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Sample records for combined tissue kinetics

  1. A Combined Tissue Kinetics and Dosimetric Model of Respiratory Tissue Exposed to Radiation

    SciTech Connect

    John R. Ford

    2005-11-01

    Existing dosimetric models of the radiation response of tissues are essentially static. Consideration of changes in the cell populations over time has not been addressed realistically. For a single acute dose this is not a concern, but for modeling chronic exposures or fractionated acute exposures, the natural turnover and progression of cells could have a significant impact on a variety of endpoints. This proposal addresses the shortcomings of current methods by combining current dose-based calculation techniques with information on the cell turnover for a model tissue. The proposed model will examine effects at the single-cell level for an exposure of a section of human bronchiole. The cell model will be combined with Monte Carlo calculations of doses to cells and cell nuclei due to varying dose-rates of different radiation qualities. Predictions from the model of effects on survival, apoptosis rates, and changes in the number of cycling and differentiating cells will be tested experimentally. The availability of dynamic dosimetric models of tissues at the single-cell level will be useful for analysis of low-level radiation exposures and in the development of new radiotherapy protocols.

  2. Development of a combined model of tissue kinetics and radiation response of human bronchiolar epithelium with single cell resolution

    NASA Astrophysics Data System (ADS)

    Ostrovskaya, Natela Grigoryevna

    2005-07-01

    Lack of accurate data for epidemiological studies of low dose radiation effects necessitates development of dosimetric models allowing prediction of cancer risks for different organs. The objective of this work is to develop a model of the radiation response of human bronchiolar tissue with single cell resolution. The computer model describes epithelial tissue as an ensemble of individual cells, with the geometry of a human bronchiole and the properties of different cell types are taken into account. The model simulates the tissue kinetics and radiation exposure in four dimensions: three spatial dimensions and a temporal dimension. The bronchiole is modeled as a regular hollow cylinder with the epithelial cells of three different types (basal, secretory, and ciliated) lining its interior. For the purposes of assessment of radiation damage to the cells only the nuclei of the cells have been modeled. Subroutines describing cellular kinetics have been developed to simulate cell turnover in a normal epithelial tissue. Monte Carlo subroutines have been developed to simulate exposure to alpha particles; the GEANT4 toolkit has been used to simulate exposure to low LET radiation. Each hit cell is provided with a record of energy deposition, and this record is passed to the progeny if the cell survives. The model output provides data on the number of basal progenitor cells in different phases of a cell life-cycle and secretory to ciliated cell ratio after several generations of cell proliferation. The model calculates labeling and mitotic indices and estimates the average cell turnover time for the bronchiolar tissue. Microdosimetric calculations are performed for cells traversed by ionizing particles. The model will be used to assess the accumulation of damage in cells due to protracted low level radiation exposure. The model output may provide directions for the future experimental design.

  3. Kinetic models of tissue fusion processes

    NASA Astrophysics Data System (ADS)

    Pearce, John A.; Thomsen, Sharon L.

    1992-06-01

    Recent studies of tissue fusion (welding) processes have reported temperature ranges but have not carefully analyzed critical exposure time data. Electron microscopic (EM) studies suggest that the fusion process in blood vessels may be dominated by random re-entwinement of thermally dissociated adventitial collagen fibrils (Type I) during the end stage heating and early cooling phases. At the light microscopic level, this bonding process is reflected by the formation of an amorphous coagulum of thermally coagulated adventitial collagen at the anastomotic site. We have constructed a numerical model of the vessel welding process, assuming CO2 laser impingement, and used it to simulate quantitative histologic data obtained from successful welds of rat femoral and canine brachial arteries (unpublished data). The model estimates smooth muscle and collagen damage based on kinetic thermal damage analysis and water loss boundaries as a function of irradiation beam parameters and heating time. Both heating and cooling phases are simulated. The results illustrate the importance of the damage kinetics and local heat transfer phenomena to the weld characteristics realized.

  4. Estradiol release kinetics determine tissue response in ovariectomized rats.

    PubMed

    Otto, Christiane; Kantner, Ingrid; Nubbemeyer, Reinhard; Schkoldow, Jenny; Fuchs, Iris; Krahl, Elisabeth; Vonk, Richardus; Schüler, Christiane; Fritzemeier, Karl-Heinrich; Erben, Reinhold G

    2012-04-01

    Estrogen replacement is an effective therapy of postmenopausal symptoms such as hot flushes, bone loss, and vaginal dryness. Undesired estrogen effects are the stimulation of uterine and mammary gland epithelial cell proliferation as well as hepatic estrogenicity. In this study, we examined the influence of different estradiol release kinetics on tissue responsivity in ovariectomized (OVX) rats. Pulsed release kinetics was achieved by ip or sc administration of estradiol dissolved in physiological saline containing 10% ethanol (EtOH/NaCl) whereas continuous release kinetics was achieved by sc injection of estradiol dissolved in benzylbenzoate/ricinus oil (1+4, vol/vol). Initial 3-d experiments in OVX rats showed that pulsed ip estradiol administration had profoundly reduced stimulatory effects on the uterus and the liver compared with continuous release kinetics. On the other hand, both administration forms prevented severe vaginal atrophy. Based on these results, we compared the effects of pulsed (sc in EtOH/NaCl) vs. continuous (sc in benzylbenzoate/ricinus oil) estradiol release kinetics on bone, uterus, mammary gland, and liver in a 4-month study in OVX rats. Ovariectomy-induced bone loss was prevented by both administration regimes. However, pulsed estradiol resulted in lower uterine weight, reduced induction of hepatic gene expression, and reduced mammary epithelial hyperplasia relative to continuous estradiol exposure. We conclude that organ responsivity is influenced by different hormone release kinetics, a fact that might be exploited to reduce undesired estradiol effects in postmenopausal women.

  5. Saccharomyces cerevisiae thermal inactivation kinetics combined with ultrasound.

    PubMed

    López-Malo, A; Guerrero, S; Alzamora, S M

    1999-10-01

    Inactivation kinetics of Saccharomyces cerevisiae during thermal treatments at moderate temperatures (45.0, 47.5, 50.0, 52.5, or 55.0 degrees C) combined with application of 20 kHz of ultrasound were evaluated. S. cerevisiae inactivation under the combined effects of heat and ultrasound followed first-order reaction kinetics, with decimal reduction times (D) that varied from 22.3 to 0.8 min. D values in treatments that combined heat and ultrasound were significantly smaller (P < 0.05) than D values obtained for thermal treatments and were more noticeable at temperatures below 50 degrees C. The dependence of the D value on temperature had a significantly (P < 0.05) greater z value for combined treatments. Yeast heat inactivation kinetics revealed decreased thermal resistance caused by ultrasound.

  6. Combined additive manufacturing approaches in tissue engineering.

    PubMed

    Giannitelli, S M; Mozetic, P; Trombetta, M; Rainer, A

    2015-09-01

    Advances introduced by additive manufacturing (AM) have significantly improved the control over the microarchitecture of scaffolds for tissue engineering. This has led to the flourishing of research works addressing the optimization of AM scaffolds microarchitecture to optimally trade-off between conflicting requirements (e.g. mechanical stiffness and porosity level). A fascinating trend concerns the integration of AM with other scaffold fabrication methods (i.e. "combined" AM), leading to hybrid architectures with complementary structural features. Although this innovative approach is still at its beginning, significant results have been achieved in terms of improved biological response to the scaffold, especially targeting the regeneration of complex tissues. This review paper reports the state of the art in the field of combined AM, posing the accent on recent trends, challenges, and future perspectives. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  7. Kinetics of a sulfadiazine-trimethoprim combination.

    PubMed

    Bergan, T; Vik-Mo, H; Anstad, U

    1977-08-01

    The pharmacokinetics of a combination of sulfadiazine and trimethoprim has been studied in 16 patients with varying degrees of reduced renal function. In normal renal function, the serum half-life (t1/2) of active sulfadiazine, total sulfadiazine, and trimethoprim were quite close: 7.7, 9.6, and 12.1 hr, respectively. There was a gradual increase in serum t1/2 with reduction in renal function for both active and total sulfadiazine and for trimethoprim. With accurate determinations of endogenous renal clearance, t1/2 estimates may be made from regression curves presented. The relative distribution in the body was unrelated to renal function. It was similar for the two fractions of sulfonamide and higher for trimethoprim. The means were 0.371, 0.176, and 1.104 L/kg, respectively, for active and total sulfadiazine, and trimethoprim.

  8. Combining Electrolysis and Electroporation for Tissue Ablation.

    PubMed

    Phillips, Mary; Rubinsky, Liel; Meir, Arie; Raju, Narayan; Rubinsky, Boris

    2015-08-01

    Electrolytic ablation is a method that operates by delivering low magnitude direct current to the target region over long periods of time, generating electrolytic products that destroy cells. This study was designed to explore the hypothesis stating that electrolytic ablation can be made more effective when the electrolysis-producing electric charges are delivered using electric pulses with field strength typical in reversible electroporation protocols. (For brevity we will refer to tissue ablation protocols that combine electroporation and electrolysis as E(2).) The mechanistic explanation of this hypothesis is related to the idea that products of electrolysis generated by E(2) protocols can gain access to the interior of the cell through the electroporation permeabilized cell membrane and therefore cause more effective cell death than from the exterior of an intact cell. The goal of this study is to provide a first-order examination of this hypothesis by comparing the charge dosage required to cause a comparable level of damage to a rat liver, in vivo, when using either conventional electrolysis or E(2) approaches. Our results show that E(2) protocols produce tissue damage that is consistent with electrolytic ablation. Furthermore, E(2) protocols cause damage comparable to that produced by conventional electrolytic protocols while delivering orders of magnitude less charge to the target tissue over much shorter periods of time.

  9. Antiretroviral Tissue Kinetics: In Vivo Imaging Using Positron Emission Tomography▿

    PubMed Central

    Di Mascio, Michele; Srinivasula, Sharat; Bhattacharjee, Abesh; Cheng, Lily; Martiniova, Lucia; Herscovitch, Peter; Lertora, Juan; Kiesewetter, Dale

    2009-01-01

    Our current knowledge on the antiviral efficacy, dosing, and toxicity of available highly active antiretroviral therapy regimens is mostly derived from plasma or blood kinetics of anti-human immunodeficiency virus (anti-HIV) drugs. However, the blood comprises only 2% of the total target cells in the body. Tissue drug levels may differ substantially from corresponding plasma levels, and drug distribution processes may be characterized by high intertissue variability, leading to suboptimal target site concentrations and the potential risk for therapeutic failures. Positron emission tomography has greatly expanded the scope of the pharmacokinetic measurements that can be performed noninvasively in animal models or humans. We have prepared [18F]FPMPA, a fluorine-18-radiolabeled analogue of tenofovir, to study antiretroviral tissue kinetics in vivo noninvasively and tested the imaging probe in rats. The biodistribution of the fluorine-18 analogue closely follows that of nonfluorinated tenofovir. Compared to that in the blood, the levels of penetration of the antiretroviral drug were found to be significantly reduced in the spleen and submandibular lymph nodes (∼2-fold), in the mesenteric lymph nodes and the testes (∼4-fold), and in the brain compartment (∼25-fold). Intersubject variability of the trough drug concentration (measured at 120 min) in certain tissues, like the colon (coefficient of variation, >100%), is not reflected by the intersubject variability in the blood compartment (coefficient of variation, 24%). Positron emission tomography imaging of the fluorine-18 analogue revealed the accumulation of the antiretroviral drug in the cortex of the kidneys, a potential correlate of tenofovir-induced nephrotoxicity observed in HIV-1-infected treated patients. Thus, [18F]FPMPA is a promising radiotracer for evaluation of tenofovir biodistribution under carefully controlled drug administration protocols. PMID:19667288

  10. Plasma and tissue kinetics of phenylbutazone and naproxen in dogs.

    PubMed

    Zech, R; Scherkl, R; Hashem, A; Frey, H H

    1993-01-01

    By means of tissue cages in which a sterile inflammation was induced after injection of carrageenan, plasma and tissue kinetics of two NSAIDs were followed. The first one, phenylbutazone, is characterized by a fairly short elimination half-life (3-6 hours) in dogs, whereas the other one, naproxen, has an average half-life of 67 hours in this species. After a single oral dose of 15 mg/kg, phenylbutazone reached concentrations of 13-20 micrograms/ml in the exudate from the tissue cages. Plasma peak concentrations of 49-75 micrograms/ml were reached. Due to a considerably longer half-life in the exudate than in plasma (7.3-18 hours), the concentration in the exudate exceeded that in plasma at about 20 hours. Naproxen (5 mg/kg, orally) showed a parallel decline in plasma and exudate concentrations for more than 200 hours. Continued treatment for one week with phenylbutazone (15 mg/kg, BID) resulted in plasma concentrations with wide fluctuations between doses, but the concentration in the exudate remained at a constant level. After administration of naproxen (5 mg/kg on the first day and then 2 mg/kg once daily), plasma concentrations remained at 40-50 microgram/ml and those in the exudate at 20-30 microgram/ml throughout the treatment period. Both drugs caused a considerable fall of the leukocyte count in the exudate which may be used as an indicator of the anti-inflammatory effect.

  11. Kinetic model of sucrose accumulation in maturing sugarcane culm tissue.

    PubMed

    Uys, Lafras; Botha, Frederik C; Hofmeyr, Jan-Hendrik S; Rohwer, Johann M

    2007-01-01

    Biochemically, it is not completely understood why or how commercial varieties of sugarcane (Saccharum officinarum) are able to accumulate sucrose in high concentrations. Such concentrations are obtained despite the presence of sucrose synthesis/breakdown cycles (futile cycling) in the culm of the storage parenchyma. Given the complexity of the process, kinetic modelling may help to elucidate the factors governing sucrose accumulation or direct the design of experimental optimisation strategies. This paper describes the extension of an existing model of sucrose accumulation (Rohwer, J.M., Botha, F.C., 2001. Analysis of sucrose accumulation in the sugar cane culm on the basis of in vitro kinetic data. Biochem. J. 358, 437-445) to account for isoforms of sucrose synthase and fructokinase, carbon partitioning towards fibre formation, and the glycolytic enzymes phosphofructokinase (PFK), pyrophosphate-dependent PFK and aldolase. Moreover, by including data on the maximal activity of the enzymes as measured in different internodes, a growth model was constructed that describes the metabolic behaviour as sugarcane parenchymal tissue matures from internodes 3-10. While there was some discrepancy between modelled and experimentally determined steady-state sucrose concentrations in the cytoplasm, steady-state fluxes showed a better fit. The model supports a hypothesis of vacuolar sucrose accumulation against a concentration gradient. A detailed metabolic control analysis of sucrose synthase showed that each isoform has a unique control profile. Fructose uptake by the cell and sucrose uptake by the vacuole had a negative control on the futile cycling of sucrose and a positive control on sucrose accumulation, while the control profile for neutral invertase was reversed. When the activities of these three enzymes were changed from their reference values, the effects on futile cycling and sucrose accumulation were amplified. The model can be run online at the JWS Online

  12. Thermogravimetric kinetic study of agricultural residue biomass pyrolysis based on combined kinetics.

    PubMed

    Wang, Xun; Hu, Mian; Hu, Wanyong; Chen, Zhihua; Liu, Shiming; Hu, Zhiquan; Xiao, Bo

    2016-11-01

    Pyrolytic kinetic of an agricultural residue (AR) feedstock, a mixture of plants (cotton, wheat, rich, corn) stems, was investigated based on combined kinetics. The most suitable mechanism for AR one-step pyrolysis was f(α)=(1-α)(1.1816)α(-1.8428) with kinetic parameters of: apparent activation energy 221.7kJ/mol, pre-exponential factor 4.17E16s(-1). Pyrolysis of AR feedstock could not be described by one-step reaction attributes to heterogeneous features of pyrolysis processes. Combined kinetics three-parallel-reaction (CK-TPR) model fitted the pyrolysis experimental data very well. Reaction mechanisms for pseudo hemicelluloses, cellulose, lignin in CK-TPR model was f(α)=(1-α)(1.6244)α(-0.3371)[-ln(1-α)](-0.0515), f(α)=(1-α)(1.0597)α(-0.6909)[-ln(1-α)](0.9026) and f(α)=(1-α)(2.9577)α(-4.7719), respectively. Apparent activation energy of three pseudo components followed the order of Elignin(197.3kJ/mol)>Ecellulose(176.3kJ/mol)>Ehemicelluloses (151.1kJ/mol). Mechanism of hemicelluloses pyrolysis could be further expressed as f(α)=(1-α)(1.4). The pyrolytic mechanism of cellulose met the Nucleation well. However, mechanism of lignin pyrolysis was complex, which possibly was the combined effects of Nucleation, Diffusion, Geometrical contraction, and Power law. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Exploring the chemical kinetics of partially oxidized intermediates by combining experiments, theory, and kinetic modeling.

    PubMed

    Hoyermann, Karlheinz; Mauß, Fabian; Olzmann, Matthias; Welz, Oliver; Zeuch, Thomas

    2017-07-19

    Partially oxidized intermediates play a central role in combustion and atmospheric chemistry. In this perspective, we focus on the chemical kinetics of alkoxy radicals, peroxy radicals, and Criegee intermediates, which are key species in both combustion and atmospheric environments. These reactive intermediates feature a broad spectrum of chemical diversity. Their reactivity is central to our understanding of how volatile organic compounds are degraded in the atmosphere and converted into secondary organic aerosol. Moreover, they sensitively determine ignition timing in internal combustion engines. The intention of this perspective article is to provide the reader with information about the general mechanisms of reactions initiated by addition of atomic and molecular oxygen to alkyl radicals and ozone to alkenes. We will focus on critical branching points in the subsequent reaction mechanisms and discuss them from a consistent point of view. As a first example of our integrated approach, we will show how experiment, theory, and kinetic modeling have been successfully combined in the first infrared detection of Criegee intermediates during the gas phase ozonolysis. As a second example, we will examine the ignition timing of n-heptane/air mixtures at low and intermediate temperatures. Here, we present a reduced, fuel size independent kinetic model of the complex chemistry initiated by peroxy radicals that has been successfully applied to simulate standard n-heptane combustion experiments.

  14. Kinetics of combined pressure-temperature inactivation of avocado polyphenoloxidase.

    PubMed

    Weemaes, C A; Ludikhuyze, L R; Van den Broeck, I; Hendrickx, M E

    1998-11-05

    Irreversible combined pressure-temperature inactivation of the food quality related enzyme polyphenoloxidase was investigated. Inactivation rate constants (k) were obtained for about one hundred combinations of constant pressure (0.1-900 MPa) and temperature (25-77.5 degrees C). According to the Eyring and Arrhenius equation, activation volumes and activation energies, respectively, representing pressure and temperature dependence of the inactivation rate constant, were calculated for all temperatures and pressures studied. In this way, temperature and pressure dependence of activation volume and activation energy, respectively, could be considered. Moreover, for the first time, a mathematical model describing the inactivation rate constant of a food quality-related enzyme as a function of pressure and temperature is formulated. Such pressure-temperature inactivation models for food quality-related aspects (e.g., the spoilage enzyme polyphenoloxidase) form the engineering basis for design, evaluation, and optimization of new preservation processes based on the combined effect of temperature and pressure. Furthermore, the generated methodology can be used to develop analogous kinetic models for microbiological aspects, which are needed from a safety and legislative point of view, and other quality aspects, e.g., nutritional factors, with a view of optimal quality and consumer acceptance. Copyright 1998 John Wiley & Sons, Inc.

  15. Kinetics of carbaryl and malathion in combination in the rat.

    PubMed

    Waldron Lechner, D; Abdel-Rahman, M S

    1986-01-01

    The disposition and metabolism of pesticides used in combination, especially carbaryl and malathion, is of considerable toxicological importance. Radioactivity was rapidly absorbed from the rat gastrointestinal tract (GIT) following the administration of 0.25 ml of 10 mg/kg [14C]carbaryl (0.80 microCi), 10/10 mg/kg [14C]carbaryl/malathion (0.80 microCi), 10 mg/kg [14C]malathion (1.03 microCi), or 10/10 mg/kg [14C]malathion/carbaryl (0.86 microCi). The. administration of carbaryl or malathion, individually and in combination, followed a two-phase elimination model. The presence of malathion decreased the rate constants of absorption and beta-phase elimination of [14C]carbaryl. In the mean time, the length of the distribution phase and the area under the curve of [14C]carbaryl were decreased by malathion administration. Although [14C]malathion's absorption half-life was unchanged in the presence of carbaryl, increases were noted in the length of the distribution phase, beta-phase elimination half-life, and area under the curve for malathion when administered simultaneously with carbaryl. Both combinations caused an increase in 14C activity to be deposited in the fat as compared to the respectively labeled pesticide. However, only malathion increased the concentration of [14C]carbaryl remaining in the GIT tissues after the administration of the combined pesticides. The subcellular distribution of the liver indicated that the highest activity was present in the cytosol. These pesticides and their combinations were excreted primarily by the kidney, followed by the lung and the intestinal route. Although there was no alteration in the metabolic pathways due to the combinations, an increase in malaoxon and malathion diacid concentration in urine was observed after the administration of [14C]malathion/carbaryl as compared to [14C]malathion. The results from this study revealed that the combination of these pesticides altered fundamental pharmacokinetic parameters, which

  16. Kinetics of combined heterogeneous catalytic reactions with a common reagent

    SciTech Connect

    Pyatnitskii, Yu.I.

    1995-01-01

    The kinetics of combined catalytic reactions with a common reagent (competitive reactions) is analyzed assuming that no changes in the reaction mechanisms occur under their conjugation. A simplified approach is advanced for determining the relative rates of competitive reactions characterized by a similar mechanism of the initial stage for the interaction between the competitive reactants and catalyst. This includes the complex reactions, in which one of the reaction product serves as a competitive agent. The effects of nontrivial mutual influence of the competitive catalytic reactions are discussed. One type of this mutual influence manifests itself as a drastic inhibition of one reaction by another; this is not due to the catalyst surface blocking. This effect is inherent to the reactions involving the reversible dissociation of a heteroatomic reagent. The other type of the mutual influence is revealed in the promotion of one reaction by another when at least one of the reaction follows the Langmuir-Hinshelwood mechanism and the adsorption of a common reagent is far from the equilibrium.

  17. Combination of biochemical and mechanical cues for tendon tissue engineering.

    PubMed

    Testa, Stefano; Costantini, Marco; Fornetti, Ersilia; Bernardini, Sergio; Trombetta, Marcella; Seliktar, Dror; Cannata, Stefano; Rainer, Alberto; Gargioli, Cesare

    2017-05-04

    Tendinopathies negatively affect the life quality of millions of people in occupational and athletic settings, as well as the general population. Tendon healing is a slow process, often with insufficient results to restore complete endurance and functionality of the tissue. Tissue engineering, using tendon progenitors, artificial matrices and bioreactors for mechanical stimulation, could be an important approach for treating rips, fraying and tissue rupture. In our work, C3H10T1/2 murine fibroblast cell line was exposed to a combination of stimuli: a biochemical stimulus provided by Transforming Growth Factor Beta (TGF-β) and Ascorbic Acid (AA); a three-dimensional environment represented by PEGylated-Fibrinogen (PEG-Fibrinogen) biomimetic matrix; and a mechanical induction exploiting a custom bioreactor applying uniaxial stretching. In vitro analyses by immunofluorescence and mechanical testing revealed that the proposed combined approach favours the organization of a three-dimensional tissue-like structure promoting a remarkable arrangement of the cells and the neo-extracellular matrix, reflecting into enhanced mechanical strength. The proposed method represents a novel approach for tendon tissue engineering, demonstrating how the combined effect of biochemical and mechanical stimuli ameliorates biological and mechanical properties of the artificial tissue compared to those obtained with single inducement. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  18. CELL POPULATION KINETICS OF AN OSTEOGENIC TISSUE · I

    PubMed Central

    Owen, Maureen

    1963-01-01

    Cell proliferation on the actively growing periosteal surface of the femur of rabbits aged 2 weeks has been investigated using autoradiographic techniques. Injections of tritiated glycine and tritiated thymidine were given simultaneously and the animals sacrificed at intervals from 1 hour to 5 days after injection. The glycine labeled the position of the bone surface at the time of injection and the thymidine labeled the cells which were synthesising DNA. The rate of increase in the cell population was determined by counting the number of cells beyond the glycine label at different times after injection. The cell kinetics of the fibroblast-pre-osteoblast-osteoblast-osteocyte system has been studied. The fibroblasts are relatively unimportant from the point of view of increase in the cell population. The main site of cell proliferation is the layer of pre-osteoblasts on the periosteal surface. The rate of movement of cells from the pre-osteoblast to the osteoblast and osteocyte compartments has been measured. The incorporation of osteoblasts into the bone is not a random process, but it appears that the osteoblast must spend a certain time on the periosteal surface before becoming either an osteocyte or a relatively inactive osteoblast lining an haversian canal. It was estimated that, on an average, an osteoblast produces 2 or 3 times its own volume of matrix during its most active period on the periosteal surface. PMID:14069793

  19. Kinetics of tissue iron in experimental autoimmune encephalomyelitis in rats.

    PubMed

    Tota, Marin; Jakovac, Hrvoje; Grebić, Damir; Marinić, Jelena; Broznić, Dalibor; Čanadi-Jurešić, Gordana; Milin, Cedomila; Radošević-Stašić, Biserka

    2011-10-01

    To elucidate the role of iron in the pathomechanisms of autoimmune CNS disorders, we estimated the tissue concentrations of Fe(2+) in the brain, spinal cord, and liver in the chronic relapsing form of experimental autoimmune encephalomyelitis (EAE). The disease was induced in Dark Agouti (DA) strain of rats, by subcutaneous injection of bovine brain homogenate in complete Freund's adjuvant (CFA). Control rats consisted of unsensitized rats and of rats treated with CFA or saline. The data obtained by clinical assessment and by inductively coupled plasma spectrometry have shown that the attacks of disease (on the 12th and 22nd post-immunization day) were followed by high accumulation of iron in the liver. Additionally, during the second attack of disease, the decreased concentration of Fe(2+) was found in cervical spinal cord. The data point to regulatory effects of iron and hepatic trace elements regulating mechanisms in the pathogenesis of EAE.

  20. Inactivation kinetics and photoreactivation of vegetable oxidative enzymes after combined UV-C processing

    USDA-ARS?s Scientific Manuscript database

    The inactivation kinetics of lipoxygenase (LOX), peroxidase (POD) and polyphenoloxidase (PPO) in phosphate buffer (pH 4.0 and 7.0) treated by combined thermal (25-65 C) and UV-C (1-10 min) processes were fitted using a traditional first-order kinetics model and the Weibull distribution function. For...

  1. Cell and tissue kinetics of the subependymal layer in mouse brain following heavy charged particle irradiation

    SciTech Connect

    Manley, N.B.; Fabrikant, J.I.; Alpen, E.L.

    1988-12-01

    The following studies investigate the cellular response and cell population kinetics of the subependymal layer in the mouse brain exposed to heavy charged particle irradiation. Partial brain irradiation with helium and neon ions was confined to one cortex of the brain. Both the irradiated and the unirradiated contralateral cortex showed similar disturbances of the cell and tissue kinetics in the subependymal layers. The irradiated hemisphere exhibited histological damage, whereas the unirradiated side appeared normal histologically. This study concerns the cell population and cell cycle kinetics of the subependymal layer in the mouse brain, and the effects of charged particle irradiations on this cell population. Quantitative high resolution autoradiography was used to study the kinetic parameters in this cell layer. This study should help in understanding the effects of these high-energy heavy ions on normal mammalian brain tissue. The response of the mammalian brain exposure to charged particle ionizing radiation may be extremely variable. It varies from minimal physiological changes to overt tissue necrosis depending on a number of factors such as: the administered dose, dose-rate, the volume of the irradiated tissue, and the biological end-point being examined.

  2. Combined ideal and kinetic effects on reversed shear Alfven eigenmodes

    SciTech Connect

    Gorelenkov, N. N.; Kramer, G. J.; Nazikian, R.

    2011-10-15

    A reversed shear Alfven eigenmodes (RSAEs) theory has been developed for reversed magnetic field shear plasmas when the safety factor minimum, q{sub min}, is at or above a rational value. The modes we study are known sometimes as either the bottom of the frequency sweep or the down sweeping RSAEs. We show that, strictly speaking, the ideal MHD theory is not compatible with the eigenmode solution in the reversed shear plasma with q{sub min} above integer values. Corrected by a special analytic finite Larmor radius (FLR) condition, MHD dispersion of these modes nevertheless can be developed. Numerically, MHD structure can serve as a good approximation for the RSAEs.The large radial scale part of the analytic RSAE solution can be obtained from ideal MHD and expressed in terms of the Legendre functions. The kinetic equation with FLR effects for the eigenmode is solved numerically and agrees with the analytic solutions. Properties of RSAEs and their potential implications for plasma diagnostics are discussed.

  3. Combined ultrasonic and photoacoustic system for deep tissue imaging

    NASA Astrophysics Data System (ADS)

    Kim, Chulhong; Erpelding, Todd N.; Jankovic, Ladislav; Wang, Lihong V.

    2011-03-01

    A combined ultrasonic and photoacoustic imaging system is presented that is capable of deep tissue imaging. The system consists of a modified clinical ultrasound array system and tunable dye laser pumped by a Nd:YAG laser. The system is designed for noninvasive detection of sentinel lymph nodes and guidance of needle biopsies for axillary lymph node staging in breast cancer patients. Using a fraction of the American National Standards Institute (ANSI) safety limit, photoacoustic imaging of methylene blue achieved penetration depths of greater than 5 cm in chicken breast tissue. Photoacoustic imaging sensitivity was measured by varying the concentration of methylene blue dye placed at a depth of 3 cm within surrounding chicken breast tissue. Signal-to-noise ratio, noise equivalent sensitivity, and axial spatial resolution were quantified versus depth based on in vivo and chicken breast tissue experiments. The system has been demonstrated in vivo for detecting sentinel lymph nodes in rats following intradermal injection of methylene blue. These results highlight the clinical potential of photoacoustic image-guided identification and needle biopsy of sentinel lymph nodes for axillary staging in breast cancer patients.

  4. Tissue distribution and kinetics of endogenous porphyrins synthesized after topical application of ALA in different vehicles

    PubMed Central

    Casas, A; Fukuda, H; Batlle, A M del C

    1999-01-01

    The use of 5-aminolaevulinic acid (ALA) is gaining increasing attention for photosensitization in photodynamic therapy of superficially localized tumours. The aim of this work was to determine the kinetics of porphyrin generation in tissues after topical application of ALA delivered in different vehicles on the skin overlying the tumour and normal skin of mice. Maximal accumulation was found in tumour 3 h after ALA application in both cream and lotion preparations. Normal and overlying tumour skin tissues showed different kinetic patterns, reflecting histological changes when the latter is invaded by tumour cells. Liver, kidney, spleen and blood porphyrins also raised from basal levels, showing that ALA and/or ALA-induced porphyrins reach all tissues after topical application. During the first 24 h of ALA topical application, precursors and porphyrins are excreted by both urine and faeces. ALA lotion applied on the skin overlying the tumour induced higher accumulation of tumoural porphyrins than cream, and lotion applied on normal skin appeared to be the most efficient upon inducing total body porphyrins. This work has demonstrated the great influence of the formulation of ALA vehicle on penetration through the skin. Knowledge of the kinetics of porphyrin generation after different conditions of ALA application is needed for the optimization of diagnosis and phototherapy in human tumours. © 1999 Cancer Research Campaign PMID:10487606

  5. Continuum theory of fibrous tissue damage mechanics using bond kinetics: application to cartilage tissue engineering.

    PubMed

    Nims, Robert J; Durney, Krista M; Cigan, Alexander D; Dusséaux, Antoine; Hung, Clark T; Ateshian, Gerard A

    2016-02-06

    This study presents a damage mechanics framework that employs observable state variables to describe damage in isotropic or anisotropic fibrous tissues. In this mixture theory framework, damage is tracked by the mass fraction of bonds that have broken. Anisotropic damage is subsumed in the assumption that multiple bond species may coexist in a material, each having its own damage behaviour. This approach recovers the classical damage mechanics formulation for isotropic materials, but does not appeal to a tensorial damage measure for anisotropic materials. In contrast with the classical approach, the use of observable state variables for damage allows direct comparison of model predictions to experimental damage measures, such as biochemical assays or Raman spectroscopy. Investigations of damage in discrete fibre distributions demonstrate that the resilience to damage increases with the number of fibre bundles; idealizing fibrous tissues using continuous fibre distribution models precludes the modelling of damage. This damage framework was used to test and validate the hypothesis that growth of cartilage constructs can lead to damage of the synthesized collagen matrix due to excessive swelling caused by synthesized glycosaminoglycans. Therefore, alternative strategies must be implemented in tissue engineering studies to prevent collagen damage during the growth process.

  6. Continuum theory of fibrous tissue damage mechanics using bond kinetics: application to cartilage tissue engineering

    PubMed Central

    Nims, Robert J.; Durney, Krista M.; Cigan, Alexander D.; Hung, Clark T.; Ateshian, Gerard A.

    2016-01-01

    This study presents a damage mechanics framework that employs observable state variables to describe damage in isotropic or anisotropic fibrous tissues. In this mixture theory framework, damage is tracked by the mass fraction of bonds that have broken. Anisotropic damage is subsumed in the assumption that multiple bond species may coexist in a material, each having its own damage behaviour. This approach recovers the classical damage mechanics formulation for isotropic materials, but does not appeal to a tensorial damage measure for anisotropic materials. In contrast with the classical approach, the use of observable state variables for damage allows direct comparison of model predictions to experimental damage measures, such as biochemical assays or Raman spectroscopy. Investigations of damage in discrete fibre distributions demonstrate that the resilience to damage increases with the number of fibre bundles; idealizing fibrous tissues using continuous fibre distribution models precludes the modelling of damage. This damage framework was used to test and validate the hypothesis that growth of cartilage constructs can lead to damage of the synthesized collagen matrix due to excessive swelling caused by synthesized glycosaminoglycans. Therefore, alternative strategies must be implemented in tissue engineering studies to prevent collagen damage during the growth process. PMID:26855751

  7. The Combination of Tissue Dissection and External Volume Expansion Generates Large Volumes of Adipose Tissue.

    PubMed

    He, Yunfan; Dong, Ziqing; Xie, Gan; Zhou, Tao; Lu, Feng

    2017-04-01

    Noninvasive external volume expansion device has been applied to stimulate nonsurgical breast enlargement in clinical settings. Although previous results demonstrate the capacity of external volume expansion to increase the number of adipocytes, this strategy alone is insufficient to reconstruct soft-tissue defects or increase breast mass. The authors combined a minimally invasive tissue dissection method with external volume expansion to generate large volumes of adipose tissue. In vitro, various densities of adipose-derived stem cells were prepared to evaluate relations between cell contacts and cell proliferation. In vivo, dorsal adipose tissue of rabbits was thoroughly dissected and the external volume expansion device was applied to maintain the released state. External volume expansion without tissue dissection served as the control. In the dissection group, the generated adipose tissue volume was much larger than that in the control group at all time points. A larger number of proliferating cells appeared in the dissection samples than in the control samples at the early stage after tissue dissection. At low cell density, adipose-derived stem cells displayed an increasing proliferation rate compared to high cell density. Protein expression analysis revealed that cell proliferation was mediated by a similar mechanism both in vivo and in vitro, involving the release of cell contact inhibition and Hippo/Yes-associated protein pathway activation. Adipose tissue dissection releases cell-to-cell contacts and induces adipose-derived stem cell proliferation. Preexpanded adipose-derived stem cells undergo adipogenesis under the adipogenic environment created by external volume expansion, leading to better adipose regeneration compared with the control.

  8. [The tissue cage in dogs--a pharmacologic model for the representation of plasma and tissue kinetics].

    PubMed

    Scherkl, R; Hashem, A; Frey, H H

    1996-05-01

    Determination of pharmacokinetic data from plasma often is not sufficient in order to predict or to explain the clinical efficacy of drugs, e.g., in non steroidal antiinflammatory drugs (NSAID) with short elimination half lives in plasma a discrepancy appears between elimination half life and clinical effect. We have studied the tissue kinetics of a drug having a long elimination half life (naproxen) in comparison with phenylbutazone and flunixin, having a short elimination half life in dogs after oral application. Tissue fluid was obtained by using so called "tissue cages" implanted laterally in the neck. An inflammatory response was produced by injecting 1-2 ml of 2% carrageenan into the chamber. The drug concentrations were determined throughout the experiments both in plasma and tissue fluid. Naproxen concentrations (elimination half life of about 72 h in dogs) achieved equilibrium between tissue fluid and plasma concentration. In the case of phenylbutazone, concentration in tissue fluid declined with a definitely longer half life than in plasma and exceeded plasma concentrations after some hours. Flunixin concentrations in plasma and exudate attained equilibrium after 2-5 h. Of clinical importance is the finding that after this time flunixin accumulated in inflammatory exudate and the concentration in exudate exceeded that in plasma two to ten times, then declined with an almost identical half-life. The number of leukocytes in exudate as a measure of inflammation was reduced during 2 days after phenylbutazone, 3-4 days after flunixin and 5-7 days after naproxen. This allows therapy with a lower dosage than calculated on the basis of plasma concentrations in the case of phenylbutazone and flunixin, possibly also with other NSAIDs having a short plasma half life.

  9. Combining Targeted Agents With Modern Radiotherapy in Soft Tissue Sarcomas

    PubMed Central

    Wong, Philip; Houghton, Peter; Kirsch, David G.; Finkelstein, Steven E.; Monjazeb, Arta M.; Xu-Welliver, Meng; Dicker, Adam P.; Ahmed, Mansoor; Vikram, Bhadrasain; Teicher, Beverly A.; Coleman, C. Norman; Machtay, Mitchell; Curran, Walter J.

    2014-01-01

    Improved understanding of soft-tissue sarcoma (STS) biology has led to better distinction and subtyping of these diseases with the hope of exploiting the molecular characteristics of each subtype to develop appropriately targeted treatment regimens. In the care of patients with extremity STS, adjunctive radiation therapy (RT) is used to facilitate limb and function, preserving surgeries while maintaining five-year local control above 85%. In contrast, for STS originating from nonextremity anatomical sites, the rate of local recurrence is much higher (five-year local control is approximately 50%) and a major cause of death and morbidity in these patients. Incorporating novel technological advancements to administer accurate RT in combination with novel radiosensitizing agents could potentially improve local control and overall survival. RT efficacy in STS can be increased by modulating biological pathways such as angiogenesis, cell cycle regulation, cell survival signaling, and cancer-host immune interactions. Previous experiences, advancements, ongoing research, and current clinical trials combining RT with agents modulating one or more of the above pathways are reviewed. The standard clinical management of patients with STS with pretreatment biopsy, neoadjuvant treatment, and primary surgery provides an opportune disease model for interrogating translational hypotheses. The purpose of this review is to outline a strategic vision for clinical translation of preclinical findings and to identify appropriate targeted agents to combine with radiotherapy in the treatment of STS from different sites and/or different histology subtypes. PMID:25326640

  10. A mechanistic description of radiation-induced damage to normal tissue and its healing kinetics

    NASA Astrophysics Data System (ADS)

    Hanin, Leonid; Zaider, Marco

    2013-02-01

    We introduce a novel mechanistic model of the yield of tissue damage at the end of radiation treatment and of the subsequent healing kinetics. We find explicit expressions for the total number of functional proliferating cells as well as doomed (functional but non-proliferating) cells as a function of time post treatment. This leads to the possibility of estimating—for any given cohort of patients undergoing radiation therapy—the probability distribution of those kinetic parameters (e.g. proliferation rates) that determine times to injury onset and ensuing resolution. The model is suitable for tissues with simple duplication organization, meaning that functionally competent cells are also responsible for tissue renewal or regeneration following injury. An extension of the model to arbitrary temporal patterns of dose rate is presented. To illustrate the practical utility of the model, as well as its limitations, we apply it to data on the time course of urethral toxicity following fractionated radiation treatment and brachytherapy for prostate cancer.

  11. Ex-vivo tissue classification of cell surface receptor concentrations using kinetic modeling

    NASA Astrophysics Data System (ADS)

    Sinha, Lagnojita; Wang, Yu; Yang, Cynthia; Khan, Altaz; Liu, Jonathan T.; Tichauer, Kenneth M.

    2015-03-01

    One of the major challenges in the complete resection of cancer is the difficulty of distinctly classifying tumor and healthy tissue. This paper investigates the capability of competing kinetic modeling approaches for identifying different tissue types based on differential cell-surface receptor expressions. These approaches require fresh resected tissues to be stained with a mixture of two probes: one targeted to a cancer specific cell-surface receptor, and another left "untargeted" to account for nonspecific retention of the targeted agent, with subsequent repeated rinsing and imaging of the probe concentrations. Analysis of the results were carried out in simulations and in animal experiments for the cancer target, epidermal growth factor receptor (EGFR), a cell surface receptor overexpressed by many cancers. In the animal experiments, subcutaneous xenografts of human glioma (U251; moderate EGFR) and human epidermoid (A431; high EGFR) tumors, grown in six athymic mice, were excised and stained with an EGFR targeted surface-enhanced Raman scattering nanoparticle (SERS NP) and untargeted SERS NP pair. The salient finding in this study was that significant non-specific retention was observed for the EGFR targeted probe [anti-EGFR antibody labeled with a surface-enhanced Raman scattering (SERS) nanoparticle], but could be corrected for by the equivalent non-specific retention of the untargeted probe (isotype control antibody labeled with a different SERS nanoparticle). Once this non-specific binding was accounted for, the kinetic model was able to predict the expected differences in EGFR concentration among different tissue types: healthy, U251, and A431 in accordance with an ex vivo flow cytometry analysis, successfully classifying different tissue types.

  12. Synergistic Combination of Electrolysis and Electroporation for Tissue Ablation

    PubMed Central

    Mikus, Paul; Klein, Nina; Rubinsky, Liel; Rubinsky, Boris

    2016-01-01

    Electrolysis, electrochemotherapy with reversible electroporation, nanosecond pulsed electric fields and irreversible electroporation are valuable non-thermal electricity based tissue ablation technologies. This paper reports results from the first large animal study of a new non-thermal tissue ablation technology that employs “Synergistic electrolysis and electroporation” (SEE). The goal of this pre-clinical study is to expand on earlier studies with small animals and use the pig liver to establish SEE treatment parameters of clinical utility. We examined two SEE methods. One of the methods employs multiple electrochemotherapy-type reversible electroporation magnitude pulses, designed in such a way that the charge delivered during the electroporation pulses generates the electrolytic products. The second SEE method combines the delivery of a small number of electrochemotherapy magnitude electroporation pulses with a low voltage electrolysis generating DC current in three different ways. We show that both methods can produce lesion with dimensions of clinical utility, without the need to inject drugs as in electrochemotherapy, faster than with conventional electrolysis and with lower electric fields than irreversible electroporation and nanosecond pulsed ablation. PMID:26866693

  13. Synergistic Combination of Electrolysis and Electroporation for Tissue Ablation.

    PubMed

    Stehling, Michael K; Guenther, Enric; Mikus, Paul; Klein, Nina; Rubinsky, Liel; Rubinsky, Boris

    2016-01-01

    Electrolysis, electrochemotherapy with reversible electroporation, nanosecond pulsed electric fields and irreversible electroporation are valuable non-thermal electricity based tissue ablation technologies. This paper reports results from the first large animal study of a new non-thermal tissue ablation technology that employs "Synergistic electrolysis and electroporation" (SEE). The goal of this pre-clinical study is to expand on earlier studies with small animals and use the pig liver to establish SEE treatment parameters of clinical utility. We examined two SEE methods. One of the methods employs multiple electrochemotherapy-type reversible electroporation magnitude pulses, designed in such a way that the charge delivered during the electroporation pulses generates the electrolytic products. The second SEE method combines the delivery of a small number of electrochemotherapy magnitude electroporation pulses with a low voltage electrolysis generating DC current in three different ways. We show that both methods can produce lesion with dimensions of clinical utility, without the need to inject drugs as in electrochemotherapy, faster than with conventional electrolysis and with lower electric fields than irreversible electroporation and nanosecond pulsed ablation.

  14. Tuning Cell and Tissue Development by Combining Multiple Mechanical Signals.

    PubMed

    Sinha, Ravi; Verdonschot, Nico; Koopman, Bart; Rouwkema, Jeroen

    2017-05-03

    Mechanical signals offer a promising way to control cell and tissue development. It has been established that cells constantly probe their mechanical microenvironment and employ force feedback mechanisms to modify themselves and when possible, their environment, to reach a homeostatic state. Thus, a correct mechanical microenvironment (external forces and mechanical properties and shapes of cellular surroundings) is necessary for the proper functioning of cells. In vitro or in the case of nonbiological implants in vivo, where cells are in an artificial environment, addition of the adequate mechanical signals can, therefore, enable the cells to function normally as in vivo. Hence, a wide variety of approaches have been developed to apply mechanical stimuli (such as substrate stretch, flow-induced shear stress, substrate stiffness, topography, and modulation of attachment area) to cells in vitro. These approaches have not just revealed the effects of the mechanical signals on cells but also provided ways for probing cellular molecules and structures that can provide a mechanistic understanding of the effects. However, they remain lower in complexity compared with the in vivo conditions, where the cellular mechanical microenvironment is the result of a combination of multiple mechanical signals. Therefore, combinations of mechanical stimuli have also been applied to cells in vitro. These studies have had varying focus-developing novel platforms to apply complex combinations of mechanical stimuli, observing the co-operation/competition between stimuli, combining benefits of multiple stimuli toward an application, or uncovering the underlying mechanisms of their action. In general, they provided new insights that could not have been predicted from previous knowledge. We present here a review of several such studies and the insights gained from them, thereby making a case for such studies to be continued and further developed.

  15. [Comparative kinetics of oxytetracycline and oxyglucocycline cotent in tissues of the ENT organs].

    PubMed

    Pluzhnikov, M S; Gevorkian, E A

    1976-10-01

    The kinetics of oxytetracycline and oxyglucocycline levels (calculated for oxytetracycline) was studied on 80 patients with chronic inflammatory diseases of the upper respiratory organs, the antibiotics being administered intramuscularly. After a single injection of oxytetrachcline hydrochloride in a dose of 1500 Units/kg body weight its levels in the blood serum and certain tissues of the ENT organs were rather low. When the dose was 3000 Units/kg the maximum antibiotic level in the blood level reached 1 Unit/ml. The drug was detected in the bacteriostatic concentrations in the blood serum and tissues within 12 hours. When the dose of oxyglucocycline was 1500 Units/kg the rate of its absorption was 4 times higher than that of oxytetracycline absorption. However, the character of its distribution in the blood and tissues of the ENT organs did not differ from distribution of oxytetracycline as dependent on the duration of the injection period. The both pharmaceutical forms had a tendency to some retention of the drugs in the tissues of the palatine tonsils. Because of better absorption and retention in the tonsils tissue oxyglucocycline may be recommended for therapy of inflammatory processes in the lymphadenoid apparatus of the pharynx.

  16. Determination of Glutamate Dehydrogenase Activity and Its Kinetics in Mouse Tissues using Metabolic Mapping (Quantitative Enzyme Histochemistry)

    PubMed Central

    Botman, Dennis; Tigchelaar, Wikky

    2014-01-01

    Glutamate dehydrogenase (GDH) catalyses the reversible conversion of glutamate into α-ketoglutarate with the concomitant reduction of NAD(P)+ to NAD(P)H or vice versa. GDH activity is subject to complex allosteric regulation including substrate inhibition. To determine GDH kinetics in situ, we assessed the effects of various glutamate concentrations in combination with either the coenzyme NAD+ or NADP+ on GDH activity in mouse liver cryostat sections using metabolic mapping. NAD+-dependent GDH Vmax was 2.5-fold higher than NADP+-dependent Vmax, whereas the Km was similar, 1.92 mM versus 1.66 mM, when NAD+ or NADP+ was used, respectively. With either coenzyme, Vmax was determined at 10 mM glutamate and substrate inhibition was observed at higher glutamate concentrations with a Ki of 12.2 and 3.95 for NAD+ and NADP+ used as coenzyme, respectively. NAD+- and NADP+-dependent GDH activities were examined in various mouse tissues. GDH activity was highest in liver and much lower in other tissues. In all tissues, the highest activity was found when NAD+ was used as a coenzyme. In conclusion, GDH activity in mice is highest in the liver with NAD+ as a coenzyme and highest GDH activity was determined at a glutamate concentration of 10 mM. PMID:25124006

  17. Studying the Kinetics of n-Butyl-Cyanoacrylate Tissue Adhesive and Its Oily Mixtures

    NASA Astrophysics Data System (ADS)

    Nedvedova, Marie; Kresalek, Vojtech; Vaskova, Hana; Provaznik, Ivo

    2016-10-01

    This study deals with the measurement of the kinetics of tissue adhesives used for supporting the hemostasis and wound closure during surgical intervention. There are available several types of adhesives of different composition which is closely related with their application. When selecting an appropriate adhesive, the time of curing could play an important role because some applications may require very fast polymerization for prompt vessel or wound closure; conversely, some situations need slower solidification because of longer manipulation with the glue during surgery. The terahertz time-domain spectroscopy is used for studying the kinetics of the n-butyl-cyanoacrylate glue in this study. An oily substance is added to the glue samples to slow the reaction rate. The technique of attenuated total reflection is used in this application; the defined amount of glue sample or its mixture is applied on the silicon crystal and the terahertz response is measured in time. This time dependences are analyzed to find time constants for mathematical description of the glue kinetics. Further, the investigated samples were analyzed using light microscopy and Raman spectroscopy for description of the structures and compositions.

  18. Cell and tissue kinetics of the subependymal layer in mouse brain following heavy charged particle irradiation

    SciTech Connect

    Manley, N.B.

    1988-01-01

    The following studies investigate the cellular response and cell population kinetics of the subependymal layer in the mouse brain exposed to heavy charged particle irradiation. Partial brain irradiation with helium and neon ions was confined to one cortex of the brain. Both the irradiated and the unirradiated contralateral cortex showed similar disturbances of the cell and tissue kinetics in the subependymal layers. The irradiated hemisphere exhibited histological damage, whereas the unirradiated side appeared normal histologically. The decrease in the values of the labeling indices 1 week after charged particle irradiation was dose- and ion-dependent. Mitotic indices 1 week after 10 and 25 Gy helium and after 10 Gy neon were the same as those seen in the control mice. Analysis of cell kinetics 1 week after 10 Gy helium and 10 Gy neon irradiation suggests the presence of a progenitor subpopulation that is proliferating with a shorter cell cycle. Comparison of the responses to the different charged particle beams indicates that neon ions are more effective in producing direct cellular damage than the helium ions, but the surviving proliferating cells several divisions later continue to maintain active cell renewal. Based on the 1 week post-irradiation H{sup 3}-TdR labeling indices, a rough estimate of the RBE for neon ions is at least 2.5 when compared to helium ions.

  19. Human receptor kinetics and lung tissue retention of the enhanced-affinity glucocorticoid fluticasone furoate

    PubMed Central

    Valotis, Anagnostis; Högger, Petra

    2007-01-01

    Fluticasone furoate (FF) – USAN approved name, a new topically active glucocorticoid has been recently identified. The aim of this study was to characterise the binding affinity of this compound to the human lung glucocorticoid receptor in relation to other glucocorticoids. Additionally, we sought to determine the binding behaviour of fluticasone furoate to human lung tissue. The glucocorticoid receptor binding kinetics of fluticasone furoate revealed a remarkably fast association and a slow dissociation resulting in a relative receptor affinity (RRA) of 2989 ± 135 with reference to dexamethasone (RRA: 100 ± 5). Thus, the RRA of FF exceeds the RRAs of all currently clinically used corticosteroids such as mometasone furoate (MF; RRA 2244), fluticasone propionate (FP; RRA 1775), ciclesonide's active metabolite (RRA 1212 – rat receptor data) or budesonide (RRA 855). FP and FF displayed pronounced retention in human lung tissue in vitro. Lowest tissue binding was found for MF. There was no indication of instability or chemical modification of FF in human lung tissue. These advantageous binding attributes may contribute to a highly efficacious profile for FF as a topical treatment for inflammatory disorders of the respiratory tract. PMID:17650349

  20. A kinetic study of bitter taste receptor sensing using immobilized porcine taste bud tissues.

    PubMed

    Wei, Lihui; Qiao, Lixin; Pang, Guangchang; Xie, Junbo

    2017-06-15

    At present, developing an efficient assay method for truly reflecting the real feelings of gustatory tissues is of great importance. In this study, a novel biosensor was fabricated to investigate the kinetic characteristics of the receptors in taste bud tissues sensing bitter substances for the first time. Porcine taste bud tissues were used as the sensing elements, and the sandwich-type sensing membrane was fixed onto a glassy carbon electrode for assembling the biosensor. With the developed sensor, the response currents induced by sucrose octaacetate, denatonium benzoate, and quercetin stimulating corresponding receptors were determined. The results demonstrated that the interaction between the analyst with their receptors were fitting to hyperbola (R(2)=0.9776, 0.9980 and 0.9601), and the activation constants were 8.748×10(-15)mol/L, 1.429×10(-12)mol/L, 6.613×10(-14)mol/L, respectively. The average number of receptors per cell was calculated as 1.75, 28.58, and 13.23, while the signal amplification factors were 1.08×10(4), 2.89×10(3) and 9.76×10(4). These suggest that the sensor can be used to quantitatively describe the interaction characteristics of cells or tissue receptors with their ligands, the role of cellular signaling cascade, the number of receptors, and the signal transmission pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Combinational feature optimization for classification of lung tissue images

    NASA Astrophysics Data System (ADS)

    Samala, Ravi K.; Zhukov, Tatyana; Zhang, Jianying; Tockman, Melvyn; Qian, Wei

    2010-03-01

    A novel approach to feature optimization for classification of lung carcinoma using tissue images is presented. The methodology uses a combination of three characteristics of computational features: F-measure, which is a representation of each feature towards classification, inter-correlation between features and pathology based information. The metadata provided from pathological parameters is used for mapping between computational features and biological information. Multiple regression analysis maps each category of features based on how pathology information is correlated with the size and location of cancer. Relatively the computational features represented the tumor size better than the location of the cancer. Based on the three criteria associated with the features, three sets of feature subsets with individual validation are evaluated to select the optimum feature subset. Based on the results from the three stages, the knowledgebase produces the best subset of features. An improvement of 5.5% was observed for normal Vs all abnormal cases with Az value of 0.731 and 74/114 correctly classified. The best Az value of 0.804 with 66/84 correct classification and improvement of 21.6% was observed for normal Vs adenocarcinoma.

  2. Kinetics and mechanism of intercellular ice propagation in a micropatterned tissue construct.

    PubMed Central

    Irimia, Daniel; Karlsson, Jens O M

    2002-01-01

    Understanding the effects of cell-cell interaction on intracellular ice formation (IIF) is required to design optimized protocols for cryopreservation of tissue. To determine the effects of cell-cell interactions during tissue freezing, without confounding effects from uncontrolled factors (such as time in culture, cell geometry, and cell-substrate interactions), HepG2 cells were cultured in pairs on glass coverslips micropatterned with polyethylene glycol disilane, such that each cell interacted with exactly one adjacent cell. Assuming the cell pair to be a finite state system, being either in an unfrozen state (no ice in either cell), a singlet state (IIF in one cell only), or a doublet state (IIF in both cells), the kinetics of state transitions were theoretically modeled and cryomicroscopically measured. The rate of intercellular ice propagation, estimated from the measured singlet state probability, increased in the first 24 h of culture and remained steady thereafter. In cell pairs cultured for 24 h and treated with the gap junction blocker 18beta-glycyrrhetinic acid before freezing, the intercellular ice propagation rate was lower than in untreated controls (p < 0.001), but significantly greater than zero (p < 0.0001). These results suggest that gap junctions mediate some, but not all, mechanisms of ice propagation in tissue. PMID:11916845

  3. Metallothionein expression and tissue metal kinetics after partial hepatectomy in mice.

    PubMed

    Jakovac, Hrvoje; Grebić, Damir; Mrakovcić-Sutić, Ines; Tota, Marin; Broznić, Dalibor; Marinić, Jelena; Tomac, Jelena; Milin, Cedomila; Radosević-Stasić, Biserka

    2006-01-01

    To better elucidate previous results showing that partial hepatectomy noticeably changes the tissue content of zinc, calcium, magnesium, and iron(II) ions in regenerating the liver, thymus, and spleen, we report on the correlation of these metal tissue kinetics in these organs with the expression of metallothionein-I+II (MT-I+II) proteins and MT-I mRNA in early postoperative period (1, 2, 6, 12, and 24 h) after one-third hepatectomy (pHx). The results showed that 2 h after pHx the regenerating liver accumulated Zn2+, Ca2+, Mg2+, and Fe2+ ions while decreasing the concentration of all these metals in the spleen and of Zn2+ in the thymus. On the 24th h, a new high accumulation of Zn2+ and Ca2+ was seen in the regenerating liver and of Zn2+, Ca2+, and Fe2+ in the spleen. Simultaneously, MT-I mRNA increased in the liver and spleen. In hepatocytes and on several spleen and thymus mononuclear lymphatic cells, the increased expression of MT proteins was found mainly in the cytoplasm and nuclei. The areas expressing MTs in regenerating liver inversely correlated with those containing apoptotic cells, suggesting that these proteins participate in tissue restoration through reduction or increase of metal ions after injury to the liver.

  4. A kinetic aggregation assay allowing selective and sensitive amyloid-β quantification in cells and tissues.

    PubMed

    Du, Deguo; Murray, Amber N; Cohen, Ehud; Kim, Hyun-Eui; Simkovsky, Ryan; Dillin, Andrew; Kelly, Jeffery W

    2011-03-15

    The process of amyloid-β (Aβ) fibril formation is genetically and pathologically linked to Alzheimer's disease (AD). Thus, a selective and sensitive method for quantifying Aβ fibrils in complex biological samples allows a variety of hypotheses to be tested. Herein, we report the basis for a quantitative in vitro kinetic aggregation assay that detects seeding-competent Aβ aggregates in mammalian cell culture media, in Caenorhabditis elegans lysate, and in mouse brain homogenate. Sonicated, proteinase K-treated Aβ fibril-containing tissue homogenates or cell culture media were added to an initially monomeric Aβ(1-40) reporter peptide to seed an in vitro nucleated aggregation reaction. The reduction in the half-time (t(50)) of the amyloid growth phase is proportional to the quantity of seeding-competent Aβ aggregates present in the biological sample. An ion-exchange resin amyloid isolation strategy from complex biological samples is demonstrated as an alternative for improving the sensitivity and linearity of the kinetic aggregation assay.

  5. Size-dependent tissue kinetics of PEG-coated gold nanoparticles

    SciTech Connect

    Cho, Wan-Seob; Cho, Minjung; Jeong, Jinyoung; Choi, Mina; Han, Beom Seok; Shin, Hyung-Seon; Hong, Jin; Chung, Bong Hyun; Jeong, Jayoung; Cho, Myung-Haing

    2010-05-15

    Gold nanoparticles (AuNPs) can be used in various biomedical applications, however, very little is known about their size-dependent in vivo kinetics. Here, we performed a kinetic study in mice with different sizes of PEG-coated AuNPs. Small AuNPs (4 or 13 nm) showed high levels in blood for 24 h and were cleared by 7 days, whereas large (100 nm) AuNPs were completely cleared by 24 h. All AuNPs in blood re-increased at 3 months, which correlated with organ levels. Levels of small AuNPs were peaked at 7 days in the liver and spleen and at 1 month in the mesenteric lymph node, and remained high until 6 months, with slow elimination. In contrast, large AuNPs were taken up rapidly (approx 30 min) into the liver, spleen, and mesenteric lymph nodes with less elimination phase. TEM showed that AuNPs were entrapped in cytoplasmic vesicles and lysosomes of Kupffer cells and macrophages of spleen and mesenteric lymph node. Small AuNPs transiently activated CYP1A1 and 2B, phase I metabolic enzymes, in liver tissues from 24 h to 7 days, which mirrored with elevated gold levels in the liver. Large AuNPs did not affect the metabolic enzymes. Thus, propensity to accumulate in the reticuloendothelial organs and activation of phase I metabolic enzymes, suggest that extensive further studies are needed for practical in vivo applications.

  6. Kinetics of Satratoxin G Tissue Distribution and Excretion Following Intranasal Exposure in the Mouse

    PubMed Central

    Amuzie, Chidozie J.; Islam, Zahidul; Kim, Jae Kyung; Seo, Ji-Hyun; Pestka, James J.

    2010-01-01

    Intranasal exposure of mice to satratoxin G (SG), a macrocyclic trichothecene produced by the indoor air mold Stachybotrys chartarum, selectively induces apoptosis in olfactory sensory neurons (OSNs) of the nose and brain. The purpose of this study was to measure the kinetics of distribution and clearance of SG in the mouse. Following intranasal instillation of female C57B16 mice with SG (500 μg/kg bw), the toxin was detectable from 5 to 60 min in blood and plasma, with the highest concentrations, 30 and 19 ng/ml, respectively, being observed at 5 min. SG clearance from plasma was rapid and followed single-compartment kinetics (t1/2 = 20 min) and differed markedly from that of other tissues. SG concentrations were maximal at 15–30 min in nasal turbinates (480 ng/g), kidney (280 ng/g), lung (250 ng/g), spleen (200 ng/g), liver (140 ng/g), thymus (90 ng/g), heart (70 ng/g), olfactory bulb (14 ng/g), and brain (3 ng/g). The half-lives of SG in the nasal turbinate and thymus were 7.6 and 10.1 h, respectively, whereas in other organs, these ranged from 2.3 to 4.4 h. SG was detectable in feces and urine, but cumulative excretion over 5 days via these routes accounted for less than 0.3% of the total dose administered. Taken together, SG was rapidly taken up from the nose, distributed to tissues involved in respiratory, immune, and neuronal function, and subsequently cleared. However, a significant amount of the toxin was retained in the nasal turbinate, which might contribute to SG’s capacity to evoke OSN death. PMID:20466779

  7. Bioceramics and Scaffolds: A Winning Combination for Tissue Engineering

    PubMed Central

    Baino, Francesco; Novajra, Giorgia; Vitale-Brovarone, Chiara

    2015-01-01

    In the last few decades, we have assisted to a general increase of elder population worldwide associated with age-related pathologies. Therefore, there is the need for new biomaterials that can substitute damaged tissues, stimulate the body’s own regenerative mechanisms, and promote tissue healing. Porous templates referred to as “scaffolds” are thought to be required for three-dimensional tissue growth. Bioceramics, a special set of fully, partially, or non-crystalline ceramics (e.g., calcium phosphates, bioactive glasses, and glass–ceramics) that are designed for the repair and reconstruction of diseased parts of the body, have high potential as scaffold materials. Traditionally, bioceramics have been used to fill and restore bone and dental defects (repair of hard tissues). More recently, this category of biomaterials has also revealed promising applications in the field of soft-tissue engineering. Starting with an overview of the fundamental requirements for tissue engineering scaffolds, this article provides a detailed picture on recent developments of porous bioceramics and composites, including a summary of common fabrication technologies and a critical analysis of structure–property and structure–function relationships. Areas of future research are highlighted at the end of this review, with special attention to the development of multifunctional scaffolds exploiting therapeutic ion/drug release and emerging applications beyond hard tissue repair. PMID:26734605

  8. Bioceramics and Scaffolds: A Winning Combination for Tissue Engineering.

    PubMed

    Baino, Francesco; Novajra, Giorgia; Vitale-Brovarone, Chiara

    2015-01-01

    In the last few decades, we have assisted to a general increase of elder population worldwide associated with age-related pathologies. Therefore, there is the need for new biomaterials that can substitute damaged tissues, stimulate the body's own regenerative mechanisms, and promote tissue healing. Porous templates referred to as "scaffolds" are thought to be required for three-dimensional tissue growth. Bioceramics, a special set of fully, partially, or non-crystalline ceramics (e.g., calcium phosphates, bioactive glasses, and glass-ceramics) that are designed for the repair and reconstruction of diseased parts of the body, have high potential as scaffold materials. Traditionally, bioceramics have been used to fill and restore bone and dental defects (repair of hard tissues). More recently, this category of biomaterials has also revealed promising applications in the field of soft-tissue engineering. Starting with an overview of the fundamental requirements for tissue engineering scaffolds, this article provides a detailed picture on recent developments of porous bioceramics and composites, including a summary of common fabrication technologies and a critical analysis of structure-property and structure-function relationships. Areas of future research are highlighted at the end of this review, with special attention to the development of multifunctional scaffolds exploiting therapeutic ion/drug release and emerging applications beyond hard tissue repair.

  9. Nickel and phosphorous sorption efficiencies, tissue accumulation kinetics and morphological effects on Eichhornia crassipes.

    PubMed

    Hadad, H R; Maine, M A; Pinciroli, M; Mufarrege, M M

    2009-07-01

    The aim of the research was to assess the uptake efficiencies of Ni and P, their distribution in tissues along time and their toxic effects on the internal and external morphologies of Eichhornia crassipes. Aquaria with plants exposed to 1 mg Ni l(-1) or 5 mg P l(-1) and control were arranged in triplicate. Water and plants (aerial parts and roots) were sampled along 30 days. Ni uptake and tissue bioaccumulation kinetics was significantly faster than that of P. Mean root length, number of leaves, biomass and chlorophyll concentration were negatively affected by Ni, while these parameters were significantly increased by P in comparison with the control. Stele and metaxylem vessel cross-sectional areas (CSA) in the P treatment were significantly lower in comparison with that obtained in the Ni treatment and in control. Metaxylem vessels CSA in plants exposed to Ni were significantly higher while the number of vessels was significantly lower than those obtained in the control. Despite the toxic effects, E. crassipes efficiently accumulated Ni, probably due to the morphological plasticity of its root system.

  10. Skin Diseases Modeling using Combined Tissue Engineering and Microfluidic Technologies.

    PubMed

    Mohammadi, Mohammad Hossein; Heidary Araghi, Behnaz; Beydaghi, Vahid; Geraili, Armin; Moradi, Farshid; Jafari, Parya; Janmaleki, Mohsen; Valente, Karolina Papera; Akbari, Mohsen; Sanati-Nezhad, Amir

    2016-10-01

    In recent years, both tissue engineering and microfluidics have significantly contributed in engineering of in vitro skin substitutes to test the penetration of chemicals or to replace damaged skins. Organ-on-chip platforms have been recently inspired by the integration of microfluidics and biomaterials in order to develop physiologically relevant disease models. However, the application of organ-on-chip on the development of skin disease models is still limited and needs to be further developed. The impact of tissue engineering, biomaterials and microfluidic platforms on the development of skin grafts and biomimetic in vitro skin models is reviewed. The integration of tissue engineering and microfluidics for the development of biomimetic skin-on-chip platforms is further discussed, not only to improve the performance of present skin models, but also for the development of novel skin disease platforms for drug screening processes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Combined heat transfer and kinetic models to predict cooking loss during heat treatment of beef meat.

    PubMed

    Kondjoyan, Alain; Oillic, Samuel; Portanguen, Stéphane; Gros, Jean-Bernard

    2013-10-01

    A heat transfer model was used to simulate the temperature in 3 dimensions inside the meat. This model was combined with a first-order kinetic models to predict cooking losses. Identification of the parameters of the kinetic models and first validations were performed in a water bath. Afterwards, the performance of the combined model was determined in a fan-assisted oven under different air/steam conditions. Accurate knowledge of the heat transfer coefficient values and consideration of the retraction of the meat pieces are needed for the prediction of meat temperature. This is important since the temperature at the center of the product is often used to determine the cooking time. The combined model was also able to predict cooking losses from meat pieces of different sizes and subjected to different air/steam conditions. It was found that under the studied conditions, most of the water loss comes from the juice expelled by protein denaturation and contraction and not from evaporation.

  12. Kinetically directed combination therapy with adriamycin and x-irradiation in a mammary tumor model

    SciTech Connect

    Braunschweiger, P.G.; Schenken, L.L.; Schiffer, L.M.

    1981-06-01

    In the present studies, the interaction of adriamycin (A) and x-irradiation (X) in T1699 mouse mammary tumors was evaluated. Mitotic indices and thymidine labeling indices were determined at various intervals after A or X alone, and after A + X given in combination. The results with A (1.0 mg/kg) and X(200 R) alone suggest that those quantities of each agent induce a G/sub 2/ progression delay of 9 to 12 h. The kinetic results after A + X in combination indicated increased S phase transit time and G/sub 2/ progression delay. Recovery kinetics after A + X were used to predict optimum sequence intervals for subsequent A + X fractions. Sequential A + X treatment schedules, up to 4 fractions, were designed and evaluated by regrowth delay measurements. The results indicated that the interaction was additive when A and X were given together in combination. Fractionation of A + X to minimize proliferative recovery between fractions resulted in an enhanced antitumor effect.

  13. Kinetics of amoxicillin and clavulanate degradation alone and in combination in aqueous solution under frozen conditions.

    PubMed

    Vahdat, L; Sunderland, V B

    2007-09-05

    Kinetics of the reactions of amoxicillin sodium and potassium clavulanate alone and in combination were investigated in the frozen state at selected pH values of 2.0, 4.6 and 7.0. Extrapolation of the rate constant values to the frozen state from the liquid state data indicated marked acceleration of the rates of amoxicillin and clavulanate degradation for the pH values investigated. The highest acceleration in rate recorded was 15.0-fold for clavulanate and the lowest value was 4.6-fold for amoxicillin at -7.3 degrees C in the hydrochloric acid system. The rate constant values obtained were interpreted in terms of the concentration model [Pincock, R.E., Kiovsky, T.E., 1966. Kinetics of reactions in frozen solution. J. Chem. Educ. 43, 358-360], phase-temperature relationship of the solutes, buffer catalysis, pH change and polymerization reactions. A kinetic model was deduced for the hydrochloric acid system providing adequate explanation of the experimental results. A large stabilizing effect of sodium chloride used for maintaining constant ionic strength (micro=0.5) was evident in this system. The shelf-life of amoxicillin was increased from 2.2 to 58.7h at -7.3 degrees C when sodium chloride was included in the hydrochloric acid system.

  14. Combining an Optical Resonance Biosensor with Enzyme Activity Kinetics to Understand Protein Adsorption and Denaturation

    PubMed Central

    Wilson, Kerry A.; Finch, Craig A.; Anderson, Phillip; Vollmer, Frank; Hickman, James J.

    2014-01-01

    Understanding protein adsorption and resultant conformation changes on modified and unmodified silicon dioxide surfaces is a subject of keen interest in biosensors, microfluidic systems and for medical diagnostics. However, it has been proven difficult to investigate the kinetics of the adsorption process on these surfaces as well as understand the topic of the denaturation of proteins and its effect on enzyme activity. A highly sensitive optical whispering gallery mode (WGM) resonator was used to study a catalytic enzyme’s adsorption processes on different silane modified glass substrates (plain glass control, DETA, 13F, and SiPEG). The WGM sensor was able to obtain high resolution kinetic data of glucose oxidase (GO) adsorption with sensitivity of adsorption better than that possible with SPR. The kinetic data, in combination with a functional assay of the enzyme activity, was used to test hypotheses on adsorption mechanisms. By fitting numerical models to the WGM sensograms for protein adsorption, and by confirming numerical predictions of enzyme activity in a separate assay, we were able to identify mechanisms for GO adsorption on different alkylsilanes and infer information about the adsorption of protein on nanostructured surfaces. PMID:25453976

  15. Combining an optical resonance biosensor with enzyme activity kinetics to understand protein adsorption and denaturation.

    PubMed

    Wilson, Kerry A; Finch, Craig A; Anderson, Phillip; Vollmer, Frank; Hickman, James J

    2015-01-01

    Understanding protein adsorption and resultant conformation changes on modified and unmodified silicon dioxide surfaces is a subject of keen interest in biosensors, microfluidic systems and for medical diagnostics. However, it has been proven difficult to investigate the kinetics of the adsorption process on these surfaces as well as understand the topic of the denaturation of proteins and its effect on enzyme activity. A highly sensitive optical whispering gallery mode (WGM) resonator was used to study a catalytic enzyme's adsorption processes on different silane modified glass substrates (plain glass control, DETA, 13 F, and SiPEG). The WGM sensor was able to obtain high resolution kinetic data of glucose oxidase (GO) adsorption with sensitivity of adsorption better than that possible with SPR. The kinetic data, in combination with a functional assay of the enzyme activity, was used to test hypotheses on adsorption mechanisms. By fitting numerical models to the WGM sensograms for protein adsorption, and by confirming numerical predictions of enzyme activity in a separate assay, we were able to identify mechanisms for GO adsorption on different alkylsilanes and infer information about the adsorption of protein on nanostructured surfaces. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats

    SciTech Connect

    Lanza-Jacoby, S.; Tabares, A. )

    1990-04-01

    The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studied by examining liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant iv infusion of (2-3H)glycerol-labeled VLDL. Clearance of VLDL-TG was also evaluated by measuring activities of lipoprotein lipase (LPL) in heart, soleus muscle, and adipose tissue from fasted control, fasted E. coli-treated, fed control, and fed E. coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 x 10(7) live E. coli colonies per 100 g body wt. Twenty-four hours after E. coli injection, serum TG, free fatty acids (FFA), and cholesterol of fasted E. coli-treated rats were elevated by 170, 76, and 16%, respectively. The elevation of serum TG may be attributed to the 67% decrease in clearance rate of VLDL-TG in fasted E. coli-treated rats compared with their fasted controls. The suppressed activities of LPL in adipose tissue, skeletal muscle, and heart were consistent with reduced clearance of TG. Secretion of VLDL-TG declined by 31% in livers of fasted E. coli-treated rats, which was accompanied by a twofold increase in the composition of liver TG. Rates of in vivo TG synthesis in livers of the fasted E. coli-treated rats were twofold higher than in those of fasted control rats. Decreased rate of TG appearance along with the increase in liver synthesis of TG contributed to the elevation of liver lipids in the fasted E. coli-treated rats.

  17. Integrating Proteomics and Enzyme Kinetics Reveals Tissue-Specific Types of the Glycolytic and Gluconeogenic Pathways.

    PubMed

    Wiśniewski, Jacek R; Gizak, Agnieszka; Rakus, Dariusz

    2015-08-07

    Glycolysis is the core metabolic pathway supplying energy to cells. Whereas the vast majority of studies focus on specific aspects of the process, global analyses characterizing simultaneously all enzymes involved in the process are scarce. Here, we demonstrate that quantitative label- and standard-free proteomics allows accurate determination of titers of metabolic enzymes and enables simultaneous measurements of titers and maximal enzymatic activities (Amax) of all glycolytic enzymes and the gluconeogenic fructose 1,6-bisphosphatase in mouse brain, liver and muscle. Despite occurrence of tissue-specific isoenzymes bearing different kinetic properties, the enzyme titers often correlated well with the Amax values. To provide a more general picture of energy metabolism, we analyzed titers of the enzymes in additional 7 mouse organs and in human cells. Across the analyzed samples, we identified two basic profiles: a "fast glucose uptake" one in brain and heart, and a "gluconeogenic rich" one occurring in liver. In skeletal muscles and other organs, we found intermediate profiles. Obtained data highlighted the glucose-flux-limiting role of hexokinase which activity was always 10- to 100-fold lower than the average activity of all other glycolytic enzymes. A parallel determination of enzyme titers and maximal enzymatic activities allowed determination of kcat values without enzyme purification. Results of our in-depth proteomic analysis of the mouse organs did not support the concepts of regulation of glycolysis by lysine acetylation.

  18. Kinetic analysis and modelling of combined high-pressure-temperature inactivation of the yeast Zygosaccharomyces bailii.

    PubMed

    Reyns, K M; Soontjens, C C; Cornelis, K; Weemaes, C A; Hendrickx, M E; Michiels, C W

    2000-06-01

    Eight foodborne yeasts were screened for sensitivity to high-pressure (HP) inactivation under a limited number of pressure-temperature combinations. The most resistant strains were Zygoascus hellenicus and Zygosaccharomyces bailii. The latter was taken for a detailed study of inactivation kinetics over a wide range of pressures (120-320 MPa) and temperatures (-5 to 45 degrees C). Isobaric and isothermal inactivation experiments were conducted in Tris-HCl buffer pH 6.5 for 48 different combinations of pressure and temperature. Inactivation was biphasic, with a first phase encompassing four to six decades and being described by first-order kinetics, followed by a tailing phase. Decimal reduction times (D) were calculated for the first-order inactivation phase and their temperature and pressure dependence was described. At constant temperature, D decreased with increasing pressure as expected. At constant pressure, D showed a maximum at around 20 degrees C, and decreased both at lower and at higher temperatures. A mathematical expression was developed to describe accurately the inactivation of Z. bailii as a function of pressure and temperature under the experimental conditions employed. A limited number of experiments in buffer at low pH (3-6) suggest that the model is, in principle, applicable at low pH. In apple and orange juice however, higher inactivation than predicted by the model was achieved.

  19. Formation of vascularized meniscal tissue by combining gene therapy with tissue engineering.

    PubMed

    Hidaka, Chisa; Ibarra, Clemente; Hannafin, Jo A; Torzilli, Peter A; Quitoriano, Mannix; Jen, Shih-Shi; Warren, Russell F; Crystal, Ronald G

    2002-02-01

    Ingrowth of host blood vessels into engineered tissues has potential benefits for successful transplantation of engineered tissues as well as healing of surrounding host tissues. In particular, the use of a vascularized bioengineered tissue could be beneficial for treating injuries to the meniscus, a structure in the knee where the lack of a vascular supply is associated with an inadequate healing response. In this study, gene transfer using an adenovirus vector encoding the hepatocyte growth factor gene (AdHGF) was used to induce blood vessel formation in tissue-engineered meniscus. Bovine meniscal cells were treated with AdHGF, a vector encoding a marker gene E. coli beta-galactosidase (Adbetagal), or no virus. Cells were seeded onto poly-glycolic acid felt scaffolds and then transplanted into the subcutaneous pouch of athymic nude mice for 8 weeks. Expression of the marker gene and HGF was detectable for several weeks after gene transfer. Ink injection studies showed that AdHGF-treated meniscal cells formed tissue which contained fourfold more blood vessels at 2 weeks (p < 0.02) and 2.5-fold more blood vessels at 8 weeks (p < 0.001) posttransplantation than controls. This study demonstrates the feasibility of using adenovirus-mediated gene transfer to engineer a blood supply in the bioengineered meniscal tissue.

  20. Thermodynamics and kinetics of carbon deposits on cobalt: a combined density functional theory and kinetic Monte Carlo study.

    PubMed

    Jansen, Antonius P J; Agrawal, Ravi; Spanu, Leonardo

    2016-10-19

    We have built a lattice gas model for cobalt-carbon interaction to investigate the thermodynamics and kinetics of carbon deposition on Co(0001) surfaces. The formation of carbon structures on cobalt is considered to be one of the causes of deactivation of a cobalt Fischer-Tropsch (FT) catalyst. The formation of graphene - the most thermodynamically stable phase under FT conditions - is kinetically inhibited during the first 30 hours of exposure of the surface to carbon, while the build-up of surface carbide is the fastest reaction. Our simulations clearly show that the kinetics of carbon deposition is the result of two competing effects: a fast subsurface diffusion and a slower surface diffusion to form a carbon-carbon bond.

  1. Effects of combined open kinetic chain and closed kinetic chain training using pulley exercise machines on muscle strength and angiogenesis factors

    PubMed Central

    Jang, Ki Soeng; Kang, Sunghwun; Woo, Sang Heon; Bae, Ju Yong; Shin, Ki Ok

    2016-01-01

    [Purpose] This study investigated the effects of combined open kinetic chain and closed kinetic chain training using pulley exercise machines on muscle strength, anaerobic power, and blood levels of angiogenesis factors. [Subjects and Methods] Twenty male university students were equally divided between control and pulley training groups. The pulley-training group underwent 8 weeks of combined training. Open kinetic chain training consisted of 2 sets of 10 repetitions at 60% of one repetition maximum; closed kinetic chain training consisted of 2 sets of 10 repetitions of resistance exercise using the subject’s own body weight. Isokinetic strength (trunk and knee), anaerobic power, vascular endothelial growth factor, angiopoietin-1, angiopoietin-2, and follistatin were analyzed. [Results] After 8 weeks, flexor and extensor muscle strength significantly increased in the trunk and knee; average and peak power also increased significantly. Angiopoietin 1 increased 25% in the control group and 48% in the pulley training group; vascular endothelial growth factor and follistatin increased significantly in the pulley-training group after 8 weeks. [Conclusion] Eight weeks of combined training using pulley exercise machines effectively increased biochemical factors related to muscle growth, as well as muscle strength in the trunk and knees. PMID:27134393

  2. Combined individual scrummaging kinetics and muscular power predict competitive team scrum success.

    PubMed

    Green, Andrew; Dafkin, Chloe; Kerr, Samantha; McKinon, Warrick

    2017-09-01

    Scrummaging is a major component of Rugby Union gameplay. Successful scrummaging is dependent on the coordination of the forward players and the strength of the eight individuals. The study aim was to determine whether individual scrummaging kinetics and other candidate factors associated with scrummaging performance discriminate team scrum performances. Sixteen club-level forwards (stature: 1.80 ± 0.1 m; mass: 99.0 ± 18.2 kg) were initially divided into two scrummaging packs. A total of 10 various scrum permutations were tested, where players were randomly swapped between the two packs. Winning scrums were determined by two observers on opposite sides of the scrum. Fatigue (100 mm visual analogue scale (VAS)) and scrummaging effort (6-20 rating of perceived exertion (RPE)) were assessed following each scrum contest. Individual scrummaging kinetics were acquired through an instrumented scrum ergometer and muscular power indicated through vertical jump heights. Student's t-tests were used to differentiate between winning and losing scrum packs. VAS and RPE were assessed using repeated measures ANOVAs. Winning scrum packs had significantly larger combined force magnitudes (p < .002), regardless of the player contribution calculations. Additionally, winning packs had less individual movement (p = .033) and higher combined vertical jump heights (p < .001) but were not significantly heavier (p = .759) than losing scrum packs. While perceived VAS and RPE values progressively increased (p < .001), no differences in the individual scrum magnitudes were observed between the 1st and 10th scrum (p = .418). The results indicated that the combination of individual forces, variation in movement and factors related to scrummaging performance, such as vertical jump height, were associated with team scrummaging success.

  3. Drying kinetics and characteristics of combined infrared-vacuum drying of button mushroom slices

    NASA Astrophysics Data System (ADS)

    Salehi, Fakhreddin; Kashaninejad, Mahdi; Jafarianlari, Ali

    2017-05-01

    Infrared-vacuum drying characteristics of button mushroom ( Agaricus bisporus) were evaluated in a combined dryer system. The effects of drying parameters, including infrared radiation power (150-375 W), system pressure (5-15 kPa) and time (0-160 min) on the drying kinetics and characteristics of button mushroom slices were investigated. Both the infrared lamp power and vacuum pressure influenced the drying time of button mushroom slices. The rate constants of the nine different kinetic's models for thin layer drying were established by nonlinear regression analysis of the experimental data which were found to be affected mainly by the infrared power level while system pressure had a little effect on the moisture ratios. The regression results showed that the Page model satisfactorily described the drying behavior of button mushroom slices with highest R value and lowest SE values. The effective moisture diffusivity increases as power increases and range between 0.83 and 2.33 × 10-9 m2/s. The rise in infrared power has a negative effect on the ΔE and with increasing in infrared radiation power it was increased.

  4. Drying kinetics and characteristics of combined infrared-vacuum drying of button mushroom slices

    NASA Astrophysics Data System (ADS)

    Salehi, Fakhreddin; Kashaninejad, Mahdi; Jafarianlari, Ali

    2016-10-01

    Infrared-vacuum drying characteristics of button mushroom (Agaricus bisporus) were evaluated in a combined dryer system. The effects of drying parameters, including infrared radiation power (150-375 W), system pressure (5-15 kPa) and time (0-160 min) on the drying kinetics and characteristics of button mushroom slices were investigated. Both the infrared lamp power and vacuum pressure influenced the drying time of button mushroom slices. The rate constants of the nine different kinetic's models for thin layer drying were established by nonlinear regression analysis of the experimental data which were found to be affected mainly by the infrared power level while system pressure had a little effect on the moisture ratios. The regression results showed that the Page model satisfactorily described the drying behavior of button mushroom slices with highest R value and lowest SE values. The effective moisture diffusivity increases as power increases and range between 0.83 and 2.33 × 10-9 m2/s. The rise in infrared power has a negative effect on the ΔE and with increasing in infrared radiation power it was increased.

  5. Combined effects of temperature, pressure, and co-solvents on the polymerization kinetics of actin.

    PubMed

    Rosin, Christopher; Estel, Kathrin; Hälker, Jessica; Winter, Roland

    2015-05-18

    In vivo studies have shown that the cytoskeleton of cells is very sensitive to changes in temperature and pressure. In particular, actin filaments get depolymerized when pressure is increased up to several hundred bars, conditions that are easily encountered in the deep sea. We quantitatively evaluate the effects of temperature, pressure, and osmolytes on the kinetics of the polymerization reaction of actin by high-pressure stopped-flow experiments in combination with fluorescence detection and an integrative stochastic simulation of the polymerization process. We show that the compatible osmolyte trimethylamine-N-oxide is not only able to compensate for the strongly retarding effect of chaotropic agents, such as urea, on actin polymerization, it is also able to largely offset the deteriorating effect of pressure on actin polymerization, thereby allowing biological cells to better cope with extreme environmental conditions.

  6. Spatio-temporal thermal kinetics of in situ MWCNT heating in biological tissues under NIR laser irradiation

    NASA Astrophysics Data System (ADS)

    Picou, Laura; McMann, Casey; Elzer, Philip H.; Enright, Frederick M.; Biris, Alexandru S.; Boldor, Dorin

    2010-10-01

    Carbon nanotubes have many potential applications in life sciences and engineering as they have very high absorbance in the near-infrared (NIR) spectrum, while biological tissues do not. The purpose of this study was to determine the effect of 1064 nm NIR laser power levels on the spatial temperature distribution and the temperature kinetics in mammalian tissue at both macroscopic and microscopic scales. The model tissue was the 'flat' of a chicken wing (the section containing the radius and ulna), which was injected under the skin in the subcutaneous layer of tissue. Specimens were exposed to laser radiation and an infrared thermography system was used to measure and record the temperature distributions in the specimens at both the macroscopic and microscopic scales. Experimental results concluded that power levels of 1536 mW easily achieved hyperthermic temperatures with localized values as high as 172.7 °C.

  7. Spatio-temporal thermal kinetics of in situ MWCNT heating in biological tissues under NIR laser irradiation.

    PubMed

    Picou, Laura; McMann, Casey; Elzer, Philip H; Enright, Frederick M; Biris, Alexandru S; Boldor, Dorin

    2010-10-29

    Carbon nanotubes have many potential applications in life sciences and engineering as they have very high absorbance in the near-infrared (NIR) spectrum, while biological tissues do not. The purpose of this study was to determine the effect of 1064 nm NIR laser power levels on the spatial temperature distribution and the temperature kinetics in mammalian tissue at both macroscopic and microscopic scales. The model tissue was the 'flat' of a chicken wing (the section containing the radius and ulna), which was injected under the skin in the subcutaneous layer of tissue. Specimens were exposed to laser radiation and an infrared thermography system was used to measure and record the temperature distributions in the specimens at both the macroscopic and microscopic scales. Experimental results concluded that power levels of 1536 mW easily achieved hyperthermic temperatures with localized values as high as 172.7 °C.

  8. New Combinational Method for Noninvasive Treatments of Superficial Tissues for Body Aesthetics Applications

    NASA Astrophysics Data System (ADS)

    Rybyanets, A. N.; Naumenko, A. A.

    The paper introduces an innovative combinational treatment method based on ultrasonic standing waves (USW) technology for noninvasive surgical, therapeutic, lypolitic or cosmetic treatment of tissues including subcutaneous adipose tissue, cellulite or skin on arbitrary body part of patient. The method is based on simultaneous or successive applying of constructively interfering physically and biologically sensed influences: USW, ultrasonic shear waves, radio-frequency (RF) heating, and vacuum massage. The paper provides basic physical principles of USW as well as critical comparison of USW and HIFU methods. The results of finite-elements and finite- difference modeling of USW transducer design and nodal pattern structure in tissue are presented. Biological effects of USW-tissue interaction and synergetic aspects of USW and RF combination are explored. Combinational treatment transducer designs and original in-vitro experiments on tissues are described.

  9. Combining polarimetry and spectropolarimetry techniques in diagnostics of cancer changes in biological tissues

    NASA Astrophysics Data System (ADS)

    Yermolenko, Sergey; Ivashko, Pavlo; Gruia, Ion; Gruia, Maria; Peresunko, Olexander; Zelinska, Natalia; Voloshynskyi, Dmytro; Fedoruk, Olexander; Zimnyakov, Dmitry; Alonova, Marina

    2015-02-01

    The aim of the study is combining polarimetry and spectropolarimetry techniques for identifying the changes of opticalgeometrical structure in different kinds of biotissues with solid tumours. It is researched that a linear dichroism appears in biotissues (human esophagus, muscle tissue of rats, human prostate tissue, cervical smear) with cancer diseases, magnitude of which depends on the type of the tissue and on the time of cancer process development.

  10. Reference Tissue-Based Kinetic Evaluation of 18F-AV-1451 for Tau Imaging.

    PubMed

    Baker, Suzanne L; Lockhart, Samuel N; Price, Julie C; He, Mark; Huesman, Ronald H; Schonhaut, Daniel; Faria, Jamie; Rabinovici, Gil; Jagust, William J

    2017-02-01

    The goal of this paper was to evaluate the in vivo kinetics of the novel tau-specific PET radioligand (18)F-AV-1451 in cognitively healthy control (HC) and Alzheimer disease (AD) subjects, using reference region analyses.

  11. STUDIES ON A LUNG TISSUE COMPONENT WHICH COMBINES WITH PNEUMONIA VIRUS OF MICE (PVM)

    PubMed Central

    Volkert, Mogens; Horsfall, Frank L.

    1947-01-01

    Evidence has been obtained which indicates that the lung tissues of mammalian species susceptible to infection with PVM contain a specific component which combines with the virus. The concentration of this tissue component appears to be directly proportional to the suceptibility of the species; in its absence infection with PVM cannot be established. The available evidence suggests that the presence of the virus-combining component in lung tissue may play a decisive ro1e in the initiation of infection with this pneumotropic virus. PMID:19871686

  12. A combined spectroscopic and plasma chemical kinetic analysis of ionospheric samarium releases

    NASA Astrophysics Data System (ADS)

    Holmes, Jeffrey M.; Dressler, Rainer A.; Pedersen, Todd R.; Caton, Ronald G.; Miller, Daniel

    2017-05-01

    Two rocket-borne releases of samarium vapor in the upper atmosphere occurred in May 2013, as part of the Metal Oxide Space Clouds experiment. The releases were characterized by a combination of optical and RF diagnostic instruments located at the Roi-Namur launch site and surrounding islands and atolls. The evolution of the optical spectrum of the solar-illuminated cloud was recorded with a spectrograph covering a 400-800 nm spectral range. The spectra exhibit two distinct spectral regions centered at 496 and 636 nm within which the relative intensities change insignificantly. The ratio between the integrated intensities within these regions, however, changes with time, suggesting that they are associated with different species. With the help of an equilibrium plasma spectral model we attribute the region centered at 496 nm to neutral samarium atoms (Sm I radiance) and features peaking at 649 nm to a molecular species. No evidence for structure due to Sm+ (Sm II) is identified. The persistence of the Sm I radiance suggests a high dissociative recombination rate for the chemi-ionization product, SmO+. A one-dimensional plasma chemical kinetic model of the evolution of the density ratio NSmO/NSm(t) demonstrates that the molecular feature peaking at 649 nm can be attributed to SmO radiance. SmO+ radiance is not identified. By adjusting the Sm vapor mass of the chemical kinetic model input to match the evolution of the total electron density determined by ionosonde data, we conclude that less than 5% of the payload samarium was vaporized.

  13. Mechanism of crystalline self-assembly in aqueous medium: a combined cryo-TEM/kinetic study.

    PubMed

    Tidhar, Yaron; Weissman, Haim; Tworowski, Dmitry; Rybtchinski, Boris

    2014-08-11

    Understanding the crystallization of organic molecules is a long-standing challenge. Herein, a mechanistic study on the self-assembly of crystalline arrays in aqueous solution is presented. The crystalline arrays are assembled from perylene diimide (PDI) amphiphiles bearing a chiral N-acetyltyrosine side group connected to the PDI aromatic core. A kinetic study of the crystallization process was performed using circular dichroism spectroscopy combined with time-resolved cryogenic transmission electron microscopy (cryo-TEM) imaging of key points along the reaction coordinate, and molecular dynamics simulation of the initial stages of the assembly. The study reveals a complex self-assembly process starting from the formation of amorphous aggregates that are transformed into crystalline material through a nucleation-growth process. Activation parameters indicate the key role of desolvation along the assembly pathway. The insights from the kinetic study correlate well with the structural data from cryo-TEM imaging. Overall, the study reveals four stages of crystalline self-assembly: 1) collapse into amorphous aggregates; 2) nucleation as partial ordering; 3) crystal growth; and 4) fusion of smaller crystalline aggregates into large crystals. These studies indicate that the assembly process proceeds according to a two-step crystallization model, whereby initially formed amorphous material is reorganized into an ordered system. This process follows Ostwald's rule of stages, evolving through a series of intermediate phases prior to forming the final structure, thus providing an insight into the crystalline self-assembly process in aqueous medium. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Combining scanning haptic microscopy and fibre optic Raman spectroscopy for tissue characterization.

    PubMed

    Candefjord, S; Murayama, Y; Nyberg, M; Hallberg, J; Ramser, K; Ljungberg, B; Bergh, A; Lindahl, O A

    2012-08-01

    The tactile resonance method (TRM) and Raman spectroscopy (RS) are promising for tissue characterization in vivo. Our goal is to combine these techniques into one instrument, to use TRM for swift scanning, and RS for increasing the diagnostic power. The aim of this study was to determine the classification accuracy, using support vector machines, for measurements on porcine tissue and also produce preliminary data on human prostate tissue. This was done by developing a new experimental set-up combining micro-scale TRM-scanning haptic microscopy (SHM)-for assessing stiffness on a micro-scale, with fibre optic RS measurements for assessing biochemical content. We compared the accuracy using SHM alone versus SHM combined with RS, for different degrees of tissue homogeneity. The cross-validation classification accuracy for healthy porcine tissue types using SHM alone was 65-81%, and when RS was added it increased to 81-87%. The accuracy for healthy and cancerous human tissue was 67-70% when only SHM was used, and increased to 72-77% for the combined measurements. This shows that the potential for swift and accurate classification of healthy and cancerous prostate tissue is high. This is promising for developing a tool for probing the surgical margins during prostate cancer surgery.

  15. Combined use of an amniotic membrane and tissue adhesive in treating corneal perforation: a case report.

    PubMed

    Su, C Y; Lin, C P

    2000-01-01

    We report a new method combining the use of an amniotic membrane and cyanocrylate tissue adhesive to seal a corneal perforation. A 47-year-old male suffered from an alkali injury complicated with corneal melting and perforation in the left eye. We placed an amniotic membrane of optimal size in the anterior chamber directly under the corneal perforation lesion. The cyanocrylate tissue adhesive was then applied over the perforation site and sealed successfully. Three weeks later, the tissue adhesive had dislodged. The amniotic membrane had sealed the perforated lesion and was well adhered to the surrounding corneal tissue with complete epithelial covering. Vision was 20/25 six months after the operation. The combined use of an amniotic membrane and tissue adhesive is a promising method in the treatment of corneal perforation.

  16. Combined spectral-domain optical coherence tomography and hyperspectral imaging applied for tissue analysis: Preliminary results

    NASA Astrophysics Data System (ADS)

    Dontu, S.; Miclos, S.; Savastru, D.; Tautan, M.

    2017-09-01

    In recent years many optoelectronic techniques have been developed for improvement and the development of devices for tissue analysis. Spectral-Domain Optical Coherence Tomography (SD-OCT) is a new medical interferometric imaging modality that provides depth resolved tissue structure information with resolution in the μm range. However, SD-OCT has its own limitations and cannot offer the biochemical information of the tissue. These data can be obtained with hyperspectral imaging, a non-invasive, sensitive and real time technique. In the present study we have combined Spectral-Domain Optical Coherence Tomography (SD-OCT) with Hyperspectral imaging (HSI) for tissue analysis. The Spectral-Domain Optical Coherence Tomography (SD-OCT) and Hyperspectral imaging (HSI) are two methods that have demonstrated significant potential in this context. Preliminary results using different tissue have highlighted the capabilities of this technique of combinations.

  17. VOXEL-LEVEL MAPPING OF TRACER KINETICS IN PET STUDIES: A STATISTICAL APPROACH EMPHASIZING TISSUE LIFE TABLES1

    PubMed Central

    O’Sullivan, Finbarr; Muzi, Mark; Mankoff, David A.; Eary, Janet F.; Spence, Alexander M.; Krohn, Kenneth A.

    2014-01-01

    Most radiotracers used in dynamic positron emission tomography (PET) scanning act in a linear time-invariant fashion so that the measured time-course data are a convolution between the time course of the tracer in the arterial supply and the local tissue impulse response, known as the tissue residue function. In statistical terms the residue is a life table for the transit time of injected radiotracer atoms. The residue provides a description of the tracer kinetic information measurable by a dynamic PET scan. Decomposition of the residue function allows separation of rapid vascular kinetics from slower blood-tissue exchanges and tissue retention. For voxel-level analysis, we propose that residues be modeled by mixtures of nonparametrically derived basis residues obtained by segmentation of the full data volume. Spatial and temporal aspects of diagnostics associated with voxel-level model fitting are emphasized. Illustrative examples, some involving cancer imaging studies, are presented. Data from cerebral PET scanning with 18F fluoro-deoxyglucose (FDG) and 15O water (H2O) in normal subjects is used to evaluate the approach. Cross-validation is used to make regional comparisons between residues estimated using adaptive mixture models with more conventional compartmental modeling techniques. Simulations studies are used to theoretically examine mean square error performance and to explore the benefit of voxel-level analysis when the primary interest is a statistical summary of regional kinetics. The work highlights the contribution that multivariate analysis tools and life-table concepts can make in the recovery of local metabolic information from dynamic PET studies, particularly ones in which the assumptions of compartmental-like models, with residues that are sums of exponentials, might not be certain. PMID:25392718

  18. Characterizing Plumbing System Dynamics Beneath Active Volcanoes by Combined Kinetic and Thermodynamic (MELTS) Modeling

    NASA Astrophysics Data System (ADS)

    Kahl, M.; Chakraborty, S.; Costa, F.; Pompilio, M.

    2011-12-01

    Understanding the dynamic processes in sub-surface magma plumbing systems requires the ability to unravel the information that is recorded in the chemical stratigraphy of compositionally zoned magmatic crystals. We present a method that combines kinetic (diffusion) and thermodynamic (MELTS) modeling of the chemical stratigraphy preserved in zoned olivine crystals in order to constrain the dynamics of the magmatic system underlying the volcanic edifice of Mt. Etna. We developed our method using the products from the recharge-eruption cycles between 1991 and 2008. These eruptive products contained five olivine populations with different zoning patterns and core plateau compositions (Fo65-69; Fo70-72; Fo73-75; Fo75-78 and Fo79-83). These could be explained (Kahl et al., 2011) as the product of magma evolution in at least three distinct reservoirs (M0 containing olivine of Fo79-83; M1with Fo75-78 and M2 with Fo70-72) with melt transfer and mixing between these. Two pathways were found to dominate the magma transfer (M0 - M1; M1 - M2). A series of magma transfer / mixing events occurred within a time span of two years, with the last event occurring only a few days before eruption. Combining these results with thermodynamic modeling using the MELTS thermodynamic database (Ghiorso & Sack, 1995), it is possible to constrain the ambient intensive variables (e.g. P, T, fO2) during these melt transfer processes. We find that the most primitive olivine compositions (Fo79-83) could have been produced from a basaltic starting composition (46.41 wt. % SiO2, 8.17 wt. % MgO and an initial water content of 2.0 wt%) at ~ 2.0 kbars, ~ 1190 °C and log fO2 -8.23. Melt evolution can produce other observed core compositions, primarily as a consequence of decompression and degassing (e.g. 200 bars, 0.7 wt%H2O and 20 bars, 0.1wt%H2O, respectively). As this corresponds to one of the dominant magma transfer pathways (M1-M2) identified from kinetic and Systems analysis, we can also simulate

  19. Combining creatinine and volume kinetics identifies missed cases of acute kidney injury following cardiac arrest

    PubMed Central

    2013-01-01

    Introduction Fluid resuscitation in the critically ill often results in a positive fluid balance, potentially diluting the serum creatinine concentration and delaying diagnosis of acute kidney injury (AKI). Methods Dilution during AKI was quantified by combining creatinine and volume kinetics to account for fluid type, and rates of fluid infusion and urine output. The model was refined using simulated patients receiving crystalloids or colloids under four glomerular filtration rate (GFR) change scenarios and then applied to a cohort of critically ill patients following cardiac arrest. Results The creatinine concentration decreased during six hours of fluid infusion at 1 litre-per-hour in simulated patients, irrespective of fluid type or extent of change in GFR (from 0% to 67% reduction). This delayed diagnosis of AKI by 2 to 9 hours. Crystalloids reduced creatinine concentration by 11 to 19% whereas colloids reduced concentration by 36 to 43%. The greatest reduction was at the end of the infusion period. Fluid dilution alone could not explain the rapid reduction of plasma creatinine concentration observed in 39 of 49 patients after cardiac arrest. Additional loss of creatinine production could account for those changes. AKI was suggested in six patients demonstrating little change in creatinine, since a 52 ± 13% reduction in GFR was required after accounting for fluid dilution and reduced creatinine production. Increased injury biomarkers within a few hours of cardiac arrest, including urinary cystatin C and plasma and urinary Neutrophil-Gelatinase-Associated-Lipocalin (biomarker-positive, creatinine-negative patients) also indicated AKI in these patients. Conclusions Creatinine and volume kinetics combined to quantify GFR loss, even in the absence of an increase in creatinine. The model improved disease severity estimation, and demonstrated that diagnostic delays due to dilution are minimally affected by fluid type. Creatinine sampling should be delayed at least

  20. [Pharmacokinetic aspects of a combination of metoclopramide and paracetamol. Results of a human kinetic study and consequences for migraine patients].

    PubMed

    Becker, A; Berner, G; Leuschner, F; Vögtle-Junkert, U

    1992-04-01

    An open trial was carried out in eight healthy male and female volunteers to examine the bioavailability as well as the main kinetic parameters of Migränerton (metoclopramide and paracetamol; CAS 364-64-5 and CAS 103-90-2, resp). in comparison with reliable literature data. The results reported here clearly show that the absorption of both active ingredients from the fixed combination is complete and that therapeutically relevant plasma concentrations are achieved within 30 min. Bioavailability as well as tmax, t1/2, and time-lag are comparable with data resulting from reliable and internationally acknowledged kinetic studies. The fixed combination was shown to be kinetically compatible with regard to all parameters determined for metoclopramide and paracetamol.

  1. In vitro hydration kinetics of recent post-mortem tissue versus pre-dried corneal stromal tissue.

    PubMed

    Aakre, B M; Doughty, M J

    1997-07-01

    Both recent post-mortem and pre-dried corneal tissue has been used for laboratory studies of stromal swelling, but it has yet to be defined whether the same hydration (H value, mg H2O/mg dry mass) is obtained after extended re-hydration. Fresh or pre-dried pieces (8x8 mm squares) of ovine stromas were immersed in 1% NaCl for 24 hr at 37 degrees C, with the wet mass assessed regularly. Pre-drying was achieved in air for 7 days (with sulphuric acid, CaSO4 or silica gel as desiccants), or in an oven for 24 hr at 60, 70 or 80 degrees C. Fresh stroma preparations (tissue (P<0.01). Following oven drying at 60, 70, and 80 degrees C, final H values of 8.5, 6.6, and 5.0 were obtained after 24 hr in saline. Recent post-mortem material showed sustained swelling over at least 24 hr. For pre-dried tissue, initial rates of hydration change over 1 hr were higher, but subsequent rates were substantially less after 2 hr. These studies indicate that fresh tissue should be used in studies concerning the swelling properties of the corneal stroma.

  2. High sensitivity phonon-mediated kinetic inductance detector with combined amplitude and phase read-out

    NASA Astrophysics Data System (ADS)

    Cardani, L.; Casali, N.; Colantoni, I.; Cruciani, A.; Bellini, F.; Castellano, M. G.; Cosmelli, C.; D'Addabbo, A.; Di Domizio, S.; Martinez, M.; Tomei, C.; Vignati, M.

    2017-01-01

    Developing wide-area cryogenic light detectors with baseline resolution better than 20 eV is one of the priorities of next generation bolometric experiments searching for rare interactions, as the simultaneous read-out of the light and heat signals enables background suppression through particle identification. Among the proposed technological approaches for the phonon sensor, the naturally multiplexed Kinetic Inductance Detectors (KIDs) stand out for their excellent intrinsic energy resolution and reproducibility. The potential of this technique was proved by the CALDER project that reached a baseline resolution of 154 ± 7 eV RMS by sampling a 2 × 2 cm2 Silicon substrate with 4 Aluminum KIDs. In this paper, we present a prototype of Aluminum KID with improved geometry and quality factor. The design improvement, as well as the combined analysis of amplitude and phase signals, allowed to reach a baseline resolution of 82 ± 4 eV by sampling the same substrate with a single Aluminum KID.

  3. Cadmium and lead interaction with diatom surfaces: A combined thermodynamic and kinetic approach

    NASA Astrophysics Data System (ADS)

    Gélabert, A.; Pokrovsky, O. S.; Schott, J.; Boudou, A.; Feurtet-Mazel, A.

    2007-08-01

    This work is devoted to the physico-chemical study of cadmium and lead interaction with diatom-water interfaces for two marine planktonic ( Thalassiosira weissflogii, TW; Skeletonema costatum, SC) and two freshwater periphytic species ( Achnanthidium minutissimum, AMIN; Navicula minima, NMIN) by combining adsorption measurements with surface complexation modeling. Adsorption kinetics was studied as a function of pH and initial metal concentration in sodium nitrate solution and in culture media. Kinetic data were consistent with a two-step mechanism in which the loss of a water molecule from the inner coordination sphere of the metal is rate limiting. Reversible adsorption experiments, with 3 h of exposure to metal, were performed as a function of pH (2-9), metal concentration in solution (10 -9-10 -3 M), and ionic strength (10 -3-1.0 M). While the shape of pH-dependent adsorption edge is similar among all four diatom species, the constant-pH adsorption isotherm and maximal binding capacities differ. Measurements of electrophoretic mobilities ( μ) revealed negative surface potential for AMIN diatom, however, the absolute value of μ decreases with increase of [Pb 2+] aq suggesting the metal adsorption on negative surface sites. These observations allowed us to construct a surface complexation model (SCM) for cadmium and lead binding by diatom surfaces that postulates the Constant Capacitance of the electric double layer and considers Cd and Pb complexation with mainly carboxylic and, partially, silanol groups. In the full range of investigated Cd concentration, the SCM is able to describe the concentration of adsorbed metal as a function of [Cd 2+] aq without implying the presence of high affinity, low abundance sites, that are typically used to model the metal interactions with natural multi-component organic substances. At the same time, Cd fast initial reaction requires the presence of "highly reactive sites" those concentration represents only 2.5-3% of the

  4. Combined alizarin red-reticulum stain for tissue localization of calcium deposits.

    PubMed

    Elbadawi, A; Musto, L A; Lilien, O M

    1981-03-01

    A method combining alizarin red and a modified silver stain for reticulum fibers in tissue sections is described. The method allows precise localization of calcium deposits and crystals in relation to epithelial and interstitial connective tissue elements. The deposits and their spatial relationships are clearly discernible by light microscopy, especially with polarization. The method is particularly useful for investigating calculogenesis and may prove to be of value in the study of the mechanism and evolution of pathologic calcification in various organs.

  5. A combined Raman-fluorescence spectroscopic probe for tissue diagnostics applications

    NASA Astrophysics Data System (ADS)

    Cicchi, Riccardo; Cosci, Alessandro; Rossari, Susanna; Sturiale, Alessandro; Giordano, Flavio; De Giorgi, Vincenzo; Maio, Vincenza; Massi, Daniela; Nesi, Gabriella; Buccoliero, Anna Maria; Tonelli, Francesco; Guerrini, Renzo; Pimpinelli, Nicola; Pavone, Francesco S.

    2013-06-01

    We designed and developed two different optical fibre probes for combined Raman and fluorescence spectroscopic measurements on human tissues. The experimental setup combines fluorescence spectroscopy and Raman spectroscopy in a multimodal approach. Two laser diodes, respectively emitting in the UV (378 nm) and in the visible (445 nm), were used for fluorescence spectroscopy. An additional laser diode emitting in the NIR (785 nm) was used for Raman spectroscopy. Laser light was delivered to the tissue under examination through a multimode optical fibre located in the centre of the fibre bundle probe. The surrounding 24 optical fibres were used for collection of the signal of interest and for delivering light to a common detection unit. Both fluorescence and Raman spectra were acquired on a cooled CCD camera, connected to a spectrograph. The device was successfully used for diagnosing melanocytic lesions in a good agreement with common routine histology. Additional measurements were performed on other human tissue samples, such as colon tissue and brain tissue in order to test the capability of the device for diagnosing a broader range of tissue lesions and malignancies. The system has the potential to improve diagnostic capabilities on a broad range of tissues and to be used for endoscopic inspections in the near future.

  6. Hyperspectral interventional imaging for enhanced tissue visualization and discrimination combining band selection methods.

    PubMed

    Nouri, Dorra; Lucas, Yves; Treuillet, Sylvie

    2016-12-01

    Hyperspectral imaging is an emerging technology recently introduced in medical applications inasmuch as it provides a powerful tool for noninvasive tissue characterization. In this context, a new system was designed to be easily integrated in the operating room in order to detect anatomical tissues hardly noticed by the surgeon's naked eye. Our LCTF-based spectral imaging system is operative over visible, near- and middle-infrared spectral ranges (400-1700 nm). It is dedicated to enhance critical biological tissues such as the ureter and the facial nerve. We aim to find the best three relevant bands to create a RGB image to display during the intervention with maximal contrast between the target tissue and its surroundings. A comparative study is carried out between band selection methods and band transformation methods. Combined band selection methods are proposed. All methods are compared using different evaluation criteria. Experimental results show that the proposed combined band selection methods provide the best performance with rich information, high tissue separability and short computational time. These methods yield a significant discrimination between biological tissues. We developed a hyperspectral imaging system in order to enhance some biological tissue visualization. The proposed methods provided an acceptable trade-off between the evaluation criteria especially in SWIR spectral band that outperforms the naked eye's capacities.

  7. Tissue accumulation kinetics of ciclesonide-active metabolite and budesonide in mice.

    PubMed

    Mårs, Ulla; d'Argy, Roland; Hallbeck, Karin; Miller-Larsson, Anna; Edsbäcker, Staffan

    2013-06-01

    Inhaled corticosteroids (ICS) are mainstay treatment of asthma and chronic obstructive pulmonary disease. However, highly lipophilic ICS accumulate in systemic tissues, which may lead to adverse systemic effects. The accumulation of a new, highly lipophilic ICS, ciclesonide and its active metabolite (des-CIC) has not yet been reported. Here, we have compared tissue accumulation of des-CIC and an ICS of a moderate lipophilicity, budesonide (BUD), after 14 days of once-daily treatment in mice. Single, three or 14 daily doses of [(3) H]-des-CIC or [(3) H]-BUD were administered subcutaneously to male CD1 albino mice, which were killed at 4 hr, 24 hr or 5 days after the last dose. Distribution of tissue concentration of radioactivity was studied by quantitative whole-body autoradiography. Pattern of radioactivity distribution across most tissues was similar for both corticosteroids after a single as well as after repeated dosing. However, tissue concentration of radioactivity differed between des-CIC and BUD. After a single dose, concentrations of radioactivity for both corticosteroids were low for most tissues but increased over 14 days of daily dosing. The tissue radioactivity of des-CIC at 24 hr and 5 days after the 14th dose was 2-3 times higher than that of BUD in majority of tissues. Tissue accumulation, assessed as concentration of tissue radioactivity 5 days after the 14th versus 3rd dose, showed an average ratio of 5.2 for des-CIC and 2.7 for BUD (p < 0.0001). In conclusion, des-CIC accumulated significantly more than BUD. Systemic accumulation may lead to increased risk of adverse systemic side effects during long-term therapy. © 2012 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

  8. Combined parental obesity negatively impacts preimplantation mouse embryo development, kinetics, morphology and metabolism.

    PubMed

    Finger, Bethany J; Harvey, Alexandra J; Green, Mark P; Gardner, David K

    2015-09-01

    -time quantitative RT-PCR (qRT-PCR) and microfluorescence were used to measure gene expression and metabolism (glucose consumption and lactate production), respectively, in embryos from Lean Parented and Combined Obese Parented matings. This research was completed in a University research laboratory. Blastocyst rate was reduced in Combined Obese Parented embryos when compared with both Single Obese (11% decrease for Maternal Obese Parented, P < 0.05; 15% for Paternal Obese Parented, P < 0.05) and Lean Parented embryos (25% decrease, P < 0.01). Time-lapse analysis of developmental kinetics highlighted a delay of 1 h at the 2-3 cell division, extending to 6 h delay by the blastocyst stage for Combined Obese Parented embryos (P < 0.05). A reduction in the total cell number of Combined Obese Parented blastocysts was a further manifestation of this developmental delay (P < 0.05). Zona pellucida width was reduced in Combined Obese Parented embryos (P < 0.05). Glucose consumption was increased in Combined Obese Parented embryos (P < 0.05), which was associated with the up-regulation of Glucose transporter 1 expression (P < 0.05). This study was completed in fertile C57BL/6 mice using a well-defined model of diet-induced obesity in which embryos were fertilized in vivo. Human obesity is complex, with many causes and co-morbidities, and therefore, the impact of combined obesity would require further investigation in human settings. This study demonstrates that combined parental obesity has a detrimental impact on mouse embryo development, a finding consistent with previous studies on individual parent obesity. Of note, the effect of combined parental obesity upon embryo development markers was greater than that of individual parental obesity. Plausibly, human embryos will be similarly impacted. The reduction in the blastocyst rate and delayed time to developmental events confirms that embryos of obese parents differ from those of lean parents. Allowance for this should therefore be

  9. Real-time and label free determination of ligand binding-kinetics to primary cancer tissue specimens; a novel tool for the assessment of biomarker targeting.

    PubMed

    Clausen, Thomas Mandel; Pereira, Marina Ayres; Oo, Htoo Zarni; Resende, Mafalda; Gustavson, Tobias; Mao, Yang; Sugiura, Nobuo; Liew, Janet; Fazli, Ladan; Theander, Thor G; Daugaard, Mads; Salanti, Ali

    2016-07-01

    In clinical oncology, diagnosis and evaluation of optimal treatment strategies are mostly based on histopathological examination combined with immunohistochemical (IHC) expression analysis of cancer-associated antigens in formalin fixed paraffin-embedded (FFPE) tissue biopsies. However, informative IHC analysis depends on both the specificity and affinity of the binding reagent, which are inherently difficult to quantify in situ. Here we describe a label-free method that allows for the direct and real-time assessment of molecular binding kinetics in situ on FFPE tissue specimens using quartz crystal microbalance (QCM) enabled biosensor technology. We analysed the interaction between the rVAR2 protein and its placental-like chondroitin sulfate (pl-CS) receptor in primary human placenta tissue and in breast and prostate tumour specimens in situ. rVAR2 interacted with FFPE human placenta and cancer tissue with an affinity in the nanomolar range, and showed no detectable interaction with pl-CS negative normal tissue. We further validated the method by including analysis with the androgen receptor N-20 antibody (anti-AR). As the KD value produced by this method is independent of the number of epitopes available, this readout offers a quantitative and unbiased readout for in situ binding-avidity and amount of binding epitopes. In summary, this method adds a new and important dimension to classical IHC-based molecular pathology by adding information about the binding characteristics in biologically relevant conditions. This can potentially be used to select optimal biologics for diagnostic and for therapeutic applications as well as guide the development of novel high affinity binding drugs.

  10. Thicker three-dimensional tissue from a "symbiotic recycling system" combining mammalian cells and algae.

    PubMed

    Haraguchi, Yuji; Kagawa, Yuki; Sakaguchi, Katsuhisa; Matsuura, Katsuhisa; Shimizu, Tatsuya; Okano, Teruo

    2017-01-31

    In this paper, we report an in vitro co-culture system that combines mammalian cells and algae, Chlorococcum littorale, to create a three-dimensional (3-D) tissue. While the C2C12 mouse myoblasts and rat cardiac cells consumed oxygen actively, intense oxygen production was accounted for by the algae even in the co-culture system. Although cell metabolism within thicker cardiac cell-layered tissues showed anaerobic respiration, the introduction of innovative co-cultivation partially changed the metabolism to aerobic respiration. Moreover, the amount of glucose consumption and lactate production in the cardiac tissues and the amount of ammonia in the culture media decreased significantly when co-cultivated with algae. In the cardiac tissues devoid of algae, delamination was observed histologically, and the release of creatine kinase (CK) from the tissues showed severe cardiac cell damage. On the other hand, the layered cell tissues with algae were observed to be in a good histological condition, with less than one-fifth decline in CK release. The co-cultivation with algae improved the culture condition of the thicker tissues, resulting in the formation of 160 μm-thick cardiac tissues. Thus, the present study proposes the possibility of creating an in vitro "symbiotic recycling system" composed of mammalian cells and algae.

  11. Comparative Kinetics and Distribution to Target Tissues of Organophosphates Using Physiologically - Based Pharmacokinetic Modeling

    DTIC Science & Technology

    2008-03-01

    to action and toxicological target tissues? What are the levels of acetylcholine (ACh) in target tissues as a resulting from different exposure...the toxicological effects of low-level exposure to 27 chemical warfare agents (Genovese, 2004, Henderson, 2002). Genovese (2004) defines a “low...the efficacy of HI 6 in percutaneous VX poisoning,” Toxicology , 224: 74-80. Calvert, J.B. (2002). Chemical Warfare. Retrieved June 20, 2007

  12. Fading of Bromophenol Blue: A Combined Synthesis and Spectrophotometric Kinetics Experiment

    ERIC Educational Resources Information Center

    Winans, Randall; Brown, Charles Allan

    1975-01-01

    Describes a general chemistry level kinetics experiment requiring three 3-hour laboratory periods. Data analyses can be accomplished with graphical techniques or a non-linear least squares computer program. (MLH)

  13. Fading of Bromophenol Blue: A Combined Synthesis and Spectrophotometric Kinetics Experiment

    ERIC Educational Resources Information Center

    Winans, Randall; Brown, Charles Allan

    1975-01-01

    Describes a general chemistry level kinetics experiment requiring three 3-hour laboratory periods. Data analyses can be accomplished with graphical techniques or a non-linear least squares computer program. (MLH)

  14. A multicompartmental model of in vivo adipose tissue glycerol kinetics and capillary permeability in lean and obese humans.

    PubMed

    Coppack, Simon W; Chinkes, David L; Miles, John M; Patterson, Bruce W; Klein, Samuel

    2005-07-01

    Lipolysis of adipose tissue triglycerides releases glycerol. Twenty-four volunteers, of whom 6 were obese and 13 were women, received a primed-constant infusion of 2H5-glycerol for 120 min during postabsorptive steady-state conditions. Arterial, abdominal venous, and interstitial (microdialysis) samples were taken, and a four-compartment model was applied to assess subcutaneous abdominal adipose tissue glycerol kinetics. Adipose tissue blood flow was measured using 133Xe washout. Venous glycerol concentrations (median 230 micromol/l [interquartile range 210-268]) were consistently greater than those of arterial blood (69.1 micromol/l [56.5-85.5]), while glycerol isotopic enrichments (tracer-to-tracee ratio) were greater in arterial blood (8.34% [7.44-10.1]) than venous blood (2.34% [1.71-2.69], P < 0.01). Microdialysate glycerol enrichment was 1.44% (1.11-1.79), indicating incomplete permeability of glycerol between capillary blood and interstitium. Calculated interstitial glycerol concentrations were between 270 micromol/l (256-350) and 332 micromol/l (281-371) (examining different boundary conditions). The calculated capillary diffusion capacity (ps) was between 2.21 ml . 100 g tissue(-1) . min(-1) (1.31-3.13) and 3.09 ml . 100 g tissue(-1) . min(-1) (1.52-4.90) and correlated inversely with adiposity (Rs< or = -0.45, P < 0.05). Our results support previous estimates of interstitial glycerol concentration within adipose tissue and reveal capillary diffusion capacity is reduced in obesity.

  15. Oncofertility: combination of ovarian stimulation with subsequent ovarian tissue extraction on the day of oocyte retrieval

    PubMed Central

    2013-01-01

    Background New anticancer treatments have increased survival rates for cancer patients, but often at the cost of sterility. Several strategies are currently available for preserving fertility. However, the chances of achieving a pregnancy with one technique are still limited. A combination of methods is therefore recommended in order to maximize women’s chances of future fertility. In this retrospective study, ovarian stimulation with subsequent ovarian tissue extraction on the day of oocyte retrieval were combined and the quality of the ovarian tissue, the numbers and quality of oocytes, time requirements, and the safety of the strategy were examined. Methods Fourteen female patients suffering from malignant diseases underwent one in vitro fertilization cycle. Different stimulation protocols were used, depending on the menstrual cycle. Transvaginal oocyte retrieval was scheduled 34–36 h after human chorionic gonadotropin administration. Immediately afterwards, ovarian tissue was extracted laparoscopically. Results A mean of 10 oocytes were retrieved per patient, and 67% of the oocytes were successfully fertilized using intracytoplasmic sperm injection. No periprocedural complications and no complications leading to postponement of the start of chemotherapy occurred. The ovarian tissues were of good quality, with a normal age-related follicular distribution and without carcinoma cell invasion. Conclusions An approach using ovarian stimulation first, followed by laparoscopic collection of ovarian tissue, is a useful strategy for increasing the efficacy of fertility preservation techniques. The ovarian tissue is not affected by prior ovarian stimulation. PMID:23510640

  16. Modeling Soft Tissue Damage and Failure Using a Combined Particle/Continuum Approach.

    PubMed

    Rausch, M K; Karniadakis, G E; Humphrey, J D

    2017-02-01

    Biological soft tissues experience damage and failure as a result of injury, disease, or simply age; examples include torn ligaments and arterial dissections. Given the complexity of tissue geometry and material behavior, computational models are often essential for studying both damage and failure. Yet, because of the need to account for discontinuous phenomena such as crazing, tearing, and rupturing, continuum methods are limited. Therefore, we model soft tissue damage and failure using a particle/continuum approach. Specifically, we combine continuum damage theory with Smoothed Particle Hydrodynamics (SPH). Because SPH is a meshless particle method, and particle connectivity is determined solely through a neighbor list, discontinuities can be readily modeled by modifying this list. We show, for the first time, that an anisotropic hyperelastic constitutive model commonly employed for modeling soft tissue can be conveniently implemented within a SPH framework and that SPH results show excellent agreement with analytical solutions for uniaxial and biaxial extension as well as finite element solutions for clamped uniaxial extension in 2D and 3D. We further develop a simple algorithm that automatically detects damaged particles and disconnects the spatial domain along rupture lines in 2D and rupture surfaces in 3D. We demonstrate the utility of this approach by simulating damage and failure under clamped uniaxial extension and in a peeling experiment of virtual soft tissue samples. In conclusion, SPH in combination with continuum damage theory may provide an accurate and efficient framework for modeling damage and failure in soft tissues.

  17. Combination of thermographic and ultrasonographic assessments for early detection of deep tissue injury.

    PubMed

    Higashino, Takuya; Nakagami, Gojiro; Kadono, Takafumi; Ogawa, Yuki; Iizaka, Shinji; Koyanagi, Hiroe; Sasaki, Sanae; Haga, Nobuhiko; Sanada, Hiromi

    2014-10-01

    Early detection and intervention of deep tissue injury are important to lead good outcome. Although the efficiency of ultrasonographic assessment of deep tissue injury has been reported previously, it requires a certain level of skill for accurate assessment. In this study, we present an investigation of the combination of thermographic and ultrasonographic assessments for early detection of deep tissue injury. We retrospectively reviewed 28 early-stage pressure ulcers (21 patients) presenting at the University of Tokyo Hospital between April 2009 and February 2010, surveying the associated thermographic and ultrasonographic findings. The wound temperature patterns were divided into low, even and high compared with the surrounding skin. Ultrasonographic findings were classified into unclear layer structure, hypoechoic lesion, discontinuous fascia and heterogeneous hypoechoic area. All 13 ulcers that were associated with low temperature showed good outcome; three ulcers had even temperatures and 12 ulcers showed high temperature on thermographic assessment. The two deep tissue injuries were rated high on thermographic assessment and showed heterogeneous hypoechoic area findings on ultrasonographic assessment. No non-deep tissue injury lesion was associated with these two findings simultaneously. The combination of thermographic and ultrasonographic assessments is expected to increase the accuracy of the early detection of deep tissue injuries.

  18. Development of A Novel Murine Model of Combined Radiation and Peripheral Tissue Trauma Injuries.

    PubMed

    Antonic, Vlado; Jackson, Isabel L; Ganga, Gurung; Shea-Donohue, Terez; Vujaskovic, Zeljko

    2017-02-01

    Detonation of a 10-kiloton nuclear bomb in an urban setting would result in >1 million casualties, the majority of which would present with combined injuries. Combined injuries, such as peripheral tissue trauma and radiation exposure, trigger inflammatory events that lead to multiple organ dysfunction (MOD) and death, with gastrointestinal (GI) and pulmonary involvement playing crucial roles. The objective of this study was to develop an animal model of combined injuries, peripheral tissue trauma (TBX animal model) combined with total body irradiation with 5% bone marrow shielding (TBI/BM5) to investigate if peripheral tissue trauma contributes to reduced survival. Male C57BL/6J mice were exposed to TBX10%, irradiation (TBI/BM5), or combined injuries (TBX10% + TBI/BM5). Experiments were conducted to evaluate mortality at day 7 after TBI/BM5. Serial euthanasia was performed at day 1, 3 and 6 or 7 after TBI/BM5 to evaluate the time course of pathophysiologic processes in combined injuries. Functional tests were performed to assess pulmonary function and GI motility. Postmortem samples of lungs and jejunum were collected to assess tissue damage. Results indicated higher lethality and shorter survival in the TBX10% +T BI/BM5 group than in the TBX10% or TBI/BM5 groups (day 1 vs. day 7 and 6, respectively). TBI/BM5 alone had no effects on the lungs but significantly impaired GI function at day 6. As expected, in the animals that received severe trauma (TBX10%), we observed impairment in lung function and delay in GI transit in the first 3 days, effects that decreased at later time points. Trauma combined with radiation (TBX10% + TBI/BM5) significantly augmented impairment of the lung and GI function in comparison to TBX10% and TBI/BM5 groups at 24 h. Histologic evaluation indicated that combined injuries caused greater tissue damage in the intestines in TBX10% + TBI/BM5 group when compared to other groups. We describe here the first combined tissue trauma

  19. Combination of fiber-guided pulsed erbium and holmium laser radiation for tissue ablation under water

    NASA Astrophysics Data System (ADS)

    Pratisto, Hans; Frenz, Martin; Ith, Michael; Altermatt, Hans J.; Jansen, E. Duco; Weber, Heinz P.

    1996-07-01

    Because of the high absorption of near-infrared laser radiation in biological tissue, erbium lasers and holmium lasers emitting at 3 and 2 mu m, respectively, have been proven to have optimal qualities for cutting or welding and coagulating tissue. To combine the advantages of both wavelengths, we realized a multiwavelength laser system by simultaneously guiding erbium and holmium laser radiation by means of a single zirconium fluoride (ZrF4) fiber. Laser-induced channel formation in water and poly(acrylamide) gel was investigated by the use of a time-resolved flash-photography setup, while pressure transients were recorded simultaneously with a needle hydrophone. The shapes and depths of vapor channels produced in water and in a submerged gel after single erbium and after combination erbium-holmium radiation delivered by means of a 400- mu m ZrF4 fiber were measured. Transmission measurements were performed to determine the amount of pulse energy available for tissue ablation. The effects of laser wavelength and the delay time between pulses of different wavelengths on the photomechanical and photothermal responses of meniscal tissue were evaluated in vitro by the use of histology. It was observed that the use of a short (200- mu s, 100-mJ) holmium laser pulse as a prepulse to generate a vapor bubble through which the ablating erbium laser pulse can be transmitted (delay time, 100 mu s) increases the cutting depth in meniscus from 450 to 1120 mu m as compared with the depth following a single erbium pulse. The results indicate that a combination of erbium and holmium laser radiation precisely and efficiently cuts tissue under water with 20-50- mu m collateral tissue damage. wave, cavitation, channel formation, infrared-fiber-delivery system, tissue damage, cartilage.

  20. Tissue classification and diagnostics using a fiber probe for combined Raman and fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Cicchi, Riccardo; Anand, Suresh; Rossari, Susanna; Sturiale, Alessandro; Giordano, Flavio; De Giorgi, Vincenzo; Maio, Vincenza; Massi, Daniela; Nesi, Gabriella; Buccoliero, Anna Maria; Tonelli, Francesco; Guerrini, Renzo; Pimpinelli, Nicola; Pavone, Francesco S.

    2015-03-01

    Two different optical fiber probes for combined Raman and fluorescence spectroscopic measurements were designed, developed and used for tissue diagnostics. Two visible laser diodes were used for fluorescence spectroscopy, whereas a laser diode emitting in the NIR was used for Raman spectroscopy. The two probes were based on fiber bundles with a central multimode optical fiber, used for delivering light to the tissue, and 24 surrounding optical fibers for signal collection. Both fluorescence and Raman spectra were acquired using the same detection unit, based on a cooled CCD camera, connected to a spectrograph. The two probes were successfully employed for diagnostic purposes on various tissues in a good agreement with common routine histology. This study included skin, brain and bladder tissues and in particular the classification of: malignant melanoma against melanocytic lesions and healthy skin; urothelial carcinoma against healthy bladder mucosa; brain tumor against dysplastic brain tissue. The diagnostic capabilities were determined using a cross-validation method with a leave-one-out approach, finding very high sensitivity and specificity for all the examined tissues. The obtained results demonstrated that the multimodal approach is crucial for improving diagnostic capabilities. The system presented here can improve diagnostic capabilities on a broad range of tissues and has the potential of being used for endoscopic inspections in the near future.

  1. Tissue classification and diagnostics using a fiber probe for combined Raman and fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Cicchi, Riccardo; Anand, Suresh; Crisci, Alfonso; Giordano, Flavio; Rossari, Susanna; De Giorgi, Vincenzo; Maio, Vincenza; Massi, Daniela; Nesi, Gabriella; Buccoliero, Anna Maria; Guerrini, Renzo; Pimpinelli, Nicola; Pavone, Francesco S.

    2015-07-01

    Two different optical fiber probes for combined Raman and fluorescence spectroscopic measurements were designed, developed and used for tissue diagnostics. Two visible laser diodes were used for fluorescence spectroscopy, whereas a laser diode emitting in the NIR was used for Raman spectroscopy. The two probes were based on fiber bundles with a central multimode optical fiber, used for delivering light to the tissue, and 24 surrounding optical fibers for signal collection. Both fluorescence and Raman spectra were acquired using the same detection unit, based on a cooled CCD camera, connected to a spectrograph. The two probes were successfully employed for diagnostic purposes on various tissues in a good agreement with common routine histology. This study included skin, brain and bladder tissues and in particular the classification of: malignant melanoma against melanocytic lesions and healthy skin; urothelial carcinoma against healthy bladder mucosa; brain tumor against dysplastic brain tissue. The diagnostic capabilities were determined using a cross-validation method with a leave-one-out approach, finding very high sensitivity and specificity for all the examined tissues. The obtained results demonstrated that the multimodal approach is crucial for improving diagnostic capabilities. The system presented here can improve diagnostic capabilities on a broad range of tissues and has the potential of being used for endoscopic inspections in the near future.

  2. Combining multiset resolution and segmentation for hyperspectral image analysis of biological tissues.

    PubMed

    Piqueras, S; Krafft, C; Beleites, C; Egodage, K; von Eggeling, F; Guntinas-Lichius, O; Popp, J; Tauler, R; de Juan, A

    2015-06-30

    Hyperspectral images can provide useful biochemical information about tissue samples. Often, Fourier transform infrared (FTIR) images have been used to distinguish different tissue elements and changes caused by pathological causes. The spectral variation between tissue types and pathological states is very small and multivariate analysis methods are required to describe adequately these subtle changes. In this work, a strategy combining multivariate curve resolution-alternating least squares (MCR-ALS), a resolution (unmixing) method, which recovers distribution maps and pure spectra of image constituents, and K-means clustering, a segmentation method, which identifies groups of similar pixels in an image, is used to provide efficient information on tissue samples. First, multiset MCR-ALS analysis is performed on the set of images related to a particular pathology status to provide basic spectral signatures and distribution maps of the biological contributions needed to describe the tissues. Later on, multiset segmentation analysis is applied to the obtained MCR scores (concentration profiles), used as compressed initial information for segmentation purposes. The multiset idea is transferred to perform image segmentation of different tissue samples. Doing so, a difference can be made between clusters associated with relevant biological parts common to all images, linked to general trends of the type of samples analyzed, and sample-specific clusters, that reflect the natural biological sample-to-sample variability. The last step consists of performing separate multiset MCR-ALS analyses on the pixels of each of the relevant segmentation clusters for the pathology studied to obtain a finer description of the related tissue parts. The potential of the strategy combining multiset resolution on complete images, multiset segmentation and multiset local resolution analysis will be shown on a study focused on FTIR images of tissue sections recorded on inflamed and non

  3. Radioresistance of granulation tissue-derived cells from skin wounds combined with total body irradiation.

    PubMed

    Dai, Tingyu; Chen, Zelin; Tan, Li; Shi, Chunmeng

    2016-04-01

    Combined radiation and wound injury (CRWI) occurs following nuclear explosions and accidents, radiological or nuclear terrorism, and radiation therapy combined with surgery. CRWI is complicated and more difficult to heal than single injuries. Stem cell‑based therapy is a promising treatment strategy for CRWI, however, sourcing stem cells remains a challenge. In the present study, the granulation tissue-derived cells (GTCs) from the skin wounds (SWs) of CRWI mice (C‑GTCs) demonstrated a higher radioresistance to the damage caused by combined injury, and were easier to isolate and harvest when compared with bone marrow‑derived mesenchymal stromal cells (BMSCs). Furthermore, the C-GTCs exhibited similar stem cell-associated properties, such as self-renewal and multilineage differentiation capacity, when compared with neonatal dermal stromal cells (DSCs) and GTCs from unirradiated SWs. Granulation tissue, which is easy to access, may present as an optimal autologous source of stem/progenitor cells for therapeutic applications in CRWI.

  4. A Substructure Combination Strategy To Create Potent and Selective Transthyretin Kinetic Stabilizers That Prevent Amyloidogenesis and Cytotoxicity

    SciTech Connect

    Choi, Sungwook; Reixach, Natlia; Connelly, Stephen; Johnson, Steven M.; Wilson, Ian A.; Kelly, Jeffery W.

    2010-08-13

    Transthyretin aggregation-associated proteotoxicity appears to cause several human amyloid diseases. Rate-limiting tetramer dissociation and monomer misfolding of transthyretin (TTR) occur before its aggregation into cross-{beta}-sheet amyloid fibrils. Small molecule binding to and preferential stabilization of the tetrameric state of TTR over the dissociative transition state raises the kinetic barrier for dissociation, imposing kinetic stabilization on TTR and preventing aggregation. This is an effective strategy to halt neurodegeneration associated with polyneuropathy, according to recent placebo-controlled clinical trial results. In three recent papers, we systematically ranked possibilities for the three substructures composing a typical TTR kinetic stabilizer, using fibril inhibition potency and plasma TTR binding selectivity data. Herein, we have successfully employed a substructure combination strategy to use these data to develop potent and selective TTR kinetic stabilizers that rescue cells from the cytotoxic effects of TTR amyloidogenesis. Of the 92 stilbene and dihydrostilbene analogues synthesized, nearly all potently inhibit TTR fibril formation. Seventeen of these exhibit a binding stoichiometry of >1.5 of a maximum of 2 to plasma TTR, while displaying minimal binding to the thyroid hormone receptor (<20%). Six analogues were definitively categorized as kinetic stabilizers by evaluating dissociation time-courses. High-resolution TTR-(kinetic stabilizer)2 crystal structures (1.31-1.70 {angstrom}) confirmed the anticipated binding orientation of the 3,5-dibromo-4-hydroxyphenyl substructure and revealed a strong preference of the isosteric 3,5-dibromo-4-aminophenyl substructure to bind to the inner thyroxine binding pocket of TTR.

  5. Proteome Dynamics: Tissue Variation in the Kinetics of Proteostasis in Intact Animals*

    PubMed Central

    Hammond, Dean E.; Claydon, Amy J.; Simpson, Deborah M.; Edward, Dominic; Stockley, Paula; Hurst, Jane L.

    2016-01-01

    Understanding the role of protein turnover in the maintenance of proteostasis requires accurate measurements of the rates of replacement of proteins in complex systems, such as intact animals. Moreover, any investigation of allometric scaling of protein turnover is likely to include species for which fully annotated proteomes are not available. We have used dietary administration of stable isotope labeled lysine to assess protein turnover rates for proteins from four tissues in the bank vole, Myodes glareolus. The annotated genome for this species is not available, so protein identification was attained through cross-species matching to the mouse. For proteins for which confident identifications were derived, the pattern of lysine incorporation over 40 days was used to define the rate of synthesis of individual proteins in the four tissues. The data were heavily filtered to retain a very high quality dataset of turnover rates for 1088 proteins. Comparative analysis of the four tissues revealed different median rates of degradation (kidney: 0.099 days−1; liver 0.136 days−1; heart, 0.054 days−1, and skeletal muscle, 0.035 days−1). These data were compared with protein degradation rates from other studies on intact animals or from cells in culture and indicate that both cell type and analytical methodology may contribute to variance in turnover data between different studies. These differences were not only due to tissue-specific proteins but were reflected in gene products common to all tissues. All data are available via ProteomeXchange with identifier PXD002054. PMID:26839000

  6. Improvement of tissue analysis and classification using optical coherence tomography combined with Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Liu, Chih-Hao; Qi, Ji; Lu, Jing; Wang, Shang; Wu, Chen; Shih, Wei-Chuan; Larin, Kirill V.

    2014-02-01

    Optical coherence tomography (OCT) is an optical imaging technique that is capable of performing high-resolution (approaching the histopathology level) and real-time imaging of tissues without use of contrast agents. Based on these advantages, the pathological features of tumors (in micro scale) can be identified during resection surgery. However, the accuracy of tumor margin prediction still needs to be enhanced for assisting the judgment of surgeons. In this regard, we present a two-dimensional computational method for advanced tissue analysis and characterization based on optical coherence tomography (OCT) and Raman spectroscopy (RS). The method combines the slope of OCT intensity signal and the Principal component (PC) of RS, and relies on the tissue optical attenuation and chemical ingredients for the classification of tissue types. Our pilot experiments were performed on mouse kidney, liver and small intestine. Results demonstrate the improvement of the tissue differentiation compared with the analysis only based on the OCT detection. This combined OCT/RS method is potentially useful as a novel optical biopsy technique for cancer detection.

  7. Combining fibre optic Raman spectroscopy and tactile resonance measurement for tissue characterization

    NASA Astrophysics Data System (ADS)

    Candefjord, Stefan; Nyberg, Morgan; Jalkanen, Ville; Ramser, Kerstin; Lindahl, Olof A.

    2010-12-01

    Tissue characterization is fundamental for identification of pathological conditions. Raman spectroscopy (RS) and tactile resonance measurement (TRM) are two promising techniques that measure biochemical content and stiffness, respectively. They have potential to complement the golden standard--histological analysis. By combining RS and TRM, complementary information about tissue content can be obtained and specific drawbacks can be avoided. The aim of this study was to develop a multivariate approach to compare RS and TRM information. The approach was evaluated on measurements at the same points on porcine abdominal tissue. The measurement points were divided into five groups by multivariate analysis of the RS data. A regression analysis was performed and receiver operating characteristic (ROC) curves were used to compare the RS and TRM data. TRM identified one group efficiently (area under ROC curve 0.99). The RS data showed that the proportion of saturated fat was high in this group. The regression analysis showed that stiffness was mainly determined by the amount of fat and its composition. We concluded that RS provided additional, important information for tissue identification that was not provided by TRM alone. The results are promising for development of a method combining RS and TRM for intraoperative tissue characterization.

  8. Combining electromagnetic gyro-kinetic particle-in-cell simulations with collisions

    NASA Astrophysics Data System (ADS)

    Slaby, Christoph; Kleiber, Ralf; Könies, Axel

    2017-09-01

    It has been an open question whether for electromagnetic gyro-kinetic particle-in-cell (PIC) simulations pitch-angle collisions and the recently introduced pullback transformation scheme (Mishchenko et al., 2014; Kleiber et al., 2016) are consistent. This question is positively answered by comparing the PIC code EUTERPE with an approach based on an expansion of the perturbed distribution function in eigenfunctions of the pitch-angle collision operator (Legendre polynomials) to solve the electromagnetic drift-kinetic equation with collisions in slab geometry. It is shown how both approaches yield the same results for the frequency and damping rate of a kinetic Alfvén wave and how the perturbed distribution function is substantially changed by the presence of pitch-angle collisions.

  9. Combined soft and skeletal tissue modelling of normal and dysmorphic midface postnatal development.

    PubMed

    Ibrahim, Amel; Suttie, Michael; Bulstrode, Neil W; Britto, Jonathan A; Dunaway, David; Hammond, Peter; Ferretti, Patrizia

    2016-11-01

    Midface hypoplasia as exemplified by Treacher Collins Syndrome (TCS) can impair appearance and function. Reconstruction involves multiple invasive surgeries with variable long-term outcomes. This study aims to describe normal and dysmorphic midface postnatal development through combined modelling of skeletal and soft tissues and to develop a surgical evaluation tool. Midface skeletal and soft tissue surfaces were extracted from computed tomography scans of 52 control and 14 TCS children, then analysed using dense surface modelling. The model was used to describe midface growth, morphology, and asymmetry, then evaluate postoperative outcomes. Parameters responsible for the greatest variation in midface size and shape showed differences between TCS and controls with close alignment between skeletal and soft tissue models. TCS children exhibited midface dysmorphology and hypoplasia when compared with controls. Asymmetry was also significantly higher in TCS midfaces. Combined modelling was used to evaluate the impact of surgery in one TCS individual who showed normalisation immediately after surgery but reversion towards TCS dysmorphology after 1 year. This is the first quantitative analysis of postnatal midface development using combined modelling of skeletal and soft tissues. We also provide an approach for evaluation of surgical outcomes, laying the foundations for future development of a preoperative planning tool. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  10. Combination Of Static And Dynami,C Stereophotogrammetry For The Kinetic Analysis Of Human Locomotion: Preliminary Results

    NASA Astrophysics Data System (ADS)

    Schaer, Alex R.; Sheffer, Daniel B.; Jones, D.; Meier, G.; Baumann, Juerg U.

    1989-04-01

    For a deeper understanding of the complexity of human walking movement not only a kinematic analysis , but also a comprehensive three-dimensional biomechanical model of the human body is required to detail the kinetic activities. This research combined static stereophotogrammetric determination of body segment mass parameters with three-dimensional gait analysis by cinephotography, direct linear transformation and two force plates. A method of combining the two independent analyses by defining the anatomical axes of each segment is shown. Practical problems arising in dynamic and stereometric analysis are demonstrated. Power spectra of a normal and a matched subject with spastic diplegia were calculated for a proper design of the kinematic analysis.

  11. The effect of continuous low dose-rate gamma irradiation on cell population kinetics of lymphoid tissue

    NASA Technical Reports Server (NTRS)

    Foster, B. R.

    1974-01-01

    Cellular response and cell population kinetics were studied during lymphopoiesis in the thymus of the mouse under continuous gamma irradiation using autoradiographic techniques and specific labeling with tritiated thymidine. On the basis of tissue weights, it is concluded that the response of both the thymus and spleen to continuous low dose-rate irradiation is multiphasic. That is, alternating periods of steady state growth, followed by collapse, which in turn is followed by another period of homeostasis. Since there are two populations of lymphocytes - short lived and long-lived, it may be that different phases of steady state growth are mediated by different lymphocytes. The spleen is affected to a greater extent with shorter periods of steady-state growth than exhibited by the thymus.

  12. Biliary elimination kinetics and tissue concentrations of oxytetracycline after intravenous administration in hens.

    PubMed

    Serrano, J M; Moreno, L; Rosado, I; Guimerá, E; Escudero, E

    1999-04-01

    The pharmacokinetics of the biliary elimination of oxytetracycline (OTC) and tissue concentrations in certain organs were studied in 10 Leghorn hens. The animals were anaesthetized using xylazine/ketamine administered by the intramuscular (i.m.) route and were immobilized for right laparotomy. Both bile ducts were cannulated and a dose of 20 mg/kg of oxytetracycline hydrochloride was administered intravenously (i.v.). Samples of bile excreted were taken at predetermined intervals during 6 h. At 6 h animals were slaughtered and tissue samples of blood, liver, kidney, pancreas, spleen, heart, lung and pectoral muscle were taken. The values for OTC biliary elimination rate times were best fitted to a one-exponential equation. The maximum value for OTC biliary excretion rate (3.69+/-0.6 microg/min/kg) was reached at approximately 17.5 min (time to maximum concentration (tmax)). The first-order rate constant for the biliary excretion (k) and the half-life (t1/2) were 6.7x10(-3) min(-1) and 110.55 min, respectively. The mean value of area under the biliary excretion rate time curve (AUC) indicated that 839.77 microg/kg body weight (b.w.) were eliminated by the biliary route. The cumulative biliary excretion data indicated that approximately 4.20% of the dose was eliminated by this route, 3.28% being eliminated during the first 6 h and 0.92% thereafter. The highest mean concentrations were found in the kidney (35.82 microg/kg) and liver (16.77 microg/g). Significant differences were found between the concentrations of the various tissues studied. Plasma concentration was lower than that of the other tissues (except lung).

  13. Analysis of four dopaminergic tracers kinetics using two different tissue input function methods.

    PubMed

    Sossi, V; Holden, J E; Chan, G; Krzywinski, M; Stoessl, A J; Ruth, T J

    2000-04-01

    The integrity of the dopaminergic system can be studied using positron emission tomography. The presynaptic tracers [11C]-methylphenidate and [11C]dihydrotetrabenazine (DTBZ) are used to investigate the dopamine transporter availability, the dopamine vesicular transporter integrity; the postsynaptic tracers [11C]-raclopride and [11C]-Schering 23990 (SCH) are used to probe the D2 and D1 receptors. These are reversible tracers, where the binding potential (BP) = Bmax/Kd often is used to quantify the amount of their specific binding to the sites of interest. The simplified tissue input methods to calculate BP are attractive, since they do not require a blood input function. The suitability and performance of two such methods were evaluated: the Logan graphical tissue method, and the Lammertsma reference tissue method (RTM). The BP estimates obtained with the two methods were nearly identical in most cases, with similar reliability and reproducibility indicating that all four tracers satisfy the assumptions required by each method. The correlations among the fitted parameters obtained from the RTM were estimated and were found not to introduce noticeable bias in the RTM BP and R1 estimates. R1 showed low intersubject and intrasubject variability. The k2 estimate showed good reliability for SCH with cerebellar input function and DTBZ with occipital input function.

  14. Surface enzyme kinetics for biopolymer microarrays: a combination of Langmuir and Michaelis-Menten concepts.

    PubMed

    Lee, Hye Jin; Wark, Alastair W; Goodrich, Terry T; Fang, Shiping; Corn, Robert M

    2005-04-26

    Real-time surface plasmon resonance (SPR) imaging measurements of surface enzymatic reactions on DNA microarrays are analyzed using a kinetics model that couples the contributions of both enzyme adsorption and surface enzyme reaction kinetics. For the case of a 1:1 binding of an enzyme molecule (E) to a surface-immobilized substrate (S), the overall enzymatic reaction can be described in terms of classical Langmuir adsorption and Michaelis-Menten concepts and three rate constants: enzyme adsorption (k(a)), enzyme desorption (k(d)) and enzyme catalysis (k(cat)). In contrast to solution enzyme kinetics, the amount of enzyme in solution is in excess as compared to the amount of substrate on the surface. Moreover, the surface concentration of the intermediary enzyme-substrate complex (ES) is not constant with time, but goes to zero as the reaction is completed. However, kinetic simulations show that the fractional surface coverage of ES on the remaining unreacted sites does reach a steady-state value throughout the course of the surface reaction. This steady-state value approaches the Langmuir equilibrium value for cases where k(a)[E] > k(cat). Experiments using the 3' --> 5' exodeoxyribonuclease activity of Exonuclease III on double-stranded DNA microarrays as a function of temperature and enzyme concentration are used to demonstrate how this model can be applied to quantitatively analyze the SPR imaging data.

  15. Reexcitation mechanisms in epicardial tissue: role of I(to) density heterogeneities and I(Na) inactivation kinetics.

    PubMed

    Cantalapiedra, Inma R; Peñaranda, Angelina; Mont, Lluis; Brugada, Josep; Echebarria, Blas

    2009-08-21

    Dispersion of action potential repolarization is known to be an important arrhythmogenic factor in cardiopathies such as Brugada syndrome. In this work, we analyze the effect of a variation in sodium current (I(Na)) inactivation and a heterogeneous rise of transient outward current (I(to)) in the probability of reentry in epicardial tissue. We use the Luo-Rudy model of epicardial ventricular action potential to study wave propagation in a one-dimensional fiber. Spatial dispersion in repolarization is introduced by splitting the fiber into zones with different strength of I(to). We then analyze the pro-arrhythmic effect of a variation in the relaxation time and steady-state of the sodium channel fast inactivating gate h. We quantify the probability of reentry measuring the percentage of reexcitations that occurs in 200 beats. We find that, for high stimulation rates, this percentage is negligible, but increases notably for pacing periods above 700ms. Surprisingly, with decreasing I(Na) inactivation time, the percentage of reexcitations does not grow monotonically, but presents vulnerable windows, separated by values of the I(Na) inactivation speed-up where reexcitation does not occur. By increasing the strength of L-type calcium current I(CaL) above a certain threshold, reexcitation disappears. Finally, we show the formation of reentry in stimulated two-dimensional epicardial tissue with modified I(Na) kinetics and I(to) heterogeneity. Thus, we confirm that while I(to) dispersion is necessary for phase-2 reentry, altered sodium inactivation kinetics influences the probability of reexcitation in a highly nonlinear fashion.

  16. Incorporation of tissue reaction kinetics in a computational fluid dynamics model for nasal extraction of inhaled hydrogen sulfide in rats.

    PubMed

    Schroeter, Jeffry D; Kimbell, Julia S; Bonner, Anna M; Roberts, Kay C; Andersen, Melvin E; Dorman, David C

    2006-03-01

    Rodents exposed to hydrogen sulfide (H2S) develop olfactory neuronal loss. This lesion has been used by the risk assessment community to develop occupational and environmental exposure standards. A correlation between lesion locations and areas of high H2S flux to airway walls has been previously demonstrated, but a quantitative dose assessment is needed to extrapolate dose at lesion sites to humans. In this study, nasal extraction (NE) of 10, 80, and 200 ppm H2S was measured in the isolated upper respiratory tract of anesthetized rats under constant unidirectional inspiratory flow rates of 75, 150, and 300 ml/min. NE was dependent on inspired H2S concentration and air flow rate: increased NE was observed when H2S exposure concentrations or inspiratory air flow rates were low. An anatomically accurate, three-dimensional computational fluid dynamics (CFD) model of rat nasal passages was used to predict NE of inhaled H2S. To account for the observed dependence of NE on H2S exposure concentration, the boundary condition used at airway walls incorporated first-order and saturable kinetics in nasal tissue to govern mass flux at the air:tissue interface. Since the kinetic parameters cannot be obtained using the CFD model, they were estimated independently by fitting a well-mixed, two-compartment pharmacokinetic (PK) model to the NE data. Predicted extraction values using this PK-motivated CFD approach were in good agreement with the experimental measurements. The CFD model provides estimates of localized H2S flux to airway walls and can be used to calibrate lesion sites by dose.

  17. Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport

    SciTech Connect

    Rebouche, C.J.; Engel, A.G.

    1984-03-01

    The human primary carnitine deficiency syndromes are potentially fatal disorders affecting children and adults. The molecular etiologies of these syndromes have not been determined. In this investigation, we considered the hypothesis that these syndromes result from defective transport of carnitine into tissues, particularly skeletal muscle. The problem was approached by mathematical modeling, by using the technique of kinetic compartmental analysis. A tracer dose of L-(methyl-3H)carnitine was administered intravenously to six normal subjects, one patient with primary muscle carnitine deficiency (MCD), and four patients with primary systemic carnitine deficiency (SCD). Specific radioactivity was followed in plasma for 28 d. A three-compartment model (extracellular fluid, muscle, and ''other tissues'') was adopted. Rate constants, fluxes, pool sizes, and turnover times were calculated. Results of these calculations indicated reduced transport of carnitine into muscle in both forms of primary carnitine deficiency. However, in SCD, the reduced rate of carnitine transport was attributed to reduced plasma carnitine concentration. In MCD, the results are consistent with an intrinsic defect in the transport process. Abnormal fluctuations of the plasma carnitine, but of a different form, occurred in MCD and SCD. The significance of these are unclear, but in SCD they suggest abnormal regulation of the muscle/plasma carnitine concentration gradient. In 8 of 11 subjects, carnitine excretion was less than dietary carnitine intake. Carnitine excretion rates calculated by kinetic compartmental analysis were higher than corresponding rates measured directly, indicating degradation of carnitine. However, we found no radioactive metabolites of L-(methyl-3H)carnitine in urine. These observations suggest that dietary carnitine was metabolized in the gastrointestinal tract.

  18. Chondrogenic induction of human mesenchymal stem cells using combined growth factors for cartilage tissue engineering.

    PubMed

    Bosetti, Michela; Boccafoschi, Francesca; Leigheb, Massimiliano; Bianchi, Andrea E; Cannas, Mario

    2012-03-01

    The objective of this study was to evaluate whether growth factors (FGF-2, FGF-4 and FGF-6) used alone or in combination with TGFβ2 are able to increase the proliferation and induce the differentiation of human bone marrow mesenchymal stem cells (hMSCs) to chondrocytes, with a view to using them in cartilage tissue engineering. Cells cultured in monolayer, used to test the activity of the growth factors on cell proliferation, showed that a combination of FGFs with TGFβ2 increases cell proliferation compared to cells cultured in control medium or in the presence of growth factors alone. The chondrogenic potential, evaluated in three-dimensional (3D) cell aggregates, showed that FGF-2 and FGF-6, when used in combination with TGFβ2 increased the size and glycosaminoglycan content of the cell aggregates without increasing cell number. Extracellular matrix (ECM) also showed higher collagen type II immunoreactivity, which was particularly evident in an area similar to a germinative pole that was observed only in pellets cultured with FGF-2 and FGF-6 combined with TGFβ2, or in pellets cultured with FGF-2 alone. Moreover, the RT-PCR assay has highlighted an increased expression of collagen type II and Sox9, used as gene markers for chondrogenesis. We can conclude that combinations of FGF-2 or FGF-6 with TGFβ2 may provide a novel tool to induce the differentiation of adult human mesenchymal stem cells for applications in cartilage tissue engineering.

  19. Combination of negative pressure wound therapy with open bone grafting for bone and soft tissue defects.

    PubMed

    Deng, Kai; Yu, Ai-Xi; Xia, Cheng-Yan; Li, Zong-Huan; Wang, Wei-Yang

    2013-08-01

    The aim of this study was to investigate the efficiency of negative pressure wound therapy (NPWT) combined with open bone graft (OBG; NPWT-OBG) for the treatment of bone and soft tissue defects with polluted wounds in an animal model. All rabbits with bone and soft tissue defects and polluted wounds were randomly divided into two groups, the experimental group (NPWT with bone graft) and the control group (OBG). The efficacy of the treatment was assessed by the wound conditions and healing time. Bacterial bioburdens and bony calluses were evaluated by bacteria counting and X-rays, respectively. Furthermore, granulation tissue samples from the wounds on days 0, 3, 7 and 14 of healing were evaluated for blood vessels and vascular endothelial growth factor (VEGF) levels. Wounds in the experimental group tended to have a shorter healing time, healthier wound conditions, lower bacterial bioburden, improvement of the bony calluses and an increased blood supply compared with those in the control group. With NPWT, wound infection was effectively controlled. For wounds with osseous and soft tissue defects, NPWT combined with bone grafting was demonstrated to be more effective than an OBG.

  20. Combined chelation therapy in reducing tissue lead concentrations in suckling rats.

    PubMed

    Kostial, K; Blanusa, M; Piasek, M; Restek-Samarzija, N; Jones, M M; Singh, P K

    1999-01-01

    The very young are more prone to lead poisoning than adults, and the treatment with chelating agents, either as monotherapy or combined treatment, is still a matter of dispute. The purpose of this work was to evaluate the efficiency of three chelating agents administered either as monotherapies or as combined treatments in sucklings. Lead acetate (5 mg Pb kg(-1) i.p.) was administered to the 7-day-old rat pups in eight litters on experimental day 1 and chelating agents on experimental days 2 and 3. Pups were divided into six groups: (1) untreated control; (2) EDTA (calcium disodium ethylendiaminetetraacetate, 0.3 mmol kg(-1) i.p. at 4 p.m.); (3) meso-DMSA (meso-2,3-dimeracaptosuccinic acid, 0.5 mmol kg(-1) p.o. at 10 a.m.); (4) rac-DMSA (racemic-2,3-dimeracaptosuccinic acid, 0.5 mmol kg(-1) p.o. at 10 a.m.); (5) EDTA+meso-DMSA; and (6) EDTA+rac-DMSA. Rats were killed on experimental day 5. Tissue element concentrations were analyzed by atomic absorption spectrometry. Treatment with EDTA did not affect tissue Pb, but it reduced Zn in the carcass and liver. Meso-DMSA reduced Pb in the kidneys and brain, and it did not affect organ essential elements. Rac-DMSA most efficiently reduced Pb concentrations in the carcass, kidneys and brain, but it also reduced Zn and Cu in the liver and Zn in the kidneys. Combined treatments with EDTA never improved the efficiency of either DMSA isoform in decreasing tissue Pb but they did reduce tissue Zn concentrations. All treatments caused the same decrease in the carcass Ca concentrations. The results do not support combined treatment in this age group, which is especially sensitive to trace element deficiencies, and suggest that meso-DMSA might be the treatment of choice in acute lead poisoning in infants.

  1. Multimodal fiber probe spectroscopy for tissue diagnostics applications: a combined Raman-fluorescence approach

    NASA Astrophysics Data System (ADS)

    Cicchi, Riccardo; Anand, Suresh; Rossari, Susanna; Sturiale, Alessandro; Giordano, Flavio; De Giorgi, Vincenzo; Maio, Vincenza; Massi, Daniela; Nesi, Gabriella; Buccoliero, Anna Maria; Tonelli, Francesco; Guerrini, Renzo; Pimpinelli, Nicola; Pavone, Francesco S.

    2014-03-01

    Two different optical fiber probes for combined Raman and fluorescence spectroscopic measurements were designed, developed and used for tissue diagnostics. Two visible laser diodes were used for fluorescence spectroscopy, whereas a laser diode emitting in the NIR was used for Raman spectroscopy. The two probes were based on fiber bundles with a central multimode optical fiber, used for delivering light to the tissue, and 24 surrounding optical fibers for signal collection. Both fluorescence and Raman spectra were acquired using the same detection unit, based on a cooled CCD camera, connected to a spectrograph. The two probes were successfully employed for diagnosing melanocytic lesions in a good agreement with common routine histology. The obtained results demonstrated that the multimodal approach is crucial for improving diagnostic capabilities. Further investigations were performed on colon and brain tissue samples in order to have a benchmark for diagnosing a broader range of tissue lesions and malignancies. The system presented here can improve diagnostic capabilities on a broad range of tissues and has the potential of being used for endoscopic inspections in the near future.

  2. Variable Combinations of Specific Ephrin Ligand/Eph Receptor Pairs Control Embryonic Tissue Separation

    PubMed Central

    Rohani, Nazanin; Parmeggiani, Andrea; Winklbauer, Rudolf; Fagotto, François

    2014-01-01

    Ephrins and Eph receptors are involved in the establishment of vertebrate tissue boundaries. The complexity of the system is puzzling, however in many instances, tissues express multiple ephrins and Ephs on both sides of the boundary, a situation that should in principle cause repulsion between cells within each tissue. Although co-expression of ephrins and Eph receptors is widespread in embryonic tissues, neurons, and cancer cells, it is still unresolved how the respective signals are integrated into a coherent output. We present a simple explanation for the confinement of repulsion to the tissue interface: Using the dorsal ectoderm–mesoderm boundary of the Xenopus embryo as a model, we identify selective functional interactions between ephrin–Eph pairs that are expressed in partial complementary patterns. The combined repulsive signals add up to be strongest across the boundary, where they reach sufficient intensity to trigger cell detachments. The process can be largely explained using a simple model based exclusively on relative ephrin and Eph concentrations and binding affinities. We generalize these findings for the ventral ectoderm–mesoderm boundary and the notochord boundary, both of which appear to function on the same principles. These results provide a paradigm for how developmental systems may integrate multiple cues to generate discrete local outcomes. PMID:25247423

  3. Characterization of atherosclerotic arterial tissue using combined SHG and FLIM microscopy

    NASA Astrophysics Data System (ADS)

    Cicchi, Riccardo; Baria, Enrico; Matthäus, Christian; Lange, Marta; Lattermann, Annika; Brehm, Bernhard R.; Popp, Jürgen; Pavone, Francesco S.

    2015-07-01

    Atherosclerosis is among the most widespread cardiovascular diseases and one of the leading cause of death in the Western World. Characterization of arterial tissue in atherosclerotic condition is extremely interesting from the diagnostic point of view, especially for what is concerning collagen content and organization because collagen plays a crucial role in plaque vulnerability. Routinely used diagnostic methods, such as histopathological examination, are limited to morphological analysis of the examined tissues, whereas an exhaustive characterization requires immunehistochemical examination and a morpho-functional approach. Non-linear microscopy techniques offer the potential for providing morpho-functional information on the examined tissues in a label-free way. In this study, we employed combined SHG and FLIM microscopy for characterizing collagen organization in both normal arterial wall and within atherosclerotic plaques. Image pattern analysis of SHG images allowed characterizing collagen organization in different tissue regions. In addition, the analysis of collagen fluorescence decay contributed to the characterization of the samples based on collagen fluorescence lifetime. Different values of collagen fiber mean size, collagen distribution, and collagen anisotropy and collagen fluorescence lifetime were found in normal arterial wall and within plaque depositions, prospectively allowing for automated classification of atherosclerotic lesions and plaque vulnerability. The presented method represents a promising diagnostic tool for evaluating atherosclerotic tissue and has the potential to find a stable place in clinical setting as well as to be applied in vivo in the near future.

  4. Non-linear imaging and characterization of atherosclerotic arterial tissue using combined SHG and FLIM microscopy

    NASA Astrophysics Data System (ADS)

    Cicchi, Riccardo; Matthäus, Christian; Meyer, Tobias; Lattermann, Annika; Dietzek, Benjamin; Brehm, Bernhard R.; Popp, Jürgen; Pavone, Francesco S.

    2015-03-01

    Atherosclerosis is among the most widespread cardiovascular diseases and one of the leading cause of death in the Western World. Characterization of arterial tissue in atherosclerotic condition is extremely interesting from the diagnostic point of view, especially for what is concerning collagen content and organization because collagen plays a crucial role in plaque vulnerability. Routinely used diagnostic methods, such as histopathological examination, are limited to morphological analysis of the examined tissues, whereas an exhaustive characterization requires immune-histochemical examination and a morpho-functional approach. Non-linear microscopy techniques offer the potential for providing morpho-functional information on the examined tissues in a label-free way. In this study, we employed combined SHG and FLIM microscopy for characterizing collagen organization in both normal arterial wall and within atherosclerotic plaques. Image pattern analysis of SHG images allowed characterizing collagen organization in different tissue regions. In addition, the analysis of collagen fluorescence decay contributed to the characterization of the samples on the basis of collagen fluorescence lifetime. Different values of collagen fiber mean size, collagen distribution, collagen anisotropy and collagen fluorescence lifetime were found in normal arterial wall and within plaque depositions, prospectively allowing for automated classification of atherosclerotic lesions and plaque vulnerability. The presented method represents a promising diagnostic tool for evaluating atherosclerotic tissue and has the potential to find a stable place in clinical setting as well as to be applied in vivo in the near future.

  5. Data-driven Model-based Combined Magnetic and Kinetic Control on DIII-D

    NASA Astrophysics Data System (ADS)

    Shi, W.; Wehner, W.; Barton, J. E.; Boyer, M. D.; Schuster, E.; Moreau, D.; Walker, M. L.; Ferron, J. R.

    2012-10-01

    In order to take into account the coupling between the different magnetic and kinetic parameters, a multi-input-multi-output (MIMO) model-based controller is introduced to regulate the rotational transform profile and βN in DIII-D. This approach is based on a linear two-time-scale model derived from experimental data. A singular value decomposition of the plasma model is carried out to decouple the system and identify the most relevant control channels. Then, a robust-control technique is used to determine a controller that minimizes the reference tracking error and rejects external disturbances with minimal control energy. Finally, the feedback controller is augmented with an anti-windup compensator, which keeps the given controller well behaved in the presence of actuator saturation. Experimental results illustrate the performance of the proposed controller, which is one of the first plasma profile controllers integrating magnetic and kinetic variables implemented in DIII-D.

  6. Laser microbeam - kinetic studies combined with molecule - structures reveal mechanisms of DNA repair

    NASA Astrophysics Data System (ADS)

    Altenberg, B.; Greulich, K. O.

    2011-10-01

    Kinetic studies on double strand DNA damages induced by a laser microbeam have allowed a precise definition of the temporal order of recruitment of repair molecules. The order is KU70 / KU80 - XRCC4 --NBS1 -- RAD51. These kinetic studies are now complemented by studies on molecular structures of the repair proteins, using the program YASARA which does not only give molecular structures but also physicochemical details on forces involved in binding processes. It turns out that the earliest of these repair proteins, the KU70 / KU80 heterodimer, has a hole with high DNA affinity. The next molecule, XRCC4, has a body with two arms, the latter with extremely high DNA affinity at their ends and a binding site for Ligase 4. Together with the laser microbeam results this provides a detailed view on the early steps of DNA double strand break repair. The sequence of DNA repair events is presented as a movie.

  7. A kinetic-allometric approach to predicting tissue radionuclide concentrations for biota

    SciTech Connect

    Higley, K. A.; Domotor, S. L.; Antonio, E. J.

    2003-01-01

    Allometry, or the biology of scaling, is the study of size and its consequences. It has become a useful tool for comparative phsiology. There are several allometric equations that relate body size to many parameters, including ingestion rate, lifespan, inhalation rate, home range and more. While these equations were originally derived from empirical observations, there is a growing body of evidence that these relationships have their origins in the dynamics of energy transport mechanisms. As part of an ongoing effort to assist the Department of Energy in developing generic methods for evaluating radiation dose to biota, we have examined the utility of applyig allometric techniques to predicting radionuclide tissue concentration across a large range of terrestrial and riparian species of animals. This particular study examined twenty-three elements. Initial investigations suggest that the allometric approach can provide a useful tool to derive limiting values of uptake and elimination factors for biota.

  8. Histomonas meleagridis in turkeys: dissemination kinetics in host tissues after cloacal infection.

    PubMed

    Huber, K; Reynaud, M C; Callait, M P; Zenner, L

    2006-06-01

    Histomonas meleagridis is a flagellated protozoa causing histomoniasis, a disease of gallinaceous fowl. This disease is characterized by necrotic typhlitis, hepatitis, and high mortality, especially in turkeys. In an attempt to detect the progression of H. meleagridis in the turkey, birds were infected via the cloaca. Between d 0 and 19, a group of 4 turkeys was killed and autopsied every 3 d. Cecal and hepatic lesion scores were used to measure severity of infection. For each turkey, 15 tissue samples were taken. Another group of 3 infected turkeys were placed separately, and samples of cecal and intestinal stool were collected every 3 d. Samples were analyzed by PCR. For samples of cecal droppings, cecum, cecal content, rectum, proventriculus, and bursa of Fabricius, the number of birds detected as positive by PCR followed the evolution of the lesion scores. Within the liver, the parasite DNA was detected only in some severe lesions. The parasite DNA was also detected in duodenum, jejuno-ileum, spleen, heart, lungs, and brain samples. The parasite DNA was not detected in the blood, kidneys, pancreas, or muscle of the thigh. Results of the PCR were in agreement with the evolution of the clinical signs and of the cecal and liver lesions.

  9. Effects of inhibition of. beta. -oxidation on tissue kinetics of C-11 palmitate in normal myocardium

    SciTech Connect

    Wijns, W.; Schwaiger, M.; Huang, S.C.; Selin, C.; Grover-McKay, M.; Hansen, H.; Phelps, M.; Schelbert, H.R.

    1985-05-01

    C-11 palmitate (CPA) clears from myocardium biexponentially. The late slow tissue clearance curve component is thought to represent tracer deposited in the endogenous lipid pool. The early rapid component is thought to be related to oxidation of CPA. The nature of the curve components can be clarified by specific inhibition of individual metabolic steps, e.g., ..beta..-oxidation. Therefore, 11 dogs were studied at control and again after inhibition of carnitine acyltransferase I with iv. tetradecylglycidic acid (TDGA; 10 mg/kg). CPA was injected into the coronary circulation. Myocardial time activity curves (TAC) were analyzed by least square fitting. After TDGA, the late slow phase was unchanged (RS=32 +- 9%; T=336 +- 146 min) but the early rapid phase was reduced (RS=18 +- 8%; T=2.9 +- 1.4 min) while 50 +- 9% of extracted CPA diffused back (T=10.8 +- 3.6 sec). Thus, inhibition of ..beta..-oxidation shifted substrate usage from FFA to carbohydrates, had no effect on esterification of CPA but enhanced its back diffusion from myocardium. As discussed in this paper the decline of the early rapid phase indicates its relationship to CPA oxidation.

  10. The influence of dietary Cu and diabetes on tissue sup 67 Cu retention kinetics in rats

    SciTech Connect

    Uriu-Hare, J.Y.; Rucker, R.B.; Keen, C.L. )

    1991-03-11

    Compared to controls, diabetes results in higher plasma, liver and kidney Cu concentrations. Since alterations in Cu metabolism may be associated with diabetic pathology, the authors investigated how Cu metabolism is affected by diabetes and dietary Cu intake. Nondiabetic and STZ diabetic rats were fed Cu suppl. or Cu def. diets for 5 wks. Rats were intubated with 28 {mu}Ci {sup 67}Cu and killed after 8, 16, 24, 32, 64, or 128 h. There were marked effects of both diet and diabetes on {sup 67}Cu metabolism. Independent of diabetes, deficient rats had a higher % of retained {sup 67}Cu, in liver, plasma, RBC, muscle, spleen, brain, lung, uterus, and intestine than adequate Cu rats. Independent of dietary Cu, diabetic rats had a lower % of retained {sup 67}Cu in liver, plasma, RBC, muscle, spleen, lung, bone, pancreas, skin, uterus and heart than controls. Differential effects were noted for kidney; adequate Cu diabetic rats had a higher % of retained {sup 67}Cu than all other groups. Marked effects of both diet and diabetes were evident when tissue Cu turnover was examined. Compared to Cu suppl. rats, Cu def. rats had a slower turnover of {sup 67}Cu, in liver, plasma, intestine, pancreas, eye, brain, muscle, spleen, lung and heart. Diabetic rats had a slower turnover of {sup 67}Cu than nondiabetic rats in liver, plasma, intestine, pancreas, eye, kidney, RBC and uterus. The data imply that a focus on Cu metabolism with regard to cellular Cu trafficking and pathology may be warranted.

  11. Effect of Basic Residue on the Kinetics of Peptide Fragmentation Examined Using Surface-Induced Dissociation Combined with Resonant Ejection

    SciTech Connect

    Laskin, Julia

    2015-11-30

    In this work, resonant ejection coupled with surface-induced dissociation (SID) in a Fourier transform ion cyclotron resonance mass spectrometer is used to examine fragmentation kinetics of two singly protonated hexapeptides, RYGGFL and KYGGFL, containing the basic arginine residue and less basic lysine residue at the N-terminus. The kinetics of individual reaction channels at different collision energies are probed by applying a short ejection pulse (1 ms) in resonance with the cyclotron frequency of a selected fragment ion and varying the delay time between ion-surface collision and resonant ejection while keeping total reaction delay time constant. Rice-Ramsperger-Kassel-Marcus (RRKM) modeling of the experimental data provides accurate threshold energies and activation entropies of individual reaction channels. Substitution of arginine with less basic lysine has a pronounced effect on the observed fragmentation kinetics of several pathways, including the b2 ion formation, but has little or no effect on formation of the b5+H2O fragment ion. The combination of resonant ejection SID, time- and collision energy-resolved SID, and RRKM modeling of both types of experimental data provides a detailed mechanistic understanding of the primary dissociation pathways of complex gaseous ions.

  12. Effects of tacrolimus and nifedipine, alone or in combination, on gingival tissues.

    PubMed

    Pamuk, Ferda; Cetinkaya, Burcu Ozkan; Gulbahar, Mustafa Yavuz; Gacar, Ayhan; Keles, Gonca Cayır; Erisgin, Zuleyha; Arik, Nurol

    2013-11-01

    The aim of this study is to compare gingival changes induced by short- and long-term tacrolimus and nifedipine administration, alone or in combination, and evaluate the expression levels of tumor suppressor phosphatase and tensin homolog (PTEN) in drug-induced gingival overgrowth. Eighty rats were equally divided into eight groups: 1) tacrolimus for 8 weeks; 2) nifedipine for 8 weeks; 3) tacrolimus and nifedipine for 8 weeks; 4) 8-week control; 5) tacrolimus for 24 weeks; 6) nifedipine for 24 weeks; 7) tacrolimus and nifedipine for 24 weeks; and 8) 24-week control. Histomorphometric analyses included measurements of epithelial thickness, connective tissue thickness, and height. Stereologic analyses included measurements of volumetric densities of fibroblasts (Vf), collagen fibers (Vcf), and blood vessels (Vbv). In addition, PTEN expression was analyzed using immunohistochemistry. Epithelial thickness and connective tissue thickness were significantly increased in groups 5, 6, and 7 compared to group 8 (P <0.05), whereas connective tissue height was significantly increased in groups 5 and 7 (P <0.001). Vf and Vcf were significantly increased in group 7 compared to group 8 (P <0.001). PTEN immunoreactivity was significantly decreased in all experimental groups compared to the control groups (P <0.05). Results suggest that duration of drug administration is a more important risk factor than drug combination. The results include a potentially new insight about PTEN's role in the etiology of drug-induced gingival overgrowth.

  13. A Combination of Radiosurgery and Soluble Tissue Factor Enhances Vascular Targeting for Experimental Glioblastoma

    PubMed Central

    Hu, Zhiqiang

    2013-01-01

    Radiosurgery for glioblastoma is limited to the development of resistance, allowing tumor cells to survive and initiate tumor recurrence. Based on our previous work that coadministration of tissue factor and lipopolysaccharide following radiosurgery selectively induced thrombosis in cerebral arteriovenous malformations, achieving thrombosis of 69% of the capillaries and 39% of medium sized vessels, we hypothesized that a rapid and selective shutdown of the capillaries in glioblastoma vasculature would decrease the delivery of oxygen and nutrients, reducing tumor growth, preventing intracranial hypertension, and improving life expectancy. Glioblastoma was formed by implantation of GL261 cells into C57Bl/6 mouse brain. Mice were intravenously injected tissue factor, lipopolysaccharide, a combination of both, or placebo 24 hours after radiosurgery. Control mice received both agents after sham irradiation. Coadministration of tissue factor and lipopolysaccharide led to the formation of thrombi in up to 87 ± 8% of the capillaries and 46 ± 4% of medium sized vessels within glioblastoma. The survival rate of mice in this group was 80% versus no survivor in placebo controls 30 days after irradiation. Animal body weight increased with time in this group (r = 0.88, P = 0.0001). Thus, radiosurgery enhanced treatment with tissue factor, and lipopolysaccharide selectively induces thrombosis in glioblastoma vasculature, improving life expectancy. PMID:24307995

  14. A computer program for enzyme kinetics that combines model discrimination, parameter refinement and sequential experimental design.

    PubMed Central

    Franco, R; Gavaldà, M T; Canela, E I

    1986-01-01

    A method of model discrimination and parameter estimation in enzyme kinetics is proposed. The experimental design and analysis of the model are carried out simultaneously and the stopping rule for experimentation is deduced by the experimenter when the probabilities a posteriori indicate that one model is clearly superior to the rest. A FORTRAN77 program specifically developed for joint designs is given. The method is very powerful, as indicated by its usefulness in the discrimination between models. For example, it has been successfully applied to three cases of enzyme kinetics (a single-substrate Michaelian reaction with product inhibition, a single-substrate complex reaction and a two-substrate reaction). By using this method the most probable model and the estimates of the parameters can be obtained in one experimental session. The FORTRAN77 program is deposited as Supplementary Publication SUP 50134 (19 pages) at the British Library (Lending Division), Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1986) 233, 5. PMID:3800965

  15. Enhanced laser tissue soldering using indocyanine green chromophore and gold nanoshells combination.

    PubMed

    Khosroshahi, Mohammad E; Nourbakhsh, Mohammad S

    2011-08-01

    Gold nanoshells (GNs) are new materials that have an optical response dictated by the plasmon resonance. The wavelength at which the resonance occurs depends on the core and shell sizes. The purposes of this study were to use the combination of indocyanine green (ICG) and different concentration of gold nanoshells for skin tissue soldering and also to examine the effect of laser soldering parameters on the properties of repaired skin. Two mixtures of albumin solder and different combinations of ICG and gold nanoshells were prepared. A full thickness incision of 2 × 20 mm(2) was made on the surface and after addition of mixtures it was irradiated by an 810 nm diode laser at different power densities. The changes of tensile strength (σ(t)) due to temperature rise, number of scan (Ns), and scan velocity (Vs) were investigated. The results showed at constant laser power density (I), σ(t) of repaired incisions increases by increasing the concentration of gold nanoshells in solder, Ns, and decreasing Vs. It was demonstrated that laser soldering using combination of ICG + GNs could be practical provided the optothermal properties of the tissue are carefully optimized. Also, the tensile strength of soldered skin is higher than skins that soldered with only ICG or GNs. In our case, this corresponds to σ(t) = 1800 g cm(-2) at I ∼ 47 Wcm(-2), T ∼ 85 [ordinal indicator, masculine]C, Ns = 10, and Vs = 0.3 mms(-1).

  16. Enhanced laser tissue soldering using indocyanine green chromophore and gold nanoshells combination

    NASA Astrophysics Data System (ADS)

    Khosroshahi, Mohammad E.; Nourbakhsh, Mohammad S.

    2011-08-01

    Gold nanoshells (GNs) are new materials that have an optical response dictated by the plasmon resonance. The wavelength at which the resonance occurs depends on the core and shell sizes. The purposes of this study were to use the combination of indocyanine green (ICG) and different concentration of gold nanoshells for skin tissue soldering and also to examine the effect of laser soldering parameters on the properties of repaired skin. Two mixtures of albumin solder and different combinations of ICG and gold nanoshells were prepared. A full thickness incision of 2 × 20 mm2 was made on the surface and after addition of mixtures it was irradiated by an 810 nm diode laser at different power densities. The changes of tensile strength (σt) due to temperature rise, number of scan (Ns), and scan velocity (Vs) were investigated. The results showed at constant laser power density (I), σt of repaired incisions increases by increasing the concentration of gold nanoshells in solder, Ns, and decreasing Vs. It was demonstrated that laser soldering using combination of ICG + GNs could be practical provided the optothermal properties of the tissue are carefully optimized. Also, the tensile strength of soldered skin is higher than skins that soldered with only ICG or GNs. In our case, this corresponds to σt = 1800 g cm-2 at I ~ 47 Wcm-2, T ~ 85 ºC, Ns = 10, and Vs = 0.3 mms-1.

  17. Effectively Identifying eQTLs from Multiple Tissues by Combining Mixed Model and Meta-analytic Approaches

    PubMed Central

    Choi, Ted; Eskin, Eleazar

    2013-01-01

    Gene expression data, in conjunction with information on genetic variants, have enabled studies to identify expression quantitative trait loci (eQTLs) or polymorphic locations in the genome that are associated with expression levels. Moreover, recent technological developments and cost decreases have further enabled studies to collect expression data in multiple tissues. One advantage of multiple tissue datasets is that studies can combine results from different tissues to identify eQTLs more accurately than examining each tissue separately. The idea of aggregating results of multiple tissues is closely related to the idea of meta-analysis which aggregates results of multiple genome-wide association studies to improve the power to detect associations. In principle, meta-analysis methods can be used to combine results from multiple tissues. However, eQTLs may have effects in only a single tissue, in all tissues, or in a subset of tissues with possibly different effect sizes. This heterogeneity in terms of effects across multiple tissues presents a key challenge to detect eQTLs. In this paper, we develop a framework that leverages two popular meta-analysis methods that address effect size heterogeneity to detect eQTLs across multiple tissues. We show by using simulations and multiple tissue data from mouse that our approach detects many eQTLs undetected by traditional eQTL methods. Additionally, our method provides an interpretation framework that accurately predicts whether an eQTL has an effect in a particular tissue. PMID:23785294

  18. Effects of hydrostatic pressure/heat combinations on water uptake and gelatinization characteristics of japonica rice grains: a kinetic study.

    PubMed

    Huang, Shih-Li; Jao, Chia-Ling; Hsu, Kuo-Chiang

    2009-10-01

    The combination effects of pressure (200 to 500 MPa) and temperature (20, 40, and 50 degrees C) on the water uptake and gelatinization characteristics of japonica rice (Tainung 71) grains were investigated. Pressure greater than 200 MPa at all temperatures increased the moisture content and volume of rice grains; meanwhile, the increase content of rice grain volume showed a high correlation with that of moisture content (r(2)= 0.96). The highest degree of gelatinization of 73% was observed at 500 MPa and 50 degrees C for 120 min, while gelatinization did not occur at pressures below 300 MPa and temperatures of 20 and 40 degrees C. The rate of gelatinization followed the 1st-order kinetics at each temperature and pressure. The higher pressures and temperatures would result in higher values of rate constant k which could be correlated with both pressure and temperature by combining Arrhenius and Eyring models.

  19. Dynamic dual-energy chest radiography: a potential tool for lung tissue motion monitoring and kinetic study.

    PubMed

    Xu, Tong; Ducote, Justin L; Wong, Jerry T; Molloi, Sabee

    2011-02-21

    Dual-energy chest radiography has the potential to provide better diagnosis of lung disease by removing the bone signal from the image. Dynamic dual-energy radiography is now possible with the introduction of digital flat-panel detectors. The purpose of this study is to evaluate the feasibility of using dynamic dual-energy chest radiography for functional lung imaging and tumor motion assessment. The dual-energy system used in this study can acquire up to 15 frames of dual-energy images per second. A swine animal model was mechanically ventilated and imaged using the dual-energy system. Sequences of soft-tissue images were obtained using dual-energy subtraction. Time subtracted soft-tissue images were shown to be able to provide information on regional ventilation. Motion tracking of a lung anatomic feature (a branch of pulmonary artery) was performed based on an image cross-correlation algorithm. The tracking precision was found to be better than 1 mm. An adaptive correlation model was established between the above tracked motion and an external surrogate signal (temperature within the tracheal tube). This model is used to predict lung feature motion using the continuous surrogate signal and low frame rate dual-energy images (0.1-3.0 frames per second). The average RMS error of the prediction was (1.1 ± 0.3) mm. The dynamic dual energy was shown to be potentially useful for lung functional imaging such as regional ventilation and kinetic studies. It can also be used for lung tumor motion assessment and prediction during radiation therapy.

  20. Dynamic dual-energy chest radiography: a potential tool for lung tissue motion monitoring and kinetic study

    PubMed Central

    Xu, Tong; Ducote, Justin L.; Wong, Jerry T.; Molloi, Sabee

    2011-01-01

    Dual-energy chest radiography has the potential to provide better diagnosis of lung disease by removing the bone signal from the image. Dynamic dual-energy radiography is now possible with the introduction of digital flat panel detectors. The purpose of this study is to evaluate the feasibility of using dynamic dual-energy chest radiography for functional lung imaging and tumor motion assessment. The dual energy system used in this study can acquire up to 15 frame of dual-energy images per second. A swine animal model was mechanically ventilated and imaged using the dual-energy system. Sequences of soft-tissue images were obtained using dual-energy subtraction. Time subtracted soft-tissue images were shown to be able to provide information on regional ventilation. Motion tracking of a lung anatomic feature (a branch of pulmonary artery) was performed based on an image cross-correlation algorithm. The tracking precision was found to be better than 1 mm. An adaptive correlation model was established between the above tracked motion and an external surrogate signal (temperature within the tracheal tube). This model is used to predict lung feature motion using the continuous surrogate signal and low frame rate dual-energy images (0.1 to 3.0 frames /sec). The average RMS error of the prediction was (1.1 ± 0.3) mm. The dynamic dual-energy was shown to be potentially useful for lung functional imaging such as regional ventilation and kinetic studies. It can also be used for lung tumor motion assessment and prediction during radiation therapy. PMID:21285477

  1. Dynamic dual-energy chest radiography: a potential tool for lung tissue motion monitoring and kinetic study

    NASA Astrophysics Data System (ADS)

    Xu, Tong; Ducote, Justin L.; Wong, Jerry T.; Molloi, Sabee

    2011-02-01

    Dual-energy chest radiography has the potential to provide better diagnosis of lung disease by removing the bone signal from the image. Dynamic dual-energy radiography is now possible with the introduction of digital flat-panel detectors. The purpose of this study is to evaluate the feasibility of using dynamic dual-energy chest radiography for functional lung imaging and tumor motion assessment. The dual-energy system used in this study can acquire up to 15 frames of dual-energy images per second. A swine animal model was mechanically ventilated and imaged using the dual-energy system. Sequences of soft-tissue images were obtained using dual-energy subtraction. Time subtracted soft-tissue images were shown to be able to provide information on regional ventilation. Motion tracking of a lung anatomic feature (a branch of pulmonary artery) was performed based on an image cross-correlation algorithm. The tracking precision was found to be better than 1 mm. An adaptive correlation model was established between the above tracked motion and an external surrogate signal (temperature within the tracheal tube). This model is used to predict lung feature motion using the continuous surrogate signal and low frame rate dual-energy images (0.1-3.0 frames per second). The average RMS error of the prediction was (1.1 ± 0.3) mm. The dynamic dual energy was shown to be potentially useful for lung functional imaging such as regional ventilation and kinetic studies. It can also be used for lung tumor motion assessment and prediction during radiation therapy.

  2. Combined Yamamoto approach for simultaneous estimation of adsorption isotherm and kinetic parameters in ion-exchange chromatography.

    PubMed

    Rüdt, Matthias; Gillet, Florian; Heege, Stefanie; Hitzler, Julian; Kalbfuss, Bernd; Guélat, Bertrand

    2015-09-25

    Application of model-based design is appealing to support the development of protein chromatography in the biopharmaceutical industry. However, the required efforts for parameter estimation are frequently perceived as time-consuming and expensive. In order to speed-up this work, a new parameter estimation approach for modelling ion-exchange chromatography in linear conditions was developed. It aims at reducing the time and protein demand for the model calibration. The method combines the estimation of kinetic and thermodynamic parameters based on the simultaneous variation of the gradient slope and the residence time in a set of five linear gradient elutions. The parameters are estimated from a Yamamoto plot and a gradient-adjusted Van Deemter plot. The combined approach increases the information extracted per experiment compared to the individual methods. As a proof of concept, the combined approach was successfully applied for a monoclonal antibody on a cation-exchanger and for a Fc-fusion protein on an anion-exchange resin. The individual parameter estimations for the mAb confirmed that the new approach maintained the accuracy of the usual Yamamoto and Van Deemter plots. In the second case, offline size-exclusion chromatography was performed in order to estimate the thermodynamic parameters of an impurity (high molecular weight species) simultaneously with the main product. Finally, the parameters obtained from the combined approach were used in a lumped kinetic model to simulate the chromatography runs. The simulated chromatograms obtained for a wide range of gradient lengths and residence times showed only small deviations compared to the experimental data. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. [Kinetics of in vitro bactericidal activity of the antiseptic biseptine combining 3 active principles].

    PubMed

    Reverdy, M E; Rougier, M; Fleurette, J

    1996-09-01

    Biseptine, is an association of chlorhexidine digluconate, benzalkonium chloride and benzylic alcohol. Little is known, in literature, on this antiseptic, used for cutaneous antisepsis. We studied killing kinetic of Biseptine, at different concentrations, on 4 AFNOR bacterial strains. Killing curves were studied at antiseptic concentration of 90 to 0.1% in 10 ml of distilled water. Bacterial counts were determined after neutralization in liquid medium. Synergy of chlorhexidine and benzalkonium chloride in Biseptine, allowed to obtain similar bactericidal activity than Hibitane champ with chlorhexidine concentrations 2 fold less. At 90, 50, 25, 10 and 5% concentrations, bactericidal activity (5 log10 reduction of the initial bacterial count) was effective in one minute. After 5 to 15 minutes, activity persisted at 1 and 0.5% concentrations. The 0.1% solution was inefficacious. This report disclosed an important security margin in antiseptic activity.

  4. New bipolar tissue ligator combines constant tissue compression and temperature guidance: histologic study and implications for treatment of hemorrhoids

    PubMed Central

    Piskun, Gregory; Tucker, Robert

    2012-01-01

    Background Several minimally invasive technologies are available to treat common soft tissue lesions including symptomatic hemorrhoids. The use of energy to deliver heat and coagulate target lesions is commonly practiced. This study compares the histologic effects produced on intestinal tissues by two energy-based systems which employ different approaches of heat delivery. Methods Two heat delivery systems were evaluated in vivo in a single porcine subject: infrared coagulator and bipolar tissue ligator utilizing constant tissue compression and temperature guidance. Eighteen treatment sites divided into three groups of six were assessed. Treatment site temperature was measured and the effects of thermal treatment in the mucosa, submucosa, submucosal vessels, and muscularis layer were scored. Lateral thermal spread beyond the energy application site was also assessed. Results Treatment site temperatures were much lower in the bipolar ligator group than in the infrared coagulator group. The mucosal and submucosal tissue changes observed in tissues treated with infrared energy and bipolar energy at 55°C were similar. Both the mucosal and submucosal tissue changes with bipolar energy at 50°C were significantly less. Conclusion Both devices achieved similar histologic results. However, the unique design of the bipolar ligator, which allows consistent capture, constant compression, and temperature monitoring of target tissue, accomplished the desired histologic changes with less muscular damage at much lower temperatures than the infrared coagulator. The use of bipolar ligation could offer clinical advantages such as reduced patient pain and a minimized chance of heat-related collateral tissue damage. PMID:23152714

  5. A tetracycline expression system in combination with Sox9 for cartilage tissue engineering.

    PubMed

    Yao, Yi; He, Yu; Guan, Qian; Wu, Qiong

    2014-02-01

    Cartilage tissue engineering using controllable transcriptional therapy together with synthetic biopolymer scaffolds shows higher potential for overcoming chondrocyte degradation and constructing artificial cartilages both in vivo and in vitro. Here, the potential regulating tetracycline expression (Tet-on) system was used to express Sox9 both in vivo and in vitro. Chondrocyte degradation was measured in vitro and overcome by Soxf9 expression. Experiments confirmed the feasibility of the combined use of Sox9 and Tet-on system in cartilage tissue engineering. Engineered poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) scaffolds were seeded with recombinant chondrocytes which were transfected with Tet-induced Sox9 expression; the scaffolds were implanted under the skin of 8-week-old rats. The experimental group was injected with Dox in the abdomen, while the control group was injected with normal saline. After 4 or 8 days of implantation in vivo, the newly formed pieces of articular chondrocytes were taken out and measured. Dox injection in vivo showed positive effect on recombinant chondrocytes, in which Sox9 expression was up-regulated by an inducible system with specific matrix proteins. The results demonstrate this controllable transcriptional therapy is a potential approach for tissue engineering. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Combining extreme learning machines using support vector machines for breast tissue classification.

    PubMed

    Daliri, Mohammad Reza

    2015-01-01

    In this paper, we present a new approach for breast tissue classification using the features derived from electrical impedance spectroscopy. This method is composed of a feature extraction method, feature selection phase and a classification step. The feature extraction phase derives the features from the electrical impedance spectra. The extracted features consist of the impedivity at zero frequency (I0), the phase angle at 500 KHz, the high-frequency slope of phase angle, the impedance distance between spectral ends, the area under spectrum, the normalised area, the maximum of the spectrum, the distance between impedivity at I0 and the real part of the maximum frequency point and the length of the spectral curve. The system uses the information theoretic criterion as a strategy for feature selection and the combining extreme learning machines (ELMs) for the classification phase. The results of several ELMs are combined using the support vector machines classifier, and the result of classification is reported as a measure of the performance of the system. The results indicate that the proposed system achieves high accuracy in classification of breast tissues using the electrical impedance spectroscopy.

  7. A combined tactile and Raman probe for tissue characterization—design considerations

    NASA Astrophysics Data System (ADS)

    Nyberg, Morgan; Candefjord, Stefan; Jalkanen, Ville; Ramser, Kerstin; Lindahl, Olof A.

    2012-06-01

    Histopathology is the golden standard for cancer diagnosis and involves the characterization of tissue components. It is labour intensive and time consuming. We have earlier proposed a combined fibre-optic near-infrared Raman spectroscopy (NIR-RS) and tactile resonance method (TRM) probe for detecting positive surgical margins as a complement to interoperative histopathology. The aims of this study were to investigate the effects of attaching an RS probe inside a cylindrical TRM sensor and to investigate how laser-induced heating of the fibre-optic NIR-RS affected the temperature of the RS probe tip and an encasing TRM sensor. In addition, the possibility to perform fibre-optic NIR-RS in a well-lit environment was investigated. A small amount of rubber latex was preferable for attaching the thin RS probe inside the TRM sensor. The temperature rise of the TRM sensor due to a fibre-optic NIR-RS at 270 mW during 20 s was less than 2 °C. Fibre-optic NIR-RS was feasible in a dimmed bright environment using a small light shield and automatic subtraction of a pre-recorded contaminant spectrum. The results are promising for a combined probe for tissue characterization.

  8. Combined modalities approach for localized adult extremity soft-tissue sarcoma.

    PubMed

    Gronchi, Alessandro; Olmi, Patrizia; Casali, Paolo Giovanni

    2007-08-01

    Extremity soft-tissue sarcomas are a heterogeneous group of rare neoplasms, characterized by a broad spectrum of biological aggressiveness and a uniform tendency for local failure if not adequately treated. Surgery is the mainstay of therapy, and the availability of multidisciplinary surgical skills allows adequate margins with acceptable morbidity to be obtained. Local therapies, such as radiation therapy or isolated limb perfusion, alone or in combination with systemic agents, may help to further improve local control, especially in difficult presentations. The possible impact of systemic treatment on survival is still a matter of debate, and the agents used so far have not provided a major breakthrough, even in selected populations at high risk of disease spread. Nevertheless, soft-tissue sarcomas are no longer considered a unique disease. More than 50 different histotypes can now be well recognized, with distinct biological and molecular characteristics, which lead to different clinical behavior and a potentially different sensitivity to targeted agents. Therefore, it is more essential than ever for treatment of these patients to be delivered in referral centers, where a dedicated multidisciplinary team is able to administer histology and clinically driven approaches. The employment of combined modalities will be able to maximize the chance of local cure even in difficult presentations, and possibly improve survival, especially in high-risk disease.

  9. Adipose-derived stem cells combined with neuregulin-1 delivery systems for heart tissue engineering.

    PubMed

    Díaz-Herráez, P; Garbayo, E; Simón-Yarza, T; Formiga, F R; Prosper, F; Blanco-Prieto, M J

    2013-09-01

    Myocardial infarction (MI) is the leading cause of death worldwide, and extensive research has therefore been performed to find a cure. Neuregulin-1 (NRG) is a growth factor involved in cardiac repair after MI. We previously described how biocompatible and biodegradable microparticles, which are able to release NRG in a sustained manner, represent a valuable approach to avoid problems related to the short half-life after systemic administration of proteins. The effectiveness of this strategy could be improved by combining NRG with several cytokines involved in cardiac regeneration. The present study investigates the potential feasibility of using NRG-releasing particle scaffold combined with adipose-derived stem cells (ADSC) as a multiple growth factor delivery-based tissue engineering strategy for implantation in the infarcted myocardium. NRG-releasing particle scaffolds with a suitable size for intramyocardial implantation were prepared by TROMS. Next, ADSC were adhered to particle scaffolds and their potential for heart administration was assessed in a MI rat model. NRG was successfully encapsulated reaching encapsulation efficiencies of 92.58 ± 3.84%. NRG maintained its biological activity after the microencapsulation process. ADSCs adhered efficiently to particle scaffolds within a few hours. The ADSC-cytokine delivery system developed proved to be compatible with intramyocardial administration in terms of injectability through a 23-gauge needle and tissue response. Interestingly, ADSC-scaffolds were present in the peri-infarted tissue 2 weeks after implantation. This proof of concept study provides important evidence required for future effectiveness studies and for the translation of this approach.

  10. Multimodal classification of prostate tissue: a feasibility study on combining multiparametric MRI and ultrasound

    NASA Astrophysics Data System (ADS)

    Ashab, Hussam Al-Deen; Haq, Nandinee Fariah; Nir, Guy; Kozlowski, Piotr; Black, Peter; Jones, Edward C.; Goldenberg, S. Larry; Salcudean, Septimiu E.; Moradi, Mehdi

    2015-03-01

    The common practice for biopsy guidance is through transrectal ultrasound, with the fusion of ultrasound and MRI-based targets when available. However, ultrasound is only used as a guidance modality in MR-targeted ultrasound-guided biopsy, even though previous work has shown the potential utility of ultrasound, particularly ultrasound vibro-elastography, as a tissue typing approach. We argue that multiparametric ultrasound, which includes B-mode and vibro-elastography images, could contain information that is not captured using multiparametric MRI (mpMRI) and therefore play a role in refining the biopsy and treatment strategies. In this work, we combine mpMRI with multiparametric ultrasound features from registered tissue areas to examine the potential improvement in cancer detection. All the images were acquired prior to radical prostatectomy and cancer detection was validated based on 36 whole mount histology slides. We calculated a set of 24 texture features from vibro-elastography and B-mode images, and five features from mpMRI. Then we used recursive feature elimination (RFE) and sparse regression through LASSO to find an optimal set of features to be used for tissue classification. We show that the set of these selected features increases the area under ROC curve from 0.87 with mpMRI alone to 0.94 with the selected mpMRI and multiparametric ultrasound features, when used with support vector machine classification on features extracted from peripheral zone. For features extracted from the whole-gland, the area under the curve was 0.75 and 0.82 for mpMRI and mpMRI along with ultrasound, respectively. These preliminary results provide evidence that ultrasound and ultrasound vibro-elastography could be used as modalities for improved cancer detection in combination with MRI.

  11. Combined in-situ dilatometer and contact angle studies of interfacial reaction kinetics in brazing.

    SciTech Connect

    Dave, V. R.; Javernick, D. A.; Thoma, D. J.; Cola, M. J.; Hollis, K. J.; Smith, F. M.; Dauelsberg, L. B.

    2001-01-01

    Multi-component dissimilar material braze joints as shown in Figure 1 consisting of dissimilar base materials, filler materials and wetting agents are of tantamount importance in a wide variely of applications. This work combines dilatometry and contact angle measurements to characterize in-situ the multiple interfacial reaction pathways that occur in such systems. Whereas both of these methods are commonly used tools in metallurgical investigation, their combined use within the context of brazing studies is new and offers considerable additional insight. Applications are discussed to joints made between Beryllium and Monel with TiH{sub 2} as the wetting agent and Cu-28%Ag as the filler material.

  12. Characterising human atherosclerotic carotid plaque tissue composition and morphology using combined spectroscopic and imaging modalities

    PubMed Central

    2015-01-01

    demonstrates the need to fully characterise the calcification structure of the plaque tissue and that a combination of FTIR and μX-CT provides the necessary information to fully understand the mechanical behaviour of the plaque tissue. PMID:25602176

  13. Combined micro-XRF and TXRF methodology for quantitative elemental imaging of tissue samples.

    PubMed

    Wróbel, Paweł M; Bała, Sławomir; Czyzycki, Mateusz; Golasik, Magdalena; Librowski, Tadeusz; Ostachowicz, Beata; Piekoszewski, Wojciech; Surówka, Artur; Lankosz, Marek

    2017-01-01

    Local differences in structural properties of biological specimens pose a major limitation to quantitative X-ray fluorescence imaging. This is because both the various tissue compartments of different density and variation in the sample thickness upon frequently used freeze-drying come up with the different values of the sample mass per unit area to be taken into account. Even though several solutions to tackle this problem based on the home-made standards for quantification in terms of thickness- and density-independent elemental mass fractions have been proposed, this issue is not addressed enough due to the samples' heterogeneity. In our recent study, we propose a calculation scheme based on combined external-standard micro X-ray fluorescence (micro-XRF) imaging and internal-standard total reflection X-ray fluorescence (TXRF) analysis to determine the corrected elemental mass fraction distributions in commonly analysed rat tissues: kidney, liver and spleen. The results of TXRF analysis of digested large tissue sections together with the mean values of elemental masses per unit area obtained with micro-XRF were employed to determine the average masses per unit area of the samples. The correction for variation of the tissue thickness and density was done through with the use of Compton intensities. Importantly, by its versatility, our novel approach can be used to produce elemental contrast in a variety of biological specimens where local variations in either the sample density or thickness are no longer the issue. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Investigation of alveolar tissue deformations using OCT combined with fluorescence microscopy

    NASA Astrophysics Data System (ADS)

    Gaertner, Maria; Cimalla, Peter; Knels, Lilla; Meissner, Sven; Schnabel, Christian; Kuebler, Wolfgang M.; Koch, Edmund

    2011-06-01

    In critical care medicine, artificial ventilation is a life saving tool providing sufficient blood oxygenation to patients suffering from respiratory failure. Essential for their survival is the use of protective ventilation strategies to prevent further lung damage due to ventilator induced lung injury (VILI). Since there is only little known about implications of lung tissue overdistension on the alveolar level, especially in the case of diseased lungs, this research deals with the investigation of lung tissue deformation on a microscale. A combined setup utilizing optical coherence tomography (OCT) and confocal fluorescence microscopy, is used to study the elastic behavior of the alveolar tissue. Three-dimensional geometrical information with voxel sizes of 6 μm × 6 μm × 11 μm (in air) is provided by OCT, structural information about localization of elastin fibers is elucidated via confocal fluorescence microscopy with a lateral resolution of around 1 μm. Imaging depths of 90 μm for OCT and 20 μm for confocal fluorescence microscopy were obtained. Dynamic studies of subpleural tissue were carried out on the basis of an in vivo mouse model post mortem, mimicking the physiological environment of an intact thorax and facilitating a window for the application of optical methods. Morphological changes were recorded by applying constant positive airway pressures of different values. With this, alveolar volume changes could clearly be recognized and quantified to form a compliance value of 3.5 • 10-6(see manuscript). The distribution of elastin fibers was detected and will be subject to further elasticity analysis.

  15. Combined Experimental and Theoretical Approach to the Kinetics of Magnetite Crystal Growth from Primary Particles

    PubMed Central

    2017-01-01

    It is now recognized that nucleation and growth of crystals can occur not only by the addition of solvated ions but also by accretion of nanoparticles, in a process called nonclassical crystallization. The theoretical framework of such processes has only started to be described, partly due to the lack of kinetic or thermodynamic data. Here, we study the growth of magnetite nanoparticles from primary particles—nanometer-sized amorphous iron-rich precursors—in aqueous solution at different temperatures. We propose a theoretical framework to describe the growth of the nanoparticles and model both a diffusion-limited and a reaction-limited pathway to determine which of these best describes the rate-limiting step of the process. We show that, based on the measured iron concentration and the related calculated concentration of primary particles at the steady state, magnetite growth is likely a reaction-limited process, and within the framework of our model, we propose a phase diagram to summarize the observations. PMID:28225626

  16. Combined ideal and kinetic effects on reversed shear Alfvén eigenmodes

    NASA Astrophysics Data System (ADS)

    Gorelenkov, N. N.; Kramer, G. J.; Nazikian, R.

    2011-10-01

    A reversed shear Alfvén eigenmodes (RSAEs) theory has been developed for reversed magnetic field shear plasmas when the safety factor minimum, q min , is at or above a rational value. The modes we study are known sometimes as either the bottom of the frequency sweep or the down sweeping RSAEs. We show that, strictly speaking, the ideal MHD theory is not compatible with the eigenmode solution in the reversed shear plasma with q min above integer values. Corrected by a special analytic finite Larmor radius (FLR) condition, MHD dispersion of these modes nevertheless can be developed. Numerically, MHD structure can serve as a good approximation for the RSAEs.The large radial scale part of the analytic RSAE solution can be obtained from ideal MHD and expressed in terms of the Legendre functions. The kinetic equation with FLR effects for the eigenmode is solved numerically and agrees with the analytic solutions. Properties of RSAEs and their potential implications for plasma diagnostics are discussed.

  17. A combined high-temperature experimental and theoretical kinetic study of the reaction of dimethyl carbonate with OH radicals.

    PubMed

    Khaled, Fethi; Giri, Binod Raj; Szőri, Milán; Mai, Tam V-T; Huynh, Lam K; Farooq, Aamir

    2017-03-08

    The reaction kinetics of dimethyl carbonate (DMC) and OH radicals were investigated behind reflected shock waves over the temperature range of 872-1295 K and at pressures near 1.5 atm. Reaction progress was monitored by detecting OH radicals at 306.69 nm using a UV laser absorption technique. The rate coefficients for the reaction of DMC with OH radicals were extracted using a detailed kinetic model developed by Glaude et al. (Proc. Combust. Inst. 2005, 30(1), 1111-1118). The experimental rate coefficients can be expressed in Arrhenius form as: kexpt'l = 5.15 × 10(13) exp(-2710.2/T) cm(3) mol(-1) s(-1). To explore the detailed chemistry of the DMC + OH reaction system, theoretical kinetic analyses were performed using high-level ab initio and master equation/Rice-Ramsperger-Kassel-Marcus (ME/RRKM) calculations. Geometry optimization and frequency calculations were carried out at the second-order Møller-Plesset (MP2) perturbation level of theory using Dunning's augmented correlation consistent-polarized valence double-ζ basis set (aug-cc-pVDZ). The energy was extrapolated to the complete basis set using single point calculations performed at the CCSD(T)/cc-pVXZ (where X = D, T) level of theory. For comparison purposes, additional ab initio calculations were also carried out using composite methods such as CBS-QB3, CBS-APNO, G3 and G4. Our calculations revealed that the H-abstraction reaction of DMC by OH radicals proceeds via an addition elimination mechanism in an overall exothermic process, eventually forming dimethyl carbonate radicals and H2O. Theoretical rate coefficients were found to be in excellent agreement with those determined experimentally. Rate coefficients for the DMC + OH reaction were combined with literature rate coefficients of four straight chain methyl ester + OH reactions to extract site-specific rates of H-abstraction from methyl esters by OH radicals.

  18. Combined Ab Initio, Kinetic Modeling, and Shock Tube Study of the Thermal Decomposition of Ethyl Formate.

    PubMed

    Ning, Hongbo; Wu, Junjun; Ma, Liuhao; Ren, Wei; Davidson, David F; Hanson, Ronald K

    2017-09-07

    The potential energy surfaces (PESs) and reaction rate constants of the unimolecular decomposition of ethyl formate (EF) were investigated using high-precision theoretical methods at the CCSD(T)/CBS(T-Q)//M06-2X/6-311++G(d,p) level of theory. The calculated PESs of EF dissociation and molecular decomposition reactions indicate that the intramolecular H-shift to produce formic acid and ethylene is the dominant decomposition pathway. A detailed chemical kinetic mechanism for EF pyrolysis was constructed by incorporating the important reactions of EF and its radicals into an existing mechanism previously developed for small methyl esters. The updated mechanism was first used to reproduce CO, CO2, and H2O concentration time histories during EF pyrolysis in the shock tube reported by Ren et al. [ Ren , W. , Mitchell Spearrin , R. , Davidson , D. F. , and Hanson , R. K. J. Phys. Chem. A 2014 , 118 , 1785 - 1798 ]. The rate of production and sensitivity analyses show that the competing dehydration and decarboxylation channels of the intermediate formic acid control the final product yields of EF pyrolysis. The EF mechanism was further validated against the shock tube data of OH, CO, CO2, and H2O time histories measured during EF oxidation (equivalence ratio Φ = 1.0) at 1331-1615 K and 1.52-1.74 atm. This revised EF mechanism captured all of the species' time histories over the entire temperature range. Such modeling capability was due to the more accurate rate constants of EF reactions determined by high-precision theoretical calculations and a high-fidelity C0-C2 basis mechanism.

  19. Combining platelet-rich plasma and tissue-engineered skin in the treatment of large skin wound.

    PubMed

    Han, Tong; Wang, Hao; Zhang, Ya Qin

    2012-03-01

    The objective of the study was to observe the effects of tissue-engineered skin in combination with platelet-rich plasma (PRP) and other preparations on the repair of large skin wound on nude mice.We first prepared PRP from venous blood by density-gradient centrifugation. Large skin wounds were created surgically on the dorsal part of nude mice. The wounds were then treated with either artificial skin, tissue-engineered skin, tissue-engineered skin combined with basic fibroblast growth factor, tissue-engineered skin combined with epidermal growth factor, or tissue-engineered skin combined with PRP. Tissue specimens were collected at different time intervals after surgery. Hematoxylin-eosin and periodic acid-Schiff staining and immunohistochemistry were performed to assess the rate of wound healing.Macroscopic observations, hematoxylin-eosin/periodic acid-Schiff staining, and immunohistochemistry revealed that the wounds treated with tissue-engineered skin in combination with PRP showed the most satisfactory wound recovery, among the 5 groups.

  20. Combined distal venous arterialization and free flap for patients with extensive tissue loss.

    PubMed

    Sasajima, Tadahiro; Azuma, Nobuyoshi; Uchida, Hisashi; Asada, Hidenori; Inaba, Masashi; Akasaka, Nobuyuki

    2010-04-01

    We evaluated the mid-term outcome of distal venous arterialization (DVA) and the role of a combined free flap as a bridgehead for blood supply. In the past 5 years, nine patients with extensive tissue loss and lacking graftable distal arteries underwent DVA. These consisted of four primary DVAs, three combined DVA and free flap procedures, and two adjuvant DVAs for hemodynamically failed distal bypasses. After nine primary DVAs, three redo DVAs were performed for early failure. Etiologies were four Buerger disease and five arteriosclerosis obliterans, including three dialysis patients. Among the nine DVA cases, there were five primary failures: two underwent amputation, two had successful redo DVA, and the remaining one did not require redo DVA. Primary patency, secondary patency, and limb salvage rates were 44.4%, 55.6%, and 77.8%, respectively. The postoperative period was 1-36 months (median 12). Angiography demonstrated DVA was effective in the early period, and development of collaterals or a capillary network from the free flap replaced the DVA function in the intermediate period. DVA can be effective as a procedure for limb salvage in patients without graftable distal arteries, and a combined free flap is effective and functions as a bridgehead for blood supply to the ischemic zone. Copyright (c) 2010 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

  1. PARAMETRIC STUDY OF TISSUE OPTICAL CLEARING BY LOCALIZED MECHANICAL COMPRESSION USING COMBINED FINITE ELEMENT AND MONTE CARLO SIMULATION.

    PubMed

    Vogt, William C; Shen, Haiou; Wang, Ge; Rylander, Christopher G

    2010-07-01

    Tissue Optical Clearing Devices (TOCDs) have been shown to increase light transmission through mechanically compressed regions of naturally turbid biological tissues. We hypothesize that zones of high compressive strain induced by TOCD pins produce localized water displacement and reversible changes in tissue optical properties. In this paper, we demonstrate a novel combined mechanical finite element model and optical Monte Carlo model which simulates TOCD pin compression of an ex vivo porcine skin sample and modified spatial photon fluence distributions within the tissue. Results of this simulation qualitatively suggest that light transmission through the skin can be significantly affected by changes in compressed tissue geometry as well as concurrent changes in tissue optical properties. The development of a comprehensive multi-domain model of TOCD application to tissues such as skin could ultimately be used as a framework for optimizing future design of TOCDs.

  2. Combination of isothermal titration calorimetry and time-resolved luminescence for high affinity antibody-ligand interaction thermodynamics and kinetics

    PubMed Central

    Aweda, Tolulope A.; Meares, Claude F.

    2011-01-01

    For experiments using synthetic ligands as probes for biological experiments, it is useful to determine the specificity and affinity of the ligands for their receptors. As ligands with higher affinities are developed (KA >108 M−1; KD <10−8 M), a new challenge arises: to measure these values accurately. Isothermal titration calorimetry measures heat produced or consumed during ligand binding, and also provides the equilibrium binding constant. However, as normally practiced, its range is limited. Displacement titration, where a competing weaker ligand is used to lower the apparent affinity of the stronger ligand, can be used to determine the binding affinity as well as the complete thermodynamic data for ligand-antibody complexes with very high affinity. These equilibrium data have been combined with kinetic measurements to yield the rate constants as well. We describe this methodology, using as an example antibody 2D12.5, which captures yttrium S-2-(4-aminobenzyl)-1, 4, 7, 10-tetraazacyclododecanetetraacetate. PMID:21964396

  3. Combined Maxwell and kinetic guiding-center theory with polarization drift: Regularized variational formulation with local charge and energy conservation

    NASA Astrophysics Data System (ADS)

    Correa-Restrepo, D.; Pfirsch, D.; Wimmel, H. K.

    1986-06-01

    A formerly derived regularization method is applied to time-dependent Lagrangian guiding-center mechanics, with the polarization drift included. This approach removes the singularity that occurs for B-fields with non-vanishing parallel curl. From the Lagrangian equations of motion, Liouville's theorem and a collisionless kinetic equation for the “regularized guiding centers” are derived. A common Lagrangian density for both the guiding centers and the Maxwell fields is obtained by using a “constrained” Hamiltonian and a formely derived, new variational principle. From this variational formalism local conservation laws for electric charge and energy are derived, together with the correct charge, current, energy and energy flux densities. These densities combined point-like contributions with electric polarization and magnetization terms.

  4. The interplay between tissue plasminogen activator domains and fibrin structures in the regulation of fibrinolysis: kinetic and microscopic studies

    PubMed Central

    Thelwell, Craig; Williams, Stella C.; Silva, Marta M. C. G.; Szabó, László; Kolev, Krasimir

    2011-01-01

    Regulation of tissue-type plasminogen activator (tPA) depends on fibrin binding and fibrin structure. tPA structure/function relationships were investigated in fibrin formed by high or low thrombin concentrations to produce a fine mesh and small pores, or thick fibers and coarse structure, respectively. Kinetics studies were performed to investigate plasminogen activation and fibrinolysis in the 2 types of fibrin, using wild-type tPA (F-G-K1-K2-P, F and K2 binding), K1K1-tPA (F-G-K1-K1-P, F binding), and delF-tPA (G-K1-K2-P, K2 binding). There was a trend of enzyme potency of tPA > K1K1-tPA > delF-tPA, highlighting the importance of the finger domain in regulating activity, but the differences were less apparent in fine fibrin. Fine fibrin was a better surface for plasminogen activation but more resistant to lysis. Scanning electron and confocal microscopy using orange fluorescent fibrin with green fluorescent protein-labeled tPA variants showed that tPA was strongly associated with agglomerates in coarse but not in fine fibrin. In later lytic stages, delF-tPA-green fluorescent protein diffused more rapidly through fibrin in contrast to full-length tPA, highlighting the importance of finger domain-agglomerate interactions. Thus, the regulation of fibrinolysis depends on the starting nature of fibrin fibers and complex dynamic interaction between tPA and fibrin structures that vary over time. PMID:20966169

  5. The interplay between tissue plasminogen activator domains and fibrin structures in the regulation of fibrinolysis: kinetic and microscopic studies.

    PubMed

    Longstaff, Colin; Thelwell, Craig; Williams, Stella C; Silva, Marta M C G; Szabó, László; Kolev, Krasimir

    2011-01-13

    Regulation of tissue-type plasminogen activator (tPA) depends on fibrin binding and fibrin structure. tPA structure/function relationships were investigated in fibrin formed by high or low thrombin concentrations to produce a fine mesh and small pores, or thick fibers and coarse structure, respectively. Kinetics studies were performed to investigate plasminogen activation and fibrinolysis in the 2 types of fibrin, using wild-type tPA (F-G-K1-K2-P, F and K2 binding), K1K1-tPA (F-G-K1-K1-P, F binding), and delF-tPA (G-K1-K2-P, K2 binding). There was a trend of enzyme potency of tPA > K1K1-tPA > delF-tPA, highlighting the importance of the finger domain in regulating activity, but the differences were less apparent in fine fibrin. Fine fibrin was a better surface for plasminogen activation but more resistant to lysis. Scanning electron and confocal microscopy using orange fluorescent fibrin with green fluorescent protein-labeled tPA variants showed that tPA was strongly associated with agglomerates in coarse but not in fine fibrin. In later lytic stages, delF-tPA-green fluorescent protein diffused more rapidly through fibrin in contrast to full-length tPA, highlighting the importance of finger domain-agglomerate interactions. Thus, the regulation of fibrinolysis depends on the starting nature of fibrin fibers and complex dynamic interaction between tPA and fibrin structures that vary over time.

  6. Combining Gene and Stem Cell Therapy for Peripheral Nerve Tissue Engineering.

    PubMed

    Busuttil, Francesca; Rahim, Ahad A; Phillips, James B

    2017-02-15

    Despite a substantially increased understanding of neuropathophysiology, insufficient functional recovery after peripheral nerve injury remains a significant clinical challenge. Nerve regeneration following injury is dependent on Schwann cells, the supporting cells in the peripheral nervous system. Following nerve injury, Schwann cells adopt a proregenerative phenotype, which supports and guides regenerating nerves. However, this phenotype may not persist long enough to ensure functional recovery. Tissue-engineered nerve repair devices containing therapeutic cells that maintain the appropriate phenotype may help enhance nerve regeneration. The combination of gene and cell therapy is an emerging experimental strategy that seeks to provide the optimal environment for axonal regeneration and reestablishment of functional circuits. This review aims to summarize current preclinical evidence with potential for future translation from bench to bedside.

  7. Amoxicillin combined with clavulanic acid for the treatment of soft tissue infections in children.

    PubMed Central

    Fleisher, G R; Wilmott, C M; Campos, J M

    1983-01-01

    We compared responses to amoxicillin combined with clavulanic acid (ACA) with a cefaclor regimen in children with skin and soft tissue infections (impetigo and cellulitis) due to Staphylococcus aureus, Streptococcus pyogenes, and Haemophilus species. All isolates from the 41 patients we were able to evaluate were susceptible to ACA by disk susceptibility testing at the onset of treatment. The 21 children receiving ACA and 18 (90%) of 20 taking cefaclor responded to therapy. Clinical cure was achieved in 18 (86%) of 21 and 18 (90%) of 20 in the two groups, respectively. Bacteriological failure occurred in 2 (10%) patients in the cefaclor group and none in the group receiving ACA; however, there were 2 (9%) relapses and 1 (5%) reinfection among the 21 children taking ACA. Adverse effects, although mild, occurred more commonly (9 of 21 versus 1 of 20; P = 0.005) with ACA than with cefaclor. PMID:6660847

  8. Tissue specificity in rat peripheral nerve regeneration through combined skeletal muscle and vein conduit grafts.

    PubMed

    Tos, P; Battiston, B; Geuna, S; Giacobini-Robecchi, M G; Hill, M A; Lanzetta, M; Owen, E R

    2000-01-01

    Diffusible factors from the distal stumps of transected peripheral nerves exert a neurotropic effect on regenerating nerves in vivo (specificity). This morphological study was designed to investigate the existence of tissue specificity in peripheral nerve fiber regeneration through a graft of vein filled with fresh skeletal muscle. This tubulization technique demonstrated experimental and clinical results similar to those obtained with traditional autologous nerve grafts. Specifically, we used Y-shaped grafts to assess the orientation pattern of regenerating axons in the distal stump tissue. Animal models were divided into four experimental groups. The proximal part of the Y-shaped conduit was sutured to a severed tibial nerve in all experiments. The two distal stumps were sutured to different targets: group A to two intact nerves (tibial and peroneal), group B to an intact nerve and an unvascularized tendon, group C to an intact nerve and a vascularized tendon, and group D to a nerve graft and an unvascularized tendon. Morphological evaluation by light and electron microscopy was conducted in the distal forks of the Y-shaped tube. Data showed that almost all regenerating nerve fibers spontaneously oriented towards the nerve tissue (attached or not to the peripheral innervation field), showing a good morphological pattern of regeneration in both the early and late phases of regeneration. When the distal choice was represented by a tendon (vascularized or not), very few nerve fibers were detected in the corresponding distal fork of the Y-shaped graft. These results show that, using the muscle-vein-combined grafting technique, regenerating axons are able to correctly grow and orientate within the basement membranes of the graft guided by the neurotropic lure of the distal nerve stump. Copyright 2000 Wiley-Liss, Inc.

  9. [Oro-maxillofacial bone tissue engineering combining biomaterials, stem cells, and gene therapy].

    PubMed

    Myon, L; Ferri, J; Chai, F; Blanchemain, N; Raoul, G

    2011-09-01

    Improvements have been made in regenerative medicine, due to the development of tissue engineering and cellular therapy. Bone regeneration is an ambitious project, leading to many applications involving skull, maxillofacial, and orthopaedic surgery. Scaffolds, stem cells, and signals support bone tissue engineering. The scaffold physical and chemical properties promote cell invasion, guide their differentiation, and enable signal transmission. Scaffold may be inorganic or organic. Their conception was improved by the use of new techniques: self-assembled nanofibres, electrospinning, solution-phase separation, micropatterned hydrogels, bioprinting, and rapid prototyping. Cellular biology processes allow us to choose between embryonic stem cells or adult stem cells for regenerative medicine. Finally, communication between cells and their environment is essential; they use various signals to do so. The study of signals and their transmission led to the discovery and the use of Bone Morphogenetic Protein (BMP). The development of cellular therapy led to the emergence of a specific field: gene therapy. It relies on viral vectors, which include: retroviruses, adenoviruses and adeno-associated vectors (AAV). Non-viral vectors include plasmids and lipoplex. Some BMP genes have successfully been transfected. The ability to control transfected cells and the capacity to combine and transfect many genes involved in osseous healing will improve gene therapy. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  10. Combined third-harmonic generation and four-wave mixing microscopy of tissues and embryos.

    PubMed

    Mahou, Pierre; Olivier, Nicolas; Labroille, Guillaume; Duloquin, Louise; Sintes, Jean-Marc; Peyriéras, Nadine; Legouis, Renaud; Débarre, Delphine; Beaurepaire, Emmanuel

    2011-10-01

    Nonlinear microscopy can be used to probe the intrinsic optical properties of biological tissues. Using femtosecond pulses, third-harmonic generation (THG) and four-wave mixing (FWM) signals can be efficiently produced and detected simultaneously. Both signals probe a similar parameter, i.e. the real part of the third-order nonlinear susceptibility χ((3)). However THG and FWM images result from different phase matching conditions and provide complementary information. We analyze this complementarity using calculations, z-scan measurements on water and oils, and THG-FWM imaging of cell divisions in live zebrafish embryos. The two signals exhibit different sensitivity to sample size and clustering in the half-wavelength regime. Far from resonance, THG images reveal spatial variations |Δχ((3))(-3ω;ω,ω,ω)| with remarkable sensitivity while FWM directly reflects the distribution of χ((3))(-2ω(1) + ω(2);ω(1), -ω(2), ω(1)). We show that FWM images provide χ((3)) maps useful for proper interpretation of cellular THG signals, and that combined imaging carries additional structural information. Finally we present simultaneous imaging of intrinsic THG, FWM, second-harmonic (SHG) and two-photon-excited fluorescence (2PEF) signals in live Caenorhabditis elegans worms illustrating the information provided by multimodal nonlinear imaging of unstained tissue.

  11. Combining collagen and bioactive glasses for bone tissue engineering: a review.

    PubMed

    Sarker, Bapi; Hum, Jasmin; Nazhat, Showan N; Boccaccini, Aldo R

    2015-01-28

    Collagen (COL), the most abundant protein in mammals, offers a wide range of attractive properties for biomedical applications which are the result of its biocompatibility and high affinity to water. However, due to the relative low mechanical properties of COL its applications are still limited. To tackle this disadvantage of COL, especially in the field of bone tissue engineering, COL can be combined with bioactive inorganic materials in a variety of composite systems. One of such systems is the collagen-bioactive glass (COL-BG) composite family, which is the theme of this Review. BG fillers can increase compressive strength and stiffness of COL-based structures. This article reviews the relevant literature published in the last 15 years discussing the fabrication of a variety of COL-BG composites. In vitro cell studies have demonstrated the osteogenic, odontogenic, and angiogenic potential of these composite systems, which has been confirmed by stimulating specific biochemical indicators of relevant cells. Bony integration and connective tissue vessel formation have also been studied by implantation of the composites in vivo. Areas of future research in the field of COL-BG systems, based on current challenges, and gaps in knowledge are highlighted.

  12. Combination of extrinsic and intrinsic pathways significantly accelerates axial vascularization of bioartificial tissues.

    PubMed

    Arkudas, Andreas; Pryymachuk, Galyna; Beier, Justus P; Weigel, Linda; Körner, Carolin; Singer, Robert F; Bleiziffer, Oliver; Polykandriotis, Elias; Horch, Raymund E; Kneser, Ulrich

    2012-01-01

    In this study, the authors present a modification of the arteriovenous loop model that combines extrinsic and intrinsic vascularization modes to enhance vascularization of bioartificial matrices. An arteriovenous loop was created in the medial thighs of 24 rats. The loop was placed in a newly developed titanium chamber, which was fabricated with an electron beam melting facility, and was embedded in a hydroxyapatite/β-tricalcium phosphate/fibrin matrix. At the explantation time points (2, 4, 6, and 8 weeks), constructs were perfused by differently colored dyes to determine the amount of tissue vascularized by either the intrinsic or the extrinsic vascular pathway. Specimens were investigated by means of micro-computed tomography and histologic and morphometric analysis. Although there was an equal number of blood vessels originating from the center and the periphery, 83 percent of all vessels displayed a connection to the arteriovenous loop already at 2 weeks. There was a continuous increase of the relative proportion of vessels connected to the arteriovenous loop over time detectable. At 8 weeks, communications between the newly formed vessels and the arteriovenous loop were visible in 97 percent of all vessels. This study demonstrates for the first time the enhancement of angiogenesis in an axially vascularized tissue by an additional extrinsic vascular pathway. By 2 weeks, both pathways showed connections, allowing transplantation of the entire construct using the arteriovenous loop pedicle. This approach will allow for reduction of the time interval between arteriovenous loop implantation and transplantation into the defect site and limitation of operative interventions.

  13. Optical properties measurement of the laser-ablated tissues for the combined laser ablation with photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Honda, Norihiro; Ishii, Katsunori; Awazu, Kunio

    2012-03-01

    Laser ablation therapy combined with photodynamic therapy (PDT) is studied for treatment of advanced cancers. The clinical outcome of PDT may be improved by the accurate knowledge about the light distribution within tissue. Optical properties [absorption coefficient (μa), scattering coefficient (μs), anisotropy factor (g), refractive index, etc.] of tissues help us realizing a light propagation through the tissue. It is important to understand of the effect of laser coagulation formed by laser ablation to PDT. The aim of this study is to estimate of influence of coagulated region to PDT for effective PDT combined laser ablation therapy. We evaluated the optical property of mouse tumor tissue in native and coagulated state using a double integrating sphere system and an inverse Monte Carlo method in the wavelength range from 350 to 1000 nm. After laser ablation, the μa and reduced scattering coefficient spectra of coagulated tissues were increased in the wavelength range from 350 to 1000 nm. The optical penetration depth of coagulated tissues is 1.2-2.9 times lower than the native state in the wavelength range from 350 to 1000 nm. The intensity of the light energy inside the coagulated tissue falls to about 60% of its original value at the end of coagulated layer. The evaluation of light energy distribution by the determination of the tissues optical properties could be useful for optimization of the treatment procedure in combined laser ablation with PDT.

  14. Combined antibacterial/tissue regeneration response in thermal burns promoted by functional chitosan/silver nanocomposites.

    PubMed

    Luna-Hernández, E; Cruz-Soto, M E; Padilla-Vaca, F; Mauricio-Sánchez, R A; Ramirez-Wong, D; Muñoz, R; Granados-López, L; Ovalle-Flores, L R; Menchaca-Arredondo, J L; Hernández-Rangel, A; Prokhorov, E; García-Rivas, J L; España-Sánchez, B L; Luna-Bárcenas, G

    2017-07-28

    We report the combined antibacterial/tissue regeneration responses to thermal burns promoted by functional chitosan/silver nanocomposites (CS/nAg) with ultralow silver content (0.018wt.%, 7-30nm). Our approach allows one to produce CS/nAg nanocomposites without silver nanoparticles (nAg) agglomeration, with bactericide potency higher than 1wt.% of nAg (ca. 10nm) content and, promoting the healing process in controlled thermal burns. CS/nAg films exhibit high antibacterial activity against S. aureus and P. aeruginosa after 1.5h of incubation, demonstrating the bacterial penetration into hydrated films and their interaction with nAg. Additionally, exceptional healing of induced thermal burns was obtained by increasing myofibroblasts, collagen remodeling, and blood vessel neoformation. These factors are associated with epiderma regeneration after 7days of treatment with no nAg release. Our results corroborate the controlled synthesis of nAg embedded in CS matrix with combined antibacterial/biocompatibility properties aiming to produce functional nanocomposites with potential use in wound dressing and health care applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Oxidation kinetics of two pesticides in natural waters by ozonation and ozone combined with hydrogen peroxide.

    PubMed

    Chelme-Ayala, Pamela; El-Din, Mohamed Gamal; Smith, Daniel W; Adams, Craig D

    2011-04-01

    The oxidation of bromoxynil and trifluralin was investigated using ozone (O(3)) and O(3) combined with hydrogen peroxide (H(2)O(2)) in natural waters using batch reactors. The results indicated that these pesticides could not be completely degraded during ozonation, achieving degradation levels lower than 50%. An enhancement of the level of degradation was observed using O(3)/H(2)O(2) process. A biphasic behaviour of O(3) was also observed. Depending on the experimental conditions, the rate constant for O(3) decomposition was estimated to be between 7.4 × 10(-4) s(-1) to 5.8 × 10(-2) s(-1), and 3.2 × 10(-3) s(-1) to 4.2 × 10(-2) s(-1) for bromoxynil and trifluralin samples, respectively. Acute toxicity analysis performed using Microtox(®) showed a decrease in the toxic effects of the samples on the luminescent bacteria during the first few minutes of treatment, followed by an increase of the toxic effects at the end of the reaction for both pesticides. The quantification of oxidation by-products generated during treatment was also addressed. The total molar balances of the degradation by-products versus the initial pesticide concentrations ranged from 60 to 103% under different experimental conditions.

  16. Some cell kinetic effects of combined injury with ionizing radiation and cyclophosphamide on mouse bladder urothelium.

    PubMed

    Reitan, J B

    1985-01-01

    Cyclophosphamide was given intraperitoneally to groups of eight female mice 48 h after local electron irradiation to the bladder with 0, 10 and 20 Gy respectively. The reactions in the urothelium were monitored by histology, incorporation of tritiated thymidine and flow cytometry. A wave of increased thymidine incorporation combined with an increase in the proportion of diploid S-phase cells was seen in the unirradiated bladders 24 h after the drug treatment, followed by normalization after 1 week. This response was significantly less pronounced in the irradiated animals. In the unirradiated animals a similar wave characterized by an increased proportion of octaploid cells was also seen, but this wave occurred later in the irradiated animals. Severe injury was observed in the rectum of the 20 Gy-irradiated animals. Irradiation prior to drug treatment led to only small effects, but a decreased ability for regenerative DNA synthesis after drug injury seems to persist. This affects both proliferation and the building up of polyploidy.

  17. Combined magnetic and kinetic control of advanced tokamak steady state scenarios based on semi-empirical modelling

    NASA Astrophysics Data System (ADS)

    Moreau, D.; Artaud, J. F.; Ferron, J. R.; Holcomb, C. T.; Humphreys, D. A.; Liu, F.; Luce, T. C.; Park, J. M.; Prater, R.; Turco, F.; Walker, M. L.

    2015-06-01

    This paper shows that semi-empirical data-driven models based on a two-time-scale approximation for the magnetic and kinetic control of advanced tokamak (AT) scenarios can be advantageously identified from simulated rather than real data, and used for control design. The method is applied to the combined control of the safety factor profile, q(x), and normalized pressure parameter, βN, using DIII-D parameters and actuators (on-axis co-current neutral beam injection (NBI) power, off-axis co-current NBI power, electron cyclotron current drive power, and ohmic coil). The approximate plasma response model was identified from simulated open-loop data obtained using a rapidly converging plasma transport code, METIS, which includes an MHD equilibrium and current diffusion solver, and combines plasma transport nonlinearity with 0D scaling laws and 1.5D ordinary differential equations. The paper discusses the results of closed-loop METIS simulations, using the near-optimal ARTAEMIS control algorithm (Moreau D et al 2013 Nucl. Fusion 53 063020) for steady state AT operation. With feedforward plus feedback control, the steady state target q-profile and βN are satisfactorily tracked with a time scale of about 10 s, despite large disturbances applied to the feedforward powers and plasma parameters. The robustness of the control algorithm with respect to disturbances of the H&CD actuators and of plasma parameters such as the H-factor, plasma density and effective charge, is also shown.

  18. Kinetic studies on enzyme-catalyzed reactions: oxidation of glucose, decomposition of hydrogen peroxide and their combination.

    PubMed

    Tao, Zhimin; Raffel, Ryan A; Souid, Abdul-Kader; Goodisman, Jerry

    2009-04-08

    The kinetics of the glucose oxidase-catalyzed reaction of glucose with O2, which produces gluconic acid and hydrogen peroxide, and the catalase-assisted breakdown of hydrogen peroxide to generate oxygen, have been measured via the rate of O2 depletion or production. The O2 concentrations in air-saturated phosphate-buffered salt solutions were monitored by measuring the decay of phosphorescence from a Pd phosphor in solution; the decay rate was obtained by fitting the tail of the phosphorescence intensity profile to an exponential. For glucose oxidation in the presence of glucose oxidase, the rate constant determined for the rate-limiting step was k = (3.0 +/- 0.7) x 10(4) M(-1) s(-1) at 37 degrees C. For catalase-catalyzed H2O2 breakdown, the reaction order in [H2O2] was somewhat greater than unity at 37 degrees C and well above unity at 25 degrees C, suggesting different temperature dependences of the rate constants for various steps in the reaction. The two reactions were combined in a single experiment: addition of glucose oxidase to glucose-rich cell-free media caused a rapid drop in [O2], and subsequent addition of catalase caused [O2] to rise and then decrease to zero. The best fit of [O2] to a kinetic model is obtained with the rate constants for glucose oxidation and peroxide decomposition equal to 0.116 s(-1) and 0.090 s(-1) respectively. Cellular respiration in the presence of glucose was found to be three times as rapid as that in glucose-deprived cells. Added NaCN inhibited O2 consumption completely, confirming that oxidation occurred in the cellular mitochondrial respiratory chain.

  19. Inhibition kinetics of certain enzymes in the nervous tissue of vector snail Lymnaea acuminata by active molluscicidal components of Sapindus mukorossi and Terminalia chebula.

    PubMed

    Upadhyay, Aparna; Singh, Dinesh K

    2011-10-01

    Effect of active molluscicidal components of Sapindus mukorossi and Terminalia chebula on the acetylcholinesterase (AChE), acid and alkaline phosphatase (ACP/ALP) activity in the nervous tissue of freshwater snail Lymnaea acuminata were studied. In vivo and in vitro exposure of saponin (active component of S. mukorossi pericarp) and tannic acid (active component of T. chebula) significantly inhibited the AChE, ACP and ALP activity in the nervous tissue of L. acuminata. The inhibition kinetics of these enzymes indicate that saponin and tannic acid caused competitive and competitive-non-competitive inhibition of AChE, respectively. Saponin also caused competitive and competitive-non-competitive inhibition of ACP and ALP, respectively, whereas tannic acid caused competitive-non-competitive inhibition of ACP and ALP. Thus the inhibition of AChE, ACP and ALP by saponin and tannic acid in the nervous tissue of L. acuminata may be the cause of molluscicidal activity of S. mukorossi and T. chebula.

  20. Penetration kinetics of dimethyl sulphoxide and glycerol in dynamic optical clearing of porcine skin tissue in vitro studied by Fourier transform infrared spectroscopic imaging.

    PubMed

    Jiang, Jingying; Boese, Matthias; Turner, Paul; Wang, Ruikang K

    2008-01-01

    By use of a Fourier transform infrared (FTIR) spectroscopic imaging technique, we examine the dynamic optical clearing processes occurring in hyperosmotically biocompatible agents penetrating into skin tissue in vitro. The sequential collection of images in a time series provides an opportunity to assess penetration kinetics of dimethyl sulphoxide (DMSO) and glycerol beneath the surface of skin tissue over time. From 2-D IR spectroscopic images and 3-D false color diagrams, we show that glycerol takes at least 30 min to finally penetrate the layer of epidermis, while DMSO can be detected in epidermis after only 4 min of being topically applied over stratum corneum sides of porcine skin. The results demonstrate the potential of a FTIR spectroscopic imaging technique as an analytical tool for the study of dynamic optical clearing effects when the bio-tissue is impregnated by hyperosmotically biocompatible agents such as glycerol and DMSO.

  1. Numerical impact simulation of gradually increased kinetic energy transfer has the potential to break up folded protein structures resulting in cytotoxic brain tissue edema.

    PubMed

    von Holst, Hans; Li, Xiaogai

    2013-07-01

    Although the consequences of traumatic brain injury (TBI) and its treatment have been improved, there is still a substantial lack of understanding the mechanisms. Numerical simulation of the impact can throw further lights on site and mechanism of action. A finite element model of the human head and brain tissue was used to simulate TBI. The consequences of gradually increased kinetic energy transfer was analyzed by evaluating the impact intracranial pressure (ICP), strain level, and their potential influences on binding forces in folded protein structures. The gradually increased kinetic energy was found to have the potential to break apart bonds of Van der Waals in all impacts and hydrogen bonds at simulated impacts from 6 m/s and higher, thereby superseding the energy in folded protein structures. Further, impacts below 6 m/s showed none or very slight increase in impact ICP and strain levels, whereas impacts of 6 m/s or higher showed a gradual increase of the impact ICP and strain levels reaching over 1000 KPa and over 30%, respectively. The present simulation study shows that the free kinetic energy transfer, impact ICP, and strain levels all have the potential to initiate cytotoxic brain tissue edema by unfolding protein structures. The definition of mild, moderate, and severe TBI should thus be looked upon as the same condition and separated only by a gradual severity of impact.

  2. Soft tissue enhancement combined with biologically oriented preparation technique (BOPT) to correct volumetric bone defects: a clinical case report.

    PubMed

    Rancitelli, Davide; Poli, Pierpaolo; Cicciù, Marco; Lini, Francesco; Roncucci, Rachele; Cervino, Gabriele; Maiorana, Carlo

    2017-06-12

    The aim of the present case report was to illustrate how to obtain an ideal alveolar ridge contour by means of peri-implant soft tissues management combined with the prosthetic approach of the biologically oriented preparation technique (BOPT). A patient presenting a moderate vertical and horizontal bone loss in the posterior maxilla was treated with sinus floor elevation and contextual implant placement. During the re-entry procedure, the horizontal defect was corrected with an apically repositioned flap combined with a connective tissue graft. To increase the volume of the inter-implant papillae, a pedunculated flap originating from the primary flap was turned within the inter-implant space. BOPT one-time abutments have been employed to maximize the space available for the papilla-like tissues. A focused and combined surgical and prosthetic procedure has permitted to enhance both peri-implant aesthetic and function without the need for further invasive and costly bone regeneration techniques.

  3. Combining chondrocytes and smooth muscle cells to engineer hybrid soft tissue constructs.

    PubMed

    Brown, A N; Kim, B S; Alsberg, E; Mooney, D J

    2000-08-01

    Engineering new tissues using cell transplantation may provide a valuable tool for reconstructive surgery applications. Chondrocyte transplantation in particular has been successfully used to engineer new tissue masses due to the low metabolic requirements of these cells. However, the engineered cartilaginous tissue is too rigid for many soft tissue applications. We propose that hybrid tissue engineered from chondrocytes and smooth muscle cells could reflect mechanical properties intermediate between these two cell types. In this study, rat aortic smooth muscle cells and pig auricular chondrocytes were co-cultured on polyglycolic acid fiber-based matrices to address this hypothesis. Mixed cell suspensions were seeded by agitating the polymer matrices and a cell suspension with an orbital shaker. After seeding, cell-polymer constructs were cultured in stirred bioreactors for 8 weeks. The cell density and extracellular matrix (collagen, elastin, and glycosaminoglycan) content of the engineered tissues were determined biochemically. After 8 weeks in culture, the hybrid tissue had a high cell density (5.8 x 108 cells/cm(3)), and elastin (519 microg/g wet tissue sample), collagen (272 microg/g wet tissue sample), and glycosaminoglycan (GAG; 10 microg/g wet tissue sample) content. Mechanical testing indicated the compressive modulus of the hybrid tissues after 8 weeks to be 40.8 +/- 4.1 kPa and the equilibrium compressive modulus to be 8.4 +/- 0.8 kPa. Thus, these hybrid tissues exhibited intermediate stiffness; they were less stiff than native cartilage but stiffer than native smooth muscle tissue. This tissue engineering approach may be useful to engineer tissues for a variety of reconstructive surgery applications.

  4. Development of a dual-modal tissue diagnostic system combining time-resolved fluorescence spectroscopy and ultrasonic backscatter microscopy

    NASA Astrophysics Data System (ADS)

    Sun, Yang; Park, Jesung; Stephens, Douglas N.; Jo, Javier A.; Sun, Lei; Cannata, Jonathan M.; Saroufeem, Ramez M. G.; Shung, K. Kirk; Marcu, Laura

    2009-06-01

    We report a tissue diagnostic system which combines two complementary techniques of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) and ultrasonic backscatter microscopy (UBM). TR-LIFS evaluates the biochemical composition of tissue, while UBM provides tissue microanatomy and enables localization of the region of diagnostic interest. The TR-LIFS component consists of an optical fiber-based time-domain apparatus including a spectrometer, gated multichannel plate photomultiplier, and fast digitizer. It records the fluorescence with high sensitivity (nM concentration range) and time resolution as low as 300 ps. The UBM system consists of a transducer, pulser, receiving circuit, and positioning stage. The transducer used here is 45 MHz, unfocused, with axial and lateral resolutions 38 and 200 μm. Validation of the hybrid system and ultrasonic and spectroscopic data coregistration were conducted both in vitro (tissue phantom) and ex vivo (atherosclerotic tissue specimens of human aorta). Standard histopathological analysis of tissue samples was used to validate the UBM-TRLIFS data. Current results have demonstrated that spatially correlated UBM and TR-LIFS data provide complementary characterization of both morphology (necrotic core and calcium deposits) and biochemistry (collagen, elastin, and lipid features) of the atherosclerotic plaques at the same location. Thus, a combination of fluorescence spectroscopy with ultrasound imaging would allow for better identification of features associated with tissue pathologies. Current design and performance of the hybrid system suggests potential applications in clinical diagnosis of atherosclerotic plaque.

  5. Impact of Triple Combinations of Retinoic Acid, Mold Spores and Citral on the F344 Rat Lung Tissue Pathology.

    PubMed

    Farah, Ibrahim O; Holt-Gray, Carlene; Cameron, Joseph A; Tucci, Michelle; Cason, Zelma; Benghuzzi, Hamed

    2016-04-01

    The impact of retinoic acid (All Trans Retinoic Acid; ATRA) and Mold spores (MLD) in the development of lung pathology and in vivo tissue remodeling have not been well established in the literature. In addition, the role of citral (inhibitor of retinoid function) in the improvement of lung pathology has not been ascertained in animal studies. Therefore, it is hypothesized that ATRA and Mold (MLD) exposure will sensitize lung tissues leading to lung tissue pathology and that Citrals (C1 and C2) will reverse, ameliorate or improve the associated pathological damage to lung tissues. The study used an IACUC approved between-subject in vivo randomized split plot factorial design (F344 rat model; N=40). Animals were exposed to seven different treatments including untreated control, MLD, ATRA, Citrals (C1 and C2) and their MLD combinations (MLD+ ATRA+ C1, and MLD+ ATRA+ C2) by intra-peritoneal route. Rat weight and blood data were collected on Days 1 and 21, all animals were sacrificed on day 21, and lung tissues were processed for histopathology. Results from weight and blood data (ANOVA and Duncan) as well as from histopathological analyses supported the findings that exposure of F344 rats to MLD combinations with ATRA and Citrals showed various levels of lung tissue damage that were impacted by either C1 or C2 exposure. This promising study showed impressive responses on the interaction of MLD, Citrals, and ATRA as related to their impact on associated lung tissue pathologies.

  6. Enhancing the growth of Physcomitrella patens by combination of monochromatic red and blue light - a kinetic study.

    PubMed

    Cerff, Martin; Posten, Clemens

    2012-04-01

    In the current work we demonstrate the relevance of monochromatic light conditions in moss plant cell culture. Light intensity and illumination wavelength are important cultivation parameters due to their impact on growth and chlorophyll formation kinetics of the moss Physcomitrella patens. This moss was chosen as a model organism due to its capability to produce complex recombinant pharmaceutical proteins. Filamentous moss cells were cultivated in mineral medium in shaking flasks. The flasks were illuminated by light emitting diodes (LED) providing nearly monochromatic red and blue light as well as white light as a reference. A maximum growth rate of 0.78 day((1) was achieved under additional CO(2) aeration and no growth inhibition was observed under high light illumination. The application of dual red and blue light is the most effective way to reach high growth and chlorophyll formation rates while minimizing energy consumption of the LEDs. These observations are discussed as effects of photo sensory pigments in the moss. The combination of monochromatic red and blue light should be considered when a large scale process is set up.

  7. Kinetic theory of ligand recombination of myoglobin: a model for a combination of entropic and enthalpic effects

    NASA Astrophysics Data System (ADS)

    Yang, Dah-Yen; Sheu, Wen-Shyan; Sheu, Sheh-Yi; Lin, S. H.

    A kinetic theory of ligand recombination of myoglobin is obtained through a microscopic model. The macroscopic time dependent rate constant is obtained by the first passage time distribution random walk method. When the ligand is outside the haem pocket, it diffuses in a continuum space. In this process, this rate corresponds to a Smoluchowski rate constant times the concentration of myoglobin. After penetrating through the hydration shell, the ligand waits in front of the gate or diffuses on the myoglobin surface for entering the gate. This waiting time refers to a large scale fluctuation of protein to open the gate. When the ligand is inside the pocket, the motion of the ligand ranges from a ballistic to a diffusive limit. To cover the whole range of friction, it is necessary to solve exactly a finite area random walk model with periodic gating in one- and two-dimensional finite lattices with slippery boundary conditions. Protein dynamics influence the ligand motion indirectly through the collision between the ligand and the heme pocket well. The first step corresponds to an adiabatic dissociation process. A branching diagram method is used to show a detailed pathway analysis of the adiabaticity by introducing intermediate states in the quintet states for the CO ligand binding. The rate theories of ligand recombination of myoglobin are a combination of entropic and enthalpic effects.

  8. CO adsorption on W(100) during temperature-programmed desorption: A combined density functional theory and kinetic Monte Carlo study

    NASA Astrophysics Data System (ADS)

    Albao, Marvin A.; Padama, Allan Abraham B.

    2017-02-01

    Using a combined density functional theory (DFT) and kinetic Monte Carlo (KMC) simulations, we study the adsorption at 800 K and subsequent desorption of CO on W(100) at higher temperatures. The resulting TPD profiles are known experimentally to exhibit three desorption peaks β1, β2, and β3 at 930 K, 1070 K, and 1375 K, respectively. Unlike more recent theoretical studies that propose that all three aforementioned peaks are molecularly rather than associatively desorbed, our KMC analyses are in support of the latter, since at 800 K dissociation is facile and that CO exists as dissociation fragments C and O. We show that these peaks arise from desorption from the same adsorption site but whose binding energy varies depending on local environment, that is, the presence of CO as well as dissociation fragments C and O nearby. Furthermore we show that several key parameters, such as desorption, dissociation and recombination barriers all play a key role in the TPD spectra-these parameter effectively controls not only the location of the TPD peaks but the shape and width of the desorption peaks as well. Moreover, our KMC simulations reveal that varying the heating rate shifts the peaks but leaves their shape intact.

  9. The V[Combining Dot Above]O2 Kinetics of Maximal and Supramaximal Running Exercises in Sprinters and Middle-Distance Runners.

    PubMed

    do Nascimento Salvador, Paulo C; Dal Pupo, Juliano; De Lucas, Ricardo D; de Aguiar, Rafael A; Arins, Francimara B; Guglielmo, Luiz G A

    2016-10-01

    do Nascimento Salvador, PC, Dal Pupo, J, De Lucas, RD, de Aguiar, RA, Arins, FB, and Guglielmo, LGA. The V[Combining Dot Above]O2 kinetics of maximal and supramaximal running exercises in sprinters and middle-distance runners. J Strength Cond Res 30(10): 2857-2863, 2016-The aim of this study was to compare the V[Combining Dot Above]O2 kinetics parameters during maximal and supramaximal running exercises in sprinters (SPR) and middle-distance runners (MDR). Twelve SPR (age 20.6 ± 3.4 years; and body mass 74.9 ± 6.2 kg) and 10 MDR (age 17.6 ± 1.4 years; and body mass 70.1 ± 11.8 kg) performed, on different days, a maximal incremental running test for determination of the velocity at maximum oxygen uptake (vV[Combining Dot Above]O2max) and 2 constant-speed tests for analysis of V[Combining Dot Above]O2 kinetics at 100 and 120% of vV[Combining Dot Above]O2max. The MDR presented significantly higher values for the critical speed (18.0 ± 1.0 vs. 14.2 ± 1.0 km·h), vV[Combining Dot Above]O2max (19.4 ± 0.7 vs. 17.2 ± 0.8 km·h), and time to exhaustion at 100% (437 ± 53 vs. 366 ± 49 seconds) than the SPR (p ≤ 0.05). However, the SPR demonstrated greater values for the anaerobic distance capacity (281.3 ± 66.1 vs. 208.0 ± 43.4 m). Although the mean response time and the time to attain the V[Combining Dot Above]O2max of the V[Combining Dot Above]O2 kinetics was higher in the maximal than supramaximal running speed (p ≤ 0.05), no difference was found in these parameters as well for V[Combining Dot Above]O2 slow component (p > 0.05) between the groups. This study showed that different aerobic and anaerobic characteristics in MDR and SPR did not affect the V[Combining Dot Above]O2 kinetics in maximal and supramaximal intensities within the severe-intensity domain. From a practical perspective, parameters of V[Combining Dot Above]O2 response may provide helpful information for training control as the duration of stimulus close to V[Combining Dot Above]O2max.

  10. Combination reactions of superoxide with 8-Oxo-7,8-dihydroguanine radicals in DNA: kinetics and end products.

    PubMed

    Misiaszek, Richard; Uvaydov, Yuriy; Crean, Conor; Geacintov, Nicholas E; Shafirovich, Vladimir

    2005-02-25

    One of the major biomarkers of oxidative stress and oxidative damage of cellular DNA is 8-oxo-7,8-dihydroguanine (8-oxoGua), which is more easily oxidized than guanine to diverse oxidative products. In this work, we have investigated further oxidative transformations of 8-oxoGua in single- and double-stranded oligonucleotides to the dehydroguanidinohydantoin, oxaluric acid, and diastereomeric spiroiminodihydantoin lesions. The relative distributions of these end products were explored by a combined kinetic laser spectroscopy and mass spectrometry approach and are shown to depend markedly on the presence of superoxide radical anions. The 8-oxaGua radicals were produced by one-electron oxidation of 8-oxoGua by 2-aminopurine radicals generated by the two-photon ionization of 2-aminopurine residues site specifically positioned in 5'-d(CC[2-aminopurine]TC[8-oxoGua]CTACC). The hydrated electrons also formed in the photoionization process were trapped by dissolved molecular oxygen thus producing superoxide. A combination reaction between the 8-oxoGua and superoxide radicals occurs with the rate constant of (1.3 +/- 0.2) x 10(8) m(-1) s(-1) and (1.0 +/- 0.5) x 10(8) m(-1) s(-1) in single- and double-stranded DNA, respectively. The major end products of this reaction are the dehydroguanidinohydantoin lesions that slowly hydrolyze to oxaluric acid residues. In the presence of Cu,Zn-superoxide dismutase, an enzyme that induces the rapid catalytic dismutation of superoxide to the less reactive H(2)O(2) and O(2), the yields of the dehydroguanidinohydantion lesions become negligible. Under these conditions, the 8-oxoGua radicals do not exhibit any observable reactivities with oxygen (k < 10(2) m(-1) s(-1)), decay on the time interval of several seconds, and the major reaction products are the spiroiminodihydantoin lesions. The possible biological implications of the 8-oxoGua oxidation are discussed.

  11. HIV Maintains an Evolving and Dispersed Population in Multiple Tissues during Suppressive Combined Antiretroviral Therapy in Individuals with Cancer.

    PubMed

    Rose, Rebecca; Lamers, Susanna L; Nolan, David J; Maidji, Ekaterina; Faria, N R; Pybus, Oliver G; Dollar, James J; Maruniak, Samuel A; McAvoy, Andrew C; Salemi, Marco; Stoddart, Cheryl A; Singer, Elyse J; McGrath, Michael S

    2016-10-15

    While combined antiretroviral therapy (cART) can result in undetectable plasma viral loads, it does not eradicate HIV infection. Furthermore, HIV-infected individuals while on cART remain at an increased risk of developing serious comorbidities, such as cancer, neurological disease, and atherosclerosis, suggesting that during cART, tissue-based HIV may contribute to such pathologies. We obtained DNA and RNA env, nef, and pol sequences using single-genome sequencing from postmortem tissues of three HIV(+) cART-treated (cART(+)) individuals with undetectable viral load and metastatic cancer at death and performed time-scaled Bayesian evolutionary analyses. We used a sensitive in situ hybridization technique to visualize HIV gag-pol mRNA transcripts in cerebellum and lymph node tissues from one patient. Tissue-associated virus evolved at similar rates in cART(+) and cART-naive (cART(-)) patients. Phylogenetic trees were characterized by two distinct features: (i) branching patterns consistent with constant viral evolution and dispersal among tissues and (ii) very recently derived clades containing both DNA and RNA sequences from multiple tissues. Rapid expansion of virus near death corresponded to wide-spread metastasis. HIV RNA(+) cells clustered in cerebellum tissue but were dispersed in lymph node tissue, mirroring the evolutionary patterns observed for that patient. Activated, infiltrating macrophages were associated with HIV RNA. Our data provide evidence that tissues serve as a sanctuary for wild-type HIV during cART and suggest the importance of macrophages as an alternative reservoir and mechanism of virus spread. Combined antiretroviral therapy (cART) reduces plasma HIV to undetectable levels; however, removal of cART results in plasma HIV rebound, thus highlighting its inability to entirely rid the body of infection. Additionally, HIV-infected individuals on cART remain at high risk of serious diseases, which suggests a contribution from residual HIV. In

  12. Thicker three-dimensional tissue from a “symbiotic recycling system” combining mammalian cells and algae

    PubMed Central

    Haraguchi, Yuji; Kagawa, Yuki; Sakaguchi, Katsuhisa; Matsuura, Katsuhisa; Shimizu, Tatsuya; Okano, Teruo

    2017-01-01

    In this paper, we report an in vitro co-culture system that combines mammalian cells and algae, Chlorococcum littorale, to create a three-dimensional (3-D) tissue. While the C2C12 mouse myoblasts and rat cardiac cells consumed oxygen actively, intense oxygen production was accounted for by the algae even in the co-culture system. Although cell metabolism within thicker cardiac cell-layered tissues showed anaerobic respiration, the introduction of innovative co-cultivation partially changed the metabolism to aerobic respiration. Moreover, the amount of glucose consumption and lactate production in the cardiac tissues and the amount of ammonia in the culture media decreased significantly when co-cultivated with algae. In the cardiac tissues devoid of algae, delamination was observed histologically, and the release of creatine kinase (CK) from the tissues showed severe cardiac cell damage. On the other hand, the layered cell tissues with algae were observed to be in a good histological condition, with less than one-fifth decline in CK release. The co-cultivation with algae improved the culture condition of the thicker tissues, resulting in the formation of 160 μm-thick cardiac tissues. Thus, the present study proposes the possibility of creating an in vitro “symbiotic recycling system” composed of mammalian cells and algae. PMID:28139713

  13. Calcium Phosphate Scaffolds Combined with Bone Morphogenetic Proteins or Mesenchymal Stem Cells in Bone Tissue Engineering

    PubMed Central

    Sun, Han; Yang, Hui-Lin

    2015-01-01

    Objective: The purpose of this study was to review the current status of calcium phosphate (CaP) scaffolds combined with bone morphogenetic proteins (BMPs) or mesenchymal stem cells (MSCs) in the field of bone tissue engineering (BTE). Date Sources: Data cited in this review were obtained primarily from PubMed and Medline in publications from 1979 to 2014, with highly regarded older publications also included. The terms BTE, CaP, BMPs, and MSC were used for the literature search. Study Selection: Reviews focused on relevant aspects and original articles reporting in vitro and/or in vivo results concerning the efficiency of CaP/BMPs or CaP/MSCs composites were retrieved, reviewed, analyzed, and summarized. Results: An ideal BTE product contains three elements: Scaffold, growth factors, and stem cells. CaP-based scaffolds are popular because of their outstanding biocompatibility, bioactivity, and osteoconductivity. However, they lack stiffness and osteoinductivity. To solve this problem, composite scaffolds of CaP with BMPs have been developed. New bone formation by CaP/BMP composites can reach levels similar to those of autografts. CaP scaffolds are compatible with MSCs and CaP/MSC composites exhibit excellent osteogenesis and stiffness. In addition, a CaP/MSC/BMP scaffold can repair bone defects more effectively than an autograft. Conclusions: Novel BTE products possess remarkable osteoconduction and osteoinduction capacities, and exhibit balanced degradation with osteogenesis. Further work should yield safe, viable, and efficient materials for the repair of bone lesions. PMID:25881610

  14. Prediction of permeability of regular scaffolds for skeletal tissue engineering: a combined computational and experimental study.

    PubMed

    Truscello, S; Kerckhofs, G; Van Bael, S; Pyka, G; Schrooten, J; Van Oosterwyck, H

    2012-04-01

    Scaffold permeability is a key parameter combining geometrical features such as pore shape, size and interconnectivity, porosity and specific surface area. It can influence the success of bone tissue engineering scaffolds, by affecting oxygen and nutrient transport, cell seeding efficiency, in vitro three-dimensional (3D) cell culture and, ultimately, the amount of bone formation. An accurate and efficient prediction of scaffold permeability would be highly useful as part of a scaffold design process. The aim of this study was (i) to determine the accuracy of computational fluid dynamics (CFD) models for prediction of the permeability coefficient of three different regular Ti6Al4V scaffolds (each having a different porosity) by comparison with experimentally measured values and (ii) to verify the validity of the semi-empirical Kozeny equation to calculate the permeability analytically. To do so, five CFD geometrical models per scaffold porosity were built, based on different geometrical inputs: either based on the scaffold's computer-aided design (CAD) or derived from 3D microfocus X-ray computed tomography (micro-CT) data of the additive manufactured (AM) scaffolds. For the latter the influence of the spatial image resolution and the image analysis algorithm used to determine the scaffold's architectural features on the predicted permeability was analysed. CFD models based on high-resolution micro-CT images could predict the permeability coefficients of the studied scaffolds: depending on scaffold porosity and image analysis algorithm, relative differences between measured and predicted permeability values were between 2% and 27%. Finally, the analytical Kozeny equation was found to be valid. A linear correlation between the ratio Φ(3)/S(s)(2) and the permeability coefficient k was found for the predicted (by means of CFD) as well as measured values (relative difference of 16.4% between respective Kozeny coefficients), thus resulting in accurate and efficient

  15. Depicting the Spatial Distribution of Proteins in Human Tumor Tissue Combining SELDI and MALDI Imaging and Immunohistochemistry

    PubMed Central

    Wehder, Liane; Ernst, Günther; Crecelius, Anna C.; Guntinas-Lichius, Orlando; Melle, Christian; Schubert, Ulrich S.; von Eggeling, Ferdinand

    2010-01-01

    Carcinoma tissue consists of not only tumor cells but also fibroblasts, endothelial cells or vascular structures, and inflammatory cells forming the supportive tumor stroma. Therefore, the spatial distribution of proteins that promote growth and proliferation in these complex functional units is of high interest. Matrix-assisted laser desorption/ionization imaging mass spectrometry is a newly developed technique that generates spatially resolved profiles of protein signals directly from thin tissue sections. Surface-enhanced laser desorption/ionization mass spectrometry (MS)combined with tissue microdissection allows analysis of defined parts of the tissue with a higher sensitivity and a broader mass range. Nevertheless, both MS-based techniques have a limited spatial resolution. IHC is a technique that allows a resolution down to the subcellular level. However, the detection and measurement of a specific protein expression level is possible only by semiquantitative methods. Moreover, prior knowledge about the identity of the proteins of interest is necessary. In this study, we combined all three techniques to gain highest spatial resolution, sensitivity, and quantitative information. We used frozen tissue from head and neck tumors and chose two exemplary proteins (HNP1–3 and S100A8) to highlight the advantages and disadvantages of each technique. It could be shown that the combination of these three techniques results in congruent but also synergetic data. (J Histochem Cytochem 58:929–937, 2010) PMID:20644210

  16. Combined soft and hard tissue peri-implant plastic surgery techniques to enhance implant rehabilitation: a case report.

    PubMed

    Baltacıoğlu, Esra; Korkmaz, Fatih Mehmet; Bağış, Nilsun; Aydın, Güven; Yuva, Pınar; Korkmaz, Yavuz Tolga; Bağış, Bora

    2014-01-01

    This case report presents an implant-aided prosthetic treatment in which peri-implant plastic surgery techniques were applied in combination to satisfactorily attain functional aesthetic expectations. Peri-implant plastic surgery enables the successful reconstruction and restoration of the balance between soft and hard tissues and allows the option of implant-aided fixed prosthetic rehabilitation.

  17. Combined Soft and Hard Tissue Peri-Implant Plastic Surgery Techniques to Enhance Implant Rehabilitation: A Case Report

    PubMed Central

    Baltacıoğlu, Esra; Korkmaz, Fatih Mehmet; Bağış, Nilsun; Aydın, Güven; Yuva, Pınar; Korkmaz, Yavuz Tolga; Bağış, Bora

    2014-01-01

    This case report presents an implant-aided prosthetic treatment in which peri-implant plastic surgery techniques were applied in combination to satisfactorily attain functional aesthetic expectations. Peri-implant plastic surgery enables the successful reconstruction and restoration of the balance between soft and hard tissues and allows the option of implant-aided fixed prosthetic rehabilitation. PMID:25489351

  18. Combinations of parabens at concentrations measured in human breast tissue can increase proliferation of MCF-7 human breast cancer cells.

    PubMed

    Charles, Amelia K; Darbre, Philippa D

    2013-05-01

    The alkyl esters of p-hydroxybenzoic acid (parabens), which are used as preservatives in consumer products, possess oestrogenic activity and have been measured in human breast tissue. This has raised concerns for a potential involvement in the development of human breast cancer. In this paper, we have investigated the extent to which proliferation of MCF-7 human breast cancer cells can be increased by exposure to the five parabens either alone or in combination at concentrations as recently measured in 160 human breast tissue samples. Determination of no-observed-effect concentrations (NOEC), lowest-observed-effect concentrations (LOEC), EC50 and EC100 values for stimulation of proliferation of MCF-7 cells by five parabens revealed that 43/160 (27%) of the human breast tissue samples contained at least one paraben at a concentration ≥ LOEC and 64/160 (40%) > NOEC. Proliferation of MCF-7 cells could be increased by combining all five parabens at concentrations down to the 50(th) percentile (median) values measured in the tissues. For the 22 tissue samples taken at the site of ER + PR + primary cancers, 12 contained a sufficient concentration of one or more paraben to stimulate proliferation of MCF-7 cells. This demonstrates that parabens, either alone or in combination, are present in human breast tissue at concentrations sufficient to stimulate the proliferation of MCF-7 cells in vitro, and that functional consequences of the presence of paraben in human breast tissue should be assessed on the basis of all five parabens and not single parabens individually. Copyright © 2013 John Wiley & Sons, Ltd.

  19. Transfusion medicine in the Formosa Fun Coast water park explosion: The role of combined tissue and blood banking.

    PubMed

    Chang, Chih-Chun; Yeh, Chin-Chuan; Chu, Fang-Yeh

    2016-10-01

    The Formosa Fun Coast explosion, occurring in a recreational water park located in the Northern Taiwan on 27 June 2015, made 499 people burn-injured. For those who had severe burn trauma, surgical intervention and fluid resuscitation were necessary, and potential blood transfusion therapy could be initiated, especially during and after broad escharotomy. Here, we reviewed the literature regarding transfusion medicine and skin grafting as well as described the practicing experience of combined tissue and blood bank in the burn disaster in Taiwan. It was reported that patients who were severely burn-injured could receive multiple blood transfusions during hospitalization. Since the use of skin graft became a mainstay alternative for wound coverage after the early debridement of burn wounds at the beginning of the 20th century, the development of tissue banking program was initiated. In Taiwan, the tissue banking program was started in 2006. And the first combined tissue and blood bank was established in Far Eastern Memorial Hospital in 2010, equipped with the non-sterile, clean and sterile zones distinctly segregated with a unidirectional movement in the sterile area. The sterile zone was a class 10000 clean room equipped with high efficiency particulate air filter (HEPAF) and positive air pressure ventilation. The combined tissue and blood bank has been able to provide the assigned blood products and tissue graft timely and accurately, with the concepts of centralized management. In the future, the training of tissue and blood bank technicians would be continued and fortified, particularly on the regulation and quality control for further bio- and hemovigilance.

  20. The combination of resveratrol and quercetin enhances the individual effects of these molecules on triacylglycerol metabolism in white adipose tissue.

    PubMed

    Arias, Noemí; Macarulla, M Teresa; Aguirre, Leixuri; Milton, Iñaki; Portillo, María P

    2016-02-01

    The aim of this study was to analyze whether the combination of resveratrol and quercetin showed additive or synergic effects on body fat accumulation and triacylglycerol metabolism in adipose tissue from rats fed an obesogenic diet. Rats were divided into four dietary groups: a control group and three groups each treated with either resveratrol (15 mg/kg/day; RSV), quercetin (30 mg/kg/day; Q), or both (15 mg resveratrol/kg/day and 30 mg quercetin/kg/day; RSV + Q) for 6 weeks. White adipose tissues from several anatomical locations were dissected. Serum parameters were analyzed by using commercial kits. The activities of fatty acid synthase and heparin-releasable lipoprotein lipase (HR-LPL) were measured using spectrophotometric and fluorimetric methods, and protein expression of acetyl-CoA carboxylase (ACC), adipose tissue triglyceride lipase (ATGL), and hormone-sensitive lipase (HSL) by western blot. The administration of either resveratrol or quercetin separately did not induce significant reductions in adipose tissue weights. By contrast, the combination of both molecules led to a significant reduction in all the fat depots analyzed. The percentage of reduction in each tissue was greater than the calculated additive effect. HR-LPL activity was reduced in RSV and RSV + Q groups. The activity of HSL was not modified. By contrast, ACC was inhibited and ATGL increased only by the combination of both polyphenols. The results obtained demonstrate a synergistic effect between resveratrol and quercetin and suggest that when these molecules are combined, a great number of metabolic pathways involved in adipose tissue triacylglycerol accumulation are affected.

  1. The combination of stem cells and tissue engineering: an advanced strategy for blood vessels regeneration and vascular disease treatment.

    PubMed

    Wang, Ying; Yin, Pei; Bian, Guang-Liang; Huang, Hao-Yue; Shen, Han; Yang, Jun-Jie; Yang, Zi-Ying; Shen, Zhen-Ya

    2017-09-15

    Over the past years, vascular diseases have continued to threaten human health and increase financial burdens worldwide. Transplantation of allogeneic and autologous blood vessels is the most convenient treatment. However, it could not be applied generally due to the scarcity of donors and the patient's condition. Developments in tissue engineering are contributing greatly with regard to this urgent need for blood vessels. Tissue engineering-derived blood vessels are promising alternatives for patients with aortic dissection/aneurysm. The aim of this review is to show the importance of advances in biomaterials development for the treatment of vascular disease. We also provide a comprehensive overview of the current status of tissue reconstruction from stem cells and transplantable cellular scaffold constructs, focusing on the combination of stem cells and tissue engineering for blood vessel regeneration and vascular disease treatment.

  2. Tissue tropisms, infection kinetics, histologic lesions, and antibody response of the MR766 strain of Zika virus in a murine model.

    PubMed

    Kawiecki, Anna B; Mayton, E Handly; Dutuze, M Fausta; Goupil, Brad A; Langohr, Ingeborg M; Del Piero, Fabio; Christofferson, Rebecca C

    2017-04-18

    The appearance of severe Zika virus (ZIKV) disease in the most recent outbreak has prompted researchers to respond through the development of tools to quickly characterize transmission and pathology. We describe here another such tool, a mouse model of ZIKV infection and pathogenesis using the MR766 strain of virus that adds to the growing body of knowledge regarding ZIKV kinetics in small animal models. We infected mice with the MR766 strain of ZIKV to determine infection kinetics via serum viremia. We further evaluated infection-induced lesions via histopathology and visualized viral antigen via immunohistochemical labeling. We also investigated the antibody response of recovered animals to both the MR766 and a strain from the current outbreak (PRVABC59). We demonstrate that the IRF3/7 DKO mouse is a susceptible, mostly non-lethal model well suited for the study of infection kinetics, pathological progression, and antibody response. Infected mice presented lesions in tissues that have been associated with ZIKV infection in the human population, such as the eyes, male gonads, and central nervous system. In addition, we demonstrate that infection with the MR766 strain produces cross-neutralizing antibodies to the PRVABC59 strain of the Asian lineage. This model provides an additional tool for future studies into the transmission routes of ZIKV, as well as for the development of antivirals and other therapeutics, and should be included in the growing list of available tools for investigations of ZIKV infection and pathogenesis.

  3. Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

    NASA Astrophysics Data System (ADS)

    Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J. T.

    2013-06-01

    Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis.

  4. Combined magnetic and kinetic control of advanced tokamak steady state scenarios based on semi-empirical modelling

    SciTech Connect

    Moreau, Didier; Artaud, J. F.; Ferron, John R.; Holcomb, Christopher T.; Humphreys, David A.; Liu, Feng; Luce, Timothy C.; Park, Jin Myung; Prater, Ronald; Turco, Francesca; Walker, Michael L.

    2015-05-01

    This paper shows that semi-empirical data-driven models based on a twotime- scale approximation for the magnetic and kinetic control of advanced tokamak (AT) scenarios can be advantageously identified from simulated rather than real data, and used for control design. The method is applied to the combined control of the safety factor profile, q(x), and normalized pressure parameter, βN, using DIII-D parameters and actuators (on-axis co-current neutral beam injection (NBI) power, off axis co-current NBI power, electron cyclotron current drive power, and ohmic coil). The approximate plasma response model was identified from simulated data obtained using a rapidly converging plasma transport code, METIS, which includes an MHD equilibrium and current diffusion solver, and combines plasma transport nonlinearity with 0-D scaling laws and 1.5-D ordinary differential equations. A number of open loop simulations were performed, in which the heating and current drive (H&CD) sources were randomly modulated around the typical values of a reference AT discharge on DIIID. Using these simulated data, a two-time-scale state space model was obtained for the coupled evolution of the poloidal flux profile and βN parameter, and a controller was synthesized based on the near-optimal ARTAEMIS algorithm [D. Moreau et al., Nucl. Fusion 53 (2013) 063020]. The paper discusses the results of closed-loop nonlinear simulations, using this controller for steady state AT operation. With feedforward plus feedback control, the steady state target q-profile and βN are satisfactorily tracked with a time scale of about ten seconds, despite large disturbances applied to the feedforward powers and plasma parameters. The effectiveness of the control algorithm is thus demonstrated for long pulse and steady state high-βN AT discharges. Its robustness with respect to disturbances of the H&CD actuators and of plasma parameters such as the H-factor, plasma density and

  5. Combined magnetic and kinetic control of advanced tokamak steady state scenarios based on semi-empirical modelling

    DOE PAGES

    Moreau, Didier; Artaud, J. F.; Ferron, John R.; ...

    2015-05-01

    This paper shows that semi-empirical data-driven models based on a twotime- scale approximation for the magnetic and kinetic control of advanced tokamak (AT) scenarios can be advantageously identified from simulated rather than real data, and used for control design. The method is applied to the combined control of the safety factor profile, q(x), and normalized pressure parameter, βN, using DIII-D parameters and actuators (on-axis co-current neutral beam injection (NBI) power, off axis co-current NBI power, electron cyclotron current drive power, and ohmic coil). The approximate plasma response model was identified from simulated data obtained using a rapidly converging plasma transportmore » code, METIS, which includes an MHD equilibrium and current diffusion solver, and combines plasma transport nonlinearity with 0-D scaling laws and 1.5-D ordinary differential equations. A number of open loop simulations were performed, in which the heating and current drive (H&CD) sources were randomly modulated around the typical values of a reference AT discharge on DIIID. Using these simulated data, a two-time-scale state space model was obtained for the coupled evolution of the poloidal flux profile and βN parameter, and a controller was synthesized based on the near-optimal ARTAEMIS algorithm [D. Moreau et al., Nucl. Fusion 53 (2013) 063020]. The paper discusses the results of closed-loop nonlinear simulations, using this controller for steady state AT operation. With feedforward plus feedback control, the steady state target q-profile and βN are satisfactorily tracked with a time scale of about ten seconds, despite large disturbances applied to the feedforward powers and plasma parameters. The effectiveness of the control algorithm is thus demonstrated for long pulse and steady state high-βN AT discharges. Its robustness with respect to disturbances of the H&CD actuators and of plasma parameters such as the H-factor, plasma density and effective charge, is also

  6. [Investigations on the physiology of the glands of carnivorous plants : IV. The kinetics of chloride secretion by the gland tissue of Nepenthes].

    PubMed

    Lüttge, U

    1966-03-01

    The transport of chloride in isolated tissue from Nepenthes pitchers was investigated using (36)Cl(-), an Aminco-Cotlove chloride-titrator for the determinations of Cl(-) concentrations, and KCN and AsO 4 (-) -as metabolic inhibitors.The tissue was brought in contact with different experimental solutions (=medium). The surface corresponding to the outside of the pitchers was cut with a razor blade to remove the cutinized epidermal layer. At this surface the Cl(-) uptake from the medium is a metabolic process which depends on the Cl(-)-concentration of the medium in a manner that corresponds to the MICHAELIS-MENTEN kinetics. The Michaelis-constant of this transport step was 3×10(-2)M. The Cl(-)-efflux into the medium, however, is a passive process.The opposite surface of the tissue slices (corresponding to the inside of the pitchers) carries the glands. The chloride secretion taking place here is also dependent on metabolism. In vitro it occurs even when a high gradient of chloride concentration has been set up between the medium and the solution which is in contact with the glands. In vivo the Cl(-)-concentration of the pitcher fluid and the amount of Cl(-) per gram of tissue water are almost equal.The rôle of chloride in the physiology of Nepenthes is still under investigation, A correlation between the chloride content of the pitcher fluid and its enzymatic activity (Casein-test), however, could already be demonstrated.

  7. Fish oil combined with SCFA synergistically prevent tissue accumulation of NEFA during weight loss in obese mice.

    PubMed

    Pedersen, Maiken H; Lauritzen, Lotte; Hellgren, Lars I

    2011-11-01

    Based on their proposed metabolic effects, we examined whether fish oil (FO) and SCFA, alone or in combination, accelerate weight loss and the resultant metabolic improvements. Obesity was induced in male C57BL/6J mice by high-energy feeding for 10 weeks. The mice were transferred to a low-fat diet (2·5w%) for 4 weeks, the source of fat being either FO, a lard-safflower oil mix (control), or both types combined with SCFA. Weight, fasting insulin, tissue and serum lipid concentrations, as well as mRNA amount of genes related to adipose inflammation and hepatic fat oxidation were determined. All groups lost weight and showed reduced fasting insulin concentrations and reduced liver TAG. However, weight loss on the control-fat diet caused significant increase in hepatic and cardiac NEFA. Substituting 20 % of the fat with SCFA increased weight loss by 48 % and reduced fasting insulin 1·5-fold more than the no-SCFA diets. It furthermore significantly increased the amount of mRNA for PPAR-α, and decreased the mRNA amount for NF-κB in the liver and white adipose tissue. The FO diets enhanced improvement of tissue lipid levels. Thus, FO improved liver TAG and NEFA levels compared with weight loss on the control diet. Combining FO and SCFA further reduced tissue NEFA accumulation. In conclusion, we found that dietary SCFA had a significant impact on gene expression in the liver and adipose tissue, and that the effect of FO on tissue NEFA content was modified by SCFA. Thus, interactions between fatty acids should be considered when studying the effects of specific fatty acids.

  8. Effects of a combined mechanical stimulation protocol: Value for skeletal muscle tissue engineering.

    PubMed

    Boonen, Kristel J M; Langelaan, Marloes L P; Polak, Roderick B; van der Schaft, Daisy W J; Baaijens, Frank P T; Post, Mark J

    2010-05-28

    Skeletal muscle is an appealing topic for tissue engineering because of its variety in applications for regenerative medicine, in vitro physiological model systems, and in vitro meat production. Besides conventional biochemical cues to promote muscle tissue maturation in vitro, biophysical stimuli are necessary to reach the desired functionality and texture of the engineered tissue. Stretch, caused by active movements of the body, is an important factor present in the niche of muscle progenitor cells in vivo. We therefore investigated the effects of uniaxial ramp stretch (2%) followed by uniaxial intermittent dynamic stretch (4%) on C2C12 and murine muscle progenitor cells in a 2D and 3D environment and found that stretch negatively influenced maturation in all cases, demonstrated by decreased expression of MRFs and sarcomere proteins at the RNA level and a delay in the formation of cross striations. We therefore conclude that the current protocol is not recommended for skeletal muscle tissue engineering purposes.

  9. Combined effect of tissue stabilization and protein extraction methods on phosphoprotein analysis.

    PubMed

    Kofanova, Olga A; Fack, Fred; Niclou, Simone P; Betsou, Fay

    2013-06-01

    Preanalytical conditions applied during sample collection and processing can affect the detection or quantification of unstable phosphoprotein biomarkers. We evaluated the consequences of tissue stabilization and protein extraction methods on phosphoprotein analysis. The effects of stabilization techniques (heat stabilization, snap-freezing) and time on the levels of phosphoproteins, including phospho-Akt, p-ERK 1/2, p-IkBα, p-JNK, and p38 MAPK, were evaluated using a BioPlex phosphoprotein assay. Additionally, two different protein extraction protocols, using different extraction buffers (8 M urea buffer, or Bio-Rad buffer without urea) were tested. For snap-frozen samples, protein extraction yields were comparable with the two buffer systems. For heat-stabilized samples, total protein yields were significantly lower following extraction in non-urea buffer. However, the concentrations of specific phosphoproteins were significantly higher in heat-stabilized samples than in the corresponding snap-frozen samples, indicating that this tissue processing method better preserved phosphoproteins. Significant differences were found between the measured phosphoprotein levels in heat-stabilized and snap-frozen tissue, suggesting that alterations occur very rapidly after tissue excision. Our results suggest that heat stabilization can be used as a tissue processing method for subsequent phosphoprotein analyses, but also suggest that the BioPlex phosphoprotein assay could be used as a possible quality control method to assess tissue sample integrity.

  10. Root coverage with a modified laterally positioned flap combined with a subepithelial connective tissue graft in advanced recession.

    PubMed

    Lee, Chun-Teh; Chang, Po-Chun; Touchan, Nawar; Royzman, Daniel

    2014-12-01

    A laterally positioned flap (LPF) combined with a subepithelial connective tissue graft (SCTG) is one of the conventional approaches for resolving gingival recession defects, with the advantages of flap flexibility and extended coverage of the tissue graft. However, thus far, evidence is lacking for the use of this technique for the treatment of advanced gingival recession defects. This report discusses three Miller class III cases with interproximal bone loss and wide and deep defects treated with a combination procedure of a modified laterally positioned flap (mLPF) and SCTG. mLPF combined with SCTG was performed for each case. The defect size and the degree of hypersensitivity at baseline and the final appointment in each case were documented. The three cases had a mean initial defect of 7.7±1.5 mm and a mean residual defect of 1.7±1 mm at the 6-, 3-, and 36-month follow-up, respectively, after the root coverage surgery. The symptom of hypersensitivity was improved, and the patients were satisfied with the clinical outcomes. The results demonstrated that the combination of mLPF with SCTG is promising for treating these advanced cases with respect to obtaining the expected root coverage with the gingival tissue.

  11. Combined chemical and structural signals of biomaterials synergistically activate cell-cell communications for improving tissue regeneration.

    PubMed

    Xu, Yachen; Peng, Jinliang; Dong, Xin; Xu, Yuhong; Li, Haiyan; Chang, Jiang

    2017-04-02

    Biomaterials are only used as carriers of cells in the conventional tissue engineering. Considering the multi-cell environment and active cell-biomaterial interactions in tissue regeneration process, in this study, structural signals of aligned electrospun nanofibers and chemical signals of bioglass (BG) ionic products in cell culture medium are simultaneously applied to activate fibroblast-endothelial co-cultured cells in order to obtain an improved skin tissue engineering construct. Results demonstrate that the combined biomaterial signals synergistically activate fibroblast-endothelial co-culture skin tissue engineering constructs through promotion of paracrine effects and stimulation of gap junctional communication between cells, which results in enhanced vascularization and extracellular matrix protein synthesis in the constructs. Structural signals of aligned electrospun nanofibers play an important role in stimulating both of paracrine and gap junctional communication while chemical signals of BG ionic products mainly enhance paracrine effects. In vivo experiments reveal that the activated skin tissue engineering constructs significantly enhance wound healing as compared to control. This study indicates the advantages of synergistic effects between different bioactive signals of biomaterials can be taken to activate communication between different types of cells for obtaining tissue engineering constructs with improved functions.

  12. Combined TGA-MS kinetic analysis of multistep processes. Thermal decomposition and ceramification of polysilazane and polysiloxane preceramic polymers.

    PubMed

    García-Garrido, C; Sánchez-Jiménez, P E; Pérez-Maqueda, L A; Perejón, A; Criado, José M

    2016-10-26

    The polymer-to-ceramic transformation kinetics of two widely employed ceramic precursors, 1,3,5,7-tetramethyl-1,3,5,7-tetravinylcyclotetrasiloxane (TTCS) and polyureamethylvinylsilazane (CERASET), have been investigated using coupled thermogravimetry and mass spectrometry (TG-MS), Raman, XRD and FTIR. The thermally induced decomposition of the pre-ceramic polymer is the critical step in the synthesis of polymer derived ceramics (PDCs) and accurate kinetic modeling is key to attaining a complete understanding of the underlying process and to attempt any behavior predictions. However, obtaining a precise kinetic description of processes of such complexity, consisting of several largely overlapping physico-chemical processes comprising the cleavage of the starting polymeric network and the release of organic moieties, is extremely difficult. Here, by using the evolved gases detected by MS as a guide it has been possible to determine the number of steps that compose the overall process, which was subsequently resolved using a semiempirical deconvolution method based on the Frasier-Suzuki function. Such a function is more appropriate that the more usual Gaussian or Lorentzian functions since it takes into account the intrinsic asymmetry of kinetic curves. Then, the kinetic parameters of each constituent step were independently determined using both model-free and model-fitting procedures, and it was found that the processes obey mostly diffusion models which can be attributed to the diffusion of the released gases through the solid matrix. The validity of the obtained kinetic parameters was tested not only by the successful reconstruction of the original experimental curves, but also by predicting the kinetic curves of the overall processes yielded by different thermal schedules and by a mixed TTCS-CERASET precursor.

  13. Kinetics of oxygen reduction in perovskite cathodes for solid oxide fuel cells: A combined modeling and experimental approach

    NASA Astrophysics Data System (ADS)

    Miara, Lincoln James

    Solid oxide fuel cells (SOFCs) have the potential to replace conventional stationary power generation technologies; however, there are major obstacles to commercialization, the most problematic of which is poor cathode performance. Commercialization of SOFCs will follow when the mechanisms occurring at the cathode are more thoroughly understood and adapted for market use. The catalytic reduction of oxygen occurring in SOFC cathodes consists of many elementary steps such as gas phase diffusion, chemical and/or electrochemical reactions which lead to the adsorption and dissociation of molecular oxygen onto the cathode surface, mass transport of oxygen species along the surface and/or through the bulk of the cathode, and full reduction and incorporation of the oxygen at the cathode/electrolyte two or three phase boundary. Electrochemical impedance spectroscopy (EIS) is the main technique used to identify the occurrence of these different processes, but when this technique is used without an explicit model describing the kinetics it is difficult to unravel the interdependence of each of these processes. The purpose of this dissertation is to identify the heterogeneous reactions occurring at the cathode of an SOFC by combining experimental EIS results with mathematical models describing the time dependent behavior of the system. This analysis is performed on two different systems. In the first case, experimental EIS results from patterned half cells composed of Ca-doped lanthanum manganite (LCM)| yttria-doped ZrO2 (YSZ) are modeled to investigate the temperature and partial pressure of oxygen, pO2, dependence of oxygen adsorption/dissociation onto the LCM surface, surface diffusion of atomic oxygen, and electrochemical reduction and incorporation of the oxygen into the electrolyte in the vicinity of the triple phase boundary (TPB). This model determines the time-independent state-space equations from which the Faradaic admittance transfer function is obtained. The

  14. Development of a Multi-modal Tissue Diagnostic System Combining High Frequency Ultrasound and Photoacoustic Imaging with Lifetime Fluorescence Spectroscopy

    PubMed Central

    Sun, Yang; Stephens, Douglas N.; Park, Jesung; Sun, Yinghua; Marcu, Laura; Cannata, Jonathan M.; Shung, K. Kirk

    2010-01-01

    We report the development and validate a multi-modal tissue diagnostic technology, which combines three complementary techniques into one system including ultrasound backscatter microscopy (UBM), photoacoustic imaging (PAI), and time-resolved laser-induced fluorescence spectroscopy (TR-LIFS). UBM enables the reconstruction of the tissue microanatomy. PAI maps the optical absorption heterogeneity of the tissue associated with structure information and has the potential to provide functional imaging of the tissue. Examination of the UBM and PAI images allows for localization of regions of interest for TR-LIFS evaluation of the tissue composition. The hybrid probe consists of a single element ring transducer with concentric fiber optics for multi-modal data acquisition. Validation and characterization of the multi-modal system and ultrasonic, photoacoustic, and spectroscopic data coregistration were conducted in a physical phantom with properties of ultrasound scattering, optical absorption, and fluorescence. The UBM system with the 41 MHz ring transducer can reach the axial and lateral resolution of 30 and 65 μm, respectively. The PAI system with 532 nm excitation light from a Nd:YAG laser shows great contrast for the distribution of optical absorbers. The TR-LIFS system records the fluorescence decay with the time resolution of ~300 ps and a high sensitivity of nM concentration range. Biological phantom constructed with different types of tissues (tendon and fat) was used to demonstrate the complementary information provided by the three modalities. Fluorescence spectra and lifetimes were compared to differentiate chemical composition of tissues at the regions of interest determined by the coregistered high resolution UBM and PAI image. Current results demonstrate that the fusion of these techniques enables sequentially detection of functional, morphological, and compositional features of biological tissue, suggesting potential applications in diagnosis of tumors

  15. New Approach for Studying Slow Fragmentation Kinetics in FT-ICR: Surface-Induced Dissociation Combined with Resonant Ejection

    SciTech Connect

    Laskin, Julia; Futrell, Jean H.

    2015-02-01

    We introduce a new approach for studying the kinetics of large ion fragmentation in the gas phase by coupling surface-induced dissociation (SID) in a Fourier transform ion cyclotron resonance mass spectrometer with resonant ejection of selected fragment ions using a relatively short (5 ms) ejection pulse. The approach is demonstrated for singly protonated angiotensin III ions excited by collisions with a self-assembled monolayer of alkylthiol on gold (HSAM). The overall decomposition rate and rate constants of individual reaction channels are controlled by varying the kinetic energy of the precursor ion in a range of 65–95 eV. The kinetics of peptide fragmentation are probed by varying the delay time between resonant ejection and fragment ion detection at a constant total reaction time. RRKM modeling indicates that the shape of the kinetics plots is strongly affected by the shape and position of the energy deposition function (EDF) describing the internal energy distribution of the ion following ion-surface collision. Modeling of the kinetics data provides detailed information on the shape of the EDF and energy and entropy effects of individual reaction channels.

  16. Combined surface micropatterning and reactive chemistry maximizes tissue adhesion with minimal inflammation

    PubMed Central

    Pereira, Maria J. N.; Sundback, Cathryn A.; Lang, Nora; Cho, Woo Kyung; Pomerantseva, Irina; Ouyang, Ben; Tao, Sarah L.; McHugh, Kevin; Mwizerwa, Olive; Vemula, Praveen K.; Mochel, Mark C.; Carter, David J.; Borenstein, Jeffrey T.; Langer, Robert; Ferreira, Lino S.; Karp, Jeffrey M.; Masiakos, Peter T.

    2014-01-01

    The use of tissue adhesives for internal clinical applications is limited due to a lack of materials that balance strong adhesion with biocompatibility. The use of substrate topography was explored to reduce the volume of a highly reactive and toxic glue without compromising adhesive strength. Micro-textured patches coated with a thin layer of cyanoacrylate glue achieved similar adhesion levels to patches employing large amounts of adhesive, and was superior to the level of adhesion achieved when a thin coating was applied to a non-textured patch. In vivo studies demonstrated reduced tissue inflammation and necrosis for patterned patches with a thinly coated layer of reactive glue, thus overcoming a significant challenge with existing tissue adhesives such as cyanoacrylate. Closure of surgical stomach and colon defects in a rat model was achieved without abdominal adhesions. Harnessing the synergy between surface topography and reactive chemistry enables controlled tissue adhesion with an improved biocompatibility profile without requiring changes in the chemical composition of reactive tissue glues. PMID:24106240

  17. Characterization and mapping of dipolar interactions within macromolecules in tissues using a combination of DQF, MT and UTE MRI.

    PubMed

    Eliav, Uzi; Komlosh, Michal; Basser, Peter J; Navon, Gil

    2012-10-01

    This study shows that by combining a double-quantum filtered magnetization transfer (DQF-MT) with an ultra-short TE (UTE) MRI that it is possible to obtain contrast between tissue compartments based on the following characteristics: (a) the residual dipolar coupling interaction within the biomacromolecules, which depends on their structure, (b) residual dipolar interactions within water molecules, and (c) the magnetization exchange rate between biomacromolecules and water. The technique is demonstrated in rat-tail specimens, where the collagenous tissue such as tendons and the annulus pulposus of the disc are highlighted in these images, and their macromolecular properties along with those of bones and muscles can be characterized. DQF-MT UTE MRI also holds promise because collagenous tissues that are typically invisible in conventional MRI experiments produce significant signal intensities using this approach. Copyright © 2012 John Wiley & Sons, Ltd.

  18. Tissue management and retraction technique combined with all-ceramic crowns: case reports.

    PubMed

    Ferrari, M; Nathanson, D

    1995-04-01

    The need to preserve the gingival health during impression making for laboratory fabricated prostheses has been emphasized in literature and clinical practice. This article presents the placement of all-ceramic crowns utilizing a relatively new soft tissue retraction material, a polymer, cut into 2 mm wide strips. The sponge-like texture of the material expands with moisture and exerts gentle pressure on the gingival tissue, effecting a retraction for impressions. The gingival tissue returns to its original position within 24 hours. The learning objective of this article is to share the experience and observations of this procedure and the materials utilized. Several case reports are presented to illustrate the clinical procedure and the results obtained.

  19. Circulatory transport and capillary-tissue exchange as determinants of the distribution kinetics of inulin and antipyrine in dog.

    PubMed

    Weiss, Michael; Krejcie, Tom C; Avram, Michael J

    2007-04-01

    A pharmacokinetic model was developed to estimate physiologically meaningful parameters of distribution kinetics from plasma concentration-time data. The model is based on simultaneously measured disposition curves of drug and vascular marker. Employing residence time distribution theory, a recirculatory model with two subsystems, the pulmonary and systemic circulation, was constructed. In addition to intravascular mixing, the axially distributed model of the systemic circulation accounts for transcapillary transport of solutes, quantified by permeability-surface area product (PS) and diffusional equilibration time. Parameters of ICG, inulin, and antipyrine were estimated from disposition data obtained in awake dogs under control conditions and during an isoproterenol infusion or moderate hypovolemia. Results suggest that distribution kinetics is (1) governed by extravascular diffusion and (2) its dependency on cardiac output decreases with increasing diffusional resistance. Hemorrhage decreased the effective PS of inulin. In conclusion, this novel mechanistic model effectively described both the permeability-limited distribution of inulin into interstitial fluid and the flow-limited distribution of antipyrine into total body water and might be useful for other drugs.

  20. THE COMBINED EFFECTS OF FORMALIN FIXATION AND INDIVIDUAL STEPS IN TISSUE PROCESSING ON IMMUNO-RECOGNITION

    PubMed Central

    Otali, Dennis; Stockard, Cecil R.; Oelschlager, Denise K.; Wan, Wen; Manne, Upender; Watts, Stephen A.; Grizzle, William E.

    2010-01-01

    It is accepted that the aldehyde-based fixation of cells can affect the immunodetection of antigens; however, the effects of tissue processing on immunodetection have not been analyzed systematically. We therefore investigated the effects of aldehyde-based fixation and the individual steps of tissue processing on immunohistochemical detection of specific antigens. DU145 (prostate) and SKOV3 (ovarian) cancer cell lines were cultured as monolayers on microscope slides. The immunohistochemical detection of Ki67/MIB-1 and PCNA was evaluated after various times of fixation in 10% neutral-buffered formalin (NBF) plus after each of the individual cumulative steps of tissue processing. The effect of antigen retrieval (AR) was evaluated concomitantly as an additional variable. Our results indicate that, in addition to fixation, each of the different steps in tissue processing has effects on immunorecognition of the epitopes recognized by these antibodies. The extensive dehydration through ethanols to absolute ethanol had only modest effects except for the detection of Ki67/MIB-1 in SKOV-3 cells where the effect was stronger. In general, however, the establishment of a hydrophobic environment by xylene resulted in the greatest decrease in immunorecognition. Antigen retrieval was able to compensate for most, but not all of the losses in staining following fixation and exposure to xylene; however, AR gave very consistent results for most steps of tissue processing, suggesting that AR should also be used in staining for PCNA. The cellular variations that were noted indicate that the effects of fixation and other steps of tissue processing may depend upon how antigens are packaged by specific cells. PMID:19886759

  1. Evaluation of a combination of continuum and truss finite elements in a model of passive and active muscle tissue.

    PubMed

    Hedenstierna, S; Halldin, P; Brolin, K

    2008-12-01

    The numerical method of finite elements (FE) is a powerful tool for analysing stresses and strains in the human body. One area of increasing interest is the skeletal musculature. This study evaluated modelling of skeletal muscle tissue using a combination of passive non-linear, viscoelastic solid elements and active Hill-type truss elements, the super-positioned muscle finite element (SMFE). The performance of the combined materials and elements was evaluated for eccentric motions by simulating a tensile experiment from a published study on a stimulated rabbit muscle including three different strain rates. It was also evaluated for isometric and concentric contractions. The resulting stress-strain curves had the same overall pattern as the experiments, with the main limitation being sensitivity to the active force-length relation. It was concluded that the SMFE could model active and passive muscle tissue at constant rate elongations for strains below failure, as well as isometric and concentric contractions.

  2. Improved cardiac motion detection from ultrasound images using TDIOF: a combined B-mode/ tissue Doppler approach

    NASA Astrophysics Data System (ADS)

    Tavakoli, Vahid; Stoddard, Marcus F.; Amini, Amir A.

    2013-03-01

    Quantitative motion analysis of echocardiographic images helps clinicians with the diagnosis and therapy of patients suffering from cardiac disease. Quantitative analysis is usually based on TDI (Tissue Doppler Imaging) or speckle tracking. These methods are based on two independent techniques - the Doppler Effect and image registration, respectively. In order to increase the accuracy of the speckle tracking technique and cope with the angle dependency of TDI, herein, a combined approach dubbed TDIOF (Tissue Doppler Imaging Optical Flow) is proposed. TDIOF is formulated based on the combination of B-mode and Doppler energy terms in an optical flow framework and minimized using algebraic equations. In this paper, we report on validations with simulated, physical cardiac phantom, and in-vivo patient data. It is shown that the additional Doppler term is able to increase the accuracy of speckle tracking, the basis for several commercially available echocardiography analysis techniques.

  3. The frontal soft tissue changes in the lower facial portion after orthodontic treatment combined with anterior segmental osteotomy.

    PubMed

    Cha, Young Min; Park, Na Seon; Bayome, Mohamed; Han, Seong-Ho; Kim, Yoonji; Kook, Yoon-Ah

    2011-01-01

    To evaluate changes of the lower facial portion on the frontal view before and after orthodontic treatment combined with anterior segmental osteotomy (ASO) in patients with bimaxillary protrusion. The sample consisted of 16 women in the experimental group who had received ASO and 24 women in the untreated control group. Twelve linear measurements, 5 angular measurements, and the lip perimeter and area were measured and analyzed using unpaired and paired t tests. The upper lip height and lower lip to chin length were significantly greater after treatment. The upper and lower vermilion heights and all vermilion areas decreased significantly, while lip width did not change. Upper lip height was significantly greater in the posttreatment group than in the control group, but there was no difference in upper and total lip areas. Treatment combined with ASO significantly improved the frontal soft tissue proportions. Anticipated frontal soft tissue changes of the lower face should be considered by clinicians for accurate diagnosis and treatment planning.

  4. Combined Raman spectroscopy and optical coherence tomography device for tissue characterization

    PubMed Central

    Patil, Chetan A.; Bosschaart, Nienke; Keller, Matthew D.; van Leeuwen, Ton G.; Mahadevan-Jansen, Anita

    2009-01-01

    We report a dual-modal device capable of sequential acquisition of Raman spectroscopy (RS) and optical coherence tomography (OCT) along a common optical axis. The device enhances application of both RS and OCT by precisely guiding RS acquisition with OCT images while also compensating for the lack of molecular specificity in OCT with the biochemical specificity of RS. We characterize the system performance and demonstrate the capability to identify structurally ambiguous features within an OCT image with RS in a scattering phantom, guide acquisition of RS from a localized malignancy in ex vivo breast tissue, and perform in vivo tissue analysis of a scab. PMID:18483537

  5. Fabrication of scalable tissue engineering scaffolds with dual-pore microarchitecture by combining 3D printing and particle leaching.

    PubMed

    Mohanty, Soumyaranjan; Sanger, Kuldeep; Heiskanen, Arto; Trifol, Jon; Szabo, Peter; Dufva, Marin; Emnéus, Jenny; Wolff, Anders

    2016-04-01

    Limitations in controlling scaffold architecture using traditional fabrication techniques are a problem when constructing engineered tissues/organs. Recently, integration of two pore architectures to generate dual-pore scaffolds with tailored physical properties has attracted wide attention in tissue engineering community. Such scaffolds features primary structured pores which can efficiently enhance nutrient/oxygen supply to the surrounding, in combination with secondary random pores, which give high surface area for cell adhesion and proliferation. Here, we present a new technique to fabricate dual-pore scaffolds for various tissue engineering applications where 3D printing of poly(vinyl alcohol) (PVA) mould is combined with salt leaching process. In this technique the sacrificial PVA mould, determining the structured pore architecture, was filled with salt crystals to define the random pore regions of the scaffold. After crosslinking the casted polymer the combined PVA-salt mould was dissolved in water. The technique has advantages over previously reported ones, such as automated assembly of the sacrificial mould, and precise control over pore architecture/dimensions by 3D printing parameters. In this study, polydimethylsiloxane and biodegradable poly(ϵ-caprolactone) were used for fabrication. However, we show that this technique is also suitable for other biocompatible/biodegradable polymers. Various physical and mechanical properties of the dual-pore scaffolds were compared with control scaffolds with either only structured or only random pores, fabricated using previously reported methods. The fabricated dual-pore scaffolds supported high cell density, due to the random pores, in combination with uniform cell distribution throughout the scaffold, and higher cell proliferation and viability due to efficient nutrient/oxygen transport through the structured pores. In conclusion, the described fabrication technique is rapid, inexpensive, scalable, and compatible

  6. The reversal of diabetes in rat model using mouse insulin producing cells - a combination approach of tissue engineering and macroencapsulation.

    PubMed

    Muthyala, Sudhakar; Raj, V R Rana; Mohanty, Mira; Mohanan, P V; Nair, Prabha D

    2011-05-01

    Type 1 diabetes is a chronic disorder resulting from the autoimmune destruction of insulin-producing cells, a leading cause of morbidity and mortality all over the world. In this study a tissue engineering approach was compared with a macroencapsulation approach to reverse type 1 diabetes in a rat model, using mouse pancreatic progenitor cell (PPC)-derived islet-like clusters and mouse islets. For the tissue engineering approach the cells were cultured on gelatin scaffolds cross-linked with EDC in the presence of polyvinylpyrrolidone in vitro (GPE scaffolds), while for the macroencapsulation approach the cells were encapsulated in polyurethane-polyvinylpyrrolidone semi-interpenetrating networks. In the combination approach the cells cultured on GPE scaffolds were further encapsulated in a polyurethane-polyvinylpyrrolidone capsule. Real time PCR studies and the glucose challenge assay have shown that cells on GPE scaffolds could express and secrete insulin and glucagon in vitro. However, under in vivo conditions the animals treated by the tissue engineering approach died within 15-20 days and showed no reversal of their diabetes, due to infiltration of immune cells such as CD4 and CD8 cells and macrophages. In the macroencapsulation approach the animals showed euglycemia within 25 days, which was maintained for further 20 days, but after that the animals died. Interestingly, in the combination approach the animals showed reversal of hyperglycemia, and remained euglycemic for up to 3 months. The time needed to achieve initial euglycemia was different with different cell types, i.e. the combination approach with mouse islets achieved euglycemia within 15 days, whereas with PPC-derived islet-like clusters euglycemia was achieved within 25 days. This study confirmed that a combination of tissue engineering and macroencapsulation with mouse islets could reverse diabetes and maintain euglycemia in an experimental diabetes rat model for 90 days.

  7. Understanding the Differences in Molecular Conformation of Carbohydrate and Protein in Endosperm Tissues of Grains with Different Biodegradation Kinetics Using Advanced Synchrotron Technology

    SciTech Connect

    Yu, P.; Block, H; Doiron, K

    2009-01-01

    Conventional 'wet' chemical analyses rely heavily on the use of harsh chemicals and derivatization, thereby altering native seed structures leaving them unable to detect any original inherent structures within an intact tissue sample. A synchrotron is a giant particle accelerator that turns electrons into light (million times brighter than sunlight) which can be used to study the structure of materials at the molecular level. Synchrotron radiation-based Fourier transform IR microspectroscopy (SR-FTIRM) has been developed as a rapid, direct, non-destructive and bioanalytical technique. This technique, taking advantage of the brightness of synchrotron light and a small effective source size, is capable of exploring the molecular chemistry within the microstructures of a biological tissue without the destruction of inherent structures at ultraspatial resolutions within cellular dimensions. This is in contrast to traditional 'wet' chemical methods, which, during processing for analysis, often result in the destruction of the intrinsic structures of feeds. To date there has been very little application of this technique to the study of plant seed tissue in relation to nutrient utilization. The objective of this study was to use novel synchrotron radiation-based technology (SR-FTIRM) to identify the differences in the molecular chemistry and conformation of carbohydrate and protein in various plant seed endosperms within intact tissues at cellular and subcellular level from grains with different biodegradation kinetics. Barley grain (cv. Harrington) with a high rate (31.3%/h) and extent (78%), corn grain (cv. Pioneer) with a low rate (9.6%/h) and extent of (57%), and wheat grain (cv. AC Barrie) with an intermediate rate (23%/h) and extent (72%) of ruminal DM degradation were selected for evaluation. SR-FTIRM evaluations were performed at the National Synchrotron Light Source at the Brookhaven National Laboratory (Brookhaven, NY). These results suggest that SR-FTIRM plus

  8. Studies on some kinetic parameters of aminotransferases in tissues of the snail, Pila globosa (Swainson) during malathion intoxication.

    PubMed

    Sahib, I K; Rao, K R

    1988-01-01

    The aspartate and alanine aminotransferases in the tissues of the snail, Pila globosa showed high catalytic potentials (low Km and high Vmax) during malathion exposure in vivo. In vitro addition of different concentrations of malathion did not influence aminotransferase activity. The results are discussed in relation to the regulative influence of the intracellular environment of the cell.

  9. Calculation of the kinetics of heating and structural changes in the cartilaginous tissue under the action of laser radiation

    SciTech Connect

    Sobol', E N; Kitai, M S

    1998-07-31

    A theoretical model is developed for the calculation of the temperature fields and determination of the size of a zone with structural changes in the cartilaginous tissue. The model is based on a simultaneous analysis of the heat and mass transfer processes and it takes into account the bulk absorption of laser radiation by the tissue, surface evaporation of water, and temperature dependences of the diffusion coefficients. It is assumed that under the influence of a phase transition between free and bound water, caused by heating of the cartilage to 70{sup 0}C, the proteoglycans of the cartilage matrix become mobile and, as a result of such mass transfer, structural changes are induced in the cartilaginous tissue causing relaxation of stresses or denaturation. It is shown that the maximum temperature is then reached not on the irradiated surface but at some distance from it, and that the size of the zones of structural changes (denaturation depth) depends strongly on the energy density of the laser radiation and its wavelength, on the duration of the irradiation, and on the cartilage thickness. This model makes it possible to calculate the temperature fields and the depth of structural changes in laser-induced relaxation of stresses and changes in the shape of the cartilaginous tissue. (interaction of laser radiation with matter)

  10. Measurement of L-(1-/sup 14/C)leucine kinetics in splanchnic and leg tissues in humans. Effect of amino acid infusion

    SciTech Connect

    Gelfand, R.A.; Glickman, M.G.; Castellino, P.; Louard, R.J.; DeFronzo, R.A.

    1988-10-01

    Although whole-body leucine flux is widely measured to study body protein turnover in humans, the contribution of specific tissues to the total-body measurement remains unknown. By combining the organ-balance technique with the systemic infusion of L-(1-14C)leucine, we quantitated leucine production and disposal by splanchnic and leg tissues and by the whole body, simultaneously, in six normal men before and during amino acid infusion. At steady state, disposal of arterial leucine by splanchnic and leg tissues was calculated from the percent extraction (E) of L-(1-14C)leucine counts: uptake = E x (Leu)a x flow. Tissue release of cold leucine (from protein turnover) into vein was calculated as the difference between leucine uptake and the net tissue leucine balance. In the postabsorptive state, despite substantial (P less than .01) extraction of L-(1-14C)leucine by splanchnic (23 +/- 1%) and leg (18 +/- 2%) tissues, net leucine balance across both tissue beds was small, indicating active simultaneous disposal and production of leucine at nearly equivalent rates. Splanchnic tissues accounted for approximately 50% of the measured total-body leucine flux. During amino acid infusion, the net leucine balance across splanchnic and leg tissues became positive, reflecting not only an increase in leucine uptake but also a marked suppression (by approximately 50%, P less than .02) of cold leucine release. This reduction in splanchnic and leg leucine release was indicated by a sharp decline in whole-body endogenous leucine flux.

  11. A system for combined three-dimensional morphological and molecular analysis of thick tissue specimens

    SciTech Connect

    Fernandez-Gonzalez, Rodrigo; Jones, Arthur; Garcia-Rodriguez, Enrique; Yuan Chen, Ping; Idica, Adam; Lockett, Stephen J.; Barcellos-Hoff, Mary Helen; Ortiz-de-Solorzano, Carlos

    2002-04-25

    We present a new system for simultaneous morphological and molecular analysis of thick tissue samples. The system is composed of a computer assisted microscope and a JAVA-based image display, analysis and visualization program that allows acquisition, annotation, meaningful storage, three-dimensional reconstruction and analysis of structures of interest in thick sectioned tissue specimens. We describe the system in detail and illustrate its use by imaging, reconstructing and analyzing two complete tissue blocks which were differently processed and stained. One block was obtained from a ductal carcinoma in situ (DCIS) lumpectomy specimen and stained alternatively with Hematoxilyn and Eosin (H&E), and with a counterstain and fluorescence in situ hybridization (FISH) to the ERB-B2 gene. The second block contained a fully sectioned mammary gland of a mouse, stained for Histology with H&E. We show how the system greatly reduces the amount of interaction required for the acquisition and analysis and is therefore suitable for studies that require morphologically driven, wide scale (e.g., whole gland) analysis of complex tissue samples or cultures.

  12. Combined ab initio and kinetic Monte Carlo simulations of C diffusion on the √(3)×√(3) β-SiC (111) surface

    NASA Astrophysics Data System (ADS)

    Righi, M. C.; Pignedoli, C. A.; di Felice, R.; Bertoni, C. M.; Catellani, A.

    2005-02-01

    We investigate the kinetic behavior of a single C adatom on the 3×3 β-SiC(111) surface by means of combined ab initio and kinetic Monte Carlo simulations. After identifying the metastable binding locations, we calculate the energy barriers the adatom must overcome when jumping among them. The presence of the 3×3 reconstruction creates considerable differences among the diffusion mechanisms that can be thermally activated. This has important implications for the C mobility on the surface, and therefore for SiC growth. The kinetic simulation at realistic temperatures and time scales revealed that C diffusion occurs mostly around the Si adatoms forming the 3×3 reconstruction. A reduced adatom mobility, as observed in many studies of surfactant-mediated growth, can favor the formation of a high density of nuclei, and thus promote a layer-by-layer growth. As a further result of the kinetic simulation we obtained the adatom diffusion coefficient, a macroscopic quantity accessible in experiments.

  13. Small-volume, ultrahigh-vacuum-compatible high-pressure reaction cell for combined kinetic and in situ IR spectroscopic measurements on planar model catalysts

    NASA Astrophysics Data System (ADS)

    Zhao, Z.; Diemant, T.; Häring, T.; Rauscher, H.; Behm, R. J.

    2005-12-01

    We describe the design and performance of a high-pressure reaction cell for simultaneous kinetic and in situ infrared reflection (IR) spectroscopic measurements on model catalysts at elevated pressures, between 10-3 and 103mbars, which can be operated both as batch reactor and as flow reactor with defined gas flow. The cell is attached to an ultrahigh-vacuum (UHV) system, which is used for sample preparation and also contains facilities for sample characterization. Specific for this design is the combination of a small cell volume, which allows kinetic measurements with high sensitivity under batch or continuous flow conditions, the complete isolation of the cell from the UHV part during UHV measurements, continuous temperature control during both UHV and high-pressure operation, and rapid transfer between UHV and high-pressure stage. Gas dosing is performed by a designed gas-handling system, which allows operation as flow reactor with calibrated gas flows at adjustable pressures. To study the kinetics of reactions on the model catalysts, a quadrupole mass spectrometer is connected to the high-pressure cell. IR measurements are possible in situ by polarization-modulation infrared reflection-absorption spectroscopy, which also allows measurements at elevated pressures. The performance of the setup is demonstrated by test measurements on the kinetics for CO oxidation and the CO adsorption on a Au /TiO2/Ru(0001) model catalyst film at 1-50 mbar total pressure.

  14. A Kinetic Study of Accumulation and Elimination of Microcystin-LR in Yellow Perch (Perca Flavescens) Tissue and Implications for Human Fish Consumption

    PubMed Central

    Dyble, Julianne; Gossiaux, Duane; Landrum, Peter; Kashian, Donna R.; Pothoven, Steven

    2011-01-01

    Fish consumption is a potential route of human exposure to the hepatotoxic microcystins, especially in lakes and reservoirs that routinely experience significant toxic Microcystis blooms. Understanding the rates of uptake and elimination for microcystins as well as the transfer efficiency into tissues of consumers are important for determining the potential for microcystins to be transferred up the food web and for predicting potential human health impacts. The main objective of this work was to conduct laboratory experiments to investigate the kinetics of toxin accumulation in fish tissue. An oral route of exposure was employed in this study, in which juvenile yellow perch (Perca flavescens) were given a single oral dose of 5 or 20 μg of microcystin-LR (MC-LR) via food and accumulation in the muscle, liver, and tank water were measured over 24 h. Peak concentrations of the water soluble fraction of microcystin were generally observed 8–10 h after dosing in the liver and after 12–16 h in the muscle, with a rapid decline in both tissues by 24 h. Up to 99% of the total recoverable (i.e., unbound) microcystin was measured in the tank water by 16 h after exposure. The relatively rapid uptake and elimination of the unbound fraction of microcystin in the liver and muscle of juvenile yellow perch within 24 h of exposure indicates that fish consumption may not be a major route of human exposure to microcystin, particularly in the Great Lakes. PMID:22363240

  15. Tissue-specific alterations in thyroid hormone homeostasis in combined Mct10 and Mct8 deficiency.

    PubMed

    Müller, Julia; Mayerl, Steffen; Visser, Theo J; Darras, Veerle M; Boelen, Anita; Frappart, Lucien; Mariotta, Luca; Verrey, Francois; Heuer, Heike

    2014-01-01

    The monocarboxylate transporter Mct10 (Slc16a10; T-type amino acid transporter) facilitates the cellular transport of thyroid hormone (TH) and shows an overlapping expression with the well-established TH transporter Mct8. Because Mct8 deficiency is associated with distinct tissue-specific alterations in TH transport and metabolism, we speculated that Mct10 inactivation may compromise the tissue-specific TH homeostasis as well. However, analysis of Mct10 knockout (ko) mice revealed normal serum TH levels and tissue TH content in contrast to Mct8 ko mice that are characterized by high serum T3, low serum T4, decreased brain TH content, and increased tissue TH concentrations in the liver, kidneys, and thyroid gland. Surprisingly, mice deficient in both TH transporters (Mct10/Mct8 double knockout [dko] mice) showed normal serum T4 levels in the presence of elevated serum T3, indicating that the additional inactivation of Mct10 partially rescues the phenotype of Mct8 ko mice. As a consequence of the normal serum T4, brain T4 content and hypothalamic TRH expression were found to be normalized in the Mct10/Mct8 dko mice. In contrast, the hyperthyroid situation in liver, kidneys, and thyroid gland of Mct8 ko mice was even more severe in Mct10/Mct8 dko animals, suggesting that in these organs, both transporters contribute to the TH efflux. In summary, our data indicate that Mct10 indeed participates in tissue-specific TH transport and also contributes to the generation of the unusual serum TH profile characteristic for Mct8 deficiency.

  16. Tissue engineering for lateral ridge augmentation with recombinant human bone morphogenetic protein 2 combination therapy: a case report.

    PubMed

    Mandelaris, George A; Spagnoli, Daniel B; Rosenfeld, Alan L; McKee, James; Lu, Mei

    2015-01-01

    This case report describes a tissue-engineered reconstruction with recombinant human bone morphogenetic protein 2/acellular collagen sponge (rhBMP-2/ ACS) + cancellous allograft and space maintenance via Medpor Contain mesh in the treatment of a patient requiring maxillary and mandibular horizontal ridge augmentation to enable implant placement. The patient underwent a previously unsuccessful corticocancellous bone graft at these sites. Multiple and contiguous sites in the maxilla and in the mandibular anterior, demonstrating advanced lateral ridge deficiencies, were managed using a tissue engineering approach as an alternative to autogenous bone harvesting. Four maxillary and three mandibular implants were placed 9 and 10 months, respectively, after tissue engineering reconstruction, and all were functioning successfully after 24 months of follow-up. Histomorphometric analysis of a bone core obtained at the time of the maxillary implant placement demonstrated a mean of 76.1% new vital bone formation, 22.2% marrow/cells, and 1.7% residual graft tissue. Tissue engineering for lateral ridge augmentation with combination therapy requires further research to determine predictability and limitations.

  17. A combined kinetic and diffusion model for pyrite oxidation in tailings: a change in controls with time

    NASA Astrophysics Data System (ADS)

    Elberling, , B.; Nicholson, R. V.; Scharer, J. M.

    1994-05-01

    Acidic drainage from the oxidation of mine tailing wastes is an important environmental problem. The purpose of this paper is to develop a model (1) to simulate the rate of oxidation of pyrite over time, (2) to verify the importance of chemical kinetic control and diffusion control on the oxidation rate with time and, (3) to evaluate the sensitivity of the model to critical parameters of the tailings, such as grain size, pyrite content and the effective diffusion coefficient. The source code comprises four main modules including parameter allocation (kinetics, transport), sulphide oxidation (shrinking particle), oxygen transport and pyrite mass balance. The results show that high oxidation rates are observed in the initial time after tailings deposition. During this initial period of high rates, an apparent shift occurs from kinetic to diffusional control over a period of time that depends on the composition and properties of the tailings. Based on the simulation results, it is evident that the overall rate of oxidation after a few years will be controlled dominantly by the diffusion of oxygen rather than by biological or non-biological kinetics in the tailings.

  18. Combined Homogeneous Surface Diffusion Model - Design of experiments approach to optimize dye adsorption considering both equilibrium and kinetic aspects.

    PubMed

    Muthukkumaran, A; Aravamudan, K

    2017-09-12

    Adsorption, a popular technique for removing azo dyes from aqueous streams, is influenced by several factors such as pH, initial dye concentration, temperature and adsorbent dosage. Any strategy that seeks to identify optimal conditions involving these factors, should take into account both kinetic and equilibrium aspects since they influence rate and extent of removal by adsorption. Hence rigorous kinetics and accurate equilibrium models are required. In this work, the experimental investigations pertaining to adsorption of acid orange 10 dye (AO10) on activated carbon were carried out using Central Composite Design (CCD) strategy. The significant factors that affected adsorption were identified to be solution temperature, solution pH, adsorbent dosage and initial solution concentration. Thermodynamic analysis showed the endothermic nature of the dye adsorption process. The kinetics of adsorption has been rigorously modeled using the Homogeneous Surface Diffusion Model (HSDM) after incorporating the non-linear Freundlich adsorption isotherm. Optimization was performed for kinetic parameters (color removal time and surface diffusion coefficient) as well as the equilibrium affected response viz. percentage removal. Finally, the optimum conditions predicted were experimentally validated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Controllable degradation kinetics of POSS nanoparticle-integrated poly(ε-caprolactone urea)urethane elastomers for tissue engineering applications

    PubMed Central

    Yildirimer, Lara; Buanz, Asma; Gaisford, Simon; Malins, Edward L.; Remzi Becer, C.; Moiemen, Naiem; Reynolds, Gary M.; Seifalian, Alexander M.

    2015-01-01

    Biodegradable elastomers are a popular choice for tissue engineering scaffolds, particularly in mechanically challenging settings (e.g. the skin). As the optimal rate of scaffold degradation depends on the tissue type to be regenerated, next-generation scaffolds must demonstrate tuneable degradation patterns. Previous investigations mainly focussed on the integration of more or less hydrolysable components to modulate degradation rates. In this study, however, the objective was to develop and synthesize a family of novel biodegradable polyurethanes (PUs) based on a poly(ε-caprolactone urea)urethane backbone integrating polyhedral oligomeric silsesquioxane (POSS-PCLU) with varying amounts of hard segments (24%, 28% and 33% (w/v)) in order to investigate the influence of hard segment chemistry on the degradation rate and profile. PUs lacking POSS nanoparticles served to prove the important function of POSS in maintaining the mechanical structures of the PU scaffolds before, during and after degradation. Mechanical testing of degraded samples revealed hard segment-dependent modulation of the materials’ viscoelastic properties, which was attributable to (i) degradation-induced changes in the PU crystallinity and (ii) either the presence or absence of POSS. In conclusion, this study presents a facile method of controlling degradation profiles of PU scaffolds used in tissue engineering applications. PMID:26463421

  20. A Combination Tissue Engineering Strategy for Schwann Cell-Induced Spinal Cord Repair

    DTIC Science & Technology

    2016-10-01

    Cytocompatibility studies of the piezoelectric scaffold formulation for controlled release. Rat SCs, isolated from adult sciatic nerve and transfected...using purified DRG explants. Lumbar DRG explants isolated from E17 rat embryos were seeded on collagen coated petri dishes in purification media for...with neural tissues in the central nerve system when used at the concentration of 15%-20% (w/w) and prolonged drug release has been achieved with

  1. Combined submuscular tissue expansion and anterior component separation technique for abdominal wall reconstruction: Long-term outcome analysis.

    PubMed

    Alleyne, Brendan; Ozturk, Cemile Nurdan; Rampazzo, Antonio; Johnson, Jeffrey; Gurunluoglu, Raffi

    2017-06-01

    We report the long-term outcome analysis of 12 patients who underwent two-stage abdominal wall reconstruction using combined submuscular tissue expansion and anterior components separation (CS) technique. Outcome measures were (1) the patients were assessed for the presence or absence of recurrence; (2) patient-reported outcomes on physical functioning in relation with the abdominal wall reconstruction were evaluated using the SF 36-item health survey. The mean age, average expansion volume, and mean time expansion were 37.5 years, 1250 cc, and 9.5 weeks, respectively. The average soft tissue deficiency size was 15.5 (width) × 19.5 (length) cm(2). The average fascial defect was 17 (width) × 21.5 (length) cm(2). No mesh-assisted technique was required. Primary closure was obtained in all. The average follow-up was 39.6 months. Hernia recurrence was noted in one patient (8.3%). All 12 patients completed the SF 36-item health survey. Moreover, 75% of the patients reported 100%, indicating "Not limited in vigorous activities," and 25% indicated "limited a little." All patients reported 100% "not limited at all" in lifting or carrying groceries, climbing several flights of stairs, climbing one flight of stairs, bending, kneeling, stooping, walking more than a mile, walking several blocks, walking one block, bathing, or dressing. Parietal laxity obtained with tissue expansion increases the possibility of direct closure of the fascial layer, skin, and subcutaneous tissue components. Combined use of tissue expansion and CS may result in favorable long-term outcomes as evidenced by patient-reported physical functioning data and low rate of hernia recurrence. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  2. Combining mechanical foaming and thermally induced phase separation to generate chitosan scaffolds for soft tissue engineering.

    PubMed

    Biswas, D P; Tran, P A; Tallon, C; O'Connor, A J

    2017-02-01

    In this paper, a novel foaming methodology consisting of turbulent mixing and thermally induced phase separation (TIPS) was used to generate scaffolds for tissue engineering. Air bubbles were mechanically introduced into a chitosan solution which forms the continuous polymer/liquid phase in the foam created. The air bubbles entrained in the foam act as a template for the macroporous architecture of the final scaffolds. Wet foams were crosslinked via glutaraldehyde and frozen at -20 °C to induce TIPS in order to limit film drainage, bubble coalescence and Ostwald ripening. The effects of production parameters, including mixing speed, surfactant concentration and chitosan concentration, on foaming are explored. Using this method, hydrogel scaffolds were successfully produced with up to 80% porosity, average pore sizes of 120 μm and readily tuneable compressive modulus in the range of 2.6 to 25 kPa relevant to soft tissue engineering applications. These scaffolds supported 3T3 fibroblast cell proliferation and penetration and therefore show significant potential for application in soft tissue engineering.

  3. Histone modifications patterns in tissues and tumours from acute promyelocytic leukemia xenograft model in response to combined epigenetic therapy.

    PubMed

    Valiulienė, Giedrė; Treigytė, Gražina; Savickienė, Jūratė; Matuzevičius, Dalius; Alksnė, Milda; Jarašienė-Burinskaja, Rasa; Bukelskienė, Virginija; Navakauskas, Dalius; Navakauskienė, Rūta

    2016-04-01

    Xenograft models are suitable for in vivo study of leukemia's pathogenesis and the preclinical development of anti-leukemia agents but understanding of epigenetic regulatory mechanisms linking to adult cell functions in pathological conditions during different in vivo treatments is yet unknown. In this study, for the first time epigenetic chromatin modifications were characterized in tissues and tumours from murine xenograft model generated using the human acute promyelocytic leukemia (APL) NB4 cells engrafted in immunodeficient NOG mice. Xenografts were subjected to combined epigenetic treatment by histone deacetylase inhibitor Belinostat, histone methyltransferase inhibitor 3-DZNeaplanocin A and all-trans-retinoic acid based on in vitro model, where such combination inhibited NB4 cell growth and enhanced retinoic acid-induced differentiation to granulocytes. Xenotransplantation was assessed by peripheral blood cells counts, the analysis of cell surface markers (CD15, CD33, CD45) and the expression of certain genes (PML-RAR alpha, CSF3, G-CSFR, WT1). The combined treatment prolonged APL xenograft mice survival and prevented tumour formation. The analysis of the expression of histone marks such as acetylation of H4, trimethylation of H3K4, H3K9 and H3K27 in APL xenograft mice tumours and tissues demonstrated tissue-specific changes in the level of histone modifications and the APL prognostic mark, WT1 protein. In summary, the effects of epigenetic agents used in this study were positive for leukemia prevention and linked to a modulation of the chromatin epigenetic environment in adult tissues of malignant organism.

  4. A Combined Kinetic and Volatility Basis Set Approach to Model Secondary Organic Aerosol from Toluene and Diesel Exhaust/Meat Cooking Mixtures

    NASA Astrophysics Data System (ADS)

    Parikh, H. M.; Carlton, A. G.; Zhang, H.; Kamens, R.; Vizuete, W.

    2011-12-01

    Secondary organic aerosol (SOA) is simulated for 6 outdoor smog chamber experiments using a SOA model based on a kinetic chemical mechanism in conjunction with a volatility basis set (VBS) approach. The experiments include toluene, a non-SOA-forming hydrocarbon mixture, diesel exhaust or meat cooking emissions and NOx, and are performed under varying conditions of relative humidity. SOA formation from toluene is modeled using a condensed kinetic aromatic mechanism that includes partitioning of lumped semi-volatile products in particle organic-phase and incorporates particle aqueous-phase chemistry to describe uptake of glyoxal and methylglyoxal. Modeling using the kinetic mechanism alone, along with primary organic aerosol (POA) from diesel exhaust (DE) /meat cooking (MC) fails to simulate the rapid SOA formation at the beginning hours of the experiments. Inclusion of a VBS approach with the kinetic mechanism to characterize the emissions and chemistry of complex mixture of intermediate volatility organic compounds (IVOCs) from DE/MC, substantially improves SOA predictions when compared with observed data. The VBS model includes photochemical aging of IVOCs and evaporation of POA after dilution. The relative contribution of SOA mass from DE/MC is as high as 95% in the morning, but substantially decreases after mid-afternoon. For high humidity experiments, aqueous-phase SOA fraction dominates the total SOA mass at the end of the day (approximately 50%). In summary, the combined kinetic and VBS approach provides a new and improved framework to semi-explicitly model SOA from VOC precursors in conjunction with a VBS approach that can be used on complex emission mixtures comprised with hundreds of individual chemical species.

  5. Effects of particle size and coating on toxicologic parameters, fecal elimination kinetics and tissue distribution of acutely ingested silver nanoparticles in a mouse model.

    PubMed

    Bergin, Ingrid L; Wilding, Laura A; Morishita, Masako; Walacavage, Kim; Ault, Andrew P; Axson, Jessica L; Stark, Diana I; Hashway, Sara A; Capracotta, Sonja S; Leroueil, Pascale R; Maynard, Andrew D; Philbert, Martin A

    2016-01-01

    Consumer exposure to silver nanoparticles (AgNP) via ingestion can occur due to incorporation of AgNP into products such as food containers and dietary supplements. AgNP variations in size and coating may affect toxicity, elimination kinetics or tissue distribution. Here, we directly compared acute administration of AgNP of two differing coatings and sizes to mice, using doses of 0.1, 1 and 10 mg/kg body weight/day administered by oral gavage for 3 days. The maximal dose is equivalent to 2000× the EPA oral reference dose. Silver acetate at the same doses was used as ionic silver control. We found no toxicity and no significant tissue accumulation. Additionally, no toxicity was seen when AgNP were dosed concurrently with a broad-spectrum antibiotic. Between 70.5% and 98.6% of the administered silver dose was recovered in feces and particle size and coating differences did not significantly influence fecal silver. Peak fecal silver was detected between 6- and 9-h post-administration and <0.5% of the administered dose was cumulatively detected in liver, spleen, intestines or urine at 48 h. Although particle size and coating did not affect tissue accumulation, silver was detected in liver, spleen and kidney of mice administered ionic silver at marginally higher levels than those administered AgNP, suggesting that silver ion may be more bioavailable. Our results suggest that, irrespective of particle size and coating, acute oral exposure to AgNP at doses relevant to potential human exposure is associated with predominantly fecal elimination and is not associated with accumulation in tissue or toxicity.

  6. Effects of particle size and coating on toxicologic parameters, fecal elimination kinetics and tissue distribution of acutely ingested silver nanoparticles in a mouse model

    PubMed Central

    Bergin, Ingrid L.; Wilding, Laura A.; Morishita, Masako; Walacavage, Kim; Ault, Andrew P.; Axson, Jessica L.; Stark, Diana I.; Hashway, Sara A.; Capracotta, Sonja S.; Leroueil, Pascale R.; Maynard, Andrew D.; Philbert, Martin A.

    2015-01-01

    Consumer exposure to silver nanoparticles (AgNP) via ingestion can occur due to incorporation of AgNP into products such as food containers and dietary supplements. AgNP variations in size and coating may affect toxicity, elimination kinetics or tissue distribution. Here, we directly compared acute administration of AgNP of two differing coatings and sizes to mice, using doses of 0.1, 1 and 10 mg/kg body weight/day administered by oral gavage for 3 days. The maximal dose is equivalent to 2000× the EPA oral reference dose. Silver acetate at the same doses was used as ionic silver control. We found no toxicity and no significant tissue accumulation. Additionally, no toxicity was seen when AgNP were dosed concurrently with a broad-spectrum antibiotic. Between 70.5% and 98.6% of the administered silver dose was recovered in feces and particle size and coating differences did not significantly influence fecal silver. Peak fecal silver was detected between 6- and 9-h post-administration and <0.5% of the administered dose was cumulatively detected in liver, spleen, intestines or urine at 48 h. Although particle size and coating did not affect tissue accumulation, silver was detected in liver, spleen and kidney of mice administered ionic silver at marginally higher levels than those administered AgNP, suggesting that silver ion may be more bioavailable. Our results suggest that, irrespective of particle size and coating, acute oral exposure to AgNP at doses relevant to potential human exposure is associated with predominantly fecal elimination and is not associated with accumulation in tissue or toxicity. PMID:26305411

  7. Growth hormone, alone and in combination with insulin, increases whole body and skeletal muscle protein kinetics in cancer patients after surgery.

    PubMed Central

    Berman, R S; Harrison, L E; Pearlstone, D B; Burt, M; Brennan, M F

    1999-01-01

    OBJECTIVE: To investigate the impact of growth hormone, alone and in combination with insulin, on the protein kinetics of patients with upper gastrointestinal (GI) tract cancer who have undergone surgery and are receiving total parenteral nutrition (TPN). SUMMARY BACKGROUND DATA: Patients with malignancies of the upper GI tract are at increased risk for malnutrition and perioperative death and complications. Standard nutritional support has not significantly altered outcome. Growth hormone (GH) and insulin have been shown to have some benefit in patients with cancer; however, their action in patients undergoing resection has not previously been studied. METHODS: Thirty patients undergoing surgery for upper GI tract malignancies were prospectively randomized into one of three nutritional support groups after surgery: 10 patients received standard TPN, 10 received TPN plus daily injections of GH, and 10 received daily GH, systemic insulin, and TPN. The patients underwent a protein kinetic radiotracer study on the fifth day after surgery to determine whole body and skeletal muscle protein kinetics. RESULTS: Patients who received standard TPN only were in a state of negative skeletal muscle protein net balance. Those who received GH and insulin had improved skeletal muscle protein net balance compared with the TPN only group. Whole body protein net balance was improved in the GH and the GH and insulin groups compared with the TPN only group. GH and insulin combined did not improve whole body net balance more than GH alone. GH administration significantly increased serum IGF-1 and GH levels. Insulin infusion significantly increased serum insulin levels and the insulin/glucagon ratio. CONCLUSION: Growth hormone and GH plus insulin regimens improve protein kinetic parameters in patients with upper GI tract cancer who are receiving TPN after undergoing surgery. PMID:9923794

  8. A new linearly-combined bi-exponential model for kinetic analysis of the isometric relaxation process of Bufo gastrocnemius under electric stimulation in vitro.

    PubMed

    Guo, Rui; Li, Sheng-bing; Zhao, Li-na; Zhao, Yun-sheng; Lu, Wei; Yuan, Pei; Deng, Ping; Liao, Fei

    2007-12-01

    There was a slow-relaxing tail of skeletal muscles in vitro upon the inhibition of Ca(2+)-pump by cyclopiazonic acid (CPA). Herein, a new linearly-combined bi-exponential model to resolve this slow-relaxing tail from the fast-relaxing phase was investigated for kinetic analysis of the isometric relaxation process of Bufo gastrocnemius in vitro, in comparison to the single exponential model and the classical bi-exponential model. During repetitive stimulations at a 2-s interval by square pulses of a 2-ms duration at 12 V direct currency (DC), the isometric tension of Bufo gastrocnemius was recorded at 100 Hz. The relaxation curve with tensions falling from 90% of the peak to the 15th datum before next stimulation was analyzed by three exponential models using a program in MATLAB 6.5. Both the goodness of fit and the distribution of the residuals for the best fitting supported the comparable validity of this new bi-exponential model for kinetic analysis of the relaxation process of the control muscles. After CPA treatment, however, this new bi-exponential model showed an obvious statistical superiority for kinetic analysis of the muscle relaxation process, and it gave the estimated rest tension consistent to that by experimentation, whereas both the classical bi-exponential model and the single exponential model gave biased rest tensions. Moreover, after the treatment of muscles by CPA, both the single exponential model and the classical bi-exponential model yielded lowered relaxation rates, nevertheless, this new bi-exponential model had relaxation rates of negligible changes except much higher rest tensions. These results suggest that this novel linearly-combined bi-exponential model is desirable for kinetic analysis of the relaxation process of muscles with altered Ca(2+)-pumping activity.

  9. Combined administration of naked DNA vectors encoding VEGF and bFGF enhances tissue perfusion and arteriogenesis in ischemic hindlimb.

    PubMed

    Lee, Jung-Sun; Kim, Jeong-Min; Kim, Koung Li; Jang, Hyung-Suk; Shin, In-Soon; Jeon, Eun-Seok; Suh, Wonhee; Byun, Jonghoe; Kim, Duk-Kyung

    2007-09-07

    Few studies have examined in detail the combined effects of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) gene delivery on collateral development. Here, we evaluated the potential synergism of naked DNA vectors encoding VEGF and bFGF using a skeletal-muscle based ex vivo angiogenesis assay and compared tissue perfusion and limb loss in a murine model of hindlimb ischemia. In the ex vivo angiogenesis assay, the VEGF+bFGF combination group had a larger capillary sprouting area than those of the LacZ, VEGF, and bFGF groups. Consistent with these results, regional blood flow recovery on day 14 was also highest in the VEGF+bFGF combination group, followed by the bFGF, VEGF, and LacZ groups. The limb loss frequency was 0% in the combination group, whereas the limb loss frequencies of the other groups were 7-29%. The ischemic muscles of the combination group revealed evidence of increased angiogenesis and arteriogenesis and the upregulated expression of genes that may be associated with arteriogenesis, such as those for cardiac ankyrin repeat protein, early growth response factor-1, and transforming growth factor-beta1. Our study has implications for the development of a combined gene therapy for the vascular occlusive diseases.

  10. A combination of resveratrol and quercetin induces browning in white adipose tissue of rats fed an obesogenic diet.

    PubMed

    Arias, Noemí; Picó, Catalina; Teresa Macarulla, M; Oliver, Paula; Miranda, Jonatan; Palou, Andreu; Portillo, María P

    2017-01-01

    To analyze whether a combination of quercetin (Q) and resveratrol (RSV) would induce a white adipose tissue (WAT) browning effect. Thirty-six rats were fed an obesogenic diet and divided into four groups: control, treated with RSV (15 mg/kg body weight/day; RSV group), treated with Q (30 mg/kg body weight/day; Q group), or treated with both polyphenols (RSV + Q group). After 6 weeks, body and WAT weights were significantly reduced in the RSV + Q group. In perirenal WAT of the control, RSV, and Q groups, white unilocular adipocytes appeared in the majority of cells, while in the RSV + Q group numerous multilocular adipocytes with positive immunostaining for UCP1 were observed. The presence of UCP1 was confirmed by Western blot. This group also revealed increased mRNA levels of Cidea, Hocx9, Bmp4, Slc27a1, Pat2, Atgl, and Atp5d. Interscapular brown adipose tissue weight showed no differences between groups, but the Cidea mRNA level was increased in the RSV group, the Cox-2 mRNA level in the RSV + Q group, and UCP1 protein expression in the RSV and the RSV + Q groups. This study demonstrated that the RSV + Q combination produces a brown-like remodeling effect in perirenal WAT, as well as increased UCP1 protein expression in interscapular brown adipose tissue. © 2016 The Obesity Society.

  11. Measurement of pressure-displacement kinetics of hemoglobin in normal breast tissue with near-infrared spectral imaging

    SciTech Connect

    Jiang, Shudong; Pogue, Brian W.; Laughney, Ashley M.; Kogel, Christine A.; Paulsen, Keith D

    2009-04-01

    Applying localized external displacement to the breast surface can change the interstitial fluid pressure such that regional transient microvascular changes occur in oxygenation and vascular volume. Imaging these dynamic responses over time, while different pressures are applied, could provide selective temporal contrast for cancer relative to the surrounding normal breast. In order to investigate this possibility in normal breast tissue, a near-infrared spectral tomography system was developed that can simultaneously acquire data at three wavelengths with a 15 s time resolution per scan. The system was tested first with heterogeneous blood phantoms. Changes in regional blood concentrations were found to be linearly related to recovered mean hemoglobin concentration (HbT) values (R{sup 2}=0.9). In a series of volunteer breast imaging exams, data from 17 asymptomatic subjects were acquired under increasing and decreasing breast compression. Calculations show that a 10 mm displacement applied to the breast results in surface pressures in the range of 0-55 kPa depending on breast density. The recovered human data indicate that HbT was reduced under compression and the normalized change was significantly correlated to the applied pressure with a p value of 0.005. The maximum HbT decreases in breast tissue were associated with body mass index (BMI), which is a surrogate indicator of breast density. No statistically valid correlations were found between the applied pressure and the changes in tissue oxygen saturation (StO2) or water percentage (H2O) across the range of BMI values studied.

  12. Tissue distribution and clearance kinetics of non-transferrin-bound iron in the hypotransferrinemic mouse: a rodent model for hemochromatosis

    SciTech Connect

    Craven, C.M.; Alexander, J.; Eldridge, M.; Kushner, J.P.; Bernstein, S.; Kaplan, J.

    1987-05-01

    Genetically hypotransferrinemic mice accumulate iron in the liver and pancreas. A similar pattern of tissue iron accumulation occurs in humans with hereditary hemochromatosis. In both disorders, there is a decrease plasma concentration of apotransferrin. To test the hypothesis that nontransferrin-bound iron exists and is clear by the parenchymal tissues, the tissue distribution of /sup 59/Fe was studied in animals lacking apotransferrin. Two groups of animals were used: normal rats and mice whose transferrin had been saturated by an intravenous injection of nonradiolabeled iron, and mice with congential hypotransferrinemia. In control animals, injected /sup 59/Fe was found primarily in the bone marrow and spleen. In the transferrin iron-saturated animals, injected /sup 59/Fe accumulated in the liver and pancreas. Gastrointestinally absorbed iron in hypotransferrinemic or transferrin iron-saturated mice was deposited in the liver. This indicates that newly absorbed iron is released from mucosal cells not bound to transferrin. Clearance studies demonstrated that transferrin-bound /sup 59/Fe was removed from the circulation of rats with a half-time of 50 min. In transferrin iron-saturated animals, injected /sup 59/Fe was removed with a half-time of <30 s. Analysis of the distribution of /sup 59/Fe in serum samples by polyacrylamide gel electrophoresis demonstrated the presence of /sup 59/Fe not bound to transferrin. These results demonstrate the existence of and uptake system for non-transferrin-bound iron. These observations support the hypothesis that parenchymal iron overload is consequence of reduced concentrations of apotransferrin.

  13. Measurement of pressure-displacement kinetics of hemoglobin in normal breast tissue with near-infrared spectral imaging

    PubMed Central

    Jiang, Shudong; Pogue, Brian W.; Laughney, Ashley M.; Kogel, Christine A.; Paulsen, Keith D.

    2009-01-01

    Applying localized external displacement to the breast surface can change the interstitial fluid pressure such that regional transient microvascular changes occur in oxygenation and vascular volume. Imaging these dynamic responses over time, while different pressures are applied, could provide selective temporal contrast for cancer relative to the surrounding normal breast. In order to investigate this possibility in normal breast tissue, a near-infrared spectral tomography system was developed that can simultaneously acquire data at three wavelengths with a 15 s time resolution per scan. The system was tested first with heterogeneous blood phantoms. Changes in regional blood concentrations were found to be linearly related to recovered mean hemoglobin concentration (HbT) values (R2 = 0.9). In a series of volunteer breast imaging exams, data from 17 asymptomatic subjects were acquired under increasing and decreasing breast compression. Calculations show that a 10 mm displacement applied to the breast results in surface pressures in the range of 0–55 kPa depending on breast density. The recovered human data indicate that HbT was reduced under compression and the normalized change was significantly correlated to the applied pressure with a p value of 0.005. The maximum HbT decreases in breast tissue were associated with body mass index (BMI), which is a surrogate indicator of breast density. No statistically valid correlations were found between the applied pressure and the changes in tissue oxygen saturation (StO2) or water percentage (H2O) across the range of BMI values studied. PMID:19340100

  14. Estimation of metabolic fluxes, expression levels and metabolite dynamics of a secondary metabolic pathway in potato using label pulse-feeding experiments combined with kinetic network modelling and simulation.

    PubMed

    Heinzle, Elmar; Matsuda, Fumio; Miyagawa, Hisashi; Wakasa, Kyo; Nishioka, Takaaki

    2007-04-01

    In this paper we present a method that allows dynamic flux analysis without a priori kinetic knowledge. This method was developed and validated using the pulse-feeding experimental data obtained in our previous study (Matsuda et al., 2005), in which incorporation of exogenously applied l-phenylalanine-d(5) into seven phenylpropanoid metabolites in potato tubers was determined. After identification of the topology of the metabolic network of these biosynthetic pathways, the system was described by dynamic mass balances in combination with power-law kinetics. After the first simulations, some reactions were removed from the network because they were not contributing significantly to network behaviour. As a next step, the exponents of the power-law kinetics were identified and then kept at fixed values during further analysis. The model was tested for statistical reliability using Monte Carlo simulations. Most fluxes could be identified with high accuracy. The two test cases, control and after elicitation, were clearly distinguished, and with elicitation fluxes to N-p-coumaroyloctopamine (pCO) and N-p-coumaroyltyramine (pCT) increased significantly, whereas those for chlorogenic acid (CGA) and p-coumaroylshikimate decreased significantly. According to the model, increases in the first two fluxes were caused by induction/derepression mechanisms. The decreases in the latter two fluxes were caused by decreased concentrations of their substrates, which in turn were caused by increased activity of the pCO- and pCT-producing enzymes. Flux-control analysis showed that, in most cases, flux control was changed after application of elicitor. Thus the results revealed potential targets for improving actions against tissue wounding and pathogen attack.

  15. Kinetic analysis of the inhibition of matrix metalloproteinases: lessons from the study of tissue inhibitors of metalloproteinases.

    PubMed

    Willenbrock, Frances; Thomas, Daniel A; Amour, Augustin

    2010-01-01

    Tissue inhibitors of metalloproteinases (TIMPs) are a group of highly potent inhibitors of matrix metalloproteinases (MMPs) and disintegrin metalloproteinases (ADAMs). The high affinity and "tight-binding" nature of the inhibition of MMPs or ADAMs by TIMPs presents challenges for the determination of both equilibrium and dissociation rate constants of these inhibitory events. Methodologies that enable some of these challenges to be overcome are described in this chapter and represent valuable lessons for the in vitro assessment of MMP or ADAM inhibitors within a drug discovery context.

  16. Calcium sulfate combined with guided tissue regeneration: A novel technique in treatment of gingival recessions.

    PubMed

    Mukherji, Arnav

    2016-01-01

    The presence of mucogingival problem around anterior teeth is a challenge to the clinician as not only biological and functional aspects has to be addressed but esthetic aspirations of the patient have to be met. The use of guided tissue regeneration (GTR) procedures for the treatment of gingival recession has shown encouraging results and is gaining clinical acceptance. However, maintenance of space under the membrane remains a problem for clinicians. Hence, this case study was an innovative attempt to evaluate the effect of adjunctive calcium sulfate placement along with collagen membrane GTR-based root coverage procedure.

  17. Calcium sulfate combined with guided tissue regeneration: A novel technique in treatment of gingival recessions

    PubMed Central

    Mukherji, Arnav

    2016-01-01

    The presence of mucogingival problem around anterior teeth is a challenge to the clinician as not only biological and functional aspects has to be addressed but esthetic aspirations of the patient have to be met. The use of guided tissue regeneration (GTR) procedures for the treatment of gingival recession has shown encouraging results and is gaining clinical acceptance. However, maintenance of space under the membrane remains a problem for clinicians. Hence, this case study was an innovative attempt to evaluate the effect of adjunctive calcium sulfate placement along with collagen membrane GTR-based root coverage procedure. PMID:27307681

  18. Hybrid dynamic modeling of Escherichia coli central metabolic network combining Michaelis-Menten and approximate kinetic equations.

    PubMed

    Costa, Rafael S; Machado, Daniel; Rocha, Isabel; Ferreira, Eugénio C

    2010-05-01

    The construction of dynamic metabolic models at reaction network level requires the use of mechanistic enzymatic rate equations that comprise a large number of parameters. The lack of knowledge on these equations and the difficulty in the experimental identification of their associated parameters, represent nowadays the limiting factor in the construction of such models. In this study, we compare four alternative modeling approaches based on Michaelis-Menten kinetics for the bi-molecular reactions and different types of simplified rate equations for the remaining reactions (generalized mass action, convenience kinetics, lin-log and power-law). Using the mechanistic model for Escherichia coli central carbon metabolism as a benchmark, we investigate the alternative modeling approaches through comparative simulations analyses. The good dynamic behavior and the powerful predictive capabilities obtained using the hybrid model composed of Michaelis-Menten and the approximate lin-log kinetics indicate that this is a possible suitable approach to model complex large-scale networks where the exact rate laws are unknown.

  19. Traits, properties, and performance: how woody plants combine hydraulic and mechanical functions in a cell, tissue, or whole plant.

    PubMed

    Lachenbruch, Barbara; McCulloh, Katherine A

    2014-12-01

    This review presents a framework for evaluating how cells, tissues, organs, and whole plants perform both hydraulic and mechanical functions. The morphological alterations that affect dual functionality are varied: individual cells can have altered morphology; tissues can have altered partitioning to functions or altered cell alignment; and organs and whole plants can differ in their allocation to different tissues, or in the geometric distribution of the tissues they have. A hierarchical model emphasizes that morphological traits influence the hydraulic or mechanical properties; the properties, combined with the plant unit's environment, then influence the performance of that plant unit. As a special case, we discuss the mechanisms by which the proxy property wood density has strong correlations to performance but without direct causality. Traits and properties influence multiple aspects of performance, and there can be mutual compensations such that similar performance occurs. This compensation emphasizes that natural selection acts on, and a plant's viability is determined by, its performance, rather than its contributing traits and properties. Continued research on the relationships among traits, and on their effects on multiple aspects of performance, will help us better predict, manage, and select plant material for success under multiple stresses in the future.

  20. Effective combination of hydrostatic pressure and aligned nanofibrous scaffolds on human bladder smooth muscle cells: implication for bladder tissue engineering.

    PubMed

    Ahvaz, Hana Hanaee; Soleimani, Masoud; Mobasheri, Hamid; Bakhshandeh, Behnaz; Shakhssalim, Naser; Soudi, Sara; Hafizi, Maryam; Vasei, Mohammad; Dodel, Masumeh

    2012-09-01

    Bladder tissue engineering has been the focus of many studies due to its highly therapeutic potential. In this regard many aspects such as biochemical and biomechanical factors need to be studied extensively. Mechanical stimulations such as hydrostatic pressure and topology of the matrices are critical features which affect the normal functions of cells involved in bladder regeneration. In this study, hydrostatic pressure (10 cm H(2)O) and stretch forces were exerted on human bladder smooth muscle cells (hBSMCs) seeded on aligned nanofibrous polycaprolactone/PLLA scaffolds, and the alterations in gene and protein expressions were studied. The gene transcription patterns for collagen type I, III, IV, elastin, α-SMA, calponin and caldesmon were monitored on days 3 and 5 quantitatively. Changes in the expressions of α-SMA, desmin, collagen type I and III were quantified by Enzyme-linked immuno-sorbent assay. The scaffolds were characterized using scanning electron microscope, contact angle measurement and tensile testing. The positive effect of mechanical forces on the functional improvement of the engineered tissue was supported by translational down-regulation of α-SMA and VWF, up-regulation of desmin and improvement of collagen type III:I ratio. Altogether, our study reveals that proper hydrostatic pressure in combination with appropriate surface stimulation on hBSMCs causes a tissue-specific phenotype that needs to be considered in bladder tissue engineering.

  1. The effect of mechanical extension stimulation combined with epithelial cell sorting on outcomes of implanted tissue-engineered muscular urethras.

    PubMed

    Fu, Qiang; Deng, Chen-Liang; Zhao, Ren-Yan; Wang, Ying; Cao, Yilin

    2014-01-01

    Urethral defects are common and frequent disorders and are difficult to treat. Simple natural or synthetic materials do not provide a satisfactory curative solution for long urethral defects, and urethroplasty with large areas of autologous tissues is limited and might interfere with wound healing. In this study, adipose-derived stem cells were used. These cells can be derived from a wide range of sources, have extensive expansion capability, and were combined with oral mucosal epithelial cells to solve the problem of finding seeding cell sources for producing the tissue-engineered urethras. We also used the synthetic biodegradable polymer poly-glycolic acid (PGA) as a scaffold material to overcome issues such as potential pathogen infections derived from natural materials (such as de-vascular stents or animal-derived collagen) and differing diameters. Furthermore, we used a bioreactor to construct a tissue-engineered epithelial-muscular lumen with a double-layer structure (the epithelial lining and the muscle layer). Through these steps, we used an epithelial-muscular lumen built in vitro to repair defects in a canine urethral defect model (1 cm). Canine urethral reconstruction was successfully achieved based on image analysis and histological techniques at different time points. This study provides a basis for the clinical application of tissue engineering of an epithelial-muscular lumen. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Live birth in a woman without ovaries after autograft of frozen-thawed ovarian tissue combined with growth factors

    PubMed Central

    2013-01-01

    Currently, cryopreservation of oocytes, embryos and ovarian tissue is considered the basis of fertility preservation programs for women with cancer and other diseases who are rendered sterile by gonadotoxic drugs or radiation. Numerous studies have confirmed that autograft of frozen-thawed ovarian tissue can restore ovarian function and fertility. A total of twenty-two live births have been reported but we still have to consider this technique as experimental. The main problem is that the implant undergoes ischemia until neoangiogenesis is restored, resulting in significant follicular loss. At the moment, there are numerous publications in different medical fields that publish successful experiences with plasma rich in platelets (PRP) in different clinical situations promoting angiogenesis. Thus, we considered the possibility of using it in the field of ovarian autologous transplantation in order to improve the vascularization of the implant and its quality. For this, both thawed ovarian tissue as practiced pockets on the rear side of the broad ligament which have been placed, have been impregnated with PRP. We can say that the implant treated in this way has had a rapid and successful response. We report a special interesting case because this is the first time that this technique is performed successfully in a woman without ovaries combined with growth factors to promote neoangiogenesis. Obviously, the results of the hormonal response come exclusively from the implanted tissue in these special conditions. PMID:23647552

  3. A Method for Combined Retinal Vascular and Tissue Oxygen Tension Imaging.

    PubMed

    Felder, Anthony E; Wanek, Justin; Tan, Michael R; Blair, Norman P; Shahidi, Mahnaz

    2017-09-06

    The retina requires adequate oxygenation to maintain cellular metabolism and visual function. Inner retinal oxygen metabolism is directly related to retinal vascular oxygen tension (PO2) and inner retinal oxygen extraction fraction (OEF), whereas outer retinal oxygen consumption (QO2) relies on oxygen availability by the choroid and is contingent upon retinal tissue oxygen tension (tPO2) gradients across the retinal depth. Thus far, these oxygenation and metabolic parameters have been measured independently by different techniques in separate animals, precluding a comprehensive and correlative assessment of retinal oxygenation and metabolism dynamics. The purpose of the current study is to report an innovative optical system for dual oxyphor phosphorescence lifetime imaging to near-simultaneously measure retinal vascular PO2 and tPO2 in rats. The use of a new oxyphor with different spectral characteristics allowed differentiation of phosphorescence signals from the retinal vasculature and tissue. Concurrent measurements of retinal arterial and venous PO 2 , tPO2 through the retinal depth, inner retinal OEF, and outer retinal QO 2 were demonstrated, permitting a correlative assessment of retinal oxygenation and metabolism. Future application of this method can be used to investigate the relations among retinal oxygen content, extraction and metabolism under pathologic conditions and thus advance knowledge of retinal hypoxia pathophysiology.

  4. Periodontal tissue regeneration by transplantation of rat adipose-derived stromal cells in combination with PLGA-based solid scaffolds.

    PubMed

    Akita, Daisuke; Morokuma, Masakazu; Saito, Yoko; Yamanaka, Katsuyuki; Akiyama, Yuko; Sato, Momoko; Mashimo, Takayuki; Toriumi, Taku; Arai, Yoshinori; Kaneko, Tadashi; Tsukimura, Naoki; Isokawa, Keitaro; Ishigami, Tomohiko; Honda, Masaki J

    2014-01-01

    Regeneration of damaged periodontium is challenging due to its multi-tissue composition. Mesenchymalstem cell-based approaches using adipose-derived stromal cells (ASCs) may contribute to periodontal reconstruction, particularly when combined with the use of scaffolds to maintain a space for new tissue growth. The aim of this study was to assess the regenerative potential of ASCs derived from inbred or outbred rats in combination with novel solid scaffolds composed of PLGA (Poly D,L-lactic-co-glycolic acid) (PLGA-scaffolds). Cultured ASCs seeded onto PLGA scaffolds (ASCs/PLGA) or PLGA-scaffolds (PLGA) alone were transplanted into periodontal fenestration defects created in F344 or Sprague Dawley (SD) rats. Micro-CT analysis showed a significantly higher percentage of bone growth in the ASCs/PLGA groups compared with the PLGA-alone groups at five weeks after surgery. Similarly, histomorphometric analysis demonstrated thicker growth of periodontal ligament and cementum layers in the ASCs/PLGA-groups compared with the PLGA-alone groups. In addition, transplanted DiI-labeled ASCs were observed in the periodontal regenerative sites. The present investigation demonstrated the marked ability of ASCs in combination with PLGA scaffolds to repair periodontal defects.

  5. Combined surgical resective and regenerative therapy for advanced peri-implantitis with concomitant soft tissue volume augmentation: a case report.

    PubMed

    Schwarz, Frank; John, Gordon; Sahm, Narja; Becker, Jürgen

    2014-01-01

    This case report presents a 3-year follow-up of the clinical outcomes of a combined surgical therapy for advanced peri-implantitis with concomitant soft tissue volume augmentation using a collagen matrix. One patient suffering from advanced peri-implantitis and a thin mucosal biotype underwent access flap surgery, implantoplasty at buccally and supracrestally exposed implant parts, and augmentation of the intrabony components using a natural bone mineral and a native collagen membrane after surface decontamination. A collagen matrix was applied to the wound area to increase soft tissue volume and support transmucosal healing. The following clinical parameters were recorded over a period of 3 years: bleeding on probing (BOP), probing depth (PD), mucosal recession (MR), clinical attachment level (CAL), and width of keratinized mucosa (KM). At 36 months, the combined surgical procedure was associated with a clinically important reduction in mean BOP (100%), PD (4.3 ± 0.5 mm), and CAL (4.4 ± 0.4 mm). Site-level analysis of the buccal aspects pointed to an increase in MR (-1.0 ± 0.4 mm) and a decrease in KM (-1.3 ± 0.5 mm) values at 12 months. However, a regain in mucosal height and KM was noted at 24 months, even reaching respective baseline values after 36 months of healing. The presented combined surgical procedure was effective in controlling an advanced peri-implantitis lesion without compromising the overall esthetic outcome in the long term.

  6. Dose-response feeding study of short chain chlorinated paraffins (SCCPs) in laying hens: effects on laying performance and tissue distribution, accumulation and elimination kinetics.

    PubMed

    Ueberschär, Karl-Heinz; Dänicke, Sven; Matthes, Siegfried

    2007-02-01

    Technical short chain chlorinated paraffins (C10-C13 with 60% chlorine) were fed to 93 laying hens from 24 to 32 weeks of age in increasing concentrations of up to 100 mg/kg feed. No significant influence on health, relative organ weights or performance (laying intensity, egg weight, feed consumption) was noted. The chlorinated paraffin content of the tissues was linearly related to the concentration of short chain paraffins of the feed. The highest concentrations were found in abdominal fat, egg yolk and fatty tissues. Breast muscle, egg albumen and bile fluid contained minimal or no residues. Less than 1% of the chlorinated paraffins ingested were incorporated into the body (without head, feet, gut and feathers), whereas about 1.5% were eliminated with the egg yolk and 30% were excreted with urine and faeces. A six-week kinetic depuration study revealed a biphasic elimination with half-lifes of 4-40 min (liver, kidneys, legs, fat, blood) for the initial rapid phase, and 15-30 days (blood, fat, liver, yolk, kidneys, legs) for the terminal slow phase.

  7. The influence of distributional kinetics into a peripheral compartment on the pharmacokinetics of substrate partitioning between blood and brain tissue.

    PubMed

    Padowski, Jeannie M; Pollack, Gary M

    2011-12-01

    Development of CNS-targeted agents often focuses on identifying compounds with "good" CNS exposure (brain-to-blood partitioning >1). Some compounds undergoing enterohepatic recycling (ER) evidence a partition coefficient, K (p,brain) (expressed as C (brain) /C (plasma)), that exceeds and then decreases to (i.e., overshoots) a plateau (distribution equilibrium) value, rather than increasing monotonically to this value. This study tested the hypothesis that overshoot in K (p,brain) is due to substrate residence in a peripheral compartment. Simulations were based on a 3-compartment model with distributional clearances between central and brain (CL (br)) and central and peripheral (CL (d)) compartments and irreversible clearance from the central compartment (CL). Parameters were varied to investigate the relationship between overshoot and peripheral compartment volume (V (p)), and how this relationship was modulated by other model parameters. Overshoot magnitude and duration were characterized as peak C (brain)/C (plasma) relative to the plateau value (%OS) and time to reach plateau (TRP). Except for systems with high CL (d), increasing V (p) increased TRP and %OS. Increasing brain (V (br)) or central (V (c)) distribution volumes eliminated V (p)-related OS. Parallel increases in all clearances shortened TRP, but did not alter %OS. Increasing either CL or CL (d) individually increased %OS related to V (p), while increasing CL (br) decreased %OS. Under realistic peripheral distribution scenarios, C (brain)/C (plasma) may overshoot substantially K (p,brain) at distribution equilibrium. This observation suggests potential for erroneous assessment of brain disposition, particularly for compounds which exhibit a large apparent V (p), and emphasizes the need for complete understanding of distributional kinetics when evaluating brain uptake.

  8. Effectiveness of combined use of imprint cytological and histological examination in CT-guided tissue-core biopsy.

    PubMed

    Yamagami, Takuji; Yoshimatsu, Rika; Kajiwara, Kenji; Ishikawa, Masaki; Matsumoto, Tomohiro; Kakizawa, Hideaki; Toyoda, Naoyuki; Hasebe, Terumitsu; Awai, Kazuo

    2014-05-01

    This study evaluated the efficacy of the combination of imprint cytology and histology in tissue-core percutaneous biopsy under real-time computed tomography (CT) fluoroscopic guidance. Between October 2009 and June 2013, 156 percutaneous needle biopsies were performed in our institution. Those obtained by tissue-core biopsy underwent both imprint cytological and histological examinations routinely after touch imprint cytology was performed on site to evaluate the samples' sufficiency for cytological and pathological examination. Final diagnosis was confirmed by independent surgical pathology, independent culture results or clinical follow-up. Rates of adequate specimens and precise diagnosis, by combined cytological and histological examination were 100 % (156/156) and 96.2 % (150/156), by cytology 94.4 % (152/156) and 83.3 % (130/156) and by histology 99.3 % (155/156) and 92.3 % (144/156). Precise diagnosis was achieved by combined examinations in 94.7 % (89/94) of thoracic lesions, 97.6 % (40/41) of musculoskeletal lesions, and 100 % (21/21) of abdominal, pelvic and retroperitoneal lesions. In all 104 lesions diagnosed as malignant by CT-guided biopsy and in 30 of 52 diagnosed as benign, specific cell types could be proved by combined examinations. Combined imprint cytology and histology performed after on-site touch imprint cytological evaluation improved the diagnostic ability of CT fluoroscopically guided biopsy. • CT-guided needle biopsy is a well-established diagnostic technique. • Touch imprint cytological evaluation on site is helpful in improving quality of CT-guided biopsy. • The rate of diagnosing malignant lymphoma specifically with cytological examination is relatively low. • The rate of specific diagnosis of benign lesion in musculoskeletal regions is low.

  9. Facial soft tissue injuries as an aid to ordering a combination head and facial computed tomography in trauma patients.

    PubMed

    Holmgren, Eric P; Dierks, Eric J; Assael, Leon A; Bell, R Bryan; Potter, Bryce E

    2005-05-01

    While the trauma computed tomography (CT) head scan is frequently ordered during resuscitation of multiply injured patients, determining when also to order facial CT in these situations can be difficult. Consequently, facial fractures are commonly missed on initial imaging evaluation. In acute trauma situations, facial soft tissue injury markers are often used to aid in this decision. A study was undertaken to identify exactly which facial soft tissue injuries correlate with facial fractures and which did not. The aim of our research was to compare the facial soft tissue injury patterns of patients receiving a combination head and facial CT who had facial fractures versus those who had no facial fractures. A retrospective trauma registry review was performed for a 5-year period at Legacy Emanuel Hospital, a level 1 trauma center. The trauma team saw a total of 9,871 trauma patients and 49.9% required head CT as part of their initial evaluation. A total of 777 (15.7%) patients had a combination head and facial CT in which 477 (61.4%) had a facial fracture and 300 (38.6%) had no facial fracture. Statistical significance was established using Bonferroni corrected P values less than .05. Lacerations occurring in areas of the lips, nose, and intraorally, as well as wounds leading to periorbital contusion and subconjunctival hemorrhage, were significantly prevalent in the fracture group. Conversely, scalp lacerations and scalp contusions were significantly higher in the nonfracture group. Other injuries such as lacerations of the tongue, chin, forehead, cheek, ear, eyelid, and eyebrow were indistinguishable between both groups. Our data demonstrate that there are certain facial soft tissue injury zones that correlate with facial fractures in trauma patients who obtain head CT. We would like to propose that the acronym LIPS-N (Lip laceration, Intraoral laceration, Periorbital contusion, Subconjunctival hemorrhage, and Nasal laceration) be used in conjunction with a

  10. A lethal combination of toxins and biofilms aids soft tissue fossilization

    NASA Astrophysics Data System (ADS)

    MacKenzie, L. A.; Hinman, N. W.; Kohn, M. J.; Olin, P. H.

    2012-12-01

    Biofilms, thin microbial communities encased in extracellular polymeric substances, are thought to aid in fossilization, particularly in cases of extraordinary preservation of soft tissues in Konservat-Lagerstätten deposits. The mechanisms by which this occurs, however, are poorly understood. Modern marine biofilms take up trace elements (e.g., Cu, P, Fe, Zn, Cd), some of which are toxic. In this study we investigated trace element patterns across worm fossils from the Early Cambrian Chengjiang biota (Yunnan, China) to explore whether toxic metals preferentially accumulated in soft tissues, retarding biodegradation and promoting extraordinary preservation. This biota is the oldest of the Burgess Shale Type (BST) Lagerstätten, which preserve soft-bodied fossils that range in age from early Cambrian to Ordovician. Concentrations of 24 light elements, transition metals, heavy metals, actinides and lanthanides were measured using laser-ablation ICP-MS in 2-4 mm long transects across rock matrix and 1-2 mm wide fossils to create matrix-worm-matrix geochemical profiles. Spatial and compositional resolutions were ~50 μm and ~1ppm. Six worm fossils were analyzed, and all show higher concentrations of P, Sc, V, Cr, Fe, Ni, Cu, Mo, Sb, Th, and U than the matrix. Increases in Na, Mg, Al, K, Ca, Mn, Co, Sr, Ba, Ce, and Pb were found in some, but not all samples. None of the samples showed significant increases in Ti. Abiotic processes cannot explain increased concentrations of all of these elements, which include both redox-sensitive and immobile elements. Instead we propose that biofilms formed on the surface of the organisms shortly after death (hours to days). Bioaccumulation of toxic trace elements sealed the worms under a thin, deadly trace-element-rich film that prevented further degradation. This process allowed diagenetic cements to form a rigid rock matrix and preserve these delicate fossils. If so, trace element accumulation by biofilms may provide the key for

  11. Comparison of three combined sequencing batch reactor followed by enhanced Fenton process for an azo dye degradation: Bio-decolorization kinetics study.

    PubMed

    Azizi, A; Alavi Moghaddam, M R; Maknoon, R; Kowsari, E

    2015-12-15

    The purpose of this research was to compare three combined sequencing batch reactor (SBR) - Fenton processes as post-treatment for the treatment of azo dye Acid Red 18 (AR18). Three combined treatment systems (CTS1, CTS2 and CTS3) were operated to investigate the biomass concentration, COD removal, AR18 dye decolorization and kinetics study. The MLSS concentration of CTS2 reached 7200 mg/L due to the use of external feeding in the SBR reactor of CTS2. The COD concentration remained 273 mg/L and 95 mg/L (initial COD=3270 mg/L) at the end of alternating anaerobic-aerobic SBR with external feeding (An-A MSBR) and CTS2, respectively, resulting in almost 65% of Fenton process efficiency. The dye concentration of 500 mg/L was finally reduced to less than 10mg/L in all systems indicating almost complete AR18 decolorization, which was also confirmed by UV-vis analysis. The dye was removed following two successive parts as parts 1 and 2 with pseudo zero-order and pseudo first-order kinetics, respectively, in all CTSs. Higher intermediate metabolites degradation was obtained using HPLC analysis in CTS2. Accordingly, a combined treatment system can be proposed as an appropriate and environmentally-friendly system for the treatment of the azo dye AR18 in wastewater. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Study of ketone body kinetics in children by a combined perfusion of /sup 13/C and /sup 2/H3 tracers

    SciTech Connect

    Bougneres, P.F.; Ferre, P.

    1987-11-01

    Ketone body kinetics were quantified in six children (3-5 yr old), who were fasted for 13-22 h, by a combined perfusion of (3-/sup 13/C)acetoacetate ((/sup 13/C)AcAc) and D-(-)-beta-(4,4,4-/sup 2/H3)hydroxybutyrate (beta-(/sup 2/H3)OHB) and gas chromatography-mass spectrometry analysis. Results were analyzed according to the single-pool (combined enrichments) or the two-accessible pools models. After 20-22 h of fasting, ketone body turnover rate was 30-50 mumol.kg-1.min-1, a rate achieved after several days of fasting in adults. At low ketosis, acetoacetate was the ketone body preferentially synthesized de novo and utilized irreversibly. When ketosis increased, acetoacetate irreversible disposal was not enhanced, since it was largely converted into beta-OHB, whereas beta-OHB irreversible disposal was very much increased. The single-pool and two-pool models gave similar ketone body turnover rates when (/sup 13/C)AcAc was the tracer, whereas the use of beta-(/sup 2/H3)OHB gave some more divergent results, especially at low ketosis. These studies demonstrate that ketogenesis is very active in short-term fasted children and that the use of a combined infusion of (/sup 13/C)AcAc and beta-(/sup 2/H3)OHB is a convenient way to give insight into individual ketone body kinetics.

  13. Kinetics of (/sup 14/C-5) 8-methoxypsoralen uptake by UVA irradiated and non-irradiated rabbit eye tissues

    SciTech Connect

    Malinin, G.I.; Glew, W.B.; Roberts, W.P.; Nigra, T.P.

    1981-05-01

    Total 8-methoxypsoralen (8-MOP) in intact and UVA irradiated rabbit eye tissues and its unaltered fraction in aqueous and eye lenses were determined over the 24 hours after i.v. injection of (/sup 14/C-5) and carrier 8-MOP at the concentration of 50 microCi and 5 mg/kg. No 8-MOP was detected at the end of 24 hours in intact and irradiated aqueous, vitreous and retina in contrast to one hour when the respective levels were congruent to 220, greater than 0 and congruent to 160 ng/g. Eye-plasma drug concentration ratios were less than 0.5 initially, but increased thereafter. While the average lens 8-MOP levels of congruent to 140 ng/g remained unchanged for 24 hours, no unaltered drug was detected beyond eight hours. Measurable amounts of label at the end of 24 hours also persisted in the cornea, iris, sclera and conjunctiva.

  14. Tailoring the degradation kinetics of poly(ester-carbonate urethane)urea thermoplastic elastomers for tissue engineering scaffolds

    PubMed Central

    Hong, Yi; Guan, Jianjun; Fujimoto, Kazuro L.; Hashizume, Ryotaro; Pelinescu, Anca L.; Wagner, William R.

    2010-01-01

    Biodegradable elastomeric scaffolds are of increasing interest for applications in soft tissue repair and regeneration, particularly in mechanically active settings. The rate at which such a scaffold should degrade for optimal outcomes, however, is not generally known and the ability to select from similar scaffolds that vary in degradation behavior to allow such optimization is limited. Our objective was to synthesize a family of biodegradable polyurethane elastomers where partial substitution of polyester segments with polycarbonate segments in the polymer backbone would lead to slower degradation behavior. Specifically, we synthesized poly(ester carbonate)urethane ureas (PECUUs) using a blended soft segment of poly(caprolactone) (PCL) and poly(1,6-hexamethylene carbonate) (PHC), a 1,4-diisocyanatobutane hard segment and chain extension with putrescine. Soft segment PCL/PHC molar ratios of 100/0, 75/25, 50/50, 25/75, and 0/100 were investigated. Polymer tensile strengths varied from 14-34 MPa with breaking strains of 660-875%, initial moduli of 8-24 MPa and 100% recovery after 10% strain. Increased PHC content was associated with softer, more distensible films. Scaffolds produced by salt leaching supported smooth muscle cell adhesion and growth in vitro. PECUU in aqueous buffer in vitro and subcutaneous implants in rats of PECUU scaffolds showed degradation slower than comparable poly(ester urethane)urea and faster than poly(carbonate urethane)urea. These slower degrading thermoplastic polyurethanes provide opportunities to investigate the role of relative degradation rates for mechanically supportive scaffolds in a variety of soft tissue repair and reconstructive procedures. PMID:20188411

  15. Telmisartan, ramipril and their combination improve endothelial function in different tissues in a murine model of cholesterol-induced atherosclerosis

    PubMed Central

    Schlimmer, N; Kratz, M; Böhm, M; Baumhäkel, M

    2011-01-01

    BACKGROUND AND PURPOSE Erectile dysfunction correlates with cardiovascular disease and its common risk factors due to the development of endothelial dysfunction. Positive effects on endothelial and erectile function have been described for substances inhibiting the renin-angiotensin-system. Here, we investigated in an atherosclerosis model, whether telmisartan (angiotensin receptor blocker) and ramipril (angiotensin converting enzyme inhibitor) are equivalent or the combination of both is superior in improving endothelial function in the aorta and the corpus cavernosum and in reducing atherosclerosis. EXPERIMENTAL APPROACH Wild-type (WT, C57/B6) and apolipoprotein-E-deficient (ApoE−/−) mice were treated with a cholesterol-rich diet for 8 weeks. ApoE−/− mice were supplemented with either telmisartan (20 mg·kg−1·day−1), ramipril (2.5 mg·kg−1·day−1) or the combination thereof. KEY RESULTS Systolic blood pressure significantly decreased in treatment groups (P < 0.001), with significantly smaller reduction under ramipril monotherapy (P < 0.05). Endothelial function (assessed by pharmacological stimulation of aortic rings and corpus cavernosum in organ bath chambers) was impaired in ApoE−/− mice compared to WT animals, which was improved by all three treatments to a comparable extent (P < 0.05). Atherosclerotic lesion size in the ascending aorta and aortic sinus (P < 0.001), the amount of lipid peroxides in cavernosal and aortic tissue (P < 0.05) and free radical load (dihydroethidium-stain) (P < 0.05) were enhanced in untreated ApoE−/− mice in comparison to WT animals and were significantly reduced by either treatment. In penile tissue, expression of eNOS could be restored by renin-angiotensin-aldosterone system blockade. CONCLUSIONS AND IMPLICATIONS Telmisartan and ramipril significantly improved endothelial function of aortic and cavernosal tissues in ApoE−/− via reduction of oxidative stress. Combination of both agents does not enhance

  16. Post-pregnancy body contouring using a combined radiofrequency, infrared light and tissue manipulation device.

    PubMed

    Winter, Marc L

    2009-12-01

    Non-invasive body contouring is an increasingly popular aesthetic application. Previous data support the efficacy of combined radiofrequency, infrared and skin manipulation for cellulite treatment. To evaluate the performance of a high-power device (50 W as opposed to 25 W) combining these energies for reshaping and improvement of skin texture/laxity in postpartum women. Twenty women received five weekly treatments to the abdomen, buttocks and thighs with the VelaShape system. We followed up each patient's weight and nutritional habits. Outcome was assessed using reproducible circumference measurements, digital photography, the physician's scores of cellulite and improvement as well as patient satisfaction. Safety was evaluated by recording subjects' comfort and tolerance. The overall mean circumferences reduction was 5.4 +/- 0.7 cm (p < 0.001). Significant (p < 0.02) improvement in skin laxity and tightening was noted by both the physician and patients. Treatments were well tolerated with no major safety concerns (one purpura, one mild burn). The enhanced capabilities of the evaluated system enabled significant results in fewer and shorter sessions without compromising patients' safety or comfort. These data suggest that postpartum reshaping via circumferential reduction and skin laxity improvement can be effectively and safely achieved using a high-energy combination of radiofrequency, infrared and mechanical manipulation.

  17. Hybrid Tissue Engineering Scaffolds by Combination of Three-Dimensional Printing and Cell Photoencapsulation

    PubMed Central

    Markovic, Marica; Van Hoorick, Jasper; Hölzl, Katja; Tromayer, Maximilian; Gruber, Peter; Nürnberger, Sylvia; Dubruel, Peter; Van Vlierberghe, Sandra; Liska, Robert; Ovsianikov, Aleksandr

    2015-01-01

    Three-dimensional (3D) printing offers versatile possibilities for adapting the structural parameters of tissue engineering scaffolds. However, it is also essential to develop procedures allowing efficient cell seeding independent of scaffold geometry and pore size. The aim of this study was to establish a method for seeding the scaffolds using photopolymerizable cell-laden hydrogels. The latter facilitates convenient preparation, and handling of cell suspension, while distributing the hydrogel precursor throughout the pores, before it is cross-linked with light. In addition, encapsulation of living cells within hydrogels can produce constructs with high initial cell loading and intimate cell-matrix contact, similar to that of the natural extra-cellular matrix (ECM). Three dimensional scaffolds were produced from poly(lactic) acid (PLA) by means of fused deposition modeling. A solution of methacrylamide-modified gelatin (Gel-MOD) in cell culture medium containing photoinitiator Li-TPO-L was used as a hydrogel precursor. Being an enzymatically degradable derivative of natural collagen, gelatin-based matrices are biomimetic and potentially support the process of cell-induced remodeling. Preosteoblast cells MC3T3-E1 at a density of 10 × 106 cells per 1 mL were used for testing the seeding procedure and cell proliferation studies. Obtained results indicate that produced constructs support cell survival and proliferation over extended duration of our experiment. The established two-step approach for scaffold seeding with the cells is simple, rapid, and is shown to be highly reproducible. Furthermore, it enables precise control of the initial cell density, while yielding their uniform distribution throughout the scaffold. Such hybrid tissue engineering constructs merge the advantages of rigid 3D printed constructs with the soft hydrogel matrix, potentially mimicking the process of ECM remodeling. PMID:26858826

  18. Combining displacement field and grip force information to determine mechanical properties of planar tissue with complicated geometry.

    PubMed

    Nagel, Tina M; Hadi, Mohammad F; Claeson, Amy A; Nuckley, David J; Barocas, Victor H

    2014-11-01

    Performing planar biaxial testing and using nominal stress-strain curves for soft-tissue characterization is most suitable when (1) the test produces homogeneous strain fields, (2) fibers are aligned with the coordinate axes, and (3) strains are measured far from boundaries. Some tissue types [such as lamellae of the annulus fibrosus (AF)] may not allow for these conditions to be met due to their natural geometry and constitution. The objective of this work was to develop and test a method utilizing a surface displacement field, grip force-stretch data, and finite-element (FE) modeling to facilitate analysis of such complex samples. We evaluated the method by regressing a simple structural model to simulated and experimental data. Three different tissues with different characteristics were used: Superficial pectoralis major (SPM) (anisotropic, aligned with axes), facet capsular ligament (FCL) (anisotropic, aligned with axes, bone attached), and a lamella from the AF (anisotropic, aligned off-axis, bone attached). We found that the surface displacement field or the grip force-stretch data information alone is insufficient to determine a unique parameter set. Utilizing both data types provided tight confidence regions (CRs) of the regressed parameters and low parameter sensitivity to initial guess. This combined fitting approach provided robust characterization of tissues with varying fiber orientations and boundaries and is applicable to tissues that are poorly suited to standard biaxial testing. The structural model, a set of C++ finite-element routines, and a Matlab routine to do the fitting based on a set of force/displacement data is provided in the on-line supplementary material.

  19. Combining electrospinning and cell sheet technology for the development of a multiscale tissue engineered ligament construct (TELC).

    PubMed

    Vaquette, Cedryck; Sudheesh Kumar, P T; Bogdan Petcu, Eugen; Ivanovski, Saso

    2017-02-07

    Ligament tissue rupture is a common sport injury. Although current treatment modalities can achieve appropriate reconstruction of the damaged ligament, they present significant drawbacks, mostly related to reduced tissue availability and pain associated with tissue harvesting. Stem cell based tissue regeneration combined with electrospun scaffolds represents a novel treatment method for torn ligaments. In this study, a low fiber density polycaprolactone (PCL) electrospun mesh and sheep mesenchymal stem cells (sMSCs) were used to develop tissue engineered ligament construct (TELC) in vitro. The assembly of the TELC was based on the spontaneous capacity of the cells to organize themselves into a cell sheet once seeded onto the electrospun mesh. The cell sheet matured over 4 weeks and strongly integrated with the low fiber density electrospun mesh which was subsequently processed into a ligament-like bundle and braided with two other bundles to develop the final construct. Live/dead assay revealed that the handling of the construct through the various phases of assembly did not cause significant difference in viability compared to the control. Mechanical evaluation demonstrated that the incorporation of the cell sheet into the braided construct resulted in significantly modifying the mechanical behavior. A stress/displacement J-curve was observed for the TELC that was similar to native ligament, whereas this particular feature was not observed in the non-cellularized specimens. The regenerative potential of the TELC was evaluated ectopically in immunocompromized rats, compared to non cellularized electrospun fiber mesh and this demonstrated that the TELC was well colonized by host cells and that a significant remodelling of the implanted construct was observed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017.

  20. Massage therapy alone and in combination with meditation for breast cancer patients undergoing autologous tissue reconstruction: A randomized pilot study.

    PubMed

    Dion, Liza J; Engen, Deborah J; Lemaine, Valerie; Lawson, Donna K; Brock, Charise G; Thomley, Barbara S; Cha, Stephen S; Sood, Amit; Bauer, Brent A; Wahner-Roedler, Dietlind L

    2016-05-01

    This study explored whether massage combined with meditation is more helpful than massage alone for women recovering from autologous tissue reconstruction after mastectomy for breast cancer. Forty patients were randomly assigned to either massage therapy or massage plus meditation on postoperative days 1 through 3. Outcome measures were 1) visual analog scale (VAS) scores for stress, anxiety, relaxation, insomnia, alertness, fatigue, tension, pain, mood, and energy, and 2) Perceived Stress Scale-14 scores. Nineteen patients in each group finished the study. Preintervention and postintervention mean total VAS scores improved significantly in both groups (P < .001), but no significant difference occurred between groups.

  1. Advances in combining gene therapy with cell and tissue engineering-based approaches to enhance healing of the meniscus

    PubMed Central

    Cucchiarini, M.; McNulty, A.L.; Mauck, R.L.; Setton, L.A.; Guilak, F.; Madry, H.

    2017-01-01

    SUMMARY Meniscal lesions are common problems in orthopaedic surgery and sports medicine, and injury or loss of the meniscus accelerates the onset of knee osteoarthritis. Despite a variety of therapeutic options in the clinics, there is a critical need for improved treatments to enhance meniscal repair. In this regard, combining gene-, cell-, and tissue engineering-based approaches is an attractive strategy to generate novel, effective therapies to treat meniscal lesions. In the present work, we provide an overview of the tools currently available to improve meniscal repair and discuss the progress and remaining challenges for potential future translation in patients. PMID:27063441

  2. Effect of severe protein-calorie malnutrition on the penetration kinetics of trimethoprim and sulfamethoxazole to the deep tissues of Wistar rats.

    PubMed

    Lares-Asseff, Ismael; Pérez, Maria Gabriela; Camacho, Guadalupe A; Toledo, Alejandra R; del Carmen López, Maria; Guillé, Adrián J; Sosa, Martha G

    2003-04-01

    This study shows the effect that severe malnourishment has on the kinetics of antibiotic penetration in tissues. A total of 104 male Wistar rats, 21 days old, were randomly divided into eight groups. Five groups of experimental rats were severely malnourished (SM) and three further groups were considered well-nourished control groups (WN). A single dose of trimethoprim-sulfamethoxazole (TMP-SMX) was administered intraperitoneally. Blood samples were taken by heart puncture and five organs were extracted 0-24 h after the administration of the drug. HPLC was used to assess the amount of trimethoprim and sulfamethoxazole in fluids. The elimination half-life for trimethoprim from plasma was longer in SM rats with a median of 3.15 h; in WN rats, it was 0.390 h. Clearance was slower in SM rats: 646.72 mL microg(-1) h(-1) vs 3036.38 mL microg(-1) h(-1) in WN rats (P < 0.05). Tissue penetration was much higher for trimethoprim, with penetration indexes of 0.80-5.66 in WN rats, compared with 0.35-2.14 in SM rats. In the case of sulfamethoxazole, penetration indexes were 0.029-1.13 for WN and 0.075-0.657 for SM rats. Similarly, the penetration ratio to muscle and heart tissue was lower in SM rats. However, penetration to kidney, lung, liver and spleen was greater in SM rats. It is evident that severe SM decreases the capacity of trimethoprim more importantly than sulfamethoxazole biotransformation.

  3. Identifying the proton transfer reaction mechanism via a proton-bound dimeric intermediate for esomeprazoles by a kinetic method combined with density functional theory calculations.

    PubMed

    Cao, Xiaoji; Zhang, Feifei; Zhu, Kundan; Ye, Xuemin; Shen, Lingxiao; Chen, Jiaoyu; Mo, Weimin

    2014-05-15

    Esomeprazole analogs are a class of important proton pump inhibitors for the treatment of gastro-esophageal reflux diseases. Understanding the fragmentation reaction mechanism of the protonated esomeprazole analogs will facilitate the characterization of their complex metabolic fate in humans. In this paper, the kinetic method and theoretical calculations were applied to evaluate the fragmentation of protonated esomeprazole analogs. All collision-induced dissociation (CID) mass spectrometry experiments were carried out using electrospray ionization (ESI) ion trap mass spectrometry in positive ion mode. Also the accurate masses of fragments were measured on by ESI quadrupole time-of-flight (QTOF) MS in positive ion mode. Theoretical calculations were carried out by the density functional theory (DFT) method with the 6-31G(d) basis set in the Gaussian 03 program. In the fragmentation of the protonated esomeprazole analogs, C-S bond breakage is observed, which gives rise to protonated 2-(sulfinylmethylene)pyridines and protonated benzimidazoles. DFT calculations demonstrate that the nitrogen atom of the pyridine part is the thermodynamically most favorable protonation site, and the C-S bond cleavage is triggered by the transfer of this ionizing proton from the nitrogen atom of the pyridine part to the carbon atom of the benzimidazole part to which the sulfinyl is attached. Moreover, with the kinetic plot, the intensity ratios of two protonated product ions yield a linear relationship with the differences in proton affinities of the corresponding neutral molecules, which provides strong experimental evidence that the reaction proceeds via proton-bound 2-(sulfinylmethylene)pyridine/benzimidazole complex intermediates. The kinetic method combined with theoretical calculations was successfully applied to probe the proton transfer reaction by proton-bound 2-(sulfinylmethylene)pyridine/benzimidazole complexes in the fragmentation of protonated esomeprazole analogs by ESI

  4. In vivo Raman flow cytometry for real-time detection of carbon nanotube kinetics in lymph, blood, and tissues

    PubMed Central

    Biris, Alexandru S.; Galanzha, Ekaterina I.; Li, Zhongrui; Mahmood, Meena; Xu, Yang; Zharov, Vladimir P.

    2016-01-01

    Nanoparticles are intensively being explored as contrast agents for medical diagnostics and therapies using various optical methods. We present the first demonstration of the use of time-resolved Raman spectroscopy for in vivo real-time detection of circulating carbon nanotubes (CNTs) or cancer cells labeled with CNTs in the lymph, blood, and tissues of live animals with fast spectral acquisition times of down to few milliseconds. After intravenously administering CNTs in the tail vein of the rat, this technique provides the ability to detect the circulation of CNTs in the blood microvessels of the intact rat ear. The capability of Raman spectroscopy is also demonstrated to monitor, identify, and image the CNTs during their transportation by lymphatics in the rat ear and mesentery. The strong and specific Raman scattering properties of CNTs make it possible to detect in vitro and in vivo single cancer cells (HeLa) tagged with CNTs. In vivo Raman flow cytometry opens a new avenue for multiparameter analysis of circulating nanoparticles with strong Raman scattering properties and their pharmokinetics in blood and lymph systems. Moreover, this technology has the potential for molecular detection and identification of circulating tumor cells, and infections labeled with CNTs. PMID:19405719

  5. Curcumin and its nano-formulation: the kinetics of tissue distribution and blood-brain barrier penetration.

    PubMed

    Tsai, Yin-Meng; Chien, Chao-Feng; Lin, Lie-Chwen; Tsai, Tung-Hu

    2011-09-15

    Curcumin has considerable neuro-protective and anti-cancer properties but is rapidly eliminated from the body. By optimizing the HPLC method for analysis of curcumin, this study evaluates how the ability of curcumin to penetrate organs and different regions of the brain is affected by nanoparticulation to increase curcumin circulation time in the body. Curcumin-loaded PLGA nanoparticles (C-NPs) were prepared by the high-pressure emulsification-solvent evaporation method. The mean particle size and entrapment efficiency were 163nm and 46.9%, respectively. The release profile of C-NPs was an initial burst effect followed by sustained diffusion. In distribution studies, curcumin could be detected in the evaluated organs, including liver, heart, spleen, lung, kidney and brain. C-NPs were found mainly in the spleen, followed by the lung. Formulation significantly raised the curcumin concentration in these organs with increases in the AUC, t(1/2) and MRT of curcumin, though this was not apparent in the heart. Curcumin and C-NPs could cross the blood-brain barrier (BBB) to enter brain tissue, where it was concentrated chiefly in the hippocampus. Nanoparticulation significantly prolonged retention time of curcumin in the cerebral cortex (increased by 96%) and hippocampus (increased by 83%). These findings provide further understanding for the possible therapeutic effects of curcumin and C-NPs in further pre-clinical and clinical research. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Freeform fabrication of tissue-simulating phantoms by combining three-dimensional printing and casting

    NASA Astrophysics Data System (ADS)

    Shen, Shuwei; Zhao, Zuhua; Wang, Haili; Han, Yilin; Dong, Erbao; Liu, Bin; Liu, Wendong; Cromeens, Barrett; Adler, Brent; Besner, Gail; Ray, William; Hoehne, Brad; Xu, Ronald

    2016-03-01

    Appropriate surgical planning is important for improved clinical outcome and minimal complications in many surgical operations, such as a conjoined twin separation surgery. We combine 3D printing with casting and assembling to produce a solid phantom of high fidelity to help surgeons for better preparation of the conjoined twin separation surgery. 3D computer models of individual organs were reconstructed based on CT scanned data of the conjoined twins. The models were sliced, processed, and converted to an appropriate format for Fused Deposition Modeling (FDM). The skeletons of the phantom were printed directly by FDM using Acrylonitrile-Butadiene-Styrene (ABS) material, while internal soft organs were fabricated by casting silicon materials of different compositions in FDM printed molds. The skeleton and the internal organs were then assembled with appropriate fixtures to maintain their relative positional accuracies. The assembly was placed in a FMD printed shell mold of the patient body for further casting. For clear differentiation of different internal organs, CT contrast agents of different compositions were added in the silicon cast materials. The produced phantom was scanned by CT again and compared with that of the original computer models of the conjoined twins in order to verify the structural and positional fidelity. Our preliminary experiments showed that combining 3D printing with casting is an effective way to produce solid phantoms of high fidelity for the improved surgical planning in many clinical applications.

  7. Kinetic analysis of acid orange 7 degradation by pulsed discharge plasma combined with activated carbon and the synergistic mechanism exploration.

    PubMed

    Guo, He; Wang, Huijuan; Wu, Qiangshun; Zhou, Guangshun; Yi, Chengwu

    2016-09-01

    The synergistic technique of pulsed discharge plasma (PDP) and activated carbon (AC) was built to investigate the kinetics of acid orange 7 (AO7) degradation under different conditions of AC addition, electrode gap, initial pH value of solution, gas variety and gas flow rate. Emission spectra of OH and O, UV-vis absorption spectra of the AO7 solution and TOC removal were measured to illustrate the synergistic mechanism of the PDP and the AC. The obtained results indicated that the kinetic constant of AO7 degradation increased from 0.00947 min(-1) to 0.01419 min(-1) when 4 g AC was added into the PDP system; AO7 degradation was higher in the case of alkaline solution when oxygen was used as the flow gas in the PDP/AC system, 2 L/min oxygen flow was more favorable for the degradation. Results of the relative emission intensities of OH and O indicated the catalytic effect of the AC on the active species formation as well as the important role of the two radicals for the AO7 degradation. There was no new peaks appeared by the UV-vis analysis of the AO7 solution after 60 min treatment. The highest TOC removal in the PDP/AC system was 30.3%, which was achieved under the condition of 4 L/min air flow rate and 3 initial pH value.

  8. Blood and tissue concentrations of trimethoprim following its administration alone and in combination with josamycin.

    PubMed

    el-Sayed, M G; Abd el-Aziz, M I; Abd el-Azem, A M

    1992-04-01

    Following a single oral dose of trimethoprim (10 mg/kg b. wt.) in normal fowls, the highest serum concentration achieved 4 hours post-administration with value of 0.64 microgram/ml. The absorption half-life time was 0.64 hours. The elimination half life was 4.73 hours. During repeated oral administration of 10 mg/kg b. wt., once daily for five consecutive days, trimethoprim peaked in serum, 4 h after each dose. Trimethoprim persisted in all fowl's tissues for 96 hours after stopping of drug administration. After oral administration of josamycin (18 mg/kg b. wt.) and trimethoprim (10 mg/kg b. wt.) in normal fowls, a maximum serum concentration of trimethoprim was recorded at 2 hours with half-life of absorption (t0.5(ab)) valued 0.74 hour. The elimination half-life (t0.5 beta) was 4.37 hours. During repeated oral administration of josamycin (18 mg/kg b. wt.) and trimethoprim (10 mg/kg b. wt.) once daily for five consecutive days in normal fowls, the highest plasma concentrations of trimethoprim occurred 2 hours post each dose. The daily maximum plasma concentrations during the repeated oral administration of both tested drugs were nearly constant.

  9. The effects of different doses of silibinin in combination with methotrexate on testicular tissue of mice.

    PubMed

    Oufi, Hayder Gaeed; Al-Shawi, Nada Naji

    2014-05-05

    Methotrexate (MTX) is widely used chemotherapeutic agent with different side effects including germ cells toxicities. Silibinin is one of the structural isomers of silymarin, with different phytotherapeutic applications, and its possible protective effects against MTX induced germ cells damage were investigated in this work. Twenty five male mice were divided into five groups (n=5) allocated as follows: Group 1 received buffer for five days given by single intraperitoneal (IP) injection per day; Group 2 in addition to buffer for five days, animals received at day five single dose of 20mg/kg of MTX IP. Groups (3, 4, and 5) received respectively, (50, 100, or 150mg/kg body weight) of silibinin IP single daily dose for five days then at day five 20mg/kg of MTX IP. Microscopic examinations of sperms, histological examinations of testis and serum testosterone had been measured. Silibinin showed a significant decrease in the percent of dead/live sperm with significant changes in interstitial space and in the diameter of spermatide. The results indicate that silibinin can mitigate some of the toxic effects of MTX in testicular tissue.

  10. Minipig-BMSCs Combined with a Self-Setting Calcium Phosphate Paste for Bone Tissue Engineering.

    PubMed

    Qiu, Gengtao; Wang, Ping; Li, Guangjun; Shi, Zhanjun; Weir, Michael D; Sun, Jinyu; Song, Yang; Wang, Jixing; Xu, Huakun H; Zhao, Liang

    2016-11-01

    Calcium phosphate cements (CPCs) are a new generation of bone repair materials with good biocompatibility for various stem cells. The minipig is a recommended large animal model for bone engineering research. This study aimed to evaluate the feasibility of utilizing CPC scaffolds for the adhesion, proliferation, and osteogenic differentiation of minipig's bone marrow mesenchymal stem cells (pBMSCs). Passage 3 pBMSCs were seeded on the CPC scaffold and cultured with osteogenic culture medium (osteogenic group) or normal medium (control group). The density of viable cells increased in both groups, and pBMSCs firmly attached and spread well on the CPC scaffold. The alkaline phosphatase (ALP) activity in the osteogenic group had significantly increased on day 7 (D7) and peaked on D14. qRT-PCR revealed that mRNA levels of ALP and three osteogenic marker genes were significantly higher on D4, D7, and D14 in the osteogenic group. Alizarin Red S staining showed a significantly higher degree of bone mineralization from D7, D14 to D21 in the osteogenic group. These results indicated that pBMSCs can attach, proliferate well on CPC scaffold, and be successfully induced to differentiate into osteogenic cells. Our findings may be helpful for bone tissue engineering and the studies of bone regeneration.

  11. In and ex-vivo Myocardial Tissue Temperature Monitoring by Combined Infrared and Ultrasonic Thermometries

    NASA Astrophysics Data System (ADS)

    Engrand, C.; Laux, D.; Ferrandis, J.-Y.; Sinquet, J.-C.; Demaria, R.; Le Clézio, E.

    The success of cardiac surgery essentially depends on tissue preservation during intervention. Consequently a hypothermic cardio-plegia is applied in order to avoid ischemia. However, myocardial temperature is not monitored during operation. The aim of this study is then to find a relevant and simple method for myocardial global temperature estimation in real time using both ultrasounds and infra-red thermography. In order to quantify the sensitivity of ultrasonic velocity to temperature, a 2.25 MHz ultrasonic probe was used for ex-vivo tests. Pig myocards (n=25) were placed in a thermostatically-controlled water bath and measurements of the ultrasound velocity were realized from 10 to 30 ˚C. The results of this study indicate that the specificity and sensitivity of the ultrasonic echo delay induced by the modification of temperature can be exploited for in-depth thermometry. In parallel, for TIR experiments, a bolometer was used to detect the myocardium surface thermal evolution during in-vivo pig heart experiments. Hypothermic cardioplegic solutions were injected and infra-red surface imaging was performed during one hour. In the near futur, the correlation of the ultrasound and the infrared measurements should allow the real time estimation of the global temperature of the heart. The final objective being to realize in vivo measurements on human hearts, this information may have a very high importance in terms of per-operation inspection as well as decision making process during medical interventions.

  12. Understanding the differences in molecular conformation of carbohydrate and protein in endosperm tissues of grains with different biodegradation kinetics using advanced synchrotron technology

    NASA Astrophysics Data System (ADS)

    Yu, P.; Block, H. C.; Doiron, K.

    2009-01-01

    Conventional "wet" chemical analyses rely heavily on the use of harsh chemicals and derivatization, thereby altering native seed structures leaving them unable to detect any original inherent structures within an intact tissue sample. A synchrotron is a giant particle accelerator that turns electrons into light (million times brighter than sunlight) which can be used to study the structure of materials at the molecular level. Synchrotron radiation-based Fourier transform IR microspectroscopy (SR-FTIRM) has been developed as a rapid, direct, non-destructive and bioanalytical technique. This technique, taking advantage of the brightness of synchrotron light and a small effective source size, is capable of exploring the molecular chemistry within the microstructures of a biological tissue without the destruction of inherent structures at ultraspatial resolutions within cellular dimensions. This is in contrast to traditional 'wet' chemical methods, which, during processing for analysis, often result in the destruction of the intrinsic structures of feeds. To date there has been very little application of this technique to the study of plant seed tissue in relation to nutrient utilization. The objective of this study was to use novel synchrotron radiation-based technology (SR-FTIRM) to identify the differences in the molecular chemistry and conformation of carbohydrate and protein in various plant seed endosperms within intact tissues at cellular and subcellular level from grains with different biodegradation kinetics. Barley grain (cv. Harrington) with a high rate (31.3%/h) and extent (78%), corn grain (cv. Pioneer) with a low rate (9.6%/h) and extent of (57%), and wheat grain (cv. AC Barrie) with an intermediate rate (23%/h) and extent (72%) of ruminal DM degradation were selected for evaluation. SR-FTIRM evaluations were performed at the National Synchrotron Light Source at the Brookhaven National Laboratory (Brookhaven, NY). The molecular structure spectral analysis

  13. Combination effects of tissue heterogeneity and geometric targeting error in stereotactic body radiotherapy for lung cancer using CyberKnife.

    PubMed

    Kang, Ki Mun; Jeong, Bae Kwon; Choi, Hoon-Sik; Yoo, Seung Hoon; Hwang, Ui-Jung; Lim, Young Kyung; Jeong, Hojin

    2015-09-08

    We have investigated the combined effect of tissue heterogeneity and its variation associated with geometric error in stereotactic body radiotherapy (SBRT) for lung cancer. The treatment plans for eight lung cancer patients were calculated using effective path length (EPL) correction and Monte Carlo (MC) algorithms, with both having the same beam configuration for each patient. These two kinds of plans for individual patients were then subsequently recalculated with adding systematic and random geometric errors. In the ordinary treatment plans calculated with no geometric offset, the EPL calculations, compared with the MC calculations, largely overestimated the doses to PTV by ~ 21%, whereas the overestimation were markedly lower in GTV by ~ 12% due to relatively higher density of GTV than of PTV. When recalculating the plans for individual patients with assigning the systematic and random geometric errors, no significant changes in the relative dose distribution, except for overall shift, were observed in the EPL calculations, whereas largely altered in the MC calculations with a consistent increase in dose to GTV. Considering the better accuracy of MC than EPL algorithms, the present results demonstrated the strong coupling of tissue heterogeneity and geometric error, thereby emphasizing the essential need for simultaneous correction for tissue heterogeneity and geometric targeting error in SBRT of lung cancer.

  14. Combining high-resolution micro-computed tomography with material composition to define the quality of bone tissue.

    PubMed

    Judex, Stefan; Boyd, Steve; Qin, Yi-Xian; Miller, Lisa; Müller, Ralph; Rubin, Clinton

    2003-06-01

    Atraumatic fractures of the skeleton in osteoporotic patients are directly related to a deterioration of bone strength. However, the failure of the bone tissue to withstand functional load bearing cannot be explained as a simple decrease in bone mineral density (quantity); strength is also significantly dependent upon bone quality. While a formal definition of bone quality is somewhat elusive, at the very least, it incorporates architectural, physical, and biologic factors that are critical to bone strength. Such factors include bone morphology (ie, trabecular connectivity, cross-sectional geometry, longitudinal curvature); the tissue's material properties (eg, stiffness, strength); its chemical composition and architecture (eg, ratio of calcium to other components of the organic and/or inorganic phase, collagen orientation, porosity, permeability); and the viability of the tissue (eg, responsivity of the bone cell population). Combining high-resolution structural indices of bone, as determined by micro-computed tomography; material properties determined by nanoindentation; and the chemical make-up of bone, as determined by infrared spectroscopy, helps to provide critical information toward a more comprehensive assessment of the interdependence of bone quality, quantity, and fracture risk.

  15. In vivo evaluation of lesion sterilization and tissue repair in primary teeth pulp therapy using two antibiotic drug combinations.

    PubMed

    Jaya, A R; Praveen, P; Anantharaj, A; Venkataraghavan, Karthik; Rani, Prathibha S

    2012-01-01

    The purpose of this study is to evaluate and compare the clinical and radiographic effectiveness of Ciprofloxacin, Minocycline, Metronidazole combination with Ciprofloxacin, Minocycline and Tinidazole combination when used for Lesion Sterilization and Tissue Repair in primary teeth. 25 healthy children, visiting Dept. of Pediatric & Preventive Dentistry, D.A.P.M.R.V. Dental College, Bangalore, India, aged between 6-9 years who were having 30 infected primary teeth are selected and divided into 2 groups. In Group A, a mixture of 3mix-MP Ciprofloxacin, Metronidazole and Minocycline was placed on the floor of the pulp chamber covering the root canal orifices. In Group B a mixture of Ciprofloxacin, Tinidazole and Minocycline was placed as a layer on the floor of the pulp chamber. The procedure was completed in a single visit. Post operative clinical evaluation was done after 1,6,12 and 24 months. Postoperative radiographic evaluation was done at 6, 12 and 24 months. No statistically significant difference is observed between both the groups and a combination of Ciprofloxacin, Minocycline and Tinidazole antibacterial drugs can be used on teeth pulpally involved with physiologic root resorption. After a 24 Month follow up, we can conclude that primary teeth with the periradicular lesions, can be conserved by using combination of Ciprofloxacin, Minocycline and Tinidazole antibacterial drugs.

  16. Endothelial cell colonization and angiogenic potential of combined nano- and micro-fibrous scaffolds for bone tissue engineering.

    PubMed

    Santos, Marina I; Tuzlakoglu, Kadriye; Fuchs, Sabine; Gomes, Manuela E; Peters, Kirsten; Unger, Ronald E; Piskin, Erhan; Reis, Rui L; Kirkpatrick, C James

    2008-11-01

    Presently the majority of tissue engineering approaches aimed at regenerating bone relies only on post-implantation vascularization. Strategies that include seeding endothelial cells (ECs) on biomaterials and promoting their adhesion, migration and functionality might be a solution for the formation of vascularized bone. Nano/micro-fiber-combined scaffolds have an innovative structure, inspired by extracellular matrix (ECM) that combines a nano-network, aimed to promote cell adhesion, with a micro-fiber mesh that provides the mechanical support. In this work we addressed the influence of this nano-network on growth pattern, morphology, inflammatory expression profile, expression of structural proteins, homotypic interactions and angiogenic potential of human EC cultured on a scaffold made of a blend of starch and poly(caprolactone). The nano-network allowed cells to span between individual micro-fibers and influenced cell morphology. Furthermore, on nano-fibers as well as on micro-fibers ECs maintained the physiological expression pattern of the structural protein vimentin and PECAM-1 between adjacent cells. In addition, ECs growing on the nano/micro-fiber-combined scaffold were sensitive to pro-inflammatory stimulus. Under pro-angiogenic conditions in vitro, the ECM-like nano-network provided the structural and organizational stability for ECs' migration and organization into capillary-like structures. The architecture of nano/micro-fiber-combined scaffolds elicited and guided the 3D distribution of ECs without compromising the structural requirements for bone regeneration.

  17. [Lateral superior genicular flap combined with Tuihuang xiaozhong decoction for the treatment of soft tissue defects around the knee joint].

    PubMed

    Wang, Jun-Yi; Li, Da-Wei; Jin, Tian-Ming; Liu, Zhong-Wen

    2010-03-01

    To evaluate the early combination of Chinese and Western medicine for anti-inflammation and lateral superior genicular flap for the treatment of soft tissue defects around the knee joint. From June 2004 to September 2008, 8 patients with soft tissue defects around the knee joint were treated with lateral superior genicular flap. Among the patients, 5 patients were male and 3 patients were female, ranging in age from 32 to 56 years, with an average of 35.2 years. The defected area ranged from 7.6 cm x 4.5 cm to 15.2 cm x 7.5 cm. The disease course ranged from 3 months to 3 years. Three patients had the defects at the posterior of the knee, 2 patients had the defects at the popliteal fossa, and 3 patients had the defects at the lateral side of the knee. At the early stage, all the patients were treated with Tuihuang Xiaozhong decoction and antibiotics for 3 to 5 days. All the flaps survived, and the knee function recovered. One patient had epidermis necrosis at the distal end of the flap of lateral side of the knee. The early combination of Chinese and Western medicine for anti-inflammation is a simple, easy to promote, and no special microsurgical instruments are needed.

  18. Relationship of psychopathology to the human serotonin1B genotype and receptor binding kinetics in postmortem brain tissue.

    PubMed

    Huang, Y Y; Grailhe, R; Arango, V; Hen, R; Mann, J J

    1999-08-01

    Knockout of the 5-HT1B gene in mice results in increased aggression, as well as alcohol and cocaine consumption. Given the clinical association of aggression, suicide, alcoholism, and substance abuse, we studied relationship of psychopathology to the human 5-HT1B receptor gene (N = 178) and postmortem human 5-HT1B receptor binding (N = 96) in the brain. The sample comprised: 71 suicide victims, 107 nonsuicides, 45 with a history of major depression and 79 without, 64 with a history of a alcoholism or substance abuse and 60 without, as well as 36 with a history of pathological aggression and 42 without. Single-strand conformational polymorphism (SSCP) analysis and DNA sequencing techniques were used to screen the coding region of the human 5-HT1B receptor gene in genomic DNA isolated from postmortem human brain tissue. Two common polymorphisms were identified in the 5-HT1B receptor gene, involving a silent C to T substitution at nucleotide 129 and a silent G to C substitution at nucleotide 861 of the coding region. These polymorphisms were found with the same frequency in the suicide and the nonsuicide groups and in those with and without a history of major depression, alcoholism, or pathological aggression. The binding indices (Bmax and KD of the 5-HT1B receptor in prefrontal cortex also did not differ in suicides and controls, major depression, alcoholism, and cases with a history of pathological aggression. The C129 or G861 allele had 20% fewer 5-HT1B receptor compared to the 129T or 861C allele. We did not identify a relationship between suicide, major depression, alcoholism, or pathological aggression with 5-HT1B receptor binding indices or genotype.

  19. Three-dimensional polycaprolactone-hydroxyapatite scaffolds combined with bone marrow cells for cartilage tissue engineering.

    PubMed

    Wei, Bo; Yao, Qingqiang; Guo, Yang; Mao, Fengyong; Liu, Shuai; Xu, Yan; Wang, Liming

    2015-08-01

    The goal of this study was to investigate the chondrogenic potential of three-dimensional polycaprolactone-hydroxyapatite (PCL-HA) scaffolds loaded with bone marrow cells in vitro and the effect of PCL-HA scaffolds on osteochondral repair in vivo. Here, bone marrow was added to the prepared PCL-HA scaffolds and cultured in chondrogenic medium for 10 weeks. Osteochondral defects were created in the trochlear groove of 29 knees in 17 New Zealand white rabbits, which were then divided into four groups that underwent: implantation of PCL-HA scaffolds (left knee, n = 17; Group 1), microfracture (right knee, n = 6; Group 2), autologous osteochondral transplantation (right knee, n = 6; Group 3), and no treatment (right knee, n = 5; Control). Extracellular matrix produced by bone marrow cells covered the surface and filled the pores of PCL-HA scaffolds after 10 weeks in culture. Moreover, many cell-laden cartilage lacunae were observed, and cartilage matrix was concentrated in the PCL-HA scaffolds. After a 12-week repair period, Group 1 showed excellent vertical and lateral integration with host bone, but incomplete cartilage regeneration and matrix accumulation. An uneven surface of regenerated cartilage and reduced distribution of cartilage matrix were observed in Group 2. In addition, abnormal bone growth and unstable integration between repaired and host tissues were detected. For Group 3, the integration between transplanted and host cartilage was interrupted. Our findings indicate that the PCL-HA scaffolds loaded with bone marrow cells improved chondrogenesis in vitro and implantation of PCL-HA scaffolds for osteochondral repairenhanced integration with host bone. However, cartilage regeneration remained unsatisfactory. The addition of trophic factors or the use of precultured cell-PCL-HA constructs for accelerated osteochondral repair requires further investigation.

  20. Vacuum Sealing Drainage Treatment Combined with Antibiotic-Impregnated Bone Cement for Treatment of Soft Tissue Defects and Infection.

    PubMed

    Liu, Xin; Liang, Jiulong; Zao, Jun; Quan, Liangliang; Jia, Xunyuan; Li, Mingchao; Tao, Kai

    2016-06-09

    BACKGROUND This study aimed to evaluate the combined effect of vacuum sealing drainage (VSD) and antibiotic-loaded bone cement on soft tissue defects and infection. MATERIAL AND METHODS This prospective non-blinded study recruited 46 patients with soft tissue defects and infection from January 2010 to May 2014 and randomly divided them into experimental and control groups (n=23). Patients in the experimental group were treated with VSD and antibiotic-loaded bone cement, while the patients in the control group were treated with VSD only. RESULTS In the experimental group, the wound was healed in 23 cases at 4 weeks postoperatively, of which direct suture was performed in 12 cases, and additional free flap transplantation or skin grafting was performed in 6 cases and 5 cases, respectively. No infection reoccurred in 1-year follow-up. In the control group, the wound was healed in 15 cases at 6 weeks postoperatively, of which direct suture was performed in 8 cases, and additional free flap transplantation or skin grafting was performed in 3 cases and 4 cases, respectively. In the other 8 cases the wound was healed at 8 weeks postoperatively. Infection reoccurred in 3 cases during the follow-up. The experimental group had significantly fewer VSD dressing renewals, shorter time needed until the wound was ready for surgery, shorter duration of antibiotic administration, faster wound healing, and shorter hospital stay than the control group (p<0.01). CONCLUSIONS The combination of VSD and antibiotic bone cement might be a better method for treatment of soft tissue defects and infection.

  1. Vacuum Sealing Drainage Treatment Combined with Antibiotic-Impregnated Bone Cement for Treatment of Soft Tissue Defects and Infection

    PubMed Central

    Liu, Xin; Liang, Jiulong; Zhao, Jun; Quan, Liangliang; Jia, Xunyuan; Li, Mingchao; Tao, Kai

    2016-01-01

    Background This study aimed to evaluate the combined effect of vacuum sealing drainage (VSD) and antibiotic-loaded bone cement on soft tissue defects and infection. Material/Methods This prospective non-blinded study recruited 46 patients with soft tissue defects and infection from January 2010 to May 2014 and randomly divided them into experimental and control groups (n=23). Patients in the experimental group were treated with VSD and antibiotic-loaded bone cement, while the patients in the control group were treated with VSD only. Results In the experimental group, the wound was healed in 23 cases at 4 weeks postoperatively, of which direct suture was performed in 12 cases, and additional free flap transplantation or skin grafting was performed in 6 cases and 5 cases, respectively. No infection reoccurred in 1-year follow-up. In the control group, the wound was healed in 15 cases at 6 weeks postoperatively, of which direct suture was performed in 8 cases, and additional free flap transplantation or skin grafting was performed in 3 cases and 4 cases, respectively. In the other 8 cases the wound was healed at 8 weeks postoperatively. Infection reoccurred in 3 cases during the follow-up. The experimental group had significantly fewer VSD dressing renewals, shorter time needed until the wound was ready for surgery, shorter duration of antibiotic administration, faster wound healing, and shorter hospital stay than the control group (p<0.01). Conclusions The combination of VSD and antibiotic bone cement might be a better method for treatment of soft tissue defects and infection. PMID:27281233

  2. Computational modeling reveals that a combination of chemotaxis and differential adhesion leads to robust cell sorting during tissue patterning.

    PubMed

    Tan, Rui Zhen; Chiam, Keng-Hwee

    2014-01-01

    Robust tissue patterning is crucial to many processes during development. The "French Flag" model of patterning, whereby naïve cells in a gradient of diffusible morphogen signal adopt different fates due to exposure to different amounts of morphogen concentration, has been the most widely proposed model for tissue patterning. However, recently, using time-lapse experiments, cell sorting has been found to be an alternative model for tissue patterning in the zebrafish neural tube. But it remains unclear what the sorting mechanism is. In this article, we used computational modeling to show that two mechanisms, chemotaxis and differential adhesion, are needed for robust cell sorting. We assessed the performance of each of the two mechanisms by quantifying the fraction of correct sorting, the fraction of stable clusters formed after correct sorting, the time needed to achieve correct sorting, and the size variations of the cells having different fates. We found that chemotaxis and differential adhesion confer different advantages to the sorting process. Chemotaxis leads to high fraction of correct sorting as individual cells will either migrate towards or away from the source depending on its cell type. However after the cells have sorted correctly, there is no interaction among cells of the same type to stabilize the sorted boundaries, leading to cell clusters that are unstable. On the other hand, differential adhesion results in low fraction of correct clusters that are more stable. In the absence of morphogen gradient noise, a combination of both chemotaxis and differential adhesion yields cell sorting that is both accurate and robust. However, in the presence of gradient noise, the simple combination of chemotaxis and differential adhesion is insufficient for cell sorting; instead, chemotaxis coupled with delayed differential adhesion is required to yield optimal sorting.

  3. Computational Modeling Reveals that a Combination of Chemotaxis and Differential Adhesion Leads to Robust Cell Sorting during Tissue Patterning

    PubMed Central

    Tan, Rui Zhen; Chiam, Keng-Hwee

    2014-01-01

    Robust tissue patterning is crucial to many processes during development. The "French Flag" model of patterning, whereby naïve cells in a gradient of diffusible morphogen signal adopt different fates due to exposure to different amounts of morphogen concentration, has been the most widely proposed model for tissue patterning. However, recently, using time-lapse experiments, cell sorting has been found to be an alternative model for tissue patterning in the zebrafish neural tube. But it remains unclear what the sorting mechanism is. In this article, we used computational modeling to show that two mechanisms, chemotaxis and differential adhesion, are needed for robust cell sorting. We assessed the performance of each of the two mechanisms by quantifying the fraction of correct sorting, the fraction of stable clusters formed after correct sorting, the time needed to achieve correct sorting, and the size variations of the cells having different fates. We found that chemotaxis and differential adhesion confer different advantages to the sorting process. Chemotaxis leads to high fraction of correct sorting as individual cells will either migrate towards or away from the source depending on its cell type. However after the cells have sorted correctly, there is no interaction among cells of the same type to stabilize the sorted boundaries, leading to cell clusters that are unstable. On the other hand, differential adhesion results in low fraction of correct clusters that are more stable. In the absence of morphogen gradient noise, a combination of both chemotaxis and differential adhesion yields cell sorting that is both accurate and robust. However, in the presence of gradient noise, the simple combination of chemotaxis and differential adhesion is insufficient for cell sorting; instead, chemotaxis coupled with delayed differential adhesion is required to yield optimal sorting. PMID:25302949

  4. Modeling [(18)F]-FDG lymphoid tissue kinetics to characterize nonhuman primate immune response to Middle East respiratory syndrome-coronavirus aerosol challenge.

    PubMed

    Chefer, Svetlana; Thomasson, David; Seidel, Jurgen; Reba, Richard C; Bohannon, J Kyle; Lackemeyer, Mathew G; Bartos, Chris; Sayre, Philip J; Bollinger, Laura; Hensley, Lisa E; Jahrling, Peter B; Johnson, Reed F

    2015-12-01

    The pathogenesis and immune response to Middle East respiratory syndrome (MERS) caused by a recently discovered coronavirus, MERS-CoV, have not been fully characterized because a suitable animal model is currently not available. (18)F-Fluorodeoxyglucose ([(18)F]-FDG)-positron emission tomography/computed tomography (PET/CT) as a longitudinal noninvasive approach can be beneficial in providing biomarkers for host immune response. [(18)F]-FDG uptake is increased in activated immune cells in response to virus entry and can be localized by PET imaging. We used [(18)F]-FDG-PET/CT to investigate the host response developing in nonhuman primates after MERS-CoV exposure and applied kinetic modeling to monitor the influx rate constant (K i ) in responsive lymphoid tissue. Multiple [(18)F]-FDG-PET and CT images were acquired on a PET/CT clinical scanner modified to operate in a biosafety level 4 environment prior to and up to 29 days after MERS-CoV aerosol exposure. Time activity curves of various lymphoid tissues were reconstructed to follow the [(18)F]-FDG uptake for approximately 60 min (3,600 s). Image-derived input function was used to calculate K i for lymphoid tissues by Patlak plot. Two-way repeated measures analysis of variance revealed alterations in K i that was associated with the time point (p < 0.001) after virus exposure and the location of lymphoid tissue (p = 0.0004). As revealed by a statistically significant interaction (p < 0.0001) between these two factors, the pattern of K i changes over time differed between three locations but not between subjects. A distinguished pattern of statistically significant elevation in K i was observed in mediastinal lymph nodes (LNs) that correlated to K i changes in axillary LNs. Changes in LNs K i were concurrent with elevations of monocytes in peripheral blood. [(18)F]-FDG-PET is able to detect subtle changes in host immune response to contain a subclinical virus infection. Full quantitative analysis is

  5. Nitrogen removal of ramie stalk treated by acid wastewater combined with Clostridium thermocellum and the kinetic study of pyrolysis.

    PubMed

    Wang, Buyun; Li, Ting; Zhu, Ning; Xiao, Bo

    2013-02-01

    A pretreatment was developed to remove nitrogen from ramie residue and cotton stalk to eliminate potential nitrogen pollutants in biomass energy production. In the pretreatment, straw was treated with acid wastewater from bioleaching for 3 h followed by Clostridium thermocellum incubation for 2 h. Most nitrogen was removed from biomass waste and the major was that in protein. Pyrolysis process revealed most hemicellulose was removed and the kinetics fitted the first-order equation well. Apparent activation energy of ramie residue increased a little and mass loss became concentrated. Ultimate analysis and pyrolysis analysis revealed the treatment did not weaken the application value of biomass in energy production. Replacing acid wastewater with sulphuric acid, a higher nitrogen removal could be achieved; however, activation energy increased sharply.

  6. HCV kinetic and modeling analyses indicate similar time to cure among sofosbuvir combination regimens with daclatasvir, simeprevir or ledipasvir

    DOE PAGES

    Dahari, Harel; Canini, Laetitia; Graw, Frederik; ...

    2016-06-01

    Recent clinical trials of direct-acting-antiviral agents (DAAs) against hepatitis C virus (HCV) achieved >90% sustained virological response (SVR) rates, suggesting that cure often took place before the end of treatment (EOT). We sought to evaluate retrospectively whether early response kinetics can provide the basis to individualize therapy to achieve optimal results while reducing duration and cost. 58 chronic HCV patients were treated with 12-week sofosbuvir + simeprevir (n = 19), sofosbuvir + daclatasvir (n = 19), or sofosbuvir + ledipasvir in three French referral centers. HCV was measured at baseline, day 2, every other week, EOT and 12 weeks postmore » EOT. Furthermore, mathematical modeling was used to predict the time to cure, i.e., <1 virus copy in the entire extracellular body fluid. All but one patient who relapsed achieved SVR. Mean age was 60 ± 11 years, 53% were male, 86% HCV genotype-1, 9% HIV coinfected, 43% advanced fibrosis (F3), and 57% had cirrhosis. At weeks 2, 4 and 6, 48%, 88% and 100% of patients had HCV <15 IU/ml, with 27%, 74% and 91% of observations having target not detected, respectively. Modeling results predicted that 23 (43%), 16 (30%), 7 (13%), 5 (9%) and 3 (5%) subjects were predicted to reach cure within 6, 8, 10, 12 and 13 weeks of therapy, respectively. The modeling suggested that the patient who relapsed would have benefitted from an additional week of sofosbuvir + ledipasvir. Adjusting duration of treatment according to the modeling predicts reduced medication costs of 43–45% and 17–30% in subjects who had HCV <15 IU/ml at weeks 2 and 4, respectively. Finally, the use of early viral kinetic analysis has the potential to individualize duration of DAA therapy with a projected average cost saving of 16–20% per 100-treated persons.« less

  7. HCV kinetic and modeling analyses indicate similar time to cure among sofosbuvir combination regimens with daclatasvir, simeprevir or ledipasvir

    SciTech Connect

    Dahari, Harel; Canini, Laetitia; Graw, Frederik; Uprichard, Susan L.; Araújo, Evaldo S. A.; Penaranda, Guillaume; Coquet, Emilie; Chiche, Laurent; Riso, Aurelie; Renou, Christophe; Bourliere, Marc; Cotler, Scott J.; Halfon, Philippe

    2016-06-01

    Recent clinical trials of direct-acting-antiviral agents (DAAs) against hepatitis C virus (HCV) achieved >90% sustained virological response (SVR) rates, suggesting that cure often took place before the end of treatment (EOT). We sought to evaluate retrospectively whether early response kinetics can provide the basis to individualize therapy to achieve optimal results while reducing duration and cost. 58 chronic HCV patients were treated with 12-week sofosbuvir + simeprevir (n = 19), sofosbuvir + daclatasvir (n = 19), or sofosbuvir + ledipasvir in three French referral centers. HCV was measured at baseline, day 2, every other week, EOT and 12 weeks post EOT. Furthermore, mathematical modeling was used to predict the time to cure, i.e., <1 virus copy in the entire extracellular body fluid. All but one patient who relapsed achieved SVR. Mean age was 60 ± 11 years, 53% were male, 86% HCV genotype-1, 9% HIV coinfected, 43% advanced fibrosis (F3), and 57% had cirrhosis. At weeks 2, 4 and 6, 48%, 88% and 100% of patients had HCV <15 IU/ml, with 27%, 74% and 91% of observations having target not detected, respectively. Modeling results predicted that 23 (43%), 16 (30%), 7 (13%), 5 (9%) and 3 (5%) subjects were predicted to reach cure within 6, 8, 10, 12 and 13 weeks of therapy, respectively. The modeling suggested that the patient who relapsed would have benefitted from an additional week of sofosbuvir + ledipasvir. Adjusting duration of treatment according to the modeling predicts reduced medication costs of 43–45% and 17–30% in subjects who had HCV <15 IU/ml at weeks 2 and 4, respectively. Finally, the use of early viral kinetic analysis has the potential to individualize duration of DAA therapy with a projected average cost saving of 16–20% per 100-treated persons.

  8. HCV kinetic and modeling analyses indicate similar time to cure among sofosbuvir combination regimens with daclatasvir, simeprevir or ledipasvir

    PubMed Central

    Dahari, Harel; Canini, Laetitia; Graw, Frederik; Uprichard, Susan L.; Araújo, Evaldo S.A.; Penaranda, Guillaume; Coquet, Emilie; Riso, Aurelie; Renou, Christophe; Bourliere, Marc; Cotler, Scott J.; Halfon, Philippe

    2016-01-01

    Background&Aims Recent clinical trials of direct-acting-antiviral agents (DAAs) against hepatitis C virus (HCV) achieved >90% sustained-virological response (SVR) rates, suggesting that cure often took place before the end of treatment (EOT). We sought to evaluate retrospectively whether early response kinetics can provide the basis to individualize therapy to achieve optimal results while reducing duration and cost. Methods 58 chronic-HCV patients were treated with 12-week sofosbuvir+simeprevir(n=19), sofosbuvir+daclatasvir(n=19), or sofosbuvir+ledipasvir in three French referral centers. HCV was measured at baseline, day 2, every other week, EOT and 12 weeks post EOT. Mathematical modeling was used to predict the time to cure,i.e,<1 virus copy in the entire extracellular-body fluid. Results All but one patient who relapsed achieved SVR. Mean age was 60±11 years, 53% were male, 86% HCV genotype-1, 9% HIV coinfected, 43% advanced fibrosis (F3), and 57% had cirrhosis. At weeks 2, 4 and 6, 48%, 88% and 100% of patients had HCV<15 IU/ml, with 27%, 74% and 91% of observations having target-not-detected, respectively. Modeling results predicted that 32(43%), 16(23%), 7(13%), 5(9%) and 3(5%) subjects were predicted to reach cure within 6, 8, 10, 12 and 13 weeks of therapy, respectively. The modeling suggested that the patient who relapsed would have benefitted from an additional week of sofosbuvir+ledipasvir. Adjusting duration of treatment according to the modeling predicts reduced medication costs of 43%-45% and 17%-30% in subjects who had HCV<15 IU/ml at weeks 2 and 4, respectively. Conclusions The use of early viral-kinetic analysis has the potential to individualize duration of DAA therapy with a projected average cost-saving of 16%-20% per 100-treated persons. PMID:26907973

  9. Combined effects of physics and physiology explain the observed pattern of nitrate uptake kinetics in the ocean

    NASA Astrophysics Data System (ADS)

    Smith, S. L.; Hohn, S.; Brandt, G.; Merico, A.; Yoshikawa, C.

    2013-12-01

    Recent trait-based modeling of nutrient uptake by microorganisms (Aksnes & Cao. Marine Ecology Progress Series 440, p. 41-51, 2011; Fiksen et al. Limnology and Oceanography 58, p. 193-202, 2013) has advanced our understanding of how the nutrient uptake kinetics should depend on cell size and extracellular diffusion of nutrient molecules. This has provided a basis for better understanding observed patterns in terms of traits and fundamental physical processes, and for formulating more realistic models of plankton ecosystems. Here we extend the trait-based models using the principle of optimality subject to a physiological trade-off between the maximum uptake rate vs. the number of uptake sites. Then we test the predictions of each model, with and without the trade-off, against observed patterns for kinetic parameters describing the rate of nitrate uptake by natural assemblages of oceanic plankton as measured by ship-board experiments. The new model is able to reproduce: 1) the tendency of half-saturation constants to increase with nitrate concentration in the ocean, in terms of the trade-off, and 2) the wide variability in measured half-saturation constants, in terms of a realistic range of cell sizes for oceanic phytoplankton. We finally present a coherent explanation for the observed pattern in terms of both adaptation of physiology to environmental nutrient concentrations, which results in greater half- saturation constants for cells of any size adapted to higher vs. lower nutrient concentrations, and cell size, which tends to increase with ambient nutrient concentration. This provides a basis for modeling size as an adaptive trait in planktonic ecosystem models.

  10. HCV kinetic and modeling analyses indicate similar time to cure among sofosbuvir combination regimens with daclatasvir, simeprevir or ledipasvir

    SciTech Connect

    Dahari, Harel; Canini, Laetitia; Graw, Frederik; Uprichard, Susan L.; Araújo, Evaldo S. A.; Penaranda, Guillaume; Coquet, Emilie; Chiche, Laurent; Riso, Aurelie; Renou, Christophe; Bourliere, Marc; Cotler, Scott J.; Halfon, Philippe

    2016-06-01

    Recent clinical trials of direct-acting-antiviral agents (DAAs) against hepatitis C virus (HCV) achieved >90% sustained virological response (SVR) rates, suggesting that cure often took place before the end of treatment (EOT). We sought to evaluate retrospectively whether early response kinetics can provide the basis to individualize therapy to achieve optimal results while reducing duration and cost. 58 chronic HCV patients were treated with 12-week sofosbuvir + simeprevir (n = 19), sofosbuvir + daclatasvir (n = 19), or sofosbuvir + ledipasvir in three French referral centers. HCV was measured at baseline, day 2, every other week, EOT and 12 weeks post EOT. Furthermore, mathematical modeling was used to predict the time to cure, i.e., <1 virus copy in the entire extracellular body fluid. All but one patient who relapsed achieved SVR. Mean age was 60 ± 11 years, 53% were male, 86% HCV genotype-1, 9% HIV coinfected, 43% advanced fibrosis (F3), and 57% had cirrhosis. At weeks 2, 4 and 6, 48%, 88% and 100% of patients had HCV <15 IU/ml, with 27%, 74% and 91% of observations having target not detected, respectively. Modeling results predicted that 23 (43%), 16 (30%), 7 (13%), 5 (9%) and 3 (5%) subjects were predicted to reach cure within 6, 8, 10, 12 and 13 weeks of therapy, respectively. The modeling suggested that the patient who relapsed would have benefitted from an additional week of sofosbuvir + ledipasvir. Adjusting duration of treatment according to the modeling predicts reduced medication costs of 43–45% and 17–30% in subjects who had HCV <15 IU/ml at weeks 2 and 4, respectively. Finally, the use of early viral kinetic analysis has the potential to individualize duration of DAA therapy with a projected average cost saving of 16–20% per 100-treated persons.

  11. A combination of parabolic and grid slope interpolation for 2D tissue displacement estimations.

    PubMed

    Albinsson, John; Ahlgren, Åsa Rydén; Jansson, Tomas; Cinthio, Magnus

    2017-08-01

    Parabolic sub-sample interpolation for 2D block-matching motion estimation is computationally efficient. However, it is well known that the parabolic interpolation gives a biased motion estimate for displacements greater than |y.2| samples (y = 0, 1, …). Grid slope sub-sample interpolation is less biased, but it shows large variability for displacements close to y.0. We therefore propose to combine these sub-sample methods into one method (GS15PI) using a threshold to determine when to use which method. The proposed method was evaluated on simulated, phantom, and in vivo ultrasound cine loops and was compared to three sub-sample interpolation methods. On average, GS15PI reduced the absolute sub-sample estimation errors in the simulated and phantom cine loops by 14, 8, and 24% compared to sub-sample interpolation of the image, parabolic sub-sample interpolation, and grid slope sub-sample interpolation, respectively. The limited in vivo evaluation of estimations of the longitudinal movement of the common carotid artery using parabolic and grid slope sub-sample interpolation and GS15PI resulted in coefficient of variation (CV) values of 6.9, 7.5, and 6.8%, respectively. The proposed method is computationally efficient and has low bias and variance. The method is another step toward a fast and reliable method for clinical investigations of longitudinal movement of the arterial wall.

  12. Effects of cryotherapy combined with therapeutic ultrasound on oxidative stress and tissue damage after musculoskeletal contusion in rats.

    PubMed

    Martins, C N; Moraes, M B; Hauck, M; Guerreiro, L F; Rossato, D D; Varela, A S; da Rosa, C E; Signori, L U

    2016-12-01

    To investigate the combined effects of cryotherapy and pulsed ultrasound therapy (PUT) on oxidative stress parameters, tissue damage markers and systemic inflammation after musculoskeletal injury. Experimental animal study. Research laboratory. Seventy male Wistar rats were divided into five groups: control, lesion, cryotherapy, PUT, and cryotherapy+PUT. The gastrocnemius muscle was injured by mechanical crushing. Cryotherapy was applied immediately after injury (immersion in water at 10°C for 20minutes). PUT was commenced 24hours after injury (1MHz, 0.4W/cm(2SPTA), 20% duty cycle, 5minutes). All animals were treated every 8hours for 3 days. Oxidative stress in muscle was evaluated by concentration of reactive oxygen species (ROS), lipid peroxidation (LPO), anti-oxidant capacity against peroxyl radicals (ACAP) and catalase. Plasma levels of creatine kinase (CK), lactate dehydrogenase (LDH) and C-reactive protein (CRP) were assessed. When applied individually, cryotherapy and PUT reduced CK, LDH, CRP and LPO caused by muscle damage. Cryotherapy+PUT in combination maintained the previous results, caused a reduction in ROS [P=0.005, mean difference -0.9×10(-8) relative area, 95% confidence interval (CI) -0.2 to -1.9], and increased ACAP {P=0.007, mean difference 0.34 1/[relative area with/without 2,2-azobis(2-methylpropionamidine)dihydrochloride], 95% CI 0.07 to 0.61} and catalase (P=0.002, mean difference 0.41units/mg protein, 95% CI 0.09 to 0.73) compared with the lesion group. Cryotherapy+PUT in combination reduced oxidative stress in muscle, contributing to a reduction in adjacent damage and tissue repair. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  13. DNA adduct kinetics in reproductive tissues of DNA repair proficient and deficient male mice after oral exposure to benzo(a)pyrene.

    PubMed

    Verhofstad, Nicole; van Oostrom, Conny Th M; van Benthem, Jan; van Schooten, Frederik J; van Steeg, Harry; Godschalk, Roger W L

    2010-03-01

    Benzo(a)pyrene (B[a]P) can induce somatic mutations, whereas its potential to induce germ cell mutations is unclear. There is circumstantial evidence that paternal exposure to B[a]P can result in germ cell mutations. Since DNA adducts are thought to be a prerequisite for B[a]P induced mutations, we studied DNA adduct kinetics by (32)P-postlabeling in sperm, testes and lung tissues of male mice after a single exposure to B[a]P (13 mg/kg bw, by gavage). To investigate DNA adduct formation at different stages of spermatogenesis, mice were sacrificed at Day 1, 4, 7, 10, 14, 21, 32, and 42 after exposure. In addition, DNA repair deficient (Xpc(-/-)) mice were used to study the contribution of nucleotide excision repair in DNA damage removal. DNA adducts were detectable with highest levels in lung followed by sperm and testis. Maximum adduct levels in the lung and testis were observed at Day 1 after exposure, while adduct levels in sperm reached maximum levels at approximately 1 week after exposure. Lung tissue and testis of Xpc(-/-) mice contained significantly higher DNA adduct levels compared to wild type (Wt) mice over the entire 42 day observation period (P < 0.05). Differences in adduct half-life between Xpc(-/-) and Wt mice were only observed in testis. In sperm, DNA adduct levels were significantly higher in Xpc(-/-) mice than in Wt mice only at Day 42 after exposure (P = 0.01). These results indicate that spermatogonia and testes are susceptible for the induction of DNA damage and rely on nucleotide excision repair for maintaining their genetic integrity. (c) 2009 Wiley-Liss, Inc.

  14. [Predictive value of combination detection of tissue Pgp1 expression and preoperative serum CEA level for colorectal cancer].

    PubMed

    Wu, Fan; Chen, Lei; Wu, Wei; Jiang, Beihai; Su, Xiangqian

    2017-04-25

    To explore the predictive value of combination detection of Pgp1 expression in cancer tissue and serum CEA level for the prognosis of colorectal cancer (CRC) patients. Clinicopathological data, complete 5-year follow-up data and CRC tissue samples of 153 CRC patients with stage I( to II( tumor undergoing radical operation in our department from January 2004 to August 2006 were retrospectively collected. Immunohistochemical staining was used to detect the expression level of Pgp1. The combined evaluation of staining intensity and positive cell percentage was performed to determine the expression level of Pgp1. Pgp1 staining (-) and (+) was defined as low expression; and staining (++) and (+++) as high expression. Electrochemiluminescence immunoassay was used to detect the level of serum CEA. CEA > 5 μg/L was defined as positive. χ(2) and Fisher's exact test were performed to analyze the association of Pgp1 expression with CEA level and clinicopathological variables. Moreover, Kaplan-Meier method was used to analyze the survival. Univariate and multivariate Cox proportional hazard regression models were used to evaluate the roles of Pgp1 expression combined with serum CEA level in prognosis prediction. Of 153 patients, 105 were males and 48 females with mean age of 59 (27 to 90) years; 41 cases were rectal cancer, and 112 cases colon cancer; 23 patients were TNM stage I( tumor, and 130 patients stage II( tumor; median follow-up time was 64 months; 30 cases were dead. Positive rate of Pgp1 expression in colorectal cancer tissues was 66.0%(101/153). The expression of Pgp1 was associated with gender, tumor location, and survival during the follow-up (all P<0.05). The preoperative positive rate of serum CEA was 28.1% (43/153). The preoperative serum CEA level was associated with tumor recurrence and survival (all P<0.05). Kaplan-Meier analysis showed the overall 5-year survival rate was 81.7%. The 5-year survival rate of patients with high expression of Pgp1 was 88

  15. Bone tissue engineering by using a combination of polymer/Bioglass composites with human adipose-derived stem cells.

    PubMed

    Lu, Wei; Ji, Kun; Kirkham, Jennifer; Yan, Yu; Boccaccini, Aldo R; Kellett, Margaret; Jin, Yan; Yang, Xuebin B

    2014-04-01

    Translational research in bone tissue engineering is essential for "bench to bedside" patient benefit. However, the ideal combination of stem cells and biomaterial scaffolds for bone repair/regeneration is still unclear. The aim of this study is to investigate the osteogenic capacity of a combination of poly(DL-lactic acid) (PDLLA) porous foams containing 5 wt% and 40 wt% of Bioglass particles with human adipose-derived stem cells (ADSCs) in vitro and in vivo. Live/dead fluorescent markers, confocal microscopy and scanning electron microscopy showed that PDLLA/Bioglass porous scaffolds supported ADSC attachment, growth and osteogenic differentiation, as confirmed by enhanced alkaline phosphatase (ALP) activity. Higher Bioglass content of the PDLLA foams increased ALP activity compared with the PDLLA only group. Extracellular matrix deposition after 8 weeks in the in vitro cultures was evident by Alcian blue/Sirius red staining. In vivo bone formation was assessed by using scaffold/ADSC constructs in diffusion chambers transplanted intraperitoneally into nude mice and recovered after 8 weeks. Histological and immunohistochemical assays indicated significant new bone formation in the 40 wt% and 5 wt% Bioglass constructs compared with the PDLLA only group. Thus, the combination of a well-developed biodegradable bioactive porous PDLLA/Bioglass composite scaffold with a high-potential stem cell source (human ADSCs) could be a promising approach for bone regeneration in a clinical setting.

  16. [Mechanisms of nitroxide-ergic dysregulation in tissues of parodontium in rats under combined excessive sodium nitrate and fluoride intake].

    PubMed

    Богданов, Алексей В; Гришко, Юлия М; Костенко, Виталий А

    intake of inorganic nitrates is typically accompanied by production of excessive amount of nitric oxide (NO), which level is maintained by the mechanism of autoregulation known as the NO cycle. Hypothetically, this process may be disrupted with fluorides that are able to suppress arginase pathway of L-arginine metabolism, which competes with NO-synthase pathway. to study mechanisms of disregulation of oxidative (NO-synthase) and non-oxidative (arginase) metabolic pathways of L-arginine in the tissues of periodontium under combined excessive sodium nitrate and fluoride intake. these investigations were carried out on 90 white Wistar rats. Homogenates of parodontium soft tissues were used to assess spectrophotometrically the total activities of NO-synthase (NOS), arginase, ornithine decarboxylase as well as the peroxynitrite concentration. typical for the isolated sodium nitrate administration inhibition of total NOS activity varies under combined administration of nitrate and sodium fluoride and is usually manifested by its hyperactivation that is accompanied by an increase in peroxynitrite concentration. At this time arginase and ornithine decarboxylase activity is observed to be substantially reduced. The administration of aminoguanidine, an iNOS inhibitor, (20 mg/kg, twice a week during the experiment) increases arginase and ornithine decarboxylase activities, and the administration of L-arginine (500 mg/kg, twice a week) results in the increase of arginase activity. The administration of L-selenomethionine, a peroxynitrite scavenger (3 mg/kg, twice a week), and JSH-23 (4-methyl-N-(3-phenylpropyl) benzene-1,2-diamine, an inhibitor of NF-κB activation (1 mg/kg, twice a week) for modeling binary nitrate and fluoride intoxication reduces the total concentration of NOS activity and peroxynitrite concentration, and increases ornithine decarboxylase activity. the combined effect of nitrate and sodium fluoride for 30 days leads to disregulatory increased activity of NO

  17. [Mechanisms of nitroxide-ergic dysregulation in tissues of parodontium in rats under combined excessive sodium nitrate and fluoride intake].

    PubMed

    Богданов, Алексей В; Гришко, Юлия М; Костенко, Виталий А

    2016-01-01

    intake of inorganic nitrates is typically accompanied by production of excessive amount of nitric oxide (NO), which level is maintained by the mechanism of autoregulation known as the NO cycle. Hypothetically, this process may be disrupted with fluorides that are able to suppress arginase pathway of L-arginine metabolism, which competes with NO-synthase pathway. to study mechanisms of disregulation of oxidative (NO-synthase) and non-oxidative (arginase) metabolic pathways of L-arginine in the tissues of periodontium under combined excessive sodium nitrate and fluoride intake. these investigations were carried out on 90 white Wistar rats. Homogenates of parodontium soft tissues were used to assess spectrophotometrically the total activities of NO-synthase (NOS), arginase, ornithine decarboxylase as well as the peroxynitrite concentration. typical for the isolated sodium nitrate administration inhibition of total NOS activity varies under combined administration of nitrate and sodium fluoride and is usually manifested by its hyperactivation that is accompanied by an increase in peroxynitrite concentration. At this time arginase and ornithine decarboxylase activity is observed to be substantially reduced. The administration of aminoguanidine, an iNOS inhibitor, (20 mg/kg, twice a week during the experiment) increases arginase and ornithine decarboxylase activities, and the administration of L-arginine (500 mg/kg, twice a week) results in the increase of arginase activity. The administration of L-selenomethionine, a peroxynitrite scavenger (3 mg/kg, twice a week), and JSH-23 (4-methyl-N-(3-phenylpropyl) benzene-1,2-diamine, an inhibitor of NF-κB activation (1 mg/kg, twice a week) for modeling binary nitrate and fluoride intoxication reduces the total concentration of NOS activity and peroxynitrite concentration, and increases ornithine decarboxylase activity. the combined effect of nitrate and sodium fluoride for 30 days leads to disregulatory increased activity of NO

  18. Effect of combining in vitro estrogenicity data with kinetic characteristics of estrogenic compounds on the in vivo predictive value.

    PubMed

    Punt, Ans; Brand, Walter; Murk, Albertinka J; van Wezel, Annemarie P; Schriks, Merijn; Heringa, Minne B

    2013-02-01

    With the ultimate aim of increasing the utility of in vitro assays for toxicological risk assessment, a method was developed to calculate in vivo estrogenic potencies from in vitro estrogenic potencies of compounds by taking into account systemic availability. In vitro estrogenic potencies of three model compounds (bisphenol A, genistein, and 4-nonylphenol) relative to ethinylestradiol (EE2), determined with the estrogen receptor alpha (ERα) transcriptional activation assay using hER-HeLa-9903 cells, were taken from literature and used to calculate the EE2 equivalent (EE2EQ) effect doses in the predominantly ERα-dependent rat uterotrophic assay. Compound-specific differences in hepatic clearance relative to the reference compound EE2 were determined in vitro to examine whether in vivo estrogenic potencies reported in literature could be more accurately estimated. The EE2EQ doses allowed to predict in vivo uterotrophic responses within a factor of 6-25 and the inclusion of the hepatic clearance further improved the prediction with a factor 1.6-2.1 for especially genistein and bisphenol A. Yet, the model compounds still were less potent in vivo than predicted based on their EE2 equivalent estrogenic potency and hepatic clearance. For further improvement of the in vitro to in vivo predictive value of in vitro assays, the relevance of other kinetic characteristics should be studied, including binding to carrier proteins, oral bioavailability and the formation of estrogenic metabolites. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Combined Thermodynamic-Kinetic Analysis of the Interfacial Reactions between Ni Metallization and Various Lead-Free Solders

    PubMed Central

    Laurila, Tomi; Vuorinen, Vesa

    2009-01-01

    In this paper we will demonstrate how a thermodynamic-kinetic method can be utilized to rationalize a wide range of interfacial phenomena between Sn-based lead-free solders and Ni metallizations. First, the effect of P on the interfacial reactions, and thus on the reliability, between Sn-based solders and electroless Ni/immersion Au (ENIG) metallizations, will be discussed. Next, the effect of small amounts of Cu in Sn-based solders on the intermetallic compound (IMC), which forms first on top of Ni metallization, will be covered. With the help of thermodynamic arguments a so called critical Cu concentration for the formation of (Cu,Ni)6Sn5 can be determined as a function of temperature. Then the important phenomenon of redeposition of (Au,Ni)Sn4 layer on top of Ni3Sn4 IMC will be discussed in detail. The reasons leading to this behaviour will be rationalized with the help of thermodynamic information and an explanation of why this phenomenon does not occur when an appropriate amount of Cu is present in the soldering system will be given. Finally, interfacial reaction issues related to low temperature Sn-Zn and Sn-Bi based solders and Ni metallization will be discussed.

  20. Species-Specific Metastasis of Human Tumor Cells in the Severe Combined Immunodeficiency Mouse Engrafted with Human Tissue

    NASA Astrophysics Data System (ADS)

    Shtivelman, Emma; Namikawa, Reiko

    1995-05-01

    We have attempted to model human metastatic disease by implanting human target organs into the immunodeficient C.B-17 scid/scid (severe combined immunodeficiency; SCID) mouse, creating SCID-hu mice. Preferential metastasis to implants of human fetal lung and human fetal bone marrow occurred after i.v. injection of human small cell lung cancer (SCLC) cells into SCID-hu mice; the homologous mouse organs were spared. Clinically more aggressive variant SCLC cells metastasized more efficiently to human fetal lung implants than did cells from classic SCLC. Metastasis of variant SCLC to human fetal bone marrow was enhanced in SCID-hu mice exposed to γ-irradiation or to interleukin 1α. These data indicate that the SCID-hu mice may provide a model in which to study species- and tissue-specific steps of the human metastatic process.

  1. Combined fiber optical thermal sensor for noninvasive monitoring of blood and human tissue through diffuse scattering and metabolic parameters

    NASA Astrophysics Data System (ADS)

    Saetchnikov, Vladimir A.; Tcherniavskaia, Elina A.; Schweiger, Gustav

    2007-07-01

    A method of noninvasive monitoring of human tissue and blood components based on optical diffuse scattering spectroscopy combined with metabolic heat measurements has been developed. Developed compact fiber optical and thermal sensor measures thermal generation, heat balance, blood flow rate, hemoglobin and it's derivative concentrations and environment conditions. It contains thermal and optical detectors, halogen lamp and LEDs, multi-leg fiber optical bundle to measure diffuse light scattering inside and through the patient body including vascular system, which contributes to the control of the body temperature. Measurements of surface cutaneous tissue thermal radiation, ambient room temperature and background radiation temperature are used to measure conduction, convection, and radiation of heat from the human body. Blood flow rate in the body is estimated from the change in temperature for the contact and adjacent thermal detectors. Multi wavelength spectroscopy provides a reflectance spectra which are converted to absorbance values. The calibration and measurement processes are performed independently. Methods of multivariate statistical analysis involving the variables from sensor signals, polynomials from various variables, regression analysis of individual patients, and cluster analysis of patients group were applied to convert various signals from the sensor pickup into physicochemical variables. Obtained data show that the method provides a foundation for noninvasive measuring several biochemical parameters of blood. Further developments of the technology which is under progress now are the following: clinical studies to further characterize the performance of this technology and development of compact and low cost sensor device for home diagnostics.

  2. Normothermic cardiopulmonary bypass increases cerebral tissue oxygenation during combined valve surgery: a single-centre, randomized trial

    PubMed Central

    Lenkin, Andrey I.; Zaharov, Viktor I.; Lenkin, Pavel I.; Smetkin, Alexey A.; Bjertnaes, Lars J.; Kirov, Mikhail Y.

    2013-01-01

    OBJECTIVES In cardiac surgery, the choice of temperature regimen during cardiopulmonary bypass (CPB) remains a subject of debate. Hypothermia reduces tissue metabolic demands, but may impair the autoregulation of cerebral blood flow and contribute to neurological morbidity. The aim of this study was to evaluate the effect of two different temperature regimens during CPB on the systemic oxygen transport and the cerebral oxygenation during surgical correction of acquired heart diseases. METHODS In a prospective study, we randomized 40 adult patients with combined valvular disorders requiring surgical correction of two or more valves into two groups: (i) a normothermic (NMTH) group (n = 20), in which the body core temperature was maintained at 36.6°C during CPB and (ii) a hypothermic (HPTH) group (n = 20), in which the body was cooled to a core temperature of 32°C maintained throughout the period of CPB. The systemic oxygen transport and the cerebral oxygen saturation (SctO2) were assessed by means of a PiCCO2 haemodynamic monitor and a cerebral oximeter, respectively. All the patients received standard perioperative monitoring. We assessed haemodynamic and oxygen transport parameters, the duration of mechanical ventilation and the length of the ICU and the hospital stays. RESULTS During CPB, central venous oxygen saturation was significantly higher in the HPTH group but SctO2 was increased in the NMTH group (P < 0.05). Cardiac index, systemic oxygen delivery and consumption increased postoperatively in both groups. However, oxygen delivery and consumption were significantly higher in the NMTH group (P < 0.05). The duration of respiratory support and the length of ICU and hospital stays did not differ between the groups. CONCLUSIONS During combined valve surgery, normothermic CPB provides lower central venous oxygen saturation, but increases cerebral tissue oxygenation when compared with the hypothermic regimen. TRIAL REGISTRATION NUMBER NCT01685554. PMID:23407696

  3. Inhibition of NF-kappaB by combination therapy with parthenolide and hyperthermia and kinetics of apoptosis induction and cell cycle arrest in human lung adenocarcinoma cells.

    PubMed

    Hayashi, Sachiko; Sakurai, Hiroaki; Hayashi, Akio; Tanaka, Yukie; Hatashita, Masanori; Shioura, Hiroki

    2010-01-01

    We investigated the mechanisms of thermosensitization related to combination therapy with sesquiterpene lactone parthenolide (PTL), a nuclear factor-kappaB (NF-kappaB) inhibitor, and hyperthermia using human lung adenocarcinoma cells A549. The kinetics of apoptosis induction and cell cycle of cells treated with PTL, heating, and combined treatment were examined by flow cytometric analysis. The flow cytometric distribution was calculated and expressed as a percentage. The ratios of the sub-G1 division, used to determine the induction of apoptosis, increased significantly with the combination therapy. Furthermore, the ratios of G2/M division increased and the ratios of G0/G1 division decreased, indicating cell cycle arrest in G2/M. The cell phase response to PTL by A549 cells synchronized in the G1/S border with hydroxyurea was also analyzed. PTL showed remarkable cytotoxicity at the S phase of the cell cycle in A549 cells at all concentrations as well as with hyperthermia, thus PTL reduced the number of cells in the proliferation phase. Inhibition of intracellular transcription factor NF-kappaB activation in A549 cells with various incubation periods after treatments with PTL, heating and combined treatment was examined by Western blot analysis. Unexpectedly, PTL alone did not inhibit NF-kappaB activation in cells stimulated with TNF-alpha, while heating alone inhibited NF-kappaB early after treatment and that effect faded over time. In contrast, PTL combined with heating completely inhibited NF-kappaB activation. Our results demonstrated that PTL and heating in combination cause significant thermosensitization of A549 cells via induction of apoptosis or cell cycle arrest in G2/M by inhibiting NF-kappaB activation in a synergistic manner.

  4. The effect of polymer matrices on the thermal hazard properties of RDX-based PBXs by using model-free and combined kinetic analysis.

    PubMed

    Yan, Qi-Long; Zeman, Svatopluk; Sánchez Jiménez, P E; Zhao, Feng-Qi; Pérez-Maqueda, L A; Málek, Jiří

    2014-04-30

    In this paper, the decomposition reaction models and thermal hazard properties of 1,3,5-trinitro-1,3,5-triazinane (RDX) and its PBXs bonded by Formex P1, Semtex 1A, C4, Viton A and Fluorel polymer matrices have been investigated based on isoconversional and combined kinetic analysis methods. The established kinetic triplets are used to predict the constant decomposition rate temperature profiles, the critical radius for thermal explosion and isothermal behavior at a temperature of 82°C. It has been found that the effect of the polymer matrices on the decomposition mechanism of RDX is significant resulting in very different reaction models. The Formex P1, Semtex and C4 could make decomposition process of RDX follow a phase boundary controlled reaction mechanism, whereas the Viton A and Fluorel make its reaction model shifts to a two dimensional Avrami-Erofeev nucleation and growth model. According to isothermal simulations, the threshold cook-off time until loss of functionality at 82°C for RDX-C4 and RDX-FM is less than 500 days, while it is more than 700 days for the others. Unlike simulated isothermal curves, when considering the charge properties and heat of decomposition, RDX-FM and RDX-C4 are better than RDX-SE in storage safety at arbitrary surrounding temperature. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Analysis of dehydration kinetics, status of water and oil distribution of microwave-assisted vacuum frying potato chips combined with NMR and confocal laser scanning microscopy.

    PubMed

    Su, Ya; Zhang, Min; Fang, Zhongxiang; Zhang, Weiming

    2017-11-01

    In this study, the dehydration kinetics, status of water and oil distribution of microwave-assisted vacuum frying (MVF) potato chips were analyzed combining with NMR and confocal laser scanning microscopy (CLSM). Results showed that the MVF markedly increased the moisture evaporation kinetics and effective moisture diffusivity compared to vacuum frying (VF). The higher microwave power level (1000W) used achieved higher moisture evaporation rate and higher effective moisture diffusivity, The Logarithmic model exhibited the best fit for the obtained data of MR versus frying time in the MVF. The NMR analysis showed the free water in the samples firstly evaporate and the linkage between water and structure of materials becomes tighter with the frying time. The total oil content, surface and structural oil content were all significantly lower in MVF samples than that in VF samples. The CLSM analysis confirmed that less oil adhere to the surface and less oil trapped in the structure in MVF slices. The surface morphology showed that there were less ruptured and damaged cells in MVF samples and helped to explain the reduction of oil content. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Dual-modality probe intended for prostate cancer detection combining Raman spectroscopy and tactile resonance technology--discrimination of normal human prostate tissues ex vivo.

    PubMed

    Nyberg, M; Jalkanen, V; Ramser, K; Ljungberg, B; Bergh, A; Lindahl, O A

    2015-04-01

    Prostate cancer is the most common cancer for men in the western world. For the first time, a dual-modality probe, combining Raman spectroscopy and tactile resonance technology, has been used for assessment of fresh human prostate tissue. The study investigates the potential of the dual-modality probe by testing its ability to differentiate prostate tissue types ex vivo. Measurements on four prostates show that the tactile resonance modality was able to discriminate soft epithelial tissue and stiff stroma (p < 0.05). The Raman spectra exhibited a strong fluorescent background at the current experimental settings. However, stroma could be discerned from epithelia by integrating the value of the spectral background. Combining both parameters by a stepwise analysis resulted in 100% sensitivity and 91% specificity. Although no cancer tissue was analysed, the results are promising for further development of the instrument and method for discriminating prostate tissues and cancer.

  7. Use of Decellularized Scaffolds Combined with Hyaluronic Acid and Basic Fibroblast Growth Factor for Skin Tissue Engineering

    PubMed Central

    Wu, Zhengzheng; Fan, Lina; Xu, Bin; Lin, Yongliang; Zhang, Peng

    2015-01-01

    Skin damage is one of the common clinical skin diseases, and the main cure is the use of skin graft, especially for large area of skin injury or deep-skin damage. However, skin graft demand is far greater than that currently available. In this study, xenogeneic decellularized scaffold was prepared with pig peritoneum by a series of biochemical treatments to retain normal three-dimensional tissue scaffold and remove cells and antigenic components from the tissue. Scaffold was combined with hyaluronic acid (HA) plus two different concentrations of basic fibroblast growth factor (bFGF) and tested for its use for the repair of skin wounds. HA enhanced bFGF to adsorb to the decellularized scaffolds and slowed the release of bFGF from the scaffolds in vitro. A total of 20 rabbits were sacrificed on day 3, 6, 11, or 14 postsurgery. The wound healing rate and the thickness of dermis layer of each wound were determined for analyzing the wound repair. Statistical analysis was performed by the two-tailed Student's t-test. Wounds covered with scaffolds containing 1 μg/mL bFGF had higher wound healing rates of 47.24%, 74.69%, and 87.54%, respectively, for days 6, 11, and 14 postsurgery than scaffolds alone with wound healing rates of 28.17%, 50.31%, and 61.36% and vaseline oil gauze with wound healing rates of 24.84%, 42.75%, and 57.62%. Wounds covered with scaffolds containing 1 μg/mL bFGF showed more dermis regeneration than the other wounds and had dermis layer of 210.60, 374.40, and 774.20 μm, respectively, for days 6, 11, and 14 postsurgery compared with scaffolds alone with dermis layer of 116.60, 200.00, and 455.40 μm and vaseline oil gauze with dermis layer of 82.60, 186.20, and 384.40 μm. There was no significant difference in wound healing rates and thickness of dermis layer between wounds covered with scaffolds containing 1 and 3 μg/mL bFGF on days 3, 6, 11, and 14 postsurgery. The decellularized scaffolds combined with HA and bFGF can be further

  8. Platelet-rich plasma and autogenous bone graft combined with guided tissue regeneration in periodontal fenestration defects in dogs.

    PubMed

    Keskiner, Ilker; Alkan, Arzu; Acikgoz, Gokhan; Arpak, Nejat; Kaplan, Suleyman; Arslan, Huseyin

    2014-01-01

    The aim of this study was to evaluate the effects of platelet-rich plasma (PRP), autogenous bone (AB), and guided tissue regeneration (GTR) combination therapy compared to GTR therapy alone on healing of bone and cementum in fenestration-type periodontal defects in dogs. Six dogs were included in this study. Fenestration-type defects were created, and the following treatment groups were established: a control group treated with GTR alone and experimental groups treated with a combination of GTR + PRP, GTR + AB, and GTR + AB + PRP. The defects were evaluated by stereologic method and histomorphometric analysis, which were performed 4, 8, and 12 weeks postoperatively. The results showed a significant increase in trabecular bone area in the GTR + PRP group as compared with the control at 4 and 8 weeks (P < .05). The GTR + AB + PRP group showed significantly more trabecular bone area than both GTR and GTR + PRP groups at all time intervals (P < .05). The 8- and 12-week results in terms of cementum area revealed a significant difference between the GTR + AB + PRP group and the control in favor of the former (P < .05). Cementum area in the GTR + AB group was significantly greater than that in the GTR group at all time intervals (P < .05). Within the limitations of this study, PRP and AB, when used under barrier membrane, resulted in significant improvement in bone and cementum formation compared to GTR alone in periodontal fenestration defects; AB, rather than PRP, was responsible for this outcome.

  9. The combined effect of nonlinear filtration and window size on the accuracy of tissue displacement estimation using detected echo signals.

    PubMed

    Behar, Vera; Adam, Dan; Lysyansky, Peter; Friedman, Zvi

    2004-03-01

    In cardiac elastography, the regional strain and strain rate imaging is based on displacement estimation of tissue sections within the heart muscle carried out with various block-matching techniques (cross-correlation, sum of absolute differences, sum of squared differences, etc.). The accuracy of these techniques depends on a combination of ultrasonic imaging parameters such as ultrasonic frequency of interrogation, signal-to-noise ratio, size of a kernel used in a block-matching algorithm, type of data and speckle decorrelation. In this paper, we discuss the possibility to enhance the accuracy of the displacement estimation via nonlinear filtering of B-mode images before block-matching operation. The combined effect of a filter algorithm and a kernel size on the accuracy of the displacement estimation is analyzed using a 36-frame sequence of grayscale B-mode images of a human heart acquired by an ultrasound system operating at 1.77 MHz. It is shown that the nonlinear filtering of images enables to obtain the desired accuracy (less than one pixel) of the displacement estimation with smaller kernels than without filtering. These results are obtained for two filters--an adaptive anisotropic diffusion filter and a nonlinear Gaussian filter chain.

  10. Extensive traumatic anterior skull base fractures with cerebrospinal fluid leak: classification and repair techniques using combined vascularized tissue flaps.

    PubMed

    Archer, Jacob B; Sun, Hai; Bonney, Phillip A; Zhao, Yan Daniel; Hiebert, Jared C; Sanclement, Jose A; Little, Andrew S; Sughrue, Michael E; Theodore, Nicholas; James, Jeffrey; Safavi-Abbasi, Sam

    2016-03-01

    This article introduces a classification scheme for extensive traumatic anterior skull base fracture to help stratify surgical treatment options. The authors describe their multilayer repair technique for cerebrospinal fluid (CSF) leak resulting from extensive anterior skull base fracture using a combination of laterally pediculated temporalis fascial-pericranial, nasoseptal-pericranial, and anterior pericranial flaps. Retrospective chart review identified patients treated surgically between January 2004 and May 2014 for anterior skull base fractures with CSF fistulas. All patients were treated with bifrontal craniotomy and received pedicled tissue flaps. Cases were classified according to the extent of fracture: Class I (frontal bone/sinus involvement only); Class II (extent of involvement to ethmoid cribriform plate); and Class III (extent of involvement to sphenoid bone/sinus). Surgical repair techniques were tailored to the types of fractures. Patients were assessed for CSF leak at follow-up. The Fisher exact test was applied to investigate whether the repair techniques were associated with persistent postoperative CSF leak. Forty-three patients were identified in this series. Thirty-seven (86%) were male. The patients' mean age was 33 years (range 11-79 years). The mean overall length of follow-up was 14 months (range 5-45 months). Six fractures were classified as Class I, 8 as Class II, and 29 as Class III. The anterior pericranial flap alone was used in 33 patients (77%). Multiple flaps were used in 10 patients (3 salvage) (28%)--1 with Class II and 9 with Class III fractures. Five (17%) of the 30 patients with Class II or III fractures who received only a single anterior pericranial flap had persistent CSF leak (p < 0.31). No CSF leak was found in patients who received multiple flaps. Although postoperative CSF leak occurred only in high-grade fractures with single anterior flap repair, this finding was not significant. Extensive anterior skull base

  11. Combined coagulation-flocculation and sequencing batch reactor with phosphorus adjustment for the treatment of high-strength landfill leachate: experimental kinetics and chemical oxygen demand fractionation.

    PubMed

    El-Fadel, M; Matar, F; Hashisho, J

    2013-05-01

    The treatability of high-strength landfill leachate is challenging and relatively limited. This study examines the feasibility of treating high-strength landfill leachate (chemical oxygen demand [COD]: 7,760-11,770 mg/L, biochemical oxygen demand [BOD5]: 2,760-3,569 mg/L, total nitrogen [TN] = 980-1,160 mg/L) using a sequencing batch reactor (SBR) preceded by a coagulation-flocculation process with phosphorus nutritional balance under various mixing and aeration patterns. Simulations were also conducted to define kinetic parameters and COD fractionation. Removal efficiencies reached 89% for BOD5, 60% for COD, and 72% for TN, similar to and better than reported studies, albeit with a relatively lower hydraulic retention time (HRT) and solid retention time (SRT). The coupled experimental and simulation results contribute in filling a gap toward managing high-strength landfill leachate and providing guidelines for corresponding SBR applications. The treatability of high-strength landfill leachate, which is challenging and relatively limited, was demonstrated using a combined coagulation-flocculation with SBR technology and nutrient balance adjustment. The most suitable coagulant, kinetic design parameters, and COD fractionation were defined using coupled experimental and simulation results contributing in filling a gap toward managing high-strength leachate by providing guidelines for corresponding SBR applications and anticipating potential constraints related to the non-biodegradable COD fraction. In this context, while the combined coagulation-flocculation and SBR process improved removal efficiencies, posttreatment may be required for high-strength leachate, depending on discharge standards and ultimate usage of the treated leachate.

  12. Mineralization and kinetics of Reactive Brilliant Red X-3B by a combined anaerobic-aerobic bioprocess inoculated with the coculture of fungus and bacterium.

    PubMed

    Shi, Shengnan; Ma, Fang; Sun, Tieheng; Li, Ang; Zhou, Jiti; Qu, Yuanyuan

    2014-01-01

    Mineralization of Reactive Brilliant Red X-3B by a combined anaerobic-aerobic process which was inoculated with the co-culture of Penicillium sp. QQ and Exiguobacterium sp. TL was studied. The optimal conditions of decolorization were investigated by response surface methodology as follows: 132.67 g/L of strain QQ wet spores, 1.09 g/L of strain TL wet cells, 2.25 g/L of glucose, 2.10 g/L of yeast extract, the initial dye concentration of 235.14 mg/L, pH 6.5, and 33 °C. The maximal decolorization rate was about 96 % within 12 h under the above conditions. According to the Haldane kinetic equation, the maximal specific decolorization rate was 89.629 mg/g˙h. It was suggested that in the anaerobic-aerobic combined process, decolorization occurred in the anaerobic unit and chemical oxygen demand (COD) was mainly removed in the aerobic one. Inoculation of fungus QQ in the anaerobic unit was important for mineralization of X-3B. Besides, the divided anaerobic-aerobic process showed better performance of COD removal than the integrated one. It was suggested that the combined anaerobic-aerobic process which was inoculated with co-culture was potentially useful for the field application.

  13. Combining a focused air-puff system with phase-sensitive optical coherence tomography for the detection of soft-tissue tumors based on elasticity measurement

    NASA Astrophysics Data System (ADS)

    Wang, Shang; Li, Jiasong; Vantipalli, Srilatha; Manapuram, Ravi Kiran; Ingram, Davis R.; Twa, Michael D.; Lazar, Alexander J.; Lev, Dina C.; Pollock, Raphael E.; Larin, Kirill V.

    2013-03-01

    We combine a focused air-puff system with phase-sensitive optical coherence tomography (PhS-OCT) to measure the elasticity of soft tissues. Surface waves (SWs) on soft tissues are induced by a low-pressure, short-duration air stream from an air-puff system and measured using a high-sensitivity PhS-OCT imaging system. Young's modulus of soft tissues can be quantified based on the group velocity of SWs. To precisely control the excitation pressure, the air-puff system was characterized with a high-resolution analog pressure transducer. We studied the feasibility of this method for the non-contact detection of soft-tissue tumors. Ex vivo human fat and myxoma were used for these pilot experiments. Results demonstrate that this optical non-contact technique can be used to differentiate soft-tissue tumors from normal tissues based on measurements of their elasticity.

  14. Perfusion changes in the RIF-1 tumour and normal tissues after carbogen and nicotinamide, individually and combined.

    PubMed Central

    Honess, D. J.; Bleehen, N. M.

    1995-01-01

    The strategy of combining carbogen breathing and nicotinamide to overcome chronic and acute hypoxia respectively is being evaluated clinically. The effects of both agents individually and in combination on relative perfusion of 400-700 mm3 RIF-1 tumours and normal tissues were measured by 86Rb extraction. Carbogen breathing alone for 6 min increased relative tumour perfusion by 50-70% compared with control at flow rates of 50 to 200 ml min-1, but the effect was lost at 300 ml min-1. All flow rates also produced similar increases in relative perfusion of lung, of between 36% and 58%, and smaller increases in skin, of between 20% and 34%. The minimum breathing time at 150 ml min-1 to produce a significant increase in relative tumour perfusion was 4.5 min, and the effect was maintained up to 9 min. Nicotinamide alone at 1000 mg kg-1 60 min before assay did not alter relative tumour perfusion. Comparing the combination of nicotinamide with 6 min carbogen breathing at 150 ml min-1 with carbogen breathing alone showed no difference in relative tumour perfusion; increases were of 36% and 42% respectively. Nicotinamide-induced alterations in microcirculation associated with reduction of acute hypoxia have therefore not been detected by 86Rb extraction. The perfusion-enhancing effect of carbogen in this tumour is probably an important component of its radiosensitising ability, in addition to its known ability to increase the oxygen-carrying capacity of the blood, and should be taken into consideration in clinical studies. PMID:7779707

  15. [Early effectiveness of combining radial forearm free flap and adjacent tissue flap in reconstruction of palatomaxillary defects].

    PubMed

    Chen, Yongfeng; Zhang, Kai; Li, Jiancheng; Xu, Jingcheng; Liao, Shengkai; Xu, Tao

    2011-09-01

    To investigate the method of combining radial forearm free flap and adjacent tissue flap in reconstruction of palatomaxillary defects and its effectiveness. Between March 2005 and May 2010, 17 patients with palatomaxillary defects were treated. There were 11 males and 6 females with an age range of 45-74 years (mean, 62.5 years), including 1 case of benign tumor and 16 cases of malignant tumors (7 cases of squamous cell carcinoma of palate, 1 case of recurring squamous cell carcinoma of palate, 1 case of malignant melanoma of palate, 1 case of adenoid cystic carcinoma of palate, 1 case of malignant melanoma of maxilla, 1 case of ductal carcinoma of maxilla, and 4 cases of squamous cell carcinoma of maxilla). The maxillectomy defect ranged from 7.0 cm x 5.5 cm to 10.0 cm x 7.5 cm. According to Brown's classification for the maxillectomy defect, there were type II in 15 cases, type III in 2 cases. Palatomaxillary defects were repaired with radial forearm free flap and buccal fat pad in 11 cases, and with radial forearm free flap, buccal fat pad, and mandibular osteomuscular flap pedicled with temporal muscle in 6 cases. The effectiveness was evaluated after operation by observing the vitality of the flap, the functions of speech, swallowing, breath, and the facial appearance. All cases were followed up 6-12 months without tumor recurrence. All flaps and skin grafts at donor sites survived. The functions of speech, swallowing, and breath were normal without obvious opening limitation. The facial appearance was satisfactory without obvious maxillofacial deformity. No enophthalmos occurred in patients with orbital floor and infraorbital rim defects. The patients had no oronasal fistula with satisfactory oral and nasal functions. According to the type of palatomaxillary defects, it can have good early effectiveness to select combining radial forearm free flap and buccal fat pad or combining radial forearm free flap, buccal fat pad, and mandibular osteomuscular flap for

  16. Repair of Segmental Bone Defect Using Totally Vitalized Tissue Engineered Bone Graft by a Combined Perfusion Seeding and Culture System

    PubMed Central

    Feng, Ya-Fei; Li, Xiang; Hu, Yun-Yu; Wang, Zhen; Ma, Zhen-Sheng; Lei, Wei

    2014-01-01

    Background The basic strategy to construct tissue engineered bone graft (TEBG) is to combine osteoblastic cells with three dimensional (3D) scaffold. Based on this strategy, we proposed the “Totally Vitalized TEBG” (TV-TEBG) which was characterized by abundant and homogenously distributed cells with enhanced cell proliferation and differentiation and further investigated its biological performance in repairing segmental bone defect. Methods In this study, we constructed the TV-TEBG with the combination of customized flow perfusion seeding/culture system and β-tricalcium phosphate (β-TCP) scaffold fabricated by Rapid Prototyping (RP) technique. We systemically compared three kinds of TEBG constructed by perfusion seeding and perfusion culture (PSPC) method, static seeding and perfusion culture (SSPC) method, and static seeding and static culture (SSSC) method for their in vitro performance and bone defect healing efficacy with a rabbit model. Results Our study has demonstrated that TEBG constructed by PSPC method exhibited better biological properties with higher daily D-glucose consumption, increased cell proliferation and differentiation, and better cell distribution, indicating the successful construction of TV-TEBG. After implanted into rabbit radius defects for 12 weeks, PSPC group exerted higher X-ray score close to autograft, much greater mechanical property evidenced by the biomechanical testing and significantly higher new bone formation as shown by histological analysis compared with the other two groups, and eventually obtained favorable healing efficacy of the segmental bone defect that was the closest to autograft transplantation. Conclusion This study demonstrated the feasibility of TV-TEBG construction with combination of perfusion seeding, perfusion culture and RP technique which exerted excellent biological properties. The application of TV-TEBG may become a preferred candidate for segmental bone defect repair in orthopedic and maxillofacial

  17. Effects of Adenosine Monophosphate Used in Combination with L-Arginine on Female Rabbit Corpus Cavernosum Tissue

    PubMed Central

    Stücker, Olivier; Pons, Catherine; Neuzillet, Yann; Laemmel, Elisabeth; Lebret, Thierry

    2014-01-01

    , Laemmel E, and Lebret T. Original research-sexual medicine: Effects of adenosine monophosphate used in combination with L-Arginine on female rabbit corpus cavernosum tissue. Sex Med 2014;2:1–7. PMID:25356295

  18. Stress response of bovine artery and rat brain tissue due to combined translational shear and fixed unconfined compression

    NASA Astrophysics Data System (ADS)

    Leahy, Lauren

    During trauma resulting from impacts and blast waves, sinusoidal waves permeate the brain and cranial arterial tissue, both non-homogeneous biological tissues with high fluid contents. The experimental shear stress response to sinusoidal translational shear deformation at 1 Hz and 25% strain amplitude and either 0% or 33% compression is compared for rat brain tissue and bovine aortic tissue. Both tissues exhibit Mullins effect in shear. Harmonic wavelet decomposition, a novel application to the mechanical response of these tissues, shows significant 1 Hz and 3 Hz components. The 3 Hz component magnitude in brain tissue, which is much larger than in aortic tissue, may correlate to interstitial fluid induced drag forces that decrease on subsequent cycles perhaps because of damage resulting in easier fluid movement. The fluid may cause the quasiperiodic, viscoelastic behavior of brain tissue. The mechanical response differences under impact may cause shear damage between arterial and brain connections.

  19. Structural bone allograft combined with genetically engineered mesenchymal stem cells as a novel platform for bone tissue engineering.

    PubMed

    Xie, Chao; Reynolds, David; Awad, Hani; Rubery, Paul T; Pelled, Gadi; Gazit, Dan; Guldberg, Robert E; Schwarz, Edward M; O'Keefe, Regis J; Zhang, Xinping

    2007-03-01

    The presence of live periosteal progenitor cells on the surface of bone autografts confers better healing than devitalized allograft. We have previously demonstrated in a murine 4 mm segmental femoral bone-grafting model that live periosteum produces robust endochondral and intramembraneous bone formation that is essential for effective healing and neovascularization of structural bone grafts. To the end of engineering a live pseudo-periosteum that could induce a similar response onto devitalized bone allograft, we seeded a mesenchymal stem cell line stably transfected with human bone morphogenic protein-2/beta-galactosidase (C9) onto devitalized bone allografts or onto a membranous small intestinal submucosa scaffold that was wrapped around the allograft. Histology showed that C9-coated allografts displayed early cartilaginous tissue formation at day 7. By 6 and 9 weeks, a new cortical shell was found bridging the segmental defect that united the host bones. Biomechanical testing showed that C9-coated allografts displayed torsional strength and stiffness equivalent to intact femurs at 6 weeks and superior to live isografts at 9 weeks. Volumetric and histomorphometric micro-computed tomography analyses demonstrated a 2-fold increase in new bone formation around C9-coated allografts, which resulted in a substantial increase in polar moment of inertia (pMOI) due to the formation of new cortical shell around the allografts. Positive correlations between biomechanics and new bone volume and pMOI were found, suggesting that the biomechanical function of the grafted femur relates to both morphological parameters. C9-coated allograft also exhibited slower resorption of the graft cortex at 9 weeks than live isograft. Both new bone formation and the persistent allograft likely contributed to the improved biomechanics of C9-coated allograft. Taken together, we propose a novel strategy to combine structural bone allograft with genetically engineered mesenchymal stem cells as

  20. Injectable alginate/hydroxyapatite gel scaffold combined with gelatin microspheres for drug delivery and bone tissue engineering.

    PubMed

    Yan, Jingxuan; Miao, Yuting; Tan, Huaping; Zhou, Tianle; Ling, Zhonghua; Chen, Yong; Xing, Xiaodong; Hu, Xiaohong

    2016-06-01

    Injectable and biodegradable alginate-based composite gel scaffolds doubly integrated with hydroxyapatite (HAp) and gelatin microspheres (GMs) were cross-linked via in situ release of calcium cations. As triggers of calcium cations, CaCO3 and glucono-D-lactone (GDL) were fixed as a mass ratio of 1:1 to control pH value ranging from 6.8 to 7.2 during gelation. Synchronously, tetracycline hydrochloride (TH) was encapsulated into GMs to enhance bioactivity of composite gel scaffolds. The effects of HAp and GMs on characteristics of gel scaffolds, including pH value, gelation time, mechanical properties, swelling ratio, degradation behavior and drug release, were investigated. The results showed that HAp and GMs successfully improved mechanical properties of gel scaffolds at strain from 0.1 to 0.5, which stabilized the gel network and decreased weight loss, as well as swelling ratio and gelation time. TH could be released from this composite gel scaffold into the local microenvironment in a controlled fashion by the organic/inorganic hybrid of hydrogel network. Our results demonstrate that the HAp and GMs doubly integrated alginate-based gel scaffolds, especially the one with 6% (w/v) HAp and 5% (w/v) GMs, have suitable physical performance and bioactive properties, thus provide a potential opportunity to be used for bone tissue engineering. The potential application of this gel scaffold in bone tissue engineering was confirmed by encapsulation behavior of osteoblasts. In combination with TH, the gel scaffold exhibited beneficial effects on osteoblast activity, which suggested a promising future for local treatment of pathologies involving bone loss.

  1. The Role of Bacterial Biofilm in Adverse Soft-Tissue Filler Reactions: A Combined Laboratory and Clinical Study.

    PubMed

    Saththianathan, Mayuran; Johani, Khalid; Taylor, Alaina; Hu, Hongua; Vickery, Karen; Callan, Peter; Deva, Anand K

    2017-03-01

    The development of chronic nodules and granulomatous inflammation after filler injections has been attributed to bacterial biofilm infection. The authors aimed to investigate the relationship between filler and bacterial biofilm using a combined in vitro and in vivo study. In vitro assays to investigate the ability of filler materials to support the growth of Staphylococcus epidermidis biofilm and the effect of multiple needle passes through a biofilm-contaminated surface were designed. Analysis of clinical biopsy specimens from patients presenting with chronic granulomas following filler administration using a number of laboratory tests for biofilm was performed. All fillers (i.e., hyaluronic acid, polyacrylamide gel, and poly-L-lactic acid) supported the growth of S. epidermidis biofilm in vitro. Multiple needle passes through a biofilm-contaminated surface resulted in significantly increased contamination of filler material by a factor of 10,000 (p < 0.001). Six clinical samples from five patients all demonstrated bacterial biofilm. The mean number of bacteria was found to be 2.2 × 10 bacteria/mg tissue (range, 5.6 × 10 to 3.7 × 10 bacteria/mg tissue). Microbiome analysis detected a predominance of Pseudomonas, Staphylococcus, and Propionibacterium as present in these samples. Filler material can support the growth of bacterial biofilm in vitro. Multiple needle passes can significantly increase the risk of filler contamination. Biofilm appears to be associated with high numbers in clinical samples of patients presenting with chronic granulomatous inflammation. Strategies to reduce the risk of bacterial contamination need to be further studied and translated into clinical practice. Therapeutic, V.

  2. Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma

    ClinicalTrials.gov

    2014-09-08

    Adult Alveolar Soft-part Sarcoma; Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Extraskeletal Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Malignant Hemangiopericytoma; Adult Malignant Mesenchymoma; Adult Neurofibrosarcoma; Adult Synovial Sarcoma; Childhood Alveolar Soft-part Sarcoma; Childhood Angiosarcoma; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Neurofibrosarcoma; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Metastatic Childhood Soft Tissue Sarcoma; Nonmetastatic Childhood Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

  3. Tissue Doppler Imaging Combined with Advanced 12-Lead ECG Analysis Might Improve Early Diagnosis of Hypertrophic Cardiomyopathy in Childhood

    NASA Technical Reports Server (NTRS)

    Femlund, E.; Schlegel, T.; Liuba, P.

    2011-01-01

    Optimization of early diagnosis of childhood hypertrophic cardiomyopathy (HCM) is essential in lowering the risk of HCM complications. Standard echocardiography (ECHO) has shown to be less sensitive in this regard. In this study, we sought to assess whether spatial QRS-T angle deviation, which has shown to predict HCM in adults with high sensitivity, and myocardial Tissue Doppler Imaging (TDI) could be additional tools in early diagnosis of HCM in childhood. Methods: Children and adolescents with familial HCM (n=10, median age 16, range 5-27 years), and without obvious hypertrophy but with heredity for HCM (n=12, median age 16, range 4-25 years, HCM or sudden death with autopsy-verified HCM in greater than or equal to 1 first-degree relative, HCM-risk) were additionally investigated with TDI and advanced 12-lead ECG analysis using Cardiax(Registered trademark) (IMED Co Ltd, Budapest, Hungary and Houston). Spatial QRS-T angle (SA) was derived from Kors regression-related transformation. Healthy age-matched controls (n=21) were also studied. All participants underwent thorough clinical examination. Results: Spatial QRS-T angle (Figure/ Panel A) and septal E/Ea ratio (Figure/Panel B) were most increased in HCM group as compared to the HCM-risk and control groups (p less than 0.05). Of note, these 2 variables showed a trend toward higher levels in HCM-risk group than in control group (p=0.05 for E/Ea and 0.06 for QRS/T by ANOVA). In a logistic regression model, increased SA and septal E/Ea ratio appeared to significantly predict both the disease (Chi-square in HCM group: 9 and 5, respectively, p less than 0.05 for both) and the risk for HCM (Chi-square in HCM-risk group: 5 and 4 respectively, p less than 0.05 for both), with further increased predictability level when these 2 variables were combined (Chi-square 10 in HCM group, and 7 in HCM-risk group, p less than 0.01 for both). Conclusions: In this small material, Tissue Doppler Imaging and spatial mean QRS-T angle

  4. The growth kinetics and metabolic and antioxidant activities of the functional synbiotic combination of Lactobacillus gasseri 505 and Cudrania tricuspidata leaf extract.

    PubMed

    Oh, Nam Su; Lee, Ji Young; Kim, Younghoon

    2016-12-01

    In a previous study, the synbiotic combination of selected Lactobacillus gasseri strains and Cudrania tricuspidata leaf extract (CT) was shown to significantly improve the functionality of fermented milk, and the greatest synbiotic effect was exhibited with L. gasseri 505. The aim of the present study was to investigate the growth kinetics and fermentation metabolism of this specific synbiotic combination. Fermentation was carried out in synthetic media and milk with or without CT supplementation using L. gasseri 505. Whole genome sequencing and comparative genomics analyses were conducted to verify the novelty of strain. Titratable acidity, pH, microbial population, and organic acid production were measured during the fermentation period. The addition of CT accelerated the acidification rate, supporting the growth of L. gasseri 505, and the production of fermentation metabolites such as lactic acid and pyruvic acid also significantly increased during fermentation of both of CT-supplemented synthetic media and milk. In particular, the formic acid and propionic acid in CT were significantly utilized during fermentation of milk by L. gasseri 505. Moreover, the antioxidant capacity of CT-supplemented fermented milk increased due to the release of bioactive compounds until the exponential growth phase, after which the antioxidant activity declined due to degradation and loss of potency. Therefore, this study established that L. gasseri 505 efficiently utilized the CT-related nutrients during fermentation producing resulting metabolites with health-promoting effects, although it is necessary to control the fermentation time to obtain dairy products with optimum functionality.

  5. Theoretical study of the ammonia nitridation rate on an Fe (100) surface: A combined density functional theory and kinetic Monte Carlo study

    SciTech Connect

    Yeo, Sang Chul; Lee, Hyuck Mo; Lo, Yu Chieh; Li, Ju

    2014-10-07

    Ammonia (NH{sub 3}) nitridation on an Fe surface was studied by combining density functional theory (DFT) and kinetic Monte Carlo (kMC) calculations. A DFT calculation was performed to obtain the energy barriers (E{sub b}) of the relevant elementary processes. The full mechanism of the exact reaction path was divided into five steps (adsorption, dissociation, surface migration, penetration, and diffusion) on an Fe (100) surface pre-covered with nitrogen. The energy barrier (E{sub b}) depended on the N surface coverage. The DFT results were subsequently employed as a database for the kMC simulations. We then evaluated the NH{sub 3} nitridation rate on the N pre-covered Fe surface. To determine the conditions necessary for a rapid NH{sub 3} nitridation rate, the eight reaction events were considered in the kMC simulations: adsorption, desorption, dissociation, reverse dissociation, surface migration, penetration, reverse penetration, and diffusion. This study provides a real-time-scale simulation of NH{sub 3} nitridation influenced by nitrogen surface coverage that allowed us to theoretically determine a nitrogen coverage (0.56 ML) suitable for rapid NH{sub 3} nitridation. In this way, we were able to reveal the coverage dependence of the nitridation reaction using the combined DFT and kMC simulations.

  6. Gametocyte Clearance Kinetics Determined by Quantitative Magnetic Fractionation in Melanesian Children with Uncomplicated Malaria Treated with Artemisinin Combination Therapy.

    PubMed

    Karl, Stephan; Laman, Moses; Moore, Brioni R; Benjamin, John; Koleala, Tamarah; Ibam, Clemencia; Kasian, Bernadine; Siba, Peter M; Waltmann, Andreea; Mueller, Ivo; Woodward, Robert C; St Pierre, Timothy G; Davis, Timothy M E

    2015-08-01

    Quantitative magnetic fractionation and a published mathematical model were used to characterize between-treatment differences in gametocyte density and prevalence in 70 Papua New Guinean children with uncomplicated Plasmodium falciparum and/or Plasmodium vivax malaria randomized to one of two artemisinin combination therapies (artemether-lumefantrine or artemisinin-naphthoquine) in an intervention trial. There was an initial rise in peripheral P. falciparum gametocyte density with both treatments, but it was more pronounced in the artemisinin-naphthoquine group. Model-derived estimates of the median pretreatment sequestered gametocyte population were 21/μl for artemether-lumefantrine and 61/μl for artemisinin-naphthoquine (P < 0.001). The median time for P. falciparum gametocyte density to fall to <2.5/μl (below which transmission becomes unlikely) was 16 days in the artemether-lumefantrine group and 20 days in artemisinin-naphthoquine group (P < 0.001). Gametocyte prevalence modeling suggested that artemisinin-naphthoquine-treated children became gametocytemic faster (median, 2.2 days) than artemether-lumefantrine-treated children (median, 5.3 days; P < 0.001) and had a longer median P. falciparum gametocyte carriage time per individual (20 versus 13 days; P < 0.001). Clearance of P. vivax gametocytes was rapid (within 3 days) in both groups; however, consistent with the reappearance of asexual forms in the main trial, nearly 40% of children in the artemether-lumefantrine group developed P. vivax gametocytemia between days 28 and 42 compared with 3% of children in the artemisinin-naphthoquine group. These data suggest that artemisinin is less active than artemether against sequestered gametocytes. Greater initial gametocyte release after artemisinin-naphthoquine increases the period of potential P. falciparum transmission by 4 days relative to artemether-lumefantrine, but the longer elimination half-life of naphthoquine than of lumefantrine suppresses P. vivax

  7. Clinical evaluation of a combined regenerative technique with enamel matrix derivative, bone grafts, and guided tissue regeneration.

    PubMed

    Harris, Randall J; Harris, Laura E; Harris, Christopher R; Harris, Anne J

    2007-04-01

    The goal of this study was to evaluate the clinical changes obtained when intra-bony defects were treated with an enamel matrix derivative (EMD), a bone graft, and guided tissue regeneration. Fifty patients with a periodontal defect not associated with a furcation and with an attachment loss of at least 7.0 mm were included in this study. Full-thickness flaps were reflected, the roots were planed, EMD was applied, a demineralized freeze-dried bone allograft combined with EMD was placed, a bioabsorbable membrane was placed, and more EMD was applied. The defect areas were then sutured. At a mean of 5.3 months after treatment, there was a mean increase in recession of 0.7 mm, a mean reduction in probing depth of 5.7 mm, and a mean gain in attachment level of 5.0 mm. In this study there was more recession in smokers than in nonsmokers and in defects associated with anterior teeth. Additionally, the deeper defects (those with greater probing depths and attachment level loss) had the greatest reductions in probing depth and gains in attachment level. Based on this study, this technique proved itself to be an effective method to improve the clinical situation when treating periodontal defects not involving furcations.

  8. Skin and soft tissue infections among HIV-infected persons in the late combination antiretroviral therapy era.

    PubMed

    Crum-Cianflone, N F; Grandits, G; Weintrob, A; Ganesan, A; Agan, B; Landrum, M

    2012-07-01

    Skin and soft tissue infections (SSTIs) occur at higher rates among HIV-infected persons, but current trends and risk factors are largely undefined. We evaluated SSTIs among a prospective cohort of HIV-infected persons during the late combination antiretroviral therapy (cART) era (2006-2010). Of the 1918 HIV-infected persons evaluated, 379 (20%) developed an SSTI during a median of 3.7 years of follow-up; of these, 118 (31%) developed at least one recurrent SSTI. The incidence rate of SSTIs was 101 (95% confidence interval [CI] 93-109) cases per 1000 person-years, and rates did not significantly change during the study period. Compared with not receiving cART and having an HIV RNA level >1000 copies/mL, patients receiving cART with an HIV RNA level <1000 copies/mL had a reduced risk of an SSTI (hazard ratio 0.64, 95% CI 0.48-0.86, P < 0.01). In summary, initial and recurrent SSTIs are common among HIV-infected persons, and HIV control is associated with a lower risk of SSTIs.

  9. Fabrication of cancellous biomimetic chitosan-based nanocomposite scaffolds applying a combinational method for bone tissue engineering.

    PubMed

    Jamalpoor, Zahra; Mirzadeh, Hamid; Joghataei, Mohammad Taghi; Zeini, Darya; Bagheri-Khoulenjani, Shadab; Nourani, Mohammad Reza

    2015-05-01

    The aim of this study was to mimic the specific structure of bone and fabricate a biomimetic nano-hydroxyapatite (HA)/chitosan (Cs)/gelatin scaffolds using combination of particle leaching and freeze drying methods eliminating mold effects. To achieve an optimum structure, scaffolds with different gelatin/Cs weight ratio were fabricated. Morphological characterization of scaffolds by scanning electron microscopy method showed highly interconnected porous structures similar to cancellous bone with mean pore size ranging from 140 to 190 μm. Nano-HA crystals were dispersed homogeneously in the polymer matrix according to the energy-dispersive X-ray spectroscopy and transmission electron microscopy images. Fourier transform infrared and X-ray diffraction results disclosed that chemical interactions were formed between nano-HA, Cs, gelatin and crystallinity of each material decreased with blending. It was found that increasing the gelatin content significantly improved water uptake, degradation rate as well as attachment, infiltration and proliferation of Saos2 cells to the scaffolds. The presented results confirm that the designed biomimetic nano-HA /Cs/gelatin scaffolds can be used as promising substitutes for bone tissue engineering.

  10. Identification of benign and malignant endometrial cancer with transvaginal ultrasonography combined with elastography and tissue hardness analysis.

    PubMed

    Zhang, Y; Luo, L; Luo, Q

    2015-01-01

    This study was designed to explore tissue hardness and distinguish benign and malignant endometrial cancer with the use of transvaginal ultrasonography combined with elastography. Color Doppler ultrasonic diasonograph was used to carry out transvaginal ultrasonography and elastography. Once the nidus was observed, features of the 2D image were analyzed. Then features of elasticity of the uterine cavity in different states were analyzed by elastography, and strain rate ratio was measured. Finally, elasticity scoring (0~5 points) was made. Receiver operating characteristic (ROC) curve was drawn based on elasticity score and strain rate ratio. The area under the elasticity score curve and strain rate ratio curve was 0.761 and 0.852, respectively, and there was no statistically significant difference between them (c2= 4.663, P>0.05). Then 2.98 was confirmed as the diagnostic cut-off value of benign and malignant lesions, based on strain rate ratio. Ultrasonic elastography as an effective assistance for transvaginal ultrasonography provides more valuable information for confirmation of lesions and offers more accurate evidence for diagnosis of disease in the uterine cavity.

  11. Differential action on cancer and normal tissue by adrenochrome monoaminoguanidine methanesulfonate and cytochrome C combined with radiotherapy

    SciTech Connect

    Nakatsugawa, S. ); Sugahara, T. )

    1994-06-15

    The possibility that radioprotective effects on potent natural killer (NK) cells by adrenochrome monoaminoguanidine methanesulfonate (AMM) + cytochrome C during radiotherapy (RT) for lung cancer might result in the radiosensitization of human lung cancer cells in vivo is examined. Human lung cancer xenografts in the right hind legs of KSN mice (10 weeks old) were locally irradiated with 20 Gy of X ray. AMM (10 mg/kg/day) and/or cytochrome C (CCC) (5 mg/kg/day) were given intraperitoneally immediately before or after RT, followed by daily administration for 4 days. Natural killer activities of host splenocytes were also tested with the standard [sup 51]Cr releasing assay with YAC-1 cells as target cells. In a clinical study, 65 patients with lung cancer were treated with more than 50 Gy of RT with or without combination with AMM + CCC, OK-432 or AMM + CCC + OK-432. Before and after RT, lymphocyte subsets in the peripheral blood were examined with dichromatic analysis using an Ortho Spectrum IIIFCM system and fluorescent MABs. In this study, the change in the absolute number of each subset was investigated. AMM + cytochrome C augumented NK activity in KSN nude mice, protected potent NK cells in patients with lung cancer against RT and sensitized the human lung cancer xenografts to RT. AMM + cytochrome C may have potential as a differential modulator of radiosensitivity of normal tissues and of tumors. 8 refs., 2 figs., 1 tab.

  12. Comparative pharmacokinetics and tissue distribution of schisandrin, deoxyschisandrin and schisandrin B in rats after combining acupuncture and herb medicine (schisandra chinensis).

    PubMed

    Wu, Xiaoyan; Zhou, Yuan; Yin, Fangzhou; Dai, Guoliang; Li, Lin; Xu, Bin; Ji, De; Sun, Yong; Mao, Chunqin; Lu, Tulin

    2014-08-01

    Recently, combination therapy with acupuncture and medicine as a practical strategy to treat diseases has gained increasing attention. The present study aimed to investigate whether acupuncture stimulation at ST.36 had a potential impact on the pharmacokinetics and tissue distribution of lignans. An HPLC-ESI/MS analytical method was established and successfully applied to a comparative study of drug concentration in plasma and tissues of three lignans. The parameters area under the plasma concentration-time curve from time zero to the final measurable point and from time zero to infinity, and peak concentration were significantly increased, with a prolonged mean residence time and a corresponding decrease in clearance in comparision with the Schisandra-alone group. Additionally, tissue concentrations of three lignans were improved in the group with acupuncture, especially in liver. The results indicated that acupuncture has a synergistic effect on the pharmacokinetics and tissue distribution of the three lignans, which could postpone their elimination, resulting in a longer blood circulating time in rat plasma and prolonged residence time in target tissues, leading to higher tissue concentration. The findings provide some scientific evidence for the mechanism of the combined use of acupuncture and herbal medicine. Furthermore, we suggest that acupuncture and its combination with herbal medicine should be investigated further as a possible adjuvant therapy in clinical treatment for liver injury.

  13. Multifunctional Hydrogel with Good Structure Integrity, Self-Healing, and Tissue-Adhesive Property Formed by Combining Diels-Alder Click Reaction and Acylhydrazone Bond.

    PubMed

    Yu, Feng; Cao, Xiaodong; Du, Jie; Wang, Gang; Chen, Xiaofeng

    2015-11-04

    Hydrogel, as a good cartilage tissue-engineered scaffold, not only has to possess robust mechanical property but also has to have an intrinsic self-healing property to integrate itself or the surrounding host cartilage. In this work a double cross-linked network (DN) was designed and prepared by combining Diels-Alder click reaction and acylhydrazone bond. The DA reaction maintained the hydrogel's structural integrity and mechanical strength in physiological environment, while the dynamic covalent acylhydrazone bond resulted in hydrogel's self-healing property and controlled the on-off switch of network cross-link density. At the same time, the aldehyde groups contained in hydrogel further promote good integration of the hydrogel to surrounding tissue based on aldehyde-amine Schiff-base reaction. This kind of hydrogel has good structural integrity, autonomous self-healing, and tissue-adhesive property and simultaneously will have a good application in tissue engineering and tissue repair field.

  14. cAMP-dependent protein kinase from brown adipose tissue: temperature effects on kinetic properties and enzyme role in hibernating ground squirrels.

    PubMed

    MacDonald, J A; Storey, K B

    1998-10-01

    Arousal from hibernation requires thermogenesis in brown adipose tissue, a process that is stimulated by beta-adrenergic signals, leading to a rise in intracellular 3',5'-cyclic adenosine monophosphate AMP (cAMP) and activating cAMP-dependent protein kinase A (PKA) to phosphorylate a suite of target proteins and activate lipolysis and uncoupled respiration. To determine whether specific adaptations (perhaps temperature-dependent) facilitate PKA kinetic properties or protein-phosphorylating ability, the catalytic subunit of PKA (PKAc) from interscapular brown adipose of the ground squirrel Spermophilus richardsonii, was purified (final specific activity = 279 nmol phosphate transferred per min per mg protein) and characterized. Physical properties of PKAc included a molecular weight of 41 kDa and an isoelectric point of 7.8 +/- 0.08. A change in assay temperature from a euthermic value (37 degrees C) to one typical of hibernating body temperature (5 degrees C) had numerous significant effects on ground squirrel PKAc including: (a) pH optimum rose from 6.8 at 37 degrees C to 8.7 at 5 degrees C, (b) K(m) values at 37 degrees C for Mg.ATP (49.2 +/- 3.4 microM) and for two phosphate acceptors, Kemptide (50.0 +/- 5.5 microM) and Histone IIA (0.41 +/- 0.05 mg/ml) decreased by 53%, 80% and 51%, respectively, at 5 degrees C, and (c) inhibition by KCl, NaCl and NH4Cl was reduced. However, temperature change had little or no effect on K(m) values of rabbit PKAc, suggesting a specific positive thermal modulation of the hibernator enzyme. Arrhenius plots also differed for the two enzymes; ground squirrel PKAc showed a break in the Arrhenius relationship at 9 degrees C and activation energies that were 29.1 +/- 1.0 kJ/mol for temperatures > 9 degrees C and 2.3-fold higher at 68.1 +/- 2.1 kJ/mol for temperatures < 9 degrees C, whereas the rabbit enzyme showed a breakpoint at 17 degrees C with a 13-fold higher activation energy over the lower temperature range. However

  15. The Negative Impact of Combining Retinoic Acid (ATRA) and Mold Spores on F344 Rat Lung and Improvement of Tissue Pathology by Citral.

    PubMed

    Farah, Ibrahim O; Holt-Gray, Carlene; Cameron, Joseph A; Tucci, Michelle; Cason, Zelma; Benghuzzi, Hamed

    2015-01-01

    The impact of retinoic acid (All Trans Retinoic Acid; ATRA) and Mold spores (MLD) in the development of lung pathology and in vivo tissue remodeling have not been well established in the literature. In addition, the role of citral (inhibitor of retinoid function) in the improvement of lung pathology has not been ascertained in animal studies. Therefore, it is hypothesized that ATRA and Mold (MLD) exposure will sensitize lung tissues leading to lung tissue pathology and that Citrals (C1 and C2) will reverse, ameliorate or improve the associated pathological damage to lung tissues. The study used an IACUC approved between-subject in vivo randomized split plot factorial design (F344 rat model; N=40). Animals were exposed to eight different treatments including vehicle, MLD, ATRA, Citrals (C1 and C2) and their MLD combinations (MLD+ ATRA, MLD+ C1, and MLD+ C2) by intra-peritoneal route. Rat weight and blood data were collected on Days 1 and 21, all animals were sacrificed on day 21, and lung tissues were processed for histopathology. Results from weight and blood data (ANOVA and Duncan) as well as from histopathological analyses supported the findings that exposure of F344 rats to MLD combinations with ATRA and Citrals showed various levels of lung tissue damage that were impacted by either C1 or C2. This promising study showed impressive responses on the interaction of MLD, Citrals, and ATRA as related to their impact on associated lung tissue pathologies.

  16. Phase II study with the combination of gemcitabine and DTIC in patients with advanced soft tissue sarcomas.

    PubMed

    Losa, R; Fra, J; López-Pousa, A; Sierra, M; Goitia, A; Uña, E; Nadal, R; Del Muro, J García; Gión, M; Maurel, J; Escudero, P; Esteban, E; Buesa, José M

    2007-02-01

    Based on the promising results of a Phase I study with a combination of gemcitabine and DTIC performed in advanced soft tissue sarcoma (ASTS) patients, and due to the limited efficacy of second or third line therapies in those patients, we designed a Phase II study to determine the activity of this new regimen. Patients with ASTS, measurable disease, pretreated with chemotherapy, received gemcitabine 1,800 mg/m2 infused over 180 min followed by DTIC 500 mg/m2 (one cycle), every 2 weeks. The pharmacokinetics (PK) of gemcitabine and 2',2'-difluorodeoxyuridine (dFdU), and the accumulation of gemcitabine triphosphate (dFdCTP) by peripheral blood mononuclear cells were studied. The influence of the sequence of administration on those parameters was examined to exclude potential drug interactions. Twenty-six patients received a total of 158 cycles (mean four cycles, range 1-18). Grade 3-4 anemia (23% of patients), granulocytopenia (46%) or thrombocytopenia (12%), and grade 3 increase in AST (18%), ALT (21%), or gamma-glutamyl-transferase (9%) were noted. Response rate in 23 patients was 4% (95% CI: 0-24%), and in 8 of 11 patients stable disease lasted > 6 months. Progression-free rate (PFR) at 3 and 6 months was, respectively, 48 and 28%, and median overall survival 37 weeks. Pooled data from the Phase I and Phase II studies showed clinical benefit in patients with leiomyosarcomas (LMS) (57%) and malignant fibrous histiocytomas (MFH) (33%). The sequence of administration did not influence PK of gemcitabine or dFdU. There was a trend (P = 0.11) toward a lower accumulation of dFdCTP when DTIC preceded gemcitabine. Although the remission rate was low, PFR figures indicate that this regimen has activity in patients with ASTS. It should be compared with DTIC, or other gemcitabine-containing combinations, in patients with LMS or MFH, to determine whether this combination offers advantages in PFR or in overall activity.

  17. Combined androgen excess and Western-style diet accelerates adipose tissue dysfunction in young adult, female nonhuman primates.

    PubMed

    Varlamov, Oleg; Bishop, Cecily V; Handu, Mithila; Takahashi, Diana; Srinivasan, Sathya; White, Ashley; Roberts, Charles T

    2017-09-01

    What are the separate and combined effects of mild hyperandrogenemia and consumption of a high-fat Western-style diet (WSD) on white adipose tissue (WAT) morphology and function in young adult female nonhuman primates? Combined exposure to mild hyperandrogenemia and WSD induces visceral omental (OM-WAT) but not subcutaneous (SC-WAT) adipocyte hypertrophy that is associated with increased uptake and reduced mobilization of free fatty acids. Mild hyperandrogenemia in females, principally in the context of polycystic ovary syndrome, is often associated with adipocyte hypertrophy, but the mechanisms of associated WAT dysfunction and depot specificity remain poorly understood. Female rhesus macaques were randomly assigned at 2.5 years of age (near menarche) to receive either cholesterol (C; n = 20) or testosterone (T; n = 20)-containing silastic implants to elevate T levels 5-fold above baseline. Half of each of these groups was then fed either a low-fat monkey chow diet or WSD, resulting in four treatment groups (C, control diet; T alone; WSD alone; T + WSD; n = 10/group) that were maintained until the current analyses were performed at 5.5 years of age (3 years of treatment, young adults). OM and SC-WAT biopsies were collected and analyzed longitudinally for in vivo changes in adipocyte area and blood vessel density, and ex vivo basal and insulin-stimulated fatty acid uptake and basal and isoproterenol-stimulated lipolysis. In years 2 and 3 of treatment, the T + WSD group exhibited a significantly greater increase in OM adipocyte size compared to all other groups (P < 0.05), while the size of SC adipocytes measured at the end of the study was not significantly different between groups. In year 3, both WAT depots from the WSD and T + WSD groups displayed a significant reduction in local capillary length and vessel junction density (P < 0.05). In year 3, insulin-stimulated fatty acid uptake in OM-WAT was increased in the T + WSD group compared to year 2 (P < 0.05). In

  18. HIV DNA Is Frequently Present within Pathologic Tissues Evaluated at Autopsy from Combined Antiretroviral Therapy-Treated Patients with Undetectable Viral Loads

    PubMed Central

    Lamers, Susanna L.; Rose, Rebecca; Maidji, Ekaterina; Agsalda-Garcia, Melissa; Nolan, David J.; Fogel, Gary B.; Salemi, Marco; Garcia, Debra L.; Bracci, Paige; Yong, William; Commins, Deborah; Said, Jonathan; Khanlou, Negar; Hinkin, Charles H.; Sueiras, Miguel Valdes; Mathisen, Glenn; Donovan, Suzanne; Shiramizu, Bruce; Stoddart, Cheryl A.; Singer, Elyse J.

    2016-01-01

    ABSTRACT HIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV-positive (HIV+) cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort. Extensive medical histories were obtained for each participant. Autopsy specimens, including at least six brain and nonbrain tissues per participant, were reviewed by study pathologists. HIV DNA, measured in tissues by quantitative and droplet digital PCR, was identified in 48/87 brain tissues and 82/142 nonbrain tissues at levels >200 HIV copies/million cell equivalents. No participant was found to be completely free of tissue HIV. Parallel sequencing studies from some tissues recovered intact HIV DNA and RNA. Abnormal histological findings were identified in all participants, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. All brain tissues demonstrated some degree of pathology. Ninety-five percent of participants had some degree of atherosclerosis, and 75% of participants died with cancer. This study assists in characterizing the anatomical locations of HIV, in particular, macrophage-rich tissues, such as the central nervous system (CNS) and testis. Additional studies are needed to determine if the HIV recovered from tissues promotes the pathogenesis of inflammatory diseases, such as HIV-associated neurocognitive disorders, cancer, and atherosclerosis. IMPORTANCE It is well-known that combined antiretroviral therapy (cART) can reduce plasma HIV to undetectable levels; however, cART cannot completely clear HIV infection. An

  19. HIV DNA Is Frequently Present within Pathologic Tissues Evaluated at Autopsy from Combined Antiretroviral Therapy-Treated Patients with Undetectable Viral Loads.

    PubMed

    Lamers, Susanna L; Rose, Rebecca; Maidji, Ekaterina; Agsalda-Garcia, Melissa; Nolan, David J; Fogel, Gary B; Salemi, Marco; Garcia, Debra L; Bracci, Paige; Yong, William; Commins, Deborah; Said, Jonathan; Khanlou, Negar; Hinkin, Charles H; Sueiras, Miguel Valdes; Mathisen, Glenn; Donovan, Suzanne; Shiramizu, Bruce; Stoddart, Cheryl A; McGrath, Michael S; Singer, Elyse J

    2016-10-15

    HIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV-positive (HIV(+)) cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort. Extensive medical histories were obtained for each participant. Autopsy specimens, including at least six brain and nonbrain tissues per participant, were reviewed by study pathologists. HIV DNA, measured in tissues by quantitative and droplet digital PCR, was identified in 48/87 brain tissues and 82/142 nonbrain tissues at levels >200 HIV copies/million cell equivalents. No participant was found to be completely free of tissue HIV. Parallel sequencing studies from some tissues recovered intact HIV DNA and RNA. Abnormal histological findings were identified in all participants, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. All brain tissues demonstrated some degree of pathology. Ninety-five percent of participants had some degree of atherosclerosis, and 75% of participants died with cancer. This study assists in characterizing the anatomical locations of HIV, in particular, macrophage-rich tissues, such as the central nervous system (CNS) and testis. Additional studies are needed to determine if the HIV recovered from tissues promotes the pathogenesis of inflammatory diseases, such as HIV-associated neurocognitive disorders, cancer, and atherosclerosis. It is well-known that combined antiretroviral therapy (cART) can reduce plasma HIV to undetectable levels; however, cART cannot completely clear HIV infection. An ongoing question is

  20. Rigorous Kinetic Modeling and Optimization Study of a Modified Claus Unit for an Integrated Gasification Combined Cycle (IGCC) Power Plant with CO{sub 2} Capture

    SciTech Connect

    Jones, Dustin; Bhattacharyya, Debangsu; Turton, Richard; Zitney, Stephen E.

    2012-02-08

    The modified Claus process is one of the most common technologies for sulfur recovery from acid gas streams. Important design criteria for the Claus unit, when part of an Integrated Gasification Combined Cycle (IGCC) power plant, are the ability to destroy ammonia completely and the ability to recover sulfur thoroughly from a relatively low purity acid gas stream without sacrificing flame stability. Because of these criteria, modifications to the conventional process are often required, resulting in a modified Claus process. For the studies discussed here, these modifications include the use of a 95% pure oxygen stream as the oxidant, a split flow configuration, and the preheating of the feeds with the intermediate pressure steam generated in the waste heat boiler (WHB). In the future, for IGCC plants with CO{sub 2} capture, the Claus unit must satisfy emission standards without sacrificing the plant efficiency in the face of typical disturbances of an IGCC plant, such as rapid change in the feed flow rates due to load-following and wide changes in the feed composition because of changes in the coal feed to the gasifier. The Claus unit should be adequately designed and efficiently operated to satisfy these objectives. Even though the Claus process has been commercialized for decades, most papers concerned with the modeling of the Claus process treat the key reactions as equilibrium reactions. Such models are validated by manipulating the temperature approach to equilibrium for a set of steady-state operating data, but they are of limited use for dynamic studies. One of the objectives of this study is to develop a model that can be used for dynamic studies. In a Claus process, especially in the furnace and the WHB, many reactions may take place. In this work, a set of linearly independent reactions has been identified, and kinetic models of the furnace flame and anoxic zones, WHB, and catalytic reactors have been developed. To facilitate the modeling of the Claus

  1. Rigorous Kinetic Modeling, Optimization, and Operability Studies of a Modified Claus Unit for an Integrated Gasification Combined Cycle (IGCC) Power Plant with CO{sub 2} Capture

    SciTech Connect

    Jones, Dustin; Bhattacharyya, Debangsu; Turton, Richard; Zitney, Stephen E

    2011-12-15

    The modified Claus process is one of the most common technologies for sulfur recovery from acid gas streams. Important design criteria for the Claus unit, when part of an Integrated Gasification Combined Cycle (IGCC) power plant, are the ability to destroy ammonia completely and the ability to recover sulfur thoroughly from a relatively low purity acid gas stream without sacrificing flame stability. Because of these criteria, modifications to the conventional process are often required, resulting in a modified Claus process. For the studies discussed here, these modifications include the use of a 95% pure oxygen stream as the oxidant, a split flow configuration, and the preheating of the feeds with the intermediate pressure steam generated in the waste heat boiler (WHB). In the future, for IGCC plants with CO{sub 2} capture, the Claus unit must satisfy emission standards without sacrificing the plant efficiency in the face of typical disturbances of an IGCC plant, such as rapid change in the feed flow rates due to load-following and wide changes in the feed composition because of changes in the coal feed to the gasifier. The Claus unit should be adequately designed and efficiently operated to satisfy these objectives. Even though the Claus process has been commercialized for decades, most papers concerned with the modeling of the Claus process treat the key reactions as equilibrium reactions. Such models are validated by manipulating the temperature approach to equilibrium for a set of steady-state operating data, but they are of limited use for dynamic studies. One of the objectives of this study is to develop a model that can be used for dynamic studies. In a Claus process, especially in the furnace and the WHB, many reactions may take place. In this work, a set of linearly independent reactions has been identified, and kinetic models of the furnace flame and anoxic zones, WHB, and catalytic reactors have been developed. To facilitate the modeling of the Claus

  2. A combination of simvastatin and methylprednisolone improves the quality of vitrified-warmed ovarian tissue after auto-transplantation.

    PubMed

    Lee, Jaewang; Kim, Eun Jung; Kong, Hyun Sun; Youm, Hye Won; Lee, Jung Ryeol; Suh, Chang Suk; Kim, Seok Hyun

    2015-11-01

    Does the preoperative administration of simvastatin and methylprednisolone enhance mouse ovarian quality after auto-transplantation of vitrified-warmed ovarian tissue (OT)? Treatment with combined simvastatin and methylprednisolone enhances the quality of transplanted mouse OTs. The prevention of ischemic injury after transplantation of OT is critical for preserving the ovarian follicles. Preoperative administration of simvastatin (a cholesterol-lowering drug) has beneficial effects on various organ transplantations. Moreover, donor treatment with simvastatin and methylprednisolone (main effects are on immune response) prevents ischemia-reperfusion injury and has a beneficial effect on allograft survival in rat cardiac allografts. A total of 232 6-week-old B6D2F1 mice were randomly distributed into fresh control, vitrified-warmed control and experimental groups (n = 10-17 per group). The experimental groups were as follows: sham control, simvastatin, methylprednisolone and co-treatment groups. In the experimental groups, the mice were administered simvastatin (5 mg/kg, orally), methylprednisolone (15 mg/kg, i.v.) or a combination of simvastatin and methylprednisolone 2 h before ovariectomy, whereas the sham control mice received normal saline. Whole ovaries were removed from the mice and vitrified by two-step vitrification procedures. The vitrified ovaries were warmed 1 week later and auto-transplanted under the bilateral kidney capsules. The ovaries and blood samples were collected 2, 7 and 21 days (D) after transplantation for histological analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, immunohistochemistry for CD31 and serum anti-Mullerian hormone (AMH) level estimation. Embryonic development was evaluated after IVF of oocytes obtained from the transplanted ovary. The group that received simvastatin and methylprednisolone showed a significantly improved intact (Grade 1) follicle ratio (D2: P < 0.001, D7: P < 0.05 and D21: P

  3. Thrombin generation assay and transmission electron microscopy: a useful combination to study tissue factor-bearing microvesicles.

    PubMed

    Gheldof, Damien; Hardij, Julie; Cecchet, Francesca; Chatelain, Bernard; Dogné, Jean-Michel; Mullier, François

    2013-01-01

    Patients with cancer have a 7- to 10-fold increased risk of developing venous thromboembolism. Circulating microvesicles could be a useful predictive biomarker for venous thromboembolism in cancer. Validated and standardised techniques that could be used to determine the complete microvesicle phenotype are required. These were two-fold: a) to characterise tissue factor (TF)-bearing microvesicles released by cultured breast cancer cells MDA-MB-231 by flow cytometry (FCM), transmission electron microscopy (TEM) and thrombin generation assay (TGA); and b) to validate the sensitivity and variability intra/inter-assay of TGA as a useful method to study the procoagulant activity (PCA) of microvesicles. Cultured breast cancer cells MDA-MB-231 were incubated for 45 minutes at 37°C. Samples were then centrifuged or not at 4,500 g for 15 minutes, and cells and MVs or MV-containing supernatants were used for TEM, FCM and TGA. In activity assays, microvesicles (i.e. cell-depleted supernatants) were incubated with anti-TF antibodies or with annexin V to assess the contribution of TF and phospholipids to the PCA. Alternatively, supernatants were filtered through 0.1, 0.22, 0.45 or 0.65 µm membranes and subjected to TGA. The majority of the PCA was associated with microvesicles smaller than 0.1 µm, and the mean microvesicle size estimated by TEM after 10,000 g centrifugation was 121±54 nm with a majority of vesicles between 100 and 200 nm. Microvesicles derived from 5,000 MDA-MB-231cells/ml were sufficient to significantly increase the thrombin generation of normal pooled plasma. TEM, FCM and filtration coupled to TGA represent a useful combination to study the PCA of TF-bearing microvesicles, whatever their size. And it will be interesting to implement these techniques in patients.

  4. Dietary CLA combined with palm oil or ovine fat differentially influences fatty acid deposition in tissues of obese Zucker rats.

    PubMed

    Martins, Susana V; Lopes, Paula A; Alves, Susana P; Alfaia, Cristina M; Castro, Matilde F; Bessa, Rui J B; Prates, José A M

    2012-01-01

    The effect of dietary conjugated linoleic acid (CLA) supplementation in combination with fat from vegetable versus animal origin on the fatty acid deposition, including that of individual 18:1 and 18:2 (conjugated and non-conjugated) isomers, in the liver and muscle of obese rats was investigated. For this purpose, 32 male Zucker rats were randomly assigned to one of four diets containing palm oil or ovine fat, supplemented or not with 1% of 1:1 cis(c)9,trans(t)11 and t10,c12 CLA isomers mixture. Total fatty acid content decreased in the liver and muscle of CLA-fed rats. In the liver, CLA increased saturated fatty acids (SFA) in 11.9% and decreased monounsaturated fatty acids (MUFA) in 6.5%. n-3 Polyunsaturated fatty acids (PUFA) relative proportions were increased in 30.6% by CLA when supplemented to the ovine fat diet. In the muscle, CLA did not affect SFA but decreased MUFA and PUFA percentages. The estimation of Δ9-indices 16 and 18 suggested that CLA inhibited the stearoyl-CoA desaturase activity in the liver (a decrease of 13-38%), in particular when supplemented to the ovine fat diet. Concerning CLA supplementation, the t10,c12 isomer percentage was 60-80% higher in the muscle than in the liver. It is of relevance that rats fed ovine fat, containing bio-formed CLA, had more c9,t11 CLA isomer deposited in both tissues than rats fed palm oil plus synthetic CLA. These results highlight the importance to further clarify the biological effects of consuming foods naturally enriched in CLA, alternatively to CLA dietary supplementation.

  5. Is poststroke complex regional pain syndrome the combination of shoulder pain and soft tissue injury of the wrist?

    PubMed Central

    Kim, Yong Wook; Kim, Yoon; Kim, Jong Moon; Hong, Ji Seong; Lim, Hyun Sun; Kim, Hyoung Seop

    2016-01-01

    Abstract Patients with poststroke complex regional pain syndrome (CRPS) show different symptoms compared to other types of CRPS, as they usually complain of shoulder and wrist pain with the elbow relatively spared. It is thus also known by the term “shoulder-hand syndrome.” The aim of this study is to present a possible pathophysiology of poststroke CRPS through ultrasonographic observation of the affected wrist before and after steroid injection at the extensor digitorum communis (EDC) tendon in patients suspected with poststroke CRPS. Prospective evaluation and observation, the STROBE guideline checklist was used. Twenty-three patients diagnosed as poststroke CRPS in accordance to clinical criteria were enrolled. They had a Three Phase Bone Scan (TPBS) done and the cross-sectional area (CSA) of EDC tendon was measured by using ultrasonography. They were then injected with steroid at the EDC tendon. The CSA of EDC tendon, visual analogue scale (VAS), and degree of swelling of the wrist were followed up 1 week after the injection. TPBS was interpreted as normal for 4 patients, suspected CRPS for 10 patients, and CRPS for 9 patients. Ultrasonographic findings of the affected wrist included swelling of the EDC tendon. After the injection of steroid to the wrist, CSA and swelling of the affected wrist compared to that before the treatment was significantly decreased (P < 0.001). The VAS score declined significantly after the injection (P < 0.001). Our results suggest that the pathophysiology of poststroke CRPS might be the combination of frozen shoulder or rotator cuff tear of shoulder and soft tissue injury of the wrist caused by the hemiplegic nature of patients with stroke. PMID:27495051

  6. Efficacy of unfractionated heparin, low molecular weight heparin and both combined for releasing total and free tissue factor pathway inhibitor.

    PubMed

    Altman, R; Scazziota, A; Rouvier, J

    1998-01-01

    Unfractionated heparin (UFH) exerts its anticoagulant properties by increasing the inactivation of thrombin and activated factor X by antithrombin III. Apart from this main action release of tissue factor pathway inhibitor (TFPI) from endothelial cells could also be important for the antithrombotic activity of heparins. Four different heparin preparations were injected subcutaneously into 5 healthy volunteers 1 week apart: (1) UFH 2,500 IU fix dose (FixUFH), (2) 1 mg/kg body weight of low molecular weight heparin (LMWH), (3) the combined LMWH-adjusted dose plus UFH 2,500 IU fix dose (ComHep) and (4) UFH 2,500 IU/10 kg body weight (UFHvar). Plasma samples were drawn before and 1, 2, 4, 6, 12 and 24 h afterwards. FixUFH did not affect the concentration of total and free TFPI. Total TFPI increased in the 1st hour after LMWH injection from 74 to 124 ng/ml (p < 0.01), after ComHep from 82 to 144 ng/ml (p < 0.01), and after UFHvar from 91 to 113 ng/ml (p < 0.05). All observed elevations were significant at the peak value (+/- 2 h, p < 0.01 compared with baselines). The increase of free TFPI produced by UFHvar (74.5 and 70.5 ng/ml) was significantly higher than with LMWH (42.8 and 38.0 ng/ml) at 2 and 4 h (p < 0.001 and p < 0.01, respectively). UFHvar and ComHep but not LMWH produced a statistically significant increase of free TFPI compared with FixUFH at 2, 4 and 6 h (p < 0. 01). We concluded that at comparable therapeutic doses, subcutaneous UFHvar released more free TFPI than LMWH and ComHep. A synergism between LMWH and low dose of UFH was found in 4-, 6- and 12-hour blood samples.

  7. Enhancement of activated sludge dewatering performance by combined composite enzymatic lysis and chemical re-flocculation with inorganic coagulants: Kinetics of enzymatic reaction and re-flocculation morphology.

    PubMed

    Chen, Zhan; Zhang, Weijun; Wang, Dongsheng; Ma, Teng; Bai, Runying

    2015-10-15

    The feasibility of combined process of composite enzymatic treatment and chemical flocculation with inorganic salt coagulants was investigated in this study. The evolution of extracellular polymeric substances (EPS) distribution, composition and morphological properties were analyzed to unravel the sludge conditioning mechanism. It was found that sludge filtration performance was deteriorated due to release of a large amount of biopolymers after enzymatic treatment. The change in EPS followed the pseudo-first-order kinetic equation well under enzymatic treatment. The feeding modes of enzymes had a significant influence on sludge lysis efficiency under compound enzymes treatment. Alpha amylase + protease was more effective in solubilization than other two addition modes (protease + α-amylase or simultaneous addition). The sludge floc re-formed and macromolecule biopolymers were effectively removed through coagulation process. At the same time, both of filtration rate and cake solid content of sludge treated with enzymes were improved with increasing dosage of coagulants, and ferric iron (FeCl3) had better performance in sludge dewaterability enhancement than polyaluminium chloride (PACl). In addition, sludge filtration property was slightly deteriorated, while the cake moisture reduction was favored at the optimal dosage of inorganic coagulants. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Combined use of thermomechanics and UV spectroscopy to rationalize the kinetics of bioactive compound (caffeine) mobility in a high solids matrix.

    PubMed

    Kasapis, Stefan; Shrinivas, Preeti

    2010-03-24

    An investigation of the diffusional mobility of a bioactive compound (caffeine) within a carbohydrate matrix (glucose syrup) at a glassy consistency is reported. The experimental temperature range was from 30 to - 70 degrees C, and the techniques of modulated differential scanning calorimetry, small-deformation dynamic oscillation on shear, and UV spectrometry were employed. It is not a straightforward matter to identify the relaxation dynamics of such a glassy matrix. This makes suggestions of the relationship between the structural properties of the matrix and the diffusional mobility of bioactive compounds reported earlier in the literature rather tenuous. To address this issue, we recorded mechanical spectra over the aforementioned temperature range and utilized the combined framework of the Williams, Landel, and Ferry (WLF) equation with the time-temperature superposition principle to rationalize results. The protocol produced a fundamental definition of the glass transition temperature and free volume parameters of the glucose syrup sample within the glass transition region. Results were related to the kinetic rates of caffeine diffusion derived by UV spectroscopy leading to the conclusion that the diffusional mobility of the chemical substance is independent of the carbohydrate matrix. This conclusion was further supported by the high level of fractional free volume of caffeine, which is congruent with the predictions of the reaction rate theory (modified Arrhenius equation), as compared to the collapsing levels of free volume in the glucose-syrup matrix that make appropriate WLF considerations.

  9. Suitable combination of promoter and micellar catalyst for kilo fold rate acceleration on benzaldehyde to benzoic acid conversion in aqueous media at room temperature: a kinetic approach.

    PubMed

    Ghosh, Aniruddha; Saha, Rumpa; Ghosh, Sumanta K; Mukherjee, Kakali; Saha, Bidyut

    2013-05-15

    The kinetics of oxidation of benzaldehyde by chromic acid in aqueous and aqueous surfactant (sodium dodecyl sulfate, SDS, alkyl phenyl polyethylene glycol, Triton X-100 and N-cetylpyridinium chloride, CPC) media have been investigated in the presence of promoter at 303 K. The pseudo-first-order rate constants (kobs) were determined from a logarithmic plot of absorbance as a function time. The rate constants were found to increase with introduction of heteroaromatic nitrogen base promoters such as Picolinic acid (PA), 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen). The product benzoic acid has been characterized by conventional melting point experiment, NMR, HRMS and FTIR spectral analysis. The mechanism of both unpromoted and promoted reaction path has been proposed for the reaction. In presence of the anionic surfactant SDS, cationic surfactant CPC and neutral surfactant TX-100 the reaction can undergo simultaneously in both aqueous and micellar phase with an enhanced rate of oxidation in the micellar phase. Both SDS and TX-100 produce normal micellar effect whereas CPC produce reverse micellar effect in the presence of benzaldehyde. The observed net enhancement of rate effects has been explained by considering the hydrophobic and electrostatic interaction between the surfactants and reactants. SDS and bipy combination is the suitable one for benzaldehyde oxidation. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. The role of electron interfacial transfer in mesoporous nano-TiO2 photocatalysis: a combined study of in situ photoconductivity and numerical kinetic simulation.

    PubMed

    Liu, Baoshun; Yang, Jingjing; Zhao, Xiujian; Yu, Jiaguo

    2017-03-29

    In this research, a combination of in situ photoconductivity (σ) and kinetic simulations was used to study the role of electron interfacial transfer (IT) in the gaseous photocatalysis of formic acid by mesoporous nanocrystalline TiO2. The effects of light intensity, initial formic acid concentrations, oxygen amounts, and temperature on the in situ σ and the photocatalytic courses were studied in detail. The temperature dependence of in situ σ clearly shows that the electron transfer is determined by the IT of electrons to O2 rather than by the transport. It was seen that the electron IT limits the photocatalysis by correlating with the recombination and the hole IT via the dynamic change in electron densities. The numerical simulation of in situ σ shows that the IT of electrons belongs to a thermally activated process that presents a thermal barrier of 0.5 eV. It is considered that this high thermal barrier limits the IT of electrons. It was also seen that the thermal activation of photocatalysis does not relate to that of the electron IT, although the overall photocatalysis is limited by the IT of electrons. Our finding shows that it is an effective way to increase the photocatalytic activity by reducing the thermal barrier of electron IT.

  11. The role of tissue harmonic imaging ultrasound combined with power Doppler ultrasound in the diagnosis of childhood febrile urinary tract infections.

    PubMed

    İlarslan, Nisa Eda Çullas; Fitöz, Ömer Suat; Öztuna, Derya Gökmen; Küçük, Nuriye Özlem; Yalçınkaya, Fatma Fatoş

    2015-06-01

    This study assessed the ability of tissue harmonic imaging ultrasound combined with power Doppler ultrasound in the detection of childhood febrile urinary tract infections in comparison with the gold standard reference method: Tc-99m dimercaptosuccinicacid renal cortical scintigraphy. This prospective study included 60 patients who were hospitalized with a first episode of febrile urinary tract infections. All children were examined with dimercaptosuccinicacid scan and tissue harmonic imaging ultrasound combined with power Doppler ultrasound within the first 3 days of admission. Signs indicative of acute infection were observed in 29 patients according to the results of tissue harmonic imaging ultrasound combined with power Doppler ultrasound while dimercaptosuccinicacid scan revealed abnormal findings in 33 patients. The sensitivity, specificity, positive predictive value and negative predictive value of tissue harmonic imaging combined with power Doppler ultrasound using dimercaptosuccinicacid scintigraphy as the reference method in patients diagnosed with first episode febrile urinary tract infections were calculated as 57.58% (95% confidence interval: 40.81%-72.76%); 62.96% (95% confidence interval: 44.23%-78.47%); 65.52% (95% confidence interval: 52.04%-77%); 54.84% (95% confidence interval: 41.54%-67.52%); respectively. Although current results exhibit inadequate success of power Doppler ultrasound, this practical and radiation-free method may soon be comprise a part of the routine ultrasonographic evaluation of febrile urinary tract infections of childhood if patients are evaluated early and under appropriate sedation.

  12. Papillary reconstruction and guided tissue regeneration for combined periodontal-endodontic lesions caused by palatogingival groove and additional root: a case report.

    PubMed

    Miao, Hui; Chen, Min; Otgonbayar, Tsetsen; Zhang, Sha Sha; Hou, Min Hong; Wu, Zhou; Wang, Yong Lan; Wu, Li Geng

    2015-12-01

    We described a combined periodontal-endodontic lesion, which was caused by a palatogingival groove and an additional root. An interdisciplinary approach involving endodontic therapy, mineral trioxide aggregate (MTA) filling, root resection, guided tissue regeneration, and papillary reconstruction was used for the case. The tooth presents morphologically and functionally normal except tooth discoloration caused by MTA.

  13. The role of tissue harmonic imaging ultrasound combined with power Doppler ultrasound in the diagnosis of childhood febrile urinary tract infections

    PubMed Central

    İlarslan, Nisa Eda Çullas; Fitöz, Ömer Suat; Öztuna, Derya Gökmen; Küçük, Nuriye Özlem; Yalçınkaya, Fatma Fatoş

    2015-01-01

    Aim: This study assessed the ability of tissue harmonic imaging ultrasound combined with power Doppler ultrasound in the detection of childhood febrile urinary tract infections in comparison with the gold standard reference method: Tc-99m dimercaptosuccinicacid renal cortical scintigraphy. Material and Methods: This prospective study included 60 patients who were hospitalized with a first episode of febrile urinary tract infections. All children were examined with dimercaptosuccinicacid scan and tissue harmonic imaging ultrasound combined with power Doppler ultrasound within the first 3 days of admission. Results: Signs indicative of acute infection were observed in 29 patients according to the results of tissue harmonic imaging ultrasound combined with power Doppler ultrasound while dimercaptosuccinicacid scan revealed abnormal findings in 33 patients. The sensitivity, specificity, positive predictive value and negative predictive value of tissue harmonic imaging combined with power Doppler ultrasound using dimercaptosuccinicacid scintigraphy as the reference method in patients diagnosed with first episode febrile urinary tract infections were calculated as 57.58% (95% confidence interval: 40.81%–72.76%); 62.96% (95% confidence interval: 44.23%–78.47%); 65.52% (95% confidence interval: 52.04%–77%); 54.84% (95% confidence interval: 41.54%–67.52%); respectively. Conclusions: Although current results exhibit inadequate success of power Doppler ultrasound, this practical and radiation-free method may soon be comprise a part of the routine ultrasonographic evaluation of febrile urinary tract infections of childhood if patients are evaluated early and under appropriate sedation. PMID:26265892

  14. ASTM lights the way for tissue engineered medical products standards: jump start for combination medical products that restore biological function of human tissues.

    PubMed

    Picciolo, G L; Stocum, D L

    2001-01-01

    Everybody hopes for better health and restoration of impaired bodily function, and now that hope is illuminated by the promise of powerful biological tools that make human cells grow and replace human tissue. ASTM Committee F04 on Medical and Surgical Materials and Devices is taking the lead by defining some of those tools as standards that can be used for the development, production, testing, and regulatory approval of medical products.

  15. Combining in vitro embryotoxicity data with physiologically based kinetic (PBK) modelling to define in vivo dose-response curves for developmental toxicity of phenol in rat and human.

    PubMed

    Strikwold, Marije; Spenkelink, Bert; Woutersen, Ruud A; Rietjens, Ivonne M C M; Punt, Ans

    2013-09-01

    In vitro assays are often used for the hazard characterisation of compounds, but their application for quantitative risk assessment purposes is limited. This is because in vitro assays cannot provide a complete in vivo dose-response curve from which a point of departure (PoD) for risk assessment can be derived, like the no observed adverse effect level (NOAEL) or the 95 % lower confidence limit of the benchmark dose (BMDL). To overcome this constraint, the present study combined in vitro data with a physiologically based kinetic (PBK) model applying reverse dosimetry. To this end, embryotoxicity of phenol was evaluated in vitro using the embryonic stem cell test (EST), revealing a concentration-dependent inhibition of differentiation into beating cardiomyocytes. In addition, a PBK model was developed on the basis of in vitro and in silico data and data available from the literature only. After evaluating the PBK model performance, effective concentrations (ECx) obtained with the EST served as an input for in vivo plasma concentrations in the PBK model. Applying PBK-based reverse dosimetry provided in vivo external effective dose levels (EDx) from which an in vivo dose-response curve and a PoD for risk assessment were derived. The predicted PoD lies within the variation of the NOAELs obtained from in vivo developmental toxicity data from the literature. In conclusion, the present study showed that it was possible to accurately predict a PoD for the risk assessment of phenol using in vitro toxicity data combined with reverse PBK modelling.

  16. Use of combined polarization-sensitive optical coherence tomography and Mueller matrix imaging for the polarimetric characterization of excised biological tissue

    NASA Astrophysics Data System (ADS)

    Chue-Sang, Joseph; Bai, Yuqiang; Stoff, Susan; Straton, David; Ramaswamy, Sharan; Ramella-Roman, Jessica C.

    2016-07-01

    Mueller matrix polarimetry and polarization-sensitive optical coherence tomography (PS-OCT) are two emerging techniques utilized in the assessment of tissue anisotropy. While PS-OCT can provide cross-sectional images of local tissue birefringence through its polarimetric sensitivity, Mueller matrix polarimetry can be used to measure bulk polarimetric properties such as depolarization, diattenuation, and retardance. To this day true quantification of PS-OCT data can be elusive, partly due to the reliance on inverse models for the characterization of tissue birefringence and the influence of instrumentation noise. Similarly for Mueller matrix polarimetry, calculation of retardance or depolarization may be influenced by tissue heterogeneities that could be monitored with PS-OCT. Here, we propose an instrument that combines Mueller matrix polarimetry and PS-OCT. Through the co-registration of the two systems, we aim at achieving a better understanding of both modalities.

  17. Spatial mapping of metals in tissue-sections using combination of mass-spectrometry and histology through image registration

    NASA Astrophysics Data System (ADS)

    Anyz, Jiri; Vyslouzilova, Lenka; Vaculovic, Tomas; Tvrdonova, Michaela; Kanicky, Viktor; Haase, Hajo; Horak, Vratislav; Stepankova, Olga; Heger, Zbynek; Adam, Vojtech

    2017-01-01

    We describe a new procedure for the parallel mapping of selected metals in histologically characterized tissue samples. Mapping is achieved via image registration of digital data obtained from two neighbouring cryosections by scanning the first as a histological sample and subjecting the second to laser ablation inductively coupled plasma mass spectrometry. This computer supported procedure enables determination of the distribution and content of metals of interest directly in the chosen histological zones and represents a substantial improvement over the standard approach, which determines these values in tissue homogenates or whole tissue sections. The potential of the described procedure was demonstrated in a pilot study that analysed Zn and Cu levels in successive development stages of pig melanoma tissue using MeLiM (Melanoma-bearing-Libechov-Minipig) model. We anticipate that the procedure could be useful for a complex understanding of the role that the spatial distribution of metals plays within tissues affected by pathological states including cancer.

  18. Spatial mapping of metals in tissue-sections using combination of mass-spectrometry and histology through image registration

    PubMed Central

    Anyz, Jiri; Vyslouzilova, Lenka; Vaculovic, Tomas; Tvrdonova, Michaela; Kanicky, Viktor; Haase, Hajo; Horak, Vratislav; Stepankova, Olga; Heger, Zbynek; Adam, Vojtech

    2017-01-01

    We describe a new procedure for the parallel mapping of selected metals in histologically characterized tissue samples. Mapping is achieved via image registration of digital data obtained from two neighbouring cryosections by scanning the first as a histological sample and subjecting the second to laser ablation inductively coupled plasma mass spectrometry. This computer supported procedure enables determination of the distribution and content of metals of interest directly in the chosen histological zones and represents a substantial improvement over the standard approach, which determines these values in tissue homogenates or whole tissue sections. The potential of the described procedure was demonstrated in a pilot study that analysed Zn and Cu levels in successive development stages of pig melanoma tissue using MeLiM (Melanoma-bearing-Libechov-Minipig) model. We anticipate that the procedure could be useful for a complex understanding of the role that the spatial distribution of metals plays within tissues affected by pathological states including cancer. PMID:28071735

  19. Application of SPECT/CT imaging system and radiochemical analysis for investigation of blood kinetics and tissue distribution of radiolabeled plumbagin in healthy and Plasmodium berghei-infected mice.

    PubMed

    Sumsakul, W; Karbwang, J; Na-Bangchang, K

    2016-02-01

    Plumbagin is a derivative of napthoquinone which is isolated from the roots of plants in several families. These compound exhibits a wide range of biological and pharmacological activities including antimalarial, antibacterial, antifungal, and anticancer activities. The aim of the study was to investigate blood kinetics and tissue distribution of plumbagin in healthy and Plasmodium berghei-infected mice using Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) and radiochemical analysis by gamma counter. Plumbagin was labeled with (99m)technetium and the reducing agent stannous chloride dihydrate (50 μg/ml) at pH 6.5. Blood kinetics and tissue distribution of the radiolabeled plumbagin were investigated in healthy and P. berghei-infected mice (2 males and 2 females for each experimental group). In vitro and in vivo stability of plumbagin complex suggested satisfactory stability profiles of (99m)Tc-plumbagin complex in plasma and normal saline (92.21-95.47%) within 24 h. Significant difference in blood kinetics parameters (Cmax, AUC, t1/2, MRT, Vd, and CL) were observed between P. berghei-infected and healthy mice. The labeled complex distributed to all organs of both healthy and infected mice but with high intensity in liver, followed by lung, stomach, large intestine and kidney. Accumulation in spleen was markedly noticeable in the infected mice. Plumbagin-labeled complex was rapidly cleared from blood and major routes of excretion were hepatobiliary and pulmonary routes. In P. berghei-infected mice, t1/2 was significantly decreased, while Vd and CL were increased compared with healthy mice. Result suggests that malaria disease state influenced the pharmacokinetics and disposition of plumbagin. SPECT/CT imaging with radiolabeled (99m)Tc is a viable non-invasive technique that can be applied for investigation of kinetics and biodistribution of plumbagin in animal models.

  20. Combined effects of heat, nisin and acidification on the inactivation of Clostridium sporogenes spores in carrot-alginate particles: from kinetics to process validation.

    PubMed

    Naim, F; Zareifard, M R; Zhu, S; Huizing, R H; Grabowski, S; Marcotte, M

    2008-10-01

    Combined effects of mild temperatures, acidification and nisin on the thermal resistance of Clostridium sporogenes ATCC 11437 spores were assessed. Inoculated carrot-alginate particles were used as a solid-food model for the validation of the spore inactivation during the flow of a solid-liquid food system through the holding tube of an aseptic processing unit. Inactivation kinetics was studied in a water bath with the spores inoculated into carrot-alginate particles and in Sorensen's phosphate buffer. For temperatures of 70-90 degrees C, D-values in the buffer were 24.9-5.7 min, much lower than those evaluated for the particles (115.1-22.2 min). Statistical analyses showed significant synergistic effects of temperature and pH on spore inactivation for both media. Acidification reduced the heat resistance of the spores by reducing the D-values. Nisin was not significantly effective at the lower concentrations (up to 750 IU/g). The combination of 90 degrees C, pH: 4.5 and 500IU/g nisin resulted in a ten-fold decrease of the D-value for spores inoculated in the particles (from 111.1 to 10.6 min). Microbial validation tests were conducted using a pilot-scale aseptic processing unit with a mixture of carrot cubes (10%) and carrier liquid of 2%-carboxymethylcellulose solution (90%). Spore-inoculated carrot-alginate particles (initial counts of 106 CFU/g, obtained after come-up-time pre-heat) with pH 3.5 and 2000 IU/g nisin were processed at 90 degrees C in the aseptic processing unit. Microbial analysis showed no spore survivors in the particles after passing through the holding tube (5.2-6.0 min of residence time). The proposed combination of these hurdles significantly enhanced the spore inactivation rate (D(90)=1.17 min) as compared to that for thermal treatment only (D(90)=19.6 min).

  1. Guided growth of the trochanteric apophysis combined with soft tissue release for Legg-Calve-Perthes disease.

    PubMed

    Stevens, Peter M; Anderson, Lucas A; Gililland, Jeremy M; Novais, Eduardo

    2014-04-01

    During the initial fragmentation stage of Perthes disease, the principle focus is to achieve containment of the femoral head within the acetabulum. Whether by bracing, abduction casts, femoral and/or pelvic osteotomy, the goals are to maximize the range of hip motion and to avoid incongruity, hoping to avert subsequent femoro-acetabular impingement or hinge abduction. A more subtle and insidious manifestation of the disease relates to growth disturbance involving the femoral neck. We have chosen to tether the greater trochanteric physis, combined with a medial soft tissue release, as part of our non-osteotomy management strategy for select children with progressive symptomatology and related radiographic changes. In addition to providing containment, we feel that this strategy addresses potential long-range issues pertaining to limb length and abductor mechanics, while avoiding iatrogenic varus deformity caused by osteotomy. This is a retrospective review of 12 patients (nine boys, three girls), average age 7.3 years old (range 5.3-9.7), who underwent non-osteotomy surgery for Perthes disease. An eight-plate was applied to the greater trochanteric apophysis at the time of arthrogram, open adductor and iliopsoas tenotomy, and Petrie cast application. We compared clinical and radiographic findings at the outset to those at an average follow-up of 49 months (range 14-78 months). Six plates were subsequently removed; the others remain in situ. Eleven of twelve patients experienced improvement in pain, and alleviation of limp and Trendelenburg sign at latest follow-up. The majority had improved or maintained range of motion and prevention of trochanteric impingement demonstrated by near normalization of abduction. Neck-shaft angles, Shenton's line, extrusion index, center edge angles and trochanteric height did not change significantly. One patient underwent subsequent trochanteric distalization and no other patients have undergone subsequent femoral or

  2. Kinetics of a putative hypoxic tissue marker, Technetium-99m-nitroimidazole (BMS181321), in normoxic, hypoxic, ischemic and stunned myocardium

    SciTech Connect

    Kusuoka, Hideo; Hashimoto, Katsuji; Fukuchi, Kazuki

    1994-08-01

    This study focused on the kinetics of the newly developed {sup 99m}TTc-nitroimidazole, propyleneamine oxime-1,2-nitroimidazole (BMS181321) in the different setting of myocardial perfusion states and oxygenation levels, and compared the kinetics of BMS181321 with those of other technetium analogues. The kinetics of BMS181321 were evaluated in isolated perfused rat hearts. Technetium-99m-hexamethyl propyleneamine oxime (HMPAO) and a non-nitroimidazole-containing analogue of BMS 181321 (6-methyl propyleneamine oxime; PAO-6-Me) were used to compare their kinetics with those of BMS181321. BMS181321 cleared quickly from normoxic hearts and the retention in the myocardium 10 min after injection was 0.84% {plus_minus} 0.04% ID/g wet wt (mean {plus_minus} s.e.m.). In contrast, BMS181321 was retained after reperfusion when it was injected before ischemia; the uptake in the myocardium 10 min after reperfusion was significantly greater than in controls (23.9% {plus_minus} 3.9%ID/g wt, p<0.05). These results indicate that {sup 99m}Tc-BMS181321 is well trapped in ischemic myocardium and moderately trapped in hypoxic myocardium, but washed out quickly in stunned myocardium. The residence time influences the amount retained. 14 refs., 7 figs., 1 tab.

  3. Real-Time Assessment of Tissue Hypoxia In Vivo with Combined Photoacoustics and High-Frequency Ultrasound

    PubMed Central

    Gerling, Marco; Zhao, Ying; Nania, Salvatore; Norberg, K. Jessica; Verbeke, Caroline S.; Englert, Benjamin; Kuiper, Raoul V.; Bergström, Åsa; Hassan, Moustapha; Neesse, Albrecht; Löhr, J. Matthias; Heuchel, Rainer L.

    2014-01-01

    Purpose: In preclinical cancer studies, non-invasive functional imaging has become an important tool to assess tumor development and therapeutic effects. Tumor hypoxia is closely associated with tumor aggressiveness and is therefore a key parameter to be monitored. Recently, photoacoustic (PA) imaging with inherently co-registered high-frequency ultrasound (US) has reached preclinical applicability, allowing parallel collection of anatomical and functional information. Dual-wavelength PA imaging can be used to quantify tissue oxygen saturation based on the absorbance spectrum differences between hemoglobin and deoxyhemoglobin. Experimental Design: A new bi-modal PA/US system for small animal imaging was employed to test feasibility and reliability of dual-wavelength PA for measuring relative tissue oxygenation. Murine models of pancreatic and colon cancer were imaged, and differences in tissue oxygenation were compared to immunohistochemistry for hypoxia in the corresponding tissue regions. Results: Functional studies proved feasibility and reliability of oxygenation detection in murine tissue in vivo. Tumor models exhibited different levels of hypoxia in localized regions, which positively correlated with immunohistochemical staining for hypoxia. Contrast-enhanced imaging yielded complementary information on tissue perfusion using the same system. Conclusion: Bimodal PA/US imaging can be utilized to reliably detect hypoxic tumor regions in murine tumor models, thus providing the possibility to collect anatomical and functional information on tumor growth and treatment response live in longitudinal preclinical studies. PMID:24723982

  4. Intentional reim plantation of a tooth with severe periodontal involvement using enamel matrix derivative in combination with guided tissue regeneration and bone grafting: a case report.

    PubMed

    Sugai, Kenji; Sato, Shuichi; Suzuki, Kuniharu; Ito, Koichi

    2008-02-01

    This case involved the intentional reimplantation of a tooth with severe periodontal involvement using regenerative therapies. The maxillary left central incisor was intentionally extracted, enamel matrix derivative (EMD) was applied, and the tooth was repositioned accurately. The bone defect was filled with a xenograft and a demineralized freeze-dried bone allograft, and a guided tissue regeneration membrane was adapted over the site. After 5 years, a reduction in probing depth and a gain in clinical attachment were observed. Conventional radiographs and cone-beam computerized tomographs showed hard tissue improvement. Favorable clinical results were obtained with reimplantation with applied EMD, combined with regenerative therapies, for treating a tooth with severe periodontal involvement.

  5. Successful treatment of skin and soft tissue infection due to carbapenem-resistant Acinetobacter baumannii by ampicillin-sulbactam and meropenem combination therapy.

    PubMed

    Hiraki, Yoichi; Yoshida, Mayumi; Masuda, Yoko; Inoue, Daisuke; Tsuji, Yasuhiro; Kamimura, Hidetoshi; Karube, Yoshiharu; Takaki, Kazutaka; Kawano, Fumio

    2013-12-01

    In recent years, carbapenem-resistant Acinetobacter baumannii infections have been responsible for outbreaks in medical facilities. A 35-year-old Japanese woman developed a skin and soft tissue infection due to carbapenem-resistant A. baumannii. The isolate was resistant to antibiotics other than ampicillin-sulbactam and colistin, suggesting drug resistance due to carbapenemase production by OXA-23. We selected a combination therapy consisting of intravenous ampicillin-sulbactam and meropenem. No changes were observed in aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, or serum creatinine during therapy, and carbapenem-resistant A. baumannii was not detected in wound exudates 3 days after therapy initiation. In our patient's case, combination therapy with ampicillin-sulbactam and meropenem was successful. Thus, combination therapy with ampicillin-sulbactam and meropenem is effective against skin and soft tissue infection due to carbapenem-resistant A. baumannii. Combination therapy with intravenous ampicillin-sulbactam and meropenem may be an option for skin and soft tissue infections due to carbapenem-resistant A. baumannii.

  6. The Combination of Chemical Fixation Procedures with High Pressure Freezing and Freeze Substitution Preserves Highly Labile Tissue Ultrastructure for Electron Tomography Applications

    PubMed Central

    Sosinsky, Gina E.; Crum, John; Jones, Ying Z.; Lanman, Jason; Smarr, Benjamin; Terada, Masako; Martone, Maryann E.; Deerinck, Thomas J.; Johnson, John E.; Ellisman, Mark H.

    2008-01-01

    The emergence of electron tomography as a tool for three dimensional structure determination of cells and tissues has brought its own challenges for the preparation of thick sections. High pressure freezing in combination with freeze substitution provides the best method for obtaining the largest volume of well-preserved tissue. However, for deeply embedded, heterogeneous, labile tissues needing careful dissection, such as brain, the damage due to anoxia and excision before cryofixation is significant. We previously demonstrated that chemical fixation prior to high pressure freezing preserves fragile tissues and produces superior tomographic reconstructions compared to equivalent tissue preserved by chemical fixation alone. Here, we provide further characterization of the technique, comparing the ultrastructure of Flock House Virus infected DL1 insect cells that were 1) high pressure frozen without fixation, 2) high pressure frozen following fixation, and 3) conventionally prepared with aldehyde fixatives. Aldehyde fixation prior to freezing produces ultrastructural preservation superior to that obtained through chemical fixation alone that is close to that obtained when cells are fast frozen without fixation. We demonstrate using a variety of nervous system tissues, including neurons that were injected with a fluorescent dye and then photooxidized, that this technique provides excellent preservation compared to chemical fixation alone and can be extended to selectively stained material where cryofixation is impractical. PMID:17962040

  7. Kinetic network study of the diversity and temperature dependence of Trp-Cage folding pathways: combining transition path theory with stochastic simulations.

    PubMed

    Zheng, Weihua; Gallicchio, Emilio; Deng, Nanjie; Andrec, Michael; Levy, Ronald M

    2011-02-17

    We present a new approach to study a multitude of folding pathways and different folding mechanisms for the 20-residue mini-protein Trp-Cage using the combined power of replica exchange molecular dynamics (REMD) simulations for conformational sampling, transition path theory (TPT) for constructing folding pathways, and stochastic simulations for sampling the pathways in a high dimensional structure space. REMD simulations of Trp-Cage with 16 replicas at temperatures between 270 and 566 K are carried out with an all-atom force field (OPLSAA) and an implicit solvent model (AGBNP). The conformations sampled from all temperatures are collected. They form a discretized state space that can be used to model the folding process. The equilibrium population for each state at a target temperature can be calculated using the weighted-histogram-analysis method (WHAM). By connecting states with similar structures and creating edges satisfying detailed balance conditions, we construct a kinetic network that preserves the equilibrium population distribution of the state space. After defining the folded and unfolded macrostates, committor probabilities (P(fold)) are calculated by solving a set of linear equations for each node in the network and pathways are extracted together with their fluxes using the TPT algorithm. By clustering the pathways into folding "tubes", a more physically meaningful picture of the diversity of folding routes emerges. Stochastic simulations are carried out on the network, and a procedure is developed to project sampled trajectories onto the folding tubes. The fluxes through the folding tubes calculated from the stochastic trajectories are in good agreement with the corresponding values obtained from the TPT analysis. The temperature dependence of the ensemble of Trp-Cage folding pathways is investigated. Above the folding temperature, a large number of diverse folding pathways with comparable fluxes flood the energy landscape. At low temperature

  8. Modeling the Combined Effect of Pressure and Mild Heat on the Inactivation Kinetics of Escherichia coli, Listeria innocua, and Staphylococcus aureus in Black Tiger Shrimp (Penaeus monodon)

    PubMed Central

    Kaur, Barjinder P.; Rao, P. Srinivasa

    2017-01-01

    The high-pressure inactivation of Escherichia coli, Listeria innocua, and Staphylococcus aureus was studied in black tiger shrimp (Penaeus monodon). The processing parameters examined included pressure (300 to 600 MPa) and temperature (30 to 50°C). In addition, the pressure-hold period (0 to 15 min) was investigated, thus allowing both single-pulse pressure effects (i.e., zero holding time) and pressure-hold effects to be explored. E. coli was found to be the most sensitive strain to single-pulse pressure, followed by L. innocua and lastly S. aureus. Higher pressures and temperatures resulted in higher destruction rates, and the value of the shape parameter (β′) accounted for the downward concavity (β′ > 1) of the survival curves. A simplified Weibull model described the non-linearity of the survival curves for the changes in the pressure-hold period well, and it was comparable to the original Weibull model. The regression coefficients (R2), root mean square error (RMSE), accuracy factor (Af), bias factor (Bf), and residual plots suggested that using linear models to represent the data was not as appropriate as using non-linear models. However, linear models produced good fits for some pressure–temperature combinations. Analogous to their use in thermal death kinetics, activation volume (Va) and activation energy (Ea) can be used to describe the pressure and temperature dependencies of the scale parameter (δ, min), respectively. The Va and Ea values showed that high pressure and temperaturefavored the inactivation process, and S. aureus was the most baro-resistant pathogen. PMID:28790979

  9. Combined pressure and cosolvent effects on enzyme activity - a high-pressure stopped-flow kinetic study on α-chymotrypsin.

    PubMed

    Luong, Trung Quan; Winter, Roland

    2015-09-21

    We investigated the combined effects of cosolvents and pressure on the hydrolysis of a model peptide catalysed by α-chymotrypsin. The enzymatic activity was measured in the pressure range from 0.1 to 200 MPa using a high-pressure stopped-flow systems with 10 ms time resolution. A kosmotropic (trimethalymine-N-oxide, TMAO) and chaotropic (urea) cosolvent and mixtures thereof were used as cosolvents. High pressure enhances the hydrolysis rate as a consequence of a negative activation volume, ΔV(#), which, depending on the cosolvent system, amounts to -2 to -4 mL mol(-1). A more negative activation volume can be explained by a smaller compression of the ES complex relative to the transition state. Kinetic constants, such as kcat and the Michaelis constant KM, were determined for all solution conditions as a function of pressure. With increasing pressure, kcat increases by about 35% and its pressure dependence by a factor of 1.9 upon addition of 2 M urea, whereas 1 M TMAO has no significant effect on kcat and its pressure dependence. Similarly, KM increases upon addition of urea 6-fold. Addition of TMAO compensates the urea-effect on kcat and KM to some extent. The maximum rate of the enzymatic reaction increases with increasing pressure in all solutions except in the TMAO : urea 1 : 2 mixture, where, remarkably, pressure is found to have no effect on the rate of the enzymatic reaction anymore. Our data clearly show that compatible solutes can easily override deleterious effects of harsh environmental conditions, such as high hydrostatic pressures in the 100 MPa range, which is the maximum pressure encountered in the deep biosphere on Earth.

  10. Enzymatic antioxidant defence mechanism in rat intestinal tissue is changed after ischemia–reperfusion. Effects of an allopurinol plus antioxidant combination

    PubMed Central

    Kaçmaz, Murat; Öztürk, H. Serdar; Karaayvaz, Muammer; Güven, Cengiz; Durak, Ílker

    1999-01-01

    Objectives To establish the antioxidant status of rat intestinal tissues after ischemia–reperfusion and to determine if pretreatment with an allopurinol and antioxidant vitamin combination gives any protection against mucosal injury. Experimental animals Twenty rats were divided into 4 groups of 5 animals each. Methods Group 1 (control) rats were not subjected to ischemia–reperfusion and received no allopurinol plus vitamin combination; group 2 rats received vitamins C (200 mg/kg) and E (100 mg/kg) and allopurinol (50 mg/kg) combination daily for 3 days preoperatively; group 3 rats were subjected to ischemia–reperfusion only; and group 4 rats were subjected to ischemia–reperfusion and received the vitamin and allopurinol combination. Main outcome measures Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) enzymes, the level of thiobarbituric acid-reagent substances (TBARS) and histologic grading of tissue samples. Results SOD and GSH-Px activities were decreased, but the CAT activity and TBARS level increased. Pretreatment of the rats with the allopurinol-vitamin C-vitamin E combination did not have any significant effect on the enzyme activities. However, it resulted in important reductions in the TBARS tissue levels. Histologic investigation revealed significant mucosal injury in group 3 rats compared with group 4 rats (mean [and standard deviation] for grading, 4.6 [0.5] versus 1.8 [0.4]). Conclusions The enzymatic antioxidant defence system was significantly changed after ischemia–reperfusion and intestinal tissue was exposed to increased oxidant stress, the results of which were peroxidation of some cellular structures and increased concentrations of oxidative products. Although antioxidant treatment did not drastically affect the enzyme activities or afford complete protection of cellular structures against deformation, it apparently could eliminate oxygen radicals and prevent peroxidative reactions. PMID

  11. Kinetic Atom.

    ERIC Educational Resources Information Center

    Wilson, David B.

    1981-01-01

    Surveys the research of scientists like Joule, Kelvin, Maxwell, Clausius, and Boltzmann as it comments on the basic conceptual issues involved in the development of a more precise kinetic theory and the idea of a kinetic atom. (Author/SK)

  12. Kinetic Atom.

    ERIC Educational Resources Information Center

    Wilson, David B.

    1981-01-01

    Surveys the research of scientists like Joule, Kelvin, Maxwell, Clausius, and Boltzmann as it comments on the basic conceptual issues involved in the development of a more precise kinetic theory and the idea of a kinetic atom. (Author/SK)

  13. Combined effects of insulin treatment and adipose tissue-specific agouti expression on the development of obesity.

    PubMed

    Mynatt, R L; Miltenberger, R J; Klebig, M L; Zemel, M B; Wilkinson, J E; Wilkinson, W O; Woychik, R P

    1997-02-04

    The agouti gene product is a secreted protein that acts in a paracrine manner to regulate coat color in mammals. Several dominant mutations at the agouti locus in mice cause the ectopic, ubiquitous expression of agouti, resulting in a condition similar to adult-onset obesity and non-insulin-dependent diabetes mellitus. The human agouti protein is 85% homologous to mouse agouti; however, unlike the mouse agouti gene, human agouti is normally expressed in adipose tissue. To address whether expression of agouti in human adipose tissue is physiologically relevant, transgenic mice were generated that express agouti in adipose tissue. Similar to most humans, these mice do not become obese or diabetic. However, we found that daily insulin injections significantly increased weight gain in the transgenic lines expressing agouti in adipose tissue, but not in nontransgenic mice. These results suggest that insulin triggers the onset of obesity and that agouti expression in adipose tissue potentiates this effect. Accordingly, the investigation of agouti's role in obesity and non-insulin-dependent diabetes mellitus in mice holds significant promise for understanding the pathophysiology of human obesity.

  14. Detection and grading of prostate cancer using temporal enhanced ultrasound: combining deep neural networks and tissue mimicking simulations.

    PubMed

    Azizi, Shekoofeh; Bayat, Sharareh; Yan, Pingkun; Tahmasebi, Amir; Nir, Guy; Kwak, Jin Tae; Xu, Sheng; Wilson, Storey; Iczkowski, Kenneth A; Lucia, M Scott; Goldenberg, Larry; Salcudean, Septimiu E; Pinto, Peter A; Wood, Bradford; Abolmaesumi, Purang; Mousavi, Parvin

    2017-08-01

    PURPOSE  : Temporal Enhanced Ultrasound (TeUS) has been proposed as a new paradigm for tissue characterization based on a sequence of ultrasound radio frequency (RF) data. We previously used TeUS to successfully address the problem of prostate cancer detection in the fusion biopsies. METHODS  : In this paper, we use TeUS to address the problem of grading prostate cancer in a clinical study of 197 biopsy cores from 132 patients. Our method involves capturing high-level latent features of TeUS with a deep learning approach followed by distribution learning to cluster aggressive cancer in a biopsy core. In this hypothesis-generating study, we utilize deep learning based feature visualization as a means to obtain insight into the physical phenomenon governing the interaction of temporal ultrasound with tissue. RESULTS  : Based on the evidence derived from our feature visualization, and the structure of tissue from digital pathology, we build a simulation framework for studying the physical phenomenon underlying TeUS-based tissue characterization. CONCLUSION  : Results from simulation and feature visualization corroborated with the hypothesis that micro-vibrations of tissue microstructure, captured by low-frequency spectral features of TeUS, can be used for detection of prostate cancer.

  15. Enzyme Kinetics.

    ERIC Educational Resources Information Center

    Moe, Owen; Cornelius, Richard

    1988-01-01

    Conveys an appreciation of enzyme kinetic analysis by using a practical and intuitive approach. Discusses enzyme assays, kinetic models and rate laws, the kinetic constants (V, velocity, and Km, Michaels constant), evaluation of V and Km from experimental data, and enzyme inhibition. (CW)

  16. Enzyme Kinetics.

    ERIC Educational Resources Information Center

    Moe, Owen; Cornelius, Richard

    1988-01-01

    Conveys an appreciation of enzyme kinetic analysis by using a practical and intuitive approach. Discusses enzyme assays, kinetic models and rate laws, the kinetic constants (V, velocity, and Km, Michaels constant), evaluation of V and Km from experimental data, and enzyme inhibition. (CW)

  17. Combination of a fillet flap, free tissue transfer, and autologous tissue grafts in pelvic reconstruction following retroperitoneal sarcoma: a case report.

    PubMed

    Saksena, Anshuman; Aho, Johnathon; Winocour, Sebastian; Maricevich, Renata; Senchenkov, Alex; Rose, Peter; Leibovich, Bradley; Zietlow, Scott; Saint-Cyr, Michel

    2015-05-01

    The resection of large pelvic tumors is challenging due to their infiltrative nature into multiple structures and organ systems. In this report, we describe the use of multiple vascularized and nonvascularized spare parts to reconstruct a pelvic defect in a patient with a uniquely large pelvic sarcoma invading the spinal canal. A 39-year-old Caucasian female who presented with a large retroperitoneal sarcoma where the tumor encased the left ureter, kidney, colon, and external iliac vessels and invaded the L3-S1 vertebral bodies. An extensive hemipelvectomy and reconstruction was performed over two days. A free thigh and leg fillet flap together with ipsilateral fibula flap, based on the superficial femoral artery and venae comitantes, was used for spinal reinforcement as well as abdominal and pelvic wall reconstruction. The postoperative course was uneventful without complications, no flap compromise or wound healing problems. After a follow-up period of 4 months, the patient had no complications and returned to activities of daily living with mild limitations. The success of this flap procedure shows the practicality and usefulness of using the full spectrum of tissue transfer for the purposes of a large pelvic reconstruction.

  18. Multimodal optical setup based on spectrometer and cameras combination for biological tissue characterization with spatially modulated illumination

    NASA Astrophysics Data System (ADS)

    Baruch, Daniel; Abookasis, David

    2017-04-01

    The application of optical techniques as tools for biomedical research has generated substantial interest for the ability of such methodologies to simultaneously measure biochemical and morphological parameters of tissue. Ongoing optimization of optical techniques may introduce such tools as alternative or complementary to conventional methodologies. The common approach shared by current optical techniques lies in the independent acquisition of tissue's optical properties (i.e., absorption and reduced scattering coefficients) from reflected or transmitted light. Such optical parameters, in turn, provide detailed information regarding both the concentrations of clinically relevant chromophores and macroscopic structural variations in tissue. We couple a noncontact optical setup with a simple analysis algorithm to obtain absorption and scattering coefficients of biological samples under test. Technically, a portable picoprojector projects serial sinusoidal patterns at low and high spatial frequencies, while a spectrometer and two independent CCD cameras simultaneously acquire the reflected diffuse light through a single spectrometer and two separate CCD cameras having different bandpass filters at nonisosbestic and isosbestic wavelengths in front of each. This configuration fills the gaps in each other's capabilities for acquiring optical properties of tissue at high spectral and spatial resolution. Experiments were performed on both tissue-mimicking phantoms as well as hands of healthy human volunteers to quantify their optical properties as proof of concept for the present technique. In a separate experiment, we derived the optical properties of the hand skin from the measured diffuse reflectance, based on a recently developed camera model. Additionally, oxygen saturation levels of tissue measured by the system were found to agree well with reference values. Taken together, the present results demonstrate the potential of this integrated setup for diagnostic and

  19. Assessment of bleeding propensity in non-human primates by combination of selective tissue factor/VIIa inhibition and aspirin compared to warfarin and aspirin treatment.

    PubMed

    Salyers, Anita K; Szalony, James A; Suleymanov, Osman D; Parlow, John J; Wood, Rhonda S; South, Michael S; Nicholson, Nancy S

    2004-02-01

    This study in non-human primates was designed to evaluate the bleeding propensity of a selective, small molecule inhibitor of tissue factor (TF)/VIIa in combination with acetylsalicylic acid (ASA) in comparison to the combination of ASA and warfarin. Bleeding time was increased by ASA but was not prolonged further by the addition of the TF/VIIa inhibitor, PHA-927, at doses that elevated the prothrombin time to 8-fold. In contrast, bleeding time was prolonged by warfarin alone and further exacerbated by the presence of ASA. Acute blood loss at the bleeding site, while not significantly increased by either warfarin or PHA-927, was increased substantially in several individuals treated with a combination of warfarin and ASA but not by the combination of TF/VIIa inhibitor and ASA. These data predict that TF/VIIa inhibition, in the presence of chronic aspirin therapy in patients with cardiovascular risk factors, will be a safe therapy for thrombotic disorders.

  20. Chemical Kinetics Database

    National Institute of Standards and Technology Data Gateway

    SRD 17 NIST Chemical Kinetics Database (Web, free access)   The NIST Chemical Kinetics Database includes essentially all reported kinetics results for thermal gas-phase chemical reactions. The database is designed to be searched for kinetics data based on the specific reactants involved, for reactions resulting in specified products, for all the reactions of a particular species, or for various combinations of these. In addition, the bibliography can be searched by author name or combination of names. The database contains in excess of 38,000 separate reaction records for over 11,700 distinct reactant pairs. These data have been abstracted from over 12,000 papers with literature coverage through early 2000.

  1. Arsenic-Induced Antioxidant Depletion, Oxidative DNA Breakage, and Tissue Damages are Prevented by the Combined Action of Folate and Vitamin B12.

    PubMed

    Acharyya, Nirmallya; Deb, Bimal; Chattopadhyay, Sandip; Maiti, Smarajit

    2015-11-01

    Arsenic is a grade I human carcinogen. It acts by disrupting one-carbon (1C) metabolism and cellular methyl (-CH3) pool. The -CH3 group helps in arsenic disposition and detoxification of the biological systems. Vitamin B12 and folate, the key promoters of 1C metabolism were tested recently (daily 0.07 and 4.0 μg, respectively/100 g b.w. of rat for 28 days) to evaluate their combined efficacy in the protection from mutagenic DNA-breakage and tissue damages. The selected tissues like intestine (first-pass site), liver (major xenobiotic metabolizer) and lung (major arsenic accumulator) were collected from arsenic-ingested (0.6 ppm/same schedule) female rats. The hemo-toxicity and liver and kidney functions were monitored. Our earlier studies on arsenic-exposed humans can correlate carcinogenesis with DNA damage. Here, we demonstrate that the supplementation of physiological/therapeutic dose of vitamin B12 and folate protected the rodents significantly from arsenic-induced DNA damage (DNA fragmentation and comet assay) and hepatic and renal tissue degeneration (histo-architecture, HE staining). The level of arsenic-induced free-radical products (TBARS and conjugated diene) was significantly declined by the restored actions of several antioxidants viz. urate, thiol, catalase, xanthine oxidase, lactoperoxidase, and superoxide dismutase in the tissues of vitamin-supplemented group. The alkaline phosphatase, transaminases, urea and creatinine (hepatic and kidney toxicity marker), and lactate dehydrogenase (tissue degeneration marker) were significantly impaired in the arsenic-fed group. But a significant protection was evident in the vitamin-supplemented group. In conclusion, the combined action of folate and B12 results in the restitution in the 1C metabolic pathway and cellular methyl pool. The cumulative outcome from the enhanced arsenic methylation and antioxidative capacity was protective against arsenic induced mutagenic DNA breakages and tissue damages.

  2. Effects of tissue plasminogen activator and annexin A2 combination therapy on long-term neurological outcomes of rat focal embolic stroke

    PubMed Central

    Wang, Xiaoshu; Fan, Xiang; Yu, Zhanyang; Liao, Zhengbu; Zhao, Jianhua; Mandeville, Emiri; Guo, Shuzhen; Lo, Eng H.; Wang, Xiaoying

    2014-01-01

    Background and Purpose Tissue type plasminogen activator (tPA) in combination with recombinant annexin A2 (rA2) is known to reduce acute brain damage after focal ischemia. Here, we ask whether tPA plus rA2 combination therapy can lead to sustained long term neurological improvements as well. Methods We compared the effects of intravenous high-dose tPA alone (10mg/kg) versus a combination of low-dose tPA (5mg/kg) plus 10 mg/kg rA2 in a model of focal embolic cerebral ischemia in rats. All rats were treated at 3 hours after embolization. Brain tissue and neurological outcomes were assessed at 1 month. Surrogate biomarkers for endogenous neurovascular remodeling in peri-infarct area were analyzed by immunohistochemistry. Results Compared to high-dose tPA alone, low-dose tPA plus rA2 significantly decreased infarction and improved neurological function at 1 month post-stroke. In peri-infarct areas, tPA-plus-rA2 combination therapy also significantly augmented microvessel density, VEGF and synaptophysin expression. Conclusions Compared to conventional high-dose tPA alone, combination low-dose tPA plus rA2 therapy may provide a safe and effective way to improve long term neurological outcomes after stroke. PMID:24368559

  3. The interaction between a combined knitted silk scaffold and microporous silk sponge with human mesenchymal stem cells for ligament tissue engineering.

    PubMed

    Liu, Haifeng; Fan, Hongbin; Wang, Yue; Toh, Siew Lok; Goh, James C H

    2008-02-01

    Cell seeding on knitted scaffolds often require a gel system, which was found to be practically unsuitable for anterior cruciate ligament (ACL) reconstruction as the cell-gel composite often gets dislodged from the scaffold in the in vivo dynamic situations. In order to solve this problem, we fabricated this combined silk scaffold with weblike microporous silk sponges formed in the openings of a knitted silk scaffold and subsequently combined with adult human bone marrow-derived mesenchymal stem cells (hMSCs) for in vitro ligament tissue engineering. Human MSCs adhered and grew well on the combined silk scaffolds. Moreover, in comparison with the knitted silk scaffolds seeded with hMSCs in fibroin gel the cellular function was more actively exhibited on the combined silk scaffolds, as evident by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for ligament-related gene markers (e.g., type I, III collagen and tenascin-C), immunohistochemical and western blot evaluations of ligament-related extracellular matrix (ECM) components. While the knitted structure holds the microporous silk sponges together and provides the structural strength of the combined silk scaffold, the microporous structure of the silk sponges mimic the ECM which consequently promotes cell proliferation, function, and differentiation. This feature overcomes the limitation of knitted scaffold for ligament tissue engineering application.

  4. Kinetics of naphthalene metabolism in target and non-target tissues of rodents and in nasal and airway microsomes from the Rhesus monkey

    SciTech Connect

    Buckpitt, Alan; Morin, Dexter; Murphy, Shannon; Edwards, Patricia; Van Winkle, Laura

    2013-07-15

    Naphthalene produces species and cell selective injury to respiratory tract epithelial cells of rodents. In these studies we determined the apparent K{sub m}, V{sub max}, and catalytic efficiency (V{sub max}/K{sub m}) for naphthalene metabolism in microsomal preparations from subcompartments of the respiratory tract of rodents and non-human primates. In tissues with high substrate turnover, major metabolites were derived directly from naphthalene oxide with smaller amounts from conjugates of diol epoxide, diepoxide, and 1,2- and 1,4-naphthoquinones. In some tissues, different enzymes with dissimilar K{sub m} and V{sub max} appeared to metabolize naphthalene. The rank order of V{sub max} (rat olfactory epithelium > mouse olfactory epithelium > murine airways ≫ rat airways) correlated well with tissue susceptibility to naphthalene. The V{sub max} in monkey alveolar subcompartment was 2% that in rat nasal olfactory epithelium. Rates of metabolism in nasal compartments of the monkey were low. The catalytic efficiencies of microsomes from known susceptible tissues/subcompartments are 10 and 250 fold higher than in rat airway and monkey alveolar subcompartments, respectively. Although the strong correlations between catalytic efficiencies and tissue susceptibility suggest that non-human primate tissues are unlikely to generate metabolites at a rate sufficient to produce cellular injury, other studies showing high levels of formation of protein adducts support the need for additional studies. - Highlights: • Naphthalene is metabolized with high catalytic efficiency in susceptible tissue. • Naphthalene is metabolized at low catalytic efficiency in non-susceptible tissue. • Respiratory tissues of the non human primate metabolize naphthalene slowly.

  5. Computational modeling of combined cell population dynamics and oxygen transport in engineered tissue subject to interstitial perfusion.

    PubMed

    Galbusera, F; Cioffi, M; Raimondi, M T; Pietrabissa, R

    2007-08-01

    This work presents a computational model of tissue growth under interstitial perfusion inside a tissue engineering bioreactor. The model accounts both for the cell population dynamics, using a model based on cellular automata, and for the hydrodynamic microenvironment imposed by the bioreactor, using a model based on the Lattice-Boltzmann equation and the convection-diffusion equation. The conditions of static culture versus perfused culture were compared, by including the population dynamics along with oxygen diffusion, convective transport and consumption. The model is able to deal with arbitrary complex geometries of the spatial domain; in the present work, the domain modeled was the void space of a porous scaffold for tissue-engineered cartilage. The cell population dynamics algorithm provided results which qualitatively resembled population dynamics patterns observed in experimental studies, and these results were in good quantitative agreement with previous computational studies. Simulation of oxygen transport and consumption showed the fundamental contribution of convective transport in maintaining a high level of oxygen concentration in the whole spatial domain of the scaffold. The model was designed with the aim to be computationally efficient and easily expandable, i.e. to allow straightforward implementability of further models of complex biological phenomena of increasing scientific interest in tissue engineering, such as chemotaxis, extracellular matrix deposition and effect of mechanical stimulation.

  6. Combined effect of protein and oxygen on reactive oxygen and nitrogen species in the plasma treatment of tissue

    NASA Astrophysics Data System (ADS)

    Gaur, Nishtha; Szili, Endre J.; Oh, Jun-Seok; Hong, Sung-Ha; Michelmore, Andrew; Graves, David B.; Hatta, Akimitsu; Short, Robert D.

    2015-09-01

    The influence of protein and molecular, ground state oxygen (O2) on the plasma generation, and transport of reactive oxygen and nitrogen species (RONS) in tissue are investigated. A tissue target, comprising a 1 mm thick gelatin film (a surrogate for real tissue), is placed on top of a 96-well plate; each well is filled with phosphate buffered saline (PBS, pH 7.4) containing one fluorescent or colorimetric reporter that is specific for one of three RONS (i.e., H2O2, NO2-, or OH•) or a broad spectrum reactive oxygen species reporter (2,7-dichlorodihydrofluorescein). A helium cold atmospheric plasma (CAP) jet contacts the top of the gelatin surface, and the concentrations of RONS generated in PBS are measured on a microplate reader. The data show that H2O2, NO2-, or OH• are generated in PBS underneath the target. Independently, measurements are made of the O2 concentration in the PBS with and without the gelatin target. Adding bovine serum albumin protein to the PBS or gelatin shows that protein either raises or inhibits RONS depending upon the O2 concentration. Our results are discussed in the context of plasma-soft tissue interactions that are important in the development of CAP technology for medicine, biology, and food manufacturing.

  7. Attenuated adipose tissue and skeletal muscle inflammation in obese mice with combined CD4+ and CD8+ T cell deficiency

    USDA-ARS?s Scientific Manuscript database

    High-fat diet feeding in mice is characterized by accumulation of alpha Beta Y+T cells in adipose tissue. However, the contribution of ab T cells to obesity-induced inflammation of skeletal muscle, a major organ of glucose uptake, is unknown. This study was undertaken to evaluate the effect of alpha...

  8. Elastic properties of soft tissue-mimicking phantoms assessed by combined use of laser ultrasonics and low coherence interferometry.

    PubMed

    Li, Chunhui; Huang, Zhihong; Wang, Ruikang K

    2011-05-23

    Advances in the field of laser ultrasonics have opened up new possibilities in medical applications. This paper evaluates this technique as a method that would allow for rapid characterization of the elastic properties of soft biological tissue. In doing so, we propose a novel approach that utilizes a low coherence interferometer to detect the laser-induced surface acoustic waves (SAW) from the tissue-mimicking phantoms. A Nd:YAG focused laser line-source is applied to one- and two-layer tissue-mimicking agar-agar phantoms, and the generated SAW signals are detected by a time domain low coherence interferometry system. SAW phase velocity dispersion curves are calculated, from which the elasticity of the specimens is evaluated. We show that the experimental results agree well with those of the theoretical expectations. This study is the first report that a laser-generated SAW phase velocity dispersion technique is applied to soft materials. This technique may open a way for laser ultrasonics to detect the mechanical properties of soft tissues, such as skin.

  9. Curative effect of paclitaxel and cisplatin combined chemotherapy on cervical cancer and its relation with tissue micro vascular and lymphatic vessels density.

    PubMed

    Gao, Zhi-Hui; Wang, Qian-Qing

    2015-09-01

    This study was to discuss the curative effect of paclitaxel and cisplatin combined chemotherapy on cervical cancer and its relation with tissue micro vascular and lymphatic vessels density. The combined chemotherapy of paclitaxel 135 mg/m² and cisplatin 25mg/m² were taken to observe the clinical curative effect. The postoperative paraffin tissue had been collected, had performed the LYVE-1 (lymphatic endothelium specific hyaluronan receptor-1) and CD31 immunohistochemical staining. The complete remission rate of high micro lymphatic vessels density group (was or more 6.0) and high micro vascular density group were obviously higher than in low micro lymphatic vessels density group and low micro vascular density group, the difference was statistically significance (P<0.05). This study further analyzed the relation of MVD and LVD with clinical pathological parameters. The difference was statistically significant (P<0.01). The curative effect of paclitaxel and cisplatin combined therapy was promising, positive and was closely related with cervical cancer tissue LVD and MVD. The LVD and MVD could be one of the predictors of early cervical CIN and early cervical cancer development.

  10. An energy transfer kinetic probe for OH-quenchers in the Nd(3+):YPO4 nanocrystals suitable for imaging in the biological tissue transparency window.

    PubMed

    Samsonova, Elena V; Popov, Alexandr V; Vanetsev, Alexander S; Keevend, Kerda; Orlovskaya, Elena O; Kiisk, Valter; Lange, Sven; Joost, Urmas; Kaldvee, Kaarel; Mäeorg, Uno; Glushkov, Nikolay A; Ryabova, Anastasiya V; Sildos, Ilmo; Osiko, Vyacheslav V; Steiner, Rudolf; Loschenov, Victor B; Orlovskii, Yurii V

    2014-12-28

    Tetragonal xenotime-type yttrium orthophosphate (YPO4) Nd(3+) doped nanoparticles suitable for biomedical applications were prepared by microwave-hydrothermal treatment. We applied the energy transfer probing based on the analysis of kinetics of impurity quenching to determine the presence and spatial position of -OH fluorescence quenching acceptors in the impurity-containing nanoparticles. We show that the impurity quenching kinetics of the 0.1 at% Nd(3+) doped YPO4 nanoparticles is a two stage (ordered and disordered) static kinetics, determined by a direct energy transfer to the -OH acceptors. Analyzing the ordered stage, we assume that the origin of the -OH groups is the protonation of the phosphate groups, while analyzing the disordered stage, we assume the presence of water molecules in the mesopores. We determine the dimension of the space of the -OH acceptors as d = 3 and quantify their absolute concentration using the disordered Förster stage of kinetics. We use the late stage of kinetics of fluorescence hopping (CDD ≫ CDA) quenching (the fluctuation asymptotics) at 1 at% Nd(3+) concentration as an energy transfer probe to quantify the relative concentration of -OH molecular groups compared to an optically active rare-earth dopant in the volume of NPs, when energy migration over Nd(3+) donors to the -OH acceptors accelerates fluorescence quenching. In doing so we use just one parameter α = γ(A)/γ(D) = n(A)√[C(DA)]/n(D)√[C(DD)], defined by the relation of concentration of the -OH acceptors to the concentration of an optically active dopant. The higher is the α, the higher is the relative concentration of -OH acceptors in the volume of nanoparticles. We find α = 2.95 for the 1 at% Nd(3+):YPO4 NPs that, according to the equation for α, and the results obtained for the values of the microparameters CDD(Nd-Nd) = 24.6 nm(6) ms(-1) and CDA(Nd-OH) = 0.6 nm(6) ms(-1), suggests twenty times higher concentration for acceptors other than donors. As the

  11. Alternative exon usage in the single CPT1 gene of Drosophila generates functional diversity in the kinetic properties of the enzyme: differential expression of alternatively spliced variants in Drosophila tissues.

    PubMed

    Price, Nigel T; Jackson, Vicky N; Müller, Jürgen; Moffat, Kevin; Matthews, Karen L; Orton, Tim; Zammit, Victor A

    2010-03-12

    The Drosophila melanogaster genome contains only one CPT1 gene (Jackson, V. N., Cameron, J. M., Zammit, V. A., and Price, N. T. (1999) Biochem. J. 341, 483-489). We have now extended our original observation to all insect genomes that have been sequenced, suggesting that a single CPT1 gene is a universal feature of insect genomes. We hypothesized that insects may be able to generate kinetically distinct variants by alternative splicing of their single CPT1 gene. Analysis of the insect genomes revealed that (a) the single CPT1 gene in each and every insect genome contains two alternative exons and (ii) in all cases, the putative alternative splicing site occurs within a small region corresponding to 21 amino acid residues that are known to be essential for the binding of substrates and of malonyl-CoA in mammalian CPT1A. We performed PCR analyses of mRNA from different Drosophila tissues; both of the anticipated splice variants of CPT1 mRNA were found to be expressed in all of the tissues tested (both in larvae and adults), with the expression level for one of the splice variants being significantly different between flight muscle and the fat body of adult Drosophila. Heterologous expression of the full-length cDNAs corresponding to the two putative variants of Drosophila CPT1 in the yeast Pichia pastoris revealed two important differences between the properties of the two variants: (i) their affinity (K(0.5)) for one of the substrates, palmitoyl-CoA, differed by 5-fold, and (ii) the sensitivity to inhibition by malonyl-CoA at fixed, higher palmitoyl-CoA concentrations was 2-fold different and associated with different kinetics of inhibition. These data indicate that alternative splicing that specifically affects a structurally crucial region of the protein is an important mechanism through which functional diversity of CPT1 kinetics is generated from the single gene that occurs in insects.

  12. Human in vitro 3D co-culture model to engineer vascularized bone-mimicking tissues combining computational tools and statistical experimental approach.

    PubMed

    Bersini, Simone; Gilardi, Mara; Arrigoni, Chiara; Talò, Giuseppe; Zamai, Moreno; Zagra, Luigi; Caiolfa, Valeria; Moretti, Matteo

    2016-01-01

    The generation of functional, vascularized tissues is a key challenge for both tissue engineering applications and the development of advanced in vitro models analyzing interactions among circulating cells, endothelium and organ-specific microenvironments. Since vascularization is a complex process guided by multiple synergic factors, it is critical to analyze the specific role that different experimental parameters play in the generation of physiological tissues. Our goals were to design a novel meso-scale model bridging the gap between microfluidic and macro-scale studies, and high-throughput screen the effects of multiple variables on the vascularization of bone-mimicking tissues. We investigated the influence of endothelial cell (EC) density (3-5 Mcells/ml), cell ratio among ECs, mesenchymal stem cells (MSCs) and osteo-differentiated MSCs (1:1:0, 10:1:0, 10:1:1), culture medium (endothelial, endothelial + angiopoietin-1, 1:1 endothelial/osteo), hydrogel type (100%fibrin, 60%fibrin+40%collagen), tissue geometry (2 × 2 × 2, 2 × 2 × 5 mm(3)). We optimized the geometry and oxygen gradient inside hydrogels through computational simulations and we analyzed microvascular network features including total network length/area and vascular branch number/length. Particularly, we employed the "Design of Experiment" statistical approach to identify key differences among experimental conditions. We combined the generation of 3D functional tissue units with the fine control over the local microenvironment (e.g. oxygen gradients), and developed an effective strategy to enable the high-throughput screening of multiple experimental parameters. Our approach allowed to identify synergic correlations among critical parameters driving microvascular network development within a bone-mimicking environment and could be translated to any vascularized tissue.

  13. Detection of hepatitis A virus in seeded oyster digestive tissue by ricin A-linked magnetic separation combined with reverse transcription PCR.

    PubMed

    Ko, Sang-Mu; Vaidya, Bipin; Kwon, Joseph; Lee, Hee-Min; Oh, Myung-Joo; Shin, Tai-Sun; Cho, Se-Young; Kim, Duwoon

    2015-05-01

    Outbreaks of hepatitis A virus (HAV) infections are most frequently associated with the consumption of contaminated oysters. A rapid and selective concentration method is necessary for the recovery of HAV from contaminated oysters prior to detection using PCR. In this study, ricin extracted from castor beans (Ricinus communis) was tested as an alternative to antibody used in immunomagnetic separation while concentrating HAV prior to its detection using reverse transcription PCR. Initially, the extracted proteins from castor beans were fractionated into 13 fractions by gel filtration chromatography. Pretreatment of different protein fractions showed a variation in binding of HAV viral protein (VP) 1 to oyster digestive tissue in the range of 25.9 to 63.9%. The protein fraction, which caused the highest reduction in binding of VP1 to the tissue, was identified as ricin A by quadrupole time-of-flight mass spectrometry. Ricin A could significantly inhibit binding of VP1 to the tissue with a 50% inhibitory concentration of 4.5 μg/ml and a maximal inhibitory concentration of 105.2%. The result showed that the rate of inhibition of HAV binding to tissue was higher compared to the rate of ricin itself binding to HAV (slope: 0.0029 versus 0.00059). However, ricin A concentration showed a higher correlation to the relative binding of ricin itself to HAV than the inhibition of binding of HAV to the tissue (coefficient of determination, R(2): 0.9739 versus 0.6804). In conclusion, ricin A-linked magnetic bead separation combined with reverse transcription PCR can successfully detect HAV in artificially seeded oyster digestive tissue up to a 10(-4) dilution of the virus stock (titer: 10(4) 50% tissue culture infective dose per ml).

  14. Complementarity of medium-throughput in situ RNA hybridization and tissue-specific transcriptomics: case study of Arabidopsis seed development kinetics

    PubMed Central

    Francoz, Edith; Ranocha, Philippe; Pernot, Clémentine; Ru, Aurélie Le; Pacquit, Valérie; Dunand, Christophe; Burlat, Vincent

    2016-01-01

    The rationale of this study is to compare and integrate two heterologous datasets intended to unravel the spatiotemporal specificities of gene expression in a rapidly growing and complex organ. We implemented medium-throughput RNA in situ hybridization (ISH) for 39 genes mainly corresponding to cell wall proteins for which we have particular interest, selected (i) on their sequence identity (24 class III peroxidase multigenic family members and 15 additional genes used as positive controls) and (ii) on their expression levels in a publicly available Arabidopsis thaliana seed tissue-specific transcriptomics study. The specificity of the hybridization signals was carefully studied, and ISH results obtained for the 39 selected genes were systematically compared with tissue-specific transcriptomics for 5 seed developmental stages. Integration of results illustrates the complementarity of both datasets. The tissue-specific transcriptomics provides high-throughput possibilities whereas ISH provides high spatial resolution. Moreover, depending on the tissues and the developmental stages considered, one or the other technique appears more sensitive than the other. For each tissue/developmental stage, we finally determined tissue-specific transcriptomic threshold values compatible with the spatiotemporally-specific detection limits of ISH for lists of hundreds to tens-of-thousands of genes. PMID:27095274

  15. Kinetics of naphthalene metabolism in target and non-target tissues of rodents and in nasal and airway microsomes from the Rhesus monkey.

    PubMed

    Buckpitt, Alan; Morin, Dexter; Murphy, Shannon; Edwards, Patricia; Van Winkle, Laura

    2013-07-15

    Naphthalene produces species and cell selective injury to respiratory tract epithelial cells of rodents. In these studies we determined the apparent Km, Vmax, and catalytic efficiency (Vmax/Km) for naphthalene metabolism in microsomal preparations from subcompartments of the respiratory tract of rodents and non-human primates. In tissues with high substrate turnover, major metabolites were derived directly from naphthalene oxide with smaller amounts from conjugates of diol epoxide, diepoxide, and 1,2- and 1,4-naphthoquinones. In some tissues, different enzymes with dissimilar Km and Vmax appeared to metabolize naphthalene. The rank order of Vmax (rat olfactory epithelium>mouse olfactory epithelium>murine airways>rat airways) correlated well with tissue susceptibility to naphthalene. The Vmax in monkey alveolar subcompartment was 2% that in rat nasal olfactory epithelium. Rates of metabolism in nasal compartments of the monkey were low. The catalytic efficiencies of microsomes from known susceptible tissues/subcompartments are 10 and 250 fold higher than in rat airway and monkey alveolar subcompartments, respectively. Although the strong correlations between catalytic efficiencies and tissue susceptibility suggest that non-human primate tissues are unlikely to generate metabolites at a rate sufficient to produce cellular injury, other studies showing high levels of formation of protein adducts support the need for additional studies. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Ultrahigh-performance liquid chromatography-ultraviolet absorbance detection-high-resolution-mass spectrometry combined with automated data processing for studying the kinetics of oxidative thermal degradation of thyroxine in the solid state.

    PubMed

    Neu, Volker; Bielow, Chris; Reinert, Knut; Huber, Christian G

    2014-12-05

    Levothyroxine as active pharmaceutical ingredient of formulations used for the treatment of hypothyroidism is distributed worldwide and taken by millions of people. An important issue in terms of compound stability is its capability to react with ambient oxygen, especially in case of long term compound storage at elevated temperature. In this study we demonstrate that ultrahigh-performance liquid chromatography coupled to UV spectrometry and high-resolution mass spectrometry (UHPLC-UV-HRMS) represent very useful approaches to investigate the influence of ambient oxygen on the degradation kinetics of levothyroxine in the solid state at enhanced degradation conditions. Moreover, the impurity pattern of oxidative degradation of levothyroxine is elucidated and classified with respect to degradation kinetics at different oxygen levels. Kinetic analysis of thyroxine bulk material at 100 °C reveals bi-phasic degradation kinetics with a distinct change in degradation phases dependent on the availability of oxygen. The results clearly show that contact of the bulk material to ambient oxygen is a key factor for fast compound degradation. Furthermore, the combination of time-resolved HRMS data and automated data processing is shown to allow insights into the kinetics and mechanism of impurity formation on individual compound basis. By comparing degradation profiles, four main classes of profiles linked to reaction pathways of thyroxine degradation were identifiable. Finally, we show the capability of automated data processing for the matching of different stressing conditions, in order to extract information about mechanistic similarities. As a result, degradation kinetics is influenced by factors like availability of oxygen, stressing time, or stressing temperature, while the degradation mechanisms appear to be conserved.

  17. Computer modeling of the combined effects of perfusion, electrical conductivity, and thermal conductivity on tissue heating patterns in radiofrequency tumor ablation.

    PubMed

    Ahmed, Muneeb; Liu, Zhengjun; Humphries, Stanley; Goldberg, S Nahum

    2008-11-01

    To use an established computer simulation model of radiofrequency (RF) ablation to characterize the combined effects of varying perfusion, and electrical and thermal conductivity on RF heating. Two-compartment computer simulation of RF heating using 2-D and 3-D finite element analysis (ETherm) was performed in three phases (n = 88 matrices, 144 data points each). In each phase, RF application was systematically modeled on a clinically relevant template of application parameters (i.e., varying tumor and surrounding tissue perfusion: 0-5 kg/m(3)-s) for internally cooled 3 cm single and 2.5 cm cluster electrodes for tumor diameters ranging from 2-5 cm, and RF application times (6-20 min). In the first phase, outer thermal conductivity was changed to reflect three common clinical scenarios: soft tissue, fat, and ascites (0.5, 0.23, and 0.7 W/m- degrees C, respectively). In the second phase, electrical conductivity was changed to reflect different tumor electrical conductivities (0.5 and 4.0 S/m, representing soft tissue and adjuvant saline injection, respectively) and background electrical conductivity representing soft tissue, lung, and kidney (0.5, 0.1, and 3.3 S/m, respectively). In the third phase, the best and worst combinations of electrical and thermal conductivity characteristics were modeled in combination. Tissue heating patterns and the time required to heat the entire tumor +/-a 5 mm margin to >50 degrees C were assessed. Increasing background tissue thermal conductivity increases the time required to achieve a 50 degrees C isotherm for all tumor sizes and electrode types, but enabled ablation of a given tumor size at higher tissue perfusions. An inner thermal conductivity equivalent to soft tissue (0.5 W/m- degrees C) surrounded by fat (0.23 W/m- degrees C) permitted the greatest degree of tumor heating in the shortest time, while soft tissue surrounded by ascites (0.7 W/m- degrees C) took longer to achieve the 50 degrees C isotherm, and complete ablation

  18. Solid phase microextraction capillary gas chromatography combined with furnace atomization plasma emission spectrometry for speciation of mercury in fish tissues

    NASA Astrophysics Data System (ADS)

    Grinberg, Patricia; Campos, Reinaldo C.; Mester, Zoltan; Sturgeon, Ralph E.

    2003-03-01

    The use of solid phase microextraction in conjunction with tandem gas chromatography-furnace atomization plasma emission spectrometry (SPME-GC-FAPES) was evaluated for the determination of methylmercury and inorganic mercury in fish tissue. Samples were digested with methanolic potassium hydroxide, derivatized with sodium tetraethylborate and extracted by SPME. After the SPME extraction, species were separated by GC and detected by FAPES. All experimental parameters were optimized for best separation and analytical response. A repeatability precision of typically 2% can be achieved with long-term (3 months) reproducibility precision of 4.3%. Certified Reference Materials DORM-2, DOLT-2 and TORT-2 from the National Research Council of Canada were analyzed to verify the accuracy of this technique. Detection limits of 1.5 ng g -1 for methylmercury and 0.7 ng g -1 for inorganic mercury in biological tissues were obtained.

  19. [INFLUENCE OF QUINAPRIL IN COMBINATION WITH ANGIOLINE ON THE CONNECTIVE TISSUE COMPONENTS IN THE RATS SERUM WITH EXPERIMENTAL HYPERTENSION].

    PubMed

    Nagornaya, A A; Magomedov, S; Gorchakova, N A; Belenichev, I F; Ghekman, I S; Kuzub, T A

    2015-01-01

    One of the most active inhibitors angiotensin-converting enzyme is quinapril that has a high affinity for tissue ACE, improves endothelial vasodilation, has a wide therapeutic range and beneficient influence on heart rate. A new biological active compound with antioxidant action that has endothelioprotective, cardioprotective, antiischemic action is angiolin. In experimental arterial hypertension in the animals blood serum the activity of collagenase, the content of free and protein connecting fractions of hydroxyproline and indicators that reflect the metabolism of glycosaminoglycans have been increased. Angiolin increases the activity of collagenase free and protein connecting fractions of hydroxyproline comparing to control. Concentration glycosoaminoglycan (GAG) also exceeds the standard data. Quinapril has similar to angiolin action directed effect to the connective tissue components, though losing as proteinconecting of hydroxiproline action. Cooperative application quinapril with angioline most effectively influence the metabolic processes stabilization in experimental animals.

  20. A polychromatic staining method for epoxy embedded tissue: a new combination of methylene blue and basic fuchsine for light microscopy.

    PubMed

    D'Amico, F

    2005-01-01

    A simple and rapid method is described for staining semithin sections of material embedded in epoxy resin for observing tissues prior to transmission electron microscopy. The method is suitable for tissue fixed with a glutaraldehyde-formaldehyde mixture and postfixed in osmium tetroxide. No etching or oxidizing procedures are necessary. Sections 0.5-0.8 microm thick are dried onto a slide and stained with either 0.75% methylene blue and 0.25% azure B or 0.5% methylene blue and 0.5% azure II in 0.5% aqueous borax and heated over a flame for 8-10 sec. The slides are rinsed with water, then stained the same way with 0.1% basic fuchsine in 5% aqueous ethanol. Cytoplasm stains blue; nuclei darker blue; collagen, mucus and elastin pink to red; fat and intracellular lipid droplets gray-green.

  1. A novel axial-stress bioreactor system combined with a substance exchanger for tissue engineering of 3D constructs.

    PubMed

    Li, Song-Tao; Liu, Yong; Zhou, Qiang; Lue, Ren-Fa; Song, Lei; Dong, Shi-Wu; Guo, Ping; Kopjar, Branko

    2014-03-01

    This study introduced a prototype of an axial-stress bioreactor system that supports long-term growth and development of engineered tissues. The main features of this bioreactor are an integrated substance exchanger and feedback control of pH and PO₂. A 21-day study was conducted to validate the system's ability to maintain a stable environment, while remaining sterile. Our results showed that the pH, PO₂, and nutrient (glucose) remained balanced at appropriate levels, while metabolic waste (lactic acid) was removed. No bacteria or fungi were detected in the system or tissue; thus, demonstrating that it was sterile. These data indicate the bioreactor's strong potential for long-term tissue culture. To explore this idea, the effect of dynamic culture, including cyclic compression and automatic substance exchange, on mouse bone-marrow mesenchymal stem cells (BMSCs) seeded in decalcified bone matrix was studied using the bioreactor prototype. Histological sections of the engineered tissues showed higher cell densities in scaffolds in dynamic culture compared to those in static culture, while cell cycle analysis showed that dynamic culture promoted BMSC proliferation (proliferation index, PI=34.02±1.77) more effectively than static culture (PI=26.66±1.81). The results from a methyl thiazolyl tetrazolium assay were consistent with the loading experimental data. Furthermore, elevated alkaline phosphatase activity and calcium content were observed in dynamic condition compared to static culture. In conclusion, this bioreactor system supplies a method of modulating the pH and PO₂ in defined ranges with only small fluctuations; it can be used as a physiological or pathological analog. Automatic control of the environment is a practical solution for long-term, steady-state culture for future commercialization.

  2. Application of HPLC combined with laser induced fluorescence for protein profile analysis of tissue homogenates in cervical cancer.

    PubMed

    Bhat, Sujatha; Patil, Ajeetkumar; Rai, Lavanya; Kartha, V B; Chidangil, Santhosh

    2012-01-01

    A highly objective method, High Performance Liquid Chromatography with Laser Induced Fluorescence (HPLC-LIF) technique was used to study the protein profiles of normal and cervical cancer tissue homogenates. A total of 44 samples including normal cervical biopsy samples from the hysterectomy patients and the patients suffering from different stages of the cervical cancer were recorded by HPLC-LIF and analysed by Principle Component Analysis (PCA) to get statistical information on different tissue components. Discrimination of different stages of the samples was carried out by considering three parameters--scores of factor, spectral residual, and Mahalanobis Distance. Diagnostic accuracy of the method was evaluated using Receiver Operating Characteristic (ROC) analysis, and Youden's index (J) plots. The PCA results showed high sensitivity and specificity (~100) for cervical cancer diagnosis. ROC and Youden's index curves for both normal and malignant standard sets show good diagnostic accuracy with high AUC values. The statistical analysis has shown that the differences in protein profiles can be used to diagnose biochemical changes in the tissue, and thus can be readily applied for the detection of cervical cancer, even in situations where a histopathology examination is not easy because of nonavailability of experienced pathologists.

  3. Tissue-Engineered Tubular Heart Valves Combining a Novel Precontraction Phase with the Self-Assembly Method.

    PubMed

    Picard-Deland, Maxime; Ruel, Jean; Galbraith, Todd; Tremblay, Catherine; Kawecki, Fabien; Germain, Lucie; Auger, François A

    2017-02-01

    Recently, the tubular shape has been suggested as an effective geometry for tissue-engineered heart valves, allowing easy fabrication, fast implantation, and a minimal crimped footprint from a transcatheter delivery perspective. This simple design is well suited for the self-assembly method, with which the only support for the cells is the extracellular matrix they produce, allowing the tissue to be completely free from exogenous materials during its entire fabrication process. Tubular constructs were produced by rolling self-assembled human fibroblast sheets on plastic mandrels. After maturation, the tubes were transferred onto smaller diameter mandrels and allowed to contract freely. This precontraction phase thickened the tissue and prevented further contraction, while improving fusion between the self-assembled layers and aligning the cells circumferentially. When mounted in a pulsed-flow bioreactor, the valves showed good functionality with large leaflets coaptation and opening area. Although physiological aortic flow conditions were not reached, the leaflets could withstand a 1 Hz pulsed flow with a 300 mL/s peak flow rate and a 70 mmHg peak transvalvular pressure. This study shows that the self-assembly method, which has already proven its potential for the production of small diameter vascular grafts, could also be used to achieve functional tubular heart valves.

  4. MAGEA4 expression in bone and soft tissue tumors: its utility as a target for immunotherapy and diagnostic marker combined with NY-ESO-1.

    PubMed

    Iura, Kunio; Kohashi, Kenichi; Ishii, Takeaki; Maekawa, Akira; Bekki, Hirofumi; Otsuka, Hiroshi; Yamada, Yuichi; Yamamoto, Hidetaka; Matsumoto, Yoshihiro; Iwamoto, Yukihide; Oda, Yoshinao

    2017-07-26

    Cancer-testis (CT) antigens have promise as targets for immunotherapy, because of their restricted expression in tumor or testis tissue. MAGEA4 is both a MAGE family member and a CT antigen, and has attracted attention as a potential immunotherapeutic target. We investigated MAGEA4 expression by immunohistochemistry in bone and soft tissue tumor specimens that consisted of 35 malignant or intermediate and 24 benign histological subtypes, in order to evaluate its possible utility as an immunotherapy target and its potential use as a diagnostic marker when combined with another CT antigen, NY-ESO-1. Among these tumors, MAGEA4 was detected in 82.2% of synovial sarcomas, 67.7% of myxoid liposarcomas, 43.8% of osteosarcomas, 41.4% of angiosarcomas, 24.6% of malignant peripheral nerve sheath tumors (MPNSTs), and 21.4% of chondrosarcomas. NY-ESO-1 expression was found in 88.2% of myxoid liposarcomas, 61.1% of synovial sarcomas, 31.3% of osteosarcomas, 21.4% of pleomorphic liposarcomas, 16.7% of desmoplastic small round cell tumors, and 14.3% of chondrosarcomas. Benign tumors and non-tumorous tissue, except for testis tissue, did not express MAGEA4 or NY-ESO-1. Combined use of MAGEA4 and NY-ESO-1 increased the sensitivity, specificity, positive predictive values, and negative predictive values for distinguishing synovial sarcoma from spindle cell tumors and other mimicking tumors, compared to individual use of MAGEA4 or NY-ESO-1. Our results support the immunotherapy targeting MAGEA4 or NY-ESO-1 can be an ancillary therapy in the above-mentioned tumors, and the potential utility of MAGEA4 as an ancillary diagnostic marker for synovial sarcoma combined with NY-ESO-1.

  5. Development of a Combined In Vitro Physiologically Based Kinetic (PBK) and Monte Carlo Modelling Approach to Predict Interindividual Human Variation in Phenol-Induced Developmental Toxicity.

    PubMed

    Strikwold, Marije; Spenkelink, Bert; Woutersen, Ruud A; Rietjens, Ivonne M C M; Punt, Ans

    2017-06-01

    With our recently developed in vitro physiologically based kinetic (PBK) modelling approach, we could extrapolate in vitro toxicity data to human toxicity values applying PBK-based reverse dosimetry. Ideally information on kinetic differences among human individuals within a population should be considered. In the present study, we demonstrated a modelling approach that integrated in vitro toxicity data, PBK modelling and Monte Carlo simulations to obtain insight in interindividual human kinetic variation and derive chemical specific adjustment factors (CSAFs) for phenol-induced developmental toxicity. The present study revealed that UGT1A6 is the primary enzyme responsible for the glucuronidation of phenol in humans followed by UGT1A9. Monte Carlo simulations were performed taking into account interindividual variation in glucuronidation by these specific UGTs and in the oral absorption coefficient. Linking Monte Carlo simulations with PBK modelling, population variability in the maximum plasma concentration of phenol for the human population could be predicted. This approach provided a CSAF for interindividual variation of 2.0 which covers the 99th percentile of the population, which is lower than the default safety factor of 3.16 for interindividual human kinetic differences. Dividing the dose-response curve data obtained with in vitro PBK-based reverse dosimetry, with the CSAF provided a dose-response curve that reflects the consequences of the interindividual variability in phenol kinetics for the developmental toxicity of phenol. The strength of the presented approach is that it provides insight in the effect of interindividual variation in kinetics for phenol-induced developmental toxicity, based on only in vitro and in silico testing. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Kinetic study of the replacement of porcine small intestinal submucosa grafts and the regeneration of meniscal-like tissue in large avascular meniscal defects in dogs.

    PubMed

    Cook, J L; Tomlinson, J L; Arnoczky, S P; Fox, D B; Reeves Cook, C; Kreeger, J M

    2001-06-01

    Porcine small intestinal submucosa (SIS) was used to replace large, avascular defects in the medial menisci of dogs. Twelve dogs received SIS grafts and 3 dogs were left untreated as controls. Dogs were evaluated at 4, 8, and 12 weeks by means of lameness scoring and ultrasonography. Dogs were sacrificed at 1, 6, or 12 weeks after implantation, and the tissue at the site of meniscal resection was evaluated for gross and histologic appearance, cross-sectional and surface area, and collagen types I and II. The femoral and tibial condyles were assessed for articular cartilage damage. Control dogs were significantly more lame than grafted dogs 8 and 12 weeks after instrumentation. Grafted dogs' replacement tissue appeared meniscal-like when evaluated grossly and ultrasonographically 12 weeks after instrumentation. The amount of replacement tissue was significantly greater in both cross-sectional and surface area for grafted dogs than for controls at all time points. Histologically, the SIS biomaterial could be identified in all grafted dogs at 1 week post-implantation, but in none at 6 weeks post-implantation. Subjectively, grafted dogs' replacement tissue was histologically superior to that of controls with respect to tissue type, organization, and architecture. Collagen types I and II immunoreactivity in grafted menisci were similar to that of normal menisci. Control dogs had significantly more articular cartilage damage than grafted dogs. SIS appears to induce regeneration of meniscal-like tissue in large, avascular meniscal defects in dogs, resulting in superior clinical function and articular cartilage protection compared to ungrafted controls.

  7. Novel mathematical models for cell-mediated cytotoxicity assays without applying enzyme kinetics but with combinations and probability: bystanders in bulk effector cells influence results of cell-mediated cytotoxicity assays.

    PubMed

    Takayanagi, Toshiaki

    2011-07-01

    Cell-mediated cytotoxicity assays are widely implemented to evaluate cell-mediated cytotoxic activity, and some assays are analyzed using the analogy of enzyme kinetics. In the analogy, the effector cell is regarded as the enzyme, the target cell as the substrate, the effector cell-target cell conjugate as the enzyme-substrate complex and the dead target cell as the product. However, the assumptions analogous to those of enzyme kinetics are not always true in cell-mediated cytotoxicity assays, and the parameter analogous to the Michaelis-Menten constant is not constant but is dependent on the number of effector cells. Therefore I present novel mathematical models for cell-mediated cytotoxicity assays without applying enzyme kinetics. I instead use combinations and probability, because analysis of cell-mediated cytotoxicity assays by applying enzyme kinetics seems controversial. With my original models, I demonstrate simulations of the data in previously published papers. The results are exhibited in the same forms as the corresponding data. Comparing the simulation results with the published data, the results seem to agree well with the data. From simulations of cytotoxic assays with bulk effector cells, it appears that bystanders in bulk effector cells increase both the cytotoxic activity and the motility of effector cells.

  8. Boron determination in liver tissue by combining quantitative neutron capture radiography (QNCR) and histological analysis for BNCT treatment planning at the TRIGA Mainz.

    PubMed

    Schütz, C; Brochhausen, C; Altieri, S; Bartholomew, K; Bortolussi, S; Enzmann, F; Gabel, D; Hampel, G; Kirkpatrick, C J; Kratz, J V; Minouchehr, S; Schmidberger, H; Otto, G

    2011-09-01

    The typical primary malignancies of the liver are hepatocellular carcinoma and cholangiocarcinoma, whereas colorectal liver metastases are the most frequently occurring secondary tumors. In many cases, only palliative treatment is possible. Boron neutron capture therapy (BNCT) represents a technique that potentially destroys tumor tissue selectively by use of externally induced, locally confined secondary particle irradiation. In 2001 and 2003, BNCT was applied to two patients with colorectal liver metastases in Pavia, Italy. To scrutinize the rationale of BNCT, a clinical pilot study on patients with colorectal liver metastases was carried out at the University of Mainz. The distribution of the (10)B carrier (p-borono-phenylalanine) in the liver and its uptake in cancerous and tumor-free tissue were determined, focusing on a potential correlation between the uptake of p-borono-phenylalanine and the biological characteristics of cancerous tissue. Samples were analyzed using quantitative neutron capture radiography of cryosections combined with histological analysis. Methodological aspects of the combination of these techniques and results from four patients enrolled in the study are presented that indicate that the uptake of p-borono-phenylalanine strongly depends on the metabolic activity of cells.

  9. Determination of clenbuterol in porcine tissues using solid-phase extraction combined with ultrasound-assisted dispersive liquid-liquid microextraction and HPLC-UV detection.

    PubMed

    Liu, Baomi; Yan, Hongyuan; Qiao, Fengxia; Geng, Yuru

    2011-01-01

    A new pretreatment method, solid-phase extraction combined with dispersive liquid-liquid microextration (SPE-DLLME), was proposed in first time for the determination of clenbuterol (CLB) in porcine tissue samples. The tissue samples were firstly extracted by SPE, then its eluents were used as dispersant of the followed DLLME for further purification and enrichment of CLB. Various parameters (such as the type of SPE sorbent, the type and volume of elution solvent, the type and volume of extractant and dispersant, etc.) that affected the efficiency of the two steps were optimized. Good linearity of CLB was ranged from 0.19 μg/kg to 192 μg/kg with correlation coefficient (r²) of 0.9995. The limit of detection (LOD) was 0.07 μg/kg (S/N=3) and the recoveries at three spiked levels were ranged from 87.9% to 103.6% with the relative standard deviation (RSD) less than 3.9% (n=3). Under the optimized conditions, the enrichment factor (EF) for CLB could up to 62 folds. The presented method that combined the advantages of SPE and DLLME, had higher selectivity than SPE method and was successfully applied to the determination of CLB in tissue samples.

  10. Soft tissue repair for tibialis anterior tendon ruptures using plate and screw fixation technique in combination with anterolateral thigh flaps transplantation.

    PubMed

    Mao, Haijun; Xu, Guanyue

    2015-09-17

    Traumatic ruptures of the tibialis anterior tendon are rare but can cause substantial functional deficiencies. This study aimed to evaluate the feasibility of a surgery for soft tissue repair of traumatic rupture of the tibialis anterior tendon by using a plate and screw fixation repair in combination with the free anterolateral thigh flaps transplantation. Eight consecutive patients with anterior tibialis tendon ruptures who visited orthopedics departments from February 2008 to February 2012 were included in our study. The ruptured tendon was reconstructed with plate and screw fixation technique, and the tissue defects were repaired with anterolateral thigh free flaps. The complications and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores were evaluated. Postoperative manual strength test was performed using a 0 to 5 scale. All flaps survived without any complications. The average preoperative and postoperative AOFAS ankle-hindfoot scores of the patients were 51 and 95, respectively. Good ankle dorsiflexion strength against strong resistance was observed in eight ankles postoperatively (manual strength of one patient was 4/5, the others were 5/5), and a substantial improvement in strength was noted compared with the preoperative examination. Soft tissue repair for tibialis anterior tendon rupture using plate and screw fixation technique in combination with anterolateral thigh flaps transplantation is a feasible technique and yield satisfactory results.

  11. Influence of different sized nanoparticles combined with ultrasound on the optical properties of in vitro normal and cancerous human lung tissue studied with OCT and diffuse reflectance spectra

    NASA Astrophysics Data System (ADS)

    Zhou, L. P.; Wu, G. Y.; Wei, H. J.; Guo, Z. Y.; Yang, H. Q.; He, Y. H.; Xie, S. S.; Liu, Y.

    2014-11-01

    The present study is concerned with the in vitro study of different sized titanium dioxide (TiO2) nanoparticles’ (NPs) penetration and accumulation in human normal lung (NL) tissue and lung adenocarcinoma tumor (LAT) tissue by the methods of continuous optical coherence tomography (OCT) monitoring and diffuse reflectance (DR) spectra measurement, and their evaluating the effects of TiO2 NPs in two sizes (60 nm and 100 nm) and their combination with ultrasound (US) on the optical properties of human NL and LAT tissue. Spectral measurements indicate that TiO2 NPs penetrate and accumulate into the tissues and thus induce enhancement of DR. The averaged and normalized OCT signal intensity suggests that light penetration depth is significantly enlarged by ultrasound. The average attenuation coefficient of NL tissue changes from 5.10  ±  0.26 mm-1 to 3.12  ±  0.43 mm-1 and 2.15  ±  0.54 mm-1 at 120 min for 60 nm TiO2 NPs and 60 nm TiO2NPs/US treatment, respectively, and from 5.54  ±  0.46 mm-1 to 3.24  ±  0.73 mm-1 and 2.69  ±  0.34 mm-1 at 150 min for 100 nm TiO2 NPs and 100 nm TiO2NPs/US, respectively. The average attenuation coefficient of LAT tissue changes from 9.12  ±  0.54 mm-1 to 4.54  ±  0.39 mm-1 and 3.61  ±  0.38 mm-1 at 120 min for 60 nm TiO2 NPs and 60 nm TiO2NPs/US treatment, respectively, and from 9.79  ±  0.32 mm-1 to 5.12  ±  0.47 mm-1 and 4.89  ±  0.59 mm-1 at 150 min for 100 nm TiO2 NPs and 100 nm TiO2NPs/US, respectively. The results suggest that the optical properties of NL and LAT tissues are greatly influenced by TiO2 NPs and their combination with ultrasound.

  12. Experimental evaluation of electrical conductivity imaging of anisotropic brain tissues using a combination of diffusion tensor imaging and magnetic resonance electrical impedance tomography

    NASA Astrophysics Data System (ADS)

    Sajib, Saurav Z. K.; Jeong, Woo Chul; Kyung, Eun Jung; Kim, Hyun Bum; Oh, Tong In; Kim, Hyung Joong; Kwon, Oh In; Woo, Eung Je

    2016-06-01

    Anisotropy of biological tissues is a low-frequency phenomenon that is associated with the function and structure of cell membranes. Imaging of anisotropic conductivity has potential for the analysis of interactions between electromagnetic fields and biological systems, such as the prediction of current pathways in electrical stimulation therapy. To improve application to the clinical environment, precise approaches are required to understand the exact responses inside the human body subjected to the stimulated currents. In this study, we experimentally evaluate the anisotropic conductivity tensor distribution of canine brain tissues, using a recently developed diffusion tensor-magnetic resonance electrical impedance tomography method. At low frequency, electrical conductivity of the biological tissues can be expressed as a product of the mobility and concentration of ions in the extracellular space. From diffusion tensor images of the brain, we can obtain directional information on diffusive movements of water molecules, which correspond to the mobility of ions. The position dependent scale factor, which provides information on ion concentration, was successfully calculated from the magnetic flux density, to obtain the equivalent conductivity tensor. By combining the information from both techniques, we can finally reconstruct the anisotropic conductivity tensor images of brain tissues. The reconstructed conductivity images better demonstrate the enhanced signal intensity in strongly anisotropic brain regions, compared with those resulting from previous methods using a global scale factor.

  13. A Hyperlipidic Diet Combined with Short-Term Ovariectomy Increases Adiposity and Hyperleptinemia and Decreases Cytokine Content in Mesenteric Adipose Tissue

    PubMed Central

    Neto, Nelson Inacio Pinto; Rodrigues, Maria Elizabeth Sousa; Hachul, Ana Claudia Losinskas; Moreno, Mayara Franzoi; Boldarine, Valter Tadeu; Ribeiro, Eliane Beraldi; Oyama, Lila Missae; Oller do Nascimento, Claudia Maria

    2015-01-01

    Four-week-old female Wistar rats were divided into two groups and fed a control diet (C) or a hyperlipidic diet (H) for 4 weeks. Rats from each group underwent ovariectomy (OVX) or sham surgery (SHAM). They received C or H for the next four weeks. The body weight gain (BW), food efficiency (FE), and carcass lipid content were higher in the OVX H than in the SHAM H. The OVX H exhibited a higher serum leptin level than other groups. IL-6, TNF-α, and IL-10 content of mesenteric (MES) adipose tissue was lower in the OVX H than in the OVX C. IL-6, TNF-α, and IL-10 content of retroperitoneal (RET) adipose tissue was lower in the SHAM H than in the SHAM C. The SHAM H showed decreased TG relative to the SHAM C. Similar results were obtained in relation to IL-6Rα, TNFR1, TLR-4, and MyD88 contents in the MES and RET white adipose tissue among the groups. A hyperlipidic diet for 8 weeks combined with short-term ovariectomy decreases the cytokine content of MES adipose tissues but increases BW, enhancing FE and elevating serum leptin levels. These suggest that the absence of estrogens promotes metabolic changes that may contribute to installation of a proinflammatory process induced by a hyperlipidic diet. PMID:26170534

  14. Three dimensional visualization of engineered bone and soft tissue by combined x-ray micro-diffraction and phase contrast tomography.

    PubMed

    Cedola, Alessia; Campi, Gaetano; Pelliccia, Daniele; Bukreeva, Inna; Fratini, Michela; Burghammer, Manfred; Rigon, Luigi; Arfelli, Fulvia; Chang Chen, Rong; Dreossi, Diego; Sodini, Nicola; Mohammadi, Sara; Tromba, Giuliana; Cancedda, Ranieri; Mastrogiacomo, Maddalena

    2014-01-06

    Computed x-ray phase contrast micro-tomography is the most valuable tool for a three dimensional (3D) and non destructive analysis of the tissue engineered bone morphology. We used a Talbot interferometer installed at SYRMEP beamline of the ELETTRA synchrotron (Trieste, Italy) for a precise 3D reconstruction of both bone and soft connective tissue, regenerated in vivo within a porous scaffold. For the first time the x-ray tomographic reconstructions have been combined with x-ray scanning micro-diffraction measurement on the same sample, in order to give an exhaustive identification of the different tissues participating to the biomineralization process. As a result, we were able to investigate in detail the different densities in the tissues, distinguishing the 3D organization of the amorphous calcium phosphate from the collagen matrix. Our experimental approach allows for a deeper understanding of the role of collagen matrix in the organic-mineral transition, which is a crucial issue for the development of new bio-inspired composites.

  15. Design and validation of a novel bioreactor principle to combine online micro-computed tomography monitoring and mechanical loading in bone tissue engineering.

    PubMed

    Hagenmüller, Henri; Hitz, Marco; Merkle, Hans P; Meinel, Lorenz; Müller, Ralph

    2010-01-01

    Mechanical loading plays an important role in bone remodeling in vivo and, therefore, has been suggested as a key parameter in stem cell-based engineering of bone-like tissue in vitro. However, the optimization of loading protocols during stem cell differentiation and subsequent bone-like tissue formation is challenged by multiple input factors, which are difficult to control and validate. These include the variable cellular performance of cells harvested from different patients, nonstandardized culture media components, the choice of the biomaterial forming the scaffold, and its morphology, impacting a broader validity of mechanical stimulation regimens. To standardize the cell culture of bone-like tissue constructs, we suggest the involvement of time-lapsed feedback loops. For this purpose we present a prototype bioreactor that combines online, nondestructive monitoring using micro-computed tomography and direct mechanical loading of three-dimensional tissue engineering constructs. Validation of this system showed displacement steps down to 1 microm and cyclic sinusoidal loadings of up to 10 Hz. Load detection resolution was 0.01 N, and micro-computed tomography data were of high quality. For the first time, the developed bioreactor links time-lapsed, nondestructive, and dynamic imaging with mechanical stimulation, designed for cell culture under sterile conditions. This system is believed to substantially improve today's experimental options to study and optimize osteogenic stem cell culture and differentiation at the interface with mechanical stimulation.

  16. Experimental evaluation of electrical conductivity imaging of anisotropic brain tissues using a combination of diffusion tensor imaging and magnetic resonance electrical impedance tomography

    SciTech Connect

    Sajib, Saurav Z. K.; Jeong, Woo Chul; Oh, Tong In; Kim, Hyung Joong E-mail: ejwoo@khu.ac.kr; Woo, Eung Je E-mail: ejwoo@khu.ac.kr; Kyung, Eun Jung; Kim, Hyun Bum; Kwon, Oh In

    2016-06-15

    Anisotropy of biological tissues is a low-frequency phenomenon that is associated with the function and structure of cell membranes. Imaging of anisotropic conductivity has potential for the analysis of interactions between electromagnetic fields and biological systems, such as the prediction of current pathways in electrical stimulation therapy. To improve application to the clinical environment, precise approaches are required to understand the exact responses inside the human body subjected to the stimulated currents. In this study, we experimentally evaluate the anisotropic conductivity tensor distribution of canine brain tissues, using a recently developed diffusion tensor-magnetic resonance electrical impedance tomography method. At low frequency, electrical conductivity of the biological tissues can be expressed as a product of the mobility and concentration of ions in the extracellular space. From diffusion tensor images of the brain, we can obtain directional information on diffusive movements of water molecules, which correspond to the mobility of ions. The position dependent scale factor, which provides information on ion concentration, was successfully calculated from the magnetic flux density, to obtain the equivalent conductivity tensor. By combining the information from both techniques, we can finally reconstruct the anisotropic conductivity tensor images of brain tissues. The reconstructed conductivity images better demonstrate the enhanced signal intensity in strongly anisotropic brain regions, compared with those resulting from previous methods using a global scale factor.

  17. Three dimensional visualization of engineered bone and soft tissue by combined x-ray micro-diffraction and phase contrast tomography

    NASA Astrophysics Data System (ADS)

    Cedola, Alessia; Campi, Gaetano; Pelliccia, Daniele; Bukreeva, Inna; Fratini, Michela; Burghammer, Manfred; Rigon, Luigi; Arfelli, Fulvia; Chen, Rong Chang; Dreossi, Diego; Sodini, Nicola; Mohammadi, Sara; Tromba, Giuliana; Cancedda, Ranieri; Mastrogiacomo, Maddalena

    2014-01-01

    Computed x-ray phase contrast micro-tomography is the most valuable tool for a three dimensional (3D) and non destructive analysis of the tissue engineered bone morphology. We used a Talbot interferometer installed at SYRMEP beamline of the ELETTRA synchrotron (Trieste, Italy) for a precise 3D reconstruction of both bone and soft connective tissue, regenerated in vivo within a porous scaffold. For the first time the x-ray tomographic reconstructions have been combined with x-ray scanning micro-diffraction measurement on the same sample, in order to give an exhaustive identification of the different tissues participating to the biomineralization process. As a result, we were able to investigate in detail the different densities in the tissues, distinguishing the 3D organization of the amorphous calcium phosphate from the collagen matrix. Our experimental approach allows for a deeper understanding of the role of collagen matrix in the organic-mineral transition, which is a crucial issue for the development of new bio-inspired composites.

  18. Tissue Localization of Lymphocystis Disease Virus (LCDV) Receptor-27.8 kDa and Its Expression Kinetics Induced by the Viral Infection in Turbot (Scophthalmus maximus)

    PubMed Central

    Sheng, Xiuzhen; Wu, Ronghua; Tang, Xiaoqian; Xing, Jing; Zhan, Wenbin

    2015-01-01

    The 27.8 kDa membrane protein expressed in flounder (Paralichthys olivaceus) gill cells was proved to be a receptor mediating lymphocystis disease virus (LCDV) infection. In this study, SDS-PAGE and Western blotting demonstrated that 27.8 kDa receptor (27.8R) was shared by flounder and turbot (Scophthalmus maximus). Indirect immunofluorescence assay (IIFA) and immunohistochemistry showed that 27.8R was widely expressed in tested tissues of healthy turbot. The indirect enzyme-linked immunosorbent assay indicated that 27.8R expression was relatively higher in stomach, gill, heart, and intestine, followed by skin, head kidney, spleen, blood cells, kidney and liver, and lower in ovary and brain in healthy turbot, and it was significantly up-regulated after LCDV infection. Meanwhile, real-time quantitative PCR demonstrated that LCDV was detected in heart, peripheral blood cells, and head kidney at 3 h post infection (p.i.), and then in other tested tissues at 12 h p.i. LCDV copies increased in a time-dependent manner, and were generally higher in the tissues with higher 27.8R expression. Additionally, IIFA showed that 27.8R and LCDV were detected at 3 h p.i. in some leukocytes. These results suggested that 27.8R also served as a receptor in turbot, and LCDV can infect some leukocytes which might result in LCDV spreading to different tissues in turbot. PMID:26556346

  19. Dye-enhanced selective photothermal laser-tissue interaction and photodynamic therapy in combination with immunoadjuvant for cancer treatment

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Bartels, Kenneth E.; Sun, Jinghai; Liu, Hong; Nordquist, Robert E.; Korbelik, Mladen

    2003-12-01

    Immunoadjuvants have been used to stimulate host immune responses. However, immunoadjuvants alone have not been very successful in treating metastatic tumors. Following the principle of combined therapy in AIDS treatment and in combination chemotherapy, immunoadjuvants have been used in conjunction with other treatment modalities. The current study is an attempt to use both selective photothermal and selective photochemical interactions to accompany a new immunoadjuvant in the treatment of metastatic tumors. The immunoadjuvant, glycated chitosan (GC), has been shown in the previous studies to be effective in inducing immune responses when combined with the treatment of laser irradiation after the intratumoral injection of indocyanine green solution. When glycated chitosan was used with photodynamic therapy (PDT), the treatment effect was significantly increased. Specifically, when glycated chitosan was injected peritumorally after Photofrin-based PDT treatment of EMT6 mammary sarcoma in mice, the tumor-free rate of the treated mice was increased from 38% to 75% using 1.5% GC solution. In mTHPC-based PDT treatment of Line-1 lung adenocarcinoma in mice, the tumor-free rates of treated mice reached 38% while PDT alone did not result in any tumor free mouse. The combination of the immunoadjuvant and selective photophysical interaction may become an effective method to treat tumors with an induced anti-tumor immunity.

  20. Effect of a dietary supplement combination on weight management, adipose tissue, cholesterol and triglycerides in obese subjects.

    PubMed

    González, Michael J; Miranda-Massari, Jorge R; Ricart, Carlos M

    2004-06-01

    A combination dietary supplement containing vitamins, minerals, herbs, fibers and amino acids was studied to determine its safety and efficacy on weight/ fat loss, cholesterol and triglycerides in a double-blind, placebo-controlled trail. Total body weight, body fat %, waist and hip measurements, total cholesterol and triglycerides were evaluated before and after 6 weeks treatment with combination supplement or placebo. The study population consisted in 27 mildly to moderately obese, otherwise healthy, volunteers. After 6 weeks of treatment, the combination supplement had a statistically significant (p<0.001, mu=0.05) positive weight reducing effect (-8.59Lb vs. +2.14 Lb). This weight reduction was associated with a corresponding statistically significant (p<0.001, mu=0.05) decrease in body fat % in the treatment group (-2.88%) vs. the placebo (+0.86%). In addition, significant decreases in total cholesterol (-22.94 mg/dL) and triglycerides (-39.29 mg/dL) were obtained plus reductions in waist and hip measurements. These positive results lead us to conclude, that the combination supplement studied herein is a safe and effective way to assist in weight/fat reduction and decreases in total cholesterol and triglycerides in relatively short time (6 weeks).

  1. The Combination of Laser Therapy and Metal Nanoparticles in Cancer Treatment Originated From Epithelial Tissues: A Literature Review

    PubMed Central

    Fekrazad, Reza; Naghdi, Nafiseh; Nokhbatolfoghahaei, Hanieh; Bagheri, Hossein

    2016-01-01

    Several methods have been employed for cancer treatment including surgery, chemotherapy and radiation therapy. Today, recent advances in medical science and development of new technologies, have led to the introduction of new methods such as hormone therapy, Photodynamic therapy (PDT), treatments using nanoparticles and eventually combinations of lasers and nanoparticles. The unique features of LASERs such as photo-thermal properties and the particular characteristics of nanoparticles, given their extremely small size, may provide an interesting combined therapeutic effect. The purpose of this study was to review the simultaneous application of lasers and metal nanoparticles for the treatment of cancers with epithelial origin. A comprehensive search in electronic sources including PubMed, Google Scholar and Science Direct was carried out between 2000 and 2013. Among the initial 400 articles, 250 articles applied nanoparticles and lasers in combination, in which more than 50 articles covered the treatment of cancer with epithelial origin. In the future, the combination of laser and nanoparticles may be used as a new or an alternative method for cancer therapy or diagnosis. Obviously, to exclude the effect of laser’s wavelength and nanoparticle’s properties more animal studies and clinical trials are required as a lack of perfect studies PMID:27330701

  2. Meniscus tissue engineering using a novel combination of electrospun scaffolds and human meniscus cells embedded within an extracellular matrix hydrogel.

    PubMed

    Baek, Jihye; Chen, Xian; Sovani, Sujata; Jin, Sungho; Grogan, Shawn P; D'Lima, Darryl D

    2015-04-01

    Meniscus injury and degeneration have been linked to the development of secondary osteoarthritis (OA). Therapies that successfully repair or replace the meniscus are, therefore, likely to prevent or delay OA progression. We investigated the novel approach of building layers of aligned polylactic acid (PLA) electrospun (ES) scaffolds with human meniscus cells embedded in extracellular matrix (ECM) hydrogel to lead to formation of neotissues that resemble meniscus-like tissue. PLA ES scaffolds with randomly oriented or aligned fibers