; Lv, Changsheng

2010-01-01

321

In Vivo Imaging of Tissue Physiological Function  

Cancer.gov

The National Cancer Institute's Radiation Biology Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize methods for in vivo imaging.

322

Sustained release of nutrients in vivo  

US Patent & Trademark Office Database

Nutritional compositions delivered in vivo in a time controlled manner sustainable over long periods of time, provide enhancing athletic performance, increased hand/eye coordination and concentration on the task at hand.

2013-10-22

323

Psychological Stress Exerts an Adjuvant Effect on Skin Dendritic Cell Functions In Vivo1  

Microsoft Academic Search

Psychological stress affects the pathophysiology of infectious, inflammatory, and autoimmune diseases. However, the mechanisms by which stress could modulate immune responses in vivo are poorly understood. In this study, we report that application of a psychological stress before immunization exerts an adjuvant effect on dendritic cell (DC), resulting in increased primary and memory Ag-specific T cell immune responses. Acute stress

Pierre Saint-Mezard; Cyril Chavagnac; Sophie Bosset; Marius Ionescu; Eric Peyron; Dominique Kaiserlian; Jean-Francois Nicolas; Frederic Berard

2003-01-01

324

Direct noninvasive observation of near infrared photobleaching of autofluorescence in human volar side fingertips in vivo  

Microsoft Academic Search

Human transdermal in vivo spectroscopic applications for tissue analysis involving near infrared (NIR) light often must contend with broadband NIR fluorescence that, depending on what kind of spectroscopy is being employed, can degrade signal to noise ratios and dynamic range. Such NIR fluorescence, i.e. \\

Bin Deng; Colin Wright; Eric Lewis-Clark; G. Shaheen; Roman Geier; J. Chaiken

2010-01-01

325

Simultaneous optical and nuclear magnetic resonance spectroscopy for monitoring cardiac energetics in vivo  

Microsoft Academic Search

There are a number of applications in which it is useful to simultaneously collect data from what are traditionally separate instrumentation modalities. In particular, in vivo physiological investigations in which data from parallel experiments must be correlated would benefit from simultaneous data collection through 1) elimination of subject variability, 2) elimination of treatment variability, and 3) a reduction in the

Roger J. McNichols; Gerard L. Coté; Jeremy S. Wasser; Steven M. Wright

2000-01-01

326

Transplantation of Ex Vivo Cultured Limbal Epithelial Stem Cells: A Review of Techniques and Clinical Results  

Microsoft Academic Search

Ex vivo cultured limbal epithelial stem cells have been used successfully to treat corneal limbal stem cell deficiency. We identified 17 reports of the application of this novel cell-based therapy in humans. In addition we identified four reports of the use of culture oral mucosal epithelial cells to treat limbal stem cell deficiency. We examined these reports to discern the

Alex J. Shortt; Genevieve A. Secker; Maria D. Notara; G. Astrid Limb; Peng T. Khaw; Stephen J. Tuft; Julie T. Daniels

2007-01-01

327

In vitro and in vivo studies on wireless powering of medical sensors and implantable devices  

Microsoft Academic Search

This paper investigates wireless electricity (witricity) and its application to medical sensors and implantable devices. Several coupling scenarios of resonators are analyzed theoretically. In vitro experiments are conducted in open air and through an agar phantom of the human head. An in vivo animal experiment is also carried out. Our studies indicate that witricity is a suitable tool for providing

Fei Zhang; Xiaoyu Liu; Steven A. Hackworth; Robert J. Sclabassi; Mingui Sun

2009-01-01

328

REVIEW ARTICLE: Nuclear-based techniques for the in vivo study of human body composition  

Microsoft Academic Search

A variety of nuclear-based techniques for the in vivo study of human body decomposition is now available for clinical diagnosis and research, and the number of centres where such work is performed is likely to grow substantially in the next few years. Their most important applications at present are in the measurement of bone mineral mass (calcium), body protein (nitrogen)

S. H. Cohn; R. M. Parr

1985-01-01

329

Nuclear-based techniques for the in vivo study of human body composition  

Microsoft Academic Search

A variety of nuclear-based techniques for the in vivo study of human body decomposition is now available for clinical diagnosis and research, and the number of centres where such work is performed is likely to grow substantially in the next few years. Their most important applications at present are in the measurement of bone mineral mass (calcium), body protein (nitrogen)

S H Cohn; R M Parr

1985-01-01

330

21 CFR 320.22 - Criteria for waiver of evidence of in vivo bioavailability or bioequivalence.  

Code of Federal Regulations, 2010 CFR

...be demonstrated by evidence obtained in vitro in lieu of in vivo data. FDA shall waive...Both drug products meet an appropriate in vitro test approved by FDA; and (iii) The...in the application, shown to meet an in vitro test that has been correlated with in...

2010-04-01

331

Optical Doppler Tomography: Imaging in vivo Blood Flow Dynamics Following Pharmacological Intervention and Photodynamic Therapy  

Microsoft Academic Search

A noninvasive optical technique has been developed for imaging in vivo blood flow dynamics and vessel structure with high spatial resolution. The technique is based on optical Doppler tomography, which combines Doppler velocimetry with optical coherence tomography to measure blood flow velocity at discrete spatial locations in turbid biological tissue. Applications of this technique for monitoring changes in blood flow

Zhongping Chen; Thomas E. Milner; Xiaojun Wang; Shyam Srinivas; J. Stuart Nelson

1998-01-01

332

In vivo rates of protein synthesis in Atlantic salmon (Salmo salar L.) smolts determined using a stable isotope flooding dose technique  

Microsoft Academic Search

In vivo rates of protein synthesis in fish have predominantly been measured using a single flooding dose injection of a solution containing 3H-Phenylalanine as a tracer. However, use of a radiolabelled tracer restricts the application of this technique to controlled laboratory conditions. In this study, the flooding dose technique was used to successfully measure in vivo rates of protein synthesis

S. F. Owen; I. D. McCarthy; P. W. Watt; V. Ladero; J. A. Sanchez; D. F. Houlihan; M. J. Rennie

1999-01-01

333

Ex Vivo and In Vivo Models for Endoscopic Submucosal Dissection Training  

PubMed Central

Endoscopic submucosal dissection is a technically challenging but highly effective technique for the treatment of well selected early neoplasms in the digestive tract. Although it is frequently performed in East Asian countries, the Western world has not adopted this technique yet, probably due in part to the difficulty to learn it. Ex vivo and in vivo animal models are invaluable tools to overcome at least the beginning of the learning curve, although the initial step is the acquisition of basic knowledge about early diagnosis of neoplasias, and observing real procedures in expert centers. The practical issues, advantages, and disadvantages of the ex vivo and in vivo models are discussed. PMID:23251881

Gonzalez, Nicolas; Arnau, Maria Rosa

2012-01-01

334

Quantum Dots for Live Cell and In Vivo Imaging  

PubMed Central

In the past few decades, technology has made immeasurable strides to enable visualization, identification, and quantitation in biological systems. Many of these technological advancements are occurring on the nanometer scale, where multiple scientific disciplines are combining to create new materials with enhanced properties. The integration of inorganic synthetic methods with a size reduction to the nano-scale has lead to the creation of a new class of optical reporters, called quantum dots. These semiconductor quantum dot nanocrystals have emerged as an alternative to organic dyes and fluorescent proteins, and are brighter and more stable against photobleaching than standard fluorescent indicators. Quantum dots have tunable optical properties that have proved useful in a wide range of applications from multiplexed analysis such as DNA detection and cell sorting and tracking, to most recently demonstrating promise for in vivo imaging and diagnostics. This review provides an in-depth discussion of past, present, and future trends in quantum dot use with an emphasis on in vivo imaging and its related applications. PMID:19333416

Walling, Maureen A; Novak, Jennifer A; Shepard, Jason R. E

2009-01-01

335

In Vivo Response to Dynamic Hyaluronic Acid Hydrogels  

PubMed Central

Tissue-specific elasticity arises in part from developmental changes in extracellular matrix over time, e.g. ~ 10-fold myocardial stiffening in the chicken embryo. When this time-dependent stiffening is mimicked in vitro with thiolated hyaluronic acid (HA-SH) hydrogels, improved cardiomyocyte maturation has been observed. However, host interactions, matrix polymerization, and stiffening kinetics remain uncertain in vivo, and each plays a critical role in therapeutic applications using HA-SH. Hematological and histological analysis of subcutaneously injected HA-SH hydrogels showed minimal systemic immune response and host cell infiltration. Most importantly, subcutaneously injected HA-SH hydrogels exhibited time dependent porosity and stiffness changes at a rate similar to hydrogels polymerized in vitro. When injected intramyocardially, host cells begin to actively degrade HA-SH hydrogels within 1-week post-injection, continuing this process while producing matrix to nearly replace the hydrogel within 1 month post-injection. While non-thiolated HA did not degrade after injection into the myocardium, it also did not elicit an immune response, unlike HA-SH, where visible granulomas and macrophage infiltration were present at 1 month post-injection, likely due to reactive thiol groups. Altogether, these data suggest that the HA-SH hydrogel responds appropriately in a less vascularized niche and stiffens as had been demonstrated in vitro, but in more vascularized tissues, in vivo applicability appears limited. PMID:23523533

Young, Jennifer L.; Tuler, Jeremy; Braden, Rebecca; Schup-Magoffin, Pamela; Schaefer, Jacquelyn; Kretchmer, Kyle; Christman, Karen L.; Engler, Adam J.

2013-01-01

336

ZAP-70 Restoration in Mice by In Vivo Thymic Electroporation  

PubMed Central

Viral and non-viral vectors have been developed for gene therapy, but their use is associated with unresolved problems of efficacy and safety. Efficient and safe methods of DNA delivery need to be found for medical application. Here we report a new monopolar system of non-viral electro-gene transfer into the thymus in vivo that consists of the local application of electrical pulses after the introduction of the DNA. We assessed the proof of concept of this approach by correcting ZAP-70 deficient severe combined immunodeficiency (SCID) in mice. The thymic electro-gene transfer of the pCMV-ZAP-70-IRES-EGFP vector in these mice resulted in rapid T cell differentiation in the thymus with mature lymphocytes detected by three weeks in secondary lymphoid organs. Moreover, this system resulted in the generation of long-term functional T lymphocytes. Peripheral reconstituted T cells displayed a diversified T cell receptor (TCR) repertoire, and were responsive to alloantigens in vivo. This process applied to the thymus could represent a simplified and effective alternative for gene therapy of T cell immunodeficiencies. PMID:18446234

Kissenpfennig, Adrien; Poulin, Lionel Franz; Leserman, Lee; Marche, Patrice N.; Jouvin-Marche, Evelyne; Berger, François; Nguyen, Catherine

2008-01-01

337

Extradiscal ultrasound thermal therapy (ExDUSTT): evaluation in ex vivo and in vivo spine models (Invited Paper)  

NASA Astrophysics Data System (ADS)

The application of heat to intervertebral discs is being clinically investigated for the treatment of discogenic back pain. The purpose of this study was to develop and test the feasibility of small ultrasound applicators that can be endoscopically placed adjacent to the disc, and deliver heating energy into the disc without puncturing the annular wall. Prototype devices were fabricated using curvilinear transducers (2.5-3.5 mm wide x 10 mm long, 5.4 - 6.5 MHz) that produce a narrow penetrating beam extending along the length of the ultrasound element. The transducer was affixed to either a flexible or rigid delivery catheter, and enclosed within an asymmetric coupling balloon with water-cooling flow. Bench measurements demonstrated 35-60% acoustic efficiencies, high-power output capabilities, and lightly focused beam patterns. The heating characteristics of these devices were evaluated with ex vivo and in vivo experiments within lumbar and cervical spine segments from sheep models and human cadaveric spine. The applicators were positioned adjacent to the annular wall of the surgically exposed discs. Ultrasound energy was focused directly into the disc to avoid heating the vertebral bodies. Multi-point thermocouple probes were placed throughout the disc to characterize the resultant temperature distributions. These studies demonstrated that ultrasound energy from these applicators penetrated the annular wall of the disc, and produced thermal coagulative temperatures of >60-65°C as far as 10 mm into the tissue. This study also showed that lower power levels and temperatures delivered for 10 minutes can generate a cytotoxic thermal dose of t43°C >240 min penetrating 5-10 mm from the annular wall.

Diederich, Chris J.; Kinsey, Adam; Nau, William H.; Shu, Richard; Lotz, Jeffrey C.

2005-04-01

338

AAV serotype influences gene transfer in corneal stroma in vivo.  

PubMed

This study evaluated the cellular tropism and relative transduction efficiency of three AAV serotypes, AAV6, AAV8 and AAV9, for corneal gene delivery using mouse cornea in vivo and donor human cornea ex vivo. The AAV6, AAV8 and AAV9 serotypes having AAV2 plasmid encoding for alkaline phosphatase (AP) gene were generated by transfecting HEK 293 cell line with pHelper, pARAP4 and pRep/Cap plasmids. Viral vectors (10(9) vg/microl) were topically applied onto mouse cornea in vivo and human cornea ex vivo after removing the epithelium. Human corneas were processed for transgene delivery at day 5 after viral vector application. Mouse corneas were harvested at 4, 14 and 30 days after vector application for AP staining. Transduction efficiency was calculated by quantifying pixels of AP-stained area using Image J software and also confirmed by functional AP enzyme activity in the corneal lysates. Cellular toxicity of the three AAV serotypes was tested with TUNEL assay. Inflammatory response was detected by immunostaining for CD11b and F4/80. All three AAV serotypes successfully transduced mouse and human corneas. The order of transduction efficiency was AAV9 > AAV8 > AAV6. The transduction efficiency of AAV9 was 1.1-1.4 fold higher (p > 0.05) as compared to AAV8 and 3.5-5.5 fold higher (p < 0.01) as compared to AAV6. The level of transgene expression for all the three serotypes was greater at 14 days compared to 4 days and this high level of transgene expression was maintained up to the tested time point of 30 days. Corneas exposed to any of the three AAV serotypes did not show significant TUNEL positive cells or any inflammatory response as tested by CD11b or F4/80 staining suggesting that tested AAV serotypes do not induce cell death or inflammation and are safe for corneal gene therapy. PMID:20599959

Sharma, Ajay; Tovey, Jonathan C K; Ghosh, Arkasubhra; Mohan, Rajiv R

2010-09-01

339

Combined Raman spectroscopy and autofluoresence imaging method for in vivo skin tumor diagnosis  

NASA Astrophysics Data System (ADS)

The fluorescence and Raman spectroscopy (RS) combined method of in vivo detection of malignant human skin cancer was demonstrated. The fluorescence analysis was used for detection of abnormalities during fast scanning of large tissue areas. In suspected cases of malignancy the Raman spectrum analysis of biological tissue was performed to determine the type of neoplasm. A special RS phase method was proposed for in vivo identification of skin tumor. Quadratic Discriminant Analysis was used for tumor type classification on phase planes. It was shown that the application of phase method provides a diagnosis of malignant melanoma with a sensitivity of 89% and a specificity of 87%.

Zakharov, V. P.; Bratchenko, I. A.; Myakinin, O. O.; Artemyev, D. N.; Khristoforova, Y. A.; Kozlov, S. V.; Moryatov, A. A.

2014-09-01

340

Detection of trace cobalt ions in in vivo plant cells using a voltammetric interlocking system.  

PubMed

This experiment was conducted to establish a system for detecting trace cobalt ions in water and plant tissues using a voltammetric in vivo sensor. Cyclic and stripping voltammetry was devised from hand-made, macro-type implantable three-electrode systems. The results reached micro and nano working ranges at 100 sec accumulation time. The statistical detection limit (S/N) was attained at 6.0 ng L(-1). For the in vivo application, direct assay of cobalt ions was carried out in Eichhornia crassipes (EC) deep tissue in real time with a preconcentration time of 100 s. Interfaced techniques can be interlocked with other control systems. PMID:23508160

Ly, Suw Young; Shin, Myoung Ho; Lee, Chang Hyun; Lee, Jin Hui; Kim, Mi Sook; Ji, Sang Woo; Park, Dong Won

2013-01-01

341

Fibered confocal spectroscopy and multicolor imaging system for in vivo fluorescence analysis  

NASA Astrophysics Data System (ADS)

We report the design and implementation of spectroscopic and multicolor imaging capabilities into a fibered confocal fluorescence microscope (FCFM) already capable of in vivo imaging. The real time imaging device and the high resolution fiber probe make this system the first reported capable of performing multi color detection in the field of FCFM. The advantages of the system will allow in vivo morphological and functional imaging. Preliminary experiments were carried out in tissue samples to demonstrate the potential of the technique. The quality of the axial sectioning achieved in the confocal fluorescence spectroscopy mode is demonstrated experimentally, and applications to multicolor imaging are shown.

Jean, Florence; Bourg-Heckly, Genevieve; Viellerobe, Bertrand

2007-04-01

342

[Research progress on the development of the strategies for siRNAs delivery in vivo].  

PubMed

RNA interference (RNAi) is a powerful endogenous process initiated by short double stranded RNAs, which results in sequence-specific posttranscriptional gene silencing. Because any protein that causes or contributes to a disease is susceptible to RNAi, the RNAi has high potential for therapeutic treatments. In a clinical setting, however, there are many obstacles to targeted delivery of small interfering RNA (siRNA) in vivo, specificity and stability of the RNAi reagents. In this review, we focus on recent progress in the development of efficient siRNA delivery vehicles to help the application of siRNA to in vivo therapy. PMID:23016434

Tang, Deping; Mao, Aihong

2012-08-01

343

In Vivo Imaging in Cancer  

PubMed Central

Imaging has become an indispensable tool in the study of cancer biology and in clinical prognosis and treatment. The rapid advances in high resolution fluorescent imaging at single cell level and MR/PET/CT image registration, combined with new molecular probes of cell types and metabolic states, will allow the physical scales imaged by each to be bridged. This holds the promise of translation of basic science insights at the single cell level to clinical application. In this article, we describe the recent advances in imaging at the macro- and micro-scale and how these advances are synergistic with new imaging agents, reporters, and labeling schemes. Examples of new insights derived from the different scales of imaging and relevant probes are discussed in the context of cancer progression and metastasis. PMID:20861158

Condeelis, John; Weissleder, Ralph

2010-01-01

344

In Vivo Mitochondrial Oxygen Tension Measured by a Delayed Fluorescence Lifetime Technique  

PubMed Central

Mitochondrial oxygen tension (mitoPO2) is a key parameter for cellular function, which is considered to be affected under various pathophysiological circumstances. Although many techniques for assessing in vivo oxygenation are available, no technique for measuring mitoPO2 in vivo exists. Here we report in vivo measurement of mitoPO2 and the recovery of mitoPO2 histograms in rat liver by a novel optical technique under normal and pathological circumstances. The technique is based on oxygen-dependent quenching of the delayed fluorescence lifetime of protoporphyrin IX. Application of 5-aminolevulinic acid enhanced mitochondrial protoporphyrin IX levels and induced oxygen-dependent delayed fluorescence in various tissues, without affecting mitochondrial respiration. Using fluorescence microscopy, we demonstrate in isolated hepatocytes that the signal is of mitochondrial origin. The delayed fluorescence lifetime was calibrated in isolated hepatocytes and isolated perfused livers. Ultimately, the technique was applied to measure mitoPO2 in rat liver in vivo. The results demonstrate mitoPO2 values of ?30–40 mmHg. mitoPO2 was highly sensitive to small changes in inspired oxygen concentration around atmospheric oxygen level. Ischemia-reperfusion interventions showed altered mitoPO2 distribution, which flattened overall compared to baseline conditions. The reported technology is scalable from microscopic to macroscopic applications, and its reliance on an endogenous compound greatly enhances its potential field of applications. PMID:18641065

Mik, Egbert G.; Johannes, Tanja; Zuurbier, Coert J.; Heinen, Andre; Houben-Weerts, Judith H. P. M.; Balestra, Gianmarco M.; Stap, Jan; Beek, Johan F.; Ince, Can

2008-01-01

345

In vivo radiobiology of heavy ions  

SciTech Connect

The radiobiology of heavy charged particles has been investigated with various animal systems in vivo at the Lawrence Berkeley Laboratory using the helium beam from the 184'' synchrocyclotron and the carbon, neon, and argon beams from the BEVALAC. Tumor experiments were carried out using the R/sub 1/ sarcoma in rats and the EMT6 mouse mammary carcinoma, comparing X rays, carbon ions, neon ions, and argon ions. In vivo normal tissue experiments have been carried out with a wide range of tissues including testis, bone marrow, intestinal crypt cells, lens of the eye, esophagus, lung, and the spinal cord. The induction of dominant lethal mutations after irradiation of the testis was assayed by in vitro embryo culture after in vivo irradiation. Experiments were also done with the Harderian gland tumor induction system.

Phillips, T.L. (Univ. of California, San Francisco); Ross, G.Y.; Goldstein, L.S.; Ainsworth, J.; Alpen, E.

1982-12-01

346

In vivo predictive release methods for medicated chewing gums.  

PubMed

Understanding the performance of a drug product in vivo plays a key role in the development of meaningful in vitro drug release methodology. In case of functional chewing gums, the mode and the mechanism of release and the site of application differ significantly from other conventional solid oral dosage forms and require a special consideration to extract meaningful information from clinical studies. In the current study, suitable drug release methodology was developed to predict the in vivo performance of an investigated chewing gum product. Different parameters of the drug release testing apparatus described in the Ph. Eur. and Pharmeuropa were evaluated. Drug release data indicate that the parameters, chewing distance, chewing frequency and twisting motion, affect the drug release. Higher drug release was observed when the frequency was changed from 40 chews/min to 60 chews/min for apparatus A and B, as was the case for the twisting motion when changed from 20º to 40º for apparatus B. As far as the chewing distance is concerned, the release rate was in the following order; apparatus A: 0.3 mm > 0.5 mm > 0.7 mm; apparatus B: 1.4 mm > 1.6 mm > 1.8 mm. A suitable apparatus set-up for in vitro release testing was identified. The method will be useful for the establishment of in vitro in vivo correlations (IVIVC) for medicated chewing gums. Interchangeability of the apparatus for a product is not generally recommended without prior knowledge of the performance of the product, as the construction and principle of operation for the apparatus differ considerably. PMID:22674680

Gajendran, Jayachandar; Kraemer, Johannes; Langguth, Peter

2012-10-01

347

In Vivo Wall Shear Measurements within the Developing Zebrafish Heart  

PubMed Central

Physical forces can influence the embryonic development of many tissues. Within the cardiovascular system shear forces resulting from blood flow are known to be one of the regulatory signals that shape the developing heart. A key challenge in investigating the role of shear forces in cardiac development is the ability to obtain shear force measurements in vivo. Utilising the zebrafish model system we have developed a methodology that allows the shear force within the developing embryonic heart to be determined. Accurate wall shear measurement requires two essential pieces of information; high-resolution velocity measurements near the heart wall and the location and orientation of the heart wall itself. We have applied high-speed brightfield imaging to capture time-lapse series of blood flow within the beating heart between 3 and 6 days post-fertilization. Cardiac-phase filtering is applied to these time-lapse images to remove the heart wall and other slow moving structures leaving only the red blood cell movement. Using particle image velocimetry to calculate the velocity of red blood cells in different regions within the heart, and using the signal-to-noise ratio of the cardiac-phase filtered images to determine the boundary of blood flow, and therefore the position of the heart wall, we have been able to generate the necessary information to measure wall shear in vivo. We describe the methodology required to measure shear in vivo and the application of this technique to the developing zebrafish heart. We identify a reduction in shear at the ventricular-bulbar valve between 3 and 6 days post-fertilization and demonstrate that the shear environment of the ventricle during systole is constantly developing towards a more uniform level. PMID:24124507

Jamison, R. Aidan; Samarage, Chaminda R.; Bryson-Richardson, Robert J.; Fouras, Andreas

2013-01-01

348

In vivo virtual intraoperative surgical photoacoustic microscopy  

SciTech Connect

We developed a virtual intraoperative surgical photoacoustic microscopy system by combining with a commercial surgical microscope and photoacoustic microscope (PAM). By sharing the common optical path in the microscope and PAM system, we could acquire the PAM and microscope images simultaneously. Moreover, by employing a beam projector to back-project 2D PAM images onto the microscope view plane as augmented reality, the conventional microscopic and 2D cross-sectional PAM images are concurrently mapped on the plane via an ocular lens of the microscope in real-time. Further, we guided needle insertion into phantom ex vivo and mice skins in vivo.

Han, Seunghoon, E-mail: hsh860504@gmail.com; Kim, Sehui, E-mail: sehui0916@nate.com; Kim, Jeehyun, E-mail: jeehk@knu.ac.kr, E-mail: chulhong@postech.edu [School of Electrical Engineering and Computer Science, Kyungpook National University, Daegu 702-701 (Korea, Republic of)] [School of Electrical Engineering and Computer Science, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Lee, Changho, E-mail: ch31037@postech.edu; Jeon, Mansik, E-mail: msjeon@postech.edu [Department of Creative IT Engineering, Pohang University of Science and Technology (POSTECH), Pohang 790-784 (Korea, Republic of)] [Department of Creative IT Engineering, Pohang University of Science and Technology (POSTECH), Pohang 790-784 (Korea, Republic of); Kim, Chulhong, E-mail: jeehk@knu.ac.kr, E-mail: chulhong@postech.edu [Department of Creative IT Engineering, Pohang University of Science and Technology (POSTECH), Pohang 790-784 (Korea, Republic of) [Department of Creative IT Engineering, Pohang University of Science and Technology (POSTECH), Pohang 790-784 (Korea, Republic of); Department of Biomedical Engineering, The State University of New York at Buffalo, Buffalo, New York 14221 (United States)

2013-11-11

349

Real time monitoring of superoxide dynamics in vivo through fluorescent proteins using a sensitive fiber probe  

NASA Astrophysics Data System (ADS)

Superoxide anion is the primary oxygen free radical generated in mitochondria that causes intracellular oxidative stress. The lack of a method to directly monitor superoxide concentration in vivo in real time has severely hindered our understanding on its pathophysiology. We made transgenic zebrafish to specifically express fluorescent proteins, which are recently developed as reversible superoxide-specific indicators, in the liver. A fiber-optic fluorescent probe was used to noninvasively monitor superoxide generation in the liver in real time. The fish were placed in microfluidic channels for manipulation and reagents administration. Several superoxide-inducing and scavenging reagents were administrated onto the fish to investigate their effects on superoxide anion balancing. The biochemical dynamics of superoxide due to the application reagents were revealed in the transient behaviors of fluorescence time courses. With the ability to monitor superoxide dynamics in vivo in real time, this method can be used as an in vivo pharmaceutical screening platform.

Chang, Yu-Chung; Ken, Chuian-Fu; Hsu, Che-Wei; Liu, Ya-Ging

2014-03-01

350

Photoclick chemistry: a fluorogenic light-triggered in vivo ligation reaction.  

PubMed

The ability to use chemical reactivity to monitor and control biomolecular processes with a spatial and temporal precision motivated the development of light-triggered in vivo chemistries. To this end, the photoinduced tetrazole-alkene cycloaddition, also termed 'photoclick chemistry' offers a very rapid chemical ligation platform for the manipulation of biomolecules and matrices in vivo. Here we outline the recent developments in the optimization of this chemistry, ranging from the search for substrates that offer two-photon photoactivatability, superior reaction kinetics, and/or genetic encodability, to the study of the reaction mechanism. The applications of the photoclick chemistry in protein labeling in vitro and in vivo as well as in preparing 'smart' hydrogels for 3D cell culture are highlighted. PMID:25022432

Ramil, Carlo P; Lin, Qing

2014-08-01

351

In vivo imaging of collagen fiber orientation with rapid polarization-resolved SHG microscopy  

NASA Astrophysics Data System (ADS)

Polarization-resolved second-harmonic-generation (SHG) microscopy is a powerful tool to visualize distribution of collagen fiber orientation in tissue with little invasion. However, long image acquisition time, resulting from mechanical rotation of a half-wave plate, makes this microscopy easy to suffer from motion artifact of a sample and hence has limited its use to in vivo application. In this paper, we constructed rapid, polarization-resolved SHG microscopy by combination of an electro-optics-modulator-based polarization modulation with improved data acquisition method. The constructed polarization-resolved SHG microscopy enables us to visualize orientation mapping of dermal collagen fiber in rat skin and human one in vivo without influence of motion artifact. This microscope will open the door for in vivo measurement of collagen fiber orientation in human skin.

Tanaka, Yuji; Hase, Eiji; Fukushima, Shuichiro; Yasui, Takeshi; Araki, Tsutomu

2013-02-01

352

In Vivo Gene Therapy of Hemophilia B: Sustained Partial Correction in Factor IX-Deficient Dogs  

NASA Astrophysics Data System (ADS)

The liver represents a model organ for gene therapy. A method has been developed for hepatic gene transfer in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature, which results in the persistent expression of exogenous genes. To determine if these technologies are applicable for the treatment of hemophilia B patients, preclinical efficacy studies were done in a hemophilia B dog model. When the canine factor IX complementary DNA was transduced directly into the hepatocytes of affected dogs in vivo, the animals constitutively expressed low levels of canine factor IX for more than 5 months. Persistent expression of the clotting. factor resulted in reductions of whole blood clotting and partial thromboplastin times of the treated animals. Thus, long-term treatment of hemophilia B patients may be feasible by direct hepatic gene therapy in vivo.

Kay, Mark A.; Rothenberg, Steven; Landen, Charles N.; Bellinger, Dwight A.; Leland, Frances; Toman, Carol; Finegold, Milton; Thompson, Arthur R.; Read, M. S.; Brinkhous, Kenneth M.; Woo, Savio L. C.

1993-10-01

353

Critical evaluation of laser-induced interstitial thermotherapy (LITT) performed on in-vitro, in-vivo, and ex-vivo models  

NASA Astrophysics Data System (ADS)

Thermal ablation techniques are experiencing application in many different fields of medicine. Recently, experimental studies have been performed by various authors concerned with dosimetry and laser-tissue interaction. In order to study the effects of interstitial laser energy on biological tissue, we examined different tissue models which compared important parameters during laser application. We have performed the following in vitro, in vivo and ex vivo studies by comparing a neodymium: YAG (1064 nm) and diode laser (830 nm) equipped with interstitial laser fibers. In vitro studies which examined the influence of changes in power and time duration of application were performed on potato, muscle, liver and kidney. In vivo studies (porcine model) also examined different power settings at designated time intervals. Ex vivo studies with isolated perfused kidney (IPK) investigated the effects of power, application time, perfusion pressure and different perfusion mediums (saline solution, anticoagulated blood). In vitro studies revealed necrotic lesions in all tissues. Although no power threshold could be obtained for liver tissue (early onset fiber damage), potato, kidney and muscle tissue demonstrated their own respective power threshold. Furthermore, when using the Nd:YAG laser, we observed that higher power settings had permitted a quicker necrosis induction, however within its own treatment power spectrum, the diode laser was capable of inducing larger lesions. In vivo studies demonstrated that early onset diffuser tip damage would prevent exact documentation of laser-tissue interaction at higher power levels. Results obtained with our standardized ex vivo model (IPK) revealed smaller necrotic lesions with saline than with blood perfusion and also demonstrated the important role which perfusion rate plays during laser-tissue interaction. We found that pigmented, well vascularized parenchymal organs with low stromal content (kidney, liver) and a higher absorption coefficient induced larger necrotic volumes than organs without these characteristics. Higher power settings demonstrated side effects, (e.g. popcorn effect or uncontrollable vaporization induced by extreme hyperthermia) in every animal tissue in all three trials. Our experimental interstitial laser studies have shown that many factors influence the size outcome of the necrotic lesion and that treatment parameters (treatment time, power setting) must be optimally combined to obtain a controlled and predictable necrotic lesion in certain tissues.

Henkel, Thomas O.; Niedergethmann, M.; Alken, Peter

1996-01-01

354

In vivo transcostal histotripsy therapy without aberration correction.  

PubMed

This study investigates the in vivo therapeutic capabilities of transcostal histotripsy without using aberration correction mechanisms and its thermal impact on overlying tissues. Non-invasive liver treatments were conducted in eight pigs, with four lesions generated through transcostal windows with full ribcage obstruction and four lesions created through transabdominal windows without rib coverage. Treatments were performed by a 750 kHz focused transducer using 5 cycle pulses at 200 Hz PRF, with estimated in situ peak negative pressures of 13-17 MPa. Temperatures on overlying tissues including the ribs were measured with needle thermocouples inserted superficially beneath the skin. Treatments of approximately 40 min were applied, allowing overlying tissue temperatures to reach saturation. Lesions yielded statistically comparable ablation volumes of 3.6 ± 1.7 cm(3) and 4.5 ± 2.0 cm(3) in transcostal and transabdominal treatments, respectively. The average temperature increase observed in transcostal treatments was 3.9 ± 2.1 °C, while transabdominal treatments showed an increase of 1.7 ± 1.3 °C. No damage was seen on the ribcage or other overlying tissues. These results indicate that histotripsy can achieve effective treatment through the ribcage in vivo without requiring correction mechanisms, while inducing no substantial thermal effects or damage to overlying tissues. Such capabilities could benefit several non-invasive therapy applications involving transcostal treatment windows. PMID:24785433

Kim, Y; Vlaisavljevich, E; Owens, G E; Allen, S P; Cain, C A; Xu, Z

2014-06-01

355

In Vivo Nanotoxicity Testing using the Zebrafish Embryo Assay  

PubMed Central

Nanoparticles are increasingly used for biomedical purposes. Many different diagnostic and therapeutic applications are envisioned for nanoparticles, but there are often also serious concerns regarding their safety. Given the fact that numerous new nanomaterials are being developed every day, and that not much is known about the long-term toxicological impact of exposure to nanoparticles, there is an urgent need to establish efficient methods for nanotoxicity testing. The zebrafish (Danio rerio) embryo assay has recently emerged as an interesting ‘intermediate’ method for in vivo nanotoxicity screening, enabling (semi-) high-throughput analyses in a system significantly more complex than cultured cells, but at the same time also less ‘invasive’ and less expensive than large-scale biocompatibility studies in mice or rats. The zebrafish embryo assay is relatively well-established in the environmental sciences, but it has not yet gained wide notice in the nanomedicine field. Using prototypic polymeric drug carriers, gold-based nanodiagnostics and nanotherapeutics, and iron oxide-based nanodiagnostics, we here show that toxicity testing using zebrafish embryos is easy, efficient and informative, and faithfully reflects, yet significantly extends, cell-based toxicity testing. We therefore expect that the zebrafish embryo assay will become a popular future tool for in vivo nanotoxicity screening. PMID:24179674

Rizzo, Larissa Y.; Golombek, Susanne K.; Mertens, Marianne E.; Pan, Yu; Laaf, Dominic; Broda, Janine; Jayapaul, Jabadurai; Mockel, Diana; Subr, Vladimir; Hennink, Wim E.; Storm, Gert; Simon, Ulrich; Jahnen-Dechent, Willi; Kiessling, Fabian; Lammers, Twan

2013-01-01

356

Photoacoustic tomography of ex vivo mouse hearts with myocardial infarction  

NASA Astrophysics Data System (ADS)

In the present study, we evaluated the applicability of ex vivo photoacoustic imaging (PAI) on small animal organs. We used photoacoustic tomography (PAT) to visualize infarcted areas within murine hearts and compared these data to other imaging techniques [magnetic resonance imaging (MRI), micro-computed tomography] and histological slices. In order to induce ischemia, an in vivo ligation of the left anterior descending artery was performed on nine wild-type mice. After varying survival periods, the hearts were excised and fixed in formaldehyde. Samples were illuminated with nanosecond laser pulses delivered by a Nd:YAG pumped optical parametric oscillator. Ultrasound detection was achieved using a Mach-Zehnder interferometer (MZI) working as an integrating line detector. The voxel data were computed using a Fourier-domain based reconstruction algorithm, followed by inverse Radon transforms. The results clearly showed the capability of PAI to visualize myocardial infarction and to produce three-dimensional images with a spatial resolution of approximately 120 ?m. Regions of affected muscle tissue in PAI corresponded well with the results of MRI and histology. Photoacoustic tomography utilizing a MZI for ultrasound detection allows for imaging of small tissue samples. Due to its high spatial resolution, good soft tissue contrast and comparatively low cost, PAT offers great potentials for imaging.

Holotta, Markus; Grossauer, Harald; Kremser, Christian; Torbica, Pavle; Völkl, Jakob; Degenhart, Gerald; Esterhammer, Regina; Nuster, Robert; Paltauf, Günther; Jaschke, Werner

2011-03-01

357

Biodegradable optode-based nanosensors for in vivo monitoring  

PubMed Central

Optode-based fluorescent nanosensors are being developed for monitoring important diseased states such as hyponatremia and diabetes. However, traditional optode-based sensors are composed of nonbiodegradable polymers such as polyvinyl chloride (PVC) raising toxicity concerns for long-term in vivo use. Here, we report the development of the first biodegradable optode-based nanosensors that maintain sensing characteristics identical to traditional optode sensors. The polymer matrix of these sensors is composed of polycaprolactone (PCL) and a citric acid ester plasticizer. The PCL-based nanosensors yielded a dynamic and reversible response to sodium, were tuned to respond to extracellular sodium concentrations, and had a lifetime of at least 14 days at physiological temperature. When in the presence of lipase, the nanosensors degraded within 4 hours at lipase concentrations found in the liver but were present after 3 days at lipase concentrations found in serum. This development of biodegradable nanosensors is not only necessary for future in vivo applications, but it has also created a new sensor platform that can be extended to other sensing mechanisms such as for small molecules or enzymes. PMID:22725692

Balaconis, Mary K.; Clark, Heather A.

2012-01-01

358

In Vivo Cellular Imaging for Translational Medical Research  

PubMed Central

Personalized treatment using stem, modified or genetically engineered, cells is becoming a reality in the field of medicine, in which allogenic or autologous cells can be used for treatment and possibly for early diagnosis of diseases. Hematopoietic, stromal and organ specific stem cells are under evaluation for cell-based therapies for cardiac, neurological, autoimmune and other disorders. Cytotoxic or genetically altered T-cells are under clinical trial for the treatment of hematopoietic or other malignant diseases. Before using stem cells in clinical trials, translational research in experimental animal models are essential, with a critical emphasis on developing noninvasive methods for tracking the temporal and spatial homing of these cells to target tissues. Moreover, it is necessary to determine the transplanted cell’s engraftment efficiency and functional capability. Various in vivo imaging modalities are in use to track the movement and incorporation of administered cells. Tagging cells with reporter genes, fluorescent dyes or different contrast agents transforms them into cellular probes or imaging agents. Recent reports have shown that magnetically labeled cells can be used as cellular magnetic resonance imaging (MRI) probes, demonstrating the cell trafficking to target tissues. In this review, we will discuss the methods to transform cells into probes for in vivo imaging, along with their advantages and disadvantages as well as the future clinical applicability of cellular imaging method and corresponding imaging modality. PMID:19768136

Arbab, Ali S; Janic, Branislava; Haller, Jodi; Pawelczyk, Edyta; Liu, Wei; Frank, Joseph A

2009-01-01

359

SQUID-Detected In Vivo MRI at Microtesla Magnetic Fields  

SciTech Connect

We use a low transition temperature (T{sub c}) Super-conducting Quantum Interference Device (SQUID) to perform in vivo magnetic resonance imaging (MRI) at magnetic fields around 100 microtesla, corresponding to proton Larmor frequencies of about 5 kHz. In such low fields, broadening of the nuclear magnetic resonance lines due to inhomogeneous magnetic fields and susceptibility variations of the sample are minimized, enabling us to obtain high quality images. To reduce environmental noise the signal is detected by a second-order gradiometer, coupled to the SQUID, and the experiment is surrounded by a 3-mm thick Al shield. To increase the signal-to-noise ratio (SNR), we prepolarize the samples in a field up to 100 mT. Three-dimensional images are acquired in less than 6 minutes with a standard spin-echo phase-encoding sequence. Using encoding gradients of {approx}100 {micro}T/m we obtain three-dimensional images of bell peppers with a resolution of 2 x 2 x 8 mm{sup 3}. Our system is ideally suited to acquiring images of small, peripheral parts of the human body such as hands and arms. In vivo images of an arm, acquired at 132 {micro}T, show 24-mm sections of the forearm with a resolution of 3 x 3 mm{sup 2} and a SNR of 10. We discuss possible applications of MRI at these low magnetic fields.

Moble, Michael; Myers, Whittier R; Lee, SeungKyun; Kelso, Nathan; Hatridge, Michael; Pines, Alexander; Clarke, John

2005-06-01

360

Triple Bioluminescence Imaging for In Vivo Monitoring of Cellular Processes  

PubMed Central

Bioluminescence imaging (BLI) has shown to be crucial for monitoring in vivo biological processes. So far, only dual bioluminescence imaging using firefly (Fluc) and Renilla or Gaussia (Gluc) luciferase has been achieved due to the lack of availability of other efficiently expressed luciferases using different substrates. Here, we characterized a codon-optimized luciferase from Vargula hilgendorfii (Vluc) as a reporter for mammalian gene expression. We showed that Vluc can be multiplexed with Gluc and Fluc for sequential imaging of three distinct cellular phenomena in the same biological system using vargulin, coelenterazine, and D-luciferin substrates, respectively. We applied this triple imaging system to monitor the effect of soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) delivered using an adeno-associated viral vector (AAV) on brain tumors in mice. Vluc imaging showed efficient sTRAIL gene delivery to the brain, while Fluc imaging revealed a robust antiglioma therapy. Further, nuclear factor-?B (NF-?B) activation in response to sTRAIL binding to glioma cells death receptors was monitored by Gluc imaging. This work is the first demonstration of trimodal in vivo bioluminescence imaging and will have a broad applicability in many different fields including immunology, oncology, virology, and neuroscience. PMID:23778500

Maguire, Casey A; Bovenberg, M Sarah; Crommentuijn, Matheus HW; Niers, Johanna M; Kerami, Mariam; Teng, Jian; Sena-Esteves, Miguel; Badr, Christian E; Tannous, Bakhos A

2013-01-01

361

Focused in vivo genetic analysis of implanted engineered myofascial constructs.  

PubMed

Successfully engineering functional muscle tissue either in vitro or in vivo to treat muscle defects rather than using the host muscle transfer would be revolutionary. Tissue engineering is on the cutting edge of biomedical research, bridging a gap between the clinic and the bench top. A new focus on skeletal muscle tissue engineering has led investigators to explore the application of satellite cells (autologous muscle precursor cells) as a vehicle for engineering tissues either in vitro or in vivo. However, few skeletal muscle tissue-engineering studies have reported on successful generation of living tissue substitutes for functional skeletal muscle replacement. Our model system combines a novel aligned collagen tube and autologous skeletal muscle satellite cells to create an engineered tissue repair for a surgically created ventral hernia as previously reported [SA Fann, L Terracio, W Yan, et al., A model of tissue-engineered ventral hernia repair, J Invest Surg. 2006;19(3):193-205]. Several key features we specifically observe are the significant persistence of transplanted skeletal muscle cell mass within the engineered repair, the integration of new tissue with adjacent native muscle, and the presence of significant neovascularization. In this study, we report on our experience investigating the genetic signals important to the integration of neoskeletal muscle tissue. The knowledge gained from our model system applies to the repair of severely injured extremities, maxillofacial reconstructions, and restorative procedures following tumor excision in other areas of the body. PMID:19191156

Propst, John T; Fann, Stephen A; Franchini, Jessica L; Lessner, Susan M; Rose, John R; Hansen, Karyn J; Terracio, Louis; Yost, Michael J

2009-01-01

362

Dexpanthenol modulates gene expression in skin wound healing in vivo.  

PubMed

Topical application of dexpanthenol is widely used in clinical practice for the improvement of wound healing. Previous in vitro experiments identified a stimulatory effect of pantothenate on migration, proliferation and gene regulation in cultured human dermal fibroblasts. To correlate these in vitro findings with the more complex in vivo situation of wound healing, a clinical trial was performed in which the dexpanthenol-induced gene expression profile in punch biopsies of previously injured and dexpanthenol-treated skin in comparison to placebo-treated skin was analyzed at the molecular level by Affymetrix® GeneChip analysis. Upregulation of IL-6, IL-1?, CYP1B1, CXCL1, CCL18 and KAP 4-2 gene expression and downregulation of psorasin mRNA and protein expression were identified in samples treated topically with dexpanthenol. This in vivo study might provide new insight into the molecular mechanisms responsible for the effect of dexpanthenol in wound healing and shows strong correlations to previous in vitro data using cultured dermal fibroblasts. PMID:22759998

Heise, R; Skazik, C; Marquardt, Y; Czaja, K; Sebastian, K; Kurschat, P; Gan, L; Denecke, B; Ekanayake-Bohlig, S; Wilhelm, K-P; Merk, H F; Baron, J M

2012-01-01

363

In vivo bone aluminum measurements in patients with renal disease  

SciTech Connect

Contamination of the dialysis solution with trace amounts of aluminum and long-term use of aluminum-based phosphate binders have led to increased body burden of aluminum in patients with end-stage renal disease. A significant clinical problem associated with aluminum-overload is the early diagnosis of aluminum-induced dialysis dementia and osteomalacic osteodystrophy. There are few, if any, blood or urine indices that provide an early monitor of this bone disease, especially in the asymptomatic patient. Although a bone biopsy is usually the basis for the final clinical diagnosis, this procedure is not recommended for routine monitoring of patients. The present technique demonstrates the direct in vivo measurement of bone aluminum levels in patients with renal failure. The interference normally present from activation of bone phosphorus is eliminated by using a thermal/epithermal neutron beam. For the clinical management of the patients, the Al/Ca ratio for the hand may be more useful than an absolute measurement of the total body or skeletal aluminum burden. The relationship between the increased serum Al levels following disferrioxamine infusion and the direct in vivo measurement of bone aluminum using the Al/Ca ratio are currently under investigation. The neutron activation procedure presented in this pilot study is a promising new technique with an immediate clinical application. 5 refs., 3 figs., 1 tab.

Ellis, K.J.; Kelleher, S.P.

1986-01-01

364

Assessing the in vivo efficacy of doxorubicin loaded hyaluronan nanoparticles.  

PubMed

Magnetic nanoparticles are attractive platforms for biomedical applications including diagnosis and treatment of diseases. We have shown previously that hyaluronan-coated superparamagnetic iron oxide nanoparticles (HA-SPIONs) enhanced the efficacy of the conjugated anticancer drug doxorubicin (DOX) in vitro against drug-sensitive and drug-resistant human ovarian cancer cells. In this manuscript, we report our findings on the efficacy of DOX loaded HA-SPIONs in vivo using subcutaneous and intraperitoneal SKOV-3 ovarian tumor models in nude mice. The accumulation of the nanoparticles in subcutaneous tumors following an intravenous nanoparticle administration was confirmed by magnetic resonance imaging, and its distribution in the tumors was evaluated by confocal microscopy and Prussian blue staining. DOX delivered by nanoparticles accumulated at much higher levels and distributed wider in the tumor tissue than intravenously injected free DOX, leading to significant reduction of tumor growth. The IVIS Spectrum for in vivo bioluminescence imaging was used to aid in therapy assessment of the DOX-loaded nanoparticles on intraperitoneal ovarian tumors formed by firefly luciferase expressing human ovarian SKOV-3 cells. DOX-loaded HA-SPIONs significantly reduced tumor growth, delayed tumor development, and extended the survival of mice. Thus, utilizing HA-SPIONs as drug delivery vehicles constitutes a promising approach to tackle CD44 expressing ovarian cancer. PMID:24308364

El-Dakdouki, Mohammad H; Xia, Jingguang; Zhu, David C; Kavunja, Herbert; Grieshaber, Jessica; O'Reilly, Sandra; McCormick, J Justin; Huang, Xuefei

2014-01-01

365

In vivo transcostal histotripsy therapy without aberration correction  

NASA Astrophysics Data System (ADS)

This study investigates the in vivo therapeutic capabilities of transcostal histotripsy without using aberration correction mechanisms and its thermal impact on overlying tissues. Non-invasive liver treatments were conducted in eight pigs, with four lesions generated through transcostal windows with full ribcage obstruction and four lesions created through transabdominal windows without rib coverage. Treatments were performed by a 750 kHz focused transducer using 5 cycle pulses at 200 Hz PRF, with estimated in situ peak negative pressures of 13-17 MPa. Temperatures on overlying tissues including the ribs were measured with needle thermocouples inserted superficially beneath the skin. Treatments of approximately 40 min were applied, allowing overlying tissue temperatures to reach saturation. Lesions yielded statistically comparable ablation volumes of 3.6 ± 1.7 cm3 and 4.5 ± 2.0 cm3 in transcostal and transabdominal treatments, respectively. The average temperature increase observed in transcostal treatments was 3.9 ± 2.1 °C, while transabdominal treatments showed an increase of 1.7 ± 1.3 °C. No damage was seen on the ribcage or other overlying tissues. These results indicate that histotripsy can achieve effective treatment through the ribcage in vivo without requiring correction mechanisms, while inducing no substantial thermal effects or damage to overlying tissues. Such capabilities could benefit several non-invasive therapy applications involving transcostal treatment windows.

Kim, Y.; Vlaisavljevich, E.; Owens, G. E.; Allen, S. P.; Cain, C. A.; Xu, Z.

2014-06-01

366

Vitamin E Reverses Multidrug Resistance In Vitro and In Vivo  

PubMed Central

Multidrug resistance (MDR) is a major obstacle to successful and effective chemotherapeutic treatments of cancers. This study explored the reversal effects of vitamin E on MDR tumor cells in vitro and in vivo, elucidating the potential mechanism of this reversal. VE at a concentration of 50 ?M exhibited a significant reversal of the MDR effect (compared to only PTX in DMSO, p < 0.05) in two human MDR cell lines (H460/taxR and KB-8-5). The MDR cell xenograft model was established to investigate the effect of VE on reversing MDR in vivo. Mice intravenously injected with Taxol (10 mg/kg) with VE (500 mg/kg, IP) showed an ability to overcome the MDR. VE and its derivatives can significantly increase intracellular accumulation of rhodamine 123 and doxorubicin (P-gp substrate), but not alter the levels of P-gp expression. These treatments also did not decrease the levels of intracellular ATP, but were still able to inhibit the verapamil-induced ATPase activity of P-gp. The new application of VE as an MDR sensitizer will be attractive due to the safety of this treatment. PMID:23624302

Tang, Jingling; Fu, Qiang; Wang, Yongjun; Racette, Kelly; Wang, Dun; Liu, Feng

2013-01-01

367

Neurovascular coupling: in vivo optical techniques for functional brain imaging  

PubMed Central

Optical imaging techniques reflect different biochemical processes in the brain, which is closely related with neural activity. Scientists and clinicians employ a variety of optical imaging technologies to visualize and study the relationship between neurons, glial cells and blood vessels. In this paper, we present an overview of the current optical approaches used for the in vivo imaging of neurovascular coupling events in small animal models. These techniques include 2-photon microscopy, laser speckle contrast imaging (LSCI), voltage-sensitive dye imaging (VSDi), functional photoacoustic microscopy (fPAM), functional near-infrared spectroscopy imaging (fNIRS) and multimodal imaging techniques. The basic principles of each technique are described in detail, followed by examples of current applications from cutting-edge studies of cerebral neurovascular coupling functions and metabolic. Moreover, we provide a glimpse of the possible ways in which these techniques might be translated to human studies for clinical investigations of pathophysiology and disease. In vivo optical imaging techniques continue to expand and evolve, allowing us to discover fundamental basis of neurovascular coupling roles in cerebral physiology and pathophysiology. PMID:23631798

2013-01-01

368

In vivo detection of magnetic labeled oxidized multi-walled carbon nanotubes by magnetic resonance imaging.  

PubMed

Functionalized carbon nanotubes (f-CNTs) have been widely used in bio-medicine as drug carriers, bio-sensors, imaging agents and tissue engineering additives, which demands better understanding of their in vivo behavior because of the increasing exposure potential to humans. However, there are limited studies to investigate the in vivo biodistribution and elimination of f-CNTs. In this study, superparamagnetic iron oxides (SPIOs) were used to label oxidized multiwalled carbon nanotubes (o-MWCNTs) for in vivo distribution study of o-MWCNTs by magnetic resonance imaging (MRI). SPIO labeled o-MWCNTs (((SPIO))o-MWCNTs) were prepared by a hydrothermal reaction process, and characterized by TEM, XRD and magnetometer. ((SPIO))o-MWCNTs exhibited superparamagnetic property, excellent biocompatibility and stability. The intravenously injected ((SPIO))o-MWCNTs were observed in liver, kidney and spleen, while the subcutaneously injected ((SPIO))o-MWCNTs could be only detected in sub mucosa. Most of the intravenously injected ((SPIO))o-MWCNTs could be eliminated from liver, spleen, kidney and sub mucosa on 4 d post injection (P.I.). However, the residual o-MWCNTs could induce 30-40% MRI signal-to-noise ratio changes in these tissues even on 30 d P.I. This in vivo biodistribution and elimination information of o-MWCNTs will greatly facilitate the application of f-CNT based nanoproducts in biomedicine. In addition, the magnetic labeling method provides an approach to investigate the in vivo biodistribution and clearance of other nanomaterials. PMID:25409786

Li, Ruibin; Wu, Ren'an; Zhao, Liang; Qin, Hongqiang; Wu, Jianlin; Zhang, Jingwen; Bao, Ruyi; Zou, Hanfa

2014-12-12

369

Tracking the Relative In Vivo Pharmacokinetics of Nanoparticles with PARACEST MRI  

PubMed Central

A noninvasive assay that tracks the relative in vivo pharmacokinetics of two nanoparticles may accelerate the development of nanoparticles for biomedical applications, and may provide a method to select personalized nanomedicines for individual patients. To develop an in vivo competitive assay, two MRI contrast agents that could be selectively detected through paramagnetic chemical exchange saturation transfer (PARACEST) were conjugated to a second generation and fifth generation polyamidoamine (PAMAM) dendrimer. The CEST effects of each agent was calibrated relative to concentration. The effects of T1 relaxivities of these dendritic PARACEST magnetic resonance imaging (MRI) contrast agents were found to be negligible relative to their CEST effects with respect to changes in image contrast, which facilitated the measurement of the ratios of their chemical exchange lifetimes. Injection of both contrast agents into a mouse model of mammary carcinoma resulted in a temporal increase in the CEST effect from each agent in the flank tumor. Although the in vivo CEST effects could not be used to determine the absolute concentrations of each agent within the tumor, the ratio of the in vivo CEST effects was used to measure the ratio of the concentrations of the agents. This result demonstrated that the relative in vivo pharmacokinetics of two nanoparticles may be evaluated using PARACEST MRI. PMID:19298054

Ali, M. Meser; Yoo, Byunghee; Pagel, Mark D.

2014-01-01

370

In vivo high-resolution structural imaging of large arteries in small rodents using two-photon laser scanning microscopy  

NASA Astrophysics Data System (ADS)

In vivo (molecular) imaging of the vessel wall of large arteries at subcellular resolution is crucial for unraveling vascular pathophysiology. We previously showed the applicability of two-photon laser scanning microscopy (TPLSM) in mounted arteries ex vivo. However, in vivo TPLSM has thus far suffered from in-frame and between-frame motion artifacts due to arterial movement with cardiac and respiratory activity. Now, motion artifacts are suppressed by accelerated image acquisition triggered on cardiac and respiratory activity. In vivo TPLSM is performed on rat renal and mouse carotid arteries, both surgically exposed and labeled fluorescently (cell nuclei, elastin, and collagen). The use of short acquisition times consistently limit in-frame motion artifacts. Additionally, triggered imaging reduces between-frame artifacts. Indeed, structures in the vessel wall (cell nuclei, elastic laminae) can be imaged at subcellular resolution. In mechanically damaged carotid arteries, even the subendothelial collagen sheet (~1 ?m) is visualized using collagen-targeted quantum dots. We demonstrate stable in vivo imaging of large arteries at subcellular resolution using TPLSM triggered on cardiac and respiratory cycles. This creates great opportunities for studying (diseased) arteries in vivo or immediate validation of in vivo molecular imaging techniques such as magnetic resonance imaging (MRI), ultrasound, and positron emission tomography (PET).

Megens, Remco T. A.; Reitsma, Sietze; Prinzen, Lenneke; Oude Egbrink, Mirjam G. A.; Engels, Wim; Leenders, Peter J. A.; Brunenberg, Ellen J. L.; Reesink, Koen D.; Janssen, Ben J. A.; Ter Haar Romeny, Bart M.; Slaaf, Dick W.; van Zandvoort, Marc A. M. J.

2010-01-01

371

Molecular Cell Optimizing Protein Stability In Vivo  

E-print Network

that directly links the in vivo stability of proteins to antibiotic resistance. It allows the identification- cate how evolution has formed today's protein sequences. Here we describe a genetic selection of stabilizing mutations within proteins. The large majority of mutants selected for improved antibiotic

Bardwell, James

372

In vivo dosimetry in external beam radiotherapy  

SciTech Connect

In vivo dosimetry (IVD) is in use in external beam radiotherapy (EBRT) to detect major errors, to assess clinically relevant differences between planned and delivered dose, to record dose received by individual patients, and to fulfill legal requirements. After discussing briefly the main characteristics of the most commonly applied IVD systems, the clinical experience of IVD during EBRT will be summarized. Advancement of the traditional aspects of in vivo dosimetry as well as the development of currently available and newly emerging noninterventional technologies are required for large-scale implementation of IVD in EBRT. These new technologies include the development of electronic portal imaging devices for 2D and 3D patient dosimetry during advanced treatment techniques, such as IMRT and VMAT, and the use of IVD in proton and ion radiotherapy by measuring the decay of radiation-induced radionuclides. In the final analysis, we will show in this Vision 20/20 paper that in addition to regulatory compliance and reimbursement issues, the rationale for in vivo measurements is to provide an accurate and independent verification of the overall treatment procedure. It will enable the identification of potential errors in dose calculation, data transfer, dose delivery, patient setup, and changes in patient anatomy. It is the authors' opinion that all treatments with curative intent should be verified through in vivo dose measurements in combination with pretreatment checks.

Mijnheer, Ben [Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam 1066 CX (Netherlands); Beddar, Sam [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Izewska, Joanna [Division of Human Health, International Atomic Energy Agency, Vienna 1400 (Austria); Reft, Chester [Department of Radiation and Cellular Oncology, University of Chicago Medical Center, Chicago, Illinois 60637 (United States)

2013-07-15

373

Human in vivo pharmacology of topical retinoids  

Microsoft Academic Search

All-trans retinoic acid is used topically for treating a variety of dermatologic conditions ranging from acne to photoaged skin. Although the clinical effects of retinoic acid treatment are often considerable, relatively little is known about the basic mechanisms underlying such effects. With the development of an in vivo human assay we have investigated the pleiotypic effects of topical retinoids from

Christopher E. M. Griffiths; John J. Voorhees

1994-01-01

374

In vivo multiphoton nanosurgery on cortical  

E-print Network

.1117/1.2798723 Keywords: in vivo imaging; long-term imaging; two-photon microscopy; laser ablation; laser surgery Abstract. Two-photon microscopy has been used to per- form high spatial resolution imaging of spine- logical consequences are then characterized with time lapse 3-D two-photon imaging over a period

Sandini, Giulio

375

In vivo dosimetry in external beam radiotherapy.  

PubMed

In vivo dosimetry (IVD) is in use in external beam radiotherapy (EBRT) to detect major errors, to assess clinically relevant differences between planned and delivered dose, to record dose received by individual patients, and to fulfill legal requirements. After discussing briefly the main characteristics of the most commonly applied IVD systems, the clinical experience of IVD during EBRT will be summarized. Advancement of the traditional aspects of in vivo dosimetry as well as the development of currently available and newly emerging noninterventional technologies are required for large-scale implementation of IVD in EBRT. These new technologies include the development of electronic portal imaging devices for 2D and 3D patient dosimetry during advanced treatment techniques, such as IMRT and VMAT, and the use of IVD in proton and ion radiotherapy by measuring the decay of radiation-induced radionuclides. In the final analysis, we will show in this Vision 20?20 paper that in addition to regulatory compliance and reimbursement issues, the rationale for in vivo measurements is to provide an accurate and independent verification of the overall treatment procedure. It will enable the identification of potential errors in dose calculation, data transfer, dose delivery, patient setup, and changes in patient anatomy. It is the authors' opinion that all treatments with curative intent should be verified through in vivo dose measurements in combination with pretreatment checks. PMID:23822404

Mijnheer, Ben; Beddar, Sam; Izewska, Joanna; Reft, Chester

2013-07-01

376

Nanocrystal targeting in vivo Maria E. kerman*  

E-print Network

Nanocrystal targeting in vivo Maria E. Ã?kerman* , Warren C. W. Chan , Pirjo Laakkonen*, Sangeeta N Gilman Drive, La Jolla, CA 92093 Contributed by Erkki Ruoslahti, August 1, 2002 Inorganic nanostructures. Nanoparticles are thought to have potential as novel intra- vascular probes for both diagnostic (e.g., imaging

Bhatia, Sangeeta

377

Photosensitizer quantitation in vivo by flourescence microsampling  

NASA Astrophysics Data System (ADS)

Photodynamic therapy can provide a reliable method of tumor destruction when the appropriate dosimetry is applied. Current dosimetry practice involves quantification of the drug and light doses applied to the tumor, but it would be desirable to monitor in vivo light and drug levels to provide the most accurate determination of dosimetry. In vivo measurements can be used to minimize variations in treatment response due to inter-animal variability, by providing animal-specific or patient-specific treatment planning. This study reports on the development of a micro-sampling method to measure fluorescence from tissue, which is not significantly affected by the tissue optical properties. The system measures fluorescence from the surface of a tissue, using a fiber bundle composed of individual 100 micron fibers which ar all spaced apart by 700 microns from one another at the tissue contact end. This design provides sampling of the fluorescence at multiple sites to increase the signal intensity, while maintaining a micro- sampling of the tissue volume just below the surface. The calibration studies here indicate that the 1/e sampling depth is near 60 microns when measured in optical phantoms, which are similar to typical tissue properties. The probe fluorescence signal is independent of blood concentration up to a maximum of 10% blood by volume, which is similar to most tumor tissue. Animal tests indicate that the sensitivity to drug concentration is essentially the same in when measured in murine liver and muscle tissues, both in vivo and ex vivo. These preliminary calibration results suggest that the probe can be used to measure photosensitizer uptake in vivo non- invasively and rapidly via conversion of fluorescence intensity to photosensitizer concentration.

Pogue, Brian W.; Burke, Gregory C.; Lee, Claudia C.; Hoopes, P. Jack

2000-06-01

378

DNA curvature and flexibility in vitro and in vivo  

PubMed Central

It has been more than 50 years since the elucidation of the structure of double-helical DNA. Despite active research and progress in DNA biology and biochemistry, much remains to be learned in the field of DNA biophysics. Predicting the sequence-dependent curvature and flexibility of DNA is difficult. Applicability of the conventional worm-like chain polymer model of DNA has been challenged. The fundamental forces responsible for the remarkable resistance of DNA to bending and twisting remain controversial. The apparent “softening” of DNA measured in vivo in the presence of kinking proteins and superhelical strain is incompletely understood. New methods and insights are being applied to these problems. This review places current work on DNA biophysics in historical context and illustrates the ongoing interplay between theory and experiment in this exciting field. PMID:20478077

Peters, Justin P.; Maher, L. James

2014-01-01

379

In vivo uptake and photodynamic activity of porphycenes  

NASA Astrophysics Data System (ADS)

Novel porphyrinoid photosensitizers are currently being considered for use in photodynamic therapy (PDT) of cancer. This class of sensitizers combines high absorption characteristics at the therapeutic wavelengths ((lambda) > 600 nm) and good tumor targeting properties. We have investigated the in-vivo uptake and photodynamic damage of several porphycenes. Our model system was the chick chorioallantoic membrane (CAM) which we have adapted for use in PDT studies. The CAM assay allows fast screening of novel drugs and obtaining statistically relevant results with minute quantities of the drug. Sensitizers were `trapped' in EPC (egg phosphatidylcholine) or in DPPC (dipalmitoyl phosphatidylcholine); their efficiencies were independent of the vehicle used for application of the sensitizer. The efficiencies of various porphycenes in PDT, as a function of drug and light dose, compare well with those of standard porphyrins and phthalocyanines.

Kimel, Sol; Gottfried, Varda; Davidi, Ronit; Averbuj, Claudia

1994-03-01

380

Radioactive uranium measurement in vivo using a handheld interfaced analyzer.  

PubMed

A trace uranium (U) detection method was developed with a handheld voltammetric analyzer that was the size of a mobile phone, with working sensors made of simple graphite pencil electrode (PE). The optimum stripping voltammetric conditions were sought, and the following results were obtained: 0.0 to 0.08 ng/L working ranges and a statistically relative standard deviation of 1.78% (RSD; n=15) at a 10.0 microg/L U spike. The experiment accumulation time used was only 150 s. Under this condition, the diagnostic detection limit approached 0.007 ng/L. The method was applied to soil of a natural rock in a radioactive mineralogy site. Earthworms that resided at this site were assayed. The method was found to be applicable in biological diagnosis or in real-time in vivo survey. PMID:20821536

Ly, Suw Young; Lee, Jin-Hui; Jung, Dong Ho

2010-05-01

381

Toxicologic screening of some surfactants using modern in vivo bioassays.  

PubMed

This paper aims to evaluate the degree of skin irritation using specific in vivo tests. The completion of the study is to develop models with wide applicability in toxicological area. HET-CAM or chorioallantoic membrane assay is a new method accepted as an INVITTOX protocol that is a substitute of Draize test. The methods applied in present study were CAM assay on embryonated egg and CD1 Nu/Nu experimental model. The evaluation of erythema that is an important toxic effect of surfactants was done using a Mexameter MX18 (Courage Khazaka research line). The main observations were that sodium lauryl sulphate is the most toxic compound on our series but the non-ionic surfactants are not completely non-noxious. Non-invasive methods can be associated with other test such as CAM assay to evaluate irritant compounds. PMID:21682193

Ardelean, Simona; Feflea, Stefana; Ionescu, Daniela; N?stase, V; Dehelean, Cristina A

2011-01-01

382

In vivo studies of brain development by magnetic resonance techniques.  

PubMed

Understanding of the morphological development of the human brain has largely come from neuropathological studies obtained postmortem. Magnetic resonance (MR) techniques have recently allowed the provision of detailed structural, metabolic, and functional information in vivo on the human brain. These techniques have been utilized in studies from premature infants to adults and have provided invaluable data on the sequence of normal human brain development. This article will focus on MR techniques including conventional structural MR imaging techniques, quantitative morphometric MR techniques, diffusion weighted MR techniques, and MR spectroscopy. In order to understand the potential applications and limitations of MR techniques, relevant physical and biological principles for each of the MR techniques are first reviewed. This is followed by a review of the understanding of the sequence of normal brain development utilizing these techniques. MRDD Research Reviews 6:59-67, 2000. PMID:10899798

Inder, T E; Huppi, P S

2000-01-01

383

In vivo dissolution measurement with indium-111 summation peak ratios  

SciTech Connect

Dissolution of (/sup 111/In)labeled tablets was measured in vivo in a totally noninvasive manner by using a modification of the perturbed angular correlation technique known as the summation peak ratio method. This method, which requires the incorporation of only 10-12 microCi into the dosage form, provided reliable dissolution data after oral administration of (/sup 111/In)lactose tablets. These results were supported by in vitro experiments which demonstrated that the dissolution rate as measured by the summation peak ratio method was in close agreement with the dissolution rate of salicylic acid in a (/sup 111/In)salicylic acid tablet. The method has the advantages of using only one detector, thereby avoiding the need for complex coincidence counting systems, requiring less radioactivity, and being potentially applicable to a gamma camera imaging system.

Jay, M.; Woodward, M.A.; Brouwer, K.R.

1985-10-01

384

Ex vivo cultured neuronal networks emit in vivo-like spontaneous activity.  

PubMed

Spontaneous neuronal activity is present in virtually all brain regions, but neither its function nor spatiotemporal patterns are fully understood. Ex vivo organotypic slice cultures may offer an opportunity to investigate some aspects of spontaneous activity, because they self-restore their networks that collapsed during slicing procedures. In hippocampal networks, we compared the levels and patterns of in vivo spontaneous activity to those in acute and cultured slices. We found that the firing rates and excitatory synaptic activity in the in vivo hippocampus are more similar to those in slice cultures compared to acute slices. The soft confidence-weighted algorithm, a machine learning technique without human bias, also revealed that hippocampal slice cultures resemble the in vivo hippocampus in terms of the overall tendency of the parameters of spontaneous activity. PMID:25208897

Okamoto, Kazuki; Ishikawa, Tomoe; Abe, Reimi; Ishikawa, Daisuke; Kobayashi, Chiaki; Mizunuma, Mika; Norimoto, Hiroaki; Matsuki, Norio; Ikegaya, Yuji

2014-11-01

385

Assessment of corneal hydration sensing in the terahertz band: in vivo results at 100 GHz  

NASA Astrophysics Data System (ADS)

Terahertz corneal hydration sensing has shown promise in ophthalmology applications and was recently shown to be capable of detecting water concentration changes of about two parts in a thousand in ex vivo corneal tissues. This technology may be effective in patient monitoring during refractive surgery and for early diagnosis and treatment monitoring in diseases of the cornea. In this work, Fuchs dystrophy, cornea transplant rejection, and keratoconus are discussed, and a hydration sensitivity of about one part in a hundred is predicted to be needed to successfully distinguish between diseased and healthy tissues in these applications. Stratified models of corneal tissue reflectivity are developed and validated using ex vivo spectroscopy of harvested porcine corneas that are hydrated using polyethylene glycol solutions. Simulation of the cornea's depth-dependent hydration profile, from 0.01 to 100 THz, identifies a peak in intrinsic reflectivity contrast for sensing at 100 GHz. A 100 GHz hydration sensing system is evaluated alongside the current standard ultrasound pachymetry technique to measure corneal hydration in vivo in four rabbits. A hydration sensitivity, of three parts per thousand or better, was measured in all four rabbits under study. This work presents the first in vivo demonstration of remote corneal hydration sensing.

Bennett, David; Taylor, Zachary; Tewari, Pria; Sung, Sijun; Maccabi, Ashkan; Singh, Rahul; Culjat, Martin; Grundfest, Warren; Hubschman, Jean-Pierre; Brown, Elliott

2012-09-01

386

Assessment of corneal hydration sensing in the terahertz band: in vivo results at 100 GHz  

PubMed Central

Abstract. Terahertz corneal hydration sensing has shown promise in ophthalmology applications and was recently shown to be capable of detecting water concentration changes of about two parts in a thousand in ex vivo corneal tissues. This technology may be effective in patient monitoring during refractive surgery and for early diagnosis and treatment monitoring in diseases of the cornea. In this work, Fuchs dystrophy, cornea transplant rejection, and keratoconus are discussed, and a hydration sensitivity of about one part in a hundred is predicted to be needed to successfully distinguish between diseased and healthy tissues in these applications. Stratified models of corneal tissue reflectivity are developed and validated using ex vivo spectroscopy of harvested porcine corneas that are hydrated using polyethylene glycol solutions. Simulation of the cornea’s depth-dependent hydration profile, from 0.01 to 100 THz, identifies a peak in intrinsic reflectivity contrast for sensing at 100 GHz. A 100 GHz hydration sensing system is evaluated alongside the current standard ultrasound pachymetry technique to measure corneal hydration in vivo in four rabbits. A hydration sensitivity, of three parts per thousand or better, was measured in all four rabbits under study. This work presents the first in vivo demonstration of remote corneal hydration sensing. PMID:23085925

Bennett, David; Taylor, Zachary; Tewari, Pria; Sung, Shijun; Maccabi, Ashkan; Singh, Rahul; Culjat, Martin; Grundfest, Warren; Hubschman, Jean-Pierre; Brown, Elliott

2012-01-01

387

Assessment of proarrhythmic activity of chloroquine in in vivo and ex vivo rabbit models  

PubMed Central

Objectives: To evaluate the prolongation of ventricular repolarization and proarrhythmic activity of antimalarial drug chloroquine in two rabbit proarrhythmia models viz., in vivo ?1 adrenoceptor-stimulated anesthetized rabbit and ex vivo isolated Langendorff rabbit heart using clofilium as standard proarrhythmic agent. Materials and Methods: In the in vivo model, three groups of rabbits, anesthetized by pentobarbitone sodium and ?-chloralose, sensitized with ?1 agonist methoxamine followed by either continuous infusion of saline (control) or clofilium (3 mg/kg) or chloroquine (21 mg/kg) for 30 min. In ex vivo model, rabbit hearts were perfused with clofilium (10 ?M) or chloroquine (300 ?M) continuously after priming along with methoxamine, acetylcholine chloride and propranolol hydrochloride. Results: In these models, prolongation of repolarization during ?1-adrenoceptor stimulation produced early after depolarization (EAD) and Torsade de pointes (TdP). Saline infusion did not induce any abnormality in the animals. Clofilium caused expected changes in the electrocardiogram in both the models including TdP (50.0% in in vivo and 66.67% in ex vivo). Chloroquine caused decrease in heart rate and increase in the corrected QT (QTc) interval in both the models. Further, apart from different stages of arrhythmia, TdP was evident in 33.33% in ex vivo model, whereas no TdP was observed in in vivo model. Conclusions: The results indicated that proarrhythmic potential of chloroquine and clofilium was well evaluated in both the models; moreover, both the models can be used to assess the proarrhythmic potential of the new drug candidates. PMID:23759957

Khobragade, Shailaja B.; Gupta, Pankaj; Gurav, Prashant; Chaudhari, Girish; Gatne, Madhumanjiri M.; Shingatgeri, Vyas M.

2013-01-01

388

In vivo lipidomics using single-cell Raman spectroscopy  

PubMed Central

We describe a method for direct, quantitative, in vivo lipid profiling of oil-producing microalgae using single-cell laser-trapping Raman spectroscopy. This approach is demonstrated in the quantitative determination of the degree of unsaturation and transition temperatures of constituent lipids within microalgae. These properties are important markers for determining engine compatibility and performance metrics of algal biodiesel. We show that these factors can be directly measured from a single living microalgal cell held in place with an optical trap while simultaneously collecting Raman data. Cellular response to different growth conditions is monitored in real time. Our approach circumvents the need for lipid extraction and analysis that is both slow and invasive. Furthermore, this technique yields real-time chemical information in a label-free manner, thus eliminating the limitations of impermeability, toxicity, and specificity of the fluorescent probes common in currently used protocols. Although the single-cell Raman spectroscopy demonstrated here is focused on the study of the microalgal lipids with biofuel applications, the analytical capability and quantitation algorithms demonstrated are applicable to many different organisms and should prove useful for a diverse range of applications in lipidomics. PMID:21310969

Wu, Huawen; Volponi, Joanne V.; Oliver, Ann E.; Parikh, Atul N.; Simmons, Blake A.; Singh, Seema

2011-01-01

389

Current Problems and Potential Techniques in In Vivo Glucose Monitoring  

Microsoft Academic Search

Accurate in vivo monitoring of glucose concentration would be a valuable asset, particularly for management of diabetes and preterm infants during critical care. In vivo glucose monitoring devices can be divided into two categories: implanted and non-invasive. Extensive research into in vivo glucose monitoring over recent decades has not resulted in the widespread use of clinically reliable monitoring systems. For

Y. Wickramasinghe; Y. Yang; S. A. Spencer

2004-01-01

390

In vivo gene electroinjection and expression in rat liver  

Microsoft Academic Search

In vivo targeted gene transfer by non-viral vectors is subjected to anatomical constraints depending on the route of administration. Transfection efficiency and gene expression in vivo using non-viral vectors is also relatively low. We report that in vivo electropermeabilization of the liver tissue of rats in the presence of genes encoding luciferase or ?-galactosidase resulted in the strong expression of

Richard Heller; Mark Jaroszeski; Andrew Atkin; Darius Moradpour; Richard Gilbert; Jack Wands; Claude Nicolau

1996-01-01

391

Lipid peroxidation biomarkers for evaluating oxidative stress and assessing antioxidant capacity in vivo  

PubMed Central

Recently, the biological roles of lipid peroxidation products have received a great deal of attention not only for elucidating pathological mechanisms but also for practical clinical applications as biomarkers. In the last 50 years, lipid peroxidation has been the subject of extensive studies from the viewpoints of mechanisms, dynamics, product analysis, involvement in diseases, inhibition, and biological signaling. Lipid hydroperoxides are formed as major primary products, but they are substrates for various enzymes and they also undergo various secondary reactions. During this decade, hydroxyoctadecadienoic acid from linoleates, F2-isoprostanes from arachidonates, and neuroprostanes from docosahexanoates have been proposed as biomarkers for evaluating oxidative stress in vivo and its related diseases. The implications of lipid peroxidation products in vivo will be briefly reviewed and their practical applications will be discussed. PMID:23341691

Yoshida, Yasukazu; Umeno, Aya; Shichiri, Mototada

2013-01-01

392

In vivo proton magnetic resonance spectroscopy of breast cancer: a review of the literature  

PubMed Central

An emerging clinical modality called proton magnetic resonance spectroscopy (1H-MRS) enables the non-invasive in vivo assessment of tissue metabolism and is demonstrating applications in improving the specificity of MR breast lesion diagnosis and monitoring tumour responsiveness to neoadjuvant chemotherapies. Variations in the concentration of choline-based cellular metabolites, detectable with 1H-MRS, have shown an association with malignant transformation of tissue in in vivo and in vitro studies. 1H-MRS exists as an adjunct to the current routine clinical breast MR examination. This review serves as an introduction to the field of breast 1H-MRS, discusses modern high-field strength and quantitative approaches and technical considerations, and reviews the literature with respect to the application of 1H-MRS for breast cancer. PMID:22515594

2012-01-01

393

Light-guiding hydrogels for cell-based sensing and optogenetic synthesis in vivo  

NASA Astrophysics Data System (ADS)

Polymer hydrogels are widely used as cell scaffolds for biomedical applications. Although the biochemical and biophysical properties of hydrogels have been investigated extensively, little attention has been paid to their potential photonic functionalities. Here, we report cell-integrated polyethylene glycol-based hydrogels for in vivo optical-sensing and therapy applications. Hydrogel patches containing cells were implanted in awake, freely moving mice for several days and shown to offer long-term transparency, biocompatibility, cell viability and light-guiding properties (loss of <1 dB cm-1). Using optogenetic, glucagon-like peptide-1 secreting cells, we conducted light-controlled therapy using the hydrogel in a mouse model with diabetes and obtained improved glucose homeostasis. Furthermore, real-time optical readout of encapsulated heat-shock-protein-coupled fluorescent reporter cells made it possible to measure the nanotoxicity of cadmium-based bare and shelled quantum dots (CdTe; CdSe/ZnS) in vivo.

Choi, Myunghwan; Choi, Jin Woo; Kim, Seonghoon; Nizamoglu, Sedat; Hahn, Sei Kwang; Yun, Seok Hyun

2013-12-01

394

In Vivo Cancer Biomarkers of Esophageal Neoplasia  

PubMed Central

Summary The emergence of in vivo cancer biomarkers is promising tool for early detection, risk stratification, and therapeutic intervention in the esophagus, where adenocarcinoma is increasing at a rate that is faster than any other in industrialized nations. Exciting advances in target identification, probe development, and optical instrumentation are creating tremendous new opportunities for advancing techniques of molecular imaging. Progress in these areas is being made with small animal models of esophageal cancer using surgical approaches to induce reflux of acid and bile, and these findings are beginning to be evaluated in the clinic. Further identification of relevant targets, characterization of specific probes, and development of endoscopic imaging technologies are needed to further this direction in the field of molecular medicine. In the future, new methods that use in vivo cancer biomarkers for the early detection of neoplastic changes in the setting of Barrett's esophagus will become available. PMID:19126962

Lu, Shaoying; Wang, Thomas D

2011-01-01

395

In vivo imaging of pancreatic endocrine islets  

NASA Astrophysics Data System (ADS)

Extended focus optical coherence microscope (xfOCM) circumvents the compromise between lateral resolution and depth of field by us of a Bessel-like illumination beam. The high sensitivity and parallel depth profiling of Fourier domain optical coherence tomography are preserved, and combined with high isotropic resolution of 1.5 - 2 ?m. To comply with the requirements for in vivo measurements, beam scanning had to be implemented. We then performed measurements, first of excised pancreas, validated by standard immunohistochemistry, to investigate the structures that can be observed. For a quantitative analysis, a semi-automatic islet detection algorithm evaluated the islet size, position, contrast and homogeneity. The influence of streptozotocin on the signature of the islets was investigated in a next step. Finally, xfOCM was applied to make measurements of the murine pancreas in situ and in vivo, visualizing pancreatic lobules, ducts, blood vessels and individual islets of Langerhans.

Villiger, Martin; Goulley, Joan; Pache, Christophe; Friedrich, Michael; Grapin-Botton, Anne; Meda, Paolo; Leitgeb, Rainer; Lasser, Theo

2009-07-01

396

In vivo imaging of virological synapses.  

PubMed

Retroviruses such as the human immunodeficiency virus, human T-cell lymphotropic virus and murine leukaemia virus are believed to spread via sites of cell-cell contact designated virological synapses. Support for this model is based on in vitro evidence in which infected cells are observed to specifically establish long-lived cell-cell contact with uninfected cells. Whether virological synapses exist in vivo is unknown. Here we apply intravital microscopy to identify a subpopulation of B cells infected with the Friend murine leukaemia virus that form virological synapses with uninfected leucocytes in the lymph node of living mice. In vivo virological synapses are, like their in vitro counterpart, dependent on the expression of the viral envelope glycoprotein and are characterized by a prolonged polarization of viral capsid to the cell-cell interface. Our results validate the concept of virological synapses and introduce intravital imaging as a tool to visualize retroviral spreading directly in living mice. PMID:23271654

Sewald, Xaver; Gonzalez, David G; Haberman, Ann M; Mothes, Walther

2012-01-01

397

In vivo imaging of virological synapses  

PubMed Central

Retroviruses such as the human immunodeficiency virus, human T-cell lymphotropic virus and murine leukaemia virus are believed to spread via sites of cell–cell contact designated virological synapses. Support for this model is based on in vitro evidence in which infected cells are observed to specifically establish long-lived cell–cell contact with uninfected cells. Whether virological synapses exist in vivo is unknown. Here we apply intravital microscopy to identify a subpopulation of B cells infected with the Friend murine leukaemia virus that form virological synapses with uninfected leucocytes in the lymph node of living mice. In vivo virological synapses are, like their in vitro counterpart, dependent on the expression of the viral envelope glycoprotein and are characterized by a prolonged polarization of viral capsid to the cell–cell interface. Our results validate the concept of virological synapses and introduce intravital imaging as a tool to visualize retroviral spreading directly in living mice. PMID:23271654

Sewald, Xaver; Gonzalez, David G.; Haberman, Ann M.; Mothes, Walther

2013-01-01

398

In Vivo Studies on Staphylococcal Penicillinase  

PubMed Central

Eyckmans, Luc (Baylor University Medical Center, Dallas, Tex.), and Ralph Tompsett. In vivo studies on staphylococcal penicillinase. J. Bacteriol. 90:589–593. 1965.—The amounts of staphylococcal penicillinase present in tissue of mice with well-established infections due to penicillin-resistant staphylococci were determined. The data indicate that, in the presence of such infection, penicillinase can be found in amounts adequate to destroy large amounts of penicillin. These results are found in the absence of any conditions which are known to induce penicillinase. Although it has been generally assumed that penicillinase does account for the penicillin resistance of certain staphylococci in vivo, the data presented here document the quantitative aspects of this phenomenon, and indicate that the amounts of penicillinase produced are sufficient to account for the high degrees of resistance observed. PMID:16562052

Eyckmans, Luc; Tompsett, Ralph

1965-01-01

399