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Sample records for tumor oxygen tension

  1. Oxygen tension measurements of tumors growing in mice

    International Nuclear Information System (INIS)

    Adam, Markus F.; Dorie, Mary Jo; Brown, J. Martin

    1999-01-01

    Purpose: Clinical studies using the Eppendorf histograph have shown that patients whose tumors have a low pO 2 have worse local control after radiotherapy, and have higher metastatic rates. Because preclinical studies of methods of overcoming, or exploiting, hypoxia generally use transplanted tumors in mice, we have compared the oxygenation of mouse tumors with human tumors to determine the appropriateness of the transplanted mouse model for such preclinical studies. Methods and Materials: We evaluated the oxygenation status of subcutaneous (s.c.) tissue and of 12 intradermally (i.d.)- and 7 s.c.-growing mouse or human transplanted tumors in mice using the Eppendorf histograph, and compared the values obtained with measurements of human head and neck nodes. Results: The normal tissue pO 2 profile of air-breathing mice showed a nearly Gaussian distribution (38.2 ± 14.9 mmHg). Breathing 10% O 2 or carbogen resulted in dramatic changes in normal tissue oxygenation. Tumors growing intradermally in the back of air-breathing mice were extremely hypoxic and resistant to expected changes in oxygenation (carbogen breathing, size, and use of anesthetics). Tumors growing s.c. in the foot showed higher oxygen profiles with marked changes in oxygenation when exposing the animals to different levels of oxygen. However, the oxygenation of the mouse tumors transplanted in either site was only a fraction of that of the majority of human tumors. Conclusion: Experimental mouse tumors are markedly hypoxic, with median values of 10-20% of those of human tumors. Hence, mouse tumors are probably good models for the most hypoxic human tumors that respond poorly to radiotherapy; however, caution has to be exercised in extrapolating data from mouse to man

  2. Simultaneous Monitoring of Vascular Oxygenation and Tissue Oxygen Tension of Breast Tumors Under Hyperbaric Oxygen Exposure

    National Research Council Canada - National Science Library

    Xia, Mengna

    2005-01-01

    The goals of the study in the first stage are 1) to develop a mathematic model by which we can derive tumor blood flow and metabolic rate of oxygen from hemoglobin concentration during interventions, 2...

  3. Simultaneous Monitoring of Vascular Oxygenation and Tissue Oxygen Tension of Breast Tumors Under Hyperbaric Oxygen Exposure

    Science.gov (United States)

    2008-04-01

    28. Alagoz, T., R. Buller, B. Anderson, K. Terrell , R...and oxygenation Ann . New Acad. Sci. 838 29–45 Chapman J D, Stobbe C C, Arnfield M R, Santus R, Lee J and McPhee M S 1991 Oxygen dependency of tumor

  4. Increase of tumor oxygen tension and potentiation of radiation effects using pentoxifylline, vinpocetine and ticlopidine hydrochloride

    International Nuclear Information System (INIS)

    Amano, Morikazu; Monzen, Hajime; Suzuki, Takatoshi; Hasegawa, Takeo

    2004-01-01

    The effects of pentoxifylline (PTX), vinpocetine (VPT) and ticlopidine hydrochloride (TCD), each drug commonly used for vascular disorders in humans, on the pO 2 in SCC-7 (squamous cell carcinoma) tumors of C3H/HeJ mice on the radioresponse of SCC-7 tumors were investigated. When the SCC-7 implanted in the leg of C3H/HeJ mice grew about 100 mm 3 , the effects of PTX, VPT and TCD on the increase oxygen tension in the tumor was determined with polarography. The mice were injected intraperitoneally (ip) with 5 ml/kg PTX, 5 ml/kg VPT, or 10 ml/kg TCD, the tumor pO 2 increased slowly, peaked about 20-50 min postinjection, and returned to its original level in 60-80 min. When the C3H/HeJ mice bearing SCC-7 tumors in the legs were injected ip with 5 ml/kg PTX, 5 ml/kg VPT or 10 ml/kg TCD and tumors were X-irradiated 30 min later, the radiation induced growth delay of the tumor was greater than that caused by X-irradiation alone. The results in the present study, PTX, VPT and TCD increase the tumor pO 2 in rodent tumors strongly suggest that each drug may be useful for increasing the radiosensitivity of human tumor. (author)

  5. Optic nerve oxygen tension

    DEFF Research Database (Denmark)

    la Cour, M; Kiilgaard, Jens Folke; Eysteinsson, T

    2000-01-01

    To investigate the influence of acute changes in intraocular pressure on the oxygen tension in the vicinity of the optic nerve head under control conditions and after intravenous administration of 500 mg of the carbonic anhydrase inhibitor dorzolamide.......To investigate the influence of acute changes in intraocular pressure on the oxygen tension in the vicinity of the optic nerve head under control conditions and after intravenous administration of 500 mg of the carbonic anhydrase inhibitor dorzolamide....

  6. Optic nerve oxygen tension

    DEFF Research Database (Denmark)

    Kiilgaard, Jens Folke; Pedersen, D B; Eysteinsson, T

    2004-01-01

    The authors have previously reported that carbonic anhydrase inhibitors such as acetazolamide and dorzolamide raise optic nerve oxygen tension (ONPO(2)) in pigs. The purpose of the present study was to investigate whether timolol, which belongs to another group of glaucoma drugs called beta...

  7. Mitochondrial Respiration and Oxygen Tension.

    Science.gov (United States)

    Shaw, Daniel S; Meitha, Karlia; Considine, Michael J; Foyer, Christine H

    2017-01-01

    Measurements of respiration and oxygen tension in plant organs allow a precise understanding of mitochondrial capacity and function within the context of cellular oxygen metabolism. Here we describe methods that can be routinely used for the isolation of intact mitochondria, and the determination of respiratory electron transport, together with techniques for in vivo determination of oxygen tension and measurement of respiration by both CO 2 production and O 2 consumption that enables calculation of the respiratory quotient [CO 2 ]/[O 2 ].

  8. Increase in tumor oxygen tension and radiosensitivity after administration of pentoxifylline

    International Nuclear Information System (INIS)

    Hasegawa, Takeo; Gu, Yeun Hwa; Nagao, Takashi; Miyata, Katsuyuki; Song, Chang W.; Tanake, Yoshimasa; Hasegawa, Takashi

    1999-01-01

    The effects of pentoxifylline (PTX) on the pO2 and radioresponse in SCK tumors of A/J mice were investigated. When the mice were injected intraperitoneally with 5 mg/kg of PTX, the tumor pO2 increased slowly, peaked 20-50 min postinjection, and returned to its original level in 70-90 min. The magnitude of the changes in tumor pO2 after on ip injection of 25 or 50 mg/kg PTX was similar to that caused by 5 mg/kg PTX. When the A/J mice bearing SCK tumors in the legs were injected ip with 50 mg/kg PTX and the tumors were X ray irradiated 20 min later, the tumor growth delay was greater than that of radiation alone

  9. Multibreath alveolar oxygen tension imaging.

    Science.gov (United States)

    Clapp, Justin; Hamedani, Hooman; Kadlecek, Stephen; Xin, Yi; Shaghaghi, Hoora; Siddiqui, Sarmad; Rossman, Milton D; Rizi, Rahim R

    2016-10-01

    This study tested the ability of a multibreath hyperpolarized HP (3) He MRI protocol to increase the accuracy of regional alveolar oxygen tension (PA O2 ) measurements by lessening the influence of gas-flow artifacts. Conventional single-breath PA O2 measurement has been susceptible to error induced by intervoxel gas flow, particularly when used to study subjects with moderate-to-severe chronic obstructive pulmonary disease (COPD). Both single-breath and multibreath PA O2 imaging schemes were implemented in seven human subjects (one healthy, three asymptomatic smokers, and three COPD). The number and location of voxels with nonphysiologic PA O2 values generated by intervoxel gas flow were compared between the two protocols. The multibreath scheme resulted in a significantly lower total percentage of nonphysiologic PA O2 values (6.0%) than the single-breath scheme (13.7%) (P = 0.006). PA O2 maps showed several patterns of gas-flow artifacts that were present in the single-breath protocol but mitigated by the multibreath approach. Multibreath imaging also allowed for the analysis of slow-filling areas that presented no signal after a single breath. A multibreath approach enhances the accuracy and completeness of noninvasive PA O2 measurement by significantly lessening the proportion of nonphysiologic values generated by intervoxel gas flow. Magn Reson Med 76:1092-1101, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  10. Oxygen tension level and human viral infections

    Energy Technology Data Exchange (ETDEWEB)

    Morinet, Frédéric, E-mail: frederic.morinet@sls.aphp.fr [Centre des Innovations Thérapeutiques en Oncologie et Hématologie (CITOH), CHU Saint-Louis, Paris (France); Université Denis Diderot, Sorbonne Paris Cité Paris, Paris (France); Casetti, Luana [Institut Cochin INSERM U1016, Paris (France); François, Jean-Hugues; Capron, Claude [Institut Cochin INSERM U1016, Paris (France); Laboratoire d' Hématologie, Hôpital Ambroise Paré, Boulogne (France); Université de Versailles Saint-Quentin en Yvelynes, Versailles (France); Pillet, Sylvie [Laboratoire de Bactériologie-Virologie-Hygiène, CHU de Saint-Etienne, Saint-Etienne (France); Université de Lyon et Université de Saint-Etienne, Jean Monnet, GIMAP EA3064, F-42023 Saint-Etienne, Lyon (France)

    2013-09-15

    The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition. - Highlights: • Oxygen tension level regulates viral replication in vitro and possibly in vivo. • Hypoxia-inducible factor 1 (HIF-1α) is the principal factor involved in Oxygen tension level. • HIF-1α upregulates gene expression for example of HIV, JC and Kaposi sarcoma viruses. • In addition to classical chemotherapy inhibition of HIF-1α may constitute a new track to treat human viral infections.

  11. Transcutaneous oxygen tension in imminent foot gangrene

    DEFF Research Database (Denmark)

    Tønnesen, K H

    1978-01-01

    Transcutaneous oxygen tension at 44 degree C and maximal isotope clearance (90m Tc-pretechnetate + histramine) just proximal to the 1st toe and systolic toe blood pressure (strain gauge) were studied on a tilt table in patients with various degrees of obstructive arteriosclerotic disease. In legs...

  12. Dorzolamide increases retinal oxygen tension after branch retinal vein occlusion

    DEFF Research Database (Denmark)

    Noergaard, Michael Hove; Bach-Holm, Daniella; Scherfig, Erik

    2008-01-01

    To study the effect of dorzolamide on the preretinal oxygen tension (RPO(2)) in retinal areas affected by experimental branch retinal vein occlusion (BRVO) in pigs.......To study the effect of dorzolamide on the preretinal oxygen tension (RPO(2)) in retinal areas affected by experimental branch retinal vein occlusion (BRVO) in pigs....

  13. A microfluidic cell culture array with various oxygen tensions.

    Science.gov (United States)

    Peng, Chien-Chung; Liao, Wei-Hao; Chen, Ying-Hua; Wu, Chueh-Yu; Tung, Yi-Chung

    2013-08-21

    Oxygen tension plays an important role in regulating various cellular functions in both normal physiology and disease states. Therefore, drug testing using conventional in vitro cell models under normoxia often possesses limited prediction capability. A traditional method of setting an oxygen tension in a liquid medium is by saturating it with a gas mixture at the desired level of oxygen, which requires bulky gas cylinders, sophisticated control, and tedious interconnections. Moreover, only a single oxygen tension can be tested at the same time. In this paper, we develop a microfluidic cell culture array platform capable of performing cell culture and drug testing under various oxygen tensions simultaneously. The device is fabricated using an elastomeric material, polydimethylsiloxane (PDMS) and the well-developed multi-layer soft lithography (MSL) technique. The prototype device has 4 × 4 wells, arranged in the same dimensions as a conventional 96-well plate, for cell culture. The oxygen tensions are controlled by spatially confined oxygen scavenging chemical reactions underneath the wells using microfluidics. The platform takes advantage of microfluidic phenomena while exhibiting the combinatorial diversities achieved by microarrays. Importantly, the platform is compatible with existing cell incubators and high-throughput instruments (liquid handling systems and plate readers) for cost-effective setup and straightforward operation. Utilizing the developed platform, we successfully perform drug testing using an anti-cancer drug, triapazamine (TPZ), on adenocarcinomic human alveolar basal epithelial cell line (A549) under three oxygen tensions ranging from 1.4% to normoxia. The developed platform is promising to provide a more meaningful in vitro cell model for various biomedical applications while maintaining desired high throughput capabilities.

  14. "Tissue oxygen tension, a determinant of resistance to infection and ...

    African Journals Online (AJOL)

    "Tissue oxygen tension, a determinant of resistance to infection and healing" - An Inaugural Lecture. K Jönsson. Abstract. An Inaugural Lecture Given in the University of Zimbabwe on 21 June 2001. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

  15. Oxygen tension and prediction of the radiation response. Polarographic study in human breast cancer

    International Nuclear Information System (INIS)

    Pappova, N.; Siracka, E.

    1982-01-01

    Serial polarographic measurement of the tissue oxygen tension (pO 2 ) was made in the course of fractionated irradiation (preoperative or sole treatment) of advanced breast cancer in 24 patients. In responsive tumors an increase in pO 2 appeared sooner before expressive tumor size reduction became noticeable. Repeated recording of unchanged pO 2 values proved to be a good prognostic indicator of local failure. The study made on this tumor model showed that serial polarographic pO 2 determinations with suitable electrodes causing minimal trauma and providing consistent and reproductive data about changes in tumor microcirculation and oxygenation may enlarge the scale of indicators of radiation response. (author)

  16. Changes in transcutaneous oxygen tension during exercise in pulmonary emphysema.

    OpenAIRE

    Hughes, J A; Gray, B J; Hutchison, D C

    1984-01-01

    Continuous measurements of transcutaneous oxygen tension (tcPO2) were made in 23 patients with radiological evidence of emphysema, at rest and during a maximal progressive exercise test. tcPO2 during the final phase of exercise was compared with tcPO2 at rest; the mean change (exercising minus resting value) in tcPO2 (delta tcPO2) was -0.8 mm Hg (SD 10.5, range -18 to +25) (-0.1 kPa (SD 1.4, range -2.4 to +3.3]. delta tcPO2 was correlated with: resting arterial oxygen tension (PaO2) (r = 0.60...

  17. Oxygen diffusion and oxygen effect in tumor tissue

    International Nuclear Information System (INIS)

    Eissa, H.M.; Hehn, G.

    1979-06-01

    The diffusion of oxygen in tumor cords of bronchus carcinoma of the lung have been studied with refined computer methods for solving the diffusion equation in axis symmetric tumor structures. In this tumor configuration we may find three different regions consisting of euoxic cells, hypoxic tumor cells and necrotic parts. In the case of oxygen supply from a capillary inside a cylinder of tumor tissue with radius 200 μm or in a tumor cord of radius 300 μm with oxygen supply by capillaries outside, we get a relation of well oxygenated cells to hypoxic cells approximately as 1:8 or as 1:1.1 respectively. Of course most of the tumor cords observed in histological slices have smaller diameters, so that an average of approximately 20% hypoxic cells can be assumed. Based on the work of Ardenne, the diffusion of oxygen and glucose in a tumor of type DS-carcinosarcom has been investigated in both intact tumor and tumor treated with ionizing radiation. We can show that a strong reoxygenation effect takes place in that the well supplied regions may increase in some tumor configurations up to a factor of four by volume. The biological consequences of the oxygen pressure determined in tumor cells are discussed in detail. The investigation of oxygen diffusion in the intercapillary tumor region should give a quantitative physical basis for considering the oxygen effect with the aim to explain the advantages of neutron therapy against conventional radiotherapy. (orig./MG) [de

  18. Oxygen Tension Regulates Human Mesenchymal Stem Cell Paracrine Functions

    OpenAIRE

    Paquet, Joseph; Deschepper, Mickael; Moya, Adrien; Logeart-Avramoglou, Delphine; Boisson-Vidal, Catherine; Petite, Hervé

    2015-01-01

    This study examined the shift of the human mesenchymal stem cell (hMSC) cytokine signature induced by oxygen tension. Conditioned media obtained from hMSCs cultured under near anoxia exhibited significantly enhanced chemotactic and proangiogenic properties and a significant decrease in the inflammatory mediator content. These results elucidate important aspects of using MSCs in regenerative medicine, contribute to improving the efficacy of such therapies, and highlight the interest in using c...

  19. Hemodynamic parameters change earlier than tissue oxygen tension in hemorrhage.

    Science.gov (United States)

    Pestel, Gunther J; Fukui, Kimiko; Kimberger, Oliver; Hager, Helmut; Kurz, Andrea; Hiltebrand, Luzius B

    2010-05-15

    Untreated hypovolemia results in impaired outcome. This study tests our hypothesis whether general hemodynamic parameters detect acute blood loss earlier than monitoring parameters of regional tissue beds. Eight pigs (23-25 kg) were anesthetized and mechanically ventilated. A pulmonary artery catheter and an arterial catheter were inserted. Tissue oxygen tension was measured with Clark-type electrodes in the jejunal and colonic wall, in the liver, and subcutaneously. Jejunal microcirculation was assessed by laser Doppler flowmetry (LDF). Intravascular volume was optimized using difference in pulse pressure (dPP) to keep dPP below 13%. Sixty minutes after preparation, baseline measurements were taken. At first, 5% of total blood volume was withdrawn, followed by another 5% increment, and then in 10% increments until death. After withdrawal of 5% of estimated blood volume, dPP increased from 6.1% +/- 3.0% to 20.8% +/- 2.7% (P < 0.01). Mean arterial pressure (MAP), mean pulmonary artery pressure (PAP) and pulmonary artery occlusion pressure (PAOP) decreased with a blood loss of 10% (P < 0.01). Cardiac output (CO) changed after a blood loss of 20% (P < 0.05). Tissue oxygen tension in central organs, and blood flow in the jejunal muscularis decreased (P < 0.05) after a blood loss of 20%. Tissue oxygen tension in the skin, and jejunal mucosa blood flow decreased (P < 0.05) after a blood loss of 40% and 50%, respectively. In this hemorrhagic pig model systemic hemodynamic parameters were more sensitive to detect acute hypovolemia than tissue oxygen tension measurements or jejunal LDF measurements. Acute blood loss was detected first by dPP. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  20. Modeling the oxygen microheterogeneity of tumors for photodynamic therapy dosimetry

    Science.gov (United States)

    Pogue, Brian W.; Paulsen, Keith D.; O'Hara, Julia A.; Hoopes, P. Jack; Swartz, Harold

    2000-03-01

    Photodynamic theory of tumors uses optical excitation of a sensitizing drug within tissue to produce large deposits of singlet oxygen, which are thought to ultimately cause the tumor destruction. Predicting dose deposition of singlet oxygen in vivo is challenging because measurement of this species in vivo is not easily achieved. But it is possible to follow the concentration of oxygen in vivo, and so measuring the oxygen concentration transients during PDT may provide a viable method of estimating the delivered dose of singlet oxygen. However modeling the microscopic heterogeneity of the oxygen distribution within a tumor is non-trivial, and predicting the microscopic dose deposition requires further study, but this study present the framework and initial calibration needed or modeling oxygen transport in complex geometries. Computational modeling with finite elements provides a versatile structure within which oxygen diffusion and consumption can be modeled within realistic tissue geometries. This study develops the basic tools required to simulate a tumor region, and examines the role of (i) oxygen supply and consumption rates, (ii) inter- capillary spacing, (iii) photosensitizer distribution, and (iv) differences between simulated tumors and those derived directly from histology. The result of these calculations indicate that realistic tumor tissue capillary networks can be simulated using the finite element method, without excessive computational burden for 2D regions near 1 mm2, and 3D regions near 0.1mm3. These simulations can provide fundamental information about tissue and ways to implement appropriate oxygen measurements. These calculations suggest that photodynamic therapy produces the majority of singlet oxygen in and near the blood vessels, because these are the sites of highest oxygen tension. These calculations support the concept that tumor vascular regions are the major targets for PDT dose deposition.

  1. Renal transplantation induces mitochondrial uncoupling, increased kidney oxygen consumption, and decreased kidney oxygen tension

    NARCIS (Netherlands)

    Papazova, Diana A.; Friederich-Persson, Malou; Joles, Jaap A.; Verhaar, Marianne C.

    2015-01-01

    Hypoxia is an acknowledged pathway to renal injury and ischemia-reperfusion (I/R) and is known to reduce renal oxygen tension (PO2). We hypothesized that renal I/R increases oxidative damage and induces mitochondrial uncoupling, resulting in increased oxygen consumption and hence kidney

  2. Cerebral Microcirculation and Oxygen Tension in the Human Secondary Cortex

    Science.gov (United States)

    Linninger, A. A.; Gould, I. G.; Marinnan, T.; Hsu, C.-Y.; Chojecki, M.; Alaraj, A.

    2013-01-01

    The three-dimensional spatial arrangement of the cortical microcirculatory system is critical for understanding oxygen exchange between blood vessels and brain cells. A three-dimensional computer model of a 3 × 3 × 3 mm3 subsection of the human secondary cortex was constructed to quantify oxygen advection in the microcirculation, tissue oxygen perfusion, and consumption in the human cortex. This computer model accounts for all arterial, capillary and venous blood vessels of the cerebral microvascular bed as well as brain tissue occupying the extravascular space. Microvessels were assembled with optimization algorithms emulating angiogenic growth; a realistic capillary bed was built with space filling procedures. The extravascular tissue was modeled as a porous medium supplied with oxygen by advection–diffusion to match normal metabolic oxygen demand. The resulting synthetic computer generated network matches prior measured morphometrics and fractal patterns of the cortical microvasculature. This morphologically accurate, physiologically consistent, multi-scale computer network of the cerebral microcirculation predicts the oxygen exchange of cortical blood vessels with the surrounding gray matter. Oxygen tension subject to blood pressure and flow conditions were computed and validated for the blood as well as brain tissue. Oxygen gradients along arterioles, capillaries and veins agreed with in vivo trends observed recently in imaging studies within experimental tolerances and uncertainty. PMID:23842693

  3. Effect of pneumatic tourniquet on muscle oxygen tension.

    Science.gov (United States)

    Santavirta, S; Höckerstedt, K; Niinikoski, J

    1978-10-01

    Recent investigations suggest that circulation in a limb can be reduced with a tourniquet to less than 1 per cent of the control limb, or even completely occluded. The development of tissue oxygen tonometry with implanted silastic tubes has provided new possibilities for assessing muscle tissue oxygen tension. In the present work, this method was employed to register the effect of tourniquet blackade on the lower limb muscle PO2 in rabbits. The duration of the tourniquet blockade was 60, 120 and 180 minutes. The baseline muscle PO2 in the tibialis anterior muscle was 22.6 +/- 0.6 mmHg. During the tourniquet blockade the oxygen tension dropped to minimal values between 9.2 +/- 0.5 and 10.7 +/- 0.6 mmHg in these experimental groups, but the tissue microclimate never reached fully anoxic conditions. The rapid response of muscle PO2 to oxygen breathing after release of the blockade suggests that limb microcirculation tolerates tourniquet occlusion well.

  4. Oxygen tension during biofilm growth influences the efficacy antimicrobial agents

    Directory of Open Access Journals (Sweden)

    Raquel Pippi ANTONIAZZI

    Full Text Available Abstract Objective To compare the antimicrobial efficacy of a 0.12% chlorhexidine (CHX and herbal green tea (Camellia sinensis solution on established biofilms formed at different oxygen tensions in an in situ model. Method Twenty-five dental students were eligible for the study. In situ devices with standardized enamel specimens (ES facing the palatal and buccal sides were inserted in the mouths of volunteers for a 7 day period. No agent was applied during the first four days. From the fifth day onward, both agents were applied to the test ES group and no agent was applied to the control ES group. After 7 days the ES fragments were removed from the devices, sonicated, plated on agar, and incubated for 24 h at 37 °C to determine and quantify the colony forming units (CFUs. Result CHX had significantly higher efficacy compared to green tea on the buccal (1330 vs. 2170 CFU/µL and palatal (2250 vs. 2520 CFU/µL ES. In addition, intragroup comparisons showed significantly higher efficacy in buccal ES over palatal ES (1330 vs. 2250 CFU/µL for CHX and 2170 vs, 2520 CFU/µL for CV for both solutions. Analysis of the ES controls showed significantly higher biofilm formation in palatal ES compared to buccal ES. Conclusion CHX has higher efficacy than green tea on 4-day biofilms. The efficacy of both agents was reduced for biofilms grown in a low oxygen tension environment. Therefore, the oxygen tension environment seems to influence the efficacy of the tested agents.

  5. Oxygen Tension Regulates Human Mesenchymal Stem Cell Paracrine Functions.

    Science.gov (United States)

    Paquet, Joseph; Deschepper, Mickael; Moya, Adrien; Logeart-Avramoglou, Delphine; Boisson-Vidal, Catherine; Petite, Hervé

    2015-07-01

    : Mesenchymal stem cells (MSCs) have captured the attention and research endeavors of the scientific world because of their differentiation potential. However, there is accumulating evidence suggesting that the beneficial effects of MSCs are predominantly due to the multitude of bioactive mediators secreted by these cells. Because the paracrine potential of MSCs is closely related to their microenvironment, the present study investigated and characterized select aspects of the human MSC (hMSC) secretome and assessed its in vitro and in vivo bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. In contrast to supernatant conditioned media (CM) obtained from hMSCs cultured at either 5% or 21% of O2, CM from hMSCs cultured under near anoxia exhibited significantly (p mesenchymal stem cell (hMSC) secretome and assessed its in vitro and in vivo biological bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. The present study provided the first evidence of a shift of the hMSC cytokine signature induced by oxygen tension, particularly near anoxia (0.1% O2). Conditioned media obtained from hMSCs cultured under near anoxia exhibited significantly enhanced chemotactic and proangiogenic properties and a significant decrease in the inflammatory mediator content. These findings provide new evidence that elucidates aspects of great importance for the use of MSCs in regenerative medicine, could contribute to improving the efficacy of such therapies, and most importantly highlighted the interest in using conditioned media in therapeutic modalities. ©AlphaMed Press.

  6. Carbonic anhydrase inhibition increases retinal oxygen tension and dilates retinal vessels

    DEFF Research Database (Denmark)

    Pedersen, Daniella Bach; Koch Jensen, Peter; la Cour, Morten

    2005-01-01

    Carbonic anhydrase inhibitors (CAIs) increase blood flow in the brain and probably also in the optic nerve and retina. Additionally they elevate the oxygen tension in the optic nerve in the pig. We propose that they also raise the oxygen tension in the retina. We studied the oxygen tension in the...... in the pig retina and optic nerve before and after dorzolamide injection. Also the retinal vessel diameters during carbonic anhydrase inhibition were studied....

  7. A method for volumetric retinal tissue oxygen tension imaging.

    Science.gov (United States)

    Felder, Anthony E; Wanek, Justin; Teng, Pang-Yu; Blair, Norman P; Shahidi, Mahnaz

    2018-01-01

    Inadequate retinal oxygenation occurs in many vision-threatening retinal diseases, including diabetic retinopathy, retinal vascular occlusions, and age-related macular degeneration. Therefore, techniques that assess retinal oxygenation are necessary to understand retinal physiology in health and disease. The purpose of the current study is to report a method for the three-dimensional (3D) imaging of retinal tissue oxygen tension (tPO 2 ) in rats. Imaging was performed in Long Evans pigmented rats under systemic normoxia (N = 6) or hypoxia (N = 3). A vertical laser line was horizontally scanned on the retina and a series of optical section phase-delayed phosphorescence images were acquired. From these images, phosphorescence volumes at each phase delay were constructed and a 3D retinal tPO 2 volume was generated. Retinal tPO 2 volumes were quantitatively analyzed by generating retinal depth profiles of mean tPO 2 (M tPO2 ) and the spatial variation of tPO 2 (SV tPO2 ). The effects of systemic condition (normoxia/hypoxia) and retinal depth on M tPO2 and SV tPO2 were determined by mixed linear model. Each 3D retinal tPO 2 volume was approximately 500 × 750 × 200 μm (horizontal × vertical × depth) and consisted of 45 en face tPO 2 images through the retinal depth. M tPO2 at the chorioretinal interface was significantly correlated with systemic arterial oxygen tension (P = 0.007; N = 9). There were significant effects of both systemic condition and retinal depth on M tPO2 and SV tPO2 , such that both were lower under hypoxia than normoxia and higher in the outer retina than inner retina (P < 0.001). For the first time, 3D imaging of retinal tPO 2 was demonstrated, with potential future application for assessment of physiological alterations in animal models of retinal diseases.

  8. Oxygen Tension in the Aqueous Humor of Human Eyes under Different Oxygenation Conditions

    Directory of Open Access Journals (Sweden)

    Farideh Sharifipour

    2013-01-01

    Full Text Available Purpose: To measure oxygen tension in the aqueous humor of human eyes under different oxygenation conditions. Methods: This prospective comparative interventional case series consisted of two parts. In the first part, 120 consecutive patients scheduled for cataract surgery were randomized into group I (control group in which surgery was performed under local anesthesia inhaling 21% oxygen; group II in whom general anesthesia using 50% oxygen was employed; and group III receiving general anesthesia with 100% oxygen. After aspirating 0.2 ml aqueous humor under sterile conditions, the aqueous sample and a simultaneously drawn arterial blood sample were immediately analyzed using a blood gas analyzer. In part II the same procedures were performed in 10 patients after fitting a contact lens and patching the eye for 20 minutes (group IV and in 10 patients after transcorneal delivery of oxygen at a flow rate of 5 L/min (group V. Results: Mean aqueous PO2 in groups I, II and III was 112.3±6.2, 141.1±20.4, and 170.1±27 mmHg, respectively (P values <0.001 and mean arterial PO2 was 85.7±7.9, 184.6±46, and 379.1±75.9 mmHg, respectively (P values <0.001. Aqueous PO2 was 77.2±9.2 mmHg in group IV and 152.3±10.9 mmHg in group V (P values <0.001. There was a significant correlation between aqueous and blood PO2 (r=0.537, P<0.001. The contribution of atmospheric oxygen to aqueous PO2 was 23.7%. Conclusion: Aqueous oxygen tension is mostly dependent on the systemic circulation and in part on the atmosphere. Increasing inspiratory oxygen and transcorneal oxygen delivery both increase aqueous PO2 levels.

  9. Bladder urine oxygen tension for assessing renal medullary oxygenation in rabbits: experimental and modeling studies

    OpenAIRE

    Sgouralis, Ioannis; Kett, Michelle M.; Ow, Connie P. C.; Abdelkader, Amany; Layton, Anita T.; Gardiner, Bruce S.; Smith, David W.; Lankadeva, Yugeesh R.; Evans, Roger G.

    2016-01-01

    Oxygen tension (Po2) of urine in the bladder could be used to monitor risk of acute kidney injury if it varies with medullary Po2. Therefore, we examined this relationship and characterized oxygen diffusion across walls of the ureter and bladder in anesthetized rabbits. A computational model was then developed to predict medullary Po2 from bladder urine Po2. Both intravenous infusion of [Phe2,Ile3,Orn8]-vasopressin and infusion of NG-nitro-l-arginine reduced urinary Po2 and medullary Po2 (8–1...

  10. Oxygen Tension Beneath Scleral Lenses of Different Clearances.

    Science.gov (United States)

    Giasson, Claude J; Morency, Jeanne; Melillo, Marc; Michaud, Langis

    2017-04-01

    To evaluate the relative partial pressure in oxygen (pO2) at the corneal surface under Boston XO2 scleral lenses (SL) fitted with targeted clearances of 200 and 400 μm (SL200 and SL400). During this prospective study, the right eyes of eight normal subjects were fitted with SL200 and SL400. Clearance, validated after 5 minutes of wear with an optical coherence tomograph, was used with lens thicknesses to calculate transmissibility and estimate pO2. Corneal pO2s were measured with an oxygen electrode after 5 minutes of (1) corneal exposure to calibrating gases with various pO2 or of (2) SL wear. Decays in pO2 were modeled to an exponential. Linear regression between exponent k of these decays and calibrating gas pO2s allowed for the calculation of corneal pO2 under SL. Differences between pO2s beneath SL200 and SL400 were tested with a mixed ANOVA. The estimated transmissibility based on thicknesses and clearances (239.7 ± 34.7; 434.5 ± 33.2 μm) predicted a corneal pO2 of 8.52 ± 0.51 and 6.37 ± 0.28% for SL200 and SL400. These values were close to measured pO2: 9.07 ± 0.86 and 6.19 ± 0.87% (mean ± SEM) (P time, an 18-mm scleral lens fitted with a 400-μm clearance reduces the oxygen tension available to the cornea by 30% compared to a similar lens fitted with a 200-μm clearance after 5 minutes of wear.

  11. Optic nerve oxygen tension in pigs and the effect of carbonic anhydrase inhibitors

    DEFF Research Database (Denmark)

    Stefánsson, E; Jensen, P K; Eysteinsson, T

    1999-01-01

    To evaluate how the oxygen tension of the optic nerve (ONP(O)2) is affected by the administration of the carbonic anhydrase inhibitors dorzolamide and acetazolamide and by alterations in oxygen and carbon dioxide in the breathing mixture.......To evaluate how the oxygen tension of the optic nerve (ONP(O)2) is affected by the administration of the carbonic anhydrase inhibitors dorzolamide and acetazolamide and by alterations in oxygen and carbon dioxide in the breathing mixture....

  12. Tumor radiation responses and tumor oxygenation in aging mice

    International Nuclear Information System (INIS)

    Rockwell, S.

    1989-01-01

    EMT6 mouse mammary tumors transplanted into aging mice are less sensitive to radiation than tumors growing in young adult animals. The experiments reported here compare the radiation dose-response curves defining the survivals of tumor cells in aging mice and in young adult mice. Cell survival curves were assessed in normal air-breathing mice and in mice asphyxiated with N 2 to produce uniform hypoxia throughout the tumors. Analyses of survival curves revealed that 41% of viable malignant cells were severely hypoxic in tumors in aging mice, while only 19% of the tumor cells in young adult animals were radiobiologically hypoxic. This did not appear to reflect anaemia in the old animals. Treatment of aging animals with a perfluorochemical emulsion plus carbogen (95% O 2 /5% CO 2 ) increased radiation response of the tumors, apparently by improving tumor oxygenation and decreasing the number of severely hypoxic, radiation resistant cells in the tumors. (author)

  13. Characterization and validation of noninvasive oxygen tension measurements in human glioma xenografts by 19F-MR relaxometry

    International Nuclear Information System (INIS)

    Sanden, Boudewijn P.J. van der; Heerschap, Arend; Simonetti, Arjan W.; Rijken, Paul F.J.W.; Peters, Hans P.W.; Stbeen, Georg; Kogel, Albert J. van der

    1999-01-01

    Purpose: The aim of this study was to characterize and to validate noninvasive 19 F-magnetic resonance relaxometry for the measurement of oxygen tensions in human glioma xenografts in nude mice. The following three questions were addressed: 1. When perfluorocarbon compounds (PFCs) are administrated intravenously, which tumor regions are assessed by 19 F-MR relaxometry? 2. Are oxygen tension as detected by 19 F-MR relaxometry (pO 2/relaxo ) comparable to Eppendorf O 2 -electrode measurements (pO 2/electrode )? 3. Can 19 F-MR relaxometry be used to detect oxygen tension changes in tumor tissue during carbogen breathing? Methods and Materials: Slice-selective 19 F-MR relaxometry was carried out with perfluoro-15-crown-5-ether as oxygen sensor. The PFC was injected i.v. 3 days before the 19 F-MR experiments. Two datasets were acquired before and two after the start of carbogen breathing. The distribution of PFCs and necrotic areas were analyzed in 19 F-Spin Echo (SE) density MR images and T 2 -weighted 1 H-SE MR images, respectively. One day after the MR investigations, oxygen tensions were measured by oxygen electrodes in the same slice along two perpendicular tracks. These measurements were followed by (immuno)histochemical analysis of the 2D distribution of perfused microvessels, hypoxic cells, necrotic areas, and macrophages. Results: The PFCs mainly became sequestered in perfused regions at the tumor periphery; thus, 19 F-MR relaxometry probed mean oxygen tensions in these regions throughout the selected MR slice. In perfused regions of the tumor, mean pO 2/relaxo values were comparable to mean pO 2/electrode values, and varied from 0.03 to 9 mmHg. Median pO 2/electrode values of both tracks were lower than mean pO 2/relaxo values, because low pO 2/electrode values that originate from hypoxic and necrotic areas were also included in calculations of median pO 2/electrode values. After 8-min carbogen breathing, the average pO 2/relaxo increase was 3.3 ± 0.8 (SEM

  14. Measuring oxygen tension modulation, induced by a new pre-radiotherapy therapeutic, in a mammary window chamber mouse model

    Science.gov (United States)

    Schafer, Rachel; Gmitro, Arthur F.

    2015-03-01

    Tumor regions under hypoxic or low oxygen conditions respond less effectively to many treatment strategies, including radiation therapy. A novel investigational therapeutic, NVX-108 (NuvOx Pharma), has been developed to increase delivery of oxygen through the use of a nano-emulsion of dodecofluoropentane. By raising pO2 levels prior to delivering radiation, treatment efficacy may be improved. To aid in evaluating the novel drug, oxygen tension was quantitatively measured, spatially and temporally, to record the effect of administrating NVX-108 in an orthotopic mammary window chamber mouse model of breast cancer. The oxygen tension was measured through the use of an oxygen-sensitive coating, comprised of phosphorescent platinum porphyrin dye embedded in a polystyrene matrix. The coating, applied to the surface of the coverslip of the window chamber through spin coating, is placed in contact with the mammary fat pad to record the oxygenation status of the surface tissue layer. Prior to implantation of the window chamber, a tumor is grown in the SCID mouse model by injection of MCF-7 cells into the mammary fat pad. Two-dimensional spatial distributions of the pO2 levels were obtained through conversion of measured maps of phosphorescent lifetime. The resulting information on the spatial and temporal variation of the induced oxygen modulation could provide valuable insight into the optimal timing between administration of NVX-108 and radiation treatment to provide the most effective treatment outcome.

  15. Effects of motexafin gadolinium on tumor oxygenation and cellular oxygen consumption

    International Nuclear Information System (INIS)

    Donnelly, E.T.; Liu, Y.; Rockwell, S.; Magda, D.

    2003-01-01

    Full text: Recent work in our laboratory showed that motexafin gadolinium (MGd, Xcytrin), a drug currently in Phase III clinical trials as an adjuvant to radiation therapy, modulates the oxygen tensions in EMT6 tumors. The median pO 2 increased from the control value of 1.5±0.4 mmHg to 7.4 ± 3.8 mmHg six hours after treatment with 40 μmol/kg MGd and the percentage of severely hypoxic readings in the tumors ( 7 plateau phase EMT6 cells in 3 mL Dulbecco's Modified Eagle's Medium supplemented with 10% dialyzed fetal bovine serum, which contains no ascorbic acid. In the absence of ascorbic acid, 100 μM MGd did not alter the cellular oxygen consumption rate for EMT6 cells significantly. Marked inhibition of cellular oxygen consumption was observed when cells were incubated with 100 μM MGd in medium supplemented with equimolar ascorbic acid (a 31.5% decrease in consumption was observed after 6 hours of treatment). The 5% mannitol vehicle solution with equimolar ascorbic acid had no discernible effect on cellular oxygen consumption. Ascorbic acid may facilitate cellular uptake of MGd via the intermediate formation of a MGd-oxalate complex. These studies suggest that changes in cellular oxygen consumption could contribute to the changes in tumor oxygenation seen after administration of MGd. These experiments were supported by Pharmacyclics and training grant T32CA09085 from the NIH (E.T.D.). We thank Dr. Raymond Russell for allowing us to use his oxygen electrode apparatus

  16. Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells

    Directory of Open Access Journals (Sweden)

    Handgretinger Rupert

    2010-01-01

    Full Text Available Abstract Background Human multipotent mesenchymal stromal cells (MSC can be isolated from various tissues including bone marrow. Here, MSC participate as bone lining cells in the formation of the hematopoietic stem cell niche. In this compartment, the oxygen tension is low and oxygen partial pressure is estimated to range from 1% to 7%. We analyzed the effect of low oxygen tensions on human MSC cultured with platelet-lysate supplemented media and assessed proliferation, morphology, chromosomal stability, immunophenotype and plasticity. Results After transferring MSC from atmospheric oxygen levels of 21% to 1%, HIF-1α expression was induced, indicating efficient oxygen reduction. Simultaneously, MSC exhibited a significantly different morphology with shorter extensions and broader cell bodies. MSC did not proliferate as rapidly as under 21% oxygen and accumulated in G1 phase. The immunophenotype, however, was unaffected. Hypoxic stress as well as free oxygen radicals may affect chromosomal stability. However, no chromosomal abnormalities in human MSC under either culture condition were detected using high-resolution matrix-based comparative genomic hybridization. Reduced oxygen tension severely impaired adipogenic and osteogenic differentiation of human MSC. Elevation of oxygen from 1% to 3% restored osteogenic differentiation. Conclusion Physiologic oxygen tension during in vitro culture of human MSC slows down cell cycle progression and differentiation. Under physiological conditions this may keep a proportion of MSC in a resting state. Further studies are needed to analyze these aspects of MSC in tissue regeneration.

  17. Tumor Oxygen Dynamics: Correlation of In Vivo MRI with Histological Findings

    Directory of Open Access Journals (Sweden)

    Dawen Zhao

    2003-07-01

    Full Text Available Tumor oxygenation has long been recognized as a significant factor influencing cancer therapy. We recently established a novel magnetic resonance in vivo approach to measuring regional tumor oxygen tension, FREDOM (Fluorocarbon Relaxometry Using Echo Planar Imaging for Dynamic Oxygen Mapping, using hexafluorobenzene (HFB as the reporter molecule. We have now investigated oxygen dynamics in the two Dunning prostate R3327 rat tumor sublines, AT1 and H. FREDOM revealed considerable intratumoral heterogeneity in the distribution of pO2 values in both sublines. The anaplastic fastergrowing AT1 tumors were more hypoxic compared with the size-matched, well-differentiated, and slower-growing H tumors. Respiratory challenge with oxygen produced significant increases in mean and median pO2 in all the H tumors (P3 cm3. Immunohistochemical studies using the hypoxia marker, pimonidazole, and the vascular endothelial cell marker, CD31, confirmed that the H tumors had more extensive vasculature and less hypoxia than the AT1 tumors. These results further validate the utilization of FREDOM to monitor tumor oxygenation and concur with the hypothesis that the level of hypoxia is related to tumor growth rate and poor vascularity.

  18. In vivo mitochondrial oxygen tension measured by a delayed fluorescence lifetime technique

    NARCIS (Netherlands)

    Mik, Egbert G.; Johannes, Tanja; Zuurbier, Coert J.; Heinen, Andre; Houben-Weerts, Judith H. P. M.; Balestra, Gianmarco M.; Stap, Jan; Beek, Johan F.; Ince, Can

    2008-01-01

    Mitochondrial oxygen tension (mitoPO(2)) is a key parameter for cellular function, which is considered to be affected under various pathophysiological circumstances. Although many techniques for assessing in vivo oxygenation are available, no technique for measuring mitoPO(2) in vivo exists. Here we

  19. Radioprotection of mouse skin by WR-2721: the critical influence of oxygen tension

    International Nuclear Information System (INIS)

    Denekamp, J.; Michael, B.D.; Rojas, A.; Stewart, F.A.

    1982-01-01

    The epidermal clone assay has been used to study the radioprotective effect of WR-2721 on mouse skin under different conditions of oxygenation and under anoxia. The skin has shown a progressive decrease in sensitivity as the inspired gas has changed from 100% oxygen towards 0% oxygen. Compared with mice breathning 100% oxygen, those breathing air are partially protected. The inspired oxygen concentration to give half the full oxygen effect is 10-12%. The radioprotecton observed with 400 mg/kg WR-2721 is markedly dependent on the ambient oxygen concentration. The protection factor is 1.1 or less in mice breathing 5%, 1% or 0% oxygen. Protection is maximal (1.95) in air and in 50% oxygen and diminishes to 1.6 at higher oxygen tensions

  20. Bladder urine oxygen tension for assessing renal medullary oxygenation in rabbits: experimental and modeling studies

    Science.gov (United States)

    Sgouralis, Ioannis; Kett, Michelle M.; Ow, Connie P. C.; Abdelkader, Amany; Layton, Anita T.; Gardiner, Bruce S.; Smith, David W.; Lankadeva, Yugeesh R.

    2016-01-01

    Oxygen tension (Po2) of urine in the bladder could be used to monitor risk of acute kidney injury if it varies with medullary Po2. Therefore, we examined this relationship and characterized oxygen diffusion across walls of the ureter and bladder in anesthetized rabbits. A computational model was then developed to predict medullary Po2 from bladder urine Po2. Both intravenous infusion of [Phe2,Ile3,Orn8]-vasopressin and infusion of NG-nitro-l-arginine reduced urinary Po2 and medullary Po2 (8–17%), yet had opposite effects on renal blood flow and urine flow. Changes in bladder urine Po2 during these stimuli correlated strongly with changes in medullary Po2 (within-rabbit r2 = 0.87–0.90). Differences in the Po2 of saline infused into the ureter close to the kidney could be detected in the bladder, although this was diminished at lesser ureteric flow. Diffusion of oxygen across the wall of the bladder was very slow, so it was not considered in the computational model. The model predicts Po2 in the pelvic ureter (presumed to reflect medullary Po2) from known values of bladder urine Po2, urine flow, and arterial Po2. Simulations suggest that, across a physiological range of urine flow in anesthetized rabbits (0.1–0.5 ml/min for a single kidney), a change in bladder urine Po2 explains 10–50% of the change in pelvic urine/medullary Po2. Thus, it is possible to infer changes in medullary Po2 from changes in urinary Po2, so urinary Po2 may have utility as a real-time biomarker of risk of acute kidney injury. PMID:27385734

  1. Discrepancies between measured changes of radiobiological hypoxic fraction and oxygen tension monitoring using two assay systems

    International Nuclear Information System (INIS)

    Sasai, K.; Brown, J.M.

    1994-01-01

    This study was conducted to assess the ability of computerized pO 2 histography to measure changes in tumor oxygenation produced by low oxygen breathing. Female syngeneic C3H/Km mice bearing SCC VII/St carcinomas were used in these experiments. Changes in tumor oxygenation produced by the mice breathing 10% oxygen were assessed with computerized pO2 histography, 3 H-misonidazole binding, and the paired survival curve assay of radiosensitivity. The hypoxic cell fraction of the tumors in mice breathing 10% oxygen was 3.1 times higher than that of tumors in mice breathing normal air determined by an in vivo-in vitro clonogenic assay. Binding of radiolabeled misonidazole to the tumors in mice breathing 10% oxygen was also significantly higher than that to tumors in mice breathing normal air (p 2 value for the tumor. The number of pO 2 readings lower than 5 mmHg in the tumor was not affected by the 10% oxygen breathing. These findings indicate that increases in radiobiological hypoxic fraction produced by lower blood oxygen levels may not correlate well with the results of polarographic measurements of tumor pO 2 levels. 29 refs., 4 figs., 1 tab

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

    Science.gov (United States)

    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 (PO 2 ) and inner retinal oxygen extraction fraction (OEF), whereas outer retinal oxygen consumption (QO 2 ) relies on oxygen availability by the choroid and is contingent upon retinal tissue oxygen tension (tPO 2 ) 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 PO 2 and tPO 2 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 , tPO 2 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.

  3. Localized increase of tissue oxygen tension by magnetic targeted drug delivery

    Science.gov (United States)

    Liong, Celine; Ortiz, Daniel; Ao-ieong, Eilleen; Navati, Mahantesh S.; Friedman, Joel M.; Cabrales, Pedro

    2014-07-01

    Hypoxia is the major hindrance to successful radiation therapy of tumors. Attempts to increase the oxygen (O2) tension (PO2) of tissue by delivering more O2 have been clinically disappointing, largely due to the way O2 is transported and released by the hemoglobin (Hb) within the red blood cells (RBCs). Systemic manipulation of O2 transport increases vascular resistance due to metabolic autoregulation of blood flow to prevent over oxygenation. This study investigates a new technology to increase O2 delivery to a target tissue by decreasing the Hb-O2 affinity of the blood circulating within the targeted tissue. As the Hb-O2 affinity decreases, the tissue PO2 to satisfy tissue O2 metabolic needs increases without increasing O2 delivery or extraction. Paramagnetic nanoparticles (PMNPs), synthetized using gadolinium oxide, were coated with the cell permeable Hb allosteric effector L35 (3,5-trichlorophenylureido-phenoxy-methylpropionic acid). L35 decreases Hb affinity for O2 and favors the release of O2. The L35-coated PMNPs (L35-PMNPs) were intravenously infused (10 mg kg-1) to hamsters instrumented with the dorsal window chamber model. A magnetic field of 3 mT was applied to localize the effects of the L35-PMNPs to the window chamber. Systemic O2 transport characteristics and microvascular tissue oxygenation were measured after administration of L35-PMNPs with and without magnetic field. The tissue PO2 in untreated control animals was 25.2 mmHg. L35-PMNPs without magnetic field decreased tissue PO2 to 23.4 mmHg, increased blood pressure, and reduced blood flow, largely due to systemic modification of Hb-O2 affinity. L35-PMNPs with magnetic field increased tissue PO2 to 27.9 mmHg, without systemic or microhemodynamic changes. These results indicate that localized modification of Hb-O2 affinity can increase PO2 of target tissue without affecting systemic O2 delivery or triggering O2 autoregulation mechanisms. This technology can be used to treat local hypoxia and to

  4. Indomethacin decreases optic nerve oxygen tension by a mechanism other than cyclo-oxygenase inhibition

    DEFF Research Database (Denmark)

    Noergaard, M Hove; Pedersen, D Bach; Bang, K

    2008-01-01

    We investigated the effect of several Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), on the preoptic nerve oxygen tension (ONPO2), as indomethacin previously has demonstrated a strong decreasing effect on ONPO2. We tested whether these NSAIDs, like indomethacin, also reduce the increasing effect...

  5. Methyl sterol and cyclopropane fatty acid composition of Methylococcus capsulatus grown at low oxygen tensions

    Science.gov (United States)

    Jahnke, L. L.; Nichols, P. D.

    1986-01-01

    The sterol and fatty acid concentrations for M. capsulatus grown in fed-batch cultures over a wide range of oxygen tensions (0.1-10.6 percent) and at a constant methane level are evaluated. The analyses reveal that the biomass decreases as oxygen levels are lowered; the sterol concentration increases when the oxygen range is between 0.5-1.1 percent and decreases when the oxygen range is below 0.5 percent; and the amount of monounsaturated C16 decreases and the concentration of cyclopropane fatty acids increases after oxygen is reduced. It is noted that growth and membrane synthesis occur at low oxygen concentrations and that the synthesis of membrane lipids responds to growth conditions.

  6. Control of oxygen tension recapitulates zone-specific functions in human liver microphysiology systems.

    Science.gov (United States)

    Lee-Montiel, Felipe T; George, Subin M; Gough, Albert H; Sharma, Anup D; Wu, Juanfang; DeBiasio, Richard; Vernetti, Lawrence A; Taylor, D Lansing

    2017-10-01

    This article describes our next generation human Liver Acinus MicroPhysiology System (LAMPS). The key demonstration of this study was that Zone 1 and Zone 3 microenvironments can be established by controlling the oxygen tension in individual devices over the range of ca. 3 to 13%. The oxygen tension was computationally modeled using input on the microfluidic device dimensions, numbers of cells, oxygen consumption rates of hepatocytes, the diffusion coefficients of oxygen in different materials and the flow rate of media in the MicroPhysiology System (MPS). In addition, the oxygen tension was measured using a ratiometric imaging method with the oxygen sensitive dye, Tris(2,2'-bipyridyl) dichlororuthenium(II) hexahydrate (RTDP) and the oxygen insensitive dye, Alexa 488. The Zone 1 biased functions of oxidative phosphorylation, albumin and urea secretion and Zone 3 biased functions of glycolysis, α1AT secretion, Cyp2E1 expression and acetaminophen toxicity were demonstrated in the respective Zone 1 and Zone 3 MicroPhysiology System. Further improvements in the Liver Acinus MicroPhysiology System included improved performance of selected nonparenchymal cells, the inclusion of a porcine liver extracellular matrix to model the Space of Disse, as well as an improved media to support both hepatocytes and non-parenchymal cells. In its current form, the Liver Acinus MicroPhysiology System is most amenable to low to medium throughput, acute through chronic studies, including liver disease models, prioritizing compounds for preclinical studies, optimizing chemistry in structure activity relationship (SAR) projects, as well as in rising dose studies for initial dose ranging. Impact statement Oxygen zonation is a critical aspect of liver functions. A human microphysiology system is needed to investigate the impact of zonation on a wide range of liver functions that can be experimentally manipulated. Because oxygen zonation has such diverse physiological effects in the liver, we

  7. Oxygen distribution in tumors: A qualitative analysis and modeling study providing a novel Monte Carlo approach

    International Nuclear Information System (INIS)

    Lagerlöf, Jakob H.; Kindblom, Jon; Bernhardt, Peter

    2014-01-01

    Purpose: To construct a Monte Carlo (MC)-based simulation model for analyzing the dependence of tumor oxygen distribution on different variables related to tumor vasculature [blood velocity, vessel-to-vessel proximity (vessel proximity), and inflowing oxygen partial pressure (pO 2 )]. Methods: A voxel-based tissue model containing parallel capillaries with square cross-sections (sides of 10 μm) was constructed. Green's function was used for diffusion calculations and Michaelis-Menten's kinetics to manage oxygen consumption. The model was tuned to approximately reproduce the oxygenational status of a renal carcinoma; the depth oxygenation curves (DOC) were fitted with an analytical expression to facilitate rapid MC simulations of tumor oxygen distribution. DOCs were simulated with three variables at three settings each (blood velocity, vessel proximity, and inflowing pO 2 ), which resulted in 27 combinations of conditions. To create a model that simulated variable oxygen distributions, the oxygen tension at a specific point was randomly sampled with trilinear interpolation in the dataset from the first simulation. Six correlations between blood velocity, vessel proximity, and inflowing pO 2 were hypothesized. Variable models with correlated parameters were compared to each other and to a nonvariable, DOC-based model to evaluate the differences in simulated oxygen distributions and tumor radiosensitivities for different tumor sizes. Results: For tumors with radii ranging from 5 to 30 mm, the nonvariable DOC model tended to generate normal or log-normal oxygen distributions, with a cut-off at zero. The pO 2 distributions simulated with the six-variable DOC models were quite different from the distributions generated with the nonvariable DOC model; in the former case the variable models simulated oxygen distributions that were more similar to in vivo results found in the literature. For larger tumors, the oxygen distributions became truncated in the lower

  8. Multiple oxygen tension environments reveal diverse patterns of transcriptional regulation in primary astrocytes.

    Directory of Open Access Journals (Sweden)

    Wayne Chadwick

    Full Text Available The central nervous system normally functions at O(2 levels which would be regarded as hypoxic by most other tissues. However, most in vitro studies of neurons and astrocytes are conducted under hyperoxic conditions without consideration of O(2-dependent cellular adaptation. We analyzed the reactivity of astrocytes to 1, 4 and 9% O(2 tensions compared to the cell culture standard of 20% O(2, to investigate their ability to sense and translate this O(2 information to transcriptional activity. Variance of ambient O(2 tension for rat astrocytes resulted in profound changes in ribosomal activity, cytoskeletal and energy-regulatory mechanisms and cytokine-related signaling. Clustering of transcriptional regulation patterns revealed four distinct response pattern groups that directionally pivoted around the 4% O(2 tension, or demonstrated coherent ascending/decreasing gene expression patterns in response to diverse oxygen tensions. Immune response and cell cycle/cancer-related signaling pathway transcriptomic subsets were significantly activated with increasing hypoxia, whilst hemostatic and cardiovascular signaling mechanisms were attenuated with increasing hypoxia. Our data indicate that variant O(2 tensions induce specific and physiologically-focused transcript regulation patterns that may underpin important physiological mechanisms that connect higher neurological activity to astrocytic function and ambient oxygen environments. These strongly defined patterns demonstrate a strong bias for physiological transcript programs to pivot around the 4% O(2 tension, while uni-modal programs that do not, appear more related to pathological actions. The functional interaction of these transcriptional 'programs' may serve to regulate the dynamic vascular responsivity of the central nervous system during periods of stress or heightened activity.

  9. Should direct measurements of tumor oxygenation relate to the radiobiological hypoxic fraction of a tumor?

    International Nuclear Information System (INIS)

    Fenton, Bruce M.; Kiani, Mohammad F.; Siemann, Dietmar W.

    1995-01-01

    Purpose: Numerous previous studies have attempted to relate the radiobiological hypoxic fraction (HF) to direct measures of tumor oxygenation such as HbO 2 saturations, tumor pO 2 levels, or hypoxic cell labeling. Although correlations have been found within tumor lines, no overall relationships were seen across tumor lines. The current objective was to examine the effect on HF of changes in the fractions of the oxygenated and anoxic tumor cells that remain clonogenic. Methods and Materials: A mathematical model was developed that relates the HF to direct measures of tumor oxygenation. The primary assumptions were that: (a) the tumor is divided into distinct compartments of either fully oxygenated or fully anoxic cells, and (b) the survival of the oxygenated cells is negligible compared to that of the anoxic cells. Based on these assumptions, the HF is plotted as a function of the fractions of clonogenic or nonclonogenic, and oxygenated or anoxic cells. Results: If all cells are clonogenic, then the HF equals the fraction of anoxic cells. If a higher fraction of anoxic than oxygenated cells are nonclonogenic, then the HF will be overestimated by the fraction of the tumor measured to be anoxic using direct measuring techniques. If a higher fraction of the oxygenated than anoxic cells are nonclonogenic, the HF will be underestimated by the fraction of anoxic cells. Conclusion: Correlations between the HF and direct measures of tumor oxygenation have been described within tumor lines evaluated under different physiological condition. However, such relationships can be totally unpredictable between different tumors if the fraction of the anoxic cells that is clonogenic varies substantially. Clearly, if tumor anoxia cannot be detected using direct measures, this is an accurate indication that the tumor is well oxygenated. When tumor anoxia is present, however, the conclusions are ambiguous. Even when a small fraction of the tumor is measured as anoxic, direct measures

  10. Additive influence of extracellular pH, oxygen tension, and pressure on invasiveness and survival of human osteosarcoma cells

    Directory of Open Access Journals (Sweden)

    Takao eMatsubara

    2013-07-01

    Full Text Available BACKGROUND/PURPOSE:The effects of chemical and physical interactions in the microenvironment of solid tumors have not been fully elucidated. We hypothesized that acidosis, hypoxia, and elevated interstitial fluid pressure (eIFP have additive effects on tumor cell biology and lead to more aggressive behavior during tumor progression. We investigated this phenomenon using 3 human osteosarcoma cell lines and a novel in vitro cell culture apparatus. MATERIALS AND METHODS:U2OS, SaOS, and MG63 cell lines were cultured in media adjusted to various pH levels, oxygen tension (hypoxia 2% O2, normoxia 20% O2, and hydrostatic gauge pressure (0 or 50 mm Hg. Growth rate, apoptosis, cell cycle parameters, and expression of mRNA for proteins associated with invasiveness and tumor microenvironment (CA IX, VEGF-A, HIF-1A, MMP-9, and TIMP-2 were analyzed. Levels of CA IX, HIF-1α, and MMP-9 were measured using immunofluorescence. The effect of pH on invasiveness was evaluated in a Matrigel chamber assay.RESULTS: Within the acidic–hypoxic–pressurized conditions that simulate the microenvironment at a tumor’s center, invasive genes were upregulated, but the cell cycle was downregulated. The combined influence of acidosis, hypoxia, and IFP promoted invasiveness and angiogenesis to a greater extent than did pH, pO2, or eIFP individually. Significant cell death after brief exposure to acidic conditions occurred in each cell line during acclimation to acidic media, while prolonged exposure to acidic media resulted in reduced cell death. Furthermore, 48-hour exposure to acidic conditions promoted tumor invasiveness in the Matrigel assay. CONCLUSION: Our findings demonstrate that tumor microenvironmental parameters—particularly pH, pO2, and eIFP—additively influence tumor proliferation, invasion, metabolism, and viability to enhance cell survival.

  11. The Role of Oxygen Tension in Penile Erection and Its Relationship to Erectile Dysfunction

    Directory of Open Access Journals (Sweden)

    Jong-Kwan Park

    2004-01-01

    Full Text Available The corpus cavernosum of the penis is one of the few vascular beds in which there is a change in oxygen tension with function (blood PO2 25-40mm Hg in the flaccid state, and 90-100mm Hg in the erect state. This change in oxygen tension exposes the components of the corpus cavernosum to a variety of cytokines, humoral, vasoactive, and growth factors which may affect the structure and function of the endothelial cells, smooth muscle cells, neurons and extracellular matrix. Among these cell types, endothelial cells are the first line of defense to blood-borne stress and can affect the underlying smooth muscle via paracrine mechanisms. Impotence is defined as the inability to obtain or sustain an erection sufficient for vaginal penetration and can result from a variety of pathological conditions, vascular disease, endocrine disease, neurological disease, and psychogenic disorders. The penis is a vascular organ and as such is susceptible to the effects of vascular diseases. This review will discuss the basic etiology of erection and vasculogenic erectile dysfunction and explore the role oxygen tension in regulating various cellular and humoral factors as well as trabecular structure and function.

  12. [Effect of different oxygen tension on the cytoskeleton remodeling of goat temporomandibular joint disc cells].

    Science.gov (United States)

    Xiaolan, He; Guangjie, Bao; Linglu, Sun; Xue, Zhang; Shanying, Bao; Hong, Kang

    2017-08-01

    Objective The effect of different oxygen tensions on the cytoskeleton remodeling of goat temporomandibular joint (TMJ) disc cells were investigated. Methods Goat TMJ disc cells were cultured under normoxia (21% O₂) and hypoxia (2%, 4%, and 8% O₂). Toluidine blue, picrosirius red, and type Ⅰ collagen immunocytochemical staining were performed to observe the changes in cell phenotype under different oxygen levels. Immunofluorescent staining and real-time reverse transcription-polymerase chain reaction analysis were then performed to identify actin, tubulin, and vimentin in the cultured disc cells. Results TMJ disc cells still displayed fibroblast characteristics under different oxygen levels and their cytoskeletons had regular arrangement. The fluorescence intensities of actin and vimentin were lowest at 4% O₂(P0.05). Actin mRNA levels were considerably decreased at 2% O₂ and 4% O₂ in hypoxic conditions, while actin mRNA expression was highest in 21% O₂. Tubulin mRNA levels considerably increased at 2% O₂, while tubulin mRNA expression was lowest in 8% O₂ (Plevels among these oxygen levels (Poxygen tensions, and 2% O₂ may be the optimal oxygen level required to proliferate TMJ disc cells.

  13. [Long-term expansion of multipotent mesenchymal stromal cells under reduced oxygen tension].

    Science.gov (United States)

    Rylova, Iu V; Buravkova, L B

    2013-01-01

    We have shown that the decrease in oxygen tension in the culture medium of multipotent mesenchymal stromal cells (MMSCs) results in a short-term reduction in the proportion of CD73(+)-cells in the population, without effecting the number of cells expressing other constitutive surface markers (CD90 and CD105). In this case, the heterogeneity of the cell population declined: large spread cells disappeared. The proliferative activity of MMSCs significantly increased and remained stable in conditions in which the oxygen content was close to the tissue oxygen levels (5% O2). At lower oxygen concentration, proliferative activity of the cells gradually reduced from passages 3-4. The increase in proliferative activity was not accompanied by increased expression of telomerase gene indicateding the alsance of cell transformation. However, genome-wide analysis of MMSC gene expression level revealed changes in expression of cyclins (CCND2 and PCNA), regulatory subunit cyclin-dependent kinase (CKS2) and an inhibitor of cyclin-dependent kinase (CDKN2C), regulating the cell cycle, which is obviously facilitated the increase in the proliferative capacity of cells at lower oxygen tension.

  14. Oxidative stress under ambient and physiological oxygen tension in tissue culture

    Science.gov (United States)

    Jagannathan, Lakshmanan; Cuddapah, Suresh; Costa, Max

    2016-01-01

    Oxygen (O2) levels range from 2–9% in vivo. However, cell culture experiments are performed at atmospheric O2 levels (21%). Oxidative stress due to generation of reactive oxygen species (ROS) in cells cultured at higher than physiological levels is implicated in multitude of deleterious effects including DNA damage, genomic instability and senescence. In addition, oxidative stress activates redox sensitive transcription factors related to inflammatory signaling and apoptotic signaling. Furthermore, several chromatin-modifying enzymes are affected by ROS, potentially impacting epigenetic regulation of gene expression. While primary cells are cultured at lower O2 levels due to their inability to grow at higher O2, the immortalized cells, which display no such apparent growth difficulties, are typically cultured at 21% O2. This review will provide an overview of issues associated with increased oxygen levels in in vitro cell culture and point out the benefits of using lower levels of oxygen tension even for immortalized cells. PMID:27034917

  15. Microcomputer-based system for registration of oxygen tension in peripheral muscle.

    Science.gov (United States)

    Odman, S; Bratt, H; Erlandsson, I; Sjögren, L

    1986-01-01

    For registration of oxygen tension fields in peripheral muscle a microcomputer based system was designed on the M6800 microprocessor. The system was designed to record the signals from a multiwire oxygen electrode, MDO, which is a multiwire electrode for measuring oxygen on the surface of an organ. The system contained patient safety isolation unit built on optocopplers and the upper frequency limit was 0.64 Hz. Collected data were corrected for drift and temperature changes during the measurement by using pre- and after calibrations and a linear compensation technique. Measure drift of the electrodes were proved to be linear and thus the drift could be compensated for. The system was tested in an experiment on pig. To study the distribution of oxygen statistically mean, standard deviation, skewness and curtosis were calculated. To see changes or differences between histograms a Kolmogorv-Smirnov test was used.

  16. Correlation of radiation response with tumor oxygenation in the Dunning prostate R3327-AT1 tumor

    International Nuclear Information System (INIS)

    Bourke, Vincent A.; Zhao Dawen; Gilio, Joseph; Chang, C.-H.; Jiang Lan; Hahn, Eric W.; Mason, Ralph P.

    2007-01-01

    Purpose: To investigate the application of pretreatment oxygenation to the AT1 subline of the Dunning R3327 prostate tumor, which is more hypoxic and faster growing than the H1 subline previously studied. Methods and Materials: Dunning prostate R3327-AT1 tumors growing on Copenhagen rats were administered 30 Gy of X-ray radiation either with or without oxygen inhalation. Tumor oxygenation was sampled by 19 F nuclear magnetic resonance echo planar imaging relaxometry of the reporter molecule hexafluorobenzene, no more than 24 h before irradiation. Results: Large tumors (>3.0 cm 3 ) exhibited significantly greater hypoxic fractions and lower mean partial pressure of oxygen (pO 2 ) than their smaller counterparts ( 3 ). However, unlike the R3327-HI subline, large AT1 tumors generally did not respond to oxygen inhalation in terms of altered hypoxic fraction or response to irradiation. Although the tumors did not respond to oxygen inhalation, each tumor had a different pO 2 , and there was a clear trend between level of oxygenation at time of irradiation and tumor growth delay, with considerably better outcome when mean pO 2 > 10 mm Hg. The comparatively small baseline hypoxic fraction in the group of small tumors was virtually eliminated by breathing oxygen, and the growth rate was significantly reduced for tumors on rats breathing oxygen during irradiation. Conclusions: These results further validate the usefulness of nuclear magnetic resonance oximetry as a predictor of response to radiation therapy

  17. Effect of epidural blockade and oxygen therapy on changes in subcutaneous oxygen tension after abdominal surgery

    DEFF Research Database (Denmark)

    Rosenberg, J; Pedersen, U; Erichsen, C J

    1994-01-01

    The effect of oxygen therapy (37% by face mask) and epidural local anesthetic blockade (9 ml 0.5% bupivacaine at Th9-11 level) on wound oxygenation was evaluated in eight otherwise healthy patients undergoing elective colorectal resection. The patients were monitored continuously for subcutaneous...... without epidural blockade and 15 (10-20) min with blockade (P surgery....

  18. Effect of oxygen tension on bioenergetics and proteostasis in young and old myoblast precursor cells.

    Science.gov (United States)

    Konigsberg, M; Pérez, V I; Ríos, C; Liu, Y; Lee, S; Shi, Y; Van Remmen, H

    2013-01-01

    In the majority of studies using primary cultures of myoblasts, the cells are maintained at ambient oxygen tension (21% O2), despite the fact that physiological O2 at the tissue level in vivo is much lower (~1-5% O2). We hypothesized that the cellular response in presence of high oxygen concentration might be particularly important in studies comparing energetic function or oxidative stress in cells isolated from young versus old animals. To test this, we asked whether oxygen tension plays a role in mitochondrial bioenergetics (oxygen consumption, glycolysis and fatty acid oxidation) or oxidative damage to proteins (protein disulfides, carbonyls and aggregates) in myoblast precursor cells (MPCs) isolated from young (3-4 m) and old (29-30 m) C57BL/6 mice. MPCs were grown under physiological (3%) or ambient (21%) O2 for two weeks prior to exposure to an acute oxidative insult (H2O2). Our results show significantly higher basal mitochondrial respiration in young versus old MPCs, an increase in basal respiration in young MPCs maintained at 3% O2 compared to cells maintained at 21% O2, and a shift toward glycolytic metabolism in old MPCs grown at 21% O2. H2O2 treatment significantly reduced respiration in old MPCs grown at 3% O2 but did not further repress respiration at 21% O2 in old MPCs. Oxidative damage to protein was higher in cells maintained at 21% O2 and increased in response to H2O2 in old MPCs. These data underscore the importance of understanding the effect of ambient oxygen tension in cell culture studies, in particular studies measuring oxidative damage and mitochondrial function.

  19. Oxygen tension regulates the osteogenic, chondrogenic and endochondral phenotype of bone marrow derived mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Sheehy, Eamon J.; Buckley, Conor T. [Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin, Dublin 2 (Ireland); Kelly, Daniel J., E-mail: kellyd9@tcd.ie [Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin, Dublin 2 (Ireland)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Expansion in low oxygen enhances MSC proliferation and osteogenesis. Black-Right-Pointing-Pointer Differentiation in low oxygen enhances chondrogenesis and suppresses hypertrophy. Black-Right-Pointing-Pointer Oxygen can regulate the MSC phenotype for use in tissue engineering applications. -- Abstract: The local oxygen tension is a key regulator of the fate of mesenchymal stem cells (MSCs). The objective of this study was to investigate the effect of a low oxygen tension during expansion and differentiation on the proliferation kinetics as well as the subsequent osteogenic and chondrogenic potential of MSCs. We first hypothesised that expansion in a low oxygen tension (5% pO{sub 2}) would improve both the subsequent osteogenic and chondrogenic potential of MSCs compared to expansion in a normoxic environment (20% pO{sub 2}). Furthermore, we hypothesised that chondrogenic differentiation in a low oxygen environment would suppress hypertrophy of MSCs cultured in both pellets and hydrogels used in tissue engineering strategies. MSCs expanded at 5% pO{sub 2} proliferated faster forming larger colonies, resulting in higher cell yields. Expansion at 5% pO{sub 2} also enhanced subsequent osteogenesis of MSCs, whereas differentiation at 5% pO{sub 2} was found to be a more potent promoter of chondrogenesis than expansion at 5% pO{sub 2}. Greater collagen accumulation, and more intense staining for collagen types I and X, was observed in pellets maintained at 20% pO{sub 2} compared to 5% pO{sub 2}. Both pellets and hydrogels stained more intensely for type II collagen when undergoing chondrogenesis in a low oxygen environment. Differentiation at 5% pO{sub 2} also appeared to inhibit hypertrophy in both pellets and hydrogels, as demonstrated by reduced collagen type X and Alizarin Red staining and alkaline phosphatase activity. This study demonstrates that the local oxygen environment can be manipulated in vitro to either stabilise a

  20. The impact of including spatially longitudinal heterogeneities of vessel oxygen content and vascular fraction in 3D tumor oxygenation models on predicted radiation sensitivity.

    Science.gov (United States)

    Lagerlöf, Jakob H; Kindblom, Jon; Bernhardt, Peter

    2014-04-01

    Oxygen distribution models have been used to analyze the influences of oxygen tensions on tissue response after radiotherapy. These distributions are often generated assuming constant oxygen tension in the blood vessels. However, as red blood cells progress through the vessels, oxygen is continuously released into the plasma and the surrounding tissue, resulting in longitudinally varying oxygen levels in the blood vessels. In the present study, the authors investigated whether a tumor oxygenation model that incorporated longitudinally varying oxygen levels would provide different predictions of necrotic fractions and radiosensitivity compared to commonly used models with a constant oxygen pressure. Our models simulated oxygen diffusion based on a Green's function approach and oxygen consumption according to the Michaelis-Menten equation. The authors constructed tumor models with different vascular fractions (VFs), from which they generated depth oxygenation curves and a look-up table of oxygen pressure gradients. The authors evaluated models of spherical tumors of various sizes, from 1 to 10(4) mg. The authors compared the results from a model with constant vessel oxygen (CVO) pressure to those from models with longitudinal variations in oxygen saturation and either a constant VF (CVF) or variable VF (VVF) within the tumor tissue. The authors monitored the necrotic fractions, defined as tumor regions with an oxygen pressure below 1 mmHg. Tumor radiation sensitivity was expressed as D99, the homogeneous radiation dose required for a tumor control probability of 0.99. In the CVO saturation model, no necrosis was observed, and decreasing the VF could only decrease the D99 by up to 10%. Furthermore, the D99 vs VF dependence was similar for different tumor masses. Compared to the CVO model, the extended CVF and VVF models provided clearly different results, including pronounced effects of VF and tumor size on the necrotic fraction and D99, necrotic fractions ranging

  1. Low Oxygen Tension Enhances Expression of Myogenic Genes When Human Myoblasts Are Activated from G0 Arrest

    DEFF Research Database (Denmark)

    Sellathurai, Jeeva; Nielsen, Joachim; Hejbøl, Eva Kildall

    2016-01-01

    -PCR, immunocytochemistry and western blot. RESULTS AND CONCLUSIONS: We found an increase in proliferation rate of myoblasts when activated at a low oxygen tension (1% O2) compared to 21% O2. In addition, the gene expression studies showed up regulation of the myogenesis related genes PAX3, PAX7, MYOD, MYOG (myogenin), MET......, NCAM, DES (desmin), MEF2A, MEF2C and CDH15 (M-cadherin), however, the fraction of DES and MYOD positive cells was not increased by low oxygen tension, indicating that 1% O2 may not have a functional effect on the myogenic response. Furthermore, the expression of genes involved in the TGFβ, Notch...... and Wnt signaling pathways were also up regulated in low oxygen tension. The differences in gene expression were most pronounced at day one after activation from G0-arrest, thus the initial activation of myoblasts seemed most sensitive to changes in oxygen tension. Protein expression of HES1 and β...

  2. Impact of low oxygen tension on stemness, proliferation and differentiation potential of human adipose-derived stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jane Ru; Pingguan-Murphy, Belinda; Wan Abas, Wan Abu Bakar [Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur (Malaysia); Noor Azmi, Mat Adenan; Omar, Siti Zawiah [Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur (Malaysia); Chua, Kien Hui [Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur (Malaysia); Wan Safwani, Wan Kamarul Zaman, E-mail: wansafwani@um.edu.my [Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur (Malaysia)

    2014-05-30

    Highlights: • Hypoxia maintains the stemness of adipose-derived stem cells (ASCs). • ASCs show an increased proliferation rate under low oxygen tension. • Oxygen level as low as 2% enhances the chondrogenic differentiation potential of ASCs. • HIF-1α may regulate the proliferation and differentiation activities of ASCs under hypoxia. - Abstract: Adipose-derived stem cells (ASCs) have been found adapted to a specific niche with low oxygen tension (hypoxia) in the body. As an important component of this niche, oxygen tension has been known to play a critical role in the maintenance of stem cell characteristics. However, the effect of O{sub 2} tension on their functional properties has not been well determined. In this study, we investigated the effects of O{sub 2} tension on ASCs stemness, differentiation and proliferation ability. Human ASCs were cultured under normoxia (21% O{sub 2}) and hypoxia (2% O{sub 2}). We found that hypoxia increased ASC stemness marker expression and proliferation rate without altering their morphology and surface markers. Low oxygen tension further enhances the chondrogenic differentiation ability, but reduces both adipogenic and osteogenic differentiation potential. These results might be correlated with the increased expression of HIF-1α under hypoxia. Taken together, we suggest that growing ASCs under 2% O{sub 2} tension may be important in expanding ASCs effectively while maintaining their functional properties for clinical therapy, particularly for the treatment of cartilage defects.

  3. Indomethacin lowers optic nerve oxygen tension and reduces the effect of carbonic anhydrase inhibition and carbon dioxide breathing

    DEFF Research Database (Denmark)

    Pedersen, D B; Eysteinsson, T; Stefánsson, E

    2004-01-01

    Prostaglandins are important in blood flow regulation. Carbon dioxide (CO(2)) breathing and carbonic anhydrase inhibition increase the oxygen tension in the retina and optic nerve. To study the mechanism of this effect and the role of cyclo-oxygenase in the regulation of optic nerve oxygen tension...... (ONPO(2)), the authors investigated how indomethacin affects ONPO(2) and the ONPO(2) increases caused by CO(2) breathing and carbonic anhydrase inhibition in the pig....

  4. Oxygenation of spontaneous canine tumors during fractionated radiation therapy

    International Nuclear Information System (INIS)

    Achermann, R.E.; Ohlerth, S.M.; Bley, C.R.; Inteeworn, N.; Schaerz, M.; Wergin, M.C.; Kaser-Hotz, B.; Gassmann, M.; Roos, M.

    2004-01-01

    Background and purpose: tumor oxygenation predicts treatment outcome, and reoxygenation is considered important in the efficacy of fractionated radiation therapy. Therefore, the purpose of this study was to document the changes of the oxygenation status in spontaneous canine tumors during fractionated radiation therapy using polarographic needle electrodes. Material and methods: tumor oxygen partial pressure (pO 2 ) measurements were performed with the eppendorf-pO 2 -Histograph. The measurements were done under general anesthesia, and probe tracks were guided with ultrasound. pO 2 was measured before radiation therapy in all dogs. In patients treated with curative intent, measurements were done sequentially up to eight times (total dose: 45-59.5 Gy). Oxygenation status of the palliative patient group was examined before each fraction of radiation therapy up to five times (total dose: 24-30 Gy). Results: 15/26 tumors had a pretreatment median pO 2 ≤ 10 mmHg. The pO 2 values appeared to be quite variable in individual tumors during fractionated radiation therapy. The pO 2 of initially hypoxic tumors (pretreatment median pO 2 ≤ 10 mmHg) remained unchanged during fractionated radiotherapy, whereas in initially normoxic tumors the pO 2 decreased. Conclusion: hypoxia is common in spontaneous canine tumors, as 57.7% of the recorded values were ≥ 10 mmHg. The data of this study showed that initially hypoxic tumors remained hypoxic, whereas normoxic tumors became more hypoxic. (orig.)

  5. Clinical oxygen enhancement ratio of tumors in carbon ion radiotherapy: the influence of local oxygenation changes

    DEFF Research Database (Denmark)

    Antonovic, Laura; Lindblom, Emely; Dasu, Alexandru

    2014-01-01

    , using the repairable–conditionally repairable (RCR) damage model with parameters for human salivary gland tumor cells. The clinical oxygen enhancement ratio (OER) was defined as the ratio of doses required for a tumor control probability of 50% for hypoxic and well-oxygenated tumors. The resulting OER...... was well above unity for all fractionations. For the hypoxic tumor, the tumor control probability was considerably higher if LOCs were assumed, rather than static oxygenation. The beneficial effect of LOCs increased with the number of fractions. However, for very low fraction doses, the improvement related...... to LOCs did not compensate for the increase in total dose required for tumor control. In conclusion, our results suggest that hypoxia can influence the outcome of carbon ion radiotherapy because of the non-negligible oxygen effect at the low LETs in the SOBP. However, if LOCs occur, a relatively high...

  6. A theoretical model for the effects of reduced hemoglobin-oxygen affinity on tumor oxygenation

    International Nuclear Information System (INIS)

    Kavanagh, Brian D.; Secomb, Timothy W.; Hsu, Richard; Lin, P.-S.; Venitz, Jurgen; Dewhirst, Mark W.

    2002-01-01

    Purpose: To develop a theoretical model for oxygen delivery to tumors, and to use the model to simulate the effects of changing the affinity of hemoglobin for oxygen on tumor oxygenation. Methods and Materials: Hemoglobin affinity is expressed in terms of P 50 , the partial pressure of oxygen (Po 2 ) at half saturation. Effects of changing P 50 on arterial Po 2 are predicted using an effective vessel approach to describe diffusive oxygen transport in the lungs, assuming fixed systemic oxygen demand and fixed blood flow rate. The decline in oxygen content of blood as it flows through normal tissue before entering the tumor region is assumed fixed. The hypoxic fraction of the tumor region is predicted using a three-dimensional simulation of diffusion from a network of vessels whose geometry is derived from observations of tumor microvasculature in the rat. Results: In air-breathing rats, predicted hypoxic fraction decreases with moderate increases in P 50 , but increases with further increases of P 50 , in agreement with previous experimental results. In rats breathing hyperoxic gases, and in humans breathing either normoxic or hyperoxic gases, increased P 50 is predicted to improve tumor oxygenation. Conclusions: The results support the administration of synthetic agents to increase P 50 during radiation treatment of tumors

  7. Cerebral interstitial tissue oxygen tension, pH, HCO3, CO2.

    Science.gov (United States)

    Charbel, F T; Hoffman, W E; Misra, M; Hannigan, K; Ausman, J I

    1997-10-01

    There are many techniques for monitoring the injured brain following trauma, subarachnoid hemorrhage, or surgery. It is thought that the major determinants for recovery of injured cerebral tissue are oxygen, glucose delivery, and the clearance of metabolites. These factors, at optimal levels, are probably responsible for the regaining of neuronal functions. These parameters are in turn dependent on the tissue's blood flow and metabolism. We have been using a single, compact, polyethylene sensor, the Paratrend 7 for the measurement of cerebral oxygen tension, CO2, pH, and temperature. This sensor is designed for continuous blood gas analysis to aid in monitoring neurosurgical patients, both during surgery and in the intensive care unit. Using the Paratrend 7 sensor, we found the normal range of values to be: PO2 33 +/- 11 mm Hg; PCO2 48 +/- 7 mm Hg; pH 7.19 +/- 0.11. Critical measurements are considered to be tissue PO2 60 mm Hg, and pH effective method of measuring tissue cerebral oxygen tension, along with carbon dioxide levels, pH, and temperature.

  8. Nuclear medicine markers of tumor oxygenation and radioresistance

    International Nuclear Information System (INIS)

    Chapman, J. Donald; Schneider, R.H.; Stobbe, C.C.; Kim, E.; Engelhardt, E.L.; Coia, L.

    1996-01-01

    Purpose/Objective: The objective of this research project was to synthesize, purify, radiolabel and characterize second-generation nuclear medicine markers of tissue oxygenation with properties superior to iodoazomycin arabinoside (IAZA) and to validate the hypoxia-marking activity of optimal compounds by independent measurements of tumor oxygenation and tumor radioresistance. Materials and Methods: Six hypoxic markers of the iodoazomycin nucleoside class with water solubilities greater than IAZA were synthesized by published procedures. The markers were purified, chemically characterized and labeled with Iodine-125 or Iodine-131. Absolute rates of marker ligation to the macromolecules of hypoxic EMT-6 tumor cells in vitro were determined as a function of marker concentration and used to establish relative marker effectiveness. Hypoxic marking activity in tumors was determined from tumor/blood (T/B) and tumor/muscle (T/M) ratios of radiolabelled marker in EMT-6 tumor-bearing C.B17/Icr scid mice. The optimal marker was administered to R3327-H and R3327-AT tumor-bearing Fischer X Copenhagen rats for estimates of tumor oxygenation by T/B and T/M ratios. Oxygen distributions in the same tumors were obtained with the Eppendorf pO 2 Histograph. The radioresistance of individual tumors was determined from in vitro plating efficiencies of cells released from tumors which had been irradiated in vivo with 20 Gy Cs-137 γ-rays. Results: Of the six iodinated azomycin nucleosides investigated, five were novel markers and all had water solubilities higher than IAZA. Iodinated azomycin xylopyranoside (β-D-IAZXP) was selected as the optimal marker of this class since it 1) exhibited the highest absolute rate of ligation to hypoxic tumor cells in vitro, 2) had the fastest plasma clearance rate in tumor-bearing mice and 3) yielded high T/B ratios in both the mouse and rat tumor models employed in this study. Planar nuclear medicine images of (I-131) β-D-IAZXP in tumor-bearing rats

  9. Tension pneumoventricle after excision of third ventricular tumor in sitting position

    Directory of Open Access Journals (Sweden)

    Nidhi Gupta

    2011-01-01

    Full Text Available Occurrence of tension pneumoventricle (symptomatic intraventricular air can result in rapid clinical deterioration in an otherwise stable patient. It is a rare clinical entity, mentioned in relation to cerebrospinal fluid (CSF diversion procedures, during the late postoperative period. We present a patient with posterior third ventricular tumor who underwent excision by midline suboccipital craniotomy in sitting position. Neurological status of the patient deteriorated rapidly in the immediate postoperative period owing to development of tension pneumoventricle. The condition improved after twist-drill burr-hole evacuation of air under water-seal. Pre-existing gross hydrocephalus, exploration of third ventricle in sitting position, and residual tumor in third ventricle were possibly the factors responsible for this complication.

  10. Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression

    DEFF Research Database (Denmark)

    Laklai, Hanane; Miroshnikova, Yekaterina A.; Pickup, Michael W.

    2016-01-01

    by increasing matricellular fibrosis and tissue tension. In contrast, epithelial STAT3 ablation attenuated tumor progression by reducing the stromal stiffening and epithelial contractility induced by loss of TGF-β signaling. In PDAC patient biopsies, higher matricellular protein and activated STAT3 were......Fibrosis compromises pancreatic ductal carcinoma (PDAC) treatment and contributes to patient mortality, yet antistromal therapies are controversial. We found that human PDACs with impaired epithelial transforming growth factor-β (TGF-β) signaling have high epithelial STAT3 activity and develop...... stiff, matricellular-enriched fibrosis associated with high epithelial tension and shorter patient survival. In several KRAS-driven mouse models, both the loss of TGF-β signaling and elevated β1-integrin mechanosignaling engaged a positive feedback loop whereby STAT3 signaling promotes tumor progression...

  11. Modifiers of hemoglobin/oxygen affinity as sensitizers of tumors to radiation

    International Nuclear Information System (INIS)

    Hirst, D.G.; Wood, P.J.

    1987-01-01

    A powerful mechanism in the control of oxygen delivery to tissues is the allosteric modification of hemoglobin. Increased or decreased release of oxygen can be achieved by altering the affinity of hemoglobin for oxygen. Several studies have shown that tumor radiosensitivity is dependent on this relationship. The authors studied affinity changes produced in two distinctly different ways. Tumor bearing mice were given isovolemic exchange blood transfusions with the blood from donor mice which had been exposed to abnormal oxygen tensions, leading to increased or slightly decreased levels of 2,3-diphosphoglycerate (2,3 DPG) in their blood. When the recipient mice were irradiated, those receiving the blood with higher 2,3 DPG levels showed greater tumor sensitivity to radiation. An alternative strategy is the use of drugs which directly alter hemoglobin/oxygen affinity. The authors studied three antihyperlipoproteinemia drugs, all of which have produced markedly reduced affinities in vivo. Preliminary data indicate that the radiosensitization produced by at least one of these compounds is less than would have been expected from the 2,3 DPG experiments

  12. Tumor oxygenation in a transplanted rat rhabdomyosarcoma during fractionated irradiation

    International Nuclear Information System (INIS)

    Zywietz, Friedrich; Reeker, Wolfram; Kochs, Eberhard

    1995-01-01

    Purpose: To quantify the changes in tumor oxygenation in the course of a fractionated radiation treatment extending over 4 weeks. Methods and Materials: Rhabdomyosarcomas R1H of the rat were irradiated with 60 Co-γ-rays with a total dose of 60 Gy, given in 20 fractions over 4 weeks. Oxygen partial pressure (pO 2 ) in tumors was measured at weekly intervals using polarographic needle probes in combination with a microprocessor-controlled device (pO 2 -Histograph/KIMOC). The pO 2 measurements were carried out in anesthetized animals under mechanical ventilation and in respiratory and hemodynamic steady state. Tumor pO 2 values were correlated to the arterial oxygen pressure p a O 2 , arterial pCO 2 , and pH determined with a blood gas analyzer. Results: Tumor oxygenation did not change significantly during the 3 weeks of irradiation (up to 45 Gy), from a median pO 2 of 23 ± 2 mmHg in untreated controls to 19 ± 4 mmHg after the third week. The decrease of the number of pO 2 values between 0 and 5 mmHg indicated that an improved oxygenation in the tumors occurred. However, with increasing radiation dose (fourth week, 60 Gy) a significant decrease in tumor oxygenation to a median pO 2 of 8 ± 2 mmHg and a rapid increase in the frequency of pO 2 values (35 ± 4%) between 0 and 5 mmHg was found. Conclusion: Improved oxygenation in rhabdomyosarcomas R1H was only present in the early phase of the fractionated irradiation. Radiation doses above 45 Gy led to a considerable decrease of tumor oxygenation in the later phase of irradiation

  13. Effects of carbogen plus fractionated irradiation on KHT tumor oxygenation

    International Nuclear Information System (INIS)

    Fenton, Bruce M.

    1997-01-01

    Background and purpose: Numerous studies have demonstrated improvements in the oxygenation of tumor cells following both irradiation and carbogen breathing. The current studies were initiated to measure the combined effects of carbogen inhalation plus single and multi-dose irradiation on tumor oxygen availability, to better define the underlying physiological relationships. Materials and methods: Using KHT murine sarcomas, radiation was delivered to the tumor-bearing legs of non-anesthetized mice. Tumors were quick-frozen prior to or following single or multifraction irradiation and carbogen breathing, and intravascular HbO 2 saturation profiles were determined cryospectrophotometrically. Results: HbO 2 levels for blood vessels located near the tumor surface initially decreased following 10 Gy irradiation, then increased and remained elevated. Interior HbO 2 levels remained unchanged. Following 2.5 Gy, HbO 2 changes were minimal. At 24 h following 10 Gy, HbO 2 levels were significantly increased compared to non-irradiated controls, and carbogen breathing produced no additional benefit. At 24 h following five fractions of 2 Gy, HbO 2 levels throughout the tumor volume were significantly higher in carbogen breathing animals than in air breathing controls. Conclusions: Although peripheral blood vessels demonstrated substantial improvements in oxygenation following irradiation, oxygen availability nearer the tumor center remained at very low levels. The utility of carbogen in enhancing tumor oxygen availability was maintained following five clinically relevant fractions. At higher doses, radiation-induced enhancements in HbO 2 levels overshadowed the carbogen effect. For either air or carbogen breathing, a decrease in the percentage of vessels with very low oxygen content did not appear to be a major factor in the reoxygenation of the KHT tumor

  14. Evaluation of multi-exponential curve fitting analysis of oxygen-quenched phosphorescence decay traces for recovering microvascular oxygen tension histograms

    NARCIS (Netherlands)

    Bezemer, Rick; Faber, Dirk J.; Almac, Emre; Kalkman, Jeroen; Legrand, Matthieu; Heger, Michal; Ince, Can

    2010-01-01

    Although it is generally accepted that oxygen-quenched phosphorescence decay traces can be analyzed using the exponential series method (ESM), its application until now has been limited to a few (patho)physiological studies, probably because the reliability of the recovered oxygen tension (pO(2))

  15. Effect of supplemental oxygen versus dobutamine administration on liver oxygen tension in dPP-guided normovolemic pigs.

    Science.gov (United States)

    Pestel, G; Fukui, K; Hager, H; Kurz, A; Hiltebrand, L

    2009-01-01

    Difference in pulse pressure (dPP) confirms adequate intravascular filling as a prerequisite for tissue perfusion. We hypothesized that both oxygen and dobutamine increase liver tissue oxygen tension (ptO(2)). Eight anesthetized pigs received dPP-guided fluid management. Hepatic pO(2) was measured with Clark-type electrodes placed subcapsularly, and on the liver surface. Pigs received: (1) supplemental oxygen (F(i)O(2) 1.0); (2) dobutamine 2.5 microg/kg/min, and (3) dobutamine 5 microg/kg/min. Data were analyzed using repeated-measures ANOVA followed by a Tukey post-test for multiple comparisons. ptO(2 )measured subcapsularly and at the liver surface were compared using the Bland-Altman plot. Variation in F(i)O(2) changed local hepatic tissue ptO(2) [subcapsular measurement: 39 +/- 12 (F(i)O(2) 0.3), 89 +/- 35 mm Hg (F(i)O(2) 1.0, p = 0.01 vs. F(i)O(2) 0.3), 44 +/- 10 mm Hg (F(i)O(2) 0.3, p = 0.05 vs. F(i)O(2) 1.0); surface measurement: 52 +/- 35 (F(i)O(2) 0.3), 112 +/- 24 mm Hg (F(i)O(2) 1.0, p = 0.001 vs. F(i)O(2) 0.3), 54 +/- 24 mm Hg (F(i)O(2) 0.3, p = 0.001 vs. F(i)O(2) 1.0)]. Surface measurements were widely scattered compared to subcapsular measurements (bias: -15 mm Hg, precision: 76.3 mm Hg). Dobutamine did not affect hepatic oxygenation. Supplemental oxygen increased hepatic tissue pO(2) while dobutamine did not. Although less invasive, the use of surface measurements is discouraged. Copyright 2009 S. Karger AG, Basel.

  16. Effect of carbogen on tumor oxygenation: combined fluorine-19 and proton MRI measurements

    International Nuclear Information System (INIS)

    Fan Xiaobing; River, Jonathan N.; Zamora, Marta; Al-Hallaq, Hania A.; Karczmar, Gregory S.

    2002-01-01

    Purpose: Blood oxygen level dependent (BOLD) contrast in magnetic resonance imaging (MRI) has been widely used for noninvasive evaluation of the effects of tumor-oxygenating agents. However, there have been few tests of the validity of this method. The goal of the present work was to use the T 1 of fluorine-19 in perfluorocarbon (PFC) emulsions as a 'gold standard' for comparison with BOLD MRI. Methods and Materials: Rats bearing R3230AC tumors implanted in the hind limb were injected with an emulsion of perfluoro-15-crown-5-ether for 2-3 days before experiments, which ensured that the PFC emulsion concentrated in the tumors. We correlated changes in tumor oxygenation caused by carbogen inhalation measured by 1 H BOLD MRI with quantitative 19 F measurements. The 19 F spin-lattice relaxation rate R 1 (= 1/T 1 ) was measured to determine initial oxygen tension (pO 2 ) in each image pixel containing the PFC, and changes in pO 2 during carbogen (95% O 2 , 5% CO 2 ) breathing. In a second carbogen breathing period, changes in water signal linewidth were measured using high spectral and spatial resolution imaging. 19 F and 1 H measurements were used to classify pixels as responders to carbogen (pixels where oxygen increased significantly) or nonresponders (no significant change in tumor oxygenation). Results: The 19 F and 1 H measurements agreed in 65% ± 11% of pixels (n = 14). Agreement was even stronger among pixels where 1 H showed increased oxygenation; 19 F measurements agreed with 1 H measurements in over 79% ± 11% of these pixels. Similarly, there was strong agreement between the two modalities in pixels where 19 F reported no change in pO 2 ; 1 H also showed no changes in 76% ± 18% of these pixels. Quantitative correlation of changes T 2 * (ΔT 2 *) in 1 H and changes R 1 (ΔR 1 ) in 19 F was weak during carbogen breathing, and averaged over the whole tumor was ∼0.40 for 14 experiments. However, the spatial patterns of 1 H and 19 F changes were qualitatively

  17. Enhanced dopaminergic differentiation of human neural stem cells by synergistic effect of Bcl-xL and reduced oxygen tension

    DEFF Research Database (Denmark)

    Krabbe, Christina; Courtois, Elise; Jensen, Pia

    2009-01-01

    Neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. Here we investigated the effect of the anti-apoptotic protein Bcl-x(L) and oxygen tension on dopaminergic different......Neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. Here we investigated the effect of the anti-apoptotic protein Bcl-x(L) and oxygen tension on dopaminergic...... days at 20% oxygen, hVMbcl-x(L) cultures contained proportionally more tyrosine hydroxylase(TH)-positive cells than hVM1 control cultures. This difference was significantly potentiated from 11 +/- 0.8% to 17.2 +/- 0.2% of total cells when the oxygen tension was lowered to 3%. Immunocytochemistry and Q...

  18. Reactive oxygen species-driven HIF1α triggers accelerated glycolysis in endothelial cells exposed to low oxygen tension

    International Nuclear Information System (INIS)

    Paik, Jin-Young; Jung, Kyung-Ho; Lee, Jin-Hee; Park, Jin-Won; Lee, Kyung-Han

    2017-01-01

    Endothelial cells and their metabolic state regulate glucose transport into underlying tissues. Here, we show that low oxygen tension stimulates human umbilical vein endothelial cell 18 F–fluorodeoxyglucose ( 18 F–FDG) uptake and lactate production. This was accompanied by augmented hexokinase activity and membrane Glut-1, and increased accumulation of hypoxia-inducible factor-1α (HIF1α). Restoration of oxygen reversed the metabolic effect, but this was blocked by HIF1α stabilization. Hypoxia-stimulated 18 F–FDG uptake was completely abrogated by silencing of HIF1α expression or by a specific inhibitor. There was a rapid and marked increase of reactive oxygen species (ROS) by hypoxia, and ROS scavenging or NADPH oxidase inhibition completely abolished hypoxia-stimulated HIF1α and 18 F–FDG accumulation, placing ROS production upstream of HIF1α signaling. Hypoxia-stimulated HIF1α and 18 F–FDG accumulation was blocked by the protein kinase C (PKC) inhibitor, staurosporine. The phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin, blocked hypoxia-stimulated 18 F–FDG uptake and attenuated hypoxia-responsive element binding of HIF1α without influencing its accumulation. Thus, ROS-driven HIF1α accumulation, along with PKC and PI3K signaling, play a key role in triggering accelerated glycolysis in endothelial cells under hypoxia, thereby contributing to 18 F–FDG transport.

  19. Correlation of radiation response with tumor oxygenation in the Dunning prostate R3327-AT1 tumor

    Energy Technology Data Exchange (ETDEWEB)

    Bourke, Vincent A [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Dawen, Zhao [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Gilio, Joseph [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Chang, C -H [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Lan, Jiang [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Hahn, Eric W [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Mason, Ralph P [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States)

    2007-03-15

    Purpose: To investigate the application of pretreatment oxygenation to the AT1 subline of the Dunning R3327 prostate tumor, which is more hypoxic and faster growing than the H1 subline previously studied. Methods and Materials: Dunning prostate R3327-AT1 tumors growing on Copenhagen rats were administered 30 Gy of X-ray radiation either with or without oxygen inhalation. Tumor oxygenation was sampled by {sup 19}F nuclear magnetic resonance echo planar imaging relaxometry of the reporter molecule hexafluorobenzene, no more than 24 h before irradiation. Results: Large tumors (>3.0 cm{sup 3}) exhibited significantly greater hypoxic fractions and lower mean partial pressure of oxygen (pO{sub 2}) than their smaller counterparts (<1.5 cm{sup 3}). However, unlike the R3327-HI subline, large AT1 tumors generally did not respond to oxygen inhalation in terms of altered hypoxic fraction or response to irradiation. Although the tumors did not respond to oxygen inhalation, each tumor had a different pO{sub 2}, and there was a clear trend between level of oxygenation at time of irradiation and tumor growth delay, with considerably better outcome when mean pO{sub 2} > 10 mm Hg. The comparatively small baseline hypoxic fraction in the group of small tumors was virtually eliminated by breathing oxygen, and the growth rate was significantly reduced for tumors on rats breathing oxygen during irradiation. Conclusions: These results further validate the usefulness of nuclear magnetic resonance oximetry as a predictor of response to radiation therapy.

  20. Towards a quantitative understanding of oxygen tension and cell density evolution in fibrin hydrogels.

    Science.gov (United States)

    Demol, Jan; Lambrechts, Dennis; Geris, Liesbet; Schrooten, Jan; Van Oosterwyck, Hans

    2011-01-01

    The in vitro culture of hydrogel-based constructs above a critical size is accompanied by problems of unequal cell distribution when diffusion is the primary mode of oxygen transfer. In this study, an experimentally-informed mathematical model was developed to relate cell proliferation and death inside fibrin hydrogels to the local oxygen tension in a quantitative manner. The predictive capacity of the resulting model was tested by comparing its outcomes to the density, distribution and viability of human periosteum derived cells (hPDCs) that were cultured inside fibrin hydrogels in vitro. The model was able to reproduce important experimental findings, such as the formation of a multilayered cell sheet at the hydrogel periphery and the occurrence of a cell density gradient throughout the hydrogel. In addition, the model demonstrated that cell culture in fibrin hydrogels can lead to complete anoxia in the centre of the hydrogel for realistic values of oxygen diffusion and consumption. A sensitivity analysis also identified these two parameters, together with the proliferation parameters of the encapsulated cells, as the governing parameters for the occurrence of anoxia. In conclusion, this study indicates that mathematical models can help to better understand oxygen transport limitations and its influence on cell behaviour during the in vitro culture of cell-seeded hydrogels. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Effect of body position and oxygen tension on foramen ovale recruitment.

    Science.gov (United States)

    Moses, Kayla L; Beshish, Arij G; Heinowski, Nicole; Baker, Kim R; Pegelow, David F; Eldridge, Marlowe W; Bates, Melissa L

    2015-01-01

    While there is an increased prevalence of stroke at altitude in individuals who are considered to be low risk for thrombotic events, it is uncertain how venous thrombi reach the brain. The patent foramen ovale (PFO) is a recruitable intracardiac shunt between the right and left atrium. We aimed to determine whether body position and oxygen tension affect blood flow through the PFO in healthy adults. We hypothesized that hypoxia and body positions that promote right atrial filling would independently recruit the PFO. Subjects with a PFO (n = 11) performed 11 trials, combining four different fractions of inhaled oxygen (FiO₂) (1.0, 0.21, 0.15, and 0.10) and three positions (upright, supine, and 45° head down), with the exception of FiO₂ = 0.10, while 45° head down. After 5 min in each position, breathing the prescribed oxygen tension, saline bubbles were injected into an antecubital vein and a four-chamber echocardiogram was obtained to evaluate PFO recruitment. We observed a high incidence of PFO recruitment in all conditions, with increased recruitment in response to severe hypoxia and some contribution of body position at moderate levels of hypoxia. We suspect that increased pulmonary vascular pressure, secondary to hypoxia-induced pulmonary vasoconstriction, increased right atrial pressure enough to recruit the PFO. Additionally, we hypothesize that the minor increase in breathing resistance that was added by the mouthpiece, used during experimental trials, affected intrathoracic pressure and venous return sufficiently to recruit the PFO. Copyright © 2015 the American Physiological Society.

  2. Oxygen tension is a determinant of the matrix-forming phenotype of cultured human meniscal fibrochondrocytes.

    Directory of Open Access Journals (Sweden)

    Adetola B Adesida

    Full Text Available BACKGROUND: Meniscal cartilage displays a poor repair capacity, especially when injury is located in the avascular region of the tissue. Cell-based tissue engineering strategies to generate functional meniscus substitutes is a promising approach to treat meniscus injuries. Meniscus fibrochondrocytes (MFC can be used in this approach. However, MFC are unable to retain their phenotype when expanded in culture. In this study, we explored the effect of oxygen tension on MFC expansion and on their matrix-forming phenotype. METHODOLOGY/PRINCIPAL FINDINGS: MFC were isolated from human menisci followed by basic fibroblast growth factor (FGF-2 mediated cell expansion in monolayer culture under normoxia (21%O(2 or hypoxia (3%O(2. Normoxia and hypoxia expanded MFC were seeded on to a collagen scaffold. The MFC seeded scaffolds (constructs were cultured in a serum free chondrogenic medium for 3 weeks under normoxia and hypoxia. Constructs containing normoxia-expanded MFC were subsequently cultured under normoxia while those formed from hypoxia-expanded MFC were subsequently cultured under hypoxia. After 3 weeks of in vitro culture, the constructs were assessed biochemically, histologically and for gene expression via real-time reverse transcription-PCR assays. The results showed that constructs under normoxia produced a matrix with enhanced mRNA ratio (3.5-fold higher; p<0.001 of collagen type II to I. This was confirmed by enhanced deposition of collagen II using immuno-histochemistry. Furthermore, the constructs under hypoxia produced a matrix with higher mRNA ratio of aggrecan to versican (3.5-fold, p<0.05. However, both constructs had the same capacity to produce a glycosaminoglycan (GAG -specific extracellular matrix. CONCLUSIONS: Our data provide evidence that oxygen tension is a key player in determining the matrix phenotype of cultured MFC. These findings suggest that the use of normal and low oxygen tension during MFC expansion and subsequent neo

  3. Oxygen tension and oocyte density during in vitro maturation affect the in vitro fertilization of bovine oocytes

    Directory of Open Access Journals (Sweden)

    Angelo Bertani Giotto

    2015-12-01

    Full Text Available Oocyte maturation is the key factor affecting the fertilization and embryonic development. Factors such as oocyte density and oxygen tension can directly influence the IMV. Thus, the objective of this study was to evaluate the effect of the association of oxygen tensions (5% or 20% with different oocyte densities (1:10?l or 1:20?l in the in vitro maturation (IVM of bovine oocytes on maturation and fertilization rates, ROS production and antioxidant activity. Three experiments were performed with bovine oocytes that were obtained from slaughterhouse ovaries. After selection, the oocytes were randomly distributed in four treatments: 1:10/5%; 1:10/20%; 1:20/5%and 1:20/20% for each experiment. In experiment I, nuclear maturation status and cytoplasmic maturation were evaluated through detection of the first polar body by immunofluorescence and the mitochondrial reorganization assay. In experiment II, ROS production and antioxidant activity were analyzed in oocytes and IVM medium after 24 h of maturation through detection of ROS, reduced glutathione (GSH and Superoxide dismutase activity by spectrofluorimetric methods. In experiment III, fertilization was evaluated through pronucleus formation, sperm penetration with or without decondensation and polyspermy rates by immunofluorescence. In experiment I, the nuclear maturation and cytoplasmic maturation were similar among treatments (P>0.05. In experiment II, reactive oxygen species in oocytes were elevated in treatments with low oxygen tension which was independent of oocyte density (P<0.05. Additionally, ROS levels in IVM medium were higher in treatments with high oocyte density by volume of medium, which was independent of oxygen tension (P<0.05. In Experiment III, the fertilization and penetration rates were higher in the treatment with 20% oxygen tension and high oocyte density (P<0.05. Furthermore, a high incidence of polyspermy was observed in groups with high oxygen tension and low oocyte

  4. The relationship between alveolar oxygen tension and the single-breath carbon monoxide diffusing capacity.

    Science.gov (United States)

    Kanner, R E; Crapo, R O

    1986-04-01

    The effects of alveolar oxygen tension (PAO2) on the single-breath carbon monoxide diffusing capacity (DLCO) were quantified and a factor was derived to accommodate for differences in PAO2 over commonly encountered altitudes and/or varying concentrations of oxygen in the test gas mixture (FIO2) We performed duplicate measurements of DLCO in 7 normal subjects with 6 different oxygen fractions (0.176, 0.196, 0.211, 0.22, 0.25, and 0.27). The PAO2 for each test was measured as the PO2 in the alveolar gas sample bag. DLCO varied inversely with PAO2 and changed by 0.35% for each mmHg change in PAO2 (r = -0.62, p less than 0.001). At an FIO2 of 0.25, PAO2 varied between subjects and was highly correlated with each subject's residual volume to total lung capacity ratio (r = -0.84, p less than 0.001). We suggest that laboratories can adjust the measured DLCO when PAO2 is not congruent to 120 mmHg by the following formula: DLCO (corrected = DLCO (measured) x [1.0 + 0.0035 (PAO2 - 120)].

  5. Enhanced proliferation and dopaminergic differentiation of ventral mesencephalic precursor cells by synergistic effect of FGF2 and reduced oxygen tension

    DEFF Research Database (Denmark)

    Jensen, Pia; Gramsbergen, Jan-Bert; Zimmer, Jens

    2011-01-01

    Effective numerical expansion of dopaminergic precursors might overcome the limited availability of transplantable cells in replacement strategies for Parkinson's disease. Here we investigated the effect of fibroblast growth factor-2 (FGF2) and FGF8 on expansion and dopaminergic differentiation o...... enzyme activity, which may explain the elevated dopamine levels. Our findings demonstrate that modulation of oxygen tension is a recognizable factor for in vitro expansion and dopaminergic differentiation of rat embryonic midbrain precursor cells....... of rat embryonic ventral mesencephalic neuroblasts cultured at high (20%) and low (3%) oxygen tension. More cells incorporated bromodeoxyuridine in cultures expanded at low as compared to high oxygen tension, and after 6 days of differentiation there were significantly more neuronal cells in low than......, switching FGF2-expanded cultures from low to high oxygen tension during the last two days of differentiation significantly enhanced dopamine release and intracellular dopamine levels as compared to all other treatment groups. In addition, the short-term exposure to high oxygen enhanced in situ assessed TH...

  6. Modulation of the tumor vasculature and oxygenation to improve therapy

    DEFF Research Database (Denmark)

    Siemann, Dietmar W; Horsman, Michael R

    2015-01-01

    The tumor microenvironment is increasingly recognized as a major factor influencing the success of therapeutic treatments and has become a key focus for cancer research. The progressive growth of a tumor results in an inability of normal tissue blood vessels to oxygenate and provide sufficient...... important are the functional consequences experienced by the tumor cells residing in such environments: adaptation to hypoxia, cell quiescence, modulation of transporters and critical signaling molecules, immune escape, and enhanced metastatic potential. Together these factors lead to therapeutic barriers...

  7. Near-simultaneous hemoglobin saturation and oxygen tension maps in mouse brain using an AOTF microscope.

    Science.gov (United States)

    Shonat, R D; Wachman, E S; Niu, W; Koretsky, A P; Farkas, D L

    1997-09-01

    A newly developed microscope using acousto-optic tunable filters (AOTFs) was used to generate in vivo hemoglobin saturation (SO2) and oxygen tension (PO2) maps in the cerebral cortex of mice. SO2 maps were generated from the spectral analysis of reflected absorbance images collected at different wavelengths, and PO2 maps were generated from the phosphorescence lifetimes of an injected palladium-porphyrin compound using a frequency-domain measurement. As the inspiratory O2 was stepped from hypoxia (10% O2), through normoxia (21% O2), to hyperoxia (60% O2), measured SO2 and PO2 levels rose accordingly and predictably throughout. A plot of SO2 versus PO2 in different arterial and venous regions of the pial vessels conformed to the sigmoidal shape of the oxygen-hemoglobin dissociation curve, providing further validation of the two mapping procedures. The study demonstrates the versatility of the AOTF microscope for in vivo physiologic investigation, allowing for the generation of nearly simultaneous SO2 and PO2 maps in the cerebral cortex, and the frequency-domain detection of phosphorescence lifetimes. This class of study opens up exciting new possibilities for investigating the dynamics of hemoglobin and O2 binding during functional activation of neuronal tissues.

  8. Effect of low oxygen tension on the biological characteristics of human bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Kim, Dae Seong; Ko, Young Jong; Lee, Myoung Woo; Park, Hyun Jin; Park, Yoo Jin; Kim, Dong-Ik; Sung, Ki Woong; Koo, Hong Hoe; Yoo, Keon Hee

    2016-11-01

    Culture of mesenchymal stem cells (MSCs) under ambient conditions does not replicate the low oxygen environment of normal physiological or pathological states and can result in cellular impairment during culture. To overcome these limitations, we explored the effect of hypoxia (1 % O 2 ) on the biological characteristics of MSCs over the course of different culture periods. The following biological characteristics were examined in human bone marrow-derived MSCs cultured under hypoxia for 8 weeks: proliferation rate, morphology, cell size, senescence, immunophenotypic characteristics, and the expression levels of stemness-associated factors and cytokine and chemokine genes. MSCs cultured under hypoxia for approximately 2 weeks showed increased proliferation and viability. During long-term culture, hypoxia delayed phenotypic changes in MSCs, such as increased cell volume, altered morphology, and the expression of senescence-associated-β-gal, without altering their characteristic immunophenotypic characteristics. Furthermore, hypoxia increased the expression of stemness and chemokine-related genes, including OCT4 and CXCR7, and did not decrease the expression of KLF4, C-MYC, CCL2, CXCL9, CXCL10, and CXCR4 compared with levels in cells cultured under normoxia. In conclusion, low oxygen tension improved the biological characteristics of MSCs during ex vivo expansion. These data suggest that hypoxic culture could be a useful method for increasing the efficacy of MSC cell therapies.

  9. Differential oxygen dynamics in two diverse Dunning prostate R3327 rat tumor sublines (MAT-Lu and HI) with respect to growth and respiratory challenge

    International Nuclear Information System (INIS)

    Zhao Dawen; Constantinescu, Anca; Hahn, Eric W.; Mason, Ralph P.

    2002-01-01

    Purpose: Since hypoxia may influence tumor response to therapy and prognosis, we have compared oxygenation of tumors known to exhibit differential growth rate and tissue differentiation. Methods and Materials: Regional tumor oxygen tension was measured using 19 F nuclear magnetic resonance echo planar imaging relaxometry of hexafluorobenzene, which provided dynamic maps with respect to respiratory intervention. Investigations used two Dunning prostate R3327 rat tumor sublines: the fast growing, highly metastatic MAT-Lu and the moderately well-differentiated, slower growing HI. Results: Both sublines showed significantly higher oxygen tension in smaller tumors ( 3 ) than in larger tumors (>3.5 cm 3 ). Pooled data showed that MAT-Lu tumors exhibited greater hypoxia compared with the size-matched HI tumors (p 2 for tumors of both sublines (p 2 , while those in the MAT-Lu tumors showed little response to respiratory intervention. Conclusions: These results concur with hypotheses that hypoxia is related to tumor growth rate and degree of differentiation. Under baseline conditions, the differences were subtle. However, response to respiratory intervention revealed highly significant differences, which, if held valid in the clinic, could have prognostic value

  10. Mapping In Vivo Tumor Oxygenation within Viable Tumor by 19F-MRI and Multispectral Analysis

    Directory of Open Access Journals (Sweden)

    Yunzhou Shi

    2013-11-01

    Full Text Available Quantifying oxygenation in viable tumor remains a major obstacle toward a better understanding of the tumor microenvironment and improving treatment strategies. Current techniques are often complicated by tumor heterogeneity. Herein, a novel in vivo approach that combines 19F magnetic resonance imaging (19F-MRIR1 mapping with diffusionbased multispectral (MS analysis is introduced. This approach restricts the partial pressure of oxygen (pO2 measurements to viable tumor, the tissue of therapeutic interest. The technique exhibited sufficient sensitivity to detect a breathing gas challenge in a xenograft tumor model, and the hypoxic region measured by MS 19F-MRI was strongly correlated with histologic estimates of hypoxia. This approach was then applied to address the effects of antivascular agents on tumor oxygenation, which is a research question that is still under debate. The technique was used to monitor longitudinal pO2 changes in response to an antibody to vascular endothelial growth factor (B20.4.1.1 and a selective dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor (GDC-0980. GDC-0980 reduced viable tumor pO2 during a 3-day treatment period, and a significant reduction was also produced by B20.4.1.1. Overall, this method provides an unprecedented view of viable tumor pO2 and contributes to a greater understanding of the effects of antivascular therapies on the tumor's microenvironment.

  11. Exogenous and endogenous angiotensin-II decrease renal cortical oxygen tension in conscious rats by limiting renal blood flow

    NARCIS (Netherlands)

    Emans, Tonja W.; Janssen, Ben J.; Pinkham, Maximilian I.; Ow, Connie P. C.; Evans, Roger G.; Joles, Jaap A.; Malpas, Simon C.; Krediet, C. T. Paul; Koeners, Maarten P.

    2016-01-01

    Our understanding of the mechanisms underlying the role of hypoxia in the initiation and progression of renal disease remains rudimentary. We have developed a method that allows wireless measurement of renal tissue oxygen tension in unrestrained rats. This method provides stable and continuous

  12. Fluctuations in pO2 in poorly and well-oxygenated spontaneous canine tumors before and during fractionated radiation therapy.

    Science.gov (United States)

    Brurberg, Kjetil G; Skogmo, Hege K; Graff, Bjørn A; Olsen, Dag R; Rofstad, Einar K

    2005-11-01

    The spatial heterogeneity in oxygen tension (pO2) in tumor tissue has been studied extensively, whereas, the information about the temporal heterogeneity is sparse. The purpose of the present study was to search for pO2 fluctuations in untreated and irradiated spontaneous canine tumors, and to investigate whether there is a relationship between overall tumor oxygenation status and pO2 fluctuation pattern. Six dogs scheduled for radiation therapy of head and neck cancer were included in the study. The primary tumors were irradiated with 18 fractions of 3 Gy. Eppendorf polarographic electrodes and OxyLite fluorescence probes were used to measure overall oxygenation status and pO2 fluctuation pattern, respectively. Tissue pO2 was recorded at three subsequent days prior to treatment, and immediately before radiation fraction 4, 7, and 10. Overall oxygenation status differed substantially among the tumors. Radiation therapy had no consistent effect on overall oxygenation status. Fluctuations in pO2 were detected in untreated as well as irradiated tumors, and independent of whether the tumors were poorly or well oxygenated. Fluctuations in pO2 can occur in untreated and irradiated spontaneous canine tumors. There is no correlation between pO2 fluctuation pattern and overall tumor oxygenation status.

  13. BIOELECTRIC POTENTIALS IN HALICYSTIS : VII. THE EFFECTS OF LOW OXYGEN TENSION.

    Science.gov (United States)

    Blinks, L R; Darsie, M L; Skow, R K

    1938-11-20

    The potential difference across the protoplasm of impaled cells of Halicystis is not affected by increase of oxygen tension in equilibrium with the sea water, nor with decrease down to about 1/10 its tension in the air (2 per cent O(2) in N(2)). When bubbling of 2 per cent O(2) is stopped, the P.D. drifts downward, to be restored on stirring the sea water, or rebubbling the gas. Bubbling 0.2 per cent O(2) causes the P.D. to drop to 20 mv. or less; 1.1 per cent O(2) to about 50 mv. Restoration of 2 per cent or higher O(2) causes recovery to 70 or 80 mv. often with a preliminary cusp which decreases the P.D. before it rises. Perfusion of aerated sea water through the vacuole is just as effective in restoring the P.D. as external aeration, indicating that the direction of the oxygen gradient is not significant. Low O(2) tension also inhibits the reversed, negative P.D. produced by adding NH(4)Cl to sea water, 0.2 per cent O(2) bringing this P.D. back to the same low positive values found without ammonia. Restoration of 2 per cent O(2) or air, restores this latent negativity. At slightly below the threshold for ammonia reversal, low O(2) may induce a temporary negativity when first bubbled, and a negative cusp may occur on aeration before positive P.D. is regained. This may be due to a decreased consumption of ammonia, or to intermediate pH changes. The locus of the P.D. alteration was tested by applying increased KCl concentrations to the cell exterior; the large cusps produced in aerated solutions become greatly decreased when the P.D. has fallen in 0.2 per cent O(2). This indicates that the originally high relative mobility or concentration of K(+) ion has approached that of Na(+) in the external protoplasmic surface under reduced O(2) tension. Results obtained with sulfate sea water indicate that Na(+) mobility approaches that of SO(4) (-) in 0.2 per cent O(2). P.D. measurements alone cannot tell whether this is due to an increase of the slower ion or a decrease of

  14. Is oxygen important in the radiocurability of human tumors

    International Nuclear Information System (INIS)

    Withers, H.R.; Suit, H.D.

    1974-01-01

    It is quite likely that untreated human tumors contain hypoxic cells. Frequently, perhaps usually, the presence of these hypoxic cells does not influence radiocurability. If hypoxia limits radiocurability, it is more likely to do so in the treatment of large tumors and maybe with greater likelihood in tumors in certain sites. Hypoxia would also be more likely to affect response to a small number of fractions, since reoxygenation would need to be more complete in order that cell killing by the larger dose fractions used would not be prejudiced by the hypoxia of a small proportion of cells. Hyperbaric oxygen is disappointing as an adjuvant to radiotherapy. Results obtained are not better than those obtained using the best conventional fractionation regimes in air. This does not prove, however, that hypoxia is not a cause of failure to control tumors locally, since physiological adaptive mechanisms against HPO such as vasoconstriction may prevent better oxygenation of the tumor. If other methods such as high LET beams are to be used to reduce any effect hypoxia may have on radiocurability, their greatest benefit would be expected in the local control of late-stage disease and this benefit may be greater in some tumor sites than others. (U.S.)

  15. Oxygen Exposure Resulting in Arterial Oxygen Tensions Above the Protocol Goal Was Associated With Worse Clinical Outcomes in Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Aggarwal, Neil R; Brower, Roy G; Hager, David N; Thompson, B Taylor; Netzer, Giora; Shanholtz, Carl; Lagakos, Adrian; Checkley, William

    2018-04-01

    High fractions of inspired oxygen may augment lung damage to exacerbate lung injury in patients with acute respiratory distress syndrome. Participants enrolled in Acute Respiratory Distress Syndrome Network trials had a goal partial pressure of oxygen in arterial blood range of 55-80 mm Hg, yet the effect of oxygen exposure above this arterial oxygen tension range on clinical outcomes is unknown. We sought to determine if oxygen exposure that resulted in a partial pressure of oxygen in arterial blood above goal (> 80 mm Hg) was associated with worse outcomes in patients with acute respiratory distress syndrome. Longitudinal analysis of data collected in these trials. Ten clinical trials conducted at Acute Respiratory Distress Syndrome Network hospitals between 1996 and 2013. Critically ill patients with acute respiratory distress syndrome. None. We defined above goal oxygen exposure as the difference between the fraction of inspired oxygen and 0.5 whenever the fraction of inspired oxygen was above 0.5 and when the partial pressure of oxygen in arterial blood was above 80 mm Hg. We then summed above goal oxygen exposures in the first five days to calculate a cumulative above goal oxygen exposure. We determined the effect of a cumulative 5-day above goal oxygen exposure on mortality prior to discharge home at 90 days. Among 2,994 participants (mean age, 51.3 yr; 54% male) with a study-entry partial pressure of oxygen in arterial blood/fraction of inspired oxygen that met acute respiratory distress syndrome criteria, average cumulative above goal oxygen exposure was 0.24 fraction of inspired oxygen-days (interquartile range, 0-0.38). Participants with above goal oxygen exposure were more likely to die (adjusted interquartile range odds ratio, 1.20; 95% CI, 1.11-1.31) and have lower ventilator-free days (adjusted interquartile range mean difference of -0.83; 95% CI, -1.18 to -0.48) and lower hospital-free days (adjusted interquartile range mean difference of -1.38; 95

  16. Regional perfusion and oxygenation of tumors upon methylxanthine derivative administration

    International Nuclear Information System (INIS)

    Kelleher, Debra K.; Thews, Oliver; Vaupel, Peter

    1998-01-01

    Purpose: The use of methylxanthine derivatives has been postulated as a means of increasing tumor perfusion and thus ameliorating tumor hypoxia. The aim of this study was to quantify and compare the effects of three methylxanthine derivatives: pentoxifylline (PX), torbafylline (TB), and HWA 138 (HW) on tumor perfusion and oxygenation. Methods and Materials: Anesthetized Sprague Dawley rats with DS-sarcomas implanted subcutaneously onto the hind foot dorsum were used in this study. Mean arterial blood pressure (MABP) was measured throughout experiments. Regional red blood cell (RBC) flux was monitored using a multichannel laser Doppler device and tumor oxygenation on a more global level was assessed polarographically using an O 2 -sensitive catheter electrode. The methylxanthine derivatives were administered as a single dose intraperitoneally (for PX 50 mg/kg; for TB and HW 75 mg/kg). Results: Following drug administration, initial decreases in MABP down to 75% of baseline values were observed for all three substances. PX, HW, and TB caused initial transient reductions in mean RBC flux followed by gradual increases to values of 137 ± 27 %, 139 ± 14 %, and 122 ± 14 % respectively at t = 60 min. Following a small initial decrease upon drug administration, O 2 partial pressure (pO 2 ) rose to 160 ± 31 %, 153 ± 34 %, and 121 ± 11 % for PX, HW, and TB, respectively at t = 60 min. At the end of the observation period (t = 90 min), increases in RBC flux and pO 2 were still evident. When individual tumors were considered, a variety of patterns (including opposing effects) for changes in RBC flux were seen, not necessarily reflected in the mean values. Thus, while the methylxanthine derivatives caused an increased average tumor perfusion, there is evidence suggesting that a redistribution of tumor blood flow occurs which may amplify preexisting heterogeneity. Conclusions: Substantial improvements in tumor oxygenation and perfusion were observed after administration of

  17. Hemoglobin as a factor in the control of tumor oxygenation

    International Nuclear Information System (INIS)

    Hirst, D.G.

    1987-01-01

    The concentration of hemoglobin in the blood has been shown to have a market effect on the radiosensitivity of human and animal tumors. Experimental studies in mice indicate that radiosensitivity is influenced by a change in the hemoglobin level rather than by the absolute concentration. This dependence may be exploited to therapeutic advantage. Recent studies of hemoglobin/oxygen affinity have shown that the concentration of 2,3 diphosphoglycerate (2,3 DPG) affects tumor sensitivity to X-rays. Increased 2,3 DPG levels increase radiosensitivity in several mouse tumors. The time dependence of this effect remains to be established. The effective application of these effects in man may depend on the development of drugs which produce changes in hemoglobin affinity without the need for blood transfusions. Several drugs are currently being investigated

  18. Development of bovine embryos cultured in CR1aa and IVD101 media using different oxygen tensions and culture systems.

    Science.gov (United States)

    Somfai, Tamás; Inaba, Yasushi; Aikawa, Yoshio; Ohtake, Masaki; Kobayashi, Shuji; Konishi, Kazuyuki; Nagai, Takashi; Imai, Kei

    2010-12-01

    The aim of the present study was to optimise the culture conditions for the in vitro production of bovine embryos. The development of in vitro fertilised bovine oocytes in CR1aa supplemented with 5% calf serum and IVD101 culture media were compared using traditional microdrops and Well of the Well (WOW) culture systems either under 5% or 20% oxygen tension. After 7 days of culture, a significantly higher blastocyst formation rate was obtained for embryos cultured in CR1aa medium compared to those cultured in IVD101, irrespective of O2 tensions and culture systems. The blastocyst formation in IVD101 was suppressed under 20% O2 compared to 5% O2 . Despite their similar total cell numbers, higher rates of inner cell mass (ICM) cells were observed in blastocysts developed in IVD101 medium than in those developed in CR1aa, irrespective of O2 tensions. There was no significant difference in blastocyst formation, total, ICM and trophectoderm (TE) cell numbers between embryos obtained by microdrop and WOW culture systems irrespective of the culture media and O2 tensions used. In conclusion, CR1aa resulted in higher blastocyst formation rates irrespective of O2 tension, whereas IVD101 supported blastocyst formation only under low O2 levels but enhanced the proliferation of ICM cells.

  19. Postnatal follow-up of the oxygenation index, arterial to alveolar oxygen tension ratio and alveolar arterial oxygen tension difference values in neonates with the respiratory distress syndrome treated with conventional ventilatory support.

    Science.gov (United States)

    Atanasov, A; Despotova-Toleva, L

    1997-01-01

    Recent development of sophisticated intensive care technique for use in newborn infants with the respiratory distress syndrome (RDS) has resulted in changes in the therapeutic strategies and moved the problem of neonatal survival into the realm of new therapeutic realities. At present, the mechanical ventilation methods form an integral part of the intensive care strategy of infants with RDS. They have come to the forefront of infant care because of their successful use in ventilatory support and children survival where other therapeutic modalities have failed. The present prospective observational longitudinal study was designed to assess the real-time convenience, reliability and accuracy of the changes in the oxygenation index (OI), arterial-to-alveolar oxygen tension ratio (a/A PO2) and alveolar-arterial oxygen gradient (A-a)DO2 in ventilator-dependent neonates with RDS, to analyze their feasibility and potential information yield in oxygen inhalation therapy as well as their prognostic implications and predictive value. Twenty neonates with RDS, heralded by respiratory failure which necessitated the initiation of oxygen inhalation therapy and ventilatory support within 24 hours of birth, were enrolled in the study. Ten of the infants survived and the remaining ten died. OI, (a/A PO2) and (A-a)DO2 were followed up sequentially and thoroughly analyzed as the primary outcome measures of the study. The indices were calculated on the basis of the complete monitoring of the ventilatory equipment parameters and acid-base status carried out on an hourly basis. Our results show that: 1. The combination of three indexes (OI, (a/A)PO2 and (A-a)DO2 we propose is a useful discriminating predictor of neonatal lung maturity reflecting arterial blood gas status in ventilator-dependent neonates with RDS. 2. The indices detect the efficacy of the modern conventional ventilatory support with real-time convenience and reliable accuracy forming the cornerstone of clinical decision

  20. Preliminary Study of Oxygen-Enhanced Longitudinal Relaxation in MRI: A Potential Novel Biomarker of Oxygenation Changes in Solid Tumors

    International Nuclear Information System (INIS)

    O'Connor, James P.B.; Naish, Josephine H.; Parker, Geoff J.M.; Waterton, John C.; Watson, Yvonne; Jayson, Gordon C.; Buonaccorsi, Giovanni A.; Cheung, Sue; Buckley, David L.; McGrath, Deirdre M.; West, Catharine M.L.; Davidson, Susan E.; Roberts, Caleb; Mills, Samantha J.; Mitchell, Claire L.; Hope, Lynn; Ton, N. Chan; Jackson, Alan

    2009-01-01

    Purpose: There is considerable interest in developing non-invasive methods of mapping tumor hypoxia. Changes in tissue oxygen concentration produce proportional changes in the magnetic resonance imaging (MRI) longitudinal relaxation rate (R 1 ). This technique has been used previously to evaluate oxygen delivery to healthy tissues and is distinct from blood oxygenation level-dependent (BOLD) imaging. Here we report application of this method to detect alteration in tumor oxygenation status. Methods and materials: Ten patients with advanced cancer of the abdomen and pelvis underwent serial measurement of tumor R 1 while breathing medical air (21% oxygen) followed by 100% oxygen (oxygen-enhanced MRI). Gadolinium-based dynamic contrast-enhanced MRI was then performed to compare the spatial distribution of perfusion with that of oxygen-induced ΔR 1 . Results: ΔR 1 showed significant increases of 0.021 to 0.058 s -1 in eight patients with either locally recurrent tumor from cervical and hepatocellular carcinomas or metastases from ovarian and colorectal carcinomas. In general, there was congruency between perfusion and oxygen concentration. However, regional mismatch was observed in some tumor cores. Here, moderate gadolinium uptake (consistent with moderate perfusion) was associated with low area under the ΔR 1 curve (consistent with minimal increase in oxygen concentration). Conclusions: These results provide evidence that oxygen-enhanced longitudinal relaxation can monitor changes in tumor oxygen concentration. The technique shows promise in identifying hypoxic regions within tumors and may enable spatial mapping of change in tumor oxygen concentration.

  1. Unusual Growth Phase and Oxygen Tension Regulation of Oxidative Stress Protection Enzymes, Catalase and Superoxide Dismutase, in the Phytopathogen Xanthomonas oryzae pv. oryzae

    OpenAIRE

    Chamnongpol, S.; Mongkolsuk, S.; Vattanaviboon, P.; Fuangthong, M.

    1995-01-01

    The enzymes catalase and superoxide dismutase play major roles in protecting phytopathogenic bacteria from oxidative stress. In Xanthomonas species, these enzymes are regulated by both growth phase and oxygen tension. The highest enzyme levels were detected within 1 h of growth. Continued growth resulted in a decline of both enzyme activities. High oxygen tension was an inducing signal for both enzyme activities. An 80,000-Da monofunctional catalase and a manganese superoxide dismutase were t...

  2. Simultaneous administration of glucose and hyperoxic gas achieves greater improvement in tumor oxygenation than hyperoxic gas alone

    International Nuclear Information System (INIS)

    Snyder, Stacey A.; Lanzen, Jennifer L.; Braun, Rod D.; Rosner, Gary; Secomb, Timothy W.; Biaglow, John; Brizel, David M.; Dewhirst, Mark W.

    2001-01-01

    Purpose: To test the feasibility of hyperglycemic reduction of oxygen consumption combined with oxygen breathing (O 2 ), to improve tumor oxygenation. Methods and Materials: Fischer-344 rats bearing 1 cm R3230Ac flank tumors were anesthetized with Nembutal. Mean arterial pressure, heart rate, tumor blood flow ([TBF], laser Doppler flowmetry), pH, and pO 2 were measured before, during, and after glucose (1 or 4 g/kg) and/or O 2 . Results: Mean arterial pressure and heart rate were unaffected by treatment. Glucose at 1 g/kg yielded maximum blood glucose of 400 mg/dL, no change in TBF, reduced tumor pH (0.17 unit), and 3 mm Hg pO 2 rise. Glucose at 4 g/kg yielded maximum blood glucose of 900 mg/dL, pH drop of 0.6 unit, no pO 2 change, and reduced TBF (31%). Oxygen tension increased by 5 mm Hg with O 2 . Glucose (1 g/Kg) + O 2 yielded the largest change in pO 2 (27 mm Hg); this is highly significant relative to baseline or either treatment alone. The effect was positively correlated with baseline pO 2 , but 6 of 7 experiments with baseline pO 2 2 to improve tumor oxygenation. However, some cell lines are not susceptible to the Crabtree effect, and the magnitude is dependent on baseline pO 2 . Additional or alternative manipulations may be necessary to achieve more uniform improvement in pO 2

  3. The quaternary state of polymerized human hemoglobin regulates oxygenation of breast cancer solid tumors: A theoretical and experimental study

    Science.gov (United States)

    Ju, Julia A.; Baek, Jin Hyen; Yalamanoglu, Ayla; Buehler, Paul W.; Gilkes, Daniele M.; Palmer, Andre F.

    2018-01-01

    A major constraint in the treatment of cancer is inadequate oxygenation of the tumor mass, which can reduce chemotherapeutic efficacy. We hypothesize that polymerized human hemoglobin (PolyhHb) can be transfused into the systemic circulation to increase solid tumor oxygenation, and improve chemotherapeutic outcomes. By locking PolyhHb in the relaxed (R) quaternary state, oxygen (O2) offloading at low O2 tensions (20 mm Hg) is facilitated with tense (T) state PolyhHb. Therefore, R-state PolyhHb may deliver significantly more O2 to hypoxic tissues. Biophysical parameters of T and R-state PolyhHb were used to populate a modified Krogh tissue cylinder model to assess O2 transport in a tumor. In general, we found that increasing the volume of transfused PolyhHb decreased the apparent viscosity of blood in the arteriole. In addition, we found that PolyhHb transfusion decreased the wall shear stress at large arteriole diameters (>20 μm), but increased wall shear stress for small arteriole diameters (state PolyhHb may be more effective than T-state PolyhHb for O2 delivery at similar transfusion volumes. Reduction in the apparent viscosity resulting from PolyhHb transfusion may result in significant changes in flow distributions throughout the tumor microcirculatory network. The difference in wall shear stress implies that PolyhHb may have a more significant effect in capillary beds through mechano-transduction. Periodic top-load transfusions of PolyhHb into mice bearing breast tumors confirmed the oxygenation potential of both PolyhHbs via reduced hypoxic volume, vascular density, tumor growth, and increased expression of hypoxia inducible genes. Tissue section analysis demonstrated primary PolyhHb clearance occurred in the liver and spleen indicating a minimal risk for renal damage. PMID:29414985

  4. Modelling of L-valine Repeated Fed-batch Fermentation Process Taking into Account the Dissolved Oxygen Tension

    Directory of Open Access Journals (Sweden)

    Tzanko Georgiev

    2009-03-01

    Full Text Available This article deals with synthesis of dynamic unstructured model of variable volume fed-batch fermentation process with intensive droppings for L-valine production. The presented approach of the investigation includes the following main procedures: description of the process by generalized stoichiometric equations; preliminary data processing and calculation of specific rates for main kinetic variables; identification of the specific rates takes into account the dissolved oxygen tension; establishment and optimisation of dynamic model of the process; simulation researches. MATLAB is used as a research environment.

  5. The relationship between tumor oxygenation and cell proliferation in human soft tissue sarcomas

    International Nuclear Information System (INIS)

    Nordsmark, Marianne; Hoeyer, Morten; Keller, Johnny; Nielsen, Ole Steen; Jensen, Oluf Myhre; Overgaard, Jens

    1996-01-01

    Purpose: In malignant tumors the oxygenation status and tumor cell proliferation are known to influence local tumor control after radiotherapy. However, the relationship between oxygenation status and tumor cell kinetics in human tumors has not yet been described. Newly developed clinically applicable techniques such as oxygen electrode measurements and assessment of tumor cell proliferation rates have been suggested as promising predictive assays. The purpose of the present study was to characterize tumor oxygenation status in soft tissue sarcomas and to compare this with tumor cell kinetics and clinical parameters. Methods and Materials: Pretreatment tumor oxygenation status was measured by polarographic oxygen needle electrodes and evaluated as the median pO 2 and the percentage of pO 2 values ≤ 5 mmHg and ≤ 2.5 mmHg in 22 patients with primary soft tissue sarcomas. All tumors were characterized by histology, grade of malignancy, the level of microscopic necrosis, the level of effective hemoglobin, and magnetic resonance imaging estimation of tumor volume. The tumor cell potential doubling time and labeling index were measured by flow cytometric and immunohistochemical analysis of tumor biopsy specimens after in vivo incorporation of iododeoxyuridine. Results: There was a significant correlation between the median pO 2 and the tumor cell potential doubling time (p = 0.041), whereas no correlation was found between the level of hypoxia expressed by the percentage of pO 2 values ≤ 2.5 and ≤ 5 mmHg, respectively, and tumor cell potential doubling time. Furthermore, no correlation was found between either of the three tumor oxygenation parameters and labeling index. The material represented large intertumor heterogeneity in oxygenation status, cell kinetics, and tumor volume, and no correlation was found between oxygenation status and either volume, histopathology, grade of malignancy, or effective hemoglobin. Conclusion: This report is the first to suggest

  6. Hypoxyradiotherapy: lack of experimental evidence for a preferential radioprotective effect on normal versus tumor tissue as shown by direct oxygenation measurements in experimental sarcomas

    International Nuclear Information System (INIS)

    Kelleher, Debra K.; Thews, Oliver; Vaupel, Peter

    1997-01-01

    Aim: In order to investigate possible pathophysiological mechanisms underlying the postulated preferential protective effect of hypoxia on normal tissue during radiotherapy, the impact of acute respiratory hypoxia (8.2% O 2 + 91.8% N 2 ) on tissue oxygenation was assessed. Methods: Tumor and normal tissue oxygenation was directly determined using O 2 -sensitive electrodes in two experimental rat tumors (DS and Yoshida sarcomas) and in the normal subcutis of the hind foot dorsum. Results: During respiratory hypoxia, arterial blood O 2 tension (pO 2 ), oxyhemoglobin saturation and mean arterial blood pressure decreased. Changes in the arterial blood gas status were accompanied by a reflex hyperventilation leading to hypocapnia and respiratory alkalosis. In the subcutis, tissue oxygenation worsened during acute hypoxia, with decreases in the mean and median pO 2 . Significant increases in the hypoxic fractions were, however, not seen. In tumor tissues, oxygenation also worsened upon hypoxic hypoxia with significant decreases in the mean and median pO 2 and increases in the size of the hypoxic fractions for both sarcomas. Conclusion: These results suggest that during respiratory hypoxia, radiobiologically relevant reductions in the oxygenation (and a subsequent selective radioprotection) of normal tissue may not be achieved. In addition, in the tumor models studied, a worsening of tumor oxygenation was seen which could result in an increased radioresistance

  7. The role of tissue oxygen tension in the control of local blood flow in the microcirculation of skeletal muscles

    DEFF Research Database (Denmark)

    Ngo, Thuc Anh

    2010-01-01

    In the microcirculation blood flow is highly regulated dependent on the metabolic activity of the tissues. Among several mechanisms, mechanisms involved in the coupling of changes in tissue oxygen tension due to changes in the metabolic activity of the tissue play an important role. In the systemic...... (inhibitor of KATP channels) in the superfusate abolished both vasodilatation and constriction to low and high oxygen superfusate, indicating that KATP channels are involved in both hypoxic vasodilatation and hyperoxic vasoconstriction. Red blood cells (RBCs) have been proposed to release ATP and...... as in the intact blood-perfused arteriole. This indicates that RBCs are not essential for hypoxic vasodilatation. In addition several potential pathways were evaluated. Application of DPCPX (inhibitor of adenosine A1 and A2 receptors) and L-NAME (inhibitor of NO-synthase) did not affect vasomotor responses to low...

  8. The effect of oxygen tension on porcine embryonic development is dependent on embryo type

    DEFF Research Database (Denmark)

    Booth, Paul; Holm, Peter; Callesen, Henrik

    2005-01-01

    of the embryos prior to culture--a study was performed to examine the effect of O2 tension during culture on three different types of porcine embryos, namely: in vivo flushed embryos, and in vitro matured oocytes either fertilized in vitro or parthenogenetically activated. In vivo embryos (n=208) were flushed...... supplemented with 10% calf serum until day 7. The gas environment for IVM/IVF was 5% CO2 in air, while that for IVC was either 5% CO2 in air or 5% O2, 5% CO2 and 90% N2. Low O2 tension increased both day 7 blastocyst rates (high versus low O2, respectively; 9.3+/-2.9%: 26/280; 23.9+/-4.2%: 71/293; P...

  9. Comparison of Preterm and Term Wharton's Jelly-Derived Mesenchymal Stem Cell Properties in Different Oxygen Tensions.

    Science.gov (United States)

    Balgi-Agarwal, Saloni; Winter, Caitlyn; Corral, Alexis; Mustafa, Shamimunisa B; Hornsby, Peter; Moreira, Alvaro

    2018-06-27

    Mesenchymal stem cells (MSCs) have shown promise as therapeutic agents in treating morbidities associated with premature birth. MSCs derived from the human umbilical cord are easy to isolate and have low immunogenicity and a robust ability to secrete paracrine factors. To date, there are no studies evaluating preterm versus term umbilical cord tissue-derived MSCs. Therefore, our aim was twofold: (1) to compare stem cell properties in preterm versus term MSCs and (2) to examine the impact of oxygen tension on stem cell behavior. Umbilical cord tissue was obtained from 5 preterm and 5 term neonates. The cells were isolated and characterized as MSCs in accordance with the International Society for Cellular Therapy. We exposed MSCs to different oxygen tensions to examine the impact of environmental factors on cell performance. We studied the following stem cell properties: (i) motility, (ii) proliferation, (iii) senescence, (iv) cell viability, (v) colony-forming unit efficiency, and (vi) inflammatory cytokine expression. Under normoxia (21% O2), cells from preterm and term infants had similar properties. Under hypoxic conditions (1% O2), term MSCs had better cell proliferation; however, cells exposed to hyperoxia (90% O2) had the slowest motility and lowest cell viability (p cytokine expression between the groups. The term cells demonstrated more colony-forming efficiency than the preterm cells. In sum, our preliminary findings suggest that MSCs derived from term and preterm umbilical cords have similar characteristics, offering the potential of future autologous/allogeneic MSC transplants in neonates. © 2018 S. Karger AG, Basel.

  10. Detection of cerebral arterial gas embolism using regional cerebral oxygen saturation, quantitative electroencephalography, and brain oxygen tension in the swine

    NARCIS (Netherlands)

    Weenink, R. P.; Hollmann, M. W.; Stevens, M. F.; Kager, J.; van Gulik, T. M.; van Hulst, R. A.

    2014-01-01

    Cerebral air emboli occur as a complication of invasive medical procedures. The sensitivity of cerebral monitoring methods for the detection of air emboli is not known. This study investigates the utility of electroencephalography and non-invasively measured cerebral oxygen saturation in the

  11. Exogenous and endogenous angiotensin-II decrease renal cortical oxygen tension in conscious rats by limiting renal blood flow.

    Science.gov (United States)

    Emans, Tonja W; Janssen, Ben J; Pinkham, Maximilian I; Ow, Connie P C; Evans, Roger G; Joles, Jaap A; Malpas, Simon C; Krediet, C T Paul; Koeners, Maarten P

    2016-11-01

    Our understanding of the mechanisms underlying the role of hypoxia in the initiation and progression of renal disease remains rudimentary. We have developed a method that allows wireless measurement of renal tissue oxygen tension in unrestrained rats. This method provides stable and continuous measurements of cortical tissue oxygen tension (PO2) for more than 2 weeks and can reproducibly detect acute changes in cortical oxygenation. Exogenous angiotensin-II reduced renal cortical tissue PO2 more than equi-pressor doses of phenylephrine, probably because it reduced renal oxygen delivery more than did phenylephrine. Activation of the endogenous renin-angiotensin system in transgenic Cyp1a1Ren2 rats reduced cortical tissue PO2; in this model renal hypoxia precedes the development of structural pathology and can be reversed acutely by an angiotensin-II receptor type 1 antagonist. Angiotensin-II promotes renal hypoxia, which may in turn contribute to its pathological effects during development of chronic kidney disease. We hypothesised that both exogenous and endogenous angiotensin-II (AngII) can decrease the partial pressure of oxygen (PO2) in the renal cortex of unrestrained rats, which might in turn contribute to the progression of chronic kidney disease. Rats were instrumented with telemeters equipped with a carbon paste electrode for continuous measurement of renal cortical tissue PO2. The method reproducibly detected acute changes in cortical oxygenation induced by systemic hyperoxia and hypoxia. In conscious rats, renal cortical PO2 was dose-dependently reduced by intravenous AngII. Reductions in PO2 were significantly greater than those induced by equi-pressor doses of phenylephrine. In anaesthetised rats, renal oxygen consumption was not affected, and filtration fraction was increased only in the AngII infused animals. Oxygen delivery decreased by 50% after infusion of AngII and renal blood flow (RBF) fell by 3.3 ml min -1 . Equi-pressor infusion of

  12. Exogenous and endogenous angiotensin‐II decrease renal cortical oxygen tension in conscious rats by limiting renal blood flow

    Science.gov (United States)

    Emans, Tonja W.; Janssen, Ben J.; Pinkham, Maximilian I.; Ow, Connie P. C.; Evans, Roger G.; Joles, Jaap A.; Malpas, Simon C.; Krediet, C. T. Paul

    2016-01-01

    Key points Our understanding of the mechanisms underlying the role of hypoxia in the initiation and progression of renal disease remains rudimentary.We have developed a method that allows wireless measurement of renal tissue oxygen tension in unrestrained rats.This method provides stable and continuous measurements of cortical tissue oxygen tension (PO2) for more than 2 weeks and can reproducibly detect acute changes in cortical oxygenation.Exogenous angiotensin‐II reduced renal cortical tissue PO2 more than equi‐pressor doses of phenylephrine, probably because it reduced renal oxygen delivery more than did phenylephrine.Activation of the endogenous renin–angiotensin system in transgenic Cyp1a1Ren2 rats reduced cortical tissue PO2; in this model renal hypoxia precedes the development of structural pathology and can be reversed acutely by an angiotensin‐II receptor type 1 antagonist.Angiotensin‐II promotes renal hypoxia, which may in turn contribute to its pathological effects during development of chronic kidney disease. Abstract We hypothesised that both exogenous and endogenous angiotensin‐II (AngII) can decrease the partial pressure of oxygen (PO2) in the renal cortex of unrestrained rats, which might in turn contribute to the progression of chronic kidney disease. Rats were instrumented with telemeters equipped with a carbon paste electrode for continuous measurement of renal cortical tissue PO2. The method reproducibly detected acute changes in cortical oxygenation induced by systemic hyperoxia and hypoxia. In conscious rats, renal cortical PO2 was dose‐dependently reduced by intravenous AngII. Reductions in PO2 were significantly greater than those induced by equi‐pressor doses of phenylephrine. In anaesthetised rats, renal oxygen consumption was not affected, and filtration fraction was increased only in the AngII infused animals. Oxygen delivery decreased by 50% after infusion of AngII and renal blood flow (RBF) fell by 3.3 ml min−1

  13. Cutaneous respirometry by dynamic measurement of mitochondrial oxygen tension for monitoring mitochondrial function in vivo.

    Science.gov (United States)

    Harms, Floor A; Voorbeijtel, Wilhelmina J; Bodmer, Sander I A; Raat, Nicolaas J H; Mik, Egbert G

    2013-09-01

    Progress in diagnosis and treatment of mitochondrial dysfunction in chronic and acute disease could greatly benefit from techniques for monitoring of mitochondrial function in vivo. In this study we demonstrate the feasibility of in vivo respirometry in skin. Mitochondrial oxygen measurements by means of oxygen-dependent delayed fluorescence of protoporphyrin IX are shown to provide a robust basis for measurement of local oxygen disappearance rate (ODR). The fundamental principles behind the technology are described, together with an analysis method for retrievel of respirometry data. The feasibility and reproducibility of this clinically useful approach are demonstrated in a series of rats. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Membrane culture and reduced oxygen tension enhances cartilage matrix formation from equine cord blood mesenchymal stromal cells in vitro.

    Science.gov (United States)

    Co, C; Vickaryous, M K; Koch, T G

    2014-03-01

    Ongoing research is aimed at increasing cartilage tissue yield and quality from multipotent mesenchymal stromal cells (MSC) for the purpose of treating cartilage damage in horses. Low oxygen culture has been shown to enhance chondrogenesis, and novel membrane culture has been proposed to increase tissue yield and homogeneity. The objective of this study was to evaluate and compare the effect of reduced oxygen and membrane culture during in vitro chondrogenesis of equine cord blood (CB) MSC. CB-MSC (n = 5 foals) were expanded at 21% oxygen prior to 3-week differentiation in membrane or pellet culture at 5% and 21% oxygen. Assessment included histological examination (H&E, toluidine Blue, immunohistochemistry (IHC) for collagen type I and II), protein quantification by hydroxyproline assay and dimethylmethylene assay, and mRNA analysis for collagen IA1, collagen IIA1, collagen XA1, HIF1α and Sox9. Among treatment groups, 5% membrane culture produced neocartilage most closely resembling hyaline cartilage. Membrane culture resulted in increased wet mass, homogenous matrix morphology and an increase in total collagen content, while 5% oxygen culture resulted in higher GAG and type II collagen content. No significant differences were observed for mRNA analysis. Membrane culture at 5% oxygen produces a comparatively larger amount of higher quality neocartilage. Matrix homogeneity is attributed to a uniform diffusion gradient and reduced surface tension. Membrane culture holds promise for scale-up for therapeutic purposes, for cellular preconditioning prior to cytotherapeutic applications, and for modeling system for gas-dependent chondrogenic differentiation studies. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  15. Ion release from magnesium materials in physiological solutions under different oxygen tensions.

    Science.gov (United States)

    Feyerabend, Frank; Drücker, Heiko; Laipple, Daniel; Vogt, Carla; Stekker, Michael; Hort, Norbert; Willumeit, Regine

    2012-01-01

    Although magnesium as degradable biomaterial already showed clinical proof of concepts, the design of new alloys requires predictive in vitro methods, which are still lacking. Incubation under cell culture conditions to obtain "physiological" corrosion may be a solution. The aim of this study was to analyse the influence of different solutions, addition of proteins and of oxygen availability on the corrosion of different magnesium materials (pure Mg, WE43, and E11) with different surface finishing. Oxygen content in solution, pH, osmolality and ion release were determined. Corrosion led to a reduction of oxygen in solution. The influence of oxygen on pH was enhanced by proteins, while osmolality was not influenced. Magnesium ion release was solution-dependent and enhanced in the initial phase by proteins with delayed release of alloying elements. The main corrosion product formed was magnesium carbonate. Therefore, cell culture conditions are proposed as first step toward physiological corrosion.

  16. Comparison Between Cerebral Tissue Oxygen Tension and Energy Metabolism in Experimental Subdural Hematoma

    DEFF Research Database (Denmark)

    Nielsen, Troels Halfeld; Engell, Susanne I; Johnsen, Rikke Aagaard

    2011-01-01

    BACKGROUND: An experimental swine model (n = 7) simulating an acute subdural hematoma (ASDH) was employed (1) to explore the relation between the brain tissue oxygenation (PbtO(2)) and the regional cerebral energy metabolism as obtained by microdialysis, and (2) to define the lowest level of PbtO(2...

  17. Oxygen-tension measurements - The first step towards prevention and early detection of anastomotic leakage

    NARCIS (Netherlands)

    Tanase, D.; French, P.J.; Komen, N.; Kleinrensink, G.J.; Jeekel, J.; Lange, J.F.; Draaijer, A.

    2007-01-01

    Many patients still die every year as a result of anastomotic leakage after surgery. The medical world needs an objective aid to detect leakage during surgery and during the critical recovery period. We propose a miniature measurement system to detect adequate tissue oxygenation pre- and

  18. Oxygenation level and hemoglobin concentration in experimental tumor estimated by diffuse optical spectroscopy

    Science.gov (United States)

    Orlova, A. G.; Kirillin, M. Yu.; Volovetsky, A. B.; Shilyagina, N. Yu.; Sergeeva, E. A.; Golubiatnikov, G. Yu.; Turchin, I. V.

    2017-07-01

    Using diffuse optical spectroscopy the level of oxygenation and hemoglobin concentration in experimental tumor in comparison with normal muscle tissue of mice have been studied. Subcutaneously growing SKBR-3 was used as a tumor model. Continuous wave fiber probe diffuse optical spectroscopy system was employed. Optical properties extraction approach was based on diffusion approximation. Decreased blood oxygen saturation level and increased total hemoglobin content were demonstrated in the neoplasm. The main reason of such differences between tumor and norm was significant elevation of deoxyhemoglobin concentration in SKBR-3. The method can be useful for diagnosis of tumors as well as for study of blood flow parameters of tumor models with different angiogenic properties.

  19. Influence of hyperoxia on the number of nucleated cells and oxygen tension in rat bone marrow after whole-body irradiation

    International Nuclear Information System (INIS)

    Zima, M.; Vodicka, I.

    1987-01-01

    The cell number in the femur bone marrow of rats determined three days after X-ray or gamma irradiation is inversely proportional to the dose while oxygen tension in the marrow shows direct dependence on the dose. With fractionation of the lethal dose of gamma radiation (9 Gy) into two doses with different time intervals between them, a greater number of bone marrow cells and a smaller oxygen tension are reached on the 3rd day after the second dose, reflecting the extent of bone marrow repair. A short-term hyperoxia (95% O 2 + 5% CO 2 ) lasting 20 min from the end of exposure compared with the euoxic conditions induced, on the 3rd day after the second fraction, a nonsignificant but reproducible increase in the marrow cell number and a decrease in partial oxygen tension in the distal part of femur marrow. The results obtained testify that immediate short-term hyperoxia facilitates regeneration of the marrow and that a greater number of cells accompanied by greater metabolic activity and oxygen consumption decrease the partial oxygen tension measured on the 3rd day following the last exposure. (author). 7 figs., 16 refs

  20. Correlation of cutaneous tension distribution and tissue oxygenation with acute external tissue expansion

    Directory of Open Access Journals (Sweden)

    Marquardt C

    2009-11-01

    Full Text Available Abstract Today, the biomechanical fundamentals of skin expansion are based on viscoelastic models of the skin. Although many studies have been conducted in vitro, analyses performed in vivo are rare. Here, we present in vivo measurements of the expansion at the skin surface as well as measurement of the corresponding intracutaneous oxygen partial pressure. In our study the average skin stretching was 24%, with a standard deviation of 11%, excluding age or gender dependency. The measurement of intracutaneous oxygen partial pressure produced strong inter-individual fluctuations, including initial values at the beginning of the measurement, as well as varying individual patient reactions to expansion of the skin. Taken together, we propose that even large defect wounds can be closed successfully using the mass displacement caused by expansion especially in areas where soft, voluminous tissue layers are present.

  1. [Spontaneous tension hemothorax due to rupture of a solitary fibrous tumor of the posterior mediastinum].

    Science.gov (United States)

    Morita, Yohei; Ichimura, Hideo; Kikuchi, Shinji; Ozawa, Yuichiro; Inoue, Kazunari; Uchida, Atsushi; Kikuchi, Kazunori; Shiigai, Masanari; Shiotani, Seiji

    2013-10-01

    A 37-year-old man was transported by ambulance to our hospital due to abrupt chest pain. The pain began when he was practicing a combative-type sport. He denied any impact or blunt trauma. A chest radiograph revealed massive left pleural effusion with a mediastinal shift. Thoracentesis revealed a hemothorax;therefore, we performed an emergency thoracotomy. The intraoperative findings revealed a rupture of a posterior mediastinal tumor itself located between the descending aorta and the thoracic vertebra. After we identified the artery of Adamkiewicz that originates away from the tumor and evaluated the degree of tumor extension into the inter-vertebral foramen, we safely performed an elective tumor resection 1 month after the initial emergency operation. In patients with a hemothorax caused by rupture of the tumor itself, an elective tumor resection after detailed investigation should be considered if hemostasis can be achieved in the emergency thoracotomy.

  2. Effect of low oxygen tension on the biological characteristics of human bone marrow mesenchymal stem cells

    OpenAIRE

    Kim, Dae Seong; Ko, Young Jong; Lee, Myoung Woo; Park, Hyun Jin; Park, Yoo Jin; Kim, Dong-Ik; Sung, Ki Woong; Koo, Hong Hoe; Yoo, Keon Hee

    2016-01-01

    Culture of mesenchymal stem cells (MSCs) under ambient conditions does not replicate the low oxygen environment of normal physiological or pathological states and can result in cellular impairment during culture. To overcome these limitations, we explored the effect of hypoxia (1 % O2) on the biological characteristics of MSCs over the course of different culture periods. The following biological characteristics were examined in human bone marrow-derived MSCs cultured under hypoxia for 8 week...

  3. Adverse effects of reduced oxygen tension on the proliferative capacity of rat kidney and insulin-secreting cell lines involve DNA damage and stress responses

    International Nuclear Information System (INIS)

    Chen Jianhua; Jones, R. Huw; Tarry-Adkins, Jane; Smith, Noel H.; Ozanne, Susan E.

    2008-01-01

    Standard cell culture conditions do not reflect the physiological environment in terms of oxygen tension (20% vs 3%). The effects of lowering oxygen tension on cell proliferation in culture can be beneficial as well as detrimental depending on the cell line studied, but the molecular mechanism underlying such effects is not fully understood. We observed that the proliferative capacity of the rat cell lines NRK and INS-1 was inhibited when cultured under 3% oxygen as compared to 20% oxygen. Suppression of proliferation in NRK cells was accompanied by induction of DNA double strand breaks whereas in INS-1 cells it was accompanied by up-regulation of p53 and p27. Although Sirt1 was up-regulated in both cell lines by 3% oxygen the effects on antioxidant enzymes (MnSOD, CuZnSOD and catalase) were cell line specific. Marked up-regulation of heme oxygenase-1 (HO-1) was detected in both NRK and INS-1 cells when cultured in 3% oxygen. HO-1 expression can be readily induced by exposure to hydrogen peroxide in culture. These results suggest that reduced oxygen tension suppresses the proliferative capacity of these two cell lines through a stress response that is similar to an oxidative stress response but the molecular events that lead to the reduced cell proliferation are cell line specific

  4. Thioredoxin and Cancer: A Role for Thioredoxin in all States of Tumor Oxygenation

    International Nuclear Information System (INIS)

    Karlenius, Therese Christina; Tonissen, Kathryn Fay

    2010-01-01

    Thioredoxin is a small redox-regulating protein, which plays crucial roles in maintaining cellular redox homeostasis and cell survival and is highly expressed in many cancers. The tumor environment is usually under either oxidative or hypoxic stress and both stresses are known up-regulators of thioredoxin expression. These environments exist in tumors because their abnormal vascular networks result in an unstable oxygen delivery. Therefore, the oxygenation patterns in human tumors are complex, leading to hypoxia/re-oxygenation cycling. During carcinogenesis, tumor cells often become more resistant to hypoxia or oxidative stress-induced cell death and most studies on tumor oxygenation have focused on these two tumor environments. However, recent investigations suggest that the hypoxic cycling occurring within tumors plays a larger role in the contribution to tumor cell survival than either oxidative stress or hypoxia alone. Thioredoxin is known to have important roles in both these cellular responses and several studies implicate thioredoxin as a contributor to cancer progression. However, only a few studies exist that investigate the regulation of thioredoxin in the hypoxic and cycling hypoxic response in cancers. This review focuses on the role of thioredoxin in the various states of tumor oxygenation

  5. Variations in tumour oxygen tension (pO2) during accelerated radiotherapy of head and neck carcinoma

    International Nuclear Information System (INIS)

    Guichard, M.; Eschwege, F.; Luboinski, B.; Wibault, P.; Weeger, P.; Lusinchi, A.; Lartigau, E.

    1998-01-01

    The study was performed to assess the effect of accelerated radiotherapy on oxygenation of primary tumours and metastatic nodes in patients with advanced head and neck tumours. In 14 patients with head and neck tumour, oxygen tension (pO 2 ) was evaluated in normal tissues and tumours (primary tumour or metastatic neck node) before (0 Gy) and after 2 weeks (32 Gy) of accelerated radiotherapy (70 Gy in 3.5 weeks, with three daily fractions). Radiotherapy was combined with carbogen breathing in 5 patients. pO 2 was measured using a polarographic technique. For pooled normal tissues, median pO 2 was 38 mmHg before treatment and 46 mmHg after 2 weeks. For tumours, very low values ( 2 12 mmHg before treatment versus 26 mmHg after 2 weeks, P 2 was 44 mmHg at 2 weeks, compared with 13.5 mmHg before treatment (P=0.05). Very low pO 2 values, corresponding to tumour hypoxia, were found in the tumours (primary and metastatic neck nodes) prior to accelerated treatment. During the first 2 weeks of accelerated treatment, an increase in median pO 2 was found in nine of the 14 tumours, together with a decrease in the frequency of very low values. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  6. Severe anemia is associated with poor tumor oxygenation in head and neck squamous cell carcinomas

    International Nuclear Information System (INIS)

    Becker, Axel; Stadler, Peter; Lavey, Robert S.; Haensgen, Gabriele; Kuhnt, Thomas; Lautenschlaeger, Christine; Feldmann, Horst Juergen; Molls, Michael; Dunst, Juergen

    2000-01-01

    Purpose: To investigate the relationship between tumor oxygenation and the blood hemoglobin (Hb) concentration in patients with squamous cell carcinoma of the head and neck (SCCHN). Methods and Materials: A total of 133 patients with SCCHN underwent pretreatment polarographic pO 2 measurements of their tumors. In 66 patients measurements were also made in sternocleidomastoid muscles. The patients were divided into three groups according to their Hb concentration--severe anemia (Hb 2 . Conclusion: Our data suggest that a low Hb concentration and cigarette smoking contribute to inadequate oxygenation of SCCHN and thus for increased radioresistance. Consequently, Hb correction and abstinence from smoking may significantly improve tumor oxygenation

  7. IVF/ICSI outcomes after culture of human embryos at low oxygen tension: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Gomes Sobrinho David B

    2011-11-01

    Full Text Available Abstract Background Improved pregnancy, implantation, and birth rates have been reported after the use of reduced O2 concentration during embryo culture, mainly due to a reduction of the cumulative detrimental effects of reactive oxygen species. However, some studies have failed to report any positive effects. The objective of this meta-analysis was to evaluate the effect of a low-O2 environment on IVF/intracytoplasmic sperm injection (ICSI outcomes. Methods All available published and ongoing randomised trials that compared the effects of low (~5%; OC~5 and atmospheric (~20%; OC~20 oxygen concentrations on IVF/ICSI outcomes were included. Search strategies included online surveys of databases from 1980 to 2011. The outcomes measured were fertilisation rate, implantation rate and ongoing pregnancy rates. The fixed effects model was used to calculate the odds ratio. Results Seven studies were included in this analysis. The pooled fertilisation rate did not differ significantly (P = 0.54 between the group of oocytes cultured at low O2 tension and the group at atmospheric O2 tension. Concerning all cycles, the implantation (P = 0.06 and ongoing pregnancy (P = 0.051 rates were not significantly different between the group receiving transferred sets containing only OC~5 embryos and the group receiving transferred sets with only OC~20 embryos. In a meta-analysis performed for only those trials in which embryos were transferred on day 2/3, implantation (P = 0.63 and ongoing pregnancy (P = 0.19 rates were not significantly different between the groups. In contrast, when a meta-analysis was performed using only trials in which embryos were transferred on days 5 and 6 (at the blastocyst stage, the group with transferred sets of only OC~5 embryos showed a statistically significantly higher implantation rate (P = 0.006 than the group receiving transferred sets with only OC~20 embryos, although the ongoing pregnancy (P = 0.19 rates were not significantly

  8. Endothelial cell respiration is affected by the oxygen tension during shear exposure: role of mitochondrial peroxynitrite.

    Science.gov (United States)

    Jones, Charles I; Han, Zhaosheng; Presley, Tennille; Varadharaj, Saradhadevi; Zweier, Jay L; Ilangovan, Govindasamy; Alevriadou, B Rita

    2008-07-01

    Cultured vascular endothelial cell (EC) exposure to steady laminar shear stress results in peroxynitrite (ONOO(-)) formation intramitochondrially and inactivation of the electron transport chain. We examined whether the "hyperoxic state" of 21% O(2), compared with more physiological O(2) tensions (Po(2)), increases the shear-induced nitric oxide (NO) synthesis and mitochondrial superoxide (O(2)(*-)) generation leading to ONOO(-) formation and suppression of respiration. Electron paramagnetic resonance oximetry was used to measure O(2) consumption rates of bovine aortic ECs sheared (10 dyn/cm(2), 30 min) at 5%, 10%, or 21% O(2) or left static at 5% or 21% O(2). Respiration was inhibited to a greater extent when ECs were sheared at 21% O(2) than at lower Po(2) or left static at different Po(2). Flow in the presence of an endothelial NO synthase (eNOS) inhibitor or a ONOO(-) scavenger abolished the inhibitory effect. EC transfection with an adenovirus that expresses manganese superoxide dismutase in mitochondria, and not a control virus, blocked the inhibitory effect. Intracellular and mitochondrial O(2)(*-) production was higher in ECs sheared at 21% than at 5% O(2), as determined by dihydroethidium and MitoSOX red fluorescence, respectively, and the latter was, at least in part, NO-dependent. Accumulation of NO metabolites in media of ECs sheared at 21% O(2) was modestly increased compared with ECs sheared at lower Po(2), suggesting that eNOS activity may be higher at 21% O(2). Hence, the hyperoxia of in vitro EC flow studies, via increased NO and mitochondrial O(2)(*-) production, leads to enhanced ONOO(-) formation intramitochondrially and suppression of respiration.

  9. Environmental oxygen tension regulates the energy metabolism and self-renewal of human embryonic stem cells.

    Science.gov (United States)

    Forristal, Catherine E; Christensen, David R; Chinnery, Fay E; Petruzzelli, Raffaella; Parry, Kate L; Sanchez-Elsner, Tilman; Houghton, Franchesca D

    2013-01-01

    Energy metabolism is intrinsic to cell viability but surprisingly has been little studied in human embryonic stem cells (hESCs). The current study aims to investigate the effect of environmental O2 tension on carbohydrate utilisation of hESCs. Highly pluripotent hESCs cultured at 5% O2 consumed significantly more glucose, less pyruvate and produced more lactate compared to those maintained at 20% O2. Moreover, hESCs cultured at atmospheric O2 levels expressed significantly less OCT4, SOX2 and NANOG than those maintained at 5% O2. To determine whether this difference in metabolism was a reflection of the pluripotent state, hESCs were cultured at 5% O2 in the absence of FGF2 for 16 hours leading to a significant reduction in the expression of SOX2. In addition, these cells consumed less glucose and produced significantly less lactate compared to those cultured in the presence of FGF2. hESCs maintained at 5% O2 were found to consume significantly less O2 than those cultured in the absence of FGF2, or at 20% O2. GLUT1 expression correlated with glucose consumption and using siRNA and chromatin immunoprecipitation was found to be directly regulated by hypoxia inducible factor (HIF)-2α at 5% O2. In conclusion, highly pluripotent cells associated with hypoxic culture consume low levels of O2, high levels of glucose and produce large amounts of lactate, while at atmospheric conditions glucose consumption and lactate production are reduced and there is an increase in oxidative metabolism. These data suggest that environmental O2 regulates energy metabolism and is intrinsic to the self-renewal of hESCs.

  10. Diet-induced weight loss decreases adipose tissue oxygen tension with parallel changes in adipose tissue phenotype and insulin sensitivity in overweight humans

    NARCIS (Netherlands)

    Vink, R.G.; Roumans, N.J.; Čajlaković, M.; Cleutjens, J.P.M.; Boekschoten, M.V.; Fazelzadeh, P.; Vogel, M.A.A.; Blaak, E.E.; Mariman, E.C.; Baak, van M.A.; Goossens, G.H.

    2017-01-01

    Background/objectives: Although adipose tissue (AT) hypoxia is present in rodent models of obesity, evidence for this in humans is limited. Here, we investigated the effects of diet-induced weight loss (WL) on abdominal subcutaneous AT oxygen tension (pO 2), AT blood flow (ATBF), AT capillary

  11. Matrix forming characteristics of inner and outer human meniscus cells on 3D collagen scaffolds under normal and low oxygen tensions.

    Science.gov (United States)

    Croutze, Roger; Jomha, Nadr; Uludag, Hasan; Adesida, Adetola

    2013-12-13

    Limited intrinsic healing potential of the meniscus and a strong correlation between meniscal injury and osteoarthritis have prompted investigation of surgical repair options, including the implantation of functional bioengineered constructs. Cell-based constructs appear promising, however the generation of meniscal constructs is complicated by the presence of diverse cell populations within this heterogeneous tissue and gaps in the information concerning their response to manipulation of oxygen tension during cell culture. Four human lateral menisci were harvested from patients undergoing total knee replacement. Inner and outer meniscal fibrochondrocytes (MFCs) were expanded to passage 3 in growth medium supplemented with basic fibroblast growth factor (FGF-2), then embedded in porous collagen type I scaffolds and chondrogenically stimulated with transforming growth factor β3 (TGF-β3) under 21% (normal or normoxic) or 3% (hypoxic) oxygen tension for 21 days. Following scaffold culture, constructs were analyzed biochemically for glycosaminoglycan production, histologically for deposition of extracellular matrix (ECM), as well as at the molecular level for expression of characteristic mRNA transcripts. Constructs cultured under normal oxygen tension expressed higher levels of collagen type II (p = 0.05), aggrecan (p oxygen tension. There was no significant difference in expression of these genes between scaffolds seeded with MFCs isolated from inner or outer regions of the tissue following 21 days chondrogenic stimulation (p > 0.05). Cells isolated from inner and outer regions of the human meniscus demonstrated equivalent differentiation potential toward chondrogenic phenotype and ECM production. Oxygen tension played a key role in modulating the redifferentiation of meniscal fibrochondrocytes on a 3D collagen scaffold in vitro.

  12. Endoscopic Resection of Tracheal Tumor in an Elderly Woman Under Extracorporeal Membrane Oxygenation

    Directory of Open Access Journals (Sweden)

    Yi-Ying Chiang

    2011-03-01

    Full Text Available Anesthetic management of patients with difficult airway is challenging, especially in patients who present with near total occlusion of the airway. Tracheal tumors occur more frequently in elderly patients who are more prone to hypoxic injury. Reliable ventilation and oxygenation are mandatory for a safe and sound intervention. Herein, we report on a 71-year-old woman with a large tracheal tumor occluding approximately 90% of the tracheal lumen. Extracorporeal membrane oxygenation under local anesthesia was used during electrocautery resection of the tumor because of the possibility of fatal airway collapse due to the degree of occlusion and location of the tumor. After the tumor had been successfully resected by means of bronchoscopy, an endotracheal tube was inserted, and the patient was weaned from extracorporeal membrane oxygenation.

  13. A multislice single breath-hold scheme for imaging alveolar oxygen tension in humans.

    Science.gov (United States)

    Hamedani, Hooman; Kadlecek, Stephen J; Emami, Kiarash; Kuzma, Nicholas N; Xu, Yinan; Xin, Yi; Mongkolwisetwara, Puttisarn; Rajaei, Jennia; Barulic, Amy; Wilson Miller, G; Rossman, Milton; Ishii, Masaru; Rizi, Rahim R

    2012-05-01

    Reliable, noninvasive, and high-resolution imaging of alveolar partial pressure of oxygen (p(A)O(2)) is a potentially valuable tool in the early diagnosis of pulmonary diseases. Several techniques have been proposed for regional measurement of p(A)O(2) based on the increased depolarization rate of hyperpolarized (3) He. In this study, we explore one such technique by applying a multislice p(A)O(2) -imaging scheme that uses interleaved-slice ordering to utilize interslice time-delays more efficiently. This approach addresses the low spatial resolution and long breath-hold requirements of earlier techniques, allowing p(A)O(2) measurements to be made over the entire human lung in 10-15 s with a typical resolution of 8.3 × 8.3 × 15.6 mm(3). PO(2) measurements in a glass syringe phantom were in agreement with independent gas analysis within 4.7 ± 4.1% (R = 0.9993). The technique is demonstrated in four human subjects (healthy nonsmoker, healthy former smoker, healthy smoker, and patient with COPD), each imaged six times on 3 different days during a 2-week span. Two independent measurements were performed in each session, consisting of 12 coronal slices. The overall p(A)O(2) mean across all subjects was 95.9 ± 12.2 Torr and correlated well with end-tidal O(2) (R = 0.805, P < 0.0001). The alveolar O(2) uptake rate was consistent with the expected range of 1-2 Torr/s. Repeatable visual features were observed in p(A)O(2) maps over different days, as were characteristic differences among the subjects and gravity-dependent effects. Copyright © 2011 Wiley Periodicals, Inc.

  14. Deleted in Malignant Brain Tumors 1 (DMBT1 is present in hyaline membranes and modulates surface tension of surfactant

    Directory of Open Access Journals (Sweden)

    Griese Matthias

    2007-10-01

    Full Text Available Abstract Background Deleted in Malignant Brain Tumors 1 (DMBT1 is a secreted scavenger receptor cysteine-rich protein that binds various bacteria and is thought to participate in innate pulmonary host defense. We hypothesized that pulmonary DMBT1 could contribute to respiratory distress syndrome in neonates by modulating surfactant function. Methods DMBT1 expression was studied by immunohistochemistry and mRNA in situ hybridization in post-mortem lungs of preterm and full-term neonates with pulmonary hyaline membranes. The effect of human recombinant DMBT1 on the function of bovine and porcine surfactant was measured by a capillary surfactometer. DMBT1-levels in tracheal aspirates of ventilated preterm and term infants were determined by ELISA. Results Pulmonary DMBT1 was localized in hyaline membranes during respiratory distress syndrome. In vitro addition of human recombinant DMBT1 to the surfactants increased surface tension in a dose-dependent manner. The DMBT1-mediated effect was reverted by the addition of calcium depending on the surfactant preparation. Conclusion Our data showed pulmonary DMBT1 expression in hyaline membranes during respiratory distress syndrome and demonstrated that DMBT1 increases lung surface tension in vitro. This raises the possibility that DMBT1 could antagonize surfactant supplementation in respiratory distress syndrome and could represent a candidate target molecule for therapeutic intervention in neonatal lung disease.

  15. Temporal variation in the response of tumors to hyperoxia with breathing carbogen and oxygen

    Science.gov (United States)

    Hou, Hua-gang; Khan, Nadeem; Du, Gai-xin; Hodge, Sassan; Swartz, Harold M.

    2016-01-01

    The effect of hyperoxygenation with carbogen (95% O2 + 5% CO2) and 100% oxygen inhalation on partial pressure of oxygen (pO2) of radiation-induced fibrosarcoma (RIF-1) tumor was investigated. RIF-1 tumors were innoculated in C3H mice, and aggregates of oximetry probe, lithium phthalocyanine (LiPc), was implanted in each tumor. A baseline tumor pO2 was measured by electron paramagnetic resonance (EPR) oximetry for 20 minutes in anesthetized mice breathing 30% O2 and then the gas was switched to carbogen or 100 % oxygen for 60 minutes. These experiments were repeated for 10 days. RIF-1 tumors were hypoxic with a baseline tissue pO2 of 6.2–8.3 mmHg in mice breathing 30% O2. Carbogen and 100% oxygen significantly increased tumor pO2 on days 1 to 5, with a maximal increase at approximately 32–45 minutes on each day. However, the extent of increase in pO2 from the baseline declined significantly on day 5 and day 10. The results provide quantitative information on the effect of hyperoxic gas inhalation on tumor pO2 over the course of 10 days. EPR oximetry can be effectively used to repeatedly monitor tumor pO2 and test hyperoxic methods for potential clinical applications. PMID:27867481

  16. Temporal variation in the response of tumors to hyperoxia with breathing carbogen and oxygen

    Directory of Open Access Journals (Sweden)

    Hua-gang Hou

    2016-01-01

    Full Text Available The effect of hyperoxygenation with carbogen (95% O 2 + 5% CO 2 and 100% oxygen inhalation on partial pressure of oxygen (pO 2 of radiation-induced fibrosarcoma (RIF-1 tumor was investigated. RIF-1 tumors were innoculated in C3H mice, and aggregates of oximetry probe, lithium phthalocyanine (LiPc, was implanted in each tumor. A baseline tumor pO 2 was measured by electron paramagnetic resonance (EPR oximetry for 20 minutes in anesthetized mice breathing 30% O 2 and then the gas was switched to carbogen or 100 % oxygen for 60 minutes. These experiments were repeated for 10 days. RIF-1 tumors were hypoxic with a baseline tissue pO 2 of 6.2-8.3 mmHg in mice breathing 30% O 2 . Carbogen and 100% oxygen significantly increased tumor pO 2 on days 1 to 5, with a maximal increase at approximately 32-45 minutes on each day. However, the extent of increase in pO 2 from the baseline declined significantly on day 5 and day 10. The results provide quantitative information on the effect of hyperoxic gas inhalation on tumor pO 2 over the course of 10 days. EPR oximetry can be effectively used to repeatedly monitor tumor pO 2 and test hyperoxic methods for potential clinical applications.

  17. Critical oxygen tension and the effect of hypoxia on the oxygen consumption of the striped catfish, Pangasius hypophthaimos (Pangasiidae)

    DEFF Research Database (Denmark)

    Lefevre, S.; Bayley, Mark; Wang, Tobias

    2008-01-01

    The striped catfish (Pangasius hypophthalmus) is an air-breathing teleost that uses a modified swim bladder for aerial gas exchange. Pangasius is of enormous importance for aquaculture industry in the Mekong Delta(Vietnam), but little is known about its physiology. We have initiated a series...... consumption (VO2), measured with intermittent closed respirometry, was 67.8 ± 5.1 mLO2/kg/h when the fish were maintained without access to air at 27 °C. The critical oxygen tension (Pcrit) at these conditions was 57.9 ± 8.9 mmHg (N = 7). The metabolic response to aquatic hypoxia was studied in fish subjected....... The ontogenetic effect of environmental PO2 on metabolism is currently under investigation with fish being reared in 30%, 60% and 100% saturation. Data on resting VO2and Pcrit will be presented and discussed for these animals....

  18. Oxygen microenvironment affects the uptake of nanoparticles in head and neck tumor cells

    Science.gov (United States)

    Chen, Eunice Y.; Hodge, Sasson; Tai, Katherine; Hou, Huagang; Khan, Nadeem; Hoopes, P. Jack; Samkoe, Kimberley S.

    2013-02-01

    Survival of head and neck cancer patients has not improved in several decades despite advances in diagnostic and therapeutic techniques. Tumor hypoxia in head and neck cancers is a critical factor that leads to poor prognosis, resistance to radiation and chemotherapies, and increased metastatic potential. Magnetic nanoparticle hyperthermia (mNPHT) is a promising therapy for hypoxic tumors because nanoparticles (NP) can be directly injected into, or targeted to, hypoxic tumor cells and exposed to alternating magnetic fields (AMF) to induce hyperthermia. Magnetic NPHT can improve therapeutic effectiveness by two modes of action: 1) direct killing of hypoxic tumor cells; and 2) increase in tumor oxygenation, which has the potential to make the tumor more susceptible to adjuvant therapies such as radiation and chemotherapy. Prior studies in breast cancer cells demonstrated that a hypoxic microenvironment diminished NP uptake in vitro; however, mNPHT with intratumoral NP injection in hypoxic tumors increased tumor oxygenation and delayed tumor growth. In this study, head and neck squamous cell carcinoma (HNSCC) cell lines were incubated in normoxic, hypoxic, and hyperoxic conditions with iron oxide NP for 4-72 hours. After incubation, the cells were analyzed for iron uptake by mass spectrometry, Prussian blue staining, and electron microscopy. In contrast to breast cancer cells, uptake of NPs was increased in hypoxic microenvironments as compared to normoxic conditions in HNSCC cells. In future studies, we will confirm the effect of the oxygen microenvironment on NP uptake and efficacy of mNPHT both in vitro and in vivo.

  19. Electron Paramagnetic Resonance pO2 Image Tumor Oxygen-Guided Radiation Therapy Optimization.

    Science.gov (United States)

    Epel, Boris; Maggio, Matt; Pelizzari, Charles; Halpern, Howard J

    2017-01-01

    Modern standards for radiation treatment do not take into account tumor oxygenation for radiation treatment planning. Strong correlation between tumor oxygenation and radiation treatment success suggests that oxygen-guided radiation therapy (OGRT) may be a promising enhancement of cancer radiation treatment. We have developed an OGRT protocol for rodents. Electron paramagnetic resonance (EPR) imaging is used for recording oxygen maps with high spatial resolution and excellent accuracy better than 1 torr. Radiation is delivered with an animal intensity modulated radiation therapy (IMRT) XRAD225Cx micro-CT/ therapy system. The radiation plan is delivered in two steps. First, a uniform 15% tumor control dose (TCD 15 ) is delivered to the whole tumor. In the second step, an additional booster dose amounting to the difference between TCD 98 and TCD 15 is delivered to radio-resistant, hypoxic tumor regions. Delivery of the booster dose is performed using a multiport conformal beam protocol. For radiation beam shaping we used individual radiation blocks 3D-printed from tungsten infused ABS polymer. Calculation of beam geometry and the production of blocks is performed next to the EPR imager, immediately after oxygen imaging. Preliminary results demonstrate the sub-millimeter precision of the radiation delivery and high dose accuracy. The efficacy of the radiation treatment is currently being tested on syngeneic FSa fibrosarcoma tumors grown in the legs of C3H mice.

  20. Interrogation of metabolic and oxygen states of tumors with fiber-based luminescence lifetime spectroscopy.

    Science.gov (United States)

    Lukina, Maria; Orlova, Anna; Shirmanova, Marina; Shirokov, Daniil; Pavlikov, Anton; Neubauer, Antje; Studier, Hauke; Becker, Wolfgang; Zagaynova, Elena; Yoshihara, Toshitada; Tobita, Seiji; Shcheslavskiy, Vladislav

    2017-02-15

    The study of metabolic and oxygen states of cells in a tumor in vivo is crucial for understanding of the mechanisms responsible for tumor development and provides background for the relevant tumor's treatment. Here, we show that a specially designed implantable fiber-optic probe provides a promising tool for optical interrogation of metabolic and oxygen states of a tumor in vivo. In our experiments, the excitation light from a ps diode laser source is delivered to the sample through an exchangeable tip via a multimode fiber, and the emission light is transferred to the detector by another multimode fiber. Fluorescence lifetime of a nicotinamid adenine dinucleotide (NAD(P)H) and phosphorescence lifetime of an oxygen sensor based on an iridium (III) complex of enzothienylpyridine (BTPDM1) are explored both in model experiment in solutions and in living mice.

  1. Magnetic resonance imaging of tumor oxygenation and metabolic profile

    DEFF Research Database (Denmark)

    Krishna, Murali C.; Matsumoto, Shingo; Saito, Keita

    2013-01-01

    The tumor microenvironment is distinct from normal tissue as a result of abnormal vascular network characterized by hypoxia, low pH, high interstitial fluid pressure and elevated glycolytic activity. This poses a barrier to treatments including radiation therapy and chemotherapy. Imaging methods...... spectroscopic imaging. Imaging pO2 in tumors is now a robust pre-clinical imaging modality with potential for implementation clinically. Pre-clinical studies and an initial clinical study with hyperpolarized metabolic MR have been successful and suggest that the method may be part of image-guided radiotherapy...

  2. Optimizing the calculation of DM,CO and VC via the single breath single oxygen tension DLCO/NO method.

    Science.gov (United States)

    Coffman, Kirsten E; Taylor, Bryan J; Carlson, Alex R; Wentz, Robert J; Johnson, Bruce D

    2016-01-15

    Alveolar-capillary membrane conductance (D(M,CO)) and pulmonary-capillary blood volume (V(C)) are calculated via lung diffusing capacity for carbon monoxide (DL(CO)) and nitric oxide (DL(NO)) using the single breath, single oxygen tension (single-FiO2) method. However, two calculation parameters, the reaction rate of carbon monoxide with blood (θ(CO)) and the D(M,NO)/D(M,CO) ratio (α-ratio), are controversial. This study systematically determined optimal θ(CO) and α-ratio values to be used in the single-FiO2 method that yielded the most similar D(M,CO) and V(C) values compared to the 'gold-standard' multiple-FiO2 method. Eleven healthy subjects performed single breath DL(CO)/DL(NO) maneuvers at rest and during exercise. D(M,CO) and V(C) were calculated via the single-FiO2 and multiple-FiO2 methods by implementing seven θ(CO) equations and a range of previously reported α-ratios. The RP θ(CO) equation (Reeves, R.B., Park, H.K., 1992. Respiration Physiology 88 1-21) and an α-ratio of 4.0-4.4 yielded DM,CO and VC values that were most similar between methods. The RP θ(CO) equation and an experimental α-ratio should be used in future studies. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Stimulation of growth of the human gastric pathogen Helicobacter pylori by atmospheric level of oxygen under high carbon dioxide tension

    Directory of Open Access Journals (Sweden)

    Lee Na

    2011-05-01

    Full Text Available Abstract Background Helicobacter pylori (Hp, a human pathogen that is associated with gastritis, peptic ulcer, and gastric cancer, has been considered a microaerophile, but there is no general consensus about its specific O2 requirements. A clear understanding of Hp physiology is needed to elucidate the pathogenic mechanism(s of Hp infection. Results We cultured Hp under a range of O2 levels with or without 10% CO2 and evaluated growth profiles, morphology, intracellular pH, and energy metabolism. We found that, in the presence of 10% CO2, the normal atmospheric level of O2 inhibited Hp growth at low density but stimulated growth at a higher density. Field emission scanning electron microscopy and fluorescence microscopy of Hp cells cultured under 20% O2 tension revealed live spiral-shaped bacteria with outer membrane vesicles on a rugged cell surface, which became smooth during the stationary phase. Fermentation products including acetate, lactate, and succinate were detected in cell culture media grown under microaerobic conditions, but not under the aerobic condition. CO2 deprivation for less than 24 h did not markedly change cytoplasmic or periplasmic pH, suggesting that cellular pH homeostasis alone cannot account for the capnophilic nature of Hp. Further, CO2 deprivation significantly increased intracellular levels of ppGpp and ATP but significantly decreased cellular mRNA levels, suggesting induction of the stringent response. Conclusions We conclude, unlike previous reports, that H. pylori may be a capnophilic aerobe whose growth is promoted by atmospheric oxygen levels in the presence of 10% CO2. Our data also suggest that buffering of intracellular pH alone cannot account for the CO2 requirement of H. pylori and that CO2 deprivation initiates the stringent response in H. pylori. Our findings may provide new insight into the physiology of this fastidious human pathogen.

  4. Oxygen tension in human tumours measured with polarographic needle electrodes and its relationship to vascular density, necrosis and hypoxia

    International Nuclear Information System (INIS)

    Lyng, Heidi; Sundfoer, Kolbein; Rofstad, Einar K.

    1997-01-01

    Background and purpose: The use of polarographic needle electrodes for measurement of oxygen tension (pO 2 ) in tumours requires documentation of the validity of the method. In the present work the pO 2 values measured polarographically with the Eppendorf pO 2 histograph in human tumours were compared with the histological appearance of the tumour tissue, i.e. vascular density, fraction of necrosis and fraction of hypoxic tissue, to investigate whether the measurements reflected the expected pO 2 . Materials and methods: The pO 2 was measured in cervix tumours in patients and in human melanoma xenografted tumours in athymic mice. Vascular density was determined in the cervix tumours by histological analysis of biopsies from the pO 2 measurement tracks. Fraction of necrosis and fraction of hypoxic tissue, i.e. tissue binding the hypoxia marker pimonidazole, were determined in the melanomas by analysis of histological sections from the tumour planes in which the pO 2 measurements were performed. Results: The pO 2 distributions showed large intratumour heterogeneity. In cervix tumours, tumour regions with vascular density (vascular length per unit tissue volume) in the range of 47-77 mm/mm 3 showed higher pO 2 than tumour regions with vascular density in the range of 20-47 mm/mm 3 , which in turn showed higher pO 2 than tumour regions with vascular density in the range of 0-20 mm/mm 3 . In melanomas, tumour regions in which necrosis and hypoxia constituted more than 50% of the tissue showed lower pO 2 than other tumour regions. Conclusions: The pO 2 measured in the tumours was consistent with the histological appearance of the tissue in which the measurements were performed, suggesting that reliable pO 2 distributions of tumours can be obtained with polarographic needle electrodes

  5. Changes in tumor oxygenation during a combined treatment with fractionated irradiation and hyperthermia: an experimental study.

    Science.gov (United States)

    Zywietz, F; Reeker, W; Kochs, E

    1997-01-01

    To determine the influence of adjuvant hyperthermia on the oxygenation status of fractionated irradiated tumors. Oxygen partial pressure (pO2) in rat rhabdomyosarcomas (R1H) was measured sequentially at weekly intervals during a fractionated irradiation with 60Co-gamma-rays (60 Gy/20f/4 weeks) in combination with local hyperthermia (8 f(HT) at 43 degrees C, 1 h/4 weeks). Tumors were heated twice weekly with a 2450 MHz microwave device at 43 degrees C, 1 h starting 10 min after irradiation. The pO2 measurements (pO2-histograph, Eppendorf, Germany) were performed in anesthetized animals during mechanical ventilation and in hemodynamic steady state. All tumor pO2 measurements were correlated to measurements of the arterial oxygen partial pressure (paO2) determined by a blood gas analyzer. The oxygenation status of R1H tumors decreased continuously from the start of the combined treatment, with increasing radiation dose and number of heat fractions. In untreated controls a median tumor pO2 of 23 +/- 2 mmHg (mean +/- SEM) was measured. Tumor pO2 decreased to 11 +/- 2 mmHg after 30 Gy + 4 HT (2 weeks), and to 6 +/- 2 mmHg after 60 Gy + 8HT (4 weeks). The increase in the frequency of pO2-values below 5 mmHg and the decrease in the range of the pO2 histograms [delta p(10/90)] further indicated that tumor hypoxia increased relatively rapidly from the start of combined treatment. After 60 Gy + 8HT 48 +/- 5% (mean +/- SEM) of the pO2-values recorded were below 5 mmHg. These findings suggest that adjuvant hyperthermia to radiotherapy induces greater changes in tumor oxygenation than radiation alone [cf. (39)]. This might be of importance for the temporary application of hyperthermia in the course of a conventional radiation treatment.

  6. Prediction of inspired oxygen fraction for targeted arterial oxygen tension following open heart surgery in non-smoking and smoking patients.

    Science.gov (United States)

    Bou-Khalil, Pierre; Zeineldine, Salah; Chatburn, Robert; Ayyoub, Chakib; Elkhatib, Farouk; Bou-Akl, Imad; El-Khatib, Mohamad

    2017-10-01

    Simple and accurate expressions describing the P a O 2 -F i O 2 relationship in mechanically ventilated patients are lacking. The current study aims to validate a novel mathematical expression for accurate prediction of the fraction of inspired oxygen that will result in a targeted arterial oxygen tension in non-smoking and smoking patients receiving mechanical ventilation following open heart surgeries. One hundred P a O 2 -F i O 2 data pairs were obtained from 25 non-smoking patients mechanically ventilated following open heart surgeries. One data pair was collected at each of F i O 2 of 40, 60, 80, and 100% while maintaining same mechanical ventilation support settings. Similarly, another 100 hundred P a O 2 -F i O 2 data pairs were obtained from 25 smoking patients mechanically ventilated following open heart surgeries. The utility of the new mathematical expression in accurately describing the P a O 2 -F i O 2 relationship in these patients was assessed by the regression and Bland-Altman analyses. Significant correlations were seen between the true and estimated F i O 2 values in non-smoking (r 2  = 0.9424; p < 0.05) and smoking (r 2  = 0.9466; p < 0.05) patients. Tight biases between the true and estimated F i O 2 values for non-smoking (3.1%) and smoking (4.1%) patients were observed. Also, significant correlations were seen between the true and estimated P a O 2 /F i O 2 ratios in non-smoking (r 2  = 0.9530; p < 0.05) and smoking (r 2  = 0.9675; p < 0.05) patients. Tight biases between the true and estimated P a O 2 /F i O 2 ratios for non-smoking (-18 mmHg) and smoking (-16 mmHg) patients were also observed. The new mathematical expression for the description of the P a O 2 -F i O 2 relationship is valid and accurate in non-smoking and smoking patients who are receiving mechanical ventilation for post cardiac surgery.

  7. Oxygen tension regulates the miRNA profile and bioactivity of exosomes released from extravillous trophoblast cells - Liquid biopsies for monitoring complications of pregnancy.

    Directory of Open Access Journals (Sweden)

    Grace Truong

    Full Text Available Our understanding of how cells communicate has undergone a paradigm shift since the recent recognition of the role of exosomes in intercellular signaling. In this study, we investigated whether oxygen tension alters the exosome release and miRNA profile from extravillous trophoblast (EVT cells, modifying their bioactivity on endothelial cells (EC. Furthermore, we have established the exosomal miRNA profile at early gestation in women who develop pre-eclampsia (PE and spontaneous preterm birth (SPTB. HTR-8/SVneo cells were used as an EVT model. The effect of oxygen tension (i.e. 8% and 1% oxygen on exosome release was quantified using nanocrystals (Qdot® coupled to CD63 by fluorescence NTA. A real-time, live-cell imaging system (Incucyte™ was used to establish the effect of exosomes on EC. Plasma samples were obtained at early gestation (<18 weeks and classified according to pregnancy outcomes. An Illumina TrueSeq Small RNA kit was used to construct a small RNA library from exosomal RNA obtained from EVT and plasma samples. The number of exosomes was significantly higher in EVT cultured under 1% compared to 8% oxygen. In total, 741 miRNA were identified in exosomes from EVT. Bioinformatic analysis revealed that these miRNA were associated with cell migration and cytokine production. Interestingly, exosomes isolated from EVT cultured at 8% oxygen increased EC migration, whilst exosomes cultured at 1% oxygen decreased EC migration. These changes were inversely proportional to TNF-α released from EC. Finally, we have identified a set of unique miRNAs in exosomes from EVT cultured at 1% oxygen and exosomes isolated from the circulation of mothers at early gestation, who later developed PE and SPTB. We suggest that aberrant exosomal signalling by placental cells is a common aetiological factor in pregnancy complications characterised by incomplete SpA remodeling and is therefore a clinically relevant biomarker of pregnancy complications.

  8. Comparison between model-predicted tumor oxygenation dynamics and vascular-/flow-related Doppler indices.

    Science.gov (United States)

    Belfatto, Antonella; Vidal Urbinati, Ailyn M; Ciardo, Delia; Franchi, Dorella; Cattani, Federica; Lazzari, Roberta; Jereczek-Fossa, Barbara A; Orecchia, Roberto; Baroni, Guido; Cerveri, Pietro

    2017-05-01

    Mathematical modeling is a powerful and flexible method to investigate complex phenomena. It discloses the possibility of reproducing expensive as well as invasive experiments in a safe environment with limited costs. This makes it suitable to mimic tumor evolution and response to radiotherapy although the reliability of the results remains an issue. Complexity reduction is therefore a critical aspect in order to be able to compare model outcomes to clinical data. Among the factors affecting treatment efficacy, tumor oxygenation is known to play a key role in radiotherapy response. In this work, we aim at relating the oxygenation dynamics, predicted by a macroscale model trained on tumor volumetric data of uterine cervical cancer patients, to vascularization and blood flux indices assessed on Ultrasound Doppler images. We propose a macroscale model of tumor evolution based on three dynamics, namely active portion, necrotic portion, and oxygenation. The model parameters were assessed on the volume size of seven cervical cancer patients administered with 28 fractions of intensity modulated radiation therapy (IMRT) (1.8 Gy/fraction). For each patient, five Doppler ultrasound tests were acquired before, during, and after the treatment. The lesion was manually contoured by an expert physician using 4D View ® (General Electric Company - Fairfield, Connecticut, United States), which automatically provided the overall tumor volume size along with three vascularization and/or blood flow indices. Volume data only were fed to the model for training purpose, while the predicted oxygenation was compared a posteriori to the measured Doppler indices. The model was able to fit the tumor volume evolution within 8% error (range: 3-8%). A strong correlation between the intrapatient longitudinal indices from Doppler measurements and oxygen predicted by the model (about 90% or above) was found in three cases. Two patients showed an average correlation value (50-70%) and the remaining

  9. Concurrent Longitudinal EPR Monitoring of Tissue Oxygenation, Acidosis, and Reducing Capacity in Mouse Xenograft Tumor Models.

    Science.gov (United States)

    Bobko, Andrey A; Evans, Jason; Denko, Nicholas C; Khramtsov, Valery V

    2017-06-01

    Tissue oxygenation, extracellular acidity, and tissue reducing capacity are among crucial parameters of tumor microenvironment (TME) of significant importance for tumor pathophysiology. In this paper, we demonstrate the complementary application of particulate lithium octa-n-butoxy-naphthalocyanine and soluble nitroxide paramagnetic probes for monitoring of these TME parameters using electron paramagnetic resonance (EPR) technique. Two different types of therapeutic interventions were studied: hypothermia and systemic administration of metabolically active drug. In summary, the results demonstrate the utility of EPR technique for non-invasive concurrent longitudinal monitoring of physiologically relevant chemical parameters of TME in mouse xenograft tumor models, including that under therapeutic intervention.

  10. Pyruvate induces transient tumor hypoxia by enhancing mitochondrial oxygen consumption and potentiates the anti-tumor effect of a hypoxia-activated prodrug TH-302.

    Directory of Open Access Journals (Sweden)

    Yoichi Takakusagi

    Full Text Available BACKGROUND: TH-302 is a hypoxia-activated prodrug (HAP of bromo isophosphoramide mustard that is selectively activated within hypoxic regions in solid tumors. Our recent study showed that intravenously administered bolus pyruvate can transiently induce hypoxia in tumors. We investigated the mechanism underlying the induction of transient hypoxia and the combination use of pyruvate to potentiate the anti-tumor effect of TH-302. METHODOLOGY/RESULTS: The hypoxia-dependent cytotoxicity of TH-302 was evaluated by a viability assay in murine SCCVII and human HT29 cells. Modulation in cellular oxygen consumption and in vivo tumor oxygenation by the pyruvate treatment was monitored by extracellular flux analysis and electron paramagnetic resonance (EPR oxygen imaging, respectively. The enhancement of the anti-tumor effect of TH-302 by pyruvate treatment was evaluated by monitoring the growth suppression of the tumor xenografts inoculated subcutaneously in mice. TH-302 preferentially inhibited the growth of both SCCVII and HT29 cells under hypoxic conditions (0.1% O2, with minimal effect under aerobic conditions (21% O2. Basal oxygen consumption rates increased after the pyruvate treatment in SCCVII cells in a concentration-dependent manner, suggesting that pyruvate enhances the mitochondrial respiration to consume excess cellular oxygen. In vivo EPR oxygen imaging showed that the intravenous administration of pyruvate globally induced the transient hypoxia 30 min after the injection in SCCVII and HT29 tumors at the size of 500-1500 mm(3. Pretreatment of SCCVII tumor bearing mice with pyruvate 30 min prior to TH-302 administration, initiated with small tumors (∼ 550 mm(3, significantly delayed tumor growth. CONCLUSIONS/SIGNIFICANCE: Our in vitro and in vivo studies showed that pyruvate induces transient hypoxia by enhancing mitochondrial oxygen consumption in tumor cells. TH-302 therapy can be potentiated by pyruvate pretreatment if started at the

  11. Pyruvate induces transient tumor hypoxia by enhancing mitochondrial oxygen consumption and potentiates the anti-tumor effect of a hypoxia-activated prodrug TH-302.

    Science.gov (United States)

    Takakusagi, Yoichi; Matsumoto, Shingo; Saito, Keita; Matsuo, Masayuki; Kishimoto, Shun; Wojtkowiak, Jonathan W; DeGraff, William; Kesarwala, Aparna H; Choudhuri, Rajani; Devasahayam, Nallathamby; Subramanian, Sankaran; Munasinghe, Jeeva P; Gillies, Robert J; Mitchell, James B; Hart, Charles P; Krishna, Murali C

    2014-01-01

    TH-302 is a hypoxia-activated prodrug (HAP) of bromo isophosphoramide mustard that is selectively activated within hypoxic regions in solid tumors. Our recent study showed that intravenously administered bolus pyruvate can transiently induce hypoxia in tumors. We investigated the mechanism underlying the induction of transient hypoxia and the combination use of pyruvate to potentiate the anti-tumor effect of TH-302. The hypoxia-dependent cytotoxicity of TH-302 was evaluated by a viability assay in murine SCCVII and human HT29 cells. Modulation in cellular oxygen consumption and in vivo tumor oxygenation by the pyruvate treatment was monitored by extracellular flux analysis and electron paramagnetic resonance (EPR) oxygen imaging, respectively. The enhancement of the anti-tumor effect of TH-302 by pyruvate treatment was evaluated by monitoring the growth suppression of the tumor xenografts inoculated subcutaneously in mice. TH-302 preferentially inhibited the growth of both SCCVII and HT29 cells under hypoxic conditions (0.1% O2), with minimal effect under aerobic conditions (21% O2). Basal oxygen consumption rates increased after the pyruvate treatment in SCCVII cells in a concentration-dependent manner, suggesting that pyruvate enhances the mitochondrial respiration to consume excess cellular oxygen. In vivo EPR oxygen imaging showed that the intravenous administration of pyruvate globally induced the transient hypoxia 30 min after the injection in SCCVII and HT29 tumors at the size of 500-1500 mm(3). Pretreatment of SCCVII tumor bearing mice with pyruvate 30 min prior to TH-302 administration, initiated with small tumors (∼ 550 mm(3)), significantly delayed tumor growth. Our in vitro and in vivo studies showed that pyruvate induces transient hypoxia by enhancing mitochondrial oxygen consumption in tumor cells. TH-302 therapy can be potentiated by pyruvate pretreatment if started at the appropriate tumor size and oxygen concentration.

  12. Non-Invasive Monitoring of Breast Tumor Oxygenation: A Key to Tumor Therapy Planning and Tumor Prognosis

    National Research Council Canada - National Science Library

    Liu, Hanli

    2004-01-01

    .... The aims have included (1) to evaluate a single-channel, dual wavelength, NIR, frequency-domain oximeter and the algorithms for obtaining tumor HbO2 against tumor PO2 measured by 19F magnetic resonance imaging (MRI), (2...

  13. Noninvasive diffuse optical monitoring of head and neck tumor blood flow and oxygenation during radiation delivery

    Science.gov (United States)

    Dong, Lixin; Kudrimoti, Mahesh; Cheng, Ran; Shang, Yu; Johnson, Ellis L.; Stevens, Scott D.; Shelton, Brent J.; Yu, Guoqiang

    2012-01-01

    This study explored using a novel diffuse correlation spectroscopy (DCS) flow-oximeter to noninvasively monitor blood flow and oxygenation changes in head and neck tumors during radiation delivery. A fiber-optic probe connected to the DCS flow-oximeter was placed on the surface of the radiologically/clinically involved cervical lymph node. The DCS flow-oximeter in the treatment room was remotely operated by a computer in the control room. From the early measurements, abnormal signals were observed when the optical device was placed in close proximity to the radiation beams. Through phantom tests, the artifacts were shown to be caused by scattered x rays and consequentially avoided by moving the optical device away from the x-ray beams. Eleven patients with head and neck tumors were continually measured once a week over a treatment period of seven weeks, although there were some missing data due to the patient related events. Large inter-patient variations in tumor hemodynamic responses were observed during radiation delivery. A significant increase in tumor blood flow was observed at the first week of treatment, which may be a physiologic response to hypoxia created by radiation oxygen consumption. Only small and insignificant changes were found in tumor blood oxygenation, suggesting that oxygen utilizations in tumors during the short period of fractional radiation deliveries were either minimal or balanced by other effects such as blood flow regulation. Further investigations in a large patient population are needed to correlate the individual hemodynamic responses with the clinical outcomes for determining the prognostic value of optical measurements. PMID:22312579

  14. Singlet oxygen treatment of tumor cells triggers extracellular singlet oxygen generation, catalase inactivation and reactivation of intercellular apoptosis-inducing signaling☆

    Science.gov (United States)

    Riethmüller, Michaela; Burger, Nils; Bauer, Georg

    2015-01-01

    Intracellular singlet oxygen generation in photofrin-loaded cells caused cell death without discrimination between nonmalignant and malignant cells. In contrast, extracellular singlet oxygen generation caused apoptosis induction selectively in tumor cells through singlet oxygen-mediated inactivation of tumor cell protective catalase and subsequent reactivation of intercellular ROS-mediated apoptosis signaling through the HOCl and the NO/peroxynitrite signaling pathway. Singlet oxygen generation by extracellular photofrin alone was, however, not sufficient for optimal direct inactivation of catalase, but needed to trigger the generation of cell-derived extracellular singlet oxygen through the interaction between H2O2 and peroxynitrite. Thereby, formation of peroxynitrous acid, generation of hydroxyl radicals and formation of perhydroxyl radicals (HO2.) through hydroxyl radical/H2O2 interaction seemed to be required as intermediate steps. This amplificatory mechanism led to the formation of singlet oxygen at a sufficiently high concentration for optimal inactivation of membrane-associated catalase. At low initial concentrations of singlet oxygen, an additional amplification step needed to be activated. It depended on singlet oxygen-dependent activation of the FAS receptor and caspase-8, followed by caspase-8-mediated enhancement of NOX activity. The biochemical mechanisms described here might be considered as promising principle for the development of novel approaches in tumor therapy that specifically direct membrane-associated catalase of tumor cells and thus utilize tumor cell-specific apoptosis-inducing ROS signaling. PMID:26225731

  15. Singlet oxygen treatment of tumor cells triggers extracellular singlet oxygen generation, catalase inactivation and reactivation of intercellular apoptosis-inducing signaling.

    Science.gov (United States)

    Riethmüller, Michaela; Burger, Nils; Bauer, Georg

    2015-12-01

    Intracellular singlet oxygen generation in photofrin-loaded cells caused cell death without discrimination between nonmalignant and malignant cells. In contrast, extracellular singlet oxygen generation caused apoptosis induction selectively in tumor cells through singlet oxygen-mediated inactivation of tumor cell protective catalase and subsequent reactivation of intercellular ROS-mediated apoptosis signaling through the HOCl and the NO/peroxynitrite signaling pathway. Singlet oxygen generation by extracellular photofrin alone was, however, not sufficient for optimal direct inactivation of catalase, but needed to trigger the generation of cell-derived extracellular singlet oxygen through the interaction between H2O2 and peroxynitrite. Thereby, formation of peroxynitrous acid, generation of hydroxyl radicals and formation of perhydroxyl radicals (HO2(.)) through hydroxyl radical/H2O2 interaction seemed to be required as intermediate steps. This amplificatory mechanism led to the formation of singlet oxygen at a sufficiently high concentration for optimal inactivation of membrane-associated catalase. At low initial concentrations of singlet oxygen, an additional amplification step needed to be activated. It depended on singlet oxygen-dependent activation of the FAS receptor and caspase-8, followed by caspase-8-mediated enhancement of NOX activity. The biochemical mechanisms described here might be considered as promising principle for the development of novel approaches in tumor therapy that specifically direct membrane-associated catalase of tumor cells and thus utilize tumor cell-specific apoptosis-inducing ROS signaling. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Determination of in vitro oxygen consumption rates for tumor cells

    International Nuclear Information System (INIS)

    Cardenas-Navia, L.I.; Moeller, B.J.; Kirkpatrick, J.P.; Laursen, T.A.; Dewhirst, M.W.

    2003-01-01

    To determine pO 2 at the surface of a monolayer of confluent HCT 116 cells, and to then determine consumption rate in vitro by examining the pO 2 profile in media above the cells. Materials and Methods: A recessed-tip polarographic oxygen microelectrode (diameter ∼10μm) was used to measure pO 2 profiles of media above a confluent monolayer of HCT 116 human colon adenocarcinoma cells in a T25 flask exposed to a 95% air, 5% CO 2 mixture. A two-dimensional finite element analysis of the diffusion equation was used to fit the data, thereby extracting a steady-state O 2 consumption rate. The diffusion equation was solved for zeroth and first-order expressions. No-flux boundary conditions were imposed on its bottom and side boundaries and experimental data was used for boundary conditions at the gas-media boundary. All flasks show an O 2 gradient in the media, with a mean (SE) media layer of 1677 (147) μm and a mean pO 2 at the cell layer/media interface of 44 (8) mm Hg (n=9). pO 2 gradient over the entire media layer is 630 (90) mm Hg/cm, equivalent to a consumption rate of 6.3 x 10 -4 (9.0 x 10 -5 ) mm Hg/s. The mean values for the zeroth and first order rate constants are 8.1 x 10 -9 (1.3 x 10 -9 ) g mol O 2 /cm 3 s and 1.0 x 10 3 (0.46 x 10 3 ) /s, respectively. Control experiments in flasks containing no cells show slight gradients in pO 2 of 38 (12) mm Hg/cm, resulting from some O 2 diffusion through the flask into the surrounding water bath. An addition of 10 -3 M NaCN to the media results in a dramatic increase in pO 2 at the cell layer, consistent with a shut-down in respiration. Under normal cell culture conditions there is an O 2 gradient present in the media of cull culture systems, resulting in physiologic O 2 concentrations at the cell layer, despite the non-physiologic O 2 concentration of the gas mixture to which the cell culture system is exposed. This significant (p -6 ) O 2 gradient in the media of cell culture systems is a result of cell O 2

  17. Oxygen tension and riboflavin gradients cooperatively regulate the migration of Shewanella oneidensis MR-1 revealed by a hydrogel-based microfluidic device

    Directory of Open Access Journals (Sweden)

    Beum Jun Kim

    2016-09-01

    Full Text Available Shewanella oneidensis (S. oneidensis is a model bacterial strain for studies of bioelectrochemical systems (BESs. It has two extracellular electron transfer pathways: 1 shuttling electrons via an excreted mediator riboflavin; and 2 direct contact between the c-type cytochromes at the cell membrane and the electrode. Despite the extensive use of S. oneidensis in bioelectrochemical systems such as microbial fuel cells and biosensors, many basic microbiology questions about S. oneidensis in the context of BES remain unanswered. Here, we present studies of motility and chemotaxis of S. oneidensis under well controlled concentration gradients of two electron acceptors, oxygen and oxidized form of riboflavin (flavin+ using a newly developed microfluidic platform. Experimental results demonstrate that either oxygen or flavin+ is a chemoattractant to S. oneidensis. The chemotactic tendency of S. oneidensis in a flavin+ concentration gradient is significantly enhanced in an anaerobic in contrast to an aerobic condition. Furthermore, either a low oxygen tension or a high flavin+ concentration considerably enhances the speed of S. oneidensis. This work presents a robust microfluidic platform for generating oxygen and/or flavin+ gradients in an aqueous environment, and demonstrates that two important electron acceptors, oxygen and oxidized riboflavin, cooperatively regulate S. oneidensis migration patterns. The microfluidic tools presented as well as the knowledge gained in this work can be used to guide the future design of BESs for efficient electron production.

  18. Encouraging effects of a short-term, adapted Nordic diet intervention on skin microvascular function and skin oxygen tension in younger and older adults.

    Science.gov (United States)

    Rogerson, David; McNeill, Scott; Könönen, Heidi; Klonizakis, Markos

    2018-05-01

    The microvascular benefits of regional diets appear in the literature; however, little is known about Nordic-type diets. We investigated the effects of a short-term, adapted, Nordic diet on microvascular function in younger and older individuals at rest and during activity. Thirteen young (mean age: 28 y; standard deviation: 5 y) and 15 older (mean age: 68 y; standard deviation: 6 y) participants consumed a modified Nordic diet for 4 wk. Laser Doppler flowmetry and transcutaneous oxygen monitoring were used to assess cutaneous microvascular function and oxygen tension pre- and postintervention; blood pressure, body mass, body fat percentage, ratings of perceived exertion, and peak heart rate during activity were examined concurrently. Axon-mediated vasodilation improved in older participants (1.17 [0.30] to 1.30 [0.30]; P Nordic diet might improve microvascular health. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Singlet oxygen explicit dosimetry to predict local tumor control for HPPH-mediated photodynamic therapy

    Science.gov (United States)

    Penjweini, Rozhin; Kim, Michele M.; Ong, Yi Hong; Zhu, Timothy C.

    2017-02-01

    This preclinical study examines four dosimetric quantities (light fluence, photosensitizer photobleaching ratio, PDT dose, and reacted singlet oxygen ([1O2]rx)) to predict local control rate (LCR) for 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH)-mediated photodynamic therapy (PDT). Mice bearing radiation-induced fibrosarcoma (RIF) tumors were treated with different in-air fluences (135, 250 and 350 J/cm2) and in-air fluence rates (50, 75 and 150 mW/cm2) at 0.25 mg/kg HPPH and a drug-light interval of 24 hours using a 1 cm diameter collimated laser beam at 665 nm wavelength. A macroscopic model was used to calculate ([1O2]rx)) based on in vivo explicit dosimetry of the initial tissue oxygenation, photosensitizer concentration, and tissue optical properties. PDT dose was defined as a temporal integral of drug concentration and fluence rate (φ) at a 3 mm tumor depth. Light fluence rate was calculated throughout the treatment volume based on Monte-Carlo simulation and measured tissue optical properties. The tumor volume of each mouse was tracked for 30 days after PDT and Kaplan-Meier analyses for LCR were performed based on a tumor volume <=100 mm3, for four dose metrics: fluence, HPPH photobleaching rate, PDT dose, and ([1O2]rx)). The results of this study showed that ([1O2]rx)) is the best dosimetric quantity that can predict tumor response and correlate with LCR.

  20. Paradox between angiogenesis and oxygen effect in the treatment of tumor

    International Nuclear Information System (INIS)

    Hayashi, Masanobu

    2008-01-01

    The paradox in the title is described on recent findings concerning the effects of anti-angiogenetic drugs on possible radiation resistance and sensitivity of tumor tissue. Suppression of angiogenesis leads to inhibition of tumor growth, based on which anti-tumor drugs like anti- vascular endotherial growth factor (VEGF) antibody bevacizumab to suppress the genesis have been developed and clinically used, but they conceivably increase the population of hypoxic tumor cells. Those drugs are essentially used in combination with other chemotherapeutic agents and/or radiation. Hypoxic tumor cells present in the tissue are generally radioresistant. There are reported findings, however, that the drugs sometimes elevate the efficacy of radiotherapy, which hypothesizes that the drugs induces a proangiogenetic state, where increased level of growth factors in the tissue is reduced to normalize the vasculature and thereby reoxygenation occurs, the oxygen effect. Because copper is a cofactor of growth factors like VEGF and basic fibroblast growth factor (bFGF) and essential for angiogenesis, authors have studied the effect of a Cu-chelator, trientine, on transplanted mouse tumors which has been shown to induce apoptosis of the target cells. Combination of the chelator with X-ray irradiation is found effective in tumor growth inhibition and in survival increase. For more effective combination therapy, the interaction occurring in combinations of regimen should be elucidated. (R.T.)

  1. Oxygen-boosted immunogenic photodynamic therapy with gold nanocages@manganese dioxide to inhibit tumor growth and metastases.

    Science.gov (United States)

    Liang, Ruijing; Liu, Lanlan; He, Huamei; Chen, Zhikuan; Han, Zhiqun; Luo, Zhenyu; Wu, Zhihao; Zheng, Mingbin; Ma, Yifan; Cai, Lintao

    2018-09-01

    Metastatic triple-negative breast cancer (mTNBC) is an aggressive disease among women worldwide, characterized by high mortality and poor prognosis despite systemic therapy with radiation and chemotherapies. Photodynamic therapy (PDT) is an important strategy to eliminate the primary tumor, however its therapeutic efficacy against metastases and recurrence is still limited. Here, we employed a template method to develop the core-shell gold nanocage@manganese dioxide (AuNC@MnO 2 , AM) nanoparticles as tumor microenvironment responsive oxygen producers and near-infrared (NIR)-triggered reactive oxygen species (ROS) generators for oxygen-boosted immunogenic PDT against mTNBC. In this platform, MnO 2 shell degrades in acidic tumor microenvironment pH/H 2 O 2 conditions and generates massive oxygen to boost PDT effect of AM nanoparticles under laser irradiation. Fluorescence (FL)/photoacoustic (PA)/magnetic resonance (MR) multimodal imaging confirms the effective accumulation of AM nanoparticles with sufficient oxygenation in tumor site to ameliorate local hypoxia. Moreover, the oxygen-boosted PDT effect of AM not only destroys primary tumor effectively but also elicits immunogenic cell death (ICD) with damage-associated molecular patterns (DAMPs) release, which subsequently induces DC maturation and effector cells activation, thereby robustly evoking systematic antitumor immune responses against mTNBC. Hence, this oxygen-boosted immunogenic PDT nanosystem offers a promising approach to ablate primary tumor and simultaneously prevent tumor metastases via immunogenic abscopal effects. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Radiobiological studies on the importance of tumor oxygenation for anti-neoplastic therapy

    International Nuclear Information System (INIS)

    Grau, C.

    1994-01-01

    The aim of the twelve studies included in the present thesis was to determine the importance of hypoxia for various anti-neoplastic treatment modalities, and to evaluate possible ways of overcoming the hypoxia problem by combined modality therapy. The murine tumor systems were the C3H mammary carcinoma with 5-12% hypoxic cells, and the SCCVII squamous cell carcinoma with 2% hypoxic cells. The radiation response was significantly improved by the use of hypoxic cell radiosensitizers such as nimorazole or misonidazole, or by allowing the mice to breathe oxygen or carbogen during irradiation. In contrast, the radiation response was significantly impaired by carbon monoxide breathing at a level comparable to what has been observed in heavy smokers. The clamped TCD 50 assay was used to classify cancer chemotherapeutic drugs according to their preferential cytotoxicity towards the different tumor subpopulations. Methotrexate had no effect on hypoxic cells and was only borderline toxic towards aerobic cells. Three drugs had significant effect against oxic cells only (5-fluorouracil, bleomycin and cisplatin). Similarly, three drugs were toxic towards hypoxic cells only (etoposide, carmustine, and mitomycin c). Three drugs were effective towards both cell types (vincristine, adriamycin, cyclophosphamide). Hypoxic cells in areas with insufficient blood supply, poor nutrition and increased acidity is known to be highly sensitive to hyperthermia. In a study where cisplatin, heat and x-rays were given together, the local tumor control was not improved when compared to radiation + heat, apparently due to a lack of enhancement in the killing of hypoxic cells. These studies have demonstrated the influence of tumor oxygenation on tumor response to treatment with drugs, hyperthermia and irradiation. New strategies targeted also against perfusion-limited hypoxia is needed. One of the most important conclusions from the present thesis can be implemented without expensive trials or

  3. The treatment of tumors by the induction of anemia and irradiation in hyperbaric oxygen

    International Nuclear Information System (INIS)

    Sealy, R.; Jacobs, P.; Wood, L.; Levin, W.; Barry, L.; Boniaszczuk, J.; Blekkenhorst, G.

    1989-01-01

    Because increased effects have been achieved when murine tumors are irradiated after a period of hypoxia and because of anecdotal clinical experiences of an improved result after irradiation of previously anemic patients in hyperbaric oxygen, the relationship between irradiation and increased survival was investigated in seventy-two patients with advanced head and neck or cervical cancer. Anemia was achieved by means of a two-stage isovolemic venesection maintained for seventy-two hours, hemoglobin was returned to a normal level, and treatment in hyperbaric oxygen was started. Marked tumor shrinkage after the induction of anemia and before radiotherapy was seen and was probably disease, site, and hemoglobin level related. As a result, a possible new approach to cancer therapy is suggested. After completion of therapy, the 1-year disease-free survival for patients with head and neck and cervical cancer was not improved, but the 21-month survival for cervical cancer was improved. Further studies are strongly urged

  4. Assessment of tumor energy and oxygenation status by bioluminescence, nuclear magnetic resonance spectroscopy, and cryospectrophotometry.

    Science.gov (United States)

    Mueller-Klieser, W; Schaefer, C; Walenta, S; Rofstad, E K; Fenton, B M; Sutherland, R M

    1990-03-15

    The energy and oxygenation status of tumors from two murine sarcoma lines (KHT, RIF-1) and two human ovarian carcinoma xenograft lines (MLS, OWI) were assessed using three independent techniques. Tumor energy metabolism was investigated in vivo by 31P nuclear magnetic resonance spectroscopy. After nuclear magnetic resonance measurements, tumors were frozen in liquid nitrogen to determine the tissue ATP concentration by imaging bioluminescence and to register the intracapillary oxyhemoglobin (HbO2) saturation using the cryospectrophotometric method. There was a positive correlation between the nucleoside triphosphate beta/total resonance ratio or a negative correlation between the Pi/total resonance ratio and the model ATP concentration obtained by bioluminescence, respectively. This was true for small tumors with no extended necrosis irrespective of tumor type. Moreover, a positive correlation was obtained between the HbO2 saturations and the ATP concentration measured with bioluminescence. The results demonstrate the potential of combined studies using noninvasive, integrating methods and high-resolution imaging techniques for characterizing the metabolic milieu in tumors.

  5. Tumor reoxygenation by aqueous oxygen solutions and its role in cancer treatment with chemotherapy and radiation therapy

    International Nuclear Information System (INIS)

    Calderwood, S.K.

    2003-01-01

    Many tumors contain significant areas of hypoxia which cause resistance to tumor radiation therapy and chemotherapy. We have used perfusion into afferent arteries with super saturated aqueous oxygen solutions (AO) to re-oxygenate the hypoxic areas of experimental tumors with the aim of restoring sensitivity to treatment and enhancing cancer therapy. We first concentrated on examining the ability of AO infusion to reoxygenate the MAT B III 13762 rat carcinoma growing in the thighs of rats. In experiments on 33 AO infused tumors using Eppendorf microelectrode monitoring, we consistently observed a significant decrease in the fraction of tumor domains with O 2 less than 5mmHg before and after AO infusion. Significant tumor reoxygenation was observed in most tumors with a volume less than 2.5 cm 3 . We next examined 15 New Zealand white rabbits transplanted with the VX2 carcinoma. Tissue oxygen studies indicated that intramuscular rabbit VX-2 tumor has a consistently lower hypoxic fraction (O 2 2 <5mm Hg). Significant reoxygenation did occur in these infused tumors although the degree of reoxygenation was slightly less than in the rat MAT B III 13762 perhaps reflecting the lower hypoxic fraction. Further studies showed that AO could also be infused directly into tumors with a reduction of hypoxic fraction of between 60-90% Overall, the experiments show that AO infusion into either arterial or intratumor sites is a viable approach to tumor reoxygenation and preliminary studies indicate increase effectiveness in treatment with cyclophosphamide / AO combination

  6. Modification of the radiation response of pig skin by manipulation of tissue oxygen tension using anesthetics and administration of BW12C

    International Nuclear Information System (INIS)

    van den Aardweg, G.J.; Hopewell, J.W.; Barnes, D.W.; Sansom, J.M.; Nethersell, A.B.

    1989-01-01

    The importance of tissue oxygen tension on radiosensitivity was studied by examining modifications in the incidence of moist desquamation in pig skin after irradiation with strontium-90 plaques. The effects were analyzed using quantal dose-response data and comparisons were made using ED50 values for moist desquamation. Under standard anesthetic conditions of 2% halothane, approximately 70% oxygen, and approximately 30% nitrous oxide, the ED50 value (+/- SE) for moist desquamation was 27.32 +/- 0.52 Gy with no significant variation in radiosensitivity between dorsal, lateral, and ventral skin sites on the flank. Irradiation with 2% halothane and air increased the ED50 to 31.25 +/- 0.94 Gy, primarily due to an increased radioresistance of the dorsal sites. When combined with BW12C, a drug which binds oxygen selectively to hemoglobin and hence reduced the oxygen availability to tissues, a further increase in the ED50 values was observed. This was approximately 39 Gy with BW12C concentrations of 30 mg/kg and 50 mg/kg b.w. of BW12C, indicating a dose modification factor (DMF) of approximately 1.26. However, when animals were breathing the standard gas mixture, this DMF was reduced to 1.15 for 30 mg/kg of BW12C, indicating that a higher level of oxygen partly counteracted the effects of the drug in these studies with BW12C. The greatest variability in radiosensitivity was seen in the dorsal fields. This suggested complex physiological adaptation, a phenomenon that might also explain the absence of any modification of the radiation response when 100 mg/kg of BW12C was used

  7. First experience with a novel luminescence-based optical sensor for measurement of oxygenation in tumors

    International Nuclear Information System (INIS)

    Jarm, T.; Miklavcic, D.; Lesnicar, H.; Sersa, G.

    2001-01-01

    Background. The purpose of this preliminary study was to evaluate a novel luminescence-based fiber-optic sensor (OxyLite system) for the measurement of partial pressure of oxygen (pO 2 ) in tumors and for the detection of changes in pO 2 as a function of time. The new method was used simultaneously with the laser Doppler flowmetry method for the measurement of relative tissue perfusion. Materials and methods. Blood perfusion and pO 2 were measured continuously via fiber-optic sensors inserted into SA-1 tumors in anesthetized A/J mice. The changes in blood flow and oxygenation of tumors were induced by transient changes of the parameters of anesthesia and by injection of a vasoactive drug hydralazine. Results. Both optical methods used in the study successfully detected the induced changes in blood flow and pO 2 . The measurements of pO 2 were well correlated with measurements of microcirculatory blood perfusion. In the majority of pO 2 measurements, we observed an unexpected behavior of the signal during the stabilization process immediately after the insertion of the probe into tumor. This behaviour of the pO 2 signal was most probably caused by local tissue damage induced by the insertion of the probe. Conclusion. The novel luminescence-based optical oximetry can reliably detect local pO 2 changes in tumors as a function of time but some aspects of prolonged pO 2 measurement by this method require further investigation. (author)

  8. The effect of oxygen tension in the sediment on the behaviour of waste radionuclides at the NEA Atlantic dumpsite

    International Nuclear Information System (INIS)

    Rutgers van der Loeff, M.M.; Waijers, D.A.

    1985-01-01

    Predictions of the transport and fate of waste radionuclides at the NEA Atlantic dumpsite require a knowledge of the behaviour of these nuclides within the sediment. Since redox conditions are known to influence the mobility of many elements in deep-sea sediments, we have investigated the speciation of some trace elements in relation to the dissolved oxygen concentration in sediments from the dumpsite. Dissolved oxygen in these sediments penetrates mostly between 50 and 100 cm, although at topographic highs and on hillsides oxygen penetrates more than 2 m into the sediment because of the special hydrodynamic and sedimentological conditions there. Remobilization at lowered redox potentials below the depth where oxygen reaches zero causes an upward diffusive transport of Mn and the manganese-associated trace metals Co and Ni. Whether this diagenetic mobilization influences other elements such as rare earth elements and actinides as well, remains to be investigated. Under normal sedimentological condition this mobilization can not be expected to return radioactivity to the water column through an oxidized sediment layer of 50 cm. However, burial of radioactivity to depths beyond the reach of deep burrowing organisms can be significantly delayed. Kd values (solid/dissolved partition coefficients) of redox sensitive elements vary over orders of magnitude and are inappropriate to model the behaviour of these elements in sediments with redox gradients

  9. Temporal changes in tumor oxygenation and perfusion upon normo- and hyperbaric inspiratory hyperoxia

    Energy Technology Data Exchange (ETDEWEB)

    Thews, Oliver [University of Halle, Institute of Physiology, Halle (Saale) (Germany); Vaupel, Peter [University Medical Center Mainz, Department of Radiooncology and Radiotherapy, Tumor Pathophysiology Section, Mainz (Germany)

    2016-03-15

    Inspiratory hyperoxia under hyperbaric conditions has been shown to effectively reduce tumor hypoxia and to improve radiosensitivity. However, applying irradiation (RT) under hyperbaric conditions is technically difficult in the clinical setting since RT after decompression may be effective only if tumor pO{sub 2} remains elevated for a certain period of time. The aim of the present study was to analyze the time course of tumor oxygenation and perfusion during and after hyperbaric hyperoxia. Tumor oxygenation, red blood cell (RBC) flux for perfusion monitoring, and vascular resistance were assessed continuously in experimental rat DS-sarcomas by polarographic catheter electrodes and laser Doppler flowmetry at 1 and 2 atm (bar) of environmental pressure during breathing of pure O{sub 2} or carbogen (95 % O{sub 2} + 5 % CO{sub 2}). During room air breathing, the tumor pO{sub 2} followed very rapidly within a few minutes the change of the ambient pressure during compression or decompression. With O{sub 2} breathing under hyperbaric conditions, the tumor pO{sub 2} increased more than expected based on the rise of the environmental pressure, although the time course was comparably rapid. Breathing carbogen, the tumor pO{sub 2} followed with a slight delay of the pressure change, and within 10 min after decompression the baseline values were reached again. RBC flux increased during carbogen breathing but remained almost constant with pure O{sub 2}, indicating a vasodilation (decrease in vascular resistance) with carbogen but a vasoconstriction (increase in vascular resistance) with O{sub 2} during hyperbaric conditions. Since the tumor pO{sub 2} directly followed the environmental pressure, teletherapy after hyperbaric conditions does not seem to be promising as the pO{sub 2} reaches baseline values again within 5-10 min after decompression. (orig.) [German] Inspiratorische Hyperoxie unter hyperbaren Bedingungen reduziert sehr effektiv die Tumorhypoxie und erhoeht die

  10. Changes in the metabolic footprint of placental explant-conditioned medium cultured in different oxygen tensions from placentas of small for gestational age and normal pregnancies.

    LENUS (Irish Health Repository)

    Horgan, R P

    2012-01-31

    Being born small for gestational age (SGA) confers significantly increased risks of perinatal morbidity and mortality. Accumulating evidence suggests that an SGA fetus results from a poorly perfused and abnormally developed placenta. Some of the placental features seen in SGA, such as abnormal cell turnover and impaired nutrient transport, can be reproduced by culture of placental explants in hypoxic conditions. Metabolic footprinting offers a hypothesis-generating strategy to investigate factors absorbed by and released from this tissue in vitro. Previously, metabolic footprinting of the conditioned culture media has identified differences in placental explants cultured under normoxic and hypoxic conditions and between normal pregnancies and those complicated by pre-eclampsia. In this study we aimed to examine the differences in the metabolic footprint of placental villous explants cultured at different oxygen (O(2)) tensions between women who deliver an SGA baby (n = 9) and those from normal controls (n = 8). Placental villous explants from cases and controls were cultured for 96 h in 1% (hypoxic), 6% (normoxic) and 20% (hyperoxic) O(2). Metabolic footprints were analysed by Ultra Performance Liquid Chromatography coupled to an electrospray hybrid LTQ-Orbitrap Mass Spectrometry (UPLC-MS). 574 metabolite features showed significant difference between SGA and normal at one or more of the oxygen tensions. SGA explant media cultured under hypoxic conditions was observed, on a univariate level, to exhibit the same metabolic signature as controls cultured under normoxic conditions in 49% of the metabolites of interest, suggesting that SGA tissue is acclimatised to hypoxic conditions in vivo. No such behaviour was observed under hyperoxic culture conditions. Glycerophospholipid and tryptophan metabolism were highlighted as areas of particular interest.

  11. Interplay of tumor vascular oxygenation and tumor pO2 observed using near-infrared spectroscopy, an oxygen needle electrode, and 19F MR pO2 mapping.

    Science.gov (United States)

    Kim, Jae G; Zhao, Dawen; Song, Yulin; Constantinescu, Anca; Mason, Ralph P; Liu, Hanli

    2003-01-01

    This study investigates the correlation of tumor blood oxygenation and tumor pO(2) with respect to carbogen inhalation. After having refined and validated the algorithms for calculating hemoglobin concentrations, we used near-infrared spectroscopy (NIRS) to measure changes of oxygenated hemoglobin concentration (delta[HbO(2)]) and used an oxygen needle electrode and (19)F MRI for pO(2) measurements in tumors. The measurements were taken from Dunning prostate R3327 tumors implanted in rats, while the anesthetized rats breathed air or carbogen. The NIRS results from tumor measurements showed significant changes in tumor vascular oxygenation in response to carbogen inhalation, while the pO(2) electrode results showed an apparent heterogeneity for tumor pO(2) response to carbogen inhalation, which was also confirmed by (19)F MR pO(2) mapping. Furthermore, we developed algorithms to estimate hemoglobin oxygen saturation, sO(2), during gas intervention based on the measured values of delta[HbO(2)] and pO(2). The algorithms have been validated through a tissue-simulating phantom and used to estimate the values of sO(2) in the animal tumor measurement based on the NIRS and global mean pO(2) values. This study demonstrates that the NIRS technology can provide an efficient, real-time, noninvasive approach to monitoring tumor physiology and is complementary to other techniques, while it also demonstrates the need for an NIR imaging technique to study spatial heterogeneity of tumor vasculature under therapeutic interventions. Copyright 2003 Society of Photo-Optical Instrumentation Engineers

  12. [Reduced muscular oxygen tension and nerve impulse transmission from antishock hose. Reduction of oxygen tension in the tibial muscle and impulse transmission in the peroneal nerve from pneumatic -1 pressure from antishock hose].

    Science.gov (United States)

    Willy, C; Völker, H U; Weber, F; Albert, U; Sterk, J; Helm, M; Gerngross, H; Thomas, A

    1998-07-01

    The aim of the study was to assess, whether the pneumatic pressure of an antishock-trouser (AST) of 20-40 mm Hg induces a decreased oxygenation of the anterior tibial muscle and attenuates muscular response potential (MRP) of n. peronaeus profundus? Among 22 normotensive, healthy volunteers the AST were tested by applying pressure values between 0 and 100 mm Hg and measuring the intracompartmental pressure, the muscular oxygen pressure as well as the MRP by electroneurographic means within a period of 6 hours. The median initial intracompartmental pressure value of the m. tibialis anterior was 12.0 mm Hg (Q25%/Q75%: 8.9/17.3), the muscular oxygen pressure 14.8 mm Hg (Q25%/Q75%: 11.5/22.0). Transmission of the pneumatic AST-leg segment pressure to the muscle: 97.7% (Q25%/Q75%: 89.2/99.8). Already in the low AST pressure field (20-40 mm Hg) a severe hypoxia occurred in one case. A reduction of MRP was noticed at an AST pressure rate of 10 mm Hg. In 5 of 6 cases AST pressure values of 60 mm Hg led to pathological pO2-values within 5-20 minutes. Almost without exception AST-pressure rates < 60 mm Hg resulted in an anoxia of the muscle and loss of the MRP. We should demand that the AST are only applied with models where the pressure generated within the single segments can be controlled by pressure gauge. The application of the AST seems to be justified for polytraumatised in severe haemorrhagic shock where the risk of a local tissue ischemia with systemical consequences must deliberately be accepted.

  13. Effects of Low and High Oxygen Tensions and Related Respiratory Conditions on Visual Performance: A Literature Review

    Science.gov (United States)

    1988-07-01

    and of the same subject after a diet that made him deficient in Vitamin A. They used only one healthy well-trained observer. Measurementv of...background intensity. The authors do not discuss hypoxia changes in some other visual process, but this improvement above 15,000 feet may reflect hypo ...these studies, Gellhorn and Spiesman (1935) induced caloric nystagmus while subjects breathed mixtures high in CO2 and low in oxygen, and also after

  14. Comparing CT perfusion with oxygen partial pressure in a rabbit VX2 soft-tissue tumor model.

    Science.gov (United States)

    Sun, Chang-Jin; Li, Chao; Lv, Hai-Bo; Zhao, Cong; Yu, Jin-Ming; Wang, Guang-Hui; Luo, Yun-Xiu; Li, Yan; Xiao, Mingyong; Yin, Jun; Lang, Jin-Yi

    2014-01-01

    The aim of this study was to evaluate the oxygen partial pressure of the rabbit model of the VX2 tumor using a 64-slice perfusion CT and to compare the results with that obtained using the oxygen microelectrode method. Perfusion CT was performed for 45 successfully constructed rabbit models of a VX2 brain tumor. The perfusion values of the brain tumor region of interest, the blood volume (BV), the time to peak (TTP) and the peak enhancement intensity (PEI) were measured. The results were compared with the partial pressure of oxygen (PO2) of that region of interest obtained using the oxygen microelectrode method. The perfusion values of the brain tumor region of interest in 45 successfully constructed rabbit models of a VX2 brain tumor ranged from 1.3-127.0 (average, 21.1 ± 26.7 ml/min/ml); BV ranged from 1.2-53.5 ml/100g (average, 22.2 ± 13.7 ml/100g); PEI ranged from 8.7-124.6 HU (average, 43.5 ± 28.7 HU); and TTP ranged from 8.2-62.3 s (average, 38.8 ± 14.8 s). The PO2 in the corresponding region ranged from 0.14-47 mmHg (average, 16 ± 14.8 mmHg). The perfusion CT positively correlated with the tumor PO2, which can be used for evaluating the tumor hypoxia in clinical practice.

  15. Oxygen tension in transplanted mouse osteosarcomas during fractionated high-LET- and low-LET radiotherapy - predictive aspects for choosing beam quality?

    International Nuclear Information System (INIS)

    Auberger, T.; Thuerriegel, B.; Freude, T.; Weissfloch, L.; Kneschaurek, P.; Molls, M.; Senekowitsch-Schmidtke, R.; Wagner, F.M.

    1999-01-01

    Murine OTS64 - osteosarcomas were tranplanted in 102 balb-C mice and irradiated by 36 Gy of photons in fractions of 3 Gy five times a week (group P-36/3) or by 12 Gy of reactor fission neutrons in fractions of 2 Gy two times a week (group N-12/2). Irradiations started at a tumor volume of 500 to 600 mm 3 . A third group received no radiotherapy, but all investigations (group CG). Tumor volume and tumor oxygenation were measured once a week under therapy and during three weeks after therapy. For in vivo-evaluation of oxygen status a computerized polarographic needle electrode system (KIMOC pO 2 histograph, Eppendorf) was used. The median pO 2 and the hypoxic fraction (pO 2 values 2 decreased from 20 mm to 8 mm Hg and the hypoxic fraction increased from 7% to 31%. After fractionated photon therapy a growth delay of three weeks was observed. Six weeks after beginning of the irradiation the median tumor volume had been doubled again. After fission neutron therapy growth delay continued until the end of the follow-up period. In both of the irradiated groups a significant decrease of median pO 2 values and an increase of the hypoxic fraction were observed under radiotherapy. Hypoxia was more intensive after neutrons with a decrease of the median pO 2 from 20 mm Hg to 1 mm Hg vs. 10 mm Hg after photon therapy and with an increase of the hypoxic fraction from 7% to 78% vs. 36% respectively. Two weeks after the end of therapy the median pO 2 and the hypoxic fraction of both treated groups reached the levels prior to irradiation indicating a complete reoxygenation. (orig.)

  16. Cellular and molecular repair of X-ray-induced damage: dependence on oxygen tension and nutritional status

    International Nuclear Information System (INIS)

    Spiro, I.J.; Kennedy, K.A.; Stickler, R.; Ling, C.C.

    1985-01-01

    Cellular and molecular repair was studied at 23 0 C using split-dose recovery and alkaline elution techniques, respectively, as a function of cellular oxygen and nutrient conditions. Hypoxic cells in full medium showed a partial reduction in the level of sublethal damage (SLD) repair relative to aerated cells; the respective repair kinetics were similar with a common repair half-time of 30 min. Similarly, hypoxic cells showed a slight reduction in strand break rejoining capacity compared to aerated cells. Under nutrient deprivation, anoxic cells displayed no SLD repair or strand break repair, while aerated cells exhibited the same level of SLD and strand break repair as for well-fed cells. In addition, nutrient deprived cells at low O 2 levels displayed normal SLD and strand break repair capability. These results indicate that both nutrient and O 2 deprivation are necessary for complete inhibition of cellular and molecular repair, and low levels of O 2 can effectively reverse this inhibition

  17. 3D modeling of effects of increased oxygenation and activity concentration in tumors treated with radionuclides and antiangiogenic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Lagerloef, Jakob H.; Kindblom, Jon; Bernhardt, Peter [Department of Radiation Physics, Goeteborg University, Goeteborg 41345 (Sweden); Department of Oncology, Sahlgrenska University Hospital, Goeteborg 41345 (Sweden); Department of Radiation Physics, Goeteborg University, Goeteborg, Sweden and Department of Nuclear Medicine, Sahlgrenska University Hospital, Goeteborg 41345 (Sweden)

    2011-08-15

    Purpose: Formation of new blood vessels (angiogenesis) in response to hypoxia is a fundamental event in the process of tumor growth and metastatic dissemination. However, abnormalities in tumor neovasculature often induce increased interstitial pressure (IP) and further reduce oxygenation (pO{sub 2}) of tumor cells. In radiotherapy, well-oxygenated tumors favor treatment. Antiangiogenic drugs may lower IP in the tumor, improving perfusion, pO{sub 2} and drug uptake, by reducing the number of malfunctioning vessels in the tissue. This study aims to create a model for quantifying the effects of altered pO{sub 2}-distribution due to antiangiogenic treatment in combination with radionuclide therapy. Methods: Based on experimental data, describing the effects of antiangiogenic agents on oxygenation of GlioblastomaMultiforme (GBM), a single cell based 3D model, including 10{sup 10} tumor cells, was developed, showing how radionuclide therapy response improves as tumor oxygenation approaches normal tissue levels. The nuclides studied were {sup 90}Y, {sup 131}I, {sup 177}Lu, and {sup 211}At. The absorbed dose levels required for a tumor control probability (TCP) of 0.990 are compared for three different log-normal pO{sub 2}-distributions: {mu}{sub 1} = 2.483, {sigma}{sub 1} = 0.711; {mu}{sub 2} = 2.946, {sigma}{sub 2} = 0.689; {mu}{sub 3} = 3.689, and {sigma}{sub 3} = 0.330. The normal tissue absorbed doses will, in turn, depend on this. These distributions were chosen to represent the expected oxygen levels in an untreated hypoxic tumor, a hypoxic tumor treated with an anti-VEGF agent, and in normal, fully-oxygenated tissue, respectively. The former two are fitted to experimental data. The geometric oxygen distributions are simulated using two different patterns: one Monte Carlo based and one radially increasing, while keeping the log-normal volumetric distributions intact. Oxygen and activity are distributed, according to the same pattern. Results: As tumor pO{sub 2

  18. Tension Headache

    Science.gov (United States)

    ... tight band around your head. A tension headache (tension-type headache) is the most common type of headache, and ... Headache after a head injury, especially if the headache gets worse ... tension or stress. But research suggests muscle contraction isn't the ...

  19. Increased Tumor Oxygenation and Drug Uptake During Anti-Angiogenic Weekly Low Dose Cyclophosphamide Enhances the Anti-Tumor Effect of Weekly Tirapazamine

    Science.gov (United States)

    Doloff, J.C.; Khan, N.; Ma, J.; Demidenko, E.; Swartz, H.M.; Jounaidi, Y.

    2010-01-01

    Metronomic cyclophosphamide treatment is associated with anti-angiogenic activity and is anticipated to generate exploitable hypoxia using hypoxia-activated prodrugs. Weekly administration of tirapazamine (TPZ; 5 mg/kg body weight i.p.) failed to inhibit the growth of 9L gliosarcoma tumors grown s.c. in scid mice. However, the anti-tumor effect of weekly cyclophosphamide (CPA) treatment (140 mg/kg BW i.p.) was substantially enhanced by weekly TPZ administration. An extended tumor free period and increased frequency of tumor eradication without overt toxicity were observed when TPZ was given 3, 4 or 5 days after each weekly CPA treatment. Following the 2nd CPA injection, Electron Paramagnetic Resonance (EPR) Oximetry indicated significant increases in tumor pO2, starting at 48 hr, which further increased after the 3rd CPA injection. pO2 levels were, however, stable in growing untreated tumors. A strong negative correlation (−0.81) between tumor pO2 and tumor volume during 21 days of weekly CPA chemotherapy was observed, indicating increasing tumor pO2 with decreasing tumor volume. Furthermore, CPA treatment resulted in increased tumor uptake of activated CPA. CPA induced increases in VEGF RNA, which reached a maximum on day 1, and in PLGF RNA which was sustained throughout the treatment, while anti-angiogenic host thrombospondin-1 increased dramatically through day 7 post-CPA treatment. Weekly cyclophosphamide treatment was anticipated to generate exploitable hypoxia. However, our findings suggest that weekly CPA treatment induces a functional improvement of tumor vasculature, which is characterized by increased tumor oxygenation and drug uptake in tumors, thus counter-intuitively, benefiting intratumoral activation of TPZ and perhaps other bioreductive drugs. PMID:19754361

  20. Deleted in Malignant Brain Tumors 1 (DMBT1) is present in hyaline membranes and modulates surface tension of surfactant

    DEFF Research Database (Denmark)

    Müller, Hanna; End, Caroline; Renner, Marcus

    2007-01-01

    BACKGROUND: Deleted in Malignant Brain Tumors 1 (DMBT1) is a secreted scavenger receptor cysteine-rich protein that binds various bacteria and is thought to participate in innate pulmonary host defense. We hypothesized that pulmonary DMBT1 could contribute to respiratory distress syndrome...

  1. Effects of in vitro low oxygen tension preconditioning of adipose stromal cells on their in vivo chondrogenic potential: application in cartilage tissue repair.

    Directory of Open Access Journals (Sweden)

    Sophie Portron

    Full Text Available PURPOSE: Multipotent stromal cell (MSC-based regenerative strategy has shown promise for the repair of cartilage, an avascular tissue in which cells experience hypoxia. Hypoxia is known to promote the early chondrogenic differentiation of MSC. The aim of our study was therefore to determine whether low oxygen tension could be used to enhance the regenerative potential of MSC for cartilage repair. METHODS: MSC from rabbit or human adipose stromal cells (ASC were preconditioned in vitro in control or chondrogenic (ITS and TGF-β medium and in 21 or 5% O2. Chondrogenic commitment was monitored by measuring COL2A1 and ACAN expression (real-time PCR. Preconditioned rabbit and human ASC were then incorporated into an Si-HPMC hydrogel and injected (i into rabbit articular cartilage defects for 18 weeks or (ii subcutaneously into nude mice for five weeks. The newly formed tissue was qualitatively and quantitatively evaluated by cartilage-specific immunohistological staining and scoring. The phenotype of ASC cultured in a monolayer or within Si-HPMC in control or chondrogenic medium and in 21 or 5% O2 was finally evaluated using real-time PCR. RESULTS/CONCLUSIONS: 5% O2 increased the in vitro expression of chondrogenic markers in ASC cultured in induction medium. Cells implanted within Si-HPMC hydrogel and preconditioned in chondrogenic medium formed a cartilaginous tissue, regardless of the level of oxygen. In addition, the 3D in vitro culture of ASC within Si-HPMC hydrogel was found to reinforce the pro-chondrogenic effects of the induction medium and 5% O2. These data together indicate that although 5% O2 enhances the in vitro chondrogenic differentiation of ASC, it does not enhance their in vivo chondrogenesis. These results also highlight the in vivo chondrogenic potential of ASC and their potential value in cartilage repair.

  2. Inverse Regulation of Early and Late Chondrogenic Differentiation by Oxygen Tension Provides Cues for Stem Cell-Based Cartilage Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Sophie Portron

    2015-01-01

    Full Text Available Background/Aims: Multipotent stem/stromal cells (MSC are considered promising for cartilage tissue engineering. However, chondrogenic differentiation of MSC can ultimately lead to the formation of hypertrophic chondrocytes responsible for the calcification of cartilage. To prevent the production of this calcified matrix at the articular site, the late hypertrophic differentiation of MSCs must be carefully controlled. Given that articular cartilage is avascular, we hypothesized that in addition to its stimulatory role in the early differentiation of chondrogenic cells, hypoxia may prevent their late hypertrophic conversion. Methods: Early and late chondrogenic differentiation were evaluated using human adipose MSC and murine ATDC5 cells cultured under either normoxic (21%O2 or hypoxic (5%O2 conditions. To investigate the effect of hypoxia on late chondrogenic differentiation, the transcriptional activity of hypoxia-inducible factor-1alpha (HIF-1α and HIF-2α were evaluated using the NoShift DNA-binding assay and through modulation of their activity (chemical inhibitor, RNA interference. Results: Our data demonstrate that low oxygen tension not only stimulates the early chondrogenic commitment of two complementary models of chondrogenic cells, but also inhibits their hypertrophic differentiation. Conclusion: These results suggest that hypoxia can be used as an instrumental tool to prevent the formation of a calcified matrix in MSC-based cartilage tissue engineering.

  3. End-Tidal CO2 Tension Is Predictive of Effective Nocturnal Oxygen Therapy in Patients with Chronic Heart Failure and Central Sleep Apnea.

    Science.gov (United States)

    Sugimura, Koichiro; Shinozaki, Tsuyoshi; Fukui, Shigefumi; Ogawa, Hiromasa; Shimokawa, Hiroaki

    2016-05-01

    Central sleep apnea (CSA) is characterized by recurring cycles of crescendo-decrescendo ventilation during sleep, and enhances sympathetic nerve activity. Thus CSA has a prognostic impact in patients with chronic heart failure (CHF). Although nocturnal oxygen (O2) therapy decreases frequency of CSA and improves functional exercise capacity, it is also known that some non-responders to the therapy exist. We thus aimed to identify predictors of responders to nocturnal O2 therapy in CHF patients with CSA. In 12 CHF patients with CSA hospitalized at our department, sleep study was performed at 2 consecutive nights. Patients nasally inhaled O2 at either the first or second night in a randomized manner. To predict the percentage reduction in apnea-hypopnea index (%ΔAHI) in response to the nocturnal O2 therapy, we performed multiple regression analysis with a stepwise method with variables including age, brain-natriuretic peptide, circulation time, baseline AHI, hypercapnic ventilatory response and end-tidal carbon dioxide tension (PETCO2). Nocturnal O2 therapy significantly decreased AHI (from 32 ± 13 /h to 12 ± 10 /h, P 50% reduction of AHI), with 88.9% of sensitivity and 66.7% of specificity. In conclusion, PETCO2 is useful to predict the efficacy of O2 therapy in CHF patients with CSA, providing important information to the current nocturnal O2 therapy.

  4. Doranidazole (PR-350), a hypoxic cell radiosensitizer, radiosensitizes human lung tumors (RERF-LC- AI) and causes changes in tumor oxygenation

    International Nuclear Information System (INIS)

    Kubota, N.; Griffin, R.J.; Williams, B.W.; Song, C.W.; Yahiro, T.

    2003-01-01

    Full text: We previously have reported the radiosensitizing capability of Doranidazole (PR-350) on SCCVII cells and tumors (Puerto Rico, 2001). In the present study, we have investigated the efficacy of PR-350 as a hypoxic cell radiosensitizer using human lung cancer cells (RERF-LC-AI) in vitro and also RERF-LC-AI tumors grown s.c. in Balb/c nude mice. Using the micronucleus assay method, we determined the effect of PR-350 on the response of RERF-LC-AI cells to radiation under hypoxic conditions and enhancement ratios (ER) of 1.45∼2.26 were obtained. The in vivo radiosensitizing effect was studied by irradiating RERF-LC-AI tumors with 15 Gy at 20 min. after i.v. injection of PR-350 (200mg/kg) and measuring the tumor growth delay. Significant growth delay occurred after i.v. injection of PR-350 before irradiation compared to radiation alone. We measured tumor pO 2 at 3, 7 and 14 days after treatment using an Eppendorf pO 2 histograph. The frequency of pO 2 values 2 in tumors treated with radiation plus PR-350 were higher than that in tumors treated with radiation plus saline. These data suggest that the O 2 consumption in tumors treated with radiation plus PR-350 was less than that in tumors treated with radiation plus saline due to greater drug and radiation-induced cell death. This hypothesis is supported by the fact that the tumor size in the combined treatment group was smaller than in radiation alone. These results suggest that PR-350 may improve the response of tumors to radiotherapy not only by increasing the radiosensitivity of hypoxic cells but also by improving tumor oxygenation over many days during fractionated radiotherapy

  5. Comparing CT perfusion with oxygen partial pressure in a rabbit VX2 soft-tissue tumor model

    International Nuclear Information System (INIS)

    Sun Changjin; Li Chao; Lv Haibo

    2014-01-01

    The aim of this study was to evaluate the oxygen partial pressure of the rabbit model of the VX2 tumor using a 64-slice perfusion CT and to compare the results with that obtained using the oxygen microelectrode method. Perfusion CT was performed for 45 successfully constructed rabbit models of a VX2 brain tumor. The perfusion values of the brain tumor region of interest, the blood volume (BV), the time to peak (TTP) and the peak enhancement intensity (PEI) were measured. The results were compared with the partial pressure of oxygen (PO2) of that region of interest obtained using the oxygen microelectrode method. The perfusion values of the brain tumor region of interest in 45 successfully constructed rabbit models of a VX2 brain tumor ranged from 1.3–127.0 (average, 21.1 ± 26.7 ml/min/ml); BV ranged from 1.2–53.5 ml/100g (average, 22.2 ± 13.7 ml/100g); PEI ranged from 8.7–124.6 HU (average, 43.5 ± 28.7 HU); and TTP ranged from 8.2–62.3 s (average, 38.8 ± 14.8 s). The PO2 in the corresponding region ranged from 0.14–47 mmHg (average, 16 ± 14.8 mmHg). The perfusion CT positively correlated with the tumor PO2, which can be used for evaluating the tumor hypoxia in clinical practice. (author)

  6. Diffuse Reflectance Spectroscopy (DRS) of radiation-induced re-oxygenation in sensitive and resistant head and neck tumor xenografts

    Science.gov (United States)

    Dadgar, Sina; Rodríguez Troncoso, Joel; Rajaram, Narasimhan

    2018-02-01

    Currently, anatomical assessment of tumor volume performed several weeks after completion of treatment is the clinical standard to determine whether a cancer patient has responded to a treatment. However, functional changes within the tumor could potentially provide information regarding treatment resistance or response much earlier than anatomical changes. We have used diffuse reflectance spectroscopy to assess the short and long-term re-oxygenation kinetics of a human head and neck squamous cell carcinoma xenografts in response to radiation therapy. First, we injected UM-SCC-22B cell line into the flank of 50 mice to grow xenografts. Once the tumor volume reached 200 mm3 (designated as Day 1), the mice were distributed into radiation and control groups. Members of radiation group underwent a clinical dose of radiation of 2 Gy/day on Days 1, 4, 7, and 10 for a cumulative dose of 8 Gy. DRS spectra of these tumors were collected for 14 days during and after therapy, and the collected spectra of each tumor were converted to its optical properties using a lookup table-base inverse model. We found statistically significant differences in tumor growth rate between two groups which is in indication of the sensitivity of this cell line to radiation. We further acquired significantly different contents of hemoglobin and scattering magnitude and size in two groups. The scattering has previously been associated with necrosis. We furthermore found significantly different time-dependent changes in vascular oxygenation and tumor hemoglobin concentration in post-radiation days.

  7. Induction of Tca8113 tumor cell apoptosis by icotinib is associated with reactive oxygen species mediated p38-MAPK activation.

    Science.gov (United States)

    Yang, Cailing; Yan, Jianguo; Yuan, Guoyan; Zhang, Yinghua; Lu, Derong; Ren, Mingxin; Cui, Weigang

    2014-08-01

    Icotinib, a selective EGFR tyrosine kinase inhibitor (EGFR-TKI), has been shown to exhibit anti-tumor activity against several tumor cell lines. However, the exact molecular mechanism of icotinib's anti-tumor effect remains unknown. This study aims to examine the zytotoxic effect of icotinib on Tca8113 cells and its potential molecular mechanism. Icotinib significantly resulted in dose-dependent cell death as determined by MTT assay, accompanied by increased levels of Bax and DNA fragmentation. Icotinib could also induce Reactive Oxygen Species (ROS) generation. Further studies confirmed that scavenging of reactive oxygen species by N-acetyl-L-cysteine (NAC), and pharmacological inhibition of MAPK reversed icotinib-induced apoptosis in Tca8113 cells. Our data provide evidence that icotinib induces apoptosis, possibly via ROS-mediated MAPK pathway in Tca8113 cells.

  8. Superiority of Transcutaneous Oxygen Tension Measurements in Predicting Limb Salvage After Below-the-Knee Angioplasty: A Prospective Trial in Diabetic Patients With Critical Limb Ischemia

    International Nuclear Information System (INIS)

    Redlich, Ulf; Xiong, Yan Y.; Pech, Maciej; Tautenhahn, Jörg; Halloul, Zuhir; Lobmann, Ralf; Adolf, Daniela; Ricke, Jens; Dudeck, Oliver

    2011-01-01

    Purpose: To assess postprocedural angiograms, the ankle–brachial index (ABI), and transcutaneous oxygen tension (TcPO 2 ) to predict outcome after infrageniculate angioplasty (PTA) in diabetic patients with critical limb ischemia (CLI) scheduled for amputation. Materials and Methods: PTA was performed in 28 diabetic patients with CLI confined to infrapopliteal vessels. We recorded patency of crural vessels, including the vascular supply of the foot as well as the ABI and TcPO 2 of the foot. Results: Technical success rate was 92.9% (n = 26), and limb-salvage rate at 12 months was 60.7% (n = 17). The number of patent straight vessels above and below the level of the malleoli increased significantly in patients avoiding amputation. Amputation was unnecessary in 88.2% (n = 15) patients when patency of at least one tibial artery was achieved. In 72.7% (n = 8) of patients, patency of the peroneal artery alone was not sufficient for limb salvage. ABI was of no predictive value for limb salvage. TcPO 2 values increased significantly only in patients not requiring amputation (P = 0.015). In patients with only one tibial artery supplying the foot or only a patent peroneal artery in postprocedural angiograms, TcPO 2 was capable of reliably predicting the outcome. Conclusion: Below-the-knee PTA as an isolated part of therapy was effective to prevent major amputation in more than a half of diabetic patients with CLI. TcPO 2 was a valid predictor for limb salvage, even when angiographic outcome criteria failed.

  9. Transcriptional and metabolic response of recombinant Escherichia coli to spatial dissolved oxygen tension gradients simulated in a scale-down system.

    Science.gov (United States)

    Lara, Alvaro R; Leal, Lidia; Flores, Noemí; Gosset, Guillermo; Bolívar, Francisco; Ramírez, Octavio T

    2006-02-05

    Escherichia coli, expressing recombinant green fluorescent protein (GFP), was subjected to dissolved oxygen tension (DOT) oscillations in a two-compartment system for simulating gradients that can occur in large-scale bioreactors. Cells were continuously circulated between the anaerobic (0% DOT) and aerobic (10% DOT) vessels of the scale-down system to mimic an overall circulation time of 50 s, and a mean residence time in the anaerobic and aerobic compartments of 33 and 17 s, respectively. Transcription levels of mixed acid fermentation genes (ldhA, poxB, frdD, ackA, adhE, pflD, and fdhF), measured by quantitative RT-PCR, increased between 1.5- to over 6-fold under oscillatory DOT compared to aerobic cultures (constant 10% DOT). In addition, the transcription level of fumB increased whereas it decreased for sucA and sucB, suggesting that the tricarboxylic acid cycle was functioning as two open branches. Gene transcription levels revealed that cytrochrome bd, which has higher affinity to oxygen but lower energy efficiency, was preferred over cytochrome bO3 in oscillatory DOT cultures. Post-transcriptional processing limited heterologous protein production in the scale-down system, as inferred from similar gfp transcription but 19% lower GFP concentration compared to aerobic cultures. Simulated DOT gradients also affected the transcription of genes of the glyoxylate shunt (aceA), of global regulators of aerobic and anaerobic metabolism (fnr, arcA, and arcB), and other relevant genes (luxS, sodA, fumA, and sdhB). Transcriptional changes explained the observed alterations in overall stoichiometric and kinetic parameters, and production of ethanol and organic acids. Differences in transcription levels between aerobic and anaerobic compartments were also observed, indicating that E. coli can respond very fast to intermittent DOT conditions. The transcriptional responses of E. coli to DOT gradients reported here are useful for establishing rational scale-up criteria and

  10. Effects of breathing a hyperoxic hypercapnic gas mixture on blood oxygenation and vascularity of head-and-neck tumors as measured by magnetic resonance imaging

    International Nuclear Information System (INIS)

    Rijpkema, Mark; Kaanders, Johannes H.A.M.; Joosten, Frank; Kogel, Albert J. van der; Heerschap, Arend

    2002-01-01

    Purpose: For head-and-neck tumors, breathing a hyperoxic hypercapnic gas mixture and administration of nicotinamide has been shown to result in a significantly improved tumor response to accelerated radiotherapy (ARCON, Accelerated Radiotherapy with CarbOgen and Nicotinamide). This may be caused by improved tumor oxygenation, possibly mediated by vascular effects. In this study, both blood oxygenation and vascular effects of breathing a hyperoxic hypercapnic gas mixture (98% O 2 +2% CO 2 ) were assessed by magnetic resonance imaging (MRI) in patients with head-and-neck tumors. Methods and Materials: Tumor vascularity and oxygenation were investigated by dynamic gadolinium contrast-enhanced MRI and blood oxygen level dependent (BOLD) MRI, respectively. Eleven patients with primary head-and-neck tumors were each measured twice; with and without breathing the hyperoxic hypercapnic gas mixture. Results: BOLD MR imaging revealed a significant increase of the MRI time constant of transverse magnetization decay (T 2 *) in the tumor during hypercapnic hyperoxygenation, which correlates to a decrease of the deoxyhemoglobin concentration. No changes in overall tumor vascularity were observed, as measured by the gadolinium contrast uptake rate in the tumor. Conclusion: Breathing a hyperoxic hypercapnic gas mixture improves tumor blood oxygenation in patients with head-and-neck tumors, which may contribute to the success of the ARCON therapy

  11. Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes

    International Nuclear Information System (INIS)

    Radogna, Flavia; Paternoster, Laura; De Nicola, Milena; Cerella, Claudia; Ammendola, Sergio; Bedini, Annalida; Tarzia, Giorgio; Aquilano, Katia; Ciriolo, Maria; Ghibelli, Lina

    2009-01-01

    Melatonin is a modified tryptophan with potent biological activity, exerted by stimulation of specific plasma membrane (MT1/MT2) receptors, by lower affinity intracellular enzymatic targets (quinone reductase, calmodulin), or through its strong anti-oxidant ability. Scattered studies also report a perplexing pro-oxidant activity, showing that melatonin is able to stimulate production of intracellular reactive oxygen species (ROS). Here we show that on U937 human monocytes melatonin promotes intracellular ROS in a fast (< 1 min) and transient (up to 5-6 h) way. Melatonin equally elicits its pro-radical effect on a set of normal or tumor leukocytes; intriguingly, ROS production does not lead to oxidative stress, as shown by absence of protein carbonylation, maintenance of free thiols, preservation of viability and regular proliferation rate. ROS production is independent from MT1/MT2 receptor interaction, since a) requires micromolar (as opposed to nanomolar) doses of melatonin; b) is not contrasted by the specific MT1/MT2 antagonist luzindole; c) is not mimicked by a set of MT1/MT2 high affinity melatonin analogues. Instead, chlorpromazine, the calmodulin inhibitor shown to prevent melatonin-calmodulin interaction, also prevents melatonin pro-radical effect, suggesting that the low affinity binding to calmodulin (in the micromolar range) may promote ROS production.

  12. A hybrid multibreath wash-in wash-out lung function quantification scheme in human subjects using hyperpolarized 3 He MRI for simultaneous assessment of specific ventilation, alveolar oxygen tension, oxygen uptake, and air trapping.

    Science.gov (United States)

    Hamedani, Hooman; Kadlecek, Stephen; Xin, Yi; Siddiqui, Sarmad; Gatens, Heather; Naji, Joseph; Ishii, Masaru; Cereda, Maurizio; Rossman, Milton; Rizi, Rahim

    2017-08-01

    To present a method for simultaneous acquisition of alveolar oxygen tension (P A O 2 ), specific ventilation (SV), and apparent diffusion coefficient (ADC) of hyperpolarized (HP) gas in the human lung, allowing reinterpretation of the P A O 2 and SV maps to produce a map of oxygen uptake (R). An imaging scheme was designed with a series of identical normoxic HP gas wash-in breaths to measure ADC, SV, P A O 2 , and R in less than 2 min. Signal dynamics were fit to an iterative recursive model that regionally solved for these parameters. This measurement was successfully performed in 12 subjects classified in three healthy, smoker, and chronic obstructive pulmonary disease (COPD) cohorts. The overall whole lung ADC, SV, P A O 2 , and R in healthy, smoker, and COPD subjects was 0.20 ± 0.03 cm 2 /s, 0.39 ± 0.06,113 ± 2 Torr, and 1.55 ± 0.35 Torr/s, respectively, in healthy subjects; 0.21 ± 0.03 cm 2 /s, 0.33 ± 0.06, 115.9 ± 4 Torr, and 0.97 ± 0.2 Torr/s, respectively, in smokers; and 0.25 ± 0.06 cm 2 /s, 0.23 ± 0.08, 114.8 ± 6.0Torr, and 0.94 ± 0.12 Torr/s, respectively, in subjects with COPD. Hetrogeneity of SV, P A O 2 , and R were indicators of both smoking-related changes and disease, and the severity of the disease correlated with the degree of this heterogeneity. Subjects with symptoms showed reduced oxygen uptake and specific ventilation. High-resolution, nearly coregistered and quantitative measures of lung function and structure were obtained with less than 1 L of HP gas. This hybrid multibreath technique produced measures of lung function that revealed clear differences among the cohorts and subjects and were confirmed by correlations with global lung measurements. Magn Reson Med 78:611-624, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  13. Radiosensitivity of Hela cells in various O2 concentrations and consideration of oxygen effect in radiotherapy

    International Nuclear Information System (INIS)

    Kuroda, Yoshikazu; Nyunoya, Koichiro

    1979-01-01

    The aim of this paper is the study of the radiosensitivity of HeLa cells in vitro in various oxygen concentrations and the consideration of the utilization of oxygen effect in radiation therapy, based on the data of HeLa cells and tumor oxygen tension. Survival curves of HeLa cells are found to be exponential as a function of radiation dose and the radiosensitivity is dependent on oxygen tension of culture medium. Relative radiosensitivity decreases remarkably at low level of oxygen, especially under 9 mmHg pO 2 . The utilization of oxygen effect in radiation may be useful in hyperbaric oxygen inhalation and not useful under local tissue hypoxia induced by tourniquet application. Reoxygenation occurs with shrinkage of tumor after irradiation and this phenomenon will diminish the value of hyperbaric oxygen in radiation therapy. (author)

  14. Singlet oxygen explicit dosimetry to predict long-term local tumor control for Photofrin-mediated photodynamic therapy

    Science.gov (United States)

    Penjweini, Rozhin; Kim, Michele M.; Ong, Yi Hong; Zhu, Timothy C.

    2017-02-01

    Although photodynamic therapy (PDT) is an established modality for the treatment of cancer, current dosimetric quantities do not account for the variations in PDT oxygen consumption for different fluence rates (φ). In this study we examine the efficacy of reacted singlet oxygen concentration ([1O2]rx) to predict long-term local control rate (LCR) for Photofrin-mediated PDT. Radiation-induced fibrosarcoma (RIF) tumors in the right shoulders of female C3H mice are treated with different in-air fluences of 225-540 J/cm2 and in-air fluence rate (φair) of 50 and 75 mW/cm2 at 5 mg/kg Photofrin and a drug-light interval of 24 hours using a 1 cm diameter collimated laser beam at 630 nm wavelength. [1O2]rx is calculated by using a macroscopic model based on explicit dosimetry of Photofrin concentration, tissue optical properties, tissue oxygenation and blood flow changes during PDT. The tumor volume of each mouse is tracked for 90 days after PDT and Kaplan-Meier analyses for LCR are performed based on a tumor volume defined as a temporal integral of photosensitizer concentration and Φ at a 3 mm tumor depth. φ is calculated throughout the treatment volume based on Monte-Carlo simulation and measured tissue optical properties. Our preliminary studies show that [1O2]rx is the best dosimetric quantity that can predict tumor response and correlate with LCR. Moreover, [1O2]rx calculated using the blood flow changes was in agreement with [1O2]rx calculated based on the actual tissue oxygenation.

  15. Tension headache.

    Science.gov (United States)

    Ziegler, D K

    1978-05-01

    Headache is an extremely common symptom, and many headaches undoubtedly have a relationship to stressful situations. The clear definition, however, of a "tension headache" complex and its differentiation from migraine in some patients is difficult. The problems are in the identification of a specific headache pattern induced by stress or "tension" and the relationship of the symptom to involuntary contraction of neck and scalp muscles. Treatment consists of analgesics and occasionally mild tranquilizers. Psychotherapy consists of reassurance and often other supportive measures, including modification of life styles. Various feedback techniques have been reported of value, but their superiority to suggestion and hypnosis is still problematic.

  16. Dynamic changes in oxygenation of intracranial tumor and contralateral brain during tumor growth and carbogen breathing: A multisite EPR oximetry with implantable resonators

    Science.gov (United States)

    Hou, Huagang; Dong, Ruhong; Li, Hongbin; Williams, Benjamin; Lariviere, Jean P.; Hekmatyar, S.K.; Kauppinen, Risto A.; Khan, Nadeem; Swartz, Harold

    2013-01-01

    Introduction Several techniques currently exist for measuring tissue oxygen; however technical difficulties have limited their usefulness and general application. We report a recently developed electron paramagnetic resonance (EPR) oximetry approach with multiple probe implantable resonators (IRs) that allow repeated measurements of oxygen in tissue at depths of greater than 10 mm. Methods The EPR signal to noise (S/N) ratio of two probe IRs was compared with that of LiPc deposits. The feasibility of intracranial tissue pO2 measurements by EPR oximetry using IRs was tested in normal rats and rats bearing intracerebral F98 tumors. The dynamic changes in the tissue pO2 were assessed during repeated hyperoxia with carbogen breathing. Results A 6–10 times increase in the S/N ratio was observed with IRs as compared to LiPc deposits. The mean brain pO2 of normal rats was stable and increased significantly during carbogen inhalation in experiments repeated for 3 months. The pO2 of F98 glioma declined gradually, while the pO2 of contralateral brain essentially remained the same. Although a significant increase in the glioma pO2 was observed during carbogen inhalation, this effect declined in experiments repeated over days. Conclusion EPR oximetry with IRs provides a significant increase in S/N ratio. The ability to repeatedly assess orthotopic glioma pO2 is likely to play a vital role in understanding the dynamics of tissue pO2 during tumor growth and therapies designed to modulate tumor hypoxia. This information could then be used to optimize chemoradiation by scheduling treatments at times of increased glioma oxygenation. PMID:22033225

  17. Manipulation of tumor oxygenation and radiosensitivity through modification of cell respiration. A critical review of approaches and imaging biomarkers for therapeutic guidance.

    Science.gov (United States)

    Gallez, Bernard; Neveu, Marie-Aline; Danhier, Pierre; Jordan, Bénédicte F

    2017-08-01

    Tumor hypoxia has long been considered as a detrimental factor for the response to irradiation. In order to improve the sensitivity of tumors cells to radiation therapy, tumor hypoxia may theoretically be alleviated by increasing the oxygen delivery or by decreasing the oxygen consumption by tumor cells. Mathematical modelling suggested that decreasing the oxygen consumption should be more efficient than increasing oxygen delivery in order to alleviate tumor hypoxia. In this paper, we review several promising strategies targeting the mitochondrial respiration for which alleviation of tumor hypoxia and increase in sensitivity to irradiation have been demonstrated. Because the translation of these approaches into the clinical arena requires the use of pharmacodynamics biomarkers able to identify shift in oxygen consumption and tumor oxygenation, we also discuss the relative merits of imaging biomarkers (Positron Emission Tomography and Magnetic Resonance) that may be used for therapeutic guidance. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Increasing the effectiveness of hyperbaric oxygen in enhancing tumor oxygenation: Effect of perfluorochemical emulsion and moderate anaemia

    International Nuclear Information System (INIS)

    Photiou, A.

    1987-01-01

    Attempts were made to increase the effectiveness of HBO in overcoming tumor hypoxia. Tumor blood flow and O/sub 2/ content were modified by inducing moderate anaemia and giving a perfluorochemical emulsion (PFC-E). Mice were anaesthetized with Ketamine and Diazepam. The PFC-E, FC-43 (0.35 ml/25 g mouse), given iv 1-2 h before irradiation, produced a favourable effect on regrowth delay in those mice treated with HBO. A 25 Gy dose produced a significantly longer regrowth delay (p<0.01) of 44 days in PFC-treated mice compared with a delay of 29 days for mice treated with HBO alone. O/sub 2/ toxicity was observed in some anesthetized mice, with or without PFC-E. Attempts were made to increase the O/sub 2/ sensitization afforded by FC-43/HBO/anaesthesia. Blood viscosity was reduced by inducing a moderate level of acute anaemia by the administration of a single of acute anaemia by the administration of a single ip injection of Phenylhydrazine HCl (40 mg/kg). This reduced the haematocrit from 42% to 32%. Tumour regrowth delay after 25 Gy was significantly reduced (p<0.02) from 44 to 37.3 days be anaemia. PFC's may prove the be useful adjuncts to radiotherapy. However, it must be established that they have no adverse effects and that normal tissue radiosensitivity is not enhanced

  19. TH-AB-209-05: Validating Hemoglobin Saturation and Dissolved Oxygen in Tumors Using Photoacoustic Computed Tomographic Spectroscopic Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Burnett, J; Sick, J; Liu, B [Purdue University, West Lafayette, IN (United States); Cao, N [University of Washington Medical Center, Seattle, WA (United States); Nakshatri, H; Mendonca, M [Indiana University - Purdue University Indianapolis, Indianapolis, IN (United States); Stantz, K [Purdue University, West Lafayette, IN (United States); Indiana University - Purdue University Indianapolis, Indianapolis, IN (United States)

    2016-06-15

    Purpose: Photoacoustic computed tomographic spectroscopy (PCT-S) provides intra-tumor measurements of oxygenation with high spatial resolution (0.2mm) and temporal fidelity (1–2 minutes) without the need for exogenous agents or ionizing radiation, thus providing a unique in vivo assay to measure SaO{sub 2} and investigate acute and chronic forms of hypoxia. The goal of this study is to validate in vivo SaO{sub 2} levels within tail artery of mice and the relationship between SaO{sub 2} and pO{sub 2} within subcutaneous breast tumors using PCT-S imaging, pulse oximetry and an OxyLite probe. Methods: A closed circuit phantom was fabricated to control blood oxygenation levels, where SaO{sub 2} was measured using a co-oximeter and pO{sub 2} using an Oxylite probe. Next, SaO{sub 2} levels within the tail arteries of mice (n=3) were measured using PCT-S and pulse oximetry while breathing high-to-low oxygen levels (6-cycles). Finally, PCT-S was used to measure SaO{sub 2} levels in MCF-7, MCF-7-VEGF165, and MDA-MB-231 xenograft breast tumors and compared to Oxylite pO{sub 2} levels values. Results: SaO{sub 2} and pO{sub 2} data obtained from the calibration phantom was fit to Hill’s equation: aO{sub 2} levels between 88 and 52% demonstrated a linear relationship (r2=0.96) and a 3.2% uncertainty between PCT-S values relative to pulse oximetry. Scatter plots of localized PCT-S measured SaO2 and Oxylite pO{sub 2} levels in MCF-7/MCF-7-VEGF165 and MDA-MD-231 breast tumors were fit to Hill’s equation: P50=17.2 and 20.7mmHg, and n=1.76 and 1.63. These results are consistent with sigmoidal form of Hill’s equation, where the lower P{sub 50} value is indicative of an acidic tumor microenvironment. Conclusion: The results demonstrate photoacoustic imaging can be used to measure SaO{sub 2} cycling and intra-tumor oxygenation, and provides a powerful in vivo assay to investigate the role of hypoxia in radiation, anti-angiogenic, and immunotherapies.

  20. A preliminary study of murine walker-256 tumor hypoxia detected by blood oxygen level dependent-MR

    International Nuclear Information System (INIS)

    Zhang Shengjian; Mao Jian; Wu Bin; Peng Weijun

    2013-01-01

    Objective: To establish Walker-256 transplantation tumor model in SD Rats. To study of R_2"* signal changes on murine Walker-256 tumor after inhaling Carbogen by blood oxygen level dependent (BOLD)-MR, and to explore the feasibility of BOLD-MRI on detecting tumor hypoxia. Methods: Walker-256 tumor cell implanted subcutaneously in right lower abdomen of 95 female SD rats. MR was performed on the tumor-forming rats when the maximum diameter of tumor reached 1-3 cm, using a 3.0 T MR scanner equipped with a 3 inch animal surface coil. BOLD-MRI was done by using a multiecho SPGR sequence during inhaling air and at 10 minute after inhaling Carbogen, respectively. All images were transferred to GE ADW 4.3 workstation, then a baseline R_2"* (R_2"* a) and R_2"* (R_2"* b) after inhaling Carbogen of tumor was calculated using R_2 Star analysis software and ΔR_2"* was calculated through ΔR_2"* = R_2"* b -R_2"* a", meanwhile the volume of tumor were calculated as well. The difference of R_2"* signal pre and post-inhaling of Carbogen was compared with a paired t test, Pearson correlation was calculated between R_2"* a, ΔR_2"* and the volume of tumor, respectively. The correlation between ΔR_2"* and R_2"* a was also assessed by Pearson correlation. Results: Sixty-eight of ninety-five female SD rats formed the tumor (71.6%). The volume of tumor was from 352 to 13 173 mm"3. Mean ΔR_2"* decreased significantly (-2.26 ± 3.90) s"-"1 from (41.18 ± 22.29) s"-"1 during breathing air to (38.91 ± 21.35) s"-"1 10 min after inhaling Carbogen (t = 4.01, P 0.05). Conclusions: BOLD-MRI can detect the R_2"* signal change of murine Walker-256 tumor pre-and post-inhaling of Carbogen. The R_2"* signal showed significant decrease after inhaling Carbogen, however, the individual variation was remarkable. (authors)

  1. L-lysine escinat, thiotriazolin, gordox and mydocalm influence on oxygen tension in the intestinal wall and acid-base balance and limited proteolysis in intestinal venous blood in terms of intraabdominal hypertension modeling

    Directory of Open Access Journals (Sweden)

    Sapegin V.I.

    2014-11-01

    Full Text Available In acute experiments on rabbits there were studied changes in oxygen tension in the intestinal wall tissues, acid-base balance and limited proteolysis and its inhibitors in intestinal venous blood, protective action of L-lysine escinat (0,15 mg/kg / single dose, thiotriazolin (25 mg/kg / single dose, aprotinin (gordox (10,000 units/kg / single dose in sequential modeling of standard levels increasing of intra-abdominal hypertension (IAH — 50, 100, 150, 200, 250, 300, 350 m H2O, and also of tolperison (mydocalm (5 mg/kg / single dose on modeling of stable 3-hour IAH 200 m H2O. The IAH modeling was performed by means of stand of our construction. Under the influence of IAH the compensated metabolic acidosis in intestinal venous blood with a compensative hyperpnoe develops, decline of oxygen tension in tissues and activating of a limited proteolysis as well as decline of its inhibitors activity in intestinal venous blood occur. By the degree of metabolic acidosis prevention investigational preparations were distributed as follows gordox > thiotriazolin = L-lysine escinat = mydocalm, and by prevention of decline of oxygen tension in tissues — thiotriazolin > L-lysine escinat > mydocalm > gordox, it is is connected with different rate of methabolic products excretion into the blood, due to the influence on blood circulation and transcapilary exchange. By the degree of prevention of proteolytic activity and inhibitory potential changes, investigational preparations were distributed as follows: gordox > mydocalm > thiotriazolin > L-lysine escinat, this is connected with inhibition of proteolysis in gordox, and in other ones – with reduction of ischemic damage of tissues. Owing to different mechanism of action thiotriazolin, L-lysine escinat and mydocalm may be simultaneously recommended for a conservative treatment of patients with intraabdominal hypertension syndrome.

  2. Singlet oxygen explicit dosimetry to predict long-term local tumor control for BPD-mediated photodynamic therapy

    Science.gov (United States)

    Kim, Michele M.; Penjweini, Rozhin; Ong, Yi Hong; Zhu, Timothy C.

    2017-02-01

    Photodynamic therapy (PDT) is a well-established treatment modality for cancer and other malignant diseases; however, quantities such as light fluence, photosensitizer photobleaching rate, and PDT dose do not fully account for all of the dynamic interactions between the key components involved. In particular, fluence rate (Φ) effects are not accounted for, which has a large effect on the oxygen consumption rate. In this preclinical study, reacted singlet oxygen [1O2]rx was investigated as a dosimetric quantity for PDT outcome. The ability of [1O2]rx to predict the long-term local tumor control rate (LCR) for BPD-mediated PDT was examined. Mice bearing radioactivelyinduced fibrosarcoma (RIF) tumors were treated with different in-air fluences (250, 300, and 350 J/cm2) and in-air ϕ (75, 100, and150 mW/cm2) with a BPD dose of 1 mg/kg and a drug-light interval of 3 hours. Treatment was delivered with a collimated laser beam of 1 cm diameter at 690 nm. Explicit dosimetry of initial tissue oxygen concentration, tissue optical properties, and BPD concentration was used to calculate [1O2]rx. Φ was calculated for the treatment volume based on Monte-Carlo simulations and measured tissue optical properties. Kaplan-Meier analyses for LCR were done for an endpoint of tumor volume defined as the product of the timeintegral of photosensitizer concentration and Φ at a 3 mm tumor depth. Preliminary studies show that [1O2]rx better correlates with LCR and is an effective dosimetric quantity that can predict treatment outcome.

  3. Measurements of partial oxygen pressure pO2 using the OxyLite system in R3327-AT tumors under isoflurane anesthesia.

    Science.gov (United States)

    Wen, Bixiu; Urano, Muneyasu; O'Donoghue, Joseph A; Ling, C Clifton

    2006-09-01

    The presence of oxygen-deficient tumor cells is a critical issue in cancer therapy. To identify tumor hypoxia, tissue partial oxygen pressure (pO2) can be measured directly. The OxyLite system allows determination of pO2 in tumors and permits continuous measurements of pO2 at a fixed point. In this study, this system was used to continuously measure pO2 in R3327-AT tumors in animals anesthetized with isoflurane. In addition, continuous pO2 measurement was performed in the muscle in non-tumor-bearing animals. In animals breathing isoflurane balanced by air, tumor pO2 at fixed positions decreased rapidly within 1-2 min of probe positioning but remained stable thereafter. In animals breathing isoflurane balanced by pure oxygen, tumor pO2 was higher and remained high. We also measured pO2 values at multiple positions in R3327-AT tumors of various sizes, with anesthetized animals breathing either air or pure oxygen. Our data showed that the frequency of pO2 measurements below 2.5 or 5.0 mmHg was significantly higher in animals breathing air than in animals breathing pure oxygen. Measurements in different-sized tumors showed that the mean pO2 value decreased as tumor volume increased, with the largest change occurring between tumor volumes of 100 and 200 mm3. Our data demonstrate that the OxyLite system, when used with isoflurane anesthesia, is a valuable tool in the study of tumor hypoxia.

  4. EPR oxygen imaging and hyperpolarized (13) C MRI of pyruvate metabolism as noninvasive biomarkers of tumor treatment response to a glycolysis inhibitor 3-bromopyruvate

    DEFF Research Database (Denmark)

    Matsumoto, Shingo; Saito, Keita; Yasui, Hironobu

    2013-01-01

    The hypoxic nature of tumors results in treatment resistance and poor prognosis. To spare limited oxygen for more crucial pathways, hypoxic cancerous cells suppress mitochondrial oxidative phosphorylation and promote glycolysis for energy production. Thereby, inhibition of glycolysis has...... the potential to overcome treatment resistance of hypoxic tumors. Here, EPR imaging was used to evaluate oxygen dependent efficacy on hypoxia-sensitive drug. The small molecule 3-bromopyruvate blocks glycolysis pathway by inhibiting hypoxia inducible enzymes and enhanced cytotoxicity of 3-bromopyruvate under...

  5. Optical Imaging of Tumor Response to Hyperbaric Oxygen Treatment and Irradiation in an Orthotopic Mouse Model of Head and Neck Squamous Cell Carcinoma

    NARCIS (Netherlands)

    J.A.M. Braks (Joanna); L. Spiegelberg (Linda); S. Koljenović (Senada); Y. Ridwan (Yanto); S. Keereweer (Stijn); R. Kanaar (Roland); E.B. Wolvius (Eppo); J. Essers (Jeroen)

    2015-01-01

    textabstractPurpose: Hyperbaric oxygen therapy (HBOT) is used in the treatment of radiation-induced tissue injury but its effect on (residual) tumor tissue is indistinct and therefore investigated in this study. Procedures: Orthotopic FaDu tumors were established in mice, and the response of the

  6. Smoking: the influence of carboxyhemoglobin (HbCO) on tumor oxygenation and response to radiation

    International Nuclear Information System (INIS)

    Siemann, D.W.; Hill, R.P.; Bush, R.S.

    1978-01-01

    The effectiveness of localized x radiation on the transplantable KHT sarcoma was studied in nonanesthetized C3H mice possessing blood carboxyhemoglobin (HbCO) levels similar to those observed in heavy smokers. HbCO values of 10 percent were induced in tumor-bearing animals, either acutely just prior to irradiation or chronically during tumor growth and irradiation, by allowing the mice to breathe gas mixtures containing carbon monoxide (CO) in air. Tumors were irradiated either with single doses of 1500, 2000, or 2500 rad or with seven 500 rad fractions given at 24 hr intervals. Tumor cell survival was determined using an in vivo lung colony or an in vitro agar colony assay. The results with single doses of radiation indicate that under conditions of both acute and chronic exposure, the presence of 10 percent HbCO in the blood of the mice at the time of irradiation increases the survival of tumor cells in the hypoxic region of the survival curve by a factor of 2. During the fractionated irradiation, tumor cell survival in the presence of a 10 percent blood HbCO level (induced either acutely or chronically) was found to be significantly higher than that observed in air breathing mice. The results indicate that HbCO levels, such as are observed in heavy smokers, result in a larger fraction of hypoxic tumor cells. These findings suggest that heavy smoking prior to treatment may worsen the prognosis of patients undergoing radiotherapy

  7. Arterial oxygen tension and pulmonary ventilation in horses placed in the Anderson Sling suspension system after a period of lateral recumbency and anaesthetised with constant rate infusions of romifidine and ketamine.

    Science.gov (United States)

    François, I; Lalèyê, F-X; Micat, M; Benredouane, K; Portier, K

    2014-09-01

    Some controversy exists over whether or not horses' recovery and cardiopulmonary function are affected by suspension in slings. To measure arterial oxygen tension and pulmonary ventilation in anaesthetised horses placed in a standing position in an Anderson Sling (AS) after a period of right lateral recumbency (RLR). Randomised crossover experimental study. Six Standardbred horses were anaesthetised twice. Catheters were inserted into the right jugular vein and the left carotid artery. After premedication with romifidine, anaesthesia was induced with diazepam and ketamine. Following 50 min in RLR, horses were maintained in either RLR or AS for an additional 60 min through to recovery. Anaesthesia was maintained i.v. with a constant rate infusion of romifidine and ketamine. Heart rate, respiratory rate, mean arterial pressure, expiratory tidal volume, minute volumes and end tidal CO2 were monitored continuously. Venous and arterial bloods were sampled for lactate concentration, creatine kinase activity and blood gas analysis before premedication, after induction, every 20 min for 100 min, as soon as the horse was standing (TR), and 24 h later. The data were averaged within 2 anaesthetic periods: P1, 0-20 min; and P2, 40-100 min. During P2, horses in the RLR group had lower arterial oxygen tension (P = 0.001), higher alveolar-arterial oxygen tension gradient (P = 0.005), higher respiratory rate (P = 0.04) and higher minute volumes (P = 0.04) than horses in the AS group. Arterial CO2 tension and mean arterial pressure increased in the AS group during P2 (P = 0.01 and 0.02 respectively). The recoveries were judged better in the AS group than in the RLR group (P = 0.01). During TR, lactate were higher in the RLR group than in the AS group (P = 0.007). Creatine kinase activities were higher in the AS group at 24 h vs. TR (P = 0.02). Anderson Sling suspension after a period of recumbency improves cardiopulmonary function and recovery quality in horses and

  8. Increase in tumor oxygenation and potentiation of radiation effects using pentoxifylline, vinpocetine and ticlopidine hydrochloride

    International Nuclear Information System (INIS)

    Amano, Morikazu; Monzen, Hajime; Suzuki, Minoru; Terai, Kaoru; Andoh, Satoshi; Tsumuraya, Akio; Hasegawa, Takeo

    2005-01-01

    The purpose of the present study was to investigate the effects of Pentoxifylline (PTX), Vinpocetine (VPT) and Ticlopidine Hydrochloride (TCD), used commonly for vascular disorders in humans, on the pO 2 in SCCVII tumors of C3H/HeJ mice and on the radioresponse of SCCVII tumors. The pO 2 in the SCCVII tumors, which were measured 30 min after intraperioneal (i.p.) injection of PTX (5 mg/kg), VPT (5 mg/kg), or TCD (10 mg/kg) using polarography, was compared to that in saline-treated control tumors. All the three drugs, PTX, VPT and TCD, yielded significant increase of the pO 2 in the SCCVII tumors from 25.6 to 26.9 mmHg, from 18.6 to 22.9 mmHg, and from 22.6 to 25.9 mmHg, respectively. Frequency histogram of the pO 2 distribution in the saline-treated SCCVII tumors did not show hypoxic fraction of less than 10 mmHg. The radioresponses of the drugs were investigated by tumor growth delay assay. In the drug-treated groups, the SCCVII tumors were irradiated with a single dose of 15 Gy 30 min after injection of the drugs at the same doses as those used in the experiments for intratumoral pO 2 measurement. Compared with the irradiation alone group, significant tumor growth delays were observed in all the drug-treated groups. The time required to reach a four-fold increase in the initial tumor volume were 4 days in the saline-treated control group, 22 days in the irradiation (IR) alone group, 28 days in the PTX+IR group, 29 days in the VPT+IR group, and 32 days in TCD+IR group. In conclusion, VPT and TCD are potentially promising drugs for increasing the intratumoral pO 2 although the mechanism for radiopotentiation observed in the present study is unknown due to small hypoxic fraction in the SCCVII tumors. Further studies on other mechanisms for radiopotentiation of PTX, VPT or TCD, besides of increasing the pO 2 in the tumor, are needed. (author)

  9. Inhibitory effects of various oxygenated sterols on the differentiation and function of tumor-specific cytotoxic T lymphocytes

    International Nuclear Information System (INIS)

    Spangrude, G.J.; Sherris, D.; Daynes, R.A.

    1982-01-01

    Irradiation of skin with ultraviolet light (UVL) is capable of causing many biological and biochemical changes in this complex organ. One early consequence is the oxidation of epidermal plasma membrane cholesterol, causing the induction of a wide variety of photoproducts. It is well recognized that some oxygenated sterols possess potent biological activity on mammalian cells by their ability to inhibit endogeneous mevalonate and cholesterol biosynthesis. In the few immunological systems that have been studied, there is general agreement that lymphocyte function is lacking, as both afferent and efferent blockades have been suggested. These studies were undertaken to determine the effect of various oxygenated sterols (representing a number of known cholesterol-derived photoproducts) on the generation (afferent) and function (efferent) of cytotoxic T lymphocytes (CTLs). Cell-mediated immune responses which result in the generation of both alloantigen-specific and syngeneic tumor-specific CTLs were evaluated

  10. Activated Macrophages as a Novel Determinant of Tumor Cell Radioresponse: The Role of Nitric Oxide-Mediated Inhibition of Cellular Respiration and Oxygen Sparing

    International Nuclear Information System (INIS)

    Jiang Heng; De Ridder, Mark; Verovski, Valeri N.; Sonveaux, Pierre; Jordan, Benedicte F.; Law, Kalun; Monsaert, Christinne; Van den Berge, Dirk L.; Verellen, Dirk; Feron, Olivier; Gallez, Bernard; Storme, Guy A.

    2010-01-01

    Purpose: Nitric oxide (NO), synthesized by the inducible nitric oxide synthase (iNOS), is known to inhibit metabolic oxygen consumption because of interference with mitochondrial respiratory activity. This study examined whether activation of iNOS (a) directly in tumor cells or (b) in bystander macrophages may improve radioresponse through sparing of oxygen. Methods and Materials: EMT-6 tumor cells and RAW 264.7 macrophages were exposed to bacterial lipopolysaccharide plus interferon-γ, and examined for iNOS expression by reverse transcription polymerase chain reaction, Western blotting and enzymatic activity. Tumor cells alone, or combined with macrophages were subjected to metabolic hypoxia and analyzed for radiosensitivity by clonogenic assay, and for oxygen consumption by electron paramagnetic resonance and a Clark-type electrode. Results: Both tumor cells and macrophages displayed a coherent picture of iNOS induction at transcriptional/translational levels and NO/nitrite production, whereas macrophages showed also co-induction of the inducible heme oxygenase-1, which is associated with carbon monoxide (CO) and bilirubin production. Activation of iNOS in tumor cells resulted in a profound oxygen sparing and a 2.3-fold radiosensitization. Bystander NO-producing, but not CO-producing, macrophages were able to block oxygen consumption by 1.9-fold and to radiosensitize tumor cells by 2.2-fold. Both effects could be neutralized by aminoguanidine, a metabolic iNOS inhibitor. An improved radioresponse was clearly observed at macrophages to tumor cells ratios ranging between 1:16 to 1:1. Conclusions: Our study is the first, as far as we are aware, to provide evidence that iNOS may induce radiosensitization through oxygen sparing, and illuminates NO-producing macrophages as a novel determinant of tumor cell radioresponse within the hypoxic tumor microenvironment.

  11. Injectable LiNc-BuO loaded microspheres as in vivo EPR oxygen sensors after co-implantation with tumor cells.

    Science.gov (United States)

    Frank, Juliane; Gündel, Daniel; Drescher, Simon; Thews, Oliver; Mäder, Karsten

    2015-12-01

    Electron paramagnetic resonance (EPR) oximetry is a technique which allows accurate and repeatable oxygen measurements. We encapsulated a highly oxygen sensitive particulate EPR spin probe into microparticles to improve its dispersibility and, hence, facilitate the administration. These biocompatible, non-toxic microspheres contained 5-10 % (w/w) spin probe and had an oxygen sensitivity of 0.60 ± 0.01 µT/mmHg. To evaluate the performance of the microparticles as oxygen sensors, they were co-implanted with syngeneic tumor cells in 2 different rat strains. Thus, tissue injury was avoided and the microparticles were distributed all over the tumor tissue. Dynamic changes of the intratumoral oxygen partial pressure during inhalation of 8 %, 21 %, or 100 % oxygen were monitored in vivo by EPR spectroscopy and quantified. Values were verified in vivo by invasive fluorometric measurements using Oxylite probes and ex vivo by pimonidazole adduct accumulation. There were no hints that the tumor physiology or tissue oxygenation had been altered by the microparticles. Hence, these microprobes offer great potential as oxygen sensors in preclinical research, not only for EPR spectroscopy but also for EPR imaging. For instance, the assessment of tissue oxygenation during therapeutic interventions might help understanding pathophysiological processes and lead to an individualized treatment planning or the use of formulations with hypoxia triggered release of active agents. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Correlation of in vivo tumor response and singlet oxygen luminescence detection in mTHPC-mediated photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Brian C. Wilson

    2015-01-01

    Full Text Available Excited-state singlet oxygen (1O2, generated during photodynamic therapy (PDT, is believed to be the primary cytotoxic agent with a number of clinically approved photosensitizers. Its relative concentration in cells or tissues can be measured directly through its near-infrared (NIR luminescence emission, which has correlated well with in vitro cell and in vivo normal skin treatment responses. Here, its correlation with the response of tumor tissue in vivo is examined, using the photosensitizer meso-tetrahydroxyphenylchlorin (mTHPC in an animal model comprising luciferase- and green fluorescent protein (GFP-transduced gliosarcoma grown in a dorsal window chamber. The change in the bioluminescence signal, imaged pretreatment and at 2, 5 and 9 d post treatment, was used as a quantitative measure of the tumor response, which was classified in individual tumors as "non", "moderate" and "strong" in order to reduce the variance in the data. Plotting the bioluminescence-based response vs the 1O2 counts demonstrated clear correlation, indicating that 1O2 luminescence provides a valid dosimetric technique for PDT in tumor tissue.

  13. Lipid nanocarriers based on natural oils with high activity against oxygen free radicals and tumor cell proliferation

    International Nuclear Information System (INIS)

    Lacatusu, I.; Badea, N.; Badea, G.; Oprea, O.; Mihaila, M.A.; Kaya, D.A.; Stan, R.; Meghea, A.

    2015-01-01

    The development of nano-dosage forms of phytochemicals represents a significant progress of the scientific approach in the biomedical research. The aim of this study was to assess the effectiveness of lipid nanocarriers based on natural oils (grape seed oil, fish oil and laurel leaf oil) in counteracting free radicals and combating certain tumor cells. No drug was encapsulated in the nanocarriers. The cytotoxic effect exerted by bioactive nanocarriers against two tumor cells, MDA-MB 231 and HeLa cell lines, and two normal cells, L929 and B16 cell lines, was measured using the MTT assay, while oxidative damage was assessed by measuring the total antioxidant activity using chemiluminescence analysis. The best performance was obtained for nanocarriers based on an association of grape seed and laurel leaf oils, with a capacity to scavenge about 98% oxygen free radicals. A dose of nanocarriers of 5 mg·mL −1 has led to a drastic decrease in tumor cell proliferation even in the absence of an antitumor drug (e.g. about 50% viability for MDA-MB 231 cell line and 60% viability for HeLa cell line). A comparative survival profile of normal and tumor cells, which were exposed to an effective dose of 2.5 mg·mL −1 lipid nanocarriers, has revealed a death rate of 20% for normal B16 cells and of 40% death rate for MDA-MB 231 and HeLa tumor cells. The results in this study imply that lipid nanocarriers based on grape seed oil in association with laurel leaf oil could be a candidate to reduce the delivery system toxicity and may significantly improve the therapeutic efficacy of antitumor drugs in clinical applications. - Highlights: • Functional lipid nanocarriers with unique features and broad spectrum effectiveness • Lipid nanocarriers based on laureal leaf oil (LLO) and grape seed oil (GSO) • Antioxidant activity has reached 98% for nanocarriers containing 25% GSO and 2% LLO. • LLO exerts a significant cytotoxic effect against HeLa and MDA-MB 231 tumor cells. • 50

  14. Lipid nanocarriers based on natural oils with high activity against oxygen free radicals and tumor cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Lacatusu, I.; Badea, N.; Badea, G.; Oprea, O. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No 1, 011061 Bucharest (Romania); Mihaila, M.A. [Institute of Virusology “Stefan S. Nicolau”, Center of Immunology, Bravu Road, No. 285, 030304 Bucharest (Romania); Kaya, D.A. [Department of Field Crops, Faculty of Agriculture, Mustafa Kemal University, 31030 Antakya, Hatay (Turkey); Stan, R., E-mail: rl_stan2000@yahoo.com [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No 1, 011061 Bucharest (Romania); Meghea, A. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No 1, 011061 Bucharest (Romania)

    2015-11-01

    The development of nano-dosage forms of phytochemicals represents a significant progress of the scientific approach in the biomedical research. The aim of this study was to assess the effectiveness of lipid nanocarriers based on natural oils (grape seed oil, fish oil and laurel leaf oil) in counteracting free radicals and combating certain tumor cells. No drug was encapsulated in the nanocarriers. The cytotoxic effect exerted by bioactive nanocarriers against two tumor cells, MDA-MB 231 and HeLa cell lines, and two normal cells, L929 and B16 cell lines, was measured using the MTT assay, while oxidative damage was assessed by measuring the total antioxidant activity using chemiluminescence analysis. The best performance was obtained for nanocarriers based on an association of grape seed and laurel leaf oils, with a capacity to scavenge about 98% oxygen free radicals. A dose of nanocarriers of 5 mg·mL{sup −1} has led to a drastic decrease in tumor cell proliferation even in the absence of an antitumor drug (e.g. about 50% viability for MDA-MB 231 cell line and 60% viability for HeLa cell line). A comparative survival profile of normal and tumor cells, which were exposed to an effective dose of 2.5 mg·mL{sup −1} lipid nanocarriers, has revealed a death rate of 20% for normal B16 cells and of 40% death rate for MDA-MB 231 and HeLa tumor cells. The results in this study imply that lipid nanocarriers based on grape seed oil in association with laurel leaf oil could be a candidate to reduce the delivery system toxicity and may significantly improve the therapeutic efficacy of antitumor drugs in clinical applications. - Highlights: • Functional lipid nanocarriers with unique features and broad spectrum effectiveness • Lipid nanocarriers based on laureal leaf oil (LLO) and grape seed oil (GSO) • Antioxidant activity has reached 98% for nanocarriers containing 25% GSO and 2% LLO. • LLO exerts a significant cytotoxic effect against HeLa and MDA-MB 231 tumor

  15. Hyperbaric oxygen and radiotherapy

    International Nuclear Information System (INIS)

    Mayer, R.; Hamilton-Farrell, M.R.; Kleij, A.J. van der

    2005-01-01

    Background: Hyperbaric oxygen (HBO) therapy is the inhalation of 100% oxygen at a pressure of at least 1.5 atmospheres absolute (150 kPa). It uses oxygen as a drug by dissolving it in the plasma and delivering it to the tissues independent of hemoglobin. For a variety of organ systems, HBO is known to promote new vessel growth into areas with reduced oxygen tension due to poor vascularity, and therewith promotes wound healing and recovery of radiation-injured tissue. Furthermore, tumors may be sensitized to irradiation by raising intratumoral oxygen tensions. Methods: A network of hyperbaric facilities exists in Europe, and a number of clinical studies are ongoing. The intergovernmental framework COST B14 action 'Hyperbaric Oxygen Therapy' started in 1999. The main goal of the Working Group Oncology is preparation and actual implementation of prospective study protocols in the field of HBO and radiation oncology in Europe. Results: In this paper a short overview on HBO is given and the following randomized clinical studies are presented: (a) reirradiation of recurrent squamous cell carcinoma of the head and neck after HBO sensitization; (b) role of HBO in enhancing radiosensitivity on glioblastoma multiforme; (c) osseointegration in irradiated patients; adjunctive HBO to prevent implant failures; (d) the role of HBO in the treatment of late irradiation sequelae in the pelvic region. The two radiosensitization protocols (a, b) allow a time interval between HBO and subsequent irradiation of 10-20 min. Conclusion: Recruitment of centers and patients is being strongly encouraged, detailed information is given on www.oxynet.org. (orig.)

  16. Serum Tumor Necrosis Factor-alpha associates with Myocardial Oxygen Demand and Exercise Tolerance in Postmenopausal Women.

    Science.gov (United States)

    Carter, Stephen J; Bryan, David R; Neumeier, William H; Glasser, Stephen P; Hunter, Gary R

    2018-01-01

    The functional implications of serum tumor necrosis factor-alpha (TNF-α), a marker of oxidative stress, on hemodynamic parameters at rest and during physical exertion are unclear. The aims of this investigation were to examine the independent associations of TNF-α on myocardial oxygen demand at rest and during submaximal exercise, while also evaluating the association of TNF-α on exercise tolerance. Forty, postmenopausal women, provided blood samples and completed a modified-Balke protocol to measure maximal oxygen uptake (VO 2max ). Large artery compliance was measured by pulse contour analyses while rate-pressure product (RPP), an index of myocardial oxygen demand, was measured at rest and during two submaximal workloads (i.e., ≈55% and ≈75% VO 2max ). RPP was calculated by dividing the product of heart rate and systolic blood pressure (via auscultation) by 100. Exercise tolerance corresponded with the cessation of the graded exercise test. During higher-intensity exertion, ≈75% VO 2max , multiple linear regression revealed a positive association ( r = 0.43; p = 0.015) between TNF-α and RPP while adjusting for maximal heart rate, VO 2max , large artery compliance, and percent body fat. Path analyses revealed a significant indirect effect of large artery compliance on exercise tolerance through TNF-α, β = 0.13, CI [0.03, 0.35], indicating greater levels of TNF-α associated with poorer exercise tolerance. These data suggest TNF-α independently associates with myocardial oxygen demand during physical exertion, thus highlighting the utility of higher-intensity efforts to expose important phenomena not apparent at rest. TNF-α also appears to be indirectly associated with the link between large artery compliance and exercise tolerance.

  17. Reactive oxygen species responsive drug releasing nanoparticle based on chondroitin sulfate-anthocyanin nanocomplex for efficient tumor therapy.

    Science.gov (United States)

    Jeong, Dooyong; Bae, Byoung-Chan; Park, Sin-Jung; Na, Kun

    2016-01-28

    To develop a reactive oxygen species (ROS) sensitive drug carrier, a chondroitin sulfate (CS)-anthocyanin (ATC) based nanocomplex was developed. Doxorubicin hydrochloride (DOX) was loaded in the CS-ATC nanocomplex (CS-ATC-DOX) via intermolecular stacking interaction. The nanocomplex was fabricated by a simple mixing method in the aqueous phase. The morphology and size of CS-ATC-DOX were determined by ATC content. In the group with 1.5mg/ml of ATC loaded CS-ATC-DOX (CS-ATC2-DOX), the drug content and loading efficiency were 8.5% and 99.1%, respectively. The ROS sensitive drug release of CS-ATC2-DOX was confirmed under in vitro physiological conditions. The results demonstrated that 1.67 times higher DOX release occurred in CS-ATC2-DOX for 48h compared to CS-DOX (ATC absent sample). Drug release and nanocomplex destruction were induced by ROS mediated ATC degradation. We determined that 66.7% of ROS was scavenged by CS-ATC2-DOX. Additionally, an HCT-116 tumor bearing animal model was used to confirm ROS sensitive therapeutic effects of CS-ATC2-DOX. The results indicate that DOX was released from the intravenously injected CS-ATC2-DOX in the tumor tissue. Thus, nuclei shrinkage and dead cells were observed in H&E staining and TUNEL assay, respectively. These data suggest that the tumor growth was effectively inhibited. This study means that CS-ATC2-DOX has potential in improving tumor therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Implantable oxygen microelectrode suitable for medium-term investigations of post-surgical tissue hypoxia and changes in tumor tissue oxygenation produced by radiotherapy

    International Nuclear Information System (INIS)

    Burke, T.R.; Johnson, R.J.; Krishnamsetty, C.B.; Sako, K.; Karakousis, C.; Wojtas, F.

    1980-01-01

    Teflon-covered platinum oxygen probes were used to monitor tissue oxygen levels in post-surgical cancer patients and those treated with radiotherapy. Progressive wound healing was usually accompanied by a decrease in tissue pO2. Radiotherapy produced a slight increase in pO2 while hyperthermia effected a significant increase in the oxygen level during 100% oxygen breathing

  19. Study of cerebral blood flow and oxygen utilization in the edematous area and ipsilateral hemispheric gray matter using positron emission tomography in brain tumors

    International Nuclear Information System (INIS)

    Ikeda, Yusuke

    1990-01-01

    We measured the cerebral blood flow and oxygen utilization of the peritumoral white matter and ipsilateral hemispheric gray matter in 50 patients with brain tumors using Positron Emission Tomography (PET). The intraaxial tumors consisted of 34 cases (25 of gliomas, 6 of metastatic tumors, and 3 others), white the extraaxial tumors (all of meningiomas) were 16 cases. The cases were divided into 2 groups on the basis of the Xray CT scan findings. The cases of Edema (+) group showed moderate or large peritumoral edema in the white matter on the Xray CT scan, while Edema (-) group showed no or small edema. The method of PET study was the 15 O steady state inhalation technique by Frackoviak's method. ROIs (region of interest) were set on the peritumoral white matter and the ipsilateral hemispheric gray matter, and the mean CBF, OEF and CMRO2 values of the white and gray matter were calculated. In the Edema (+) group, the mean values of blood flow and oxygen utilization were low in the peritumoral white matter, and there were no obvious differences of values between intra and extraaxial tumors. But, the values in the ipsilateral hemispheric gray matter of intraaxial tumors were lower than those of extraaxial tumor. In the Edema (-) group, the mean values were almost normal in the white and gray matter, and there were no differences between intra and extraaxial tumors. The consideration about significance of the above stated results was discussed added with literature. (author)

  20. EPR oxygen imaging and hyperpolarized 13C MRI of pyruvate metabolism as non-invasive biomarkers of tumor treatment response to a glycolysis inhibitor 3-bromopyruvate

    Science.gov (United States)

    Matsumoto, Shingo; Saito, Keita; Yasui, Hironobu; Morris, H. Douglas; Munasinghe, Jeeva P.; Lizak, Martin; Merkle, Hellmut; Ardenkjaer-Larsen, Jan Henrik; Choudhuri, Rajani; Devasahayam, Nallathamby; Subramanian, Sankaran; Koretsky, Alan P.; Mitchell, James B.; Krishna, Murali C.

    2012-01-01

    The hypoxic nature of tumors results in treatment resistance and poor prognosis. To spare limited oxygen for more crucial pathways, hypoxic cancerous cells suppress mitochondrial oxidative phosphorylation, and promote glycolysis for energy production. Thereby, inhibition of glycolysis has the potential to overcome treatment resistance of hypoxic tumors. Here, EPR imaging was used to evaluate oxygen dependent efficacy on hypoxia-sensitive drug. The small molecule 3-bromopyruvate (3-BP) blocks glycolysis pathway by inhibiting hypoxia inducible enzymes, and enhanced cytotoxicity of 3-BP under hypoxic conditions has been reported in vitro. However, the efficacy of 3-BP was substantially attenuated in hypoxic tumor regions (pO2 < 10 mmHg) in vivo using squamous cell carcinoma (SCCVII)-bearing mouse model. Metabolic MRI studies using hyperpolarized 13C-labeled pyruvate showed that monocarboxylate transporter-1 (MCT1) is the major transporter for pyruvate and the analog 3-BP in SCCVII tumor. The discrepant results between in vitro and in vivo data were attributed to biphasic oxygen dependent expression of MCT1 in vivo. Expression of MCT1 was enhanced in moderately hypoxic (8–15 mmHg) tumor regions, but down regulated in severely hypoxic (< 5 mmHg) tumor regions. These results emphasize the importance of non-invasive imaging biomarkers to confirm the action of hypoxia-activated drugs. PMID:22692861

  1. EPR oxygen imaging and hyperpolarized 13C MRI of pyruvate metabolism as noninvasive biomarkers of tumor treatment response to a glycolysis inhibitor 3-bromopyruvate.

    Science.gov (United States)

    Matsumoto, Shingo; Saito, Keita; Yasui, Hironobu; Morris, H Douglas; Munasinghe, Jeeva P; Lizak, Martin; Merkle, Hellmut; Ardenkjaer-Larsen, Jan Henrik; Choudhuri, Rajani; Devasahayam, Nallathamby; Subramanian, Sankaran; Koretsky, Alan P; Mitchell, James B; Krishna, Murali C

    2013-05-01

    The hypoxic nature of tumors results in treatment resistance and poor prognosis. To spare limited oxygen for more crucial pathways, hypoxic cancerous cells suppress mitochondrial oxidative phosphorylation and promote glycolysis for energy production. Thereby, inhibition of glycolysis has the potential to overcome treatment resistance of hypoxic tumors. Here, EPR imaging was used to evaluate oxygen dependent efficacy on hypoxia-sensitive drug. The small molecule 3-bromopyruvate blocks glycolysis pathway by inhibiting hypoxia inducible enzymes and enhanced cytotoxicity of 3-bromopyruvate under hypoxic conditions has been reported in vitro. However, the efficacy of 3-bromopyruvate was substantially attenuated in hypoxic tumor regions (pO23-bromopyruvate in SCCVII tumor. The discrepant results between in vitro and in vivo data were attributed to biphasic oxygen dependent expression of monocarboxylate transporter-1 in vivo. Expression of monocarboxylate transporter-1 was enhanced in moderately hypoxic (8-15 mmHg) tumor regions but down regulated in severely hypoxic (<5 mmHg) tumor regions. These results emphasize the importance of noninvasive imaging biomarkers to confirm the action of hypoxia-activated drugs. Copyright © 2012 Wiley Periodicals, Inc.

  2. Experimental studies on radiation effects under high pressure oxygen

    Energy Technology Data Exchange (ETDEWEB)

    Fujimura, E [Osaka Univ. (Japan). School of Dentistry

    1974-06-01

    The effect of oxygen tension on the radiosensitivity of tumor cells is well known, but its clinical application for radiotherapy is not yet established. Rabbits with V x 2 carcinoma in the maxilla were irradiated by /sup 60/Co under high pressure oxygen (experimental group), and compared with those treated in air (control group). For the purpose of examining the clinical effects of high pressure oxygen, an experiment was made in vivo. The following items were compared respectively: a) Tumor regression effect b) Tumor clearance rate c) Survival days d) Half size reduction time e) Inhibition of DNA synthesis in the tumor tissue. Results obtained were as follows: a) 56 per cent of animals showed tumor regression in the experimental group, whereas it occured 26 per cent in the control group. b) 53 per cent of animals showed tumor disappearance in the experimental group, while it was observed only in 13 per cent in the control group. c) Only 2 of 30 rabbits irradiated in air survived over 180 days, whereas 11 of 30 rabbits survived meanwhile in the group irradiated under high pressure oxygen. d) About 11 days were necessary to reduce the tumor size by half after irradiation in the group under high pressure oxygen, while it took 17 days in the group treated in normal air. e) DNA synthesis was inhibited more prominently in the group irradiated under high pressure oxygen in normal air.

  3. Radiation-induced DNA damage in tumors and normal tissues. II. Influence of dose, residual DNA damage and physiological factors in oxygenated cells

    International Nuclear Information System (INIS)

    Zhang, H.; Wheeler, K.T.

    1994-01-01

    Detection and quantification of hypoxic cells in solid tumors is important for many experimental and clinical situations. Several laboratories, including ours, have suggested that assays which measure radiation-induced DNA strand breaks and DNA-protein crosslinks (DPCs) might be used to detect or quantify hypoxic cells in tumors and normal tissues. Recently, we demonstrated the feasibility of using an alkaline elution assay that measures strand breaks and DPCs to detect and/or quantify hypoxic cells in tissues. For this approach to be valid, DPCs must not be formed to any great extent in irradiated oxygenated cells, and the formation and repair of strand breaks and DPCs in oxygenated cells must not be modified appreciably by physiological factors (e.g., temperature, pH and nutrient depletion) that are often found in solid tumors. To address these issues, two sets of experiments were performed. In one set of experiments, oxygenated 9L cells in tissue culture, subcutaneous 9L tumors and rat cerebella were irradiated with doses of 15 or 50 Gy and allowed to repair until the residual strand break damage was low enough to detect DPCs. In another set of experiments, oxygenated exponentially growing or plateau-phase 9L cells in tissue culture were irradiated with a dose of 15 Gy at 37 or 20 degrees C, while the cells were maintained at a pH of either 6.6 or 7.3. DNA-protein crosslinks were formed in oxygenated cells about 100 times less efficiently than in hypoxic cells. In addition, temperature, pH, nutrient depletion and growth phase did not appreciably alter the formation and repair of strand breaks or the formation of DPCs in oxygenated 9L cells. These results support the use of this DNA damage assay for the detection and quantification of hypoxic cells in solid tumors. 27 refs., 5 tabs

  4. On developing a thesis for Reproductive Endocrinology and Infertility fellowship: a case study of ultra-low (2%) oxygen tension for extended culture of human embryos.

    Science.gov (United States)

    Kaser, Daniel J

    2017-03-01

    Fellows in Reproductive Endocrinology and Infertility training are expected to complete 18 months of clinical, basic, or epidemiological research. The goal of this research is not only to provide the basis for the thesis section of the oral board exam but also to spark interest in reproductive medicine research and to provide the next generation of physician-scientists with a foundational experience in research design and implementation. Incoming fellows often have varying degrees of training in research methodology and, likewise, different career goals. Ideally, selection of a thesis topic and mentor should be geared toward defining an "answerable" question and building a practical skill set for future investigation. This contribution to the JARG Young Investigator's Forum revisits the steps of the scientific method through the lens of one recently graduated fellow and his project aimed to test the hypothesis that "sequential oxygen exposure (5% from days 1 to 3, then 2% from days 3 to 5) improves blastocyst yield and quality compared to continuous exposure to 5% oxygen among human preimplantation embryos."

  5. Optical imaging of tumor hypoxia dynamics

    Science.gov (United States)

    Palmer, Gregory M.; Fontanella, Andrew N.; Zhang, Guoqing; Hanna, Gabi; Fraser, Cassandra L.; Dewhirst, Mark W.

    2010-11-01

    The influence of the tumor microenvironment and hypoxia plays a significant role in determining cancer progression, treatment response, and treatment resistance. That the tumor microenvironment is highly heterogeneous with significant intratumor and intertumor variability presents a significant challenge in developing effective cancer therapies. Critical to understanding the role of the tumor microenvironment is the ability to dynamically quantify oxygen levels in the vasculature and tissue in order to elucidate the roles of oxygen supply and consumption, spatially and temporally. To this end, we describe the use of hyperspectral imaging to characterize hemoglobin absorption to quantify hemoglobin content and oxygen saturation, as well as dual emissive fluorescent/phosphorescent boron nanoparticles, which serve as ratiometric indicators of tissue oxygen tension. Applying these techniques to a window-chamber tumor model illustrates the role of fluctuations in hemoglobin saturation in driving changes in tissue oxygenation, the two being significantly correlated (r = 0.77). Finally, a green-fluorescence-protein reporter for hypoxia inducible factor-1 (HIF-1) provides an endpoint for hypoxic stress in the tumor, which is used to demonstrate a significant association between tumor hypoxia dynamics and HIF-1 activity in an in vivo demonstration of the technique.

  6. Intra-operative tissue oxygen tension is increased by local insufflation of humidified-warm CO2 during open abdominal surgery in a rat model.

    Directory of Open Access Journals (Sweden)

    Jean K Marshall

    Full Text Available Maintenance of high tissue oxygenation (PtO2 is recommended during surgery because PtO2 is highly predictive of surgical site infection and colonic anastomotic leakage. However, surgical site perfusion is often sub-optimal, creating an obstructive hurdle for traditional, systemically applied therapies to maintain or increase surgical site PtO2. This research tested the hypothesis that insufflation of humidified-warm CO2 into the abdominal cavity would increase sub-peritoneal PtO2 during open abdominal surgery.15 Wistar rats underwent laparotomy under general anesthesia. Three sets of randomized cross-over experiments were conducted in which the abdominal cavity was subjected to alternating exposure to 1 humidified-warm CO2 & ambient air; 2 humidified-warm CO2 & dry-cold CO2; and 3 dry-cold CO2 & ambient air. Sub-peritoneal PtO2 and tissue temperature were measured with a polarographic oxygen probe.Upon insufflation of humidified-warm CO2, PtO2 increased by 29.8 mmHg (SD 13.3; p<0.001, or 96.6% (SD 51.9, and tissue temperature by 3.0°C (SD 1.7 p<0.001, in comparison with exposure to ambient air. Smaller, but significant, increases in PtO2 were seen in experiments 2 and 3. Tissue temperature decreased upon exposure to dry-cold CO2 compared with ambient air (-1.4°C, SD 0.5, p = 0.001.In a rat model, insufflation of humidified-warm CO2 into the abdominal cavity during open abdominal surgery causes an immediate and potentially clinically significant increase in PtO2. The effect is an additive result of the delivery of CO2 and avoidance of evaporative cooling via the delivery of the CO2 gas humidified at body temperature.

  7. Pivotal Roles of Ginsenoside Rg3 in Tumor Apoptosis Through Regulation of Reactive Oxygen Species.

    Science.gov (United States)

    Sun, Hwa Yeon; Lee, Jun Hee; Han, Yong-Seok; Yoon, Yeo Min; Yun, Chul Won; Kim, Jae Heon; Song, Yun Seob; Lee, Sang Hun

    2016-09-01

    Elevated production of reactive oxygen species (ROS) is observed in various cancer types and pathophysiological conditions. In cancer cells, ROS induce cell proliferation, genetic instability, and a malignant phenotype. Ginsenoside Rg3 is the main pharmacologically active component in ginseng and has been reported to have an antioxidant effect. To overcome lung cancer by regulating the ROS level, we investigated the antitumor effect and mechanism of Rg3 and its antioxidative property on Lewis lung carcinoma (LLC) cells. Inhibition of ROS was suppressed in LLC cells by Rg3 treatment, and these cells were used to investigate the antioxidant, antiproliferative, and antitumor effects in LLC cells. ROS production was increased in cells grown in serum-containing media (conditioned media) compared to those grown in serum-free media. The high level of ROS induced LLC cell proliferation, but treatment with Rg3 (200 ng/ml) resulted in reduction of ROS, leading to inhibition of cell proliferation. Treatment with Rg3 significantly reduced cyclin and cyclin-dependent kinase expression in LLC cells. Additionally, Rg3 treatment significantly suppressed activation of mitogen-activated protein kinases and induced LLC cell apoptosis through activation of pro-apoptotic proteins and suppression of anti-apoptotic proteins. Taken together, these findings demonstrate the role of Rg3 in reduction of the intracellular ROS level, attenuation of proliferation via augmentation of cell cycle- and cell proliferation-associated proteins, and activation of apoptosis through regulation of apoptosis-associated proteins in LLC. These findings suggest that Rg3 could be used as a therapeutic agent in lung cancer. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  8. Monitoring Tumor Response to Carbogen Breathing by Oxygen-Sensitive Magnetic Resonance Parameters to Predict the Outcome of Radiation Therapy: A Preclinical Study

    Energy Technology Data Exchange (ETDEWEB)

    Cao-Pham, Thanh-Trang; Tran, Ly-Binh-An; Colliez, Florence; Joudiou, Nicolas [Université Catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Brussels (Belgium); El Bachiri, Sabrina [Université Catholique de Louvain, IMMAQ Technological Platform, Methodology and Statistical Support, Louvain-la-Neuve (Belgium); Grégoire, Vincent [Université Catholique de Louvain, Institute of Experimental and Clinical Research, Center for Molecular Imaging, Radiotherapy and Oncology, Brussels (Belgium); Levêque, Philippe; Gallez, Bernard [Université Catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Brussels (Belgium); Jordan, Bénédicte F., E-mail: benedicte.jordan@uclouvain.be [Université Catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Brussels (Belgium)

    2016-09-01

    Purpose: In an effort to develop noninvasive in vivo methods for mapping tumor oxygenation, magnetic resonance (MR)-derived parameters are being considered, including global R{sub 1}, water R{sub 1}, lipids R{sub 1}, and R{sub 2}*. R{sub 1} is sensitive to dissolved molecular oxygen, whereas R{sub 2}* is sensitive to blood oxygenation, detecting changes in dHb. This work compares global R{sub 1}, water R{sub 1}, lipids R{sub 1}, and R{sub 2}* with pO{sub 2} assessed by electron paramagnetic resonance (EPR) oximetry, as potential markers of the outcome of radiation therapy (RT). Methods and Materials: R{sub 1}, R{sub 2}*, and EPR were performed on rhabdomyosarcoma and 9L-glioma tumor models, under air and carbogen breathing conditions (95% O{sub 2}, 5% CO{sub 2}). Because the models demonstrated different radiosensitivity properties toward carbogen, a growth delay (GD) assay was performed on the rhabdomyosarcoma model and a tumor control dose 50% (TCD50) was performed on the 9L-glioma model. Results: Magnetic resonance imaging oxygen-sensitive parameters detected the positive changes in oxygenation induced by carbogen within tumors. No consistent correlation was seen throughout the study between MR parameters and pO{sub 2}. Global and lipids R{sub 1} were found to be correlated to pO{sub 2} in the rhabdomyosarcoma model, whereas R{sub 2}* was found to be inversely correlated to pO{sub 2} in the 9L-glioma model (P=.05 and .03). Carbogen increased the TCD50 of 9L-glioma but did not increase the GD of rhabdomyosarcoma. Only R{sub 2}* was predictive (P<.05) for the curability of 9L-glioma at 40 Gy, a dose that showed a difference in response to RT between carbogen and air-breathing groups. {sup 18}F-FAZA positron emission tomography imaging has been shown to be a predictive marker under the same conditions. Conclusion: This work illustrates the sensitivity of oxygen-sensitive R{sub 1} and R{sub 2}* parameters to changes in tumor oxygenation. However, R{sub 1

  9. Monitoring Tumor Response to Carbogen Breathing by Oxygen-Sensitive Magnetic Resonance Parameters to Predict the Outcome of Radiation Therapy: A Preclinical Study

    International Nuclear Information System (INIS)

    Cao-Pham, Thanh-Trang; Tran, Ly-Binh-An; Colliez, Florence; Joudiou, Nicolas; El Bachiri, Sabrina; Grégoire, Vincent; Levêque, Philippe; Gallez, Bernard; Jordan, Bénédicte F.

    2016-01-01

    Purpose: In an effort to develop noninvasive in vivo methods for mapping tumor oxygenation, magnetic resonance (MR)-derived parameters are being considered, including global R_1, water R_1, lipids R_1, and R_2*. R_1 is sensitive to dissolved molecular oxygen, whereas R_2* is sensitive to blood oxygenation, detecting changes in dHb. This work compares global R_1, water R_1, lipids R_1, and R_2* with pO_2 assessed by electron paramagnetic resonance (EPR) oximetry, as potential markers of the outcome of radiation therapy (RT). Methods and Materials: R_1, R_2*, and EPR were performed on rhabdomyosarcoma and 9L-glioma tumor models, under air and carbogen breathing conditions (95% O_2, 5% CO_2). Because the models demonstrated different radiosensitivity properties toward carbogen, a growth delay (GD) assay was performed on the rhabdomyosarcoma model and a tumor control dose 50% (TCD50) was performed on the 9L-glioma model. Results: Magnetic resonance imaging oxygen-sensitive parameters detected the positive changes in oxygenation induced by carbogen within tumors. No consistent correlation was seen throughout the study between MR parameters and pO_2. Global and lipids R_1 were found to be correlated to pO_2 in the rhabdomyosarcoma model, whereas R_2* was found to be inversely correlated to pO_2 in the 9L-glioma model (P=.05 and .03). Carbogen increased the TCD50 of 9L-glioma but did not increase the GD of rhabdomyosarcoma. Only R_2* was predictive (P<.05) for the curability of 9L-glioma at 40 Gy, a dose that showed a difference in response to RT between carbogen and air-breathing groups. "1"8F-FAZA positron emission tomography imaging has been shown to be a predictive marker under the same conditions. Conclusion: This work illustrates the sensitivity of oxygen-sensitive R_1 and R_2* parameters to changes in tumor oxygenation. However, R_1 parameters showed limitations in terms of predicting the outcome of RT in the tumor models studied, whereas R_2* was found to be

  10. Effect of culture at low oxygen tension on the expression of heat shock proteins in a panel of melanoma cell lines.

    Directory of Open Access Journals (Sweden)

    Christopher Shipp

    Full Text Available Tumours are commonly hypoxic and this can be associated with aggressive tumour type, metastasis and resistance to therapy. Heat shock proteins (hsps are induced in response to hypoxia, provide cancer cells with protection against tumour-associated stressors and chaperone oncoproteins that drive tumour proliferation. This study examined the effect of different oxygen concentrations on the expression of hsps in melanoma cell lines.Melanoma cell lines were cultured in 2% and 20% O(2. Expression of Hsp90, Hsp70, Hsp60, Hsp40 and Hsp32 proteins were determined by flow cytometry.Growth rates and viability were reduced in the majority of cell lines by culture in 2% O(2. Hsp expression was different in 2% compared to 20% O(2 and changes in Hsp90 expression correlated with cell line generation time (P<0.005 and viability (P<0.01. Greater total hsp expression correlated with improved viability in 2% but not 20% O(2 (P<0.05. Relative expression of the different hsps was consistent across cell lines and each correlated with the others (P = 0.0001 but not with Hsp32. Hsp expression was inversely correlated with cell line adhesion to laminin as well as collagen type IV and Breslow depth of the original primary tumour tissue (P<0.05, but not with Clark level or patient survival. All five hsps were identified on the cell surface.Culture in 2% O(2 variably altered hsp expression in a panel of melanoma cell lines. Hsp expression was associated with certain cell line characteristics and clinical parameters of the originating tumour.

  11. Effects of hyperoxia on 18F-fluoro-misonidazole brain uptake and tissue oxygen tension following middle cerebral artery occlusion in rodents: Pilot studies.

    Directory of Open Access Journals (Sweden)

    Tim D Fryer

    Full Text Available Mapping brain hypoxia is a major goal for stroke diagnosis, pathophysiology and treatment monitoring. 18F-fluoro-misonidazole (FMISO positron emission tomography (PET is the gold standard hypoxia imaging method. Normobaric hyperoxia (NBO is a promising therapy in acute stroke. In this pilot study, we tested the straightforward hypothesis that NBO would markedly reduce FMISO uptake in ischemic brain in Wistar and spontaneously hypertensive rats (SHRs, two rat strains with distinct vulnerability to brain ischemia, mimicking clinical heterogeneity.Thirteen adult male rats were randomized to distal middle cerebral artery occlusion under either 30% O2 or 100% O2. FMISO was administered intravenously and PET data acquired dynamically for 3hrs, after which magnetic resonance imaging (MRI and tetrazolium chloride (TTC staining were carried out to map the ischemic lesion. Both FMISO tissue uptake at 2-3hrs and FMISO kinetic rate constants, determined based on previously published kinetic modelling, were obtained for the hypoxic area. In a separate group (n = 9, tissue oxygen partial pressure (PtO2 was measured in the ischemic tissue during both control and NBO conditions.As expected, the FMISO PET, MRI and TTC lesion volumes were much larger in SHRs than Wistar rats in both the control and NBO conditions. NBO did not appear to substantially reduce FMISO lesion size, nor affect the FMISO kinetic rate constants in either strain. Likewise, MRI and TTC lesion volumes were unaffected. The parallel study showed the expected increases in ischemic cortex PtO2 under NBO, although these were small in some SHRs with very low baseline PtO2.Despite small samples, the apparent lack of marked effects of NBO on FMISO uptake suggests that in permanent ischemia the cellular mechanisms underlying FMISO trapping in hypoxic cells may be disjointed from PtO2. Better understanding of FMISO trapping processes will be important for future applications of FMISO imaging.

  12. Radiation-induced DNA damage in tumors and normal tissues. III. Oxygen dependence of the formation of strand breaks and DNA-protein crosslinks

    International Nuclear Information System (INIS)

    Zhang, H.; Wallen, C.A.; Wheeler, K.T.; Joch, C.J.

    1995-01-01

    Results from several laboratories, including ours, have suggested that measurements of radiation-induced DNA strand breaks and DNA-protein crosslinks (DPCs) may be used to estimate the hypoxic fraction or fractional hypoxic volume of tumors and normal tissues. This suggestion has been predicated on both published and nonpublished information that (1) the oxygen dependence of the formation of strand breaks in irradiated mammalian cells is similar to the oxygen dependence of radiation-produced cell killing, and (2) the oxygen dependence of the formation of DPCs in irradiated mammalian cells is the mirror image of the oxygen dependence of radiation-induced cell killing. However, the published studies that attempted to determine the relationship between the oxygen dependence of the formation of strand breaks and the radiation sensitivity of mammalian cells were not performed at 37 degrees C, the exact oxygen concentrations were not always known, and the results were conflicting. In addition, most of the data on the oxygen dependence of the formation of DPCs are unpublished. Consequently, we have undertaken a comprehensive investigation of one cell line, 9L/Ro rat brain tumor cells, to determine if the shape of the oxygen dependence curve and the K m value for radiation-induced strand breaks and DPCs were similar when 9L cells were irradiated under both ideal gas-liquid equilibrium conditions at 4 degrees C and nonideal gas-liquid equilibrium conditions at 37 degrees C. At 4 degrees C under ideal gas-liquid equilibrium conditions, the K m for the formation of strand breaks was approximately 0.0045 mM, and Km for radiation sensitivity was approximately 0.005mM. A similar comparison for the formation of DPCs at 4 degrees C could not be made, because the efficiency of the formation of DPC was much lower at 4 degrees C than at 37 degrees C. 30 refs., 3 figs

  13. Evaluation and Immunohistochemical Qualification of Carbogen-Induced ΔR{sub 2}* as a Noninvasive Imaging Biomarker of Improved Tumor Oxygenation

    Energy Technology Data Exchange (ETDEWEB)

    Baker, Lauren C.J., E-mail: lauren.baker@icr.ac.uk [Cancer Research UK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey (United Kingdom); Boult, Jessica K.R.; Jamin, Yann; Gilmour, Lesley D.; Walker-Samuel, Simon; Burrell, Jake S. [Cancer Research UK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey (United Kingdom); Ashcroft, Margaret [Division of Medicine, Centre for Cell Signalling and Molecular Genetics, University College London, London (United Kingdom); Howe, Franklyn A. [St. George' s, University of London, London (United Kingdom); Griffiths, John R. [Cancer Research UK Cambridge Institute, Cambridge (United Kingdom); Raleigh, James A. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); Kogel, Albert J. van der [University of Nijmegen Medical Centre, Nijmegen (Netherlands); Robinson, Simon P. [Cancer Research UK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey (United Kingdom)

    2013-09-01

    Purpose: To evaluate and histologically qualify carbogen-induced ΔR{sub 2}* as a noninvasive magnetic resonance imaging biomarker of improved tumor oxygenation using a double 2-nitroimidazole hypoxia marker approach. Methods and Materials: Multigradient echo images were acquired from mice bearing GH3 prolactinomas, preadministered with the hypoxia marker CCI-103F, to quantify tumor R{sub 2}* during air breathing. With the mouse remaining positioned within the magnet bore, the gas supply was switched to carbogen (95% O{sub 2}, 5% CO{sub 2}), during which a second hypoxia marker, pimonidazole, was administered via an intraperitoneal line, and an additional set of identical multigradient echo images acquired to quantify any changes in tumor R{sub 2}*. Hypoxic fraction was quantified histologically using immunofluorescence detection of CCI-103F and pimonidazole adduct formation from the same whole tumor section. Carbogen-induced changes in tumor pO{sub 2} were further validated using the Oxylite fiberoptic probe. Results: Carbogen challenge significantly reduced mean tumor R{sub 2}* from 116 ± 13 s{sup −1} to 97 ± 9 s{sup −1} (P<.05). This was associated with a significantly lower pimonidazole adduct area (2.3 ± 1%), compared with CCI-103F (6.3 ± 2%) (P<.05). A significant correlation was observed between ΔR{sub 2}* and Δhypoxic fraction (r=0.55, P<.01). Mean tumor pO{sub 2} during carbogen breathing significantly increased from 6.3 ± 2.2 mm Hg to 36.0 ± 7.5 mm Hg (P<.01). Conclusions: The combined use of intrinsic susceptibility magnetic resonance imaging with a double hypoxia marker approach corroborates carbogen-induced ΔR{sub 2}* as a noninvasive imaging biomarker of increased tumor oxygenation.

  14. Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenation

    International Nuclear Information System (INIS)

    Moen, Ingrid; Øyan, Anne M; Stuhr, Linda EB; Jevne, Charlotte; Wang, Jian; Kalland, Karl-Henning; Chekenya, Martha; Akslen, Lars A; Sleire, Linda; Enger, Per Ø; Reed, Rolf K

    2012-01-01

    The tumor microenvironment is pivotal in tumor progression. Thus, we aimed to develop a mammary tumor model to elucidate molecular characteristics in the stroma versus the tumor cell compartment by global gene expression. Secondly, since tumor hypoxia influences several aspects of tumor pathophysiology, we hypothesized that hyperoxia might have an inhibitory effect on tumor growth per se. Finally, we aimed to identify differences in gene expression and key molecular mechanisms, both in the native state and following treatment. 4T1 dsRed breast cancer cells were injected into eGFP expressing NOD/SCID mice. Group 1 was exposed to 3 intermittent HBO treatments (Day 1, 4 and 7), Group 2 to 7 daily HBO treatments (both 2.5bar, 100% O 2 , à 90 min), whereas the controls were exposed to a normal atmosphere. Tumor growth, histology, vascularisation, cell proliferation, cell death and metastasis were assessed. Fluorescence-activated cell sorting was used to separate tumor cells from stromal cells prior to gene expression analysis. The purity of sorted cells was verified by fluorescence microscopy. Gene expression profiling demonstrated that highly expressed genes in the untreated tumor stroma included constituents of the extracellular matrix and matrix metalloproteinases. Tumor growth was significantly inhibited by HBO, and the MAPK pathway was found to be significantly reduced. Immunohistochemistry indicated a significantly reduced microvessel density after intermittent HBO, whereas daily HBO did not show a similar effect. The anti-angiogenic response was reflected in the expression trends of angiogenic factors. The present in vivo mammary tumor model enabled us to separate tumor and stromal cells, and demonstrated that the two compartments are characterized by distinct gene expressions, both in the native state and following HBO treatments. Furthermore, hyperoxia induced a significant tumor growth-inhibitory effect, with significant down-regulation of the MAPK pathway

  15. HIGD1A Regulates Oxygen Consumption, ROS Production, and AMPK Activity during Glucose Deprivation to Modulate Cell Survival and Tumor Growth

    Directory of Open Access Journals (Sweden)

    Kurosh Ameri

    2015-02-01

    Full Text Available Hypoxia-inducible gene domain family member 1A (HIGD1A is a survival factor induced by hypoxia-inducible factor 1 (HIF-1. HIF-1 regulates many responses to oxygen deprivation, but viable cells within hypoxic perinecrotic solid tumor regions frequently lack HIF-1α. HIGD1A is induced in these HIF-deficient extreme environments and interacts with the mitochondrial electron transport chain to repress oxygen consumption, enhance AMPK activity, and lower cellular ROS levels. Importantly, HIGD1A decreases tumor growth but promotes tumor cell survival in vivo. The human Higd1a gene is located on chromosome 3p22.1, where many tumor suppressor genes reside. Consistent with this, the Higd1a gene promoter is differentially methylated in human cancers, preventing its hypoxic induction. However, when hypoxic tumor cells are confronted with glucose deprivation, DNA methyltransferase activity is inhibited, enabling HIGD1A expression, metabolic adaptation, and possible dormancy induction. Our findings therefore reveal important new roles for this family of mitochondrial proteins in cancer biology.

  16. Measurement of pO2 in a Pre-clinical Model of Rabbit Tumor Using OxyChip, a Paramagnetic Oxygen Sensor.

    Science.gov (United States)

    Hou, H; Khan, N; Kuppusamy, P

    2017-01-01

    The objective of this work was to establish a novel and robust technology, based on electron paramagnetic resonance (EPR) oximetry, as a practical tool for measurement of tumor oxygen. Previously, we have reported on the development of oxygen-sensing paramagnetic crystals (LiNc-BuO) encapsulated in a biocompatible polymer, called OxyChip. In this report we present our recent data on the use of OxyChip for pO 2 measurements in the tumor of a pre-clinical, large-animal rabbit model. The results establish that OxyChip is capable of noninvasive and repeated measurement of pO 2 in a large animal model.

  17. Reactor vessel stud tensioner

    International Nuclear Information System (INIS)

    Malandra, L.J.; Beer, R.W.; Salton, R.B.; Spiegelman, S.R.; Cognevich, M.L.

    1982-01-01

    A quick-acting stud tensioner, for facilitating the loosening or tightening of a stud nut on a reactor vessel stud, has gripper jaws which when the tensioner is lowered into engagement with the upper end of the stud are moved inwards to grip the upper end and which when the tensioner is lifted move outward to release the upper end. (author)

  18. Effects of reactive oxygen species on metabolism monitored by longitudinal 1H single voxel MRS follow-up in patients with mitochondrial disease or cerebral tumors

    International Nuclear Information System (INIS)

    Constans, J M; Collet, S; Hossu, G; Courtheoux, P; Guillamo, J S; Lechapt-Zalcman, E; Valable, S; Lacombe, S; Houee Levin, C; Gauduel, Y A; Dou, W; Ruan, S; Barre, L; Rioult, F; Derlon, J M; Chapon, F; Fong, V; Kauffmann, F

    2011-01-01

    Free radicals, or Reactive Oxygen Species (ROS), have an effect on energy and glycolytic metabolism, mitochondrial function, lipid metabolism, necrosis and apoptosis, cell proliferation, and infiltration. These changes could be monitored longitudinally (every 4 months over 6 years) in humans with glial brain tumors (low and high grade) after therapy, using conventional magnetic resonance imaging (MRI) and spectroscopy (MRS) and MR perfusion. Some examples of early clinical data from longitudinal follow-up monitoring in humans of energy and glycolytic metabolism, lipid metabolism, necrosis, proliferation, and infiltration measured by conventional MRI, MRS and perfusion, and positron emission tomography (PET) are shown in glial brain tumors after therapy. Despite the difficulty, the variability and unknown factors, these repeated measurements give us a better insight into the nature of the different processes, tumor progression and therapeutic response.

  19. Effects of reactive oxygen species on metabolism monitored by longitudinal {sup 1}H single voxel MRS follow-up in patients with mitochondrial disease or cerebral tumors

    Energy Technology Data Exchange (ETDEWEB)

    Constans, J M; Collet, S; Hossu, G; Courtheoux, P [MRI Unit, Caen University Hospital, Caen, Normandy (France); Guillamo, J S; Lechapt-Zalcman, E; Valable, S [CERVOxy Group, CI-NAPS, UMR 6232 CI-NAPS, Cyceron, Caen, Normandy (France); Lacombe, S; Houee Levin, C [Paris-Sud 11 University-CNRS, Orsay (France); Gauduel, Y A [LOA, Ecole Polytechnique - ENSTA ParisTech, Palaiseau (France); Dou, W [Tsinghua University, Beijing (China); Ruan, S [CReSTIC EA 3804, IUT Troyes, Troyes (France); Barre, L [GDMTEP, Group CI-NAPS, UMR 6232 CI-NAPS, Cyceron, Caen (France); Rioult, F [CNRS UMR 6072, GREYC, Caen, Normandy (France); Derlon, J M [Neurosurgery and Neurology, Caen University Hospital, Caen, Normandy (France); Chapon, F [Pathology, Caen University Hospital, Caen, Normandy (France); Fong, V [Caen University (France); Kauffmann, F, E-mail: constans-jm@chu-caen.fr [Mathematics LMNO CNRS UMR 6139, Caen University, Caen, Normandy (France)

    2011-01-01

    Free radicals, or Reactive Oxygen Species (ROS), have an effect on energy and glycolytic metabolism, mitochondrial function, lipid metabolism, necrosis and apoptosis, cell proliferation, and infiltration. These changes could be monitored longitudinally (every 4 months over 6 years) in humans with glial brain tumors (low and high grade) after therapy, using conventional magnetic resonance imaging (MRI) and spectroscopy (MRS) and MR perfusion. Some examples of early clinical data from longitudinal follow-up monitoring in humans of energy and glycolytic metabolism, lipid metabolism, necrosis, proliferation, and infiltration measured by conventional MRI, MRS and perfusion, and positron emission tomography (PET) are shown in glial brain tumors after therapy. Despite the difficulty, the variability and unknown factors, these repeated measurements give us a better insight into the nature of the different processes, tumor progression and therapeutic response.

  20. Prostate tumor-induced angiogenesis is blocked by exosomes derived from menstrual stem cells through the inhibition of reactive oxygen species

    Science.gov (United States)

    Alcayaga-Miranda, Francisca; González, Paz L.; Lopez-Verrilli, Alejandra; Varas-Godoy, Manuel; Aguila-Díaz, Carolina; Contreras, Luis; Khoury, Maroun

    2016-01-01

    Mesenchymal stem cells (MSCs) secrete exosomes that are capable of modifying the tumor environment through different mechanisms including changes in the cancer-cell secretome. This activity depends on their cargo content that is largely defined by their cellular origin. Endometrial cells are fine regulators of the angiogenic process during the menstrual cycle that includes an angiostatic condition that is associated with the end of the cycle. Hence, we studied the angiogenic activity of menstrual stem cells (MenSCs)-secreted exosomes on prostate PC3 tumor cells. Our results showed that exosomes induce a reduction in VEGF secretion and NF-κB activity. Lower reactive oxygen species (ROS) production in exosomes-treated cells was detected by the DCF method, suggesting that the inhibition of the intracellular ROS impacts both NF-κB and VEGF pathways. We confirmed using tubule formation and plug transplantation assays that MenSCs-exosomes suppress the secretion of pro-angiogenic factors by the PC3 cells in a ROS-dependent manner. The inhibition of the tumor angiogenesis and, consequently, the tumor growth was also confirmed using a xenograft mouse model. Additionally, the anti-tumoral effect was associated with a reduction of tumor hemoglobin content, vascular density and inhibition of VEGF and HIF-1α expression. Importantly, we demonstrate that the exosomes anti-angiogenic effect is specific to the menstrual cell source, as bone marrow MSCs-derived exosomes showed an opposite effect on the VEGF and bFGF expression in tumor cells. Altogether, our results indicate that MenSCs-derived exosomes acts as blockers of the tumor-induced angiogenesis and therefore could be suitable for anti-cancer therapies. PMID:27286448

  1. Development of an oxygen-sensitive degradable peptide probe for the imaging of hypoxia-inducible factor-1-active regions in tumors.

    Science.gov (United States)

    Ueda, Masashi; Ogawa, Kei; Miyano, Azusa; Ono, Masahiro; Kizaka-Kondoh, Shinae; Saji, Hideo

    2013-12-01

    We aimed to develop a radiolabeled peptide probe for the imaging of hypoxia-inducible factor-1 (HIF-1)-active tumors. We synthesized the peptide probes that contain or lack an essential sequence of the oxygen-dependent degradation of HIF-1α in proteasomes ((123/125)I-DKOP30 or (125)I-mDKOP, respectively). The degradation of probes was evaluated in vitro using cell lysates containing proteasomes. In vivo biodistribution study, planar imaging, autoradiography, and comparison between probe accumulation and HIF-1 transcriptional activity were also performed. The (125)I-DKOP30 underwent degradation in a proteasome-dependent manner, while (125)I-mDKOP was not degraded. Biodistribution analysis showed (125)I-DKOP30 accumulation in tumors. The tumors were clearly visualized by in vivo imaging, and intratumoral distribution of (125)I-DKOP30 coincided with the HIF-1α-positive hypoxic regions. Tumoral accumulation of (125)I-DKOP30 was significantly correlated with HIF-1-dependent luciferase bioluminescence, while that of (125)I-mDKOP was not. (123)I-DKOP30 is a useful peptide probe for the imaging of HIF-1-active tumors.

  2. Dynamics of tumor oxygenation, CD31 staining and transforming growth factor-β levels after treatment with radiation or cyclophosphamide in the rat 13762 mammary carcinoma

    International Nuclear Information System (INIS)

    Kakeji, Yoshihiro; Maehara, Yoshihiko; Ikebe, Masahiko; Teicher, Beverly A.

    1997-01-01

    Purpose: Tumors are dynamic tissues that undergo marked molecular, biochemical, and physiologic changes in response to cytotoxic anticancer therapies. Understanding the changes in tumor oxygenation and transforming growth factor-β expression may allow improved treatment regimens to be developed. Methods and Materials: The effects of a single dose of radiation therapy (20 Gy) or a single dose of chemotherapy (cyclophosphamide, 250 mg/kg) on several molecular and physiologic parameters of the rat 13762 mammary carcinoma growing subcutaneously in female Fischer 344 rats were explored. Results: Treatment of the tumor-bearing animals with 20 Gy of radiation killed about two logs (99%) of the 13762 tumor cells, and treatment with cyclophosphamide (250 mg/kg) killed about 1.5 logs (95%) of the 13762 tumor cells. Hypoxia, as determined by a pO 2 electrode, initially decreased in the tumors of treated animals until 6 h. posttreatment and then increased, so that 24 h. after administration of the radiation therapy or the chemotherapy the number of intratumoral vessels as determined by CD31 staining increased until about 24 h after cytotoxic therapy. Transforming growth factor-β1, measured by radioimmunoassay, peaked in the serum between 6 h and 18 h and again between 72 h and 96 h after radiation therapy and peaked in the tumor at 24 h and again at 72 h after radiation therapy. The first serum peak after cyclophosphamide was 3 h after drug injection, with second peaks at 36 h and 48 h after drug administration. In the tumor, transforming growth factor-β1 peaked between 6 h and 8 h after drug administration and again 36 h and 72 h after drug. Apoptosis was maximal 6 h after 20 Gy and 24 h after cyclophosphamide. Vascular endothelial growth factor was also increased in tumors after cytotoxic therapy. Conclusions: These changes in the tumor physiologic status are sufficient to protect the tumor from a second cytotoxic insult administered days afterwards and to result in a

  3. Matching the reaction-diffusion simulation to dynamic [18F]FMISO PET measurements in tumors: extension to a flow-limited oxygen-dependent model.

    Science.gov (United States)

    Shi, Kuangyu; Bayer, Christine; Gaertner, Florian C; Astner, Sabrina T; Wilkens, Jan J; Nüsslin, Fridtjof; Vaupel, Peter; Ziegler, Sibylle I

    2017-02-01

    Positron-emission tomography (PET) with hypoxia specific tracers provides a noninvasive method to assess the tumor oxygenation status. Reaction-diffusion models have advantages in revealing the quantitative relation between in vivo imaging and the tumor microenvironment. However, there is no quantitative comparison of the simulation results with the real PET measurements yet. The lack of experimental support hampers further applications of computational simulation models. This study aims to compare the simulation results with a preclinical [ 18 F]FMISO PET study and to optimize the reaction-diffusion model accordingly. Nude mice with xenografted human squamous cell carcinomas (CAL33) were investigated with a 2 h dynamic [ 18 F]FMISO PET followed by immunofluorescence staining using the hypoxia marker pimonidazole and the endothelium marker CD 31. A large data pool of tumor time-activity curves (TAC) was simulated for each mouse by feeding the arterial input function (AIF) extracted from experiments into the model with different configurations of the tumor microenvironment. A measured TAC was considered to match a simulated TAC when the difference metric was below a certain, noise-dependent threshold. As an extension to the well-established Kelly model, a flow-limited oxygen-dependent (FLOD) model was developed to improve the matching between measurements and simulations. The matching rate between the simulated TACs of the Kelly model and the mouse PET data ranged from 0 to 28.1% (on average 9.8%). By modifying the Kelly model to an FLOD model, the matching rate between the simulation and the PET measurements could be improved to 41.2-84.8% (on average 64.4%). Using a simulation data pool and a matching strategy, we were able to compare the simulated temporal course of dynamic PET with in vivo measurements. By modifying the Kelly model to a FLOD model, the computational simulation was able to approach the dynamic [ 18 F]FMISO measurements in the investigated

  4. Tumor-Derived Microvesicles Modulate Antigen Cross-Processing via Reactive Oxygen Species-Mediated Alkalinization of Phagosomal Compartment in Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Federico Battisti

    2017-09-01

    Full Text Available Dendritic cells (DCs are the only antigen-presenting cells able to prime naïve T cells and cross-prime antigen-specific CD8+ T cells. Their functionality is a requirement for the induction and maintenance of long-lasting cancer immunity. Albeit intensively investigated, the in vivo mechanisms underlying efficient antigen cross-processing and presentation are not fully understood. Several pieces of evidence indicate that antigen transfer to DCs mediated by microvesicles (MVs enhances antigen immunogenicity. This mechanism is also relevant for cross-presentation of those tumor-associated glycoproteins such as MUC1 that are blocked in HLA class II compartment when internalized by DCs as soluble molecules. Here, we present pieces of evidence that the internalization of tumor-derived MVs modulates antigen-processing machinery of DCs. Employing MVs derived from ovarian cancer ascites fluid and established tumor cell lines, we show that MV uptake modifies DC phagosomal microenvironment, triggering reactive oxygen species (ROS accumulation and early alkalinization. Indeed, tumor MVs carry radical species and the MV uptake by DCs counteracts the chemically mediated acidification of the phagosomal compartment. Further pieces of evidence suggest that efficacious antigen cross-priming of the MUC1 antigen carried by the tumor MVs results from the early signaling induced by MV internalization and the function of the antigen-processing machinery of DCs. These results strongly support the hypothesis that tumor-derived MVs impact antigen immunogenicity by tuning the antigen-processing machinery of DCs, besides being carrier of tumor antigens. Furthermore, these findings have important implications for the exploitation of MVs as antigenic cell-free immunogen for DC-based therapeutic strategies.

  5. Proton pump inhibitors induce apoptosis of human B-cell tumors through a caspase-independent mechanism involving reactive oxygen species.

    Science.gov (United States)

    De Milito, Angelo; Iessi, Elisabetta; Logozzi, Mariantonia; Lozupone, Francesco; Spada, Massimo; Marino, Maria Lucia; Federici, Cristina; Perdicchio, Maurizio; Matarrese, Paola; Lugini, Luana; Nilsson, Anna; Fais, Stefano

    2007-06-01

    Proton pumps like the vacuolar-type H+ ATPase (V-ATPase) are involved in the control of cellular pH in normal and tumor cells. Treatment with proton pump inhibitors (PPI) induces sensitization of cancer cells to chemotherapeutics via modifications of cellular pH gradients. It is also known that low pH is the most suitable condition for a full PPI activation. Here, we tested whether PPI treatment in unbuffered culture conditions could affect survival and proliferation of human B-cell tumors. First, we showed that PPI treatment increased the sensitivity to vinblastine of a pre-B acute lymphoblastic leukemia (ALL) cell line. PPI, per se, induced a dose-dependent inhibition of proliferation of tumor B cells, which was associated with a dose- and time-dependent apoptotic-like cytotoxicity in B-cell lines and leukemic cells from patients with pre-B ALL. The effect of PPI was mediated by a very early production of reactive oxygen species (ROS), that preceded alkalinization of lysosomal pH, lysosomal membrane permeabilization, and cytosol acidification, suggesting an early destabilization of the acidic vesicular compartment. Lysosomal alterations were followed by mitochondrial membrane depolarization, release of cytochrome c, chromatin condensation, and caspase activation. However, inhibition of caspase activity did not affect PPI-induced cell death, whereas specific inhibition of ROS by an antioxidant (N-acetylcysteine) significantly delayed cell death and protected both lysosomal and mitochondrial membranes. The proapoptotic activity of PPI was consistent with a clear inhibition of tumor growth following PPI treatment of B-cell lymphoma in severe combined immunodeficient mice. This study further supports the importance of acidity and pH gradients in tumor cell homeostasis and suggests new therapeutic approaches for human B-cell tumors based on PPI.

  6. A Case of Pulmonary Tumor Thrombotic Microangiopathy Diagnosed by Transbronchial Lung Biopsy and Treated with Chemotherapy and Long-Term Oxygen and Anticoagulation Therapies

    Directory of Open Access Journals (Sweden)

    Atsushi Kitamura

    2013-01-01

    Full Text Available A 41-year-old woman, who underwent breast resection for cancer of the right breast and adjuvant chemotherapy 2 years ago, was admitted to our hospital due to shortness of breath upon exertion. High-resolution computed tomography of the chest showed small nodular opacities in the peribronchiolar area in both lungs, as well as mediastinal and hilar lymphadenopathy. A transbronchial lung biopsy revealed breast cancer metastasis and pulmonary tumor thrombotic microangiopathy (PTTM. Treatment of PTTM is rarely reported due to the difficulty of antemortem diagnosis; however, the patient was effectively treated with chemotherapy and oxygen and anticoagulation therapies for 3 months.

  7. Tension type headache

    Directory of Open Access Journals (Sweden)

    Debashish Chowdhury

    2012-01-01

    Full Text Available Tension type headaches are common in clinical practice. Earlier known by various names, the diagnosis has had psychological connotations. Recent evidence has helped clarify the neurobiological basis and the disorder is increasingly considered more in the preview of neurologists. The classification, clinical features, differential diagnosis and treatment of tension type headache are discussed in this paper.

  8. Tensions in Distributed Leadership

    Science.gov (United States)

    Ho, Jeanne; Ng, David

    2017-01-01

    Purpose: This article proposes the utility of using activity theory as an analytical lens to examine the theoretical construct of distributed leadership, specifically to illuminate tensions encountered by leaders and how they resolved these tensions. Research Method: The study adopted the naturalistic inquiry approach of a case study of an…

  9. Perfluorocarbon-Loaded Lipid Nanocapsules to Assess the Dependence of U87-Human Glioblastoma Tumor pO2 on In Vitro Expansion Conditions.

    Science.gov (United States)

    Lemaire, Laurent; Nel, Janske; Franconi, Florence; Bastiat, Guillaume; Saulnier, Patrick

    2016-01-01

    Growing tumor cell lines, such as U87-MG glioma cells, under mild hypoxia (3% O2) leads to a ca. 40% reduction in growth rate once implanted in the brain of nude mice, as compared to normoxia (21% O2) grown cells, wherein the former over-express HIF-1 and VEGF-A. Despite developing differently, the tumors have similar: blood perfusion, oxygen consumption, and vascular surface area parameters, whereas the number of blood vessels is nearly doubled in the tumor arising from normoxia cultured cells. Interestingly, tumor oxygen tension, measured using 19F-oximetry, showed that the normoxia grown cells led to tumors characterized by mild hypoxic environment (approximately 4%) conditions, whilst the hypoxia grown cells led to tumors characterized by physioxic environment (approximately 6%) conditions. This reversal in oxygen concentration may be responsible for the apparent paradoxical growth profiles.

  10. Optic nerve oxygenation

    DEFF Research Database (Denmark)

    Stefánsson, Einar; Pedersen, Daniella Bach; Jensen, Peter Koch

    2005-01-01

    The oxygen tension of the optic nerve is regulated by the intraocular pressure and systemic blood pressure, the resistance in the blood vessels and oxygen consumption of the tissue. The oxygen tension is autoregulated and moderate changes in intraocular pressure or blood pressure do not affect...... the optic nerve oxygen tension. If the intraocular pressure is increased above 40 mmHg or the ocular perfusion pressure decreased below 50 mmHg the autoregulation is overwhelmed and the optic nerve becomes hypoxic. A disturbance in oxidative metabolism in the cytochromes of the optic nerve can be seen...... at similar levels of perfusion pressure. The levels of perfusion pressure that lead to optic nerve hypoxia in the laboratory correspond remarkably well to the levels that increase the risk of glaucomatous optic nerve atrophy in human glaucoma patients. The risk for progressive optic nerve atrophy in human...

  11. Effects of the differentiating agents sodium butyrate and N-methylformamide on the oxygen enhancement ratio of human colon tumor cells

    International Nuclear Information System (INIS)

    Hallows, K.R.; Bliven, S.F.; Leith, J.T.

    1988-01-01

    We have previously shown that chronic adaptation of human tumor cells to the differentiation-inducing agents N-methylformamide (NMF) and sodium butyrate (NAB) increases the sensitivity of oxic cells to graded single doses of X rays. These studies were carried out to define the sensitivity of hypoxic cells after adaptation. Clone A colon tumor cells were grown for three passages in medium containing 170 mM NMF or 2 mM NAB and irradiated in suspension culture, after gassing with either oxygen (60 min) or ultrapure nitrogen (90 min), and complete survival curves were generated. Using the linear-quadratic equation to describe the data, it was found that NMF and NAB produced increased X-ray killing of hypoxic cells. At the 10% level of survival, the dose-modifying factors were about 1.20 and 1.25 for NMF- and NAB-adapted hypoxic cells, respectively, as compared to hypoxic control cells. However, since both oxic and hypoxic cells exhibited increased sensitivity after NMF and NAB adaptation, there was no major change in the oxygen enhancement ratio

  12. Development of a novel fluorescent imaging probe for tumor hypoxia by use of a fusion protein with oxygen-dependent degradation domain of HIF-1α

    Science.gov (United States)

    Tanaka, Shotaro; Kizaka-Kondoh, Shinae; Harada, Hiroshi; Hiraoka, Masahiro

    2007-02-01

    More malignant tumors contain more hypoxic regions. In hypoxic tumor cells, expression of a series of hypoxiaresponsive genes related to malignant phenotype such as angiogenesis and metastasis are induced. Hypoxia-inducible factor-1 (HIF-1) is a master transcriptional activator of such genes, and thus imaging of hypoxic tumor cells where HIF-1 is active, is important in cancer therapy. We have been developing PTD-ODD fusion proteins, which contain protein transduction domain (PTD) and the VHL-mediated protein destruction motif in oxygen-dependent degradation (ODD) domain of HIF-1 alpha subunit (HIF-1α). Thus PTD-ODD fusion proteins can be delivered to any tissue in vivo through PTD function and specifically stabilized in hypoxic cells through ODD function. To investigate if PTD-ODD fusion protein can be applied to construct hypoxia-specific imaging probes, we first constructed a fluorescent probe because optical imaging enable us to evaluate a probe easily, quickly and economically in a small animal. We first construct a model fusion porein PTD-ODD-EGFP-Cy5.5 named POEC, which is PTD-ODD protein fused with EGFP for in vitro imaging and stabilization of fusion protein, and conjugated with a near-infrared dye Cy5.5. This probe is designed to be degraded in normoxic cells through the function of ODD domain and followed by quick clearance of free fluorescent dye. On the other hand, this prove is stabilized in hypoxic tumor cells and thus the dye is stayed in the cells. Between normoxic and hypoxic conditions, the difference in the clearance rate of the dye will reveals suited contrast for tumor-hypoxia imaging. The optical imaging probe has not been optimized yet but the results presented here exhibit a potential of PTD-ODD fusion protein as a hypoxia-specific imaging probe.

  13. Closed Loop Control of Oxygen Delivery and Oxygen Generation

    Science.gov (United States)

    2017-08-01

    were used for this study and were connected via a USB cable to allow communication. The ventilator was modified to allow closed loop control of oxygen...connected via a USB cable to allow communication. The ventilator was modified to allow closed loop control of oxygen based on the oxygen saturation...2017-4119, 28 Aug 2017. oximetry (SpO2) and intermittent arterial blood sampling for arterial oxygen tension (partial pressure of oxygen [PaO2]) and

  14. Quantifying oxygen in paper-based cell cultures with luminescent thin film sensors.

    Science.gov (United States)

    Boyce, Matthew W; Kenney, Rachael M; Truong, Andrew S; Lockett, Matthew R

    2016-04-01

    Paper-based scaffolds are an attractive material for generating 3D tissue-like cultures because paper is readily available and does not require specialized equipment to pattern, cut, or use. By controlling the exchange of fresh culture medium with the paper-based scaffolds, we can engineer diffusion-dominated environments similar to those found in spheroids or solid tumors. Oxygen tension directly regulates cellular phenotype and invasiveness through hypoxia-inducible transcription factors and also has chemotactic properties. To date, gradients of oxygen generated in the paper-based cultures have relied on cellular response-based readouts. In this work, we prepared a luminescent thin film capable of quantifying oxygen tensions in apposed cell-containing paper-based scaffolds. The oxygen sensors, which are polystyrene films containing a Pd(II) tetrakis(pentafluorophenyl)porphyrin dye, are photostable, stable in culture conditions, and not cytotoxic. They have a linear response for oxygen tensions ranging from 0 to 160 mmHg O2, and a Stern-Volmer constant (K sv) of 0.239 ± 0.003 mmHg O2 (-1). We used these oxygen-sensing films to measure the spatial and temporal changes in oxygen tension for paper-based cultures containing a breast cancer line that was engineered to constitutively express a fluorescent protein. By acquiring images of the oxygen-sensing film and the fluorescently labeled cells, we were able to approximate the oxygen consumption rates of the cells in our cultures.

  15. Method for the determination of oxygen consumption rates and diffusion coefficients in multicellular spheroids

    OpenAIRE

    Mueller-Klieser, W.

    1984-01-01

    A method has been developed for the quantitative evaluation of oxygen tension (PO2) distributions in multicellular spheroids measured with O2-sensitive microelectrodes. The experimental data showed that multicellular tumor spheroids in stirred growth media were characterized by a diffusion-depleted zone surrounding the spheroids. This zone was elicited by an unstirred layer of medium next to the spheroid leading to a continuous decrease in the PO2 values from the bulk medium towards the spher...

  16. Parachute Cord Tension Sensor

    Data.gov (United States)

    National Aeronautics and Space Administration — To design and fabricate a light weight (few oz), very small (~2 inch length) parachute cord tension sensor demonstrator device.A major challenge for the CPAS (The...

  17. Leadership. Using Creative Tension.

    Science.gov (United States)

    Cook, David L.

    1986-01-01

    Leadership involves maintaining a balance of the variables which comprise leadership. Love and fear, types of power, success and effectiveness, and driving and restraining forces are discussed as sources of the creative tension a leader uses to influence others. (MT)

  18. Spontaneous tension haemopneumothorax

    OpenAIRE

    Patterson, Benjamin Oliver; Itam, Sarah; Probst, Fey

    2008-01-01

    Abstract We present a patient with sudden onset progressive shortness of breath and no history of trauma, who rapidly became haemodynamically compromised with a pneumothorax and pleural effusion seen on chest radiograph. He was treated for spontaneous tension pneumothorax but this was soon revealed to be a tension haemopneumothorax. He underwent urgent thoracotomy after persistent bleeding to explore an apical vascular abnormality seen on CT scanning. To our knowledge this is the first such c...

  19. Experimental studies on the effect of perfluorochemicals in tumor irradiation

    International Nuclear Information System (INIS)

    Shinoda, Jun; Iwai, Tomohiko; Hattori, Tatsuaki; Kondo, Hiroaki; Sakai, Noboru; Yamada, Hiroshi

    1984-01-01

    The effects of radiation therapy with Fluosol-DA on rat mammary tumors were studied. The tissue oxygen tension values of tumors in breathing mixed gas (5% carbon dioxide and 95% oxygen) with Fluosol-DA (25 ml/kg, i.v.) were significantly higher than those in room air without Fluosol-DA. The rats were divided into three groups: Group I received Fluosol-DA but no irradiation, Group II was treated with 1000 rads of irradiation using 60 Co without Fluosol-DA in room air and Group III received the same irradiation and Fluosol-DA in breathig mixed gas. In the latter group we observed a prolongation of the survival time and suppression of the tumor growth. (author)

  20. CR108, a novel vitamin K3 derivative induces apoptosis and breast tumor inhibition by reactive oxygen species and mitochondrial dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Chun-Ru [Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30068, Taiwan (China); Liao, Wei-Siang [Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu 30068, Taiwan (China); Wu, Ya-Hui [Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30068, Taiwan (China); Murugan, Kaliyappan [Department of Chemistry, National Dong Hwa University, Hualien 974, Taiwan (China); Chen, Chinpiao, E-mail: chinpiao@mail.ndhu.edu.tw [Department of Chemistry, National Dong Hwa University, Hualien 974, Taiwan (China); Chao, Jui-I, E-mail: jichao@faculty.nctu.edu.tw [Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30068, Taiwan (China); Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu 30068, Taiwan (China)

    2013-12-15

    Vitamin K3 derivatives have been shown to exert anticancer activities. Here we show a novel vitamin K3 derivative (S)-2-(2-hydroxy-3-methylbutylthio)naphthalene-1,4-dione, which is named as CR108 that induces apoptosis and tumor inhibition through reactive oxygen species (ROS) and mitochondrial dysfunction in human breast cancer. CR108 is more effective on the breast cancer cell death than other vitamin K3 derivatives. Moreover, CR108 induced apoptosis in both the non-HER-2-overexpressed MCF-7 and HER-2-overexpressed BT-474 breast cancer cells. CR108 caused the loss of mitochondrial membrane potential, cytochrome c released from mitochondria to cytosol, and cleaved PARP proteins for apoptosis induction. CR108 markedly increased ROS levels in breast cancer cells. N-acetylcysteine (NAC), a general ROS scavenger, completely blocked the CR108-induced ROS levels, mitochondrial dysfunction and apoptosis. Interestingly, CR108 increased the phosphorylation of p38 MAP kinase but conversely inhibited the survivin protein expression. NAC treatment prevented the activation of p38 MAP kinase and rescued the survivin protein levels. SB202190, a specific p38 MAP kinase inhibitor, recovered the survivin protein levels and attenuated the cytotoxicity of CR108-treated cells. Furthermore, CR108 inhibited the xenografted human breast tumor growth in nude mice. Together, we demonstrate that CR108 is a novel vitamin K3 derivative that induces apoptosis and tumor inhibition by ROS production and mitochondrial dysfunction and associates with the phosphorylation of p38 MAP kinase and the inhibition of survivin in the human breast cancer. - Highlights: • CR108 is more effective on the cell death than other vitamin K3 derivatives. • CR108 induces apoptosis and tumor inhibition by ROS and mitochondrial dysfunction. • CR108 induces apoptosis by p38 kinase activation and survivin inhibition. • CR108 is a potent vitamin K3 analog that can develop for breast cancer therapy.

  1. CR108, a novel vitamin K3 derivative induces apoptosis and breast tumor inhibition by reactive oxygen species and mitochondrial dysfunction

    International Nuclear Information System (INIS)

    Yang, Chun-Ru; Liao, Wei-Siang; Wu, Ya-Hui; Murugan, Kaliyappan; Chen, Chinpiao; Chao, Jui-I

    2013-01-01

    Vitamin K3 derivatives have been shown to exert anticancer activities. Here we show a novel vitamin K3 derivative (S)-2-(2-hydroxy-3-methylbutylthio)naphthalene-1,4-dione, which is named as CR108 that induces apoptosis and tumor inhibition through reactive oxygen species (ROS) and mitochondrial dysfunction in human breast cancer. CR108 is more effective on the breast cancer cell death than other vitamin K3 derivatives. Moreover, CR108 induced apoptosis in both the non-HER-2-overexpressed MCF-7 and HER-2-overexpressed BT-474 breast cancer cells. CR108 caused the loss of mitochondrial membrane potential, cytochrome c released from mitochondria to cytosol, and cleaved PARP proteins for apoptosis induction. CR108 markedly increased ROS levels in breast cancer cells. N-acetylcysteine (NAC), a general ROS scavenger, completely blocked the CR108-induced ROS levels, mitochondrial dysfunction and apoptosis. Interestingly, CR108 increased the phosphorylation of p38 MAP kinase but conversely inhibited the survivin protein expression. NAC treatment prevented the activation of p38 MAP kinase and rescued the survivin protein levels. SB202190, a specific p38 MAP kinase inhibitor, recovered the survivin protein levels and attenuated the cytotoxicity of CR108-treated cells. Furthermore, CR108 inhibited the xenografted human breast tumor growth in nude mice. Together, we demonstrate that CR108 is a novel vitamin K3 derivative that induces apoptosis and tumor inhibition by ROS production and mitochondrial dysfunction and associates with the phosphorylation of p38 MAP kinase and the inhibition of survivin in the human breast cancer. - Highlights: • CR108 is more effective on the cell death than other vitamin K3 derivatives. • CR108 induces apoptosis and tumor inhibition by ROS and mitochondrial dysfunction. • CR108 induces apoptosis by p38 kinase activation and survivin inhibition. • CR108 is a potent vitamin K3 analog that can develop for breast cancer therapy

  2. Role of nuclear factor kappa B and reactive oxygen species in the tumor necrosis factor-a-induced epithelial-mesenchymal transition of MCF-7 cells

    Directory of Open Access Journals (Sweden)

    R. Dong

    2007-08-01

    Full Text Available The microenvironment of the tumor plays an important role in facilitating cancer progression and activating dormant cancer cells. Most tumors are infiltrated with inflammatory cells which secrete cytokines such as tumor necrosis factor-a (TNF-a. To evaluate the role of TNF-a in the development of cancer we studied its effects on cell migration with a migration assay. The migrating cell number in TNF-a -treated group is about 2-fold of that of the control group. Accordingly, the expression of E-cadherin was decreased and the expression of vimentin was increased upon TNF-a treatment. These results showed that TNF-a can promote epithelial-mesenchymal transition (EMT of MCF-7 cells. Further, we found that the expression of Snail, an important transcription factor in EMT, was increased in this process, which is inhibited by the nuclear factor kappa B (NFkB inhibitor aspirin while not affected by the reactive oxygen species (ROS scavenger N-acetyl cysteine. Consistently, specific inhibition of NFkB by the mutant IkBa also blocked the TNF-a-induced upregulation of Snail promoter activity. Thus, the activation of NFkB, which causes an increase in the expression of the transcription factor Snail is essential in the TNF-a-induced EMT. ROS caused by TNF-a seemed to play a minor role in the TNF-a-induced EMT of MCF-7 cells, though ROS per se can promote EMT. These findings suggest that different mechanisms might be responsible for TNF-a - and ROS-induced EMT, indicating the need for different strategies for the prevention of tumor metastasis induced by different stimuli.

  3. pO polarography, contrast enhanced color duplex sonography (CDS), [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography: validated methods for the evaluation of therapy-relevant tumor oxygenation or only bricks in the puzzle of tumor hypoxia?

    International Nuclear Information System (INIS)

    Gagel, Bernd; Hamacher, Kurt; Coenen, Heinz H; Scholbach, Thomas; Maneschi, Payam; DiMartino, Ercole; Eble, Michael J; Piroth, Marc; Pinkawa, Michael; Reinartz, Patrick; Zimny, Michael; Kaiser, Hans J; Stanzel, Sven; Asadpour, Branka; Demirel, Cengiz

    2007-01-01

    The present study was conducted to analyze the value of ([ 18 F] fluoromisonidazole (FMISO) and [ 18 F]-2-fluoro-2'-deoxyglucose (FDG) PET as well as color pixel density (CPD) and tumor perfusion (TP) assessed by color duplex sonography (CDS) for determination of therapeutic relevant hypoxia. As a standard for measuring tissue oxygenation in human tumors, the invasive, computerized polarographic needle electrode system (pO 2 histography) was used for comparing the different non invasive measurements. Until now a total of 38 Patients with malignancies of the head and neck were examined. Tumor tissue pO 2 was measured using a pO 2 -histograph. The needle electrode was placed CT-controlled in the tumor without general or local anesthesia. To assess the biological and clinical relevance of oxygenation measurement, the relative frequency of pO 2 readings, with values ≤ 2.5, ≤ 5.0 and ≤ 10.0 mmHg, as well as mean and median pO 2 were stated. FMISO PET consisted of one static scan of the relevant region, performed 120 min after intravenous administration. FMISO tumor to muscle ratios (FMISO T/M ) and tumor to blood ratios (FMISO T/B ) were calculated. FDG PET of the lymph node metastases was performed 71 ± 17 min after intravenous administration. To visualize as many vessels as possible by CDS, a contrast enhancer (Levovist ® , Schering Corp., Germany) was administered. Color pixel density (CPD) was defined as the ratio of colored to grey pixels in a region of interest. From CDS signals two parameters were extracted: color hue – defining velocity (v) and color area – defining perfused area (A). Signal intensity as a measure of tissue perfusion (TP) was quantified as follows: TP = v mean × A mean . In order to investigate the degree of linear association, we calculated the Pearson correlation coefficient. Slight (|r| > 0.4) to moderate (|r| > 0.6) correlation was found between the parameters of pO 2 polarography (pO 2 readings with values ≤ 2.5, ≤ 5

  4. The Neuroprotection Effect of Oxygen Therapy: A Systematic Review ...

    African Journals Online (AJOL)

    2018-04-04

    Apr 4, 2018 ... investigating the neuroprotective effect of oxygen, but the outcomes as well as ...... Neuroprotective gases – Fantasy or reality for clinical use? Prog .... of oxygen on brain tissue oxygen tension in children with severe traumatic ...

  5. Systemic depletion of L-cyst(e)ine with cyst(e)inase increases reactive oxygen species and suppresses tumor growth.

    Science.gov (United States)

    Cramer, Shira L; Saha, Achinto; Liu, Jinyun; Tadi, Surendar; Tiziani, Stefano; Yan, Wupeng; Triplett, Kendra; Lamb, Candice; Alters, Susan E; Rowlinson, Scott; Zhang, Yan Jessie; Keating, Michael J; Huang, Peng; DiGiovanni, John; Georgiou, George; Stone, Everett

    2017-01-01

    Cancer cells experience higher oxidative stress from reactive oxygen species (ROS) than do non-malignant cells because of genetic alterations and abnormal growth; as a result, maintenance of the antioxidant glutathione (GSH) is essential for their survival and proliferation. Under conditions of elevated ROS, endogenous L-cysteine (L-Cys) production is insufficient for GSH synthesis. This necessitates uptake of L-Cys that is predominantly in its disulfide form, L-cystine (CSSC), via the xCT(-) transporter. We show that administration of an engineered and pharmacologically optimized human cyst(e)inase enzyme mediates sustained depletion of the extracellular L-Cys and CSSC pool in mice and non-human primates. Treatment with this enzyme selectively causes cell cycle arrest and death in cancer cells due to depletion of intracellular GSH and ensuing elevated ROS; yet this treatment results in no apparent toxicities in mice even after months of continuous treatment. Cyst(e)inase suppressed the growth of prostate carcinoma allografts, reduced tumor growth in both prostate and breast cancer xenografts and doubled the median survival time of TCL1-Tg:p53 -/- mice, which develop disease resembling human chronic lymphocytic leukemia. It was observed that enzyme-mediated depletion of the serum L-Cys and CSSC pool suppresses the growth of multiple tumors, yet is very well tolerated for prolonged periods, suggesting that cyst(e)inase represents a safe and effective therapeutic modality for inactivating antioxidant cellular responses in a wide range of malignancies.

  6. CR108, a novel vitamin K3 derivative induces apoptosis and breast tumor inhibition by reactive oxygen species and mitochondrial dysfunction.

    Science.gov (United States)

    Yang, Chun-Ru; Liao, Wei-Siang; Wu, Ya-Hui; Murugan, Kaliyappan; Chen, Chinpiao; Chao, Jui-I

    2013-12-15

    Vitamin K3 derivatives have been shown to exert anticancer activities. Here we show a novel vitamin K3 derivative (S)-2-(2-hydroxy-3-methylbutylthio)naphthalene-1,4-dione, which is named as CR108 that induces apoptosis and tumor inhibition through reactive oxygen species (ROS) and mitochondrial dysfunction in human breast cancer. CR108 is more effective on the breast cancer cell death than other vitamin K3 derivatives. Moreover, CR108 induced apoptosis in both the non-HER-2-overexpressed MCF-7 and HER-2-overexpressed BT-474 breast cancer cells. CR108 caused the loss of mitochondrial membrane potential, cytochrome c released from mitochondria to cytosol, and cleaved PARP proteins for apoptosis induction. CR108 markedly increased ROS levels in breast cancer cells. N-acetylcysteine (NAC), a general ROS scavenger, completely blocked the CR108-induced ROS levels, mitochondrial dysfunction and apoptosis. Interestingly, CR108 increased the phosphorylation of p38 MAP kinase but conversely inhibited the survivin protein expression. NAC treatment prevented the activation of p38 MAP kinase and rescued the survivin protein levels. SB202190, a specific p38 MAP kinase inhibitor, recovered the survivin protein levels and attenuated the cytotoxicity of CR108-treated cells. Furthermore, CR108 inhibited the xenografted human breast tumor growth in nude mice. Together, we demonstrate that CR108 is a novel vitamin K3 derivative that induces apoptosis and tumor inhibition by ROS production and mitochondrial dysfunction and associates with the phosphorylation of p38 MAP kinase and the inhibition of survivin in the human breast cancer. © 2013.

  7. Spontaneous tension haemopneumothorax.

    Science.gov (United States)

    Patterson, Benjamin Oliver; Itam, Sarah; Probst, Fey

    2008-10-31

    We present a patient with sudden onset progressive shortness of breath and no history of trauma, who rapidly became haemodynamically compromised with a pneumothorax and pleural effusion seen on chest radiograph. He was treated for spontaneous tension pneumothorax but this was soon revealed to be a tension haemopneumothorax. He underwent urgent thoracotomy after persistent bleeding to explore an apical vascular abnormality seen on CT scanning. To our knowledge this is the first such case reported.Aetiology and current approach to spontaneous haemothorax are discussed briefly.

  8. Spontaneous tension haemopneumothorax

    Directory of Open Access Journals (Sweden)

    Itam Sarah

    2008-10-01

    Full Text Available Abstract We present a patient with sudden onset progressive shortness of breath and no history of trauma, who rapidly became haemodynamically compromised with a pneumothorax and pleural effusion seen on chest radiograph. He was treated for spontaneous tension pneumothorax but this was soon revealed to be a tension haemopneumothorax. He underwent urgent thoracotomy after persistent bleeding to explore an apical vascular abnormality seen on CT scanning. To our knowledge this is the first such case reported. Aetiology and current approach to spontaneous haemothorax are discussed briefly.

  9. Radiotherapy plus cis-retinoic acid/interferon-α in cervical cancers: response and impact of cRA/IFN on tumor tissue oxygenation

    International Nuclear Information System (INIS)

    Haensgen, Gabriele; Koehler, Uwe; Dunst, Juergen

    1997-01-01

    Background: We have evaluated the impact of 13-cis-retinoic acid plus interferon in combination with radiotherapy on response and on tumor oxygenation in a phase II-study. Materials and methods: From June 1995 through April 1996, thirty-four patients with squamous cell carcinoma FIGO IIB (N=8) and IIIB (N=26) of the cervix who were scheduled for definitive radiotherapy with curative intent received additional treatment with 13-cis-retinoic acid (cRA, isotretinoin) plus interferon-α-2a (IFN-α-2a) as part of a phase-II-protocol at the Universities of Halle-Wittenberg (N=25), Leipzig (N=7) and Dresden (N=2). cRA/IFN-α-2a started 14 days prior to radiotherapy (1 mg per kilogramm body weight cRA orally daily plus 6x10 6 I.U. IFN-α-2a subcutaneously daily). After this induction period, standard radiotherapy was administered (external irradiation with 45Gy in 25 fractions of 1.8Gy plus HDR-brachytherapy with 5x7Gy). During radiotherapy, cRA/IFN-α-2a-treatment was continued with 50% of the daily doses. In 14 patients treated at the University of Halle-Wittenberg, tumor tissue pO 2 -measurements were performed prior to radiotherapy, at 20Gy, and at the end of radiotherapy with an Eppendorf-pO 2 -histograph. The oxygenation data of these patients were compared to 14 patients who had also pO 2 -measurements but had refused to participate in the cRA/IFN-α-2a-protocol and received radiotherapy alone during the same period. Results: All 8 patients with FIGO IIB tumors had a complete clinical remission 3 months after radiotherapy. In FIGO IIIB cancers, (19(26)) (73%) achieved a cCR, 5 (19%) had a PR and 2 died within six months after treatment due to intercurrent disease. The toxicity of cRA/IFN-α-2a was only mild to moderate (fever 43%, skin toxicity 36%, diarrhea 20%, elevation of liver enzymes 20%) with no grade (3(4)) toxicity. The 14 patients with cRA/IFN-α-2a-pretreatment prior to radiotherapy had significant higher median pO 2 -values in their tumors at the

  10. Creating Tension in Writing.

    Science.gov (United States)

    Folta, Bernarr

    This paper discusses the rationale and teaching methods for a six-week unit, for a high school freshman English Class, on perception, semantics, and writing, which places special focus on developing tension in student writing. The first four objectives of the course focus on perception and the next two focus on semantics. The seventh…

  11. Tension-filled Governance?

    DEFF Research Database (Denmark)

    Celik, Tim Holst

    on the statesituated tension-filled functional relationship between legitimation and accumulation, the study both historically and theoretically reworks this approach and reapplies it for the post-1970s/1990s governance period. It asks whether and to what extent governance has served as a distinctive post- 1970s/1990s...

  12. Rein tension during canter

    NARCIS (Netherlands)

    Egenvall, Agneta; Eisersiö, Marie; Rhodin, Marie; van Weeren, P.R.; Roepstorff, Lars

    2015-01-01

    Riders generally use reins as a means for communication with the horse. At present, the signalling pattern is poorly understood. The aim of this study was to illustrate and analyse the rein tension patterns in a number of rider/horse combinations across a variety of exercises in the canter gait. Our

  13. Enhancement of alpha particles-induced cell transformation by oxygen free radicals and tumor necrosis factor released from phagocytes

    International Nuclear Information System (INIS)

    Gong Yifen; Guo Renfeng; Zhu Maoxiang; Shou Jiang; Ge Guixiu; Yang Zhihua; Hieber, L.; Peters, K.; Schippel, C.

    1997-01-01

    To illustrate the role of several endogenous factors released from phagocytes under chronic inflammation in radiation-induced cancer. C 3 T 10 T 1/2 and SHE cells were used as targets, and 238 Pu alpha source was used in alpha irradiation. The enhancement of TF in alpha particles-induced cell transformation by PMA-stimulated human blood and zymosan-stimulated U-937 cells was studied using formation of transformed foci. Transformation frequency (TF) of C 3 H 10 T 1/2 cells exposed to alpha particles of 0.5 Gy increased 2.1 and 2.8 fold by PMA-and PMA-stimulated neutrophils, respectively. TF of irradiated SHE cells at a dose of 0.5 Gy increased 12 fold by the addition of the supernatant of macrophage-like U-937 cell line. It was shown that TF of irradiated SHE cells at above dose increased 8 fold by the supernatant treated with anti-TNF-α could be subcultured continuously in vitro. The cells at 40 th passage and two lines of monoclone cells have the ability to develop malignant tumors in nude mice. The overdose of free radicals and TNF-α released from neutrophils and macrophages have played an important role in low dose radiation-induced cancer

  14. Coulomb string tension, asymptotic string tension, and the gluon chain

    OpenAIRE

    Greensite, Jeff; Szczepaniak, Adam P.

    2014-01-01

    We compute, via numerical simulations, the non-perturbative Coulomb potential of pure SU(3) gauge theory in Coulomb gauge. We find that that the Coulomb potential scales nicely in accordance with asymptotic freedom, that the Coulomb potential is linear in the infrared, and that the Coulomb string tension is about four times larger than the asymptotic string tension. We explain how it is possible that the asymptotic string tension can be lower than the Coulomb string tension by a factor of four.

  15. Celastrol targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent cytotoxicity in tumor cells

    Directory of Open Access Journals (Sweden)

    Xu Yuanji

    2011-05-01

    Full Text Available Abstract Background Celastrol is an active ingredient of the traditional Chinese medicinal plant Tripterygium Wilfordii, which exhibits significant antitumor activity in different cancer models in vitro and in vivo; however, the lack of information on the target and mechanism of action of this compound have impeded its clinical application. In this study, we sought to determine the mode of action of celastrol by focusing on the processes that mediate its anticancer activity. Methods The downregulation of heat shock protein 90 (HSP90 client proteins, phosphorylation of c-Jun NH2-terminal kinase (JNK, and cleavage of PARP, caspase 9 and caspase 3 were detected by western blotting. The accumulation of reactive oxygen species (ROS was analyzed by flow cytometry and fluorescence microscopy. Cell cycle progression, mitochondrial membrane potential (MMP and apoptosis were determined by flow cytometry. Absorption spectroscopy was used to determine the activity of mitochondrial respiratory chain (MRC complexes. Results Celastrol induced ROS accumulation, G2-M phase blockage, apoptosis and necrosis in H1299 and HepG2 cells in a dose-dependent manner. N-acetylcysteine (NAC, an antioxidative agent, inhibited celastrol-induced ROS accumulation and cytotoxicity. JNK phosphorylation induced by celastrol was suppressed by NAC and JNK inhibitor SP600125 (SP. Moreover, SP significantly inhibited celastrol-induced loss of MMP, cleavage of PARP, caspase 9 and caspase 3, mitochondrial translocation of Bad, cytoplasmic release of cytochrome c, and cell death. However, SP did not inhibit celastrol-induced ROS accumulation. Celastrol downregulated HSP90 client proteins but did not disrupt the interaction between HSP90 and cdc37. NAC completely inhibited celastrol-induced decrease of HSP90 client proteins, catalase and thioredoxin. The activity of MRC complex I was completely inhibited in H1299 cells treated with 6 μM celastrol in the absence and presence of NAC

  16. Imaging lysosomal highly reactive oxygen species and lighting up cancer cells and tumors enabled by a Si-rhodamine-based near-infrared fluorescent probe.

    Science.gov (United States)

    Zhang, Hongxing; Liu, Jing; Liu, Chenlu; Yu, Pengcheng; Sun, Minjia; Yan, Xiaohan; Guo, Jian-Ping; Guo, Wei

    2017-07-01

    Lysosomes have recently been regarded as the attractive pharmacological targets for selectively killing of cancer cells via lysosomal cell death (LCD) pathway that is closely associated with reactive oxygen species (ROS). However, the details on the ROS-induced LCD of cancer cells are still poorly understood, partially due to the absence of a lysosome-targetable, robust, and biocompatible imaging tool for ROS. In this work, we brought forward a Si-rhodamine-based fluorescent probe, named PSiR, which could selectively and sensitively image the pathologically more relavent highly reactive oxygen species (hROS: HClO, HO, and ONOO - ) in lysosomes of cancer cells. Compared with many of the existing hROS fluorescent probes, its superiorities are mainly embodied in the high stability against autoxidation and photoxidation, near-infrared exitation and emission, fast fluorescence off-on response, and specific lysosomal localization. Its practicality has been demonstrated by the real-time imaging of hROS generation in lysosomes of human non-small-cell lung cancer cells stimulated by anticancer drug β-lapachone. Moreover, the probe was sensitive enough for basal hROS in cancer cells, allowing its further imaging applications to discriminate not only cancer cells from normal cells, but also tumors from healthy tissues. Overall, our results strongly indicated that PSiR is a very promising imaging tool for the studies of ROS-related LCD of cancer cells, screening of new anticancer drugs, and early diagnosis of cancers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. A 2-week pretreatment with 13-cis-retinoic acid + interferon-α-2a prior to definitive radiation improves tumor tissue oxygenation in cervical cancers

    International Nuclear Information System (INIS)

    Dunst, J.; Haensgen, G.; Becker, A.; Krause, U.; Fuechsel, G.; Koehler, U.

    1998-01-01

    Background: We have evaluated the tumor tissue pO 2 in cervical cancers in patients treated with 13-cis-retinoic acid and interferon-α-2a prior to and during radiotherapy. Patients and methods: From June 1995 through April 1997, 22 patients with squamous cell carcinoma FIGO IIB/III of the cervix who were scheduled for definitive radiotherapy with curative intent received additional treatment with 13-cis-retinoic acid (cRA, isotretinoin) plus interferon-α-2a (IFN-α-2a) as part of a phase-II protocol. cRA/IFN-α-2a started 14 days prior to radiotherapy (1 mg per kilogramme body weight cRA orally daily plus 6x10 6 IU IFN-α-2a subcutaneously daily). After this indicution period, standard radiotherapy was administered (external irradiation with 50.4 Gy in 28 fractions of 1.8 Gy plus HDR-brachytherapy). During radiotherapy, cRA/IFN-α-2a-treatment was continued with 50% of the daily doses. Tumor tissue pO 2 -measurements were performed prior to and after the cRA/IFN-induction period as well as at 20 Gy and at the end of radiotherapy with an Eppendorf-pO 2 -histograph. Results: In 11 out of the 22 patients, pO 2 -measurements were performed prior to the cRA/IFN-induction therapy. The median pO 2 of these untreated tumors was 17.7±16.3 mm Hg. The relative frequency of hypoxic readings with pO 2 -values below 5 mm Hg ranged from 0% to 60.6% (mean 24.3±21.0%). After the 2-week induction period with cRA/IFN, the median pO 2 had increased from 17.7pm16.3 mm Hg to 27.6±19.1 mm Hg (not significant). In all 5 patients with hypoxic tumors prior to cRA/IFN (median pO 2 of 10 mm Hg or less), the median pO 2 was above 20 mm Hg after the 2-week cRA/IFN-induction. In this subgroup of hypoxic tumors, the median pO 2 increased from 6.3±2.7 mm Hg to 27.0±5.6 mm Hg (p=0.004, t-test for paired samples). The frequency of hypoxic readings (pO 2 -values 2 below 10 mm Hg prior to treatment), 4/5 achieved complete remission. Conclusions: Pretreatment with cRA/IFN improves oxygenation of

  18. The build oxygenation T{sub 2}{sup *} values of resectable esophageal squamous cell carcinomas as measured by 3T magnetic resonance imaging: Association with tumor stage

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yu Lian; Zhang, Xiao Ming; Huang, Yu Cheng; Chen, Tian Wu; Chen, Yan Il; Chen, Fan; Zeng, Nan Lin; Li, Rui [Sichuan Key Laboratory of Medical Imaging, Affiliated Hospital of North Sichuan Medical College, Nanchong (China); Yang, Zhi Gang [Dept. of Radiology, West China Hospital of Sichuan University, Chengdu (China); Hu, Jiani [Dept. of Radiology, Wayne State University, Detroit (United States)

    2017-08-01

    To explore the association between the blood oxygenation T{sub 2}{sup *} values of resectable esophageal squamous cell carcinomas (ESCCs) and tumor stages. This study included 48 ESCC patients and 20 healthy participants who had undergone esophageal T{sub 2}{sup *} -weighted imaging to obtain T{sub 2}{sup *} values of the tumors and normal esophagus. ESCC patients underwent surgical resections less than one week after imaging. Statistical analyses were performed to identify the association between T{sub 2}{sup *} values of ESCCs and tumor stages. One-way ANOVA and Student-Newman-Keuls tests revealed that the T{sub 2}{sup *} value could differentiate stage T1 ESCCs (17.7 ± 3.3 ms) from stage T2 and T3 tumors (24.6 ± 2.7 ms and 27.8 ± 5.6 ms, respectively; all ps < 0.001). Receiver operating curve (ROC) analysis showed the suitable cutoff T{sub 2}{sup *} value of 21.3 ms for either differentiation. The former statistical tests demonstrated that the T{sub 2}{sup *} value could not differentiate between stages T2 and T3 (24.6 ± 2.7 ms vs. 27.8 ± 5.6 ms, respectively, p > 0.05) or between N stages (N1 vs. N2 vs. N3: 24.7 ± 6.9 ms vs. 25.4 ± 4.5 ms vs. 26.8 ± 3.9 ms, respectively; all ps > 0.05). The former tests illustrated that the T{sub 2}{sup *} value could differentiate anatomic stages I and II (18.8 ± 4.8 ms and 26.9 ± 5.9 ms, respectively) or stages I and III (27.3 ± 3.6 ms). ROC analysis depicted the same cutoff T{sub 2}{sup *} value of 21.3 ms for either differentiation. In addition, the Student's t test revealed that the T{sub 2}{sup *} value could determine grouped T stages (T0 vs. T1–3: 17.0 ± 2.9 ms vs. 25.2 ± 6.2 ms; T0–1 vs. T2–3: 17.3 ± 3.0 ms vs. 27.1 ± 5.3 ms; and T0–2 vs. T3: 18.8 ± 4.2 ms vs. 27.8 ± 5.6 ms, all ps < 0.001). ROC analysis indicated that the T{sub 2}{sup *} value could detect ESCCs (cutoff, 20 ms), and discriminate between stages T0–1 and T2–3 (cutoff, 21.3 ms) and between T0–2 and T3 (cutoff, 20.4 ms

  19. Oxygen, nitric oxide and articular cartilage

    Directory of Open Access Journals (Sweden)

    B Fermor

    2007-04-01

    Full Text Available Molecular oxygen is required for the production of nitric oxide (NO, a pro-inflammatory mediator that is associated with osteoarthritis and rheumatoid arthritis. To date there has been little consideration of the role of oxygen tension in the regulation of nitric oxide production associated with arthritis. Oxygen tension may be particularly relevant to articular cartilage since it is avascular and therefore exists at a reduced oxygen tension. The superficial zone exists at approximately 6% O2, while the deep zone exists at less than 1% O2. Furthermore, oxygen tension can alter matrix synthesis, and the material properties of articular cartilage in vitro.The increase in nitric oxide associated with arthritis can be caused by pro-inflammatory cytokines and mechanical stress. Oxygen tension significantly alters endogenous NO production in articular cartilage, as well as the stimulation of NO in response to both mechanical loading and pro-inflammatory cytokines. Mechanical loading and pro-inflammatory cytokines also increase the production of prostaglandin E2 (PGE2. There is a complex interaction between NO and PGE2, and oxygen tension can alter this interaction. These findings suggest that the relatively low levels of oxygen within the joint may have significant influences on the metabolic activity, and inflammatory response of cartilage as compared to ambient levels. A better understanding of the role of oxygen in the production of inflammatory mediators in response to mechanical loading, or pro-inflammatory cytokines, may aid in the development of strategies for therapeutic intervention in arthritis.

  20. Regional tumor oximetry: 19F NMR spectroscopy of hexafluorobenzene

    International Nuclear Information System (INIS)

    Hunjan, Sandeep; Mason, Ralph P.; Constantinescu, Anca; Peschke, Peter; Hahn, Eric W.; Antich, Peter P.

    1998-01-01

    Purpose: An accurate method for monitoring oxygen tension (pO 2 ) of individual tumors could be valuable for optimizing treatment plans. We have recently shown that 19 F nuclear magnetic resonance (NMR) spin-lattice relaxometry of hexafluorobenzene (HFB) provides a highly sensitive indicator of tumor oxygenation. We have now refined the methodology to provide enhanced precision, and applied the method to investigate dynamic changes in tumor oxygenation. Methods and Materials: Dunning prostate adenocarcinoma R3327-AT1 was grown in the form of pedicles on the foreback of male Copenhagen rats. When the tumors reached ≅1 cm diameter, HFB (20 μl) was administered, either centrally or peripherally, by direct intratumoral (IT) injection. Local pO 2 was determined using pulse-burst saturation recovery (PBSR) 19 F NMR spectroscopy on the basis of the spin-lattice relaxation rate, R1. Results: Interrogation of the central region of tumors provided typical values in the range pO 2 = 1.4-6.4 mmHg, with a typical stability of ±2 mmHg over a period of 20 min, when rats breathed 33% O 2 . Altering the inhaled gas to oxygen or carbogen (95% O 2 /5% CO 2 ) produced no significant change. In contrast, interrogation of tumor periphery indicated baseline pO 2 in the range 7.9-78.9 mmHg. Altering inspired gas produced significant changes (p 2 or carbogen, although the change was generally greater with carbogen. In each case, pO 2 returned to baseline within 16 min of returning the inhaled gas to baseline. Conclusion: We believe this method provides a valuable new approach with the requisite precision and accuracy to investigate tumor pO 2

  1. Tension-type headache

    DEFF Research Database (Denmark)

    Bendtsen, Lars; Jensen, Rigmor; Bendtsen, Lars

    2009-01-01

    The substantial societal and individual burdens associated with tension-type headache (TTH) constitute a previously overlooked major public health issue. TTH is prevalent, affecting up to 78% of the general population, and 3% suffer from chronic TTH. Pericranial myofascial nociception probably...... is important for the pathophysiology of episodic TTH, whereas sensitization of central nociceptive pathways seems responsible for the conversion of episodic to chronic TTH. Headache-related disability usually can be reduced by identification of trigger factors combined with nonpharmacologic and pharmacologic...... treatments, but effective treatment modalities are lacking. Benefits can be gained by development of specific and effective treatment strategies....

  2. A Comparative pO2 Probe and [18F]-Fluoro-Azomycinarabino-Furanoside ([18F]FAZA) PET Study Reveals Anesthesia-Induced Impairment of Oxygenation and Perfusion in Tumor and Muscle.

    Science.gov (United States)

    Mahling, Moritz; Fuchs, Kerstin; Thaiss, Wolfgang M; Maier, Florian C; Feger, Martina; Bukala, Daniel; Harant, Maren; Eichner, Martin; Reutershan, Jörg; Lang, Florian; Reischl, Gerald; Pichler, Bernd J; Kneilling, Manfred

    2015-01-01

    CT26 colon carcinoma-bearing mice were anesthetized with isoflurane (IF) or ketamine/xylazine (KX) while breathing air or oxygen (O2). We performed 10 min static PET scans 1 h, 2 h and 3 h after [18F]FAZA injection and calculated the [18F]FAZA-uptake and tumor-to-muscle ratios (T/M). In another experimental group, we placed a pO2 probe in the tumor as well as in the gastrocnemius muscle to measure the pO2 and perfusion. Ketamine/xylazine-anesthetized mice yielded up to 3.5-fold higher T/M-ratios compared to their isoflurane-anesthetized littermates 1 h, 2 h and 3 h after [18F]FAZA injection regardless of whether the mice breathed air or oxygen (3 h, KX-air: 7.1 vs. IF-air: 1.8, p = 0.0001, KX-O2: 4.4 vs. IF-O2: 1.4, p pO2 probe measurements yielded enhanced intra-tumoral pO2 values in air- and oxygen-breathing ketamine/xylazine-anesthetized mice compared to isoflurane-anesthetized mice (KX-air: 1.01 mmHg, IF-air: 0.45 mmHg; KX-O2 9.73 mmHg, IF-O2: 6.25 mmHg). Muscle oxygenation was significantly higher in air-breathing isoflurane-anesthetized (56.9 mmHg) than in ketamine/xylazine-anesthetized mice (33.8 mmHg, p = 0.0003). [18F]FAZA tumor uptake was highest in ketamine/xylazine-anesthetized mice regardless of whether the mice breathed air or oxygen. The generally lower [18F]FAZA whole-body uptake in isoflurane-anesthetized mice could be due to the higher muscle pO2-values in these mice compared to ketamine/xylazine-anesthetized mice. When performing preclinical in vivo hypoxia PET studies, oxygen should be avoided, and ketamine/xylazine-anesthesia might alleviate the identification of tumor hypoxia areals.

  3. General definition of gravitational tension

    International Nuclear Information System (INIS)

    Harmark, T.; Obers, N.A.

    2004-01-01

    In this note we give a general definition of the gravitational tension in a given asymptotically translationally-invariant spatial direction of a space-time. The tension is defined via the extrinsic curvature in analogy with the Hawking-Horowitz definition of energy. We show the consistency with the ADM tension formulas for asymptotically-flat space-times, in particular for Kaluza-Klein black hole solutions. Moreover, we apply the general tension formula to near-extremal branes, constituting a check for non-asymptotically flat space-times. (author)

  4. Bilateral tension pneumothorax related to acupuncture.

    Science.gov (United States)

    Tagami, Rumi; Moriya, Takashi; Kinoshita, Kosaku; Tanjoh, Katsuhisa

    2013-06-01

    We report on a patient with a rare case of bilateral tension pneumothorax that occurred after acupuncture. A 69-year-old large-bodied man, who otherwise had no risk factors for spontaneous pneumothorax, presented with chest pressure, cold sweats and shortness of breath. Immediately after bilateral pneumothorax had been identified on a chest radiograph in the emergency room, his blood pressure and percutaneous oxygen saturation suddenly decreased to 78 mm Hg and 86%, respectively. We confirmed deterioration in his cardiopulmonary status and diagnosed bilateral tension pneumothorax. We punctured his chest bilaterally and inserted chest tubes for drainage. His vital signs promptly recovered. After the bilateral puncture and drainage, we learnt that he had been treated with acupuncture on his upper back. We finally diagnosed a bilateral tension pneumothorax based on the symptoms that appeared 8 h after the acupuncture. Because the patient had no risk factors for spontaneous pneumothorax, no alternative diagnosis was proposed. We recommend that patients receiving acupuncture around the chest wall must be adequately informed of the possibility of complications and expected symptoms, as a definitive diagnosis can be difficult without complete information.

  5. Ambient oxygen promotes tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Ho Joong Sung

    2011-05-01

    Full Text Available Oxygen serves as an essential factor for oxidative stress, and it has been shown to be a mutagen in bacteria. While it is well established that ambient oxygen can also cause genomic instability in cultured mammalian cells, its effect on de novo tumorigenesis at the organismal level is unclear. Herein, by decreasing ambient oxygen exposure, we report a ∼50% increase in the median tumor-free survival time of p53-/- mice. In the thymus, reducing oxygen exposure decreased the levels of oxidative DNA damage and RAG recombinase, both of which are known to promote lymphomagenesis in p53-/- mice. Oxygen is further shown to be associated with genomic instability in two additional cancer models involving the APC tumor suppressor gene and chemical carcinogenesis. Together, these observations represent the first report directly testing the effect of ambient oxygen on de novo tumorigenesis and provide important physiologic evidence demonstrating its critical role in increasing genomic instability in vivo.

  6. Computed Tomography Demonstration of the Production and Distribution of Oxygen Gas Following Intratumoral Injection of a New Radiosensitizer (KORTUC) for Patients with Breast Cancer-Is Intratumoral Injection Not an Ideal Approach to Solve the Major Problem of Tumor Hypoxia in Radiotherapy?

    Science.gov (United States)

    Hayashi, Naoya; Ogawa, Yasuhiro; Kubota, Kei; Okino, Kazuhiro; Akima, Ryo; Morita-Tokuhiro, Shiho; Tsuzuki, Akira; Yaogawa, Shin; Nishioka, Akihito; Miyamura, Mitsuhiko

    2016-04-01

    We previously developed a new enzyme-targeting radiosensitization treatment named Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II), which contains hydrogen peroxide and sodium hyaluronate for injection into various types of tumors. For breast cancer treatment, the radiosensitization agent was injected into the tumor tissue twice a week under ultrasonographic guidance, immediately prior to each administration of radiation therapy. At approximately three hours after the second or third injection, computed tomography (CT) was performed to confirm the production and distribution of oxygen gas generated from the KORTUC radiosensitization agent by catalysis of peroxidases contained mainly in tumor tissue. The purpose of this study was to demonstrate that tumor hypoxia could be overcome by such a procedure and to evaluate the method of intratumoral injection in terms of confirming oxygen distribution in the target tumor tissue and around the tumor to be visualized on dedicated CT imaging. Three-dimensional reconstructed maximum intensity projection imaging of contrast-enhanced breast magnetic resonance imaging was used to compare the position of the tumor and that of the generated oxygen. Distributed oxygen gas was confirmed in the tumor tissue and around it in all 10 patients examined in the study. A region of oxygen gas was measured as an average value of -457.2 Hounsfield units (HU) as a region of interest. A slightly increased HU value compared to the density of air or oxygen was considered due to the presence of tumor tissue in the low-density area on 5-mm-thick reconstructed CT imaging. The results of this study showed that intratumoral oxygen was successfully produced by intratumoral KORTUC injection under ultrasonographic guidance, and that tumor hypoxia, which is considered a main cause of radioresistance in currently used Linac (linear accelerator) radiation therapy for malignant neoplasms, could be resolved by this method.

  7. An Automatic Occlusion Device for Remote Control of Tumor Tissue Ischemia

    Science.gov (United States)

    El-Dahdah, Hamid; Wang, Bei; He, Guanglong; Xu, Ronald X.

    2015-01-01

    We developed an automatic occlusion device for remote control of tumor tissue ischemia. The device consists of a flexible cannula encasing a shape memory alloy wire with its distal end connected to surgical suture. Regional tissue occlusion was tested on both the benchtop and the animal models. In the benchtop test, the occlusion device introduced quantitative and reproducible changes of blood flow in a tissue simulating phantom embedding a vessel simulator. In the animal test, the device generated a cyclic pattern of reversible ischemia in the right hinder leg tissue of a black male C57BL/6 mouse. We also developed a multimodal detector that integrates near infrared spectroscopy and electron paramagnetic resonance spectroscopy for continuous monitoring of tumor tissue oxygenation, blood content, and oxygen tension changes. The multimodal detector was tested on a cancer xenograft nude mouse undergoing reversible tumor ischemia. The automatic occlusion device and the multi-modal detector can be potentially integrated for closed-loop feedback control of tumor tissue ischemia. Such an integrated occlusion device may be used in multiple clinical applications such as regional hypoperfusion control in tumor resection surgeries and thermal ablation processes. In addition, the proposed occlusion device can also be used as a research tool to understand tumor oxygen transport and hemodynamic characteristics. PMID:20082532

  8. Tension type headaches: a review

    African Journals Online (AJOL)

    Location of the pain:There is often a typical location for tension- type headaches, as ... Cranial nerve abnormalities, including papilloedema. • Signs of ... peripheral and central mechanisms underlie tension-type ... Physiotherapy has been shown to be an effective management option for .... Acupuncture in primary headache.

  9. Inadequate cerebral oxygen delivery and central fatigue during strenuous exercise

    DEFF Research Database (Denmark)

    Nybo, Lars; Rasmussen, Peter

    2007-01-01

    Under resting conditions, the brain is protected against hypoxia because cerebral blood flow increases when the arterial oxygen tension becomes low. However, during strenuous exercise, hyperventilation lowers the arterial carbon dioxide tension and blunts the increase in cerebral blood flow, which...... can lead to an inadequate oxygen delivery to the brain and contribute to the development of fatigue....

  10. Reassessment of FDG uptake in tumor cells: High FDG uptake as a reflection of oxygen-independent glycolysis dominant energy production

    Energy Technology Data Exchange (ETDEWEB)

    Waki, A.; Fujibayashi, Y.; Yonekura, Y.; Sadato, N.; Ishii, Y.; Yokoyama, A

    1997-10-01

    To determine appropriate use of 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose (FDG) in the diagnosis of malignant tumors, the mechanism of enhanced FDG uptake in tumor cells was reassessed using in vitro cultured cell lines and {sup 3}H-deoxyglucose (DG), in combination with possible parameters of aerobic and anaerobic energy production. The high DG uptake in the tumor cells reflected the dependency of energy production on anaerobic glycolysis, and paradoxically on low levels of aerobic oxidative phosphorylation in mitochondria. We discuss here factors underlying anaerobic glycolysis in tumor cells.

  11. MUSCLE TENSION DYSPHONIA

    Directory of Open Access Journals (Sweden)

    Irena Hočevar Boltežar

    2004-07-01

    Full Text Available Background. Muscle tension dysphonia (MTD is the cause of hoarseness in almost one half of the patients with voice disorders. The otorhinolaryngologic examination discovers no evident organic lesions in the larynx at least in the beginning of the voice problems. The reason for the hoarse voice is a disordered and maladjusted activity of the muscles taking part in phonation and/or articulation. In some patients, the irregular function of the larynx results in mucosal lesions on vocal folds. The factors participating in the development of MTD, directly or indirectly influence the quality of laryngeal mucosa, the activity of the phonatory muscles and/or increase of the vocal load. In the diagnostics and treatment of the MTD a phoniatrician, a speech and language therapist and a psychologist closely cooperate with the patient who must take an active role. The treatment is a long-lasting one but resulted in a high percentage of clinical success.Conclusions. Most likely, MTD is not a special disease but only a reflection of any disorder in the complicated system of regulation and realization of phonation. The prognosis of treatment is good when all unfavourable factors participating in development of MTD are eliminated and a proper professional voice- and psychotherapy started.

  12. Oxygen dependency of porfiromycin cytotoxicity

    International Nuclear Information System (INIS)

    Marshall, R.S.; Rauth, A.M.

    1987-01-01

    The authors determined the oxygen dependency of toxicity for the bioreductive alkylating agents mitomycin C (MMC) and porfiromycin (PM) to investigate whether the toxicities of these agents increase in the range of oxygen tensions over which cells become increasingly radioresistant. In the present work the oxygen dependency of PM in CHO cells was determined by assaying survival as a function of time of exposure to 1.0 μg/ml PM under various known levels of oxygen. While PM demonstrated preferential hypoxic cell toxicity, aerobic cell survival was reduced ten-fold after five hours of exposure. Conversely, PM toxicity after a five hour hypoxic exposure to <0.001% oxygen appeared to be greater than that observed for similar MMC exposures, suggesting that PM may be more selective than MMC in killing hypoxic rather than aerobic cells. The authors are currently investigating this preferential toxicity in two human cell lines, one of which is resistant to these agents. At present, these observations suggest that PM may be more effective than MMC at destroying tumour cells in regions of intermediate and low oxygen tensions which may survive radiotherapy, though the range of oxygen tensions which mediate toxicity is similar for both agents

  13. Tension pneumocephalus: Mount Fuji sign

    Directory of Open Access Journals (Sweden)

    Pulastya Sanyal

    2015-01-01

    Full Text Available A 13-year-old male was operated for a space occupying lesion in the brain. A noncontrast computed tomography scan done in the late postoperative period showed massive subdural air collection causing compression of bilateral frontal lobes with widening of interhemispheric fissure and the frontal lobes acquiring a peak like configuration - causing tension pneumocephalus-"Mount Fuji sign." Tension pneumocephalus occurs when air enters the extradural or intradural spaces in sufficient volume to exert a mass or pressure effect on the brain, leading to brain herniation. Tension pneumocephalus is a surgical emergency, which needs immediate intervention in the form of decompression of the cranial cavity by a burr hole or needle aspiration. The Mount Fuji sign differentiates tension pneumocephalus from pneumocephalus.

  14. Tumor Necrosis Factor-α and Apoptosis Signal-Regulating Kinase 1 Control Reactive Oxygen Species Release, Mitochondrial Autophagy and C-Jun N-Terminal Kinase/P38 Phosphorylation During Necrotizing Enterocolitis

    Directory of Open Access Journals (Sweden)

    Naira Baregamian

    2009-01-01

    Full Text Available Background: Oxidative stress and inflammation may contribute to the disruption of the protective gut barrier through various mechanisms; mitochondrial dysfunction resulting from inflammatory and oxidative injury may potentially be a significant source of apoptosis during necrotizing enterocolitis (NEC. Tumor necrosis factor (TNFα is thought to generate reactive oxygen species (ROS and activate the apoptosis signal-regulating kinase 1 (ASK1-c-Jun N-terminal kinase (JNK/p38 pathway. Hence, the focus of our study was to examine the effects of TNFα/ROs on mitochondrial function, ASK1-JNK/p38 cascade activation in intestinal epithelial cells during NEC.

  15. Intraoperative transfusion threshold and tissue oxygenation

    DEFF Research Database (Denmark)

    Nielsen, K; Dahl, B; Johansson, P I

    2012-01-01

    Transfusion with allogeneic red blood cells (RBCs) may be needed to maintain oxygen delivery during major surgery, but the appropriate haemoglobin (Hb) concentration threshold has not been well established. We hypothesised that a higher level of Hb would be associated with improved subcutaneous...... oxygen tension during major spinal surgery....

  16. Magnetic tension and gravitational collapse

    International Nuclear Information System (INIS)

    Tsagas, Christos G

    2006-01-01

    The gravitational collapse of a magnetized medium is investigated by studying qualitatively the convergence of a timelike family of non-geodesic worldlines in the presence of a magnetic field. Focusing on the field's tension, we illustrate how the winding of the magnetic forcelines due to the fluid's rotation assists the collapse, while shear-like distortions in the distribution of the field's gradients resist contraction. We also show that the relativistic coupling between magnetism and geometry, together with the tension properties of the field, lead to a magneto-curvature stress that opposes the collapse. This tension stress grows stronger with increasing curvature distortion, which means that it could potentially dominate over the gravitational pull of the matter. If this happens, a converging family of non-geodesic worldlines can be prevented from focusing without violating the standard energy conditions

  17. High Glucose Promotes Tumor Invasion and Increases Metastasis-Associated Protein Expression in Human Lung Epithelial Cells by Upregulating Heme Oxygenase-1 via Reactive Oxygen Species or the TGF-β1/PI3K/Akt Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Xiaowen Kang

    2015-02-01

    Full Text Available Background: Growing evidence indicates that heme oxygenase-1 (HO-1 is up-regulated in malignancies and subsequently alters tumor aggressiveness and various cancer-related factors, such as high glucose (HG levels. HO-1 expression can be induced when glucose concentrations are above 25 mM; however, the role of HO-1 in lung cancer patients with diabetes remains unknown. Therefore, in this study we investigated the promotion of tumor cell invasion and the expression of metastasis-associated proteins by inducing the up-regulation of HO-1 expression by HG treatment in A549 human lung epithelial cells. Methods: The expression of HO-1and metastasis-associated protein expression was explored by western blot analysis. HO-1 enzymatic activity, reactive oxygen species (ROS production and TGF-β1 production were examined by ELISA. Invasiveness was analyzed using a Transwell chamber. Results: HG treatment of A549 cells induced an increase in HO-1 expression, which was mediated by the HG-induced generation of reactive oxygen species (ROS and transforming growth factor-β1 (TGF-β1 in a concentration- and time-dependent manner. Following the increase in HO-1 expression, the enzymatic activity of HO-1 also increased in HG-treated cells. Pretreatment with N-acetyl-L-cysteine (NAC or with phosphatidylinositol 3-kinase (PI3K/Akt inhibitors attenuated the HG-induced increase in HO-1 expression. HG treatment of A549 cells enhanced the invasion potential of these cells, as shown with a Transwell assay, and increased metastasis-associated protein expression. However, HO-1 siRNA transfection significantly decreased these capabilities. Conclusion: this study is the first to demonstrate that HG treatment of A549 human lung epithelial cells promotes tumor cell invasion and increases metastasis-associated protein expression by up-regulating HO-1 expression via ROS or the TGF-β1/PI3K/Akt signaling pathway.

  18. AUTOGENIC THERAPY IN TENSION HEADACHE

    Science.gov (United States)

    Amruthraj, Brunda; Mishra, H.; Kumaraiah, V.

    1987-01-01

    SUMMARY Ten subjects diagnosed as Psychalgia were taken for study. A multiple baseline design was adapted and clients were subjected to 30 sessions of autogenic training. They were assessed using physiological (EMG and thermal change) and behavioural measures (Visual analogue scale and behavioural symptom checklist). Findings revealed autogenic therapy to be effective in reducing tension headache. PMID:21927245

  19. Tensions of Corporate Social Responsibility

    DEFF Research Database (Denmark)

    Strand, Robert

    , and formally rational tools like key performance indicators (KPIs) can be developed and employed in service of the selected substantively rational ends. I show how these KPIs can serve to highlight tensions between substantively rational ends. As such, I argue the CSR bureaucracy can create a space...

  20. AUTOGENIC THERAPY IN TENSION HEADACHE

    OpenAIRE

    Amruthraj, Brunda; Mishra, H.; Kumaraiah, V.

    1987-01-01

    SUMMARY Ten subjects diagnosed as Psychalgia were taken for study. A multiple baseline design was adapted and clients were subjected to 30 sessions of autogenic training. They were assessed using physiological (EMG and thermal change) and behavioural measures (Visual analogue scale and behavioural symptom checklist). Findings revealed autogenic therapy to be effective in reducing tension headache.

  1. [Case of tension pneumothorax associated with asthma attack during general anesthesia].

    Science.gov (United States)

    Komasawa, Nobuyasu; Ueki, Ryusuke; Kusuyama, Kazuki; Okano, Yukari; Tatara, Tsuneo; Tashiro, Chikara

    2010-05-01

    We report a case of tension pneumothorax associated with asthma attack during general anesthesia. An 86-year-old woman with dementia underwent cataract surgery under general anesthesia. At 70 min after the start of operation, airway pressure suddenly increased from 19 to 28 cm HO2O. In spite of bag ventilation with 100% oxygen, Sp(O2) decreased to 81%. Chest-Xp showed typical image of tension pneumothorax. Chest drainage was immediately performed, after which Pa(O2) recovered soon. She was extubated on postoperative day 1 without any neurological disorder. Hyperinflation of fragile alveoli by mechanical ventilation was likely a cause of tension pneumothorax.

  2. Oxygenation measurement by multi-wavelength oxygen-dependent phosphorescence and delayed fluorescence: catchment depth and application in intact heart

    NARCIS (Netherlands)

    Balestra, Gianmarco M.; Aalders, Maurice C. G.; Specht, Patricia A. C.; Ince, Can; Mik, Egbert G.

    2015-01-01

    Oxygen delivery and metabolism represent key factors for organ function in health and disease. We describe the optical key characteristics of a technique to comprehensively measure oxygen tension (PO(2)) in myocardium, using oxygen-dependent quenching of phosphorescence and delayed fluorescence of

  3. Urinary incontinence - tension-free vaginal tape

    Science.gov (United States)

    ... ency/article/007377.htm Urinary incontinence - tension-free vaginal tape To use the sharing features on this page, please enable JavaScript. Placement of tension-free vaginal tape is surgery to help control stress urinary ...

  4. Robust Tensioned Kevlar Suspension Design

    Science.gov (United States)

    Young, Joseph B.; Naylor, Bret J.; Holmes, Warren A.

    2012-01-01

    One common but challenging problem in cryogenic engineering is to produce a mount that has excellent thermal isolation but is also rigid. Such mounts can be achieved by suspending the load from a network of fibers or strings held in tension. Kevlar fibers are often used for this purpose owing to their high strength and low thermal conductivity. A suite of compact design elements has been developed to improve the reliability of suspension systems made of Kevlar.

  5. Surface Tension Confines Cryogenic Liquid

    Science.gov (United States)

    Castles, Stephen H.; Schein, Michael E.

    1989-01-01

    New type of Dewar provides passive, constant-temperature cryogenic cooling for scientific instruments under normal-to low-gravity conditions. Known as Surface-Tension-Contained Liquid Cryogen Cooler (STCLCC), keeps liquid cryogen in known location inside the Dewar by trapping liquid inside spongelike material. Unique sponge material fills most of volume of inner tank. Sponge is all-silica, open-cell material similar to that used for Space Shuttle thermal-protection tiles.

  6. Delayed Tension Pneumothorax During Surgery

    Directory of Open Access Journals (Sweden)

    Ying-Lun Chen

    2005-10-01

    Full Text Available Tension pneumothorax is a life-threatening emergency that rapidly results in cardiopulmonary arrest. It requires prompt diagnosis and treatment. We present 2 cases from our practice, 1 caused by blunt chest trauma and the other resulting from laparoscopic surgery. Both were successfully treated by insertion of a chest tube. The diagnosis and treatment of intraoperative pneumothorax is discussed together with a review of the literature.

  7. Tumor Tension Induces Persistent Inflammation and Promotes Breast Cancer Aggression

    Science.gov (United States)

    2016-10-01

    law , no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB...expression data were obtain from Szasz AM et al. Oncotarget. 2016. DOI: 10.18632/oncotarget. Figure 5. Early macrophage depletion attenuates fibrosis and

  8. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  9. Oxygen toxicity

    Directory of Open Access Journals (Sweden)

    C. A. van der Westhuizen

    1990-07-01

    Full Text Available Oxygen has been discovered about 200 years ago. Since then the vital physiological involvement of oxygen in various biologi­cal processes, mainly energy production, has been established. However, in the body molecular oxygen can be converted to toxic oxygen metabolites such as superoxide anion, hydrogen peroxide, the hydroxyl radical and singlet oxygen. These toxic metabolites are produced mainly in the mitochondria, plasma membranes and endoplasmic reticulum.

  10. Mangosenone F, A Furanoxanthone from Garciana mangostana, Induces Reactive Oxygen Species-Mediated Apoptosis in Lung Cancer Cells and Decreases Xenograft Tumor Growth.

    Science.gov (United States)

    Seo, Kyung Hye; Ryu, Hyung Won; Park, Mi Jin; Park, Ki Hun; Kim, Jin Hyo; Lee, Mi-Ja; Kang, Hyeon Jung; Kim, Sun Lim; Lee, Jin Hwan; Seo, Woo Duck

    2015-11-01

    Mangosenone F (MSF), a natural xanthone, was isolated form Carcinia mangotana, and a few studies have reported its glycosidase inhibitor effect. In this study we investigated the anti lung cancer effect of MSF both in vitro and in vivo. MSF inhibited cancer cell cytotoxicity and induced and induced apoptosis via reactive oxygen species (ROS) generation in NCI-H460. MSF treatment also showed in pronounced release of apoptogenic cytochrome c from the mitochondria to the cytosol, downregulation of Bcl-2 and Bcl-xL, and upregulation of Bax, suggesting that caspase-mediated pathways were involved in MSF-induced apoptosis. ROS activation of the mitogen-activated protein kinase signaling pathway was shown to play a predominant role in the apoptosis mechanism of MSF. Compared with cisplatin treatment, MSF treatment showed significantly increased inhibition of the growth of NCI-H460 cells xenografted in nude mice. Together, these results indicate the potential of MSF as a candidate natural anticancer drug by promoting ROS production. Copyright © 2015 John Wiley & Sons, Ltd.

  11. Development of pulmonary vascular response to oxygen

    International Nuclear Information System (INIS)

    Morin, F.C. III; Egan, E.A.; Ferguson, W.; Lundgren, C.E.

    1988-01-01

    The ability of the pulmonary circulation of the fetal lamb to respond to a rise in oxygen tension was studied from 94 to 146 days of gestation. The unanesthetized ewe breathed room air at normal atmospheric pressure, followed by 100% oxygen at three atmospheres absolute pressure in a hyperbaric chamber. In eleven near-term lambs, fetal arterial oxygen tension (Pa O 2 ) increased from 25 to 55 Torr, which increased the proportion or right ventricular output distributed to the fetal lungs from 8 to 59%. In five very immature lambs fetal Pa O 2 increased from 27 to 174 Torr, but the proportion of right ventricular output distributed to the lung did not change. In five of the near-term lambs, pulmonary blood flow was measured. For each measurement of the distribution of blood flow, approximately 8 x 10 5 spheres of 15-μm diameter, labeled with either 153 Gd, 113 Sn, 103 Ru, 95 Nb, or 46 Sc were injected. It increased from 34 to 298 ml · kg fetal wt -1 · min -1 , an 8.8-fold increase. The authors conclude that the pulmonary circulation of the fetal lamb does not respond to an increase in oxygen tension before 101 days of gestation; however, near term an increase in oxygen tension alone can induce the entire increase in pulmonary blood flow that normally occurs after the onset of breathing at birth

  12. Oxygen Modulates Human Decidual Natural Killer Cell Surface Receptor Expression and Interactions with Trophoblasts1

    Science.gov (United States)

    Wallace, Alison E.; Goulwara, Sonu S.; Whitley, Guy S.; Cartwright, Judith E.

    2014-01-01

    Decidual natural killer (dNK) cells have been shown to both promote and inhibit trophoblast behavior important for decidual remodeling in pregnancy and have a distinct phenotype compared to peripheral blood NK cells. We investigated whether different levels of oxygen tension, mimicking the physiological conditions of the decidua in early pregnancy, altered cell surface receptor expression and activity of dNK cells and their interactions with trophoblast. dNK cells were isolated from terminated first-trimester pregnancies and cultured in oxygen tensions of 3%, 10%, and 21% for 24 h. Cell surface receptor expression was examined by flow cytometry, and the effects of secreted factors in conditioned medium (CM) on the trophoblast cell line SGHPL-4 were assessed in vitro. SGHPL-4 cells treated with dNK cell CM incubated in oxygen tensions of 10% were significantly more invasive (P cells treated with dNK cell CM incubated in oxygen tensions of 3% or 21%. After 24 h, a lower percentage of dNK cells expressed CD56 at 21% oxygen (P cells expressed NKG2D at 10% oxygen (P oxygen tensions, with large patient variation. This study demonstrates dNK cell phenotype and secreted factors are modulated by oxygen tension, which induces changes in trophoblast invasion and endovascular-like differentiation. Alterations in dNK cell surface receptor expression and secreted factors at different oxygen tensions may represent regulation of function within the decidua during the first trimester of pregnancy. PMID:25232021

  13. The Plastic Tension Field Method

    DEFF Research Database (Denmark)

    Hansen, Thomas

    2005-01-01

    This paper describes a calculation method for steel plate girders with transverse web stiffeners subjected to shear. It may be used for predicting the failure load or, as a design method, to determine the optimal amount of internal web stiffeners. The new method is called the plastic tension field...... method. The method is based on the theory of plasticity and is analogous to the so-called diagonal compression field method developed for reinforced concrete beams with transverse stirrups, which is adopted in the common European concrete code (Eurocode 2). Many other theories have been developed...

  14. Axelrod's model with surface tension

    Science.gov (United States)

    Pace, Bruno; Prado, Carmen P. C.

    2014-06-01

    In this work we propose a subtle change in Axelrod's model for the dissemination of culture. The mechanism consists of excluding from the set of potentially interacting neighbors those that would never possibly exchange. Although the alteration proposed does not alter the state space topologically, it yields significant qualitative changes, specifically the emergence of surface tension, driving the system in some cases to metastable states. The transient behavior is considerably richer, and cultural regions become stable leading to the formation of different spatiotemporal patterns. A metastable "glassy" phase emerges between the globalized phase and the disordered, multicultural phase.

  15. Update on normal tension glaucoma

    Directory of Open Access Journals (Sweden)

    Jyotiranjan Mallick

    2016-01-01

    Full Text Available Normal tension glaucoma (NTG is labelled when typical glaucomatous disc changes, visual field defects and open anterior chamber angles are associated with intraocular pressure (IOP constantly below 21 mmHg. Chronic low vascular perfusion, Raynaud's phenomenon, migraine, nocturnal systemic hypotension and over-treated systemic hypertension are the main causes of normal tension glaucoma. Goldmann applanation tonometry, gonioscopy, slit lamp biomicroscopy, optical coherence tomography and visual field analysis are the main tools of investigation for the diagnosis of NTG. Management follows the same principles of treatment for other chronic glaucomas: To reduce IOP by a substantial amount, sufficient to prevent disabling visual loss. Treatment is generally aimed to lower IOP by 30% from pre-existing levels to 12-14 mmHg. Betaxolol, brimonidine, prostaglandin analogues, trabeculectomy (in refractory cases, systemic calcium channel blockers (such as nifedipine and 24-hour monitoring of blood pressure are considered in the management of NTG. The present review summarises risk factors, causes, pathogenesis, diagnosis and management of NTG.

  16. Oxygen Therapy

    Science.gov (United States)

    ... their breathing to dangerously low levels. Will I need oxygen when I sleep? Usually if you use supplemental oxygen during the ... your health care provider tells you you only need to use oxygen for exercise or sleep. Even if you feel “fine” off of your ...

  17. The study and design of tension controller

    Science.gov (United States)

    Jun, G.; Lamei, X.

    2018-02-01

    Tension control is a wide used technology in areas such as textiles, paper and plastic films. In this article, the tension control system release and winding process is analyzed and the mathematical model of tension control system is established, and a high performance tension controller is designed. In hardware design, STM32F130 single chip microcomputer is used as the control core, which has the characteristics of fast running speed and rich peripheral features. In software design, μC/OS-II operating system is introduced to improve the efficiency of single chip microcomputer, and enhance the independence of each module, and make development and maintenance more convenient. The taper tension control is adopted in the winding part, which can effectively solve the problem of rolling shrinkage. The results show that the tension controller has the characteristics of simple structure, easy operation and stable performance.

  18. Soft-tissue tension total knee arthroplasty.

    Science.gov (United States)

    Asano, Hiroshi; Hoshino, Akiho; Wilton, Tim J

    2004-08-01

    It is far from clear how best to define the proper strength of soft-tissue tensioning in total knee arthroplasty (TKA). We attached a torque driver to the Monogram balancer/tensor device and measured soft-tissue tension in full extension and 90 degrees flexion during TKA. In our surgical procedure, when we felt proper soft-tissue tension was being applied, the mean distraction force was noted to be 126N in extension and 121N in flexion. There was no significant correlation between soft-tissue tension and the postoperative flexion angle finally achieved. To the best of our knowledge, this is the first study to assess the actual distraction forces in relation to soft-tissue tension in TKA. Further study may reveal the most appropriate forces to achieve proper soft-tissue tension in the wide variety of circumstances presenting at knee arthroplasty.

  19. Bone tumors

    International Nuclear Information System (INIS)

    Unni, K.K.

    1988-01-01

    This book contains the proceedings on bone tumors. Topics covered include: Bone tumor imaging: Contribution of CT and MRI, staging of bone tumors, perind cell tumors of bone, and metastatic bone disease

  20. The Equilibrium Spreading Tension of Pulmonary Surfactant

    OpenAIRE

    Dagan, Maayan P.; Hall, Stephen B.

    2015-01-01

    Monomolecular films at an air/water interface coexist at the equilibrium spreading tension (γe) with the bulk phase from which they form. For individual phospholipids, γe is single-valued, and separates conditions at which hydrated vesicles adsorb from tensions at which overcompressed monolayers collapse. With pulmonary surfactant, isotherms show that monolayers compressed on the surface of bubbles coexist with the three-dimensional collapsed phase over a range of surface tensions. γe therefo...

  1. Intervention of oxygen-control ability to radiation sensitivity, cell aging and cell transformation

    International Nuclear Information System (INIS)

    Yoshii, Hanako; Watanabe, Masami

    2009-01-01

    Oxygen is essential for life, and cells have therefore developed numerous adaptive responses to oxygen change. Here, we examined the difference in oxygen-control functions of human (HE), mouse (ME), and Syrian hamster embryo (SHE) cells cultured under different oxygen conditions (0.5%, 2% and 20%), and also examined whether oxygen tensions contributed to cellular lifespan and transformation. HE cells had their replicative lifespan slightly extended under hypoxic (0.5% and 2% oxygen) conditions, but were not immortalized under any of the oxygen concentrations. On the other hand, although ME cells cultured under 20% oxygen tension decreased their proliferation potency temporarily at early stage, all rodent cells were immortalized and acquired anchorage-independency, regardless of oxygen tension. These results suggest that cellular oxygen control function is related to sensitivities cellular immortalization and transformation. To understand intervention of oxygen control ability on cellular immortalization and transformation, we examined the intracellular oxidative level, mitochondria functions and radiation sensitivity. Intracellular oxidative levels of hypoxically cultured rodent cells were significantly enhanced. Mitochondrial membrane potential was altered depend on oxygen tensions, but the change was not parallel to mitochondria number in rodent cells. ME cells were particularly sensitive to oxygen change, and showed a clear oxygen effect on the X-ray survival. However, there was no difference in frequency of radiation-induced micronuclei between HE and ME cells. These results suggest that the response to oxygen change differs markedly in HE and rodent cells. (author)

  2. Oxygen Therapy

    Directory of Open Access Journals (Sweden)

    Bonnie Solmes

    2000-01-01

    Full Text Available LTOT is prescribed for people with chronic lung disease in whom there is a decrease in the ability of the lungs to supply enough oxygen to the body. The heart is obliged to pump faster to meet the body's oxygen requirements. This may place undue stress on the heart, resulting in palpitations, dizziness and fatigue. A low oxygen level in arterial blood is also harmful to the heart, the brain and the pulmonary blood vessels. Oxygen therapy is used to break this cycle. A person with low blood oxygen will often be able to accomplish more with less fatigue with the help of supplemental oxygen therapy. Shortness of breath is a mechanical problem resulting from the effects of chronic obstructive pulmonary disease. Oxygen therapy may or may not reduce shortness of breath, but it will help the lungs and heart to function with less stress.

  3. Tension pneumothorax accompanied by type A aortic dissection.

    Science.gov (United States)

    Hifumi, Toru; Kiriu, Nobuaki; Inoue, Junichi; Koido, Yuichi

    2012-11-09

    A 51-year-old man was brought to the emergency room because of a sudden onset of severe dysponea. On presentation, his blood pressure was 94/55 mm Hg. Oxygen saturation was 86% while he was receiving 10 l/min oxygen through a non-rebreather mask. On physical examination, no jugular venous distention was noted, but breath sounds over the left lung were diminished. A bedside chest radiograph showed left tension pneumothorax, for which urgent needle decompression followed by chest thoracostomy was performed. Ventricular tachycardia developed, but a biphasic shock at 120 J immediately restored normal sinus rhythm. His vital signs, however, did not improve. A CT scan of the chest showed type A aortic dissection with bullae in the upper lobe of the left lung. He had an emergency operation for distal aortic arch displacement and was discharged on the 37th day of hospitalisation.

  4. Actin filaments as tension sensors.

    Science.gov (United States)

    Galkin, Vitold E; Orlova, Albina; Egelman, Edward H

    2012-02-07

    The field of mechanobiology has witnessed an explosive growth over the past several years as interest has greatly increased in understanding how mechanical forces are transduced by cells and how cells migrate, adhere and generate traction. Actin, a highly abundant and anomalously conserved protein, plays a large role in forming the dynamic cytoskeleton that is so essential for cell form, motility and mechanosensitivity. While the actin filament (F-actin) has been viewed as dynamic in terms of polymerization and depolymerization, new results suggest that F-actin itself may function as a highly dynamic tension sensor. This property may help explain the unusual conservation of actin's sequence, as well as shed further light on actin's essential role in structures from sarcomeres to stress fibers. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Matrix stiffness and oxigen tension modulate epigenetic conversion of mouse dermal fibroblasts into insulin producing cells.

    Directory of Open Access Journals (Sweden)

    Alessandro Zenobi

    2017-05-01

    Full Text Available In vivo, cells are surrounded by a three-dimensional (3-D organization of supporting matrix, neighboring cells and a gradient of chemical and mechanical signals (Antoni, et al., 2015. However, the present understanding of many biological processes is mainly based on two-dimensional (2-D systems that typically provides a static environment. In the present study, we tested two different 3-D culture systems and apply them to the epigenetic conversion of mouse dermal fibroblasts into insulin producing-cells (Pennarossa, et al., 2013; Brevini, et al., 2015, combining also the use of two oxygen tensions. In particular, cells were differentiated using the Polytetrafluoroethylene micro-bioreactor (PTFE and the Polyacrylamide (PAA gels with different stiffness (1 kPa; 4 kPa, maintained either in the standard 20% or in the more physiological 5% oxygen tensions. Standard differentiation performed on plastic substrates was assessed as a control. Cell morphology (Fig.1A, insulin expression and release were analyzed to evaluate the role of both stiffness and oxygen tension in the process. The results obtained showed that 1 kPa PAA gel and PTFE system induced a significantly higher insulin expression and release than plastic and 4 kPa PAA gel, especially in low oxygen condition (Fig.1B. Furthermore, comparing the efficiency of the two systems tested, 1 kPa PAA gel ensured a higher insulin transcription than PTFE (Fig.1C. Recent studies show the direct influence of substrates on lineage commitment and cell differentiation (Engler, et al., 2006; Evans, et al., 2009. The evidence here presented confirm that the use of an appropriate stiffness (similar to the pancreatic tissue, combined with a physiological oxygen tension, promote β-cell differentiation, with beneficial effects on cell functional activity and insulin release. The present results highlight the importance of 3-D cell rearrangement and oxigen tension to promote in vitro epigenetic conversion of

  6. Theoretical analysis of the dose dependence of the oxygen enhancement ratio and its relevance for clinical applications

    International Nuclear Information System (INIS)

    Wenzl, Tatiana; Wilkens, Jan J

    2011-01-01

    The increased resistance of hypoxic cells to ionizing radiation is usually believed to be the primary reason for treatment failure in tumors with oxygen-deficient areas. This oxygen effect can be expressed quantitatively by the oxygen enhancement ratio (OER). Here we investigate theoretically the dependence of the OER on the applied local dose for different types of ionizing irradiation and discuss its importance for clinical applications in radiotherapy for two scenarios: small dose variations during hypoxia-based dose painting and larger dose changes introduced by altered fractionation schemes. Using the widespread Alper-Howard-Flanders and standard linear-quadratic (LQ) models, OER calculations are performed for T1 human kidney and V79 Chinese hamster cells for various dose levels and various hypoxic oxygen partial pressures (pO2) between 0.01 and 20 mmHg as present in clinical situations in vivo. Our work comprises the analysis for both low linear energy transfer (LET) treatment with photons or protons and high-LET treatment with heavy ions. A detailed analysis of experimental data from the literature with respect to the dose dependence of the oxygen effect is performed, revealing controversial opinions whether the OER increases, decreases or stays constant with dose. The behavior of the OER with dose per fraction depends primarily on the ratios of the LQ parameters alpha and beta under hypoxic and aerobic conditions, which themselves depend on LET, pO2 and the cell or tissue type. According to our calculations, the OER variations with dose in vivo for low-LET treatments are moderate, with changes in the OER up to 11% for dose painting (1 or 3 Gy per fraction compared to 2 Gy) and up to 22% in hyper-/hypofractionation (0.5 or 20 Gy per fraction compared to 2 Gy) for oxygen tensions between 0.2 and 20 mmHg typically measured clinically in hypoxic tumors. For extremely hypoxic cells (0.01 mmHg), the dose dependence of the OER becomes more pronounced (up to 36

  7. Oxygen status during haemodialysis. The Cord-Group

    DEFF Research Database (Denmark)

    Nielsen, A L; Jensen, H Æ; Hegbrant, J

    1995-01-01

    Hypoxia during haemodialysis, mainly acetate, has been reported several times. In our study we have monitored oxygen status during 258 bicarbonate haemodialyses. A significant drop below 80 mmHg in mean oxygen tension occurred. Mean oxygen saturation reflected this drop but did not reach levels...... below 90%. The mean oxygen concentration was on the whole critical low, though slightly increasing during each haemodialysis session due to ultrafiltration. It is concluded that both hypoxia and hypoxaemia do occur during bicarbonate haemodialysis. To a group of patients generally having limited cardiac...... reserves, a poor oxygen status is a potentially serious complication to haemodialysis. Monitoring oxygen status is thus advisable....

  8. Cycling Hypoxia Induces a Specific Amplified Inflammatory Phenotype in Endothelial Cells and Enhances Tumor-Promoting Inflammation In Vivo

    Directory of Open Access Journals (Sweden)

    Céline Tellier

    2015-01-01

    Full Text Available Abnormal architecture of the tumor blood network, as well as heterogeneous erythrocyte flow, leads to temporal fluctuations in tissue oxygen tension exposing tumor and stromal cells to cycling hypoxia. Inflammation is another feature of tumor microenvironment and is considered as a new enabling characteristic of tumor progression. As cycling hypoxia is known to participate in tumor aggressiveness, the purpose of this study was to evaluate its role in tumor-promoting inflammation. Firstly, we assessed the impact of cycling hypoxia in vitro on endothelial inflammatory response induced by tumor necrosis factor α. Results showed that endothelial cells exposed to cycling hypoxia displayed an amplified proinflammatory phenotype, characterized by an increased expression of inflammatory cytokines, namely, interleukin (IL-6 and IL-8; by an increased expression of adhesion molecules, in particular intercellular adhesion molecule–1 (ICAM-1; and consequently by an increase in THP-1 monocyte adhesion. This exacerbation of endothelial inflammatory phenotype occurs through nuclear factor–κB overactivation. Secondly, the role of cycling hypoxia was studied on overall tumor inflammation in vivo in tumor-bearing mice. Results showed that cycling hypoxia led to an enhanced inflammation in tumors as prostaglandin-endoperoxide synthase 2 (PTGS2, IL-6, CXCL1 (C-X-C motif ligand 1, and macrophage inflammatory protein 2 (murine IL-8 functional homologs mRNA expression was increased and as a higher leukocyte infiltration was evidenced. Furthermore, cycling hypoxia–specific inflammatory phenotype, characterized by a simultaneous (baculoviral inhibitor of apoptosis repeat-containing 5low/PTGS2high/ICAM-1high/IL-6high/IL-8high expression, is associated with a poor prognosis in human colon cancer. This new phenotype could thus be used in clinic to more precisely define prognosis for colon cancer patients. In conclusion, our findings evidenced for the first time the

  9. Cerebral oxygenation is reduced during hyperthermic exercise in humans

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Nybo, Lars; Volianitis, S.

    2010-01-01

    Abstract Aim: Cerebral mitochondrial oxygen tension (P(mito)O(2)) is elevated during moderate exercise, while it is reduced when exercise becomes strenuous, reflecting an elevated cerebral metabolic rate for oxygen (CMRO(2)) combined with hyperventilation-induced attenuation of cerebral blood flo...

  10. Normal-tension glaucoma (Low-tension glaucoma)

    Science.gov (United States)

    Anderson, Douglas R

    2011-01-01

    Glaucoma is now considered an abnormal physiology in the optic nerve head that interacts with the level of intraocular pressure (IOP), with the degree and rate of damage depending on the IOP and presumably the degree of abnormal physiology. Diagnosis of normal-tension glaucoma (NTG), defined as glaucoma without a clearly abnormal IOP, depends on recognizing symptoms and signs associated with optic nerve vulnerability, in addition to absence of other explanations for disc abnormality and visual field loss. Among the findings are a halo or crescent of absence of retinal pigment epithelium around the disc, bilateral pre-chiasmal visual field defects, splinter hemorrhages at the disc margin, vascular dysregulation (low blood pressure, cold hands and feet, migraine headache with aura, and the like), or a family history of glaucoma. Possibly relevant, is a history of hemodynamic crisis, arterial obstructive disease, or sleep apnea. Neurological evaluation with imaging is needed only for atypical cases or ones that progress unexpectedly. Management follows the same principle of other chronic glaucomas, to lower the IOP by a substantial amount, enough to prevent disabling visual loss. However, many NTG cases are non-progressive. Therefore, it may often be wisein mild cases to determine whether the case is progressive and the rate of progression before deciding on how aggressivene to be with therapy. Efforts at neuroprotection and improvement in blood flow have not yet been shown effective. PMID:21150042

  11. Normal-tension glaucoma (Low-tension glaucoma

    Directory of Open Access Journals (Sweden)

    Anderson Douglas

    2011-12-01

    Full Text Available Glaucoma is now considered an abnormal physiology in the optic nerve head that interacts with the level of intraocular pressure (IOP, with the degree and rate of damage depending on the IOP and presumably the degree of abnormal physiology. Diagnosis of normal-tension glaucoma (NTG, defined as glaucoma without a clearly abnormal IOP, depends on recognizing symptoms and signs associated with optic nerve vulnerability, in addition to absence of other explanations for disc abnormality and visual field loss. Among the findings are a halo or crescent of absence of retinal pigment epithelium around the disc, bilateral pre-chiasmal visual field defects, splinter hemorrhages at the disc margin, vascular dysregulation (low blood pressure, cold hands and feet, migraine headache with aura, and the like, or a family history of glaucoma. Possibly relevant, is a history of hemodynamic crisis, arterial obstructive disease, or sleep apnea. Neurological evaluation with imaging is needed only for atypical cases or ones that progress unexpectedly. Management follows the same principle of other chronic glaucomas, to lower the IOP by a substantial amount, enough to prevent disabling visual loss. However, many NTG cases are non-progressive. Therefore, it may often be wisein mild cases to determine whether the case is progressive and the rate of progression before deciding on how aggressivene to be with therapy. Efforts at neuroprotection and improvement in blood flow have not yet been shown effective.

  12. Traumatic tension pneumocephalus: Two case reports

    Directory of Open Access Journals (Sweden)

    Abubaker Al-Aieb

    2017-01-01

    Conclusions: These are two rare cases with posttraumatic tension pneumocephalus treated conservatively with a favorable outcome. Early diagnosis of tension pneumocephalus is a crucial step to facilitate early recovery; however, the associated injuries need attention as they could influence the hospital course.

  13. Embracing Tensions in Feminist Organizational Communication Pedagogies

    Science.gov (United States)

    Linabary, Jasmine R.; Long, Ziyu; Mouton, Ashton; Rao, Ranjani L.; Buzzanell, Patrice M.

    2017-01-01

    Feminist pedagogies hold potential to create more inclusive and transformative classrooms. Adopting a tension-centered approach, we draw on our individual and collective reflections on the design and instruction of a multi-section undergraduate organizational communication course to build an autoethnographic account of the tensions associated with…

  14. Tending the tensions in co-creation

    DEFF Research Database (Denmark)

    Phillips, Professor MSO Louise; Nordentoft, Helle Merete; Pedersen, Lektor Christina Hee

    -for-granted positive value. In the panel we de-romanticise “co-creation” and explore how it is enacted in particular organisational contexts, concentrating on context-specific tensions arising in the meeting between different knowledge forms and interests. These include tensions BETWEEN dialogic views of knowledge co-creation...

  15. Post-tensioning system surveillance program

    International Nuclear Information System (INIS)

    Drew, G.E.

    1979-01-01

    Nuclear power plant containment structure post-tensioning system tendon surveillance program is described in detail. Data collected over three yearly post-tensioning system Surveillance Programs is presented and evaluated to correlate anticipated stress losses with actual losses. In addition corrosion protected system performance is analyzed

  16. Tension and robustness in multitasking cellular networks.

    Directory of Open Access Journals (Sweden)

    Jeffrey V Wong

    Full Text Available Cellular networks multitask by exhibiting distinct, context-dependent dynamics. However, network states (parameters that generate a particular dynamic are often sub-optimal for others, defining a source of "tension" between them. Though multitasking is pervasive, it is not clear where tension arises, what consequences it has, and how it is resolved. We developed a generic computational framework to examine the source and consequences of tension between pairs of dynamics exhibited by the well-studied RB-E2F switch regulating cell cycle entry. We found that tension arose from task-dependent shifts in parameters associated with network modules. Although parameter sets common to distinct dynamics did exist, tension reduced both their accessibility and resilience to perturbation, indicating a trade-off between "one-size-fits-all" solutions and robustness. With high tension, robustness can be preserved by dynamic shifting of modules, enabling the network to toggle between tasks, and by increasing network complexity, in this case by gene duplication. We propose that tension is a general constraint on the architecture and operation of multitasking biological networks. To this end, our work provides a framework to quantify the extent of tension between any network dynamics and how it affects network robustness. Such analysis would suggest new ways to interfere with network elements to elucidate the design principles of cellular networks.

  17. Tension Pneumothorax following an Accidental Kerosene Poisoning ...

    African Journals Online (AJOL)

    Tension pneumothorax is a rare complication following an accidental kerosene poisoning. In such situation, a bed-side needle thoracocentesis is performed because of its potential of becoming fatal; hence its clinical importance. A case of 15 month old boy with tension pneumothorax following accidental kerosene ...

  18. Initial tension loss in cerclage cables.

    Science.gov (United States)

    Ménard, Jérémie; Émard, Maxime; Canet, Fanny; Brailovski, Vladimir; Petit, Yvan; Laflamme, George Y

    2013-10-01

    Cerclage cables, frequently used in the management of fractures and osteotomies, are associated with a high failure rate and significant loosening during surgery. This study compared the capacity to maintain tension of different types of orthopaedic cable systems. Multifilament Cobalt-Chrome (CoCr) cables with four different crimp/clamp devices (DePuy, Stryker, Zimmer and Smith&Nephew) and one non-metallic Nylon (Ny) cable from Kinamed were instrumented with a load cell to measure tension during insertion. Significant tension loss was observed with crimping for all cables (Ptensioner led to an additional unexpected tension loss (CoCr-DePuy: 18%, CoCr-Stryker: 29%, CoCr-Smith&Nephew: 33%, Ny: 46%, and CoCr-Zimmer: 52%). The simple CoCr (DePuy) cable system outperformed the more sophisticated locking devices due to its significantly better ability to prevent tension loss. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Front instabilities and invasiveness of simulated 3D avascular tumors.

    Directory of Open Access Journals (Sweden)

    Nikodem J Poplawski

    2010-05-01

    Full Text Available We use the Glazier-Graner-Hogeweg model to simulate three-dimensional (3D, single-phenotype, avascular tumors growing in an homogeneous tissue matrix (TM supplying a single limiting nutrient. We study the effects of two parameters on tumor morphology: a diffusion-limitation parameter defined as the ratio of the tumor-substrate consumption rate to the substrate-transport rate, and the tumor-TM surface tension. This initial model omits necrosis and oxidative/hypoxic metabolism effects, which can further influence tumor morphology, but our simplified model still shows significant parameter dependencies. The diffusion-limitation parameter determines whether the growing solid tumor develops a smooth (noninvasive or fingered (invasive interface, as in our earlier two-dimensional (2D simulations. The sensitivity of 3D tumor morphology to tumor-TM surface tension increases with the size of the diffusion-limitation parameter, as in 2D. The 3D results are unexpectedly close to those in 2D. Our results therefore may justify using simpler 2D simulations of tumor growth, instead of more realistic but more computationally expensive 3D simulations. While geometrical artifacts mean that 2D sections of connected 3D tumors may be disconnected, the morphologies of 3D simulated tumors nevertheless correlate with the morphologies of their 2D sections, especially for low-surface-tension tumors, allowing the use of 2D sections to partially reconstruct medically-important 3D-tumor structures.

  20. Dynamical modeling of surface tension

    International Nuclear Information System (INIS)

    Brackbill, J.U.; Kothe, D.B.

    1996-01-01

    In a recent review it is said that free-surface flows ''represent some of the difficult remaining challenges in computational fluid dynamics''. There has been progress with the development of new approaches to treating interfaces, such as the level-set method and the improvement of older methods such as the VOF method. A common theme of many of the new developments has been the regularization of discontinuities at the interface. One example of this approach is the continuum surface force (CSF) formulation for surface tension, which replaces the surface stress given by Laplace's equation by an equivalent volume force. Here, we describe how CSF might be made more useful. Specifically, we consider a derivation of the CSF equations from a minimization of surface energy as outlined by Jacqmin. This reformulation suggests that if one eliminates the computation of curvature in terms of a unit normal vector, parasitic currents may be eliminated For this reformulation to work, it is necessary that transition region thickness be controlled. Various means for this, in addition to the one discussed by Jacqmin are discussed

  1. Bilateral tension pneumothorax after acupuncture.

    Science.gov (United States)

    Mohammad, Nurashikin

    2018-04-19

    Acupuncture is an ancient complementary medicine which is currently used worldwide. Many serious adverse events have been reported which include a spectrum of mild-to-fatal complications. However, the level of awareness with regard to complications is still low both to physicians and patients. We report a 63-year-old who presented with acute shortness of breath 2 hours after having had acupuncture. On examination, there was absent breath sound heard on the left lung and slightly reduced breath sound on the right lung. She had type 1 respiratory failure. Urgent chest radiograph confirmed bilateral pneumothorax which was more severe on the left with tension pneumothorax and mediastinal shift. Chest tubes were inserted bilaterally after failed needle aspiration attempts. Subsequently, the pneumothoraces resolved, and she was discharged well. The bilateral pneumothoraces caused by acupuncture were curable but could have been potentially fatal if diagnosis was delayed. This case report adds to the limited current literature on the complications of acupuncture leading to bilateral pneumothoraces. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Hypoxia Pathway Proteins As Central Mediators of Metabolism in the Tumor Cells and Their Microenvironment

    Directory of Open Access Journals (Sweden)

    Sundary Sormendi

    2018-01-01

    Full Text Available Low oxygen tension or hypoxia is a determining factor in the course of many different processes in animals, including when tissue expansion and cellular metabolism result in high oxygen demands that exceed its supply. This is mainly happening when cells actively proliferate and the proliferating mass becomes distant from the blood vessels, such as in growing tumors. Metabolic alterations in response to hypoxia can be triggered in a direct manner, such as the switch from oxidative phosphorylation to glycolysis or inhibition of fatty acid desaturation. However, as the modulated action of hypoxia-inducible factors or the oxygen sensors (prolyl hydroxylase domain-containing enzymes can also lead to changes in enzyme expression, these metabolic changes can also be indirect. With this review, we want to summarize our current knowledge of the hypoxia-induced changes in metabolism during cancer development, how they are affected in the tumor cells and in the cells of the microenvironment, most prominently in immune cells.

  3. Transcriptional response to hypoxia in human tumors.

    NARCIS (Netherlands)

    Lal, A.; Peters, H.; Croix, B. St.; Haroon, Z.A.; Dewhirst, M.W.; Strausberg, R.L.; Kaanders, J.H.A.M.; Kogel, A.J. van der; Riggins, G.J.

    2001-01-01

    BACKGROUND: The presence of hypoxic regions within solid tumors is associated with a more malignant tumor phenotype and worse prognosis. To obtain a blood supply and protect against cellular damage and death, oxygen-deprived cells in tumors alter gene expression, resulting in resistance to therapy.

  4. Gastrothorax or tension pneumothorax: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Singh Sarvesh

    2011-01-01

    Full Text Available Gastrothorax, a rare complication following thoracoabdominal aortic aneurysm repair, is reported. The clinical features of a gastrothorax and tension pneumothorax are similar and thus, a gastrothorax can masquerade as a tension pneumothorax. The diagnosis is made by a high level of clinical suspicion, chest X-ray shows a distended stomach with air fluid levels and a computerised tomography is useful in assessing the diaphragm and establishing the positions of the various intra-abdominal organs. Also, the risk of an intercostal drainage tube placement and the role of nasogastric tube in avoiding the development of a tension gastrothorax is highlighted.

  5. Capillary-oxygenation-level-dependent near-infrared spectrometry in frontal lobe of humans

    NARCIS (Netherlands)

    Rasmussen, Peter; Dawson, Ellen A.; Nybo, Lars; van Lieshout, Johannes J.; Secher, Niels H.; Gjedde, Albert

    2007-01-01

    Brain function requires oxygen and maintenance of brain capillary oxygenation is important. We evaluated how faithfully frontal lobe near-infrared spectroscopy (NIRS) follows haemoglobin saturation (SCap) and how calculated mitochondrial oxygen tension (PMitoO2) influences motor performance. Twelve

  6. Radiosensitizers and the oxygen effects in mammalian cells

    International Nuclear Information System (INIS)

    Millar, B.C.; Fielden, E.M.; Steele, J.J.

    1979-01-01

    The survival curves for Chinese Hamster cells irradiated under various oxygen tensions have been determined. The variation in OER with oxygen concentration shows two distinct components. Between 1.4 and 7.0 μM the OER is constant with a value of 1.9. Experiments with nitroaromatic radiosensitizers in combination with low concentrations of oxygen show that they can all mimic the 'low concentration' oxygen effect. Of the compounds tested only misonidazole can apparently mimic the 'high concentration' oxygen effect although the full OER cannot be obtained with the authors cell line because of toxicity by the sensitizer. (Auth.)

  7. Managing Tensions And Forging Creative Synergies Between ...

    African Journals Online (AJOL)

    Managing Tensions And Forging Creative Synergies Between Indigenous And Modern Settlement Planning Concepts And Practices: Lessons For The Design And Planning For Sustainable Settlements And Built-Forms In Southern Africa.

  8. Tension perturbations of black brane spacetimes

    International Nuclear Information System (INIS)

    Traschen, Jennie; Fox, Daniel

    2004-01-01

    We consider black brane spacetimes that have at least one spatial translation Killing field that is tangent to the brane. A new parameter, the tension of a spacetime, is defined. The tension parameter is associated with spatial translations in much the same way that the ADM mass is associated with the time translation Killing field. In this work, we explore the implications of the spatial translation symmetry for small perturbations around a background black brane. For static-charged black branes we derive a law which relates the tension perturbation to the surface gravity times the change in the horizon area, plus terms that involve variations in the charges and currents. We find that as a black brane evaporates the tension decreases. We also give a simple derivation of a first law for black brane spacetimes. These constructions hold when the background stress-energy is governed by a Hamiltonian, and the results include arbitrary perturbative stress-energy sources

  9. Notch effects in uniaxial tension specimens

    International Nuclear Information System (INIS)

    Delph, T.J.

    1979-03-01

    Results of a literature survey on the effect of notches on the time-dependent failure of uniaxial tension specimens at elevated temperatures are presented. Particular attention is paid to the failure of notched specimens containing weldments

  10. Tension waves in tethered satellite cables

    Science.gov (United States)

    Lallman, F. J.

    1984-01-01

    A one-degree-of-freedom simulation of the Tethered Satellite System (TSS) was programmed using a distributed system model of the tether based on the one-dimensional wave equation. This model represents the time varying tension profile along the tether as the sum of two traveling waves of tension moving in opposite directions. A control loop was devised which combines a deployment rate command with the measured tension at the deployer to produce a smooth, stable rate of deployment of the subsatellite. Simulation results show a buildup of periodic bursts of high frequency oscillation in tension. This report covers the mathematical modelling and simulation results and explains the reason for the observed oscillations. The design of a possible vibration damping device is discussed.

  11. Tension Hydrothorax Related to Disseminated Endometriosis

    Directory of Open Access Journals (Sweden)

    AnnaKate Deal, MD

    2016-01-01

    Full Text Available We present the case of a 34-year-old woman presenting to the emergency department (ED with dyspnea, cough, and fever. She was found to have a tension hydrothorax and was treated with ultrasound-guided thoracentesis in the ED. Subsequent inpatient evaluation showed the patient had disseminated endometriosis. Tension hydrothorax has not been previously described in the literature as a complication of this disease.

  12. Density and surface tension of ionic liquids.

    Science.gov (United States)

    Kolbeck, C; Lehmann, J; Lovelock, K R J; Cremer, T; Paape, N; Wasserscheid, P; Fröba, A P; Maier, F; Steinrück, H-P

    2010-12-30

    We measured the density and surface tension of 9 bis[(trifluoromethyl)sulfonyl]imide ([Tf(2)N](-))-based and 12 1-methyl-3-octylimidazolium ([C(8)C(1)Im](+))-based ionic liquids (ILs) with the vibrating tube and the pendant drop method, respectively. This comprehensive set of ILs was chosen to probe the influence of the cations and anions on density and surface tension. When the alkyl chain length in the [C(n)C(1)Im][Tf(2)N] series (n = 1, 2, 4, 6, 8, 10, 12) is increased, a decrease in density is observed. The surface tension initially also decreases but reaches a plateau for alkyl chain lengths greater than n = 8. Functionalizing the alkyl chains with ethylene glycol groups results in a higher density as well as a higher surface tension. For the dependence of density and surface tension on the chemical nature of the anion, relations are only found for subgroups of the studied ILs. Density and surface tension values are discussed with respect to intermolecular interactions and surface composition as determined by angle-resolved X-ray photoelectron spectroscopy (ARXPS). The absence of nonvolatile surface-active contaminants was proven by ARXPS.

  13. Toward a general psychological model of tension and suspense.

    Science.gov (United States)

    Lehne, Moritz; Koelsch, Stefan

    2015-01-01

    Tension and suspense are powerful emotional experiences that occur in a wide variety of contexts (e.g., in music, film, literature, and everyday life). The omnipresence of tension and suspense suggests that they build on very basic cognitive and affective mechanisms. However, the psychological underpinnings of tension experiences remain largely unexplained, and tension and suspense are rarely discussed from a general, domain-independent perspective. In this paper, we argue that tension experiences in different contexts (e.g., musical tension or suspense in a movie) build on the same underlying psychological processes. We discuss key components of tension experiences and propose a domain-independent model of tension and suspense. According to this model, tension experiences originate from states of conflict, instability, dissonance, or uncertainty that trigger predictive processes directed at future events of emotional significance. We also discuss possible neural mechanisms underlying tension and suspense. The model provides a theoretical framework that can inform future empirical research on tension phenomena.

  14. Oxygenation measurements in head and neck cancers during hyperbaric oxygenation

    International Nuclear Information System (INIS)

    Becker, A.; Kuhnt, T.; Dunst, J.; Liedtke, H.; Krivokuca, A.; Bloching, M.

    2002-01-01

    Background: Tumor hypoxia has proven prognostic impact in head and neck cancers and is associated with poor response to radiotherapy. Hyperbaric oxygenation (HBO) offers an approach to overcome hypoxia. We have performed pO 2 measurements in selected patients with head and neck cancers under HBO to determine in how far changes in the oxygenation occur and whether a possible improvement of oxygenation parameters is maintained after HBO. Patients and Methods: Seven patients (five male, two female, age 51-63 years) with squamous cell cancers of the head and neck were investigated (six primaries, one local recurrence). The median pO 2 prior to HBO was determined with the Eppendorf histograph. Sites of measurement were enlarged cervical lymph nodes (n = 5), the primary tumor (n = 1) and local recurrence (n = 1). Patients then underwent HBO (100% O 2 at 240 kPa for 30 minutes) and the continuous changes in the oxygenation during HBO were determined with a Licox probe. Patients had HBO for 30 minutes (n = 6) to 40 minutes (n = 1). HBO was continued because the pO 2 had not reached a steady state after 30 minutes. After decompression, patients ventilated pure oxygen under normobaric conditions and the course of the pO 2 was further measured over about 15 minutes. Results: Prior to HBO, the median tumor pO 2 in the Eppendorf histography was 8.6 ± 5.4 mm Hg (range 3-19 mm Hg) and the pO 2 measured with the Licox probe was 17.3 ± 25.5 mm Hg (range 0-73 mm Hg). The pO 2 increased significantly during HBO to 550 ± 333 mm Hg (range 85-984 mm Hg, p = 0.018). All patients showed a marked increase irrespective of the oxygenation prior to HBO. The maximum pO 2 in the tumor was reached after 10-33 minutes (mean 17 minutes). After leaving the hyperbaric chamber, the pO 2 was 282 ± 196 mm Hg. All patients maintained an elevated pO 2 for further 5-25 minutes (138 ± 128 mm Hg, range 42-334 mm Hg, p = 0.028 vs the pO 2 prior to HBO). Conclusions: Hyperbaric oxygenation resulted in a

  15. Measurement of brain oxygenation changes using dynamic T1-weighted imaging

    DEFF Research Database (Denmark)

    Haddock, Bryan; Larsson, Henrik B W; Hansen, Adam E

    2013-01-01

    Magnetic resonance imaging (MRI) has proven useful in evaluating oxygenation in several types of tissue and blood. This study evaluates brain tissue oxygenation changes between normoxia and hyperoxia in healthy subjects using dynamic T1 and T2*-weighted imaging sequences. The change in FiO2 induced...... by hyperoxia caused a significant decrease in T1. A model to determine changes in tissue oxygen tension from the T1-weighted MRI signal is presented based on previous findings that T1 is sensitive to oxygen tension whereas T2* is sensitive to blood saturation. The two sequences produce results with different...... regional and temporal dynamics. These differences combined with results from simulations of the T1 signal intensities, indicate an increase in extravascular oxygen tension during hyperoxia. This study concludes that T1 and T2* responses to FiO2 serve as independent biomarkers of oxygen physiology...

  16. Tumor hypoxia and the positron data paradox

    International Nuclear Information System (INIS)

    De Schryver, A.; De Vis, K.; Schelstraete, K.

    1991-01-01

    It is possible using positron emission tomography (PET) techniques to obtain a fair estimate of both oxygen uptake and blood flow in human tumors. Oxygen uptake is measured by making use of tomographic recording during inhalation of oxygen 15, while blood flow can be determined either after injection of 13 N-ammonia or inhalation of 15 O-carbon dioxyde. A tomographic view is shown of a large sarcoma of right thigh, with ample oxygen concentration in its peripheral parts. Their oxygen concentration is higher than in surrounding normal tissues. The central core of the tumor, however, is clearly much less well provided with oxygen -this is what was expected. A similar picture emerges when blood flow is studied, f.ex, as in this case, using C 15 O 2 inhalation. Again, not surprising. There is, however, one more thing we can do: let the computer calculate the amount of oxygen extracted by the tumor as a function of blood flow (oxygen extraction ratio or OE x R) - pixel by pixel. If done so, it appears that those tumor parts where blood flow is low do not -as expected- extract more oxygen from whatever reduced flow is reaching them, than parts with normal flow do. Indeed, the resulting picture of the OE x R distribution denotes a remarkable homogeneity whether in the central or in the peripheral parts of the tumor. (author). 3 refs.; 1 tab

  17. A novel approach to pipeline tensioner modeling

    Energy Technology Data Exchange (ETDEWEB)

    O' Grady, Robert; Ilie, Daniel; Lane, Michael [MCS Software Division, Galway (Ireland)

    2009-07-01

    As subsea pipeline developments continue to move into deep and ultra-deep water locations, there is an increasing need for the accurate prediction of expected pipeline fatigue life. A significant factor that must be considered as part of this process is the fatigue damage sustained by the pipeline during installation. The magnitude of this installation-related damage is governed by a number of different agents, one of which is the dynamic behavior of the tensioner systems during pipe-laying operations. There are a variety of traditional finite element methods for representing dynamic tensioner behavior. These existing methods, while basic in nature, have been proven to provide adequate forecasts in terms of the dynamic variation in typical installation parameters such as top tension and sagbend/overbend strain. However due to the simplicity of these current approaches, some of them tend to over-estimate the frequency of tensioner pay out/in under dynamic loading. This excessive level of pay out/in motion results in the prediction of additional stress cycles at certain roller beds, which in turn leads to the prediction of unrealistic fatigue damage to the pipeline. This unwarranted fatigue damage then equates to an over-conservative value for the accumulated damage experienced by a pipeline weld during installation, and so leads to a reduction in the estimated fatigue life for the pipeline. This paper describes a novel approach to tensioner modeling which allows for greater control over the velocity of dynamic tensioner pay out/in and so provides a more accurate estimation of fatigue damage experienced by the pipeline during installation. The paper reports on a case study, as outlined in the proceeding section, in which a comparison is made between results from this new tensioner model and from a more conventional approach. The comparison considers typical installation parameters as well as an in-depth look at the predicted fatigue damage for the two methods

  18. Emergency percutaneous needle decompression for tension pneumoperitoneum

    Directory of Open Access Journals (Sweden)

    Körner Markus

    2011-05-01

    Full Text Available Abstract Background Tension pneumoperitoneum as a complication of iatrogenic bowel perforation during endoscopy is a dramatic condition in which intraperitoneal air under pressure causes hemodynamic and ventilatory compromise. Like tension pneumothorax, urgent intervention is required. Immediate surgical decompression though is not always possible due to the limitations of the preclinical management and sometimes to capacity constraints of medical staff and equipment in the clinic. Methods This is a retrospective analysis of cases of pneumoperitoneum and tension pneumoperitoneum due to iatrogenic bowel perforation. All patients admitted to our surgical department between January 2005 and October 2010 were included. Tension pneumoperitoneum was diagnosed in those patients presenting signs of hemodynamic and ventilatory compromise in addition to abdominal distension. Results Between January 2005 and October 2010 eleven patients with iatrogenic bowel perforation were admitted to our surgical department. The mean time between perforation and admission was 36 ± 14 hrs (range 30 min - 130 hrs, between ER admission and begin of the operation 3 hrs and 15 min ± 47 min (range 60 min - 9 hrs. Three out of eleven patients had clinical signs of tension pneumoperitoneum. In those patients emergency percutaneous needle decompression was performed with a 16G venous catheter. This improved significantly the patients' condition (stabilization of vital signs, reducing jugular vein congestion, bridging the time to the start of the operation. Conclusions Hemodynamical and respiratory compromise in addition to abdominal distension shortly after endoscopy are strongly suggestive of tension pneumoperitoneum due to iatrogenic bowel perforation. This is a rare but life threatening condition and it can be managed in a preclinical and clinical setting with emergency percutaneous needle decompression like tension pneumothorax. Emergency percutaneous decompression is no

  19. Surface tension in soap films: revisiting a classic demonstration

    International Nuclear Information System (INIS)

    Behroozi, F

    2010-01-01

    We revisit a classic demonstration for surface tension in soap films and introduce a more striking variation of it. The demonstration shows how the film, pulling uniformly and normally on a loose string, transforms it into a circular arc under tension. The relationship between the surface tension and the string tension is analysed and presented in a useful graphical form. (letters and comments)

  20. Surface tension in soap films: revisiting a classic demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Behroozi, F [Department of Physics, University of Northern Iowa, Cedar Falls, IA 50614 (United States)], E-mail: behroozi@uni.edu

    2010-01-15

    We revisit a classic demonstration for surface tension in soap films and introduce a more striking variation of it. The demonstration shows how the film, pulling uniformly and normally on a loose string, transforms it into a circular arc under tension. The relationship between the surface tension and the string tension is analysed and presented in a useful graphical form. (letters and comments)

  1. Mentoring Preservice Teachers: Identifying Tensions and Possible Resolutions

    Science.gov (United States)

    Hudson, Peter; Hudson, Sue

    2018-01-01

    Tensions can occur in the mentor-mentee relationship during school-based professional experiences that require problem solving. What are the tensions for mentor teachers in preservice teacher education and how might these tensions be resolved? This qualitative study collected data from 31 high school mentor teachers about tensions experienced with…

  2. Exploratory experimental investigations on post-tensioned structural glass beams

    DEFF Research Database (Denmark)

    Louter, C.; Nielsen, Jens Henrik; Belis, J.

    2013-01-01

    This paper discusses two projects on post-tensioned glass beams, performed at EPFL and DTU, respectively. In these projects small scale glass beams (length of 1.5m and 1m) are post-tensioned by means of steel threaded rods tensioned at the beam ends. The purpose of post-tensioning glass beams...

  3. Combined tumor therapy

    International Nuclear Information System (INIS)

    Wrba, H.

    1990-01-01

    This comprehensive survey of current methods and achievements first takes a look at the two basic therapies, devoting a chapter each to the surgery and radiotherapy of tumors. The principal subjects of the book, however, are the systemic, adjuvant therapy, biological therapies, hyperthermia and various other therapies (as e.g. treatment with ozone, oxygen, or homeopathic means), and psychotherapy. (MG) With 54 figs., 86 tabs [de

  4. Emerging roles of hypoxia-inducible factors and reactive oxygen species in cancer and pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Shigeo Saito

    2015-06-01

    Full Text Available Eukaryotic organisms require oxygen homeostasis to maintain proper cellular function for survival. During conditions of low oxygen tension (hypoxia, cells activate the transcription of genes that induce an adaptive response, which supplies oxygen to tissues. Hypoxia and hypoxia-inducible factors (HIFs may contribute to the maintenance of putative cancer stem cells, which can continue self-renewal indefinitely and express stemness genes in hypoxic stress environments (stem cell niches. Reactive oxygen species (ROS have long been recognized as toxic by-products of aerobic metabolism that are harmful to living cells, leading to DNA damage, senescence, or cell death. HIFs may promote a cancer stem cell state, whereas the loss of HIFs induces the production of cellular ROS and activation of proteins p53 and p16Ink4a, which lead to tumor cell death and senescence. ROS seem to inhibit HIF regulation in cancer cells. By contrast, controversial data have suggested that hypoxia increases the generation of ROS, which prevents hydroxylation of HIF proteins by inducing their transcription as negative feedback. Moreover, hypoxic conditions enhance the generation of induced pluripotent stem cells (iPSCs. During reprogramming of somatic cells into a PSC state, cells attain a metabolic state typically observed in embryonic stem cells (ESCs. ESCs and iPSCs share similar bioenergetic metabolisms, including decreased mitochondrial number and activity, and induced anaerobic glycolysis. This review discusses the current knowledge regarding the emerging roles of ROS homeostasis in cellular reprogramming and the implications of hypoxic regulation in cancer development.

  5. Tumor Blood Vessel Dynamics

    Science.gov (United States)

    Munn, Lance

    2009-11-01

    ``Normalization'' of tumor blood vessels has shown promise to improve the efficacy of chemotherapeutics. In theory, anti-angiogenic drugs targeting endothelial VEGF signaling can improve vessel network structure and function, enhancing the transport of subsequent cytotoxic drugs to cancer cells. In practice, the effects are unpredictable, with varying levels of success. The predominant effects of anti-VEGF therapies are decreased vessel leakiness (hydraulic conductivity), decreased vessel diameters and pruning of the immature vessel network. It is thought that each of these can influence perfusion of the vessel network, inducing flow in regions that were previously sluggish or stagnant. Unfortunately, when anti-VEGF therapies affect vessel structure and function, the changes are dynamic and overlapping in time, and it has been difficult to identify a consistent and predictable normalization ``window'' during which perfusion and subsequent drug delivery is optimal. This is largely due to the non-linearity in the system, and the inability to distinguish the effects of decreased vessel leakiness from those due to network structural changes in clinical trials or animal studies. We have developed a mathematical model to calculate blood flow in complex tumor networks imaged by two-photon microscopy. The model incorporates the necessary and sufficient components for addressing the problem of normalization of tumor vasculature: i) lattice-Boltzmann calculations of the full flow field within the vasculature and within the tissue, ii) diffusion and convection of soluble species such as oxygen or drugs within vessels and the tissue domain, iii) distinct and spatially-resolved vessel hydraulic conductivities and permeabilities for each species, iv) erythrocyte particles advecting in the flow and delivering oxygen with real oxygen release kinetics, v) shear stress-mediated vascular remodeling. This model, guided by multi-parameter intravital imaging of tumor vessel structure

  6. Oxygen safety

    Science.gov (United States)

    ... sure you have working smoke detectors and a working fire extinguisher in your home. If you move around the house with your oxygen, you may need more than one fire extinguisher in different locations. Smoking can be very dangerous. No one should smoke ...

  7. On relation between the quark-gluon bag surface tension and the colour tube string tension

    International Nuclear Information System (INIS)

    Bugaev, K.A.; Zinovjev, G.M.

    2010-01-01

    We revisit the bag phenomenology of deconfining phase transition aiming to replenish it by introducing systematically the bag surface tension. Comparing the free energies of such bags and the strings confining the static quark-antiquark pair, we express the string tension in terms of the bag surface tension and the bulk pressure in order to estimate the bag characteristics using the lattice QCD (LQCD) data. Our analysis of the bag entropy density demonstrates that the surface tension coefficient is amazingly negative at the cross-over (continuous transition). The approach developed allows us to naturally account for an origin of a pronounced maximum (observed in the LQCD studies) in the behaviour of heavy quark-antiquark pair entropy. The vicinity of the (tri-)critical endpoint is also analyzed to clarify the meaning of vanishing surface tension coefficient.

  8. Optimal oxygen saturation in premature infants

    Directory of Open Access Journals (Sweden)

    Meayoung Chang

    2011-09-01

    Full Text Available There is a delicate balance between too little and too much supplemental oxygen exposure in premature infants. Since underuse and overuse of supplemental oxygen can harm premature infants, oxygen saturation levels must be monitored and kept at less than 95% to prevent reactive oxygen species-related diseases, such as retinopathy of prematurity and bronchopulmonary dysplasia. At the same time, desaturation below 80 to 85% must be avoided to prevent adverse consequences, such as cerebral palsy. It is still unclear what range of oxygen saturation is appropriate for premature infants; however, until the results of further studies are available, a reasonable target for pulse oxygen saturation (SpO2 is 90 to 93% with an intermittent review of the correlation between SpO2 and the partial pressure of arterial oxygen tension (PaO2. Because optimal oxygenation depends on individuals at the bedside making ongoing adjustments, each unit must define an optimal target range and set alarm limits according to their own equipment or conditions. All staff must be aware of these values and adjust the concentration of supplemental oxygen frequently.

  9. Oxygen therapy - infants

    Science.gov (United States)

    ... breathe increased amounts of oxygen to get normal levels of oxygen in their blood. Oxygen therapy provides babies with the extra oxygen. Information Oxygen is a gas that the cells in your body need to work properly. The ...

  10. Fatigue in tension perpendicular to the grain

    DEFF Research Database (Denmark)

    Clorius, Christian Odin; Pedersen, Martin Bo Uhre; Hoffmeyer, Preben

    1999-01-01

    Traditinally fatigue resistance is quantified as number of cycles to failure at a given stress level. A previous study by the authors showed that fatigue in compression parallel to the grain is governed partly by duration of load and partly by an effect of loading, i.e. a combination of a creep...... mechanism and a mechanism connected to damage introduce in the loading sequences. The purpose of the present study is to disentangle the effect of duration of load from the effect of load oscillation in fatigue in tension perpendicular to the grain. Fatigue experiments are made on small specimens...... and on dowel type joints with slotted in steel plates. In series of ten, the small specimens are taken to fatigue failure in uniform tension at square wave shaped load cycles at 0.01 Hz and 0.1 Hz. In order to test the predictive validity of the result from the small tension specimens, fatigue experiments...

  11. Fatigue In Tension Perpendicular to the Grain

    DEFF Research Database (Denmark)

    Clorius, Christian Odin; Pedersen, Martin Uhre; Hoffmeyer, Preben

    2004-01-01

    Traditionally fatigue resistance is quantified as number of cycles to failure at a given stress level. A previous study by the authors showed that fatigue in compression parallel to the grain is governed partly by duration of load and partly by an effect of loading, i.e. a combination of a creep...... mechanism and a mechanism connected to damage introduced in the loading sequences. The purpose of the present study is to disentangle the effect of duration of load from the effect of load oscillation in fatigue in tension perpendicular to the grain. Fatigue experiments are made on small specimens...... and on dowel type joints with slotted in steel plates. In series of ten, the small specimens are taken to fatigue failure in uniform tension at square wave shaped load cycles at 0.01 Hz and 0.1 Hz. In arder to test the predictive validity of the result from the small tension specimens, fatigue experiments...

  12. Tensions between Teams and Their Leaders

    Directory of Open Access Journals (Sweden)

    J. David Johnson

    2016-10-01

    Full Text Available The intersection of teamwork and leadership results in tensions, dilemmas, and paradoxes for both individuals and for institutions such as simultaneously empowering individuals at the same time it frustrates them when our naive, cultural understanding of leadership centralizes power and values leaders who can impose their will and vision on others. Perhaps the fundamental paradox of teamwork and leadership is that the more leadership is focused on an individual the less likely a team’s potential will be realized. Six specific domains where tensions arise are: at team boundaries; culture; who is in charge, rationality/cognition; diversity; and collaborations. Three approaches - clarifying different levels of analysis, temporal factors, and overarching concepts - to resolving tensions are discussed. New conceptions of leadership and the importance of the larger cultural frame within which they are embedded are needed for the management of technology and innovation.

  13. Cellular control of connective tissue matrix tension.

    Science.gov (United States)

    Langevin, Helene M; Nedergaard, Maiken; Howe, Alan K

    2013-08-01

    The biomechanical behavior of connective tissue in response to stretching is generally attributed to the molecular composition and organization of its extracellular matrix. It also is becoming apparent that fibroblasts play an active role in regulating connective tissue tension. In response to static stretching of the tissue, fibroblasts expand within minutes by actively remodeling their cytoskeleton. This dynamic change in fibroblast shape contributes to the drop in tissue tension that occurs during viscoelastic relaxation. We propose that this response of fibroblasts plays a role in regulating extracellular fluid flow into the tissue, and protects against swelling when the matrix is stretched. This article reviews the evidence supporting possible mechanisms underlying this response including autocrine purinergic signaling. We also discuss fibroblast regulation of connective tissue tension with respect to lymphatic flow, immune function, and cancer. Copyright © 2013 Wiley Periodicals, Inc.

  14. Surface tension of normal and heavy water

    International Nuclear Information System (INIS)

    Straub, J.; Rosner, N.; Grigull, V.

    1980-01-01

    A Skeleton Table and simple interpolation equation for the surface tension of light water was developed by the Working Group III of the International Association for the Properties of Steam and is recommended as an International Standard. The Skeleton Table is based on all known measurements of the surface tension and individual data were weighted corresponding to the accuracy of the measurements. The form of the interpolation equation is based on a physical concept. It represents an extension of van der Waals-equation, where the exponent conforms to the 'Scaling Laws'. In addition for application purposes simple relations for the Laplace-coefficient and for the density difference between the liquid and gaseous phases of light water are given. The same form of interpolation equation for the surface tension can be used for heavy water, for which the coefficients are given. However, this equation is based only on a single set of data. (orig.) [de

  15. Tension Stiffened and Tendon Actuated Manipulator

    Science.gov (United States)

    Doggett, William R. (Inventor); Dorsey, John T. (Inventor); Ganoe, George G. (Inventor); King, Bruce D. (Inventor); Jones, Thomas C. (Inventor); Mercer, Charles D. (Inventor); Corbin, Cole K. (Inventor)

    2015-01-01

    A tension stiffened and tendon actuated manipulator is provided performing robotic-like movements when acquiring a payload. The manipulator design can be adapted for use in-space, lunar or other planetary installations as it is readily configurable for acquiring and precisely manipulating a payload in both a zero-g environment and in an environment with a gravity field. The manipulator includes a plurality of link arms, a hinge connecting adjacent link arms together to allow the adjacent link arms to rotate relative to each other and a cable actuation and tensioning system provided between adjacent link arms. The cable actuation and tensioning system includes a spreader arm and a plurality of driven and non-driven elements attached to the link arms and the spreader arm. At least one cable is routed around the driven and non-driven elements for actuating the hinge.

  16. Sinus Tumors

    Science.gov (United States)

    ... RESOURCES Medical Societies Patient Education About this Website Font Size + - Home > CONDITIONS > Sinus Tumors Adult Sinusitis Pediatric ... and they vary greatly in location, size and type. Care for these tumors is individualized to each ...

  17. Tumors markers

    International Nuclear Information System (INIS)

    Yamaguchi-Mizumoto, N.H.

    1989-01-01

    In order to study blood and cell components alterations (named tumor markers) that may indicate the presence of a tumor, several methods are presented. Aspects as diagnostic, prognostic, therapeutic value and clinical evaluation are discussed. (M.A.C.)

  18. Wilms tumor

    Science.gov (United States)

    ... suggested. Alternative Names Nephroblastoma; Kidney tumor - Wilms Images Kidney anatomy Wilms tumor References Babaian KN, Delacroix SE, Wood CG, Jonasch E. Kidney cancer. In: Skorecki K, Chertow GM, Marsden PA, ...

  19. Spinal tumors

    International Nuclear Information System (INIS)

    Goethem, J.W.M. van; Hauwe, L. van den; Oezsarlak, Oe.; Schepper, A.M.A. de; Parizel, P.M.

    2004-01-01

    Spinal tumors are uncommon lesions but may cause significant morbidity in terms of limb dysfunction. In establishing the differential diagnosis for a spinal lesion, location is the most important feature, but the clinical presentation and the patient's age and gender are also important. Magnetic resonance (MR) imaging plays a central role in the imaging of spinal tumors, easily allowing tumors to be classified as extradural, intradural-extramedullary or intramedullary, which is very useful in tumor characterization. In the evaluation of lesions of the osseous spine both computed tomography (CT) and MR are important. We describe the most common spinal tumors in detail. In general, extradural lesions are the most common with metastasis being the most frequent. Intradural tumors are rare, and the majority is extramedullary, with meningiomas and nerve sheath tumors being the most frequent. Intramedullary tumors are uncommon spinal tumors. Astrocytomas and ependymomas comprise the majority of the intramedullary tumors. The most important tumors are documented with appropriate high quality CT or MR images and the characteristics of these tumors are also summarized in a comprehensive table. Finally we illustrate the use of the new World Health Organization (WHO) classification of neoplasms affecting the central nervous system

  20. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  1. Urogenital tumors

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1994-03-01

    An overview is provided for veterinary care of urogenital tumors in companion animals, especially the dog. Neoplasms discussed include tumors of the kidney, urinary bladder, prostate, testis, ovary, vagina, vulva and the canine transmissible venereal tumor. Topics addressed include description, diagnosis and treatment.

  2. Oxygen dynamics around buried lesser sandeels Ammodytes tobianus (Linnaeus 1785): mode of ventilation and oxygen requirements

    DEFF Research Database (Denmark)

    Behrens, Jane W; Stahl, Henrik J; Steffensen, John F

    2007-01-01

    The oxygen environment around buried sandeels (Ammodytes tobianus) was monitored by planar optodes. The oxygen penetration depth at the sediment interface was only a few mm. Thus fish, typically buried at 1-4 cm depth, were generally in anoxic sediment. However, they induced an advective transport...... down along the body, referred to as ;plume ventilation'. Yet, within approximately 30 min the oxic plume was replenished by oxygen-depleted water from the gills. The potential for cutaneous respiration by the buried fish was thus of no quantitative importance. Calculations derived by three independent...... methods (each with N=3) revealed that the oxygen uptake of sandeel buried for 6-7 h was 40-50% of previous estimates on resting respirometry of non-buried fish, indicating lower O(2) requirements during burial on a diurnal timescale. Buried fish exposed to decreasing oxygen tensions gradually approached...

  3. Tumor immunology

    International Nuclear Information System (INIS)

    Otter, W. den

    1987-01-01

    Tumor immunology, the use of immunological techniques for tumor diagnosis and approaches to immunotherapy of cancer are topics covered in this multi-author volume. Part A, 'Tumor Immunology', deals with present views on tumor-associated antigens, the initiation of immune reactions of tumor cells, effector cell killing, tumor cells and suppression of antitumor immunity, and one chapter dealing with the application of mathematical models in tumor immunology. Part B, 'Tumor Diagnosis and Imaging', concerns the use of markers to locate the tumor in vivo, for the histological diagnosis, and for the monitoring of tumor growth. In Part C, 'Immunotherapy', various experimental approaches to immunotherapy are described, such as the use of monoclonal antibodies to target drugs, the use of interleukin-2 and the use of drugs inhibiting suppression. In the final section, the evaluation, a pathologist and a clinician evaluate the possibilities and limitations of tumor immunology and the extent to which it is useful for diagnosis and therapy. refs.; figs.; tabs

  4. Focal adhesions, stress fibers and mechanical tension

    Energy Technology Data Exchange (ETDEWEB)

    Burridge, Keith, E-mail: Keith_Burridge@med.unc.edu [Department of Cell Biology and Physiology, and Lineberger Comprehensive Cancer Center, 12-016 Lineberger, CB#7295, University of North Carolina, Chapel Hill, NC (United States); Guilluy, Christophe, E-mail: christophe.guilluy@univ-nantes.fr [Inserm UMR-S1087, CNRS UMR-C6291, L' institut du Thorax, and Université de Nantes, Nantes (France)

    2016-04-10

    Stress fibers and focal adhesions are complex protein arrays that produce, transmit and sense mechanical tension. Evidence accumulated over many years led to the conclusion that mechanical tension generated within stress fibers contributes to the assembly of both stress fibers themselves and their associated focal adhesions. However, several lines of evidence have recently been presented against this model. Here we discuss the evidence for and against the role of mechanical tension in driving the assembly of these structures. We also consider how their assembly is influenced by the rigidity of the substratum to which cells are adhering. Finally, we discuss the recently identified connections between stress fibers and the nucleus, and the roles that these may play, both in cell migration and regulating nuclear function. - Highlights: • The different types of stress fiber and focal adhesion are described. • We discuss the controversy about tension and assembly of these structures. • We describe the different models used to investigate assembly of these structures. • The influence of substratum rigidity is discussed. • Stress fiber connections to the nucleus are reviewed.

  5. Inclusion and Participation: Working with the Tensions

    Directory of Open Access Journals (Sweden)

    Gideon Calder

    2011-12-01

    Full Text Available Democracy is crucially about inclusion: a theory of democracy must account for who is to be included in the democratic process, how, and on what terms. Inclusion, if conceived democratically, is fraught with tensions. This article identifies three such tensions, arising respectively in: (i the inauguration of the democratic public; (ii enabling equal participation; and (iii the relationship between instrumental and non-instrumental accounts of democracy’s value. In each case, I argue, rather than seeking somehow to dissolve or avoid such tensions, theories of democracy should allow us to live with their implications reflexively: to work with them. Such tensions are counter-democratic to the extent that they derail what Nancy Fraser calls “participatory parity,” under which citizens count as “full partners in social interaction.” But the extent to which they do this is not itself dependent on points of paradox in the very idea of inclusion. Such parity relies on complex factors, social and economic, which democratic institutions and procedures will not by themselves address. To achieve full democratic inclusion we must already have addressed such factors; no account of democracy itself, however finely-tuned, will do this.

  6. Tension and relaxation in the individual.

    Science.gov (United States)

    Newbury, C R

    1979-06-01

    Increasing materialism in society is resulting in more wide spread nervous tension in all age groups. While some degree of nervous tension is necessary in everyday living, its adverse effects require that we must learn to bring it under control. Total tension is shown to have two components: a controllable element arising from factors in the environment and the inbuilt uncontrollable residue which is basic in the individual temperament. The effects of excessive or uncontrolled stress can be classified as 1) emotional reactions such as neurotic behaviour (anxiety hypochondria, hysteria, phobia, depression obsessions and compulsions) or psychotic behaviour and 2) psychosomatic reactions (nervous asthma, headache, insomnia, heart attack). Nervous energy can be wastefully expended by such factors as loss of temper, wrong attitudes to work, job frustration and marital strains. Relaxation is the only positive way to control undesirable nervous tension and its techniques require to be learned. A number of techniques (progressive relaxation, differential relaxation, hypnosis, the use of biofeedback, Yoga and Transcendental Meditation) are described and their application to dental practice is discussed.

  7. WORRY, ANXIETY AND TENSION — IMPORTANCE ...

    African Journals Online (AJOL)

    Enrique

    cognitive. Tension: Increased and unpleasant motor and psychological activity or a state of mental or ... MRC Research Unit on Anxiety and Stress. Disorders ... and brain imaging. Worry ... serve an adaptive function to the daily challenges of our environment. ... connection to physical symptoms ... Experience-conditioning.

  8. Surface Tension Measurements with a Smartphone

    Science.gov (United States)

    Goy, Nicolas-Alexandre; Denis, Zakari; Lavaud, Maxime; Grolleau, Adrian; Dufour, Nicolas; Deblais, Antoine; Delabre, Ulysse

    2017-01-01

    Smartphones are increasingly used in higher education and at university in mechanics, acoustics, and even thermodynamics as they offer a unique way to do simple science experiments. In this article, we show how smartphones can be used in fluid mechanics to measure surface tension of various liquids, which could help students understand the concept…

  9. Rebellion and Agrarian Tensions in Sierra Leone

    NARCIS (Netherlands)

    Peters, K.; Richards, P.

    2011-01-01

    This paper assesses the extent to which customary governance in Sierra Leone can be held responsible for an increasingly unstable two-class agrarian society. A case is made for regarding the civil war (1991–2002) as being an eruption of long-term, entrenched agrarian tensions exacerbated by chiefly

  10. Normal tension glaucoma and Alzheimer disease

    DEFF Research Database (Denmark)

    Bach-Holm, Daniella; Kessing, Svend Vedel; Mogensen, Ulla Brasch

    2012-01-01

    Purpose: To investigate whether normal tension glaucoma (NTG) is associated with increased risk of developing dementia/Alzheimer disease (AD). Methods: A total of 69 patients with NTG were identified in the case note files in the Glaucoma Clinic, University Hospital of Copenhagen (Rigshospitalet...

  11. Coexisting tensions between the 'traditionmodernity' and the ...

    African Journals Online (AJOL)

    Coexisting tensions between the 'traditionmodernity' and the 'sustainability- integration' approaches to urban development policy and planning practices in Botswana. ... exists at several levels and manifest in urban planning's preoccupation with the physicality of spatial forms, often justified in the embracing of globalization.

  12. Tension and Approximation in Poetic Translation

    Science.gov (United States)

    Al-Shabab, Omar A. S.; Baka, Farida H.

    2015-01-01

    Simple observation reveals that each language and each culture enjoys specific linguistic features and rhetorical traditions. In poetry translation difference and the resultant linguistic tension create a gap between Source Language and Target language, a gap that needs to be bridged by creating an approximation processed through the translator's…

  13. Internationalization and Global Tension: Lessons From History

    Science.gov (United States)

    Altbach, Philip G.; de Wit, Hans

    2015-01-01

    Increasing political and military tension in several parts of the world will inevitably affect international higher education. Nationalist, religious, and ideological conflicts challenge the original ideas of international cooperation and exchange in higher education as promoters of peace and mutual understanding and of global engagement. Since…

  14. Educational Leadership: Key Challenges and Ethical Tensions

    Science.gov (United States)

    Duignan, Patrick

    2007-01-01

    "Educational Leadership" is a major research book on contemporary leadership challenges for educational leaders. In this groundbreaking new work, educational leaders in schools, including teachers, are provided with ways of analysing and resolving common but complex leadership challenges. Ethical tensions inherent in these challenges are…

  15. Tension Builds over AFT Reform Agenda

    Science.gov (United States)

    Sawchuk, Stephen

    2012-01-01

    Can a teachers' union successfully be both a hardball-playing defender of its rights and a collaborative force for the common good? It is both a question of philosophy and, increasingly, one of policy direction for the American Federation of Teachers (AFT), whose biennial convention in Detroit showed delegates grappling with the tension between…

  16. Exact analytical density profiles and surface tension

    Indian Academy of Sciences (India)

    journal of. May 2005 physics pp. 785–801. Classical charged fluids at equilibrium near ... is provided by the excess surface tension for an air–water interface, which is determined ... the potential drop created by the electric layer which appears as soon as the fluid has ...... radii, by symmetry, the charge density profile is flat,.

  17. Transitions of tethered chain molecules under tension.

    Science.gov (United States)

    Luettmer-Strathmann, Jutta; Binder, Kurt

    2014-09-21

    An applied tension force changes the equilibrium conformations of a polymer chain tethered to a planar substrate and thus affects the adsorption transition as well as the coil-globule and crystallization transitions. Conversely, solvent quality and surface attraction are reflected in equilibrium force-extension curves that can be measured in experiments. To investigate these effects theoretically, we study tethered chains under tension with Wang-Landau simulations of a bond-fluctuation lattice model. Applying our model to pulling experiments on biological molecules we obtain a good description of experimental data in the intermediate force range, where universal features dominate and finite size effects are small. For tethered chains in poor solvent, we observe the predicted two-phase coexistence at transitions from the globule to stretched conformations and also discover direct transitions from crystalline to stretched conformations. A phase portrait for finite chains constructed by evaluating the density of states for a broad range of solvent conditions and tensions shows how increasing tension leads to a disappearance of the globular phase. For chains in good solvents tethered to hard and attractive surfaces we find the predicted scaling with the chain length in the low-force regime and show that our results are well described by an analytical, independent-bond approximation for the bond-fluctuation model for the highest tensions. Finally, for a hard or slightly attractive surface the stretching of a tethered chain is a conformational change that does not correspond to a phase transition. However, when the surface attraction is sufficient to adsorb a chain it will undergo a desorption transition at a critical value of the applied force. Our results for force-induced desorption show the transition to be discontinuous with partially desorbed conformations in the coexistence region.

  18. Interstitial administration of perfluorochemical emulsions for reoxygenation of hypoxic tumor cells

    International Nuclear Information System (INIS)

    Woo, D.V.; Seegenschmiedt, H.; Schweighardt, F.K.; Emrich, J.; McGarvey, K.; Caridi, M.; Brady, L.W.

    1987-01-01

    Microparticulate perfluorochemical (PFC) emulsions have the capacity to solubilize significant quantities of oxygen compared to water. Although systemic administration of such emulsions may enhance oxygen delivery to some tissues, hypoxic tumor cells have marginal vascular supplies. The authors report studies which directly attempt to oxygenate hypoxic tumor cells by interstitial administration of oxygenated PFC emulsions followed by radiation therapy. Fortner MMI malignant melanomas (21 day old) grown in Syrian Golden hamsters were injected directly with either oxygenated PFC emulsions or Ringers solution. The volume of test substance administered was equal to 50% of the tumor volume. The tumors were immediately irradiated with 25 Gy of 10 MeV photons (Clinac 18). The tumor dimensions were measured daily post irradiation and the tumor doubling time determined. The results suggest that interstitial administration of oxygenated PFC emulsions directly into tumors followed by radiation therapy may increase the likelihood of killing hypoxic tumor cells

  19. Cryospectrophotometric determination of tumor intravascular oxyhemoglobin saturations: dependence on vascular geometry and tumor growth.

    Science.gov (United States)

    Fenton, B M; Rofstad, E K; Degner, F L; Sutherland, R M

    1988-12-21

    To delineate the complex relationships between overall tumor oxygenation and vascular configuration, intravascular oxyhemoglobin (HbO2) saturation distributions were measured with cryospectrophotometric techniques. Four factors related to vascular morphometry and tumor growth were evaluated: a) vessel diameter, b) distance of vessel from the tumor surface, c) tumor volume, and d) vascular density. To measure intertumor heterogeneity, two murine sarcomas (RIF-1 and KHT) and two human ovarian carcinoma xenografts (OWI and MLS) were utilized. In contrast to skeletal muscle, a preponderance of very low HbO2 saturations was observed for both large and small tumors of all lines. Saturations up to about 90% were also generally present, however, even in very large tumors. Variations in vascular configuration were predominantly tumor-line dependent rather than due to inherent characteristics of the host vasculature, and widely disparate HbO2 distributions were found for alternate lines implanted in identical host mice. Although peripheral saturations remained fairly constant with tumor growth, HbO2 values were markedly lower for vessels nearer the tumor center and further decreased with increasing tumor volume. HbO2 saturations did not change substantially with increasing vascular density (except for KHT tumors), although density did decrease with increasing distance from tumor surface. Combined effects of vessel diameter, tumor volume, and vessel location on HbO2 saturations were complex and varied markedly with both tumor line and vessel class. For specific classes, HbO2 distributions correlated closely with radiobiological hypoxic fractions, i.e., for tumor lines in which hypoxic fraction increased substantially with tumor volume, corresponding HbO2 values decreased, while for lines in which hypoxic fraction remained constant, HbO2 values also were unchanged. Although these trends may also be a function of differing oxygen consumption rates between tumor lines

  20. Necessary Tension in Marine Risers Tension des colonnes montantes en mer

    Directory of Open Access Journals (Sweden)

    Lubinski A.

    2006-11-01

    Full Text Available The tension governing transverse static and dynamic deflections in a riser is not the actual tension but the so-called « effective tension » The concept of effective tension and effective compression is thoroughly explained, and means for calculating effective forces are given. Numerical examples are worked out for risers whose length is between 152 m (520 ft and 920 m (3020 ft. The reciprocal of maximum bending moment of the vicinity of the hall joint is plotted versus the effective tension of the ball joint. Bending moments used were obtained through use of static and dynamic computer programs applied ta a variety of conditions of wave loading, use or non-use of buoyant moterial sleeves, etc. The most important parameters affecting riser performance are the effective La tension régissant les déflections transversales statiques et dynamiques d'une colonne montante n'est pas la tension réelle mais ce qu'on appelle « la tension effective ». Le concept de tension ou de compression effective est expliqué en détail et la façon de calculer les forces effectives est indiquée dans cet article. Des exemples numériques sont développés pour des colonnes montantes de longueur comprise entre 152 m (520 ft et 920 m (3 020 ft. On a tracé la courbe de l'inverse du moment fléchissant en fonction de la tension effective à l'articulation. Les moments fléchissants utilisés ont été calculés par ordinateur en utilisant des programmes dynamiques et statiques pour des conditions variées d'action des vagues, la colonne montante étant ou non munie de manchettes de flottabilité, etc. Les deux paramètres les plus importants qui affectent le bon comportement d'une colonne montante sont la tension effective et la charge latérale.

  1. Real-time Tumor Oxygenation Changes After Single High-dose Radiation Therapy in Orthotopic and Subcutaneous Lung Cancer in Mice: Clinical Implication for Stereotactic Ablative Radiation Therapy Schedule Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Song, Changhoon [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Hong, Beom-Ju; Bok, Seoyeon; Lee, Chan-Ju; Kim, Young-Eun [Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk (Korea, Republic of); Jeon, Sang-Rok [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Wu, Hong-Gyun [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul (Korea, Republic of); Lee, Yun-Sang [Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cheon, Gi Jeong; Paeng, Jin Chul [Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul (Korea, Republic of); Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Carlson, David J. [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States); and others

    2016-07-01

    Purpose: To investigate the serial changes of tumor hypoxia in response to single high-dose irradiation by various clinical and preclinical methods to propose an optimal fractionation schedule for stereotactic ablative radiation therapy. Methods and Materials: Syngeneic Lewis lung carcinomas were grown either orthotopically or subcutaneously in C57BL/6 mice and irradiated with a single dose of 15 Gy to mimic stereotactic ablative radiation therapy used in the clinic. Serial [{sup 18}F]-misonidazole (F-MISO) positron emission tomography (PET) imaging, pimonidazole fluorescence-activated cell sorting analyses, hypoxia-responsive element-driven bioluminescence, and Hoechst 33342 perfusion were performed before irradiation (day −1), at 6 hours (day 0), and 2 (day 2) and 6 (day 6) days after irradiation for both subcutaneous and orthotopic lung tumors. For F-MISO, the tumor/brain ratio was analyzed. Results: Hypoxic signals were too low to quantitate for orthotopic tumors using F-MISO PET or hypoxia-responsive element-driven bioluminescence imaging. In subcutaneous tumors, the maximum tumor/brain ratio was 2.87 ± 0.483 at day −1, 1.67 ± 0.116 at day 0, 2.92 ± 0.334 at day 2, and 2.13 ± 0.385 at day 6, indicating that tumor hypoxia was decreased immediately after irradiation and had returned to the pretreatment levels at day 2, followed by a slight decrease by day 6 after radiation. Pimonidazole analysis also revealed similar patterns. Using Hoechst 33342 vascular perfusion dye, CD31, and cleaved caspase 3 co-immunostaining, we found a rapid and transient vascular collapse, which might have resulted in poor intratumor perfusion of F-MISO PET tracer or pimonidazole delivered at day 0, leading to decreased hypoxic signals at day 0 by PET or pimonidazole analyses. Conclusions: We found tumor hypoxia levels decreased immediately after delivery of a single dose of 15 Gy and had returned to the pretreatment levels 2 days after irradiation and had decreased

  2. Reactive Oxygen Species

    DEFF Research Database (Denmark)

    Franchina, Davide G.; Dostert, Catherine; Brenner, Dirk

    2018-01-01

    T cells are a central component of defenses against pathogens and tumors. Their effector functions are sustained by specific metabolic changes that occur upon activation, and these have been the focus of renewed interest. Energy production inevitably generates unwanted products, namely reactive...... and transcription factors, influencing the outcome of the T cell response. We discuss here how ROS can directly fine-tune metabolism and effector functions of T cells....... oxygen species (ROS), which have long been known to trigger cell death. However, there is now evidence that ROS also act as intracellular signaling molecules both in steady-state and upon antigen recognition. The levels and localization of ROS contribute to the redox modeling of effector proteins...

  3. Radiosensitization of mouse skin by oxygen and depletion of glutathione

    International Nuclear Information System (INIS)

    Stevens, Graham; Joiner, Michael; Joiner, Barbara; Johns, Helen; Denekamp, Juliana

    1995-01-01

    Purpose: To determine the oxygen enhancement ratio (OER) and shape of the oxygen sensitization curve of mouse foot skin, the extent to which glutathione (GSH) depletion radiosensitized skin, and the dependence of such sensitization on the ambient oxygen tension. Methods and Materials: The feet of WHT mice were irradiated with single doses of 240 kVp x-rays while mice were exposed to carbogen or gases with oxygen/nitrogen mixtures containing 8-100% O 2 . The anoxic response was obtained by occluding the blood supply to the leg of anesthetized mice with a tourniquet, surrounding the foot with nitrogen, and allowing the mice to breathe 10% O 2 . Further experiments were performed to assess the efficacy of this method to obtain an anoxic response. Radiosensitivity of skin was assessed using the acute skin-reaction assay. Glutathione levels were modified using two schedules of dl-buthionine sulphoximine (BSO) and diethylmaleate (DEM), which were considered to produce extensive and intermediate levels of GSH depletion in the skin of the foot during irradiation. Results: Carbogen caused the greatest radiosensitization of skin, with a reproducible enhancement of 2.2 relative to the anoxic response. The OER of 2.2 is lower than other reports for mouse skin. This may indicate that the extremes of oxygenation were not produced, although there was no direct evidence for this. When skin radiosensitivity was plotted against the logarithm of the oxygen tension in the ambient gas, a sigmoid curve with a K value of 17-21% O 2 in the ambient gas was obtained. Depletion of GSH caused minimal radiosensitization when skin was irradiated under anoxic or well-oxygenated conditions. Radiosensitization by GSH depletion was maximal at intermediate oxygen tensions of 10-21% O 2 in the ambient gas. Increasing the extent of GSH depletion led to increasing radiosensitization, with sensitization enhancement ratios of 1.2 and 1.1, respectively, for extensive and intermediate levels of GSH

  4. Assessment and reduction of diaphragmatic tension during hiatal hernia repair.

    Science.gov (United States)

    Bradley, Daniel Davila; Louie, Brian E; Farivar, Alexander S; Wilshire, Candice L; Baik, Peter U; Aye, Ralph W

    2015-04-01

    During hiatal hernia repair there are two vectors of tension: axial and radial. An optimal repair minimizes the tension along these vectors. Radial tension is not easily recognized. There are no simple maneuvers like measuring length that facilitate assessment of radial tension. The aims of this project were to: (1) establish a simple intraoperative method to evaluate baseline tension of the diaphragmatic hiatal muscle closure; and, (2) assess if tension is reduced by relaxing maneuvers and if so, to what degree. Diaphragmatic characteristics and tension were assessed during hiatal hernia repair with a tension gage. We compared tension measured after hiatal dissection and after relaxing maneuvers were performed. Sixty-four patients (29 M:35F) underwent laparoscopic hiatal hernia repair. Baseline hiatal width was 2.84 cm and tension 13.6 dag. There was a positive correlation between hiatal width and tension (r = 0.55) but the strength of association was low (r (2) = 0.31). Four different hiatal shapes (slit, teardrop, "D", and oval) were identified and appear to influence tension and the need for relaxing incision. Tension was reduced by 35.8 % after a left pleurotomy (12 patients); by 46.2 % after a right crural relaxing incision (15 patients); and by 56.1 % if both maneuvers were performed (6 patients). Tension on the diaphragmatic hiatus can be measured with a novel device. There was a limited correlation with width of the hiatal opening. Relaxing maneuvers such as a left pleurotomy or a right crural relaxing incision reduced tension. Longer term follow-up will determine whether outcomes are improved by quantifying and reducing radial tension.

  5. Thermal Analysis of Bending Under Tension Test

    DEFF Research Database (Denmark)

    Ceron, Ermanno; Martins, Paulo A.F.; Bay, Niels

    2014-01-01

    during testing is similar to the one in the production tool. A universal sheet tribo-tester has been developed, which can run multiple tests automatically from coil. This allows emulating the temperature increase as in production. The present work performs finite element analysis of the evolution......The tribological conditions in deep drawing can be simulated in the Bending Under Tension test to evaluate the performance of new lubricants, tool materials, etc. Deep drawing production with automatic handling runs normally at high rate. This implies considerable heating of the tools, which...... sometimes can cause lubricant film breakdown and galling. In order to replicate the production conditions in bending under tension testing it is thus important to control the tool/workpiece interface temperature. This can be done by pre-heating the tool, but it is essential that the interface temperature...

  6. Quantum surface tension in ideal gases

    International Nuclear Information System (INIS)

    Sisman, A.

    2005-01-01

    Due to wave character of atoms, an ideal gas confined in a finite domain exhibits Casimir like size effects. These effects become appreciable in a domain with at least one dimension in the order of micron. On this scale, thermodynamic state functions of an ideal gas become shape and size dependent and some new effects appear. In the literature, only some domains of regular shapes have been considered. In this study, the results are generalized to a domain of an arbitrary shape by using Weyl s conjecture for density of states. It is seen that free energy expression of an ideal Maxwellian gas consists of a classical volume dependent term and also a quantum originated surface dependent term, which causes a quantum surface tension. In a rectangular box filled by an ideal gas and separated by a movable wall into two parts, it is shown that a lateral force appears on the movable wall due to quantum surface tension

  7. Separation anxiety: Stress, tension and cytokinesis

    International Nuclear Information System (INIS)

    Mohan, Krithika; Iglesias, Pablo A.; Robinson, Douglas N.

    2012-01-01

    Cytokinesis, the physical separation of a mother cell into two daughter cells, progresses through a series of well-defined changes in morphology. These changes involve distinct biochemical and mechanical processes. Here, we review the mechanical features of cells during cytokinesis, discussing both the material properties as well as sources of stresses, both active and passive, which lead to the observed changes in morphology. We also describe a mechanosensory feedback control system that regulates protein localization and shape progression during cytokinesis. -- Highlights: ► Cytokinesis progresses through three distinct mechanical phases. ► Cortical tension initially resists deformation of mother cell. ► Late in cytokinesis, cortical tension provides stress, enabling furrow ingression. ► A mechanosensory feedback control system regulates cytokinesis.

  8. Tension Tests On Bored Piles In Sand

    DEFF Research Database (Denmark)

    Krabbenhøft, Sven; Clausen, Johan; Damkilde, Lars

    2006-01-01

    The lengths of the bored piles varied from 2 m to 6 m and all were of a diameter of 140 mm. The piles were tested to failure in tension and the load-displacement relations were recorded. The investigation has shown pronounced differences between the load bearing capacities obtained by different...... design methods. The methods proposed by Fleming et al. and Reese & O’Neill seem to produce the best match with the test results....

  9. Surface tension confined liquid cryogen cooler

    Science.gov (United States)

    Castles, Stephen H. (Inventor); Schein, Michael E. (Inventor)

    1989-01-01

    A cryogenic cooler is provided for use in craft such as launch, orbital, and space vehicles subject to substantial vibration, changes in orientation, and weightlessness. The cooler contains a small pore, large free volume, low density material to restrain a cryogen through surface tension effects during launch and zero-g operations and maintains instrumentation within the temperature range of 10 to 140 K. The cooler operation is completely passive, with no inherent vibration or power requirements.

  10. Surface tension of H2O and D2O

    International Nuclear Information System (INIS)

    Vargaftik, N.B.; Voljak, L.D.; Volkov, B.N.

    1975-01-01

    There is a great number of works on surface tension of clean water (H 2 O) at temperatures up to 100 deg C and very few above the boiling point. Works on surface tension of heavy water (D 2 O) are insufficient. A review of works on surface tension of both kinds of water is given

  11. Tension-induced binding of semiflexible biopolymers

    International Nuclear Information System (INIS)

    Benetatos, Panayotis; Heydt, Alice von der; Zippelius, Annette

    2014-01-01

    We investigate theoretically the effect of polymer tension on the collective behavior of reversibly binding cross-links. For this purpose, we employ a model of two weakly bending wormlike chains aligned in parallel by a tensile force, with a sequence of inter-chain binding sites regularly spaced along the contours. Reversible cross-links attach and detach at the sites with an affinity controlled by a chemical potential. In a mean-field approach, we calculate the free energy of the system and find the emergence of a free-energy barrier which controls the reversible (un)binding. The tension affects the conformational entropy of the chains which competes with the binding energy of the cross-links. This competition gives rise to a sudden increase in the fraction of bound sites as the tension increases. We show that this transition is related to the cross-over between weak and strong localization of a directed polymer in a pinning potential. The cross-over to the strongly bound state can be interpreted as a mechanism for force-stiffening which exceeds the capabilities of single-chain elasticity and thus available only to reversibly cross-linked polymers. (paper)

  12. Generalized surface tension bounds in vacuum decay

    Science.gov (United States)

    Masoumi, Ali; Paban, Sonia; Weinberg, Erick J.

    2018-02-01

    Coleman and De Luccia (CDL) showed that gravitational effects can prevent the decay by bubble nucleation of a Minkowski or AdS false vacuum. In their thin-wall approximation this happens whenever the surface tension in the bubble wall exceeds an upper bound proportional to the difference of the square roots of the true and false vacuum energy densities. Recently it was shown that there is another type of thin-wall regime that differs from that of CDL in that the radius of curvature grows substantially as one moves through the wall. Not only does the CDL derivation of the bound fail in this case, but also its very formulation becomes ambiguous because the surface tension is not well defined. We propose a definition of the surface tension and show that it obeys a bound similar in form to that of the CDL case. We then show that both thin-wall bounds are special cases of a more general bound that is satisfied for all bounce solutions with Minkowski or AdS false vacua. We discuss the limit where the parameters of the theory attain critical values and the bound is saturated. The bounce solution then disappears and a static planar domain wall solution appears in its stead. The scalar field potential then is of the form expected in supergravity, but this is only guaranteed along the trajectory in field space traced out by the bounce.

  13. Tension-induced binding of semiflexible biopolymers

    Science.gov (United States)

    Benetatos, Panayotis; von der Heydt, Alice; Zippelius, Annette

    2015-03-01

    We investigate theoretically the effect of polymer tension on the collective behaviour of reversible cross-links. We use a model of two parallel-aligned, weakly-bending wormlike chains with a regularly spaced sequence of binding sites subjected to a tensile force. Reversible cross-links attach and detach at the binding sites with an affinity controlled by a chemical potential. In a mean-field approach, we calculate the free energy of the system and we show the emergence of a free energy barrier which controls the reversible (un)binding. The tension affects the conformational entropy of the chains which competes with the binding energy of the cross-links. This competition gives rise to a sudden increase in the fraction of bound sites as the polymer tension increases. The force-induced first-order transition in the number of cross-links implies a sudden force-induced stiffening of the effective stretching modulus of the polymers. This mechanism may be relevant to the formation and stress-induced strengthening of stress fibers in the cytoskeleton. We acknowledge support by the Deutsche Forschungsgemeinschaft (DFG) via grant SFB-937/A1.

  14. Detection of low tension cosmic superstrings

    Science.gov (United States)

    Chernoff, David F.; Tye, S.-H. Henry

    2018-05-01

    Cosmic superstrings of string theory differ from conventional cosmic strings of field theory. We review how the physical and cosmological properties of the macroscopic string loops influence experimental searches for these relics from the epoch of inflation. The universe's average density of cosmic superstrings can easily exceed that of conventional cosmic strings having the same tension by two or more orders of magnitude. The cosmological behavior of the remnant superstring loops is qualitatively distinct because the string tension is exponentially smaller than the string scale in flux compactifications in string theory. Low tension superstring loops live longer, experience less recoil (rocket effect from the emission of gravitational radiation) and tend to cluster like dark matter in galaxies. Clustering enhances the string loop density with respect to the cosmological average in collapsed structures in the universe. The enhancement at the Sun's position is ~ 105. We develop a model encapsulating the leading order string theory effects, the current understanding of the string network loop production and the influence of cosmological structure formation suitable for forecasting the detection of superstring loops via optical microlensing, gravitational wave bursts and fast radio bursts. We evaluate the detection rate of bursts from cusps and kinks by LIGO- and LISA-like experiments. Clustering dominates rates for G μ 10‑14.2 (LIGO cusp), G μ>10‑15 (LISA cusp) and G μ>10‑ 14.1 (LISA kink).

  15. Macrophages Under Low Oxygen Culture Conditions Respond to Ion Parametric Resonance Magnetic Fields

    Science.gov (United States)

    Macrophages, when entering inflamed tissue, encounter low oxygen tension due to the impairment of blood supply and/or the massive infiltration of cells that consume oxygen. Previously, we showed that such macrophages release more bacteriotoxic hydrogen peroxide (H202) when expose...

  16. Tumoral tracers

    International Nuclear Information System (INIS)

    Camargo, E.E.

    1979-01-01

    Direct tumor tracers are subdivided in the following categories:metabolite tracers, antitumoral tracers, radioactive proteins and cations. Use of 67 Ga-citrate as a clinically important tumoral tracer is emphasized and gallium-67 whole-body scintigraphy is discussed in detail. (M.A.) [pt

  17. Animal tumors

    International Nuclear Information System (INIS)

    Gillette, E.L.

    1983-01-01

    There are few trained veterinary radiation oncologists and the expense of facilities has limited the extent to which this modality is used. In recent years, a few cobalt teletherapy units and megavoltage x-ray units have been employed in larger veterinary institutions. In addition, some radiation oncologists of human medical institutions are interested and willing to cooperate with veterinarians in the treatment of animal tumors. Carefully designed studies of the response of animal tumors to new modalities serve two valuable purposes. First, these studies may lead to improved tumor control in companion animals. Second, these studies may have important implications to the improvement of therapy of human tumors. Much remains to be learned of animal tumor biology so that appropriate model systems can be described for such studies. Many of the latter studies can be sponsored by agencies interested in the improvement of cancer management

  18. In vivo studies of radiation potentiaton by iodoacetamide and observations on tumor transplantation immunity

    Energy Technology Data Exchange (ETDEWEB)

    Richards, W. Robert [Univ. of California, Berkeley, CA (United States); Kelly, Lola S. [Univ. of California, Berkeley, CA (United States)

    1970-10-01

    Iodoacetamide has been shown by others to be a radiation sensitizer for bacteria and for certain mammalian cells tested in vitro. This work describes an examination of the effectiveness of iodoacetamide used in vivo. Survival of ascites tumor cells maintained in the peritoneal cavity of mice was used as an indicator of sensitization. Survival was assessed using TD50 and total tumor cell population determination methods. A comparison of results obtained by these methods is made. The effects of oxygen tension and radiation dose rate upon results was examined. Iodoacetamide was found to be effective as a radiation sensitizer under all conditions although to a lesser degree than that reported by others for in vitro experiments with bacteria. Radioactive tracer studies indicate that iodoacetamide has rapid and total access to most if not all tissues of the body. This fact coupled with the observation of a sensitization in an in vivo system where the anoxia so prevalent in well developed tumors was present, suggests the possibility of clinical usefulness of iodoacetamide in cancer radiation therapy. Certain observations are reported on the effect of various cell and host treatment procedures upon cell population growth kinetics seen subsequent to inoculation of hosts with the cells. A hypothesis is presented which can account for the observations made by the author and also for those made by some others who report that large inocula, i.e., greater than 10 cells, are required to give rise to a lethal tumor in isologous hosts of the strain of tumor origin. The hypothesis may also account for what is known in the literature as the 'Hybrid Effect.'

  19. Pulmonary Scintigraphy for Tumour Diagnosis; La Gammagrafia Pulmonar en Diagnostico Tumoral

    Energy Technology Data Exchange (ETDEWEB)

    Esteban, J.; Lasa, D.; Herranz, R.; Galvez, F.; Negueruela, J.; Perez-Modrego, S. [Hospital Oncologico Provincial, Madrid (Spain)

    1969-05-15

    Scanning of the lungs with albumin aggregates is one of the most useful methods for studying variations in pulmonary circulation and diagnosing embolisms and infarcts. However, its utilization for the diagnosis of tumours is barely in the trial stage. Using scintillation scanning, the authors have centered their attention on the study of patients with primary pulmonary tumours and secondary tumours at-other sites, and have observed that the tracer distribution pattern differs fundamentally according to the type of tumour. With metastatic tumours, the repercussion of the lesions in scintillation scanning is slight and is entirely dependent on the volume of the zone of condensation. The tumorous nodules behave entirely like inactive zones within a mass of active functional parenchyma and their effect on the scanning image depends solely on the size of the tumorous region and the amount of healthy parenchyma intervening between it and the detector. With primary pulmonary tumours and more especially those located in the hilar region, relatively small lesions give rise to defects in uptake in extensive areas of the lung, and these may affect various segments, a lobe or even the entire lung. This decrease in uptake cannot be entirely explained by the image of the tumour or by the associated zones of atelectasia, but must be due to serious alteration in the haemodynamics of the lung affected. Various kinds of phenomena associated with tumorous development may cause vascular changes affecting even the periphery of the lung: changes in breathing conditions accompanied by a reduction of oxygen tension, leading to change in haemodynamic conditions; pulmonary hypertension through compression of the veins in the lungs which are less resistant than the arteries; and direct nervous stimulation due to irritation of the bronchial plexi as a result of the growth of the tumour and, associated reactive. phenomena. (author) [Spanish] La gammagraffa de pulmon con agregados de albumina

  20. Imaging probe for tumor malignancy

    Science.gov (United States)

    Tanaka, Shotaro; Kizaka-Kondoh, Shinae; Hiraoka, Hasahiro

    2009-02-01

    Solid tumors possess unique microenvironments that are exposed to chronic hypoxic conditions ("tumor hypoxia"). Although more than half a century has passed since it was suggested that tumor hypoxia correlated with poor treatment outcomes and contributed to cancer recurrence, a fundamental solution to this problem has yet to be found. Hypoxia-inducible factor (HIF-1) is the main transcription factor that regulates the cellular response to hypoxia. It induces various genes whose functions are strongly associated with malignant alteration of the entire tumor. The cellular changes induced by HIF-1 are extremely important targets of cancer therapy, particularly in therapy against refractory cancers. Imaging of the HIF-1-active microenvironment is therefore important for cancer therapy. To image HIF-1activity in vivo, we developed a PTD-ODD fusion protein, POHA, which was uniquely labeled with near-infrared fluorescent dye at the C-terminal. POHA has two functional domains: protein transduction domain (PTD) and VHL-mediated protein destruction motif in oxygen-dependent degradation (ODD) domain of the alpha subunit of HIF-1 (HIF-1α). It can therefore be delivered to the entire body and remain stabilized in the HIF-1-active cells. When it was intravenously injected into tumor-bearing mice, a tumor-specific fluorescence signal was detected in the tumor 6 h after the injection. These results suggest that POHA can be used an imaging probe for tumor malignancy.

  1. Speaker and Observer Perceptions of Physical Tension during Stuttering.

    Science.gov (United States)

    Tichenor, Seth; Leslie, Paula; Shaiman, Susan; Yaruss, J Scott

    2017-01-01

    Speech-language pathologists routinely assess physical tension during evaluation of those who stutter. If speakers experience tension that is not visible to clinicians, then judgments of severity may be inaccurate. This study addressed this potential discrepancy by comparing judgments of tension by people who stutter and expert clinicians to determine if clinicians could accurately identify the speakers' experience of physical tension. Ten adults who stutter were audio-video recorded in two speaking samples. Two board-certified specialists in fluency evaluated the samples using the Stuttering Severity Instrument-4 and a checklist adapted for this study. Speakers rated their tension using the same forms, and then discussed their experiences in a qualitative interview so that themes related to physical tension could be identified. The degree of tension reported by speakers was higher than that observed by specialists. Tension in parts of the body that were less visible to the observer (chest, abdomen, throat) was reported more by speakers than by specialists. The thematic analysis revealed that speakers' experience of tension changes over time and that these changes may be related to speakers' acceptance of stuttering. The lack of agreement between speaker and specialist perceptions of tension suggests that using self-reports is a necessary component for supporting the accurate diagnosis of tension in stuttering. © 2018 S. Karger AG, Basel.

  2. Recapitulation of tumor heterogeneity and molecular signatures in a 3D brain cancer model with decreased sensitivity to histone deacetylase inhibition.

    Directory of Open Access Journals (Sweden)

    Stuart J Smith

    Full Text Available INTRODUCTION: Physiologically relevant pre-clinical ex vivo models recapitulating CNS tumor micro-environmental complexity will aid development of biologically-targeted agents. We present comprehensive characterization of tumor aggregates generated using the 3D Rotary Cell Culture System (RCCS. METHODS: CNS cancer cell lines were grown in conventional 2D cultures and the RCCS and comparison with a cohort of 53 pediatric high grade gliomas conducted by genome wide gene expression and microRNA arrays, coupled with immunohistochemistry, ex vivo magnetic resonance spectroscopy and drug sensitivity evaluation using the histone deacetylase inhibitor, Vorinostat. RESULTS: Macroscopic RCCS aggregates recapitulated the heterogeneous morphology of brain tumors with a distinct proliferating rim, necrotic core and oxygen tension gradient. Gene expression and microRNA analyses revealed significant differences with 3D expression intermediate to 2D cultures and primary brain tumors. Metabolic profiling revealed differential profiles, with an increase in tumor specific metabolites in 3D. To evaluate the potential of the RCCS as a drug testing tool, we determined the efficacy of Vorinostat against aggregates of U87 and KNS42 glioblastoma cells. Both lines demonstrated markedly reduced sensitivity when assaying in 3D culture conditions compared to classical 2D drug screen approaches. CONCLUSIONS: Our comprehensive characterization demonstrates that 3D RCCS culture of high grade brain tumor cells has profound effects on the genetic, epigenetic and metabolic profiles of cultured cells, with these cells residing as an intermediate phenotype between that of 2D cultures and primary tumors. There is a discrepancy between 2D culture and tumor molecular profiles, and RCCS partially re-capitulates tissue specific features, allowing drug testing in a more relevant ex vivo system.

  3. Structural design significance of tension-tension fatigue data on composites

    Science.gov (United States)

    Grimes, G. C.

    1977-01-01

    Constant cycle tension-tension fatigue and related static tension data have been generated on six single composite material/orientation combinations and twenty-one hybrid composite material/orientation combinations. Anomalies are related to the temperature rise and stopped interval creep, whereas endurance limit stresses (runouts) are associated with static proportional limit values, when they occur, and internal damage. The significance of these room temperature-dry data on the design allowables and weight of aerodynamic structueres is discussed. Such structures are helicopter rotor blades and wing and horizontal stabilizer lower surfaces. Typical criteria for turning these data into preliminary allowables are shown, as are examples of such allowables developed from the data. These values are then compared to those that might be used if the structures were made of metal.

  4. Determination of the oxygen enhancement ratio (OER) of human colon tumor cells in vitro after chronic exposure to the differentiation-inducing agents n-methylformamide (NMF) and sodium butyrate (NAB)

    International Nuclear Information System (INIS)

    Hallows, K.; Bliven, S.; Leith, J.T.

    1987-01-01

    The authors previously showed that both rodent and human tumor cells in either exponentially growing or plateau phase cultures can be sensitized to X-irradiation by chronic exposure to NMF or NAB. This effect is particularly evident in the low dose region of the survival curve as noted by a significant increase in the term of the linear-quadratic equation or by a significant decrease in the D/sub q/ value using single-hit, multitarget nomenclature. However, these agents are operationally distinct, as these changes are accompanied by inhibition of sublethal damage recovery (SLDR) after NAB treatment, while no effect on SLDR is seen with NMF treatment. As they think that the use of differentiation-inducing agent such as NMF or NAB may be useful in combining modality therapy of solid tumors, the authors extended their previous studies to note if any change in the OER accompanying this observed radiosensitization of oxic cells could be found. Tumor cells were grown in either 170mM NMF or 2 mM NAB and were irradiated with 250 kVp x-rays. Data is presented

  5. Pituitary Tumors

    Science.gov (United States)

    ... Association (ABTA) International RadioSurgery Association National Brain Tumor Society National Institute of Child Health and Human Development ... Definition The pituitary is a small, bean-sized gland ...

  6. Hypothalamic tumor

    Science.gov (United States)

    ... in the brain to reduce spinal fluid pressure. Risks of radiation therapy include damage to healthy brain cells when tumor cells are destroyed. Common side effects from chemotherapy include loss of appetite, nausea and vomiting, and fatigue.

  7. Cuerpo y subjetividad: materiales y tensiones

    OpenAIRE

    Cachorro, Gabriel

    2007-01-01

    En este artículo se efectúa un abordaje del tema cuerpo y subjetividad a través de un ejercicio exploratorio de sus materiales y tensiones. Las preguntas posibles de formular son: ¿Qué discusiones tenemos por debajo de la subjetividad corporal?, ¿cuáles son las raíces históricas de este tema?, ¿qué problemáticas lo atraviesan? La enunciación de estos interrogantes nos ayuda a establecer la posición de investigador y a explicitar los argumentos teóricos. Se desprende de esta propuest...

  8. Temporomandibular disorders and tension-type headache.

    Science.gov (United States)

    Mongini, Franco

    2007-12-01

    Pathologies currently defined as temporomandibular disorders may be different in nature. Temporomandibular joint (TMJ) disorders and craniofacial and cervical myogenous pain (MP) are distinct pathologies but may be superimposed and share some etiologic factors. Tension-type headache (TTH) may often be associated with craniofacial and cervical pain, and the same pharmacologic and nonpharmacologic treatment may be efficacious for both. Psychiatric comorbidity (depression and/or anxiety disorder) is less frequent in sheer TMJ disorders, compared with MP and TTH. A screening for the presence of an underlying psychiatric disorder should be part of the clinical evaluation in patients suffering from headache and facial pain.

  9. Small-Bolt Torque-Tension Tester

    Science.gov (United States)

    Posey, Alan J.

    2009-01-01

    The device described here measures the torque-tension relationship for fasteners as small as #0. The small-bolt tester consists of a plate of high-strength steel into which three miniature load cells are recessed. The depth of the recess is sized so that the three load cells can be shimmed, the optimum height depending upon the test hardware. The three miniature load cells are arranged in an equilateral triangular configuration with the test bolt aligned with the centroid of the three. This is a kinematic arrangement.

  10. Superficial tension: experimental model with simple materials

    Directory of Open Access Journals (Sweden)

    Tintori Ferreira, María Alejandra

    2012-09-01

    Full Text Available In this work appears a didactic offer based on an experimental activity using materials of very low cost, orientated to achieving that the student understand and interpret the phenomenon of superficial tension together with the importance of the modeling in sciences. It has as principal aim of education bring the student over to the mechanics of the static fluids and the intermolecular forces, combining scientific contents with questions near to the student what provides an additional motivation to the reflection of the scientific investigation.

  11. Effective tension and fluctuations in active membranes

    OpenAIRE

    Loubet, Bastien; Seifert, Udo; Lomholt, Michael Andersen

    2011-01-01

    We calculate the fluctuation spectrum of the shape of a lipid vesicle or cell exposed to a nonthermal source of noise. In particular we take into account constraints on the membrane area and the volume of fluid that it encapsulates when obtaining expressions for the dependency of the membrane tension on the noise. We then investigate three possible origins of the non-thermal noise taken from the literature: A direct force, which models an external medium pushing on the membrane. A curvature f...

  12. A polarized view on DNA under tension

    Science.gov (United States)

    van Mameren, Joost; Vermeulen, Karen; Wuite, Gijs J. L.; Peterman, Erwin J. G.

    2018-03-01

    In the past decades, sensitive fluorescence microscopy techniques have contributed significantly to our understanding of the dynamics of DNA. The specific labeling of DNA using intercalating dyes has allowed for quantitative measurement of the thermal fluctuations the polymers undergo. On the other hand, recent advances in single-molecule manipulation techniques have unraveled the mechanical and elastic properties of this intricate polymer. Here, we have combined these two approaches to study the conformational dynamics of DNA under a wide range of tensions. Using polarized fluorescence microscopy in conjunction with optical-tweezers-based manipulation of YOYO-intercalated DNA, we controllably align the YOYO dyes using DNA tension, enabling us to disentangle the rapid dynamics of the dyes from that of the DNA itself. With unprecedented control of the DNA alignment, we resolve an inconsistency in reports about the tilted orientation of intercalated dyes. We find that intercalated dyes are on average oriented perpendicular to the long axis of the DNA, yet undergo fast dynamics on the time scale of absorption and fluorescence emission. In the overstretching transition of double-stranded DNA, we do not observe changes in orientation or orientational dynamics of the dyes. Only beyond the overstretching transition, a considerable depolarization is observed, presumably caused by an average tilting of the DNA base pairs. Our combined approach thus contributes to the elucidation of unique features of the molecular dynamics of DNA.

  13. Tumor Types: Understanding Brain Tumors

    Science.gov (United States)

    ... May cause excessive secretion of hormones Common among men and women in their 50s-80s Accounts for about 13 percent of all brain tumors Symptoms Headache Depression Vision loss Nausea or vomiting Behavioral and cognitive ...

  14. Shape accuracy optimization for cable-rib tension deployable antenna structure with tensioned cables

    Science.gov (United States)

    Liu, Ruiwei; Guo, Hongwei; Liu, Rongqiang; Wang, Hongxiang; Tang, Dewei; Song, Xiaoke

    2017-11-01

    Shape accuracy is of substantial importance in deployable structures as the demand for large-scale deployable structures in various fields, especially in aerospace engineering, increases. The main purpose of this paper is to present a shape accuracy optimization method to find the optimal pretensions for the desired shape of cable-rib tension deployable antenna structure with tensioned cables. First, an analysis model of the deployable structure is established by using finite element method. In this model, geometrical nonlinearity is considered for the cable element and beam element. Flexible deformations of the deployable structure under the action of cable network and tensioned cables are subsequently analyzed separately. Moreover, the influence of pretension of tensioned cables on natural frequencies is studied. Based on the results, a genetic algorithm is used to find a set of reasonable pretension and thus minimize structural deformation under the first natural frequency constraint. Finally, numerical simulations are presented to analyze the deployable structure under two kinds of constraints. Results show that the shape accuracy and natural frequencies of deployable structure can be effectively improved by pretension optimization.

  15. Tumor immunology.

    Science.gov (United States)

    Mocellin, Simone; Lise, Mario; Nitti, Donato

    2007-01-01

    Advances in tumor immunology are supporting the clinical implementation of several immunological approaches to cancer in the clinical setting. However, the alternate success of current immunotherapeutic regimens underscores the fact that the molecular mechanisms underlying immune-mediated tumor rejection are still poorly understood. Given the complexity of the immune system network and the multidimensionality of tumor/host interactions, the comprehension of tumor immunology might greatly benefit from high-throughput microarray analysis, which can portrait the molecular kinetics of immune response on a genome-wide scale, thus accelerating the discovery pace and ultimately catalyzing the development of new hypotheses in cell biology. Although in its infancy, the implementation of microarray technology in tumor immunology studies has already provided investigators with novel data and intriguing new hypotheses on the molecular cascade leading to an effective immune response against cancer. Although the general principles of microarray-based gene profiling have rapidly spread in the scientific community, the need for mastering this technique to produce meaningful data and correctly interpret the enormous output of information generated by this technology is critical and represents a tremendous challenge for investigators, as outlined in the first section of this book. In the present Chapter, we report on some of the most significant results obtained with the application of DNA microarray in this oncology field.

  16. Pancreatic islet cell tumor

    Science.gov (United States)

    ... cell tumors; Islet of Langerhans tumor; Neuroendocrine tumors; Peptic ulcer - islet cell tumor; Hypoglycemia - islet cell tumor ... stomach acid. Symptoms may include: Abdominal pain Diarrhea ... and small bowel Vomiting blood (occasionally) Glucagonomas make ...

  17. The tension of framed membranes from computer simulations

    DEFF Research Database (Denmark)

    Hamkens, Daniel; Jeppesen, Claus; Ipsen, John H.

    2018-01-01

    the membranes display power-law characteristics for the equation of state, while higher tension levels includes both an extended linear (elastic) as well as a highly non-linear stretching regime. For semi-flexible membranes a transition from extended to buckled conformations takes place at negative frame......Abstract.: We have analyzed the behavior of a randomly triangulated, self-avoiding surface model of a flexible, fluid membrane subject to a circular boundary by Wang-Landau Monte Carlo computer simulation techniques. The dependence of the canonical free energy and frame tension on the frame area...... is obtained for flexible membranes. It is shown that for low bending rigidities the framed membrane is only stable above a threshold tension, suggesting a discontinuous transition from the collapsed (branched polymer) state to a finite tension extended state. In a tension range above this threshold tension...

  18. No oxygen delivery limitation in hepatic encephalopathy

    DEFF Research Database (Denmark)

    Gjedde, Albert; Keiding, Susanne; Vilstrup, Hendrik

    2010-01-01

    to choose between cause and effect in three groups of volunteers, including healthy control subjects (HC), patients with cirrhosis of the liver without hepatic encephalopathy (CL), and patients with cirrhosis with acute hepatic encephalopathy. Compared to HC subjects, blood flow and energy metabolism had......Hepatic encephalopathy is a condition of reduced brain functioning in which both blood flow and brain energy metabolism declined. It is not known whether blood flow or metabolism is the primary limiting factor of brain function in this condition. We used calculations of mitochondrial oxygen tension...

  19. Surface tension of liquid Al-Cu binary alloys.

    OpenAIRE

    Schmitz, Julianna; Brillo, Jürgen; Egry, Ivan; Schmid-Fetzer, Rainer

    2009-01-01

    Surface tension data of liquid Al–Cu binary alloys have been measured contactlessly using the technique of electromagnetic levitation. A digital CMOS-camera (400 fps) recorded image sequences of the oscillating liquid sample and surface tensions were determined from analysis of the frequency spectra. Measurements were performed for samples covering the entire range of composition and precise data were obtained in a broad temperature range. It was found that the surface tensions can ...

  20. Imaging of brain tumors

    International Nuclear Information System (INIS)

    Gaensler, E.H.L.

    1995-01-01

    The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.)

  1. Imaging of brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Gaensler, E H.L. [California Univ., San Francisco, CA (United States). Dept. of Radiology

    1996-12-31

    The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.).

  2. Oxygen transfer rate during the production of alginate by Azotobacter vinelandii under oxygen-limited and non oxygen-limited conditions

    Directory of Open Access Journals (Sweden)

    Peña Carlos F

    2011-02-01

    Full Text Available Abstract Background The oxygen transfer rate (OTR and dissolved oxygen tension (DOT play an important role in determining alginate production and its composition; however, no systematic study has been reported about the independent influence of the OTR and DOT. In this paper, we report a study about alginate production and the evolution of the molecular mass of the polymer produced by a wild-type A. vinelandii strain ATCC 9046, in terms of the maximum oxygen transfer rate (OTRmax in cultures where the dissolved oxygen tension (DOT was kept constant. Results The results revealed that in the two dissolved oxygen conditions evaluated, strictly controlled by gas blending at 0.5 and 5% DOT, an increase in the agitation rate (from 300 to 700 rpm caused a significant increase in the OTRmax (from 17 to 100 mmol L-1 h-1 for DOT of 5% and from 6 to 70 mmol L-1 h-1 for DOT of 0.5%. This increase in the OTRmax improved alginate production, as well as the specific alginate production rate (SAPR, reaching a maximal alginate concentration of 3.1 g L-1 and a SAPR of 0.031 g alg g biom-1 h-1 in the cultures at OTRmax of 100 mmol L-1 h-1. In contrast, the mean molecular mass (MMM of the alginate isolated from cultures developed under non-oxygen limited conditions increased by decreasing the OTRmax, reaching a maximal of 550 kDa at an OTRmax of 17 mmol L-1 h-1 . However, in the cultures developed under oxygen limitation (0.5% DOT, the MMM of the polymer was practically the same (around 200 kDa at 300 and 700 rpm, and this remained constant throughout the cultivation. Conclusions Overall, our results showed that under oxygen-limited and non oxygen-limited conditions, alginate production and its molecular mass are linked to the OTRmax, independently of the DOT of the culture.

  3. Bending Under Tension Test with Direct Friction Measurement

    DEFF Research Database (Denmark)

    Andreasen, Jan Lasson; Olsson, David Dam; Chodnikiewicz, K.

    2006-01-01

    A special Bending-Under-Tension (BUT) transducer has been developed in which friction around the tool radius can be directly measured when drawing a plane sheet strip around a cylindrical tool-pin under constant back tension. The front tension, back tension and torque on the tool-pin are all...... measured directly, thus enabling accurate measurement of friction and direct determination of lubricant film breakdown for varying normal pressure, sliding speed, tool radius and tool preheat temperature. The transducer is applied in an experimental investigation focusing on limits of lubrication...

  4. The law of corresponding states and surface tension of metals

    International Nuclear Information System (INIS)

    Digilov, R.

    2001-01-01

    Full Text: Surface tension of liquid metals is one of fundamental and most important quantities in theory and practice of material processing and its temperature dependence leads to the well-known Marangoni convection. Although currently methods are sufficiently precise to measure the surface tension, there are uncertainties in experimental data and its temperature dependence mainly due to impurity, which even a trace of it strongly affects the results of measurements. The theoretical treatment from the first principles is unwieldy and not always permits one to calculate the surface tension with certainty. Another active research field deals with empirical correlation between the surface tension and bulk thermodynamic properties, which we interpret as a simple consequence of the law of corresponding states. In order to relate the surface tension and to bulk properties of liquid metals the reduced formula is derived by scaling with the melting point T m (0) at p = 0 and atomic volume Ω 0 2/3 at T = 0 K as macroscopic parameters for scaling ε and a characterizing the interatomic potential in metals. The reduced surface tension and the reduced surface entropy obtained in high temperature limit are discussed and compared with the experiment. The reduced temperature coefficient of the surface tension found is a universal constant for the metals of the same structure. It is shown that pressure dependence of the surface tension, so called baric coefficient of the surface tension, can be described by pressure dependence of scaling parameters T m (p) and Ω 0 (p). (author)

  5. Strain Capacity of Reinforced Concrete Members Subjected to Uniaxial Tension

    DEFF Research Database (Denmark)

    Hagsten, Lars German; Rasmussen, Annette Beedholm; Fisker, Jakob

    2017-01-01

    The aim of this paper is to set up a method to determine the strain capacity of tension bars of reinforced concrete (RC) subjected to pure tension. Due to the interaction between reinforcement and concrete and due to the presence of cracks, the stresses in both reinforcement and concrete...... are varying along the length of the tension bar. The strain capacity of the tension bar is seen as the average strain in the reinforcement at the load level corresponding to the ultimate stress capacity of the reinforcement at the cracks. The result of the approach is in overall good agreement when comparing...

  6. An automatic tension measurement system of MWPC wires

    International Nuclear Information System (INIS)

    D'Antone, I.; Lolli, M.; Torromeo, G.

    1992-01-01

    An electronic system is presented for automatic mechanical tension measurement to test wire chambers. The developed system works in the tension range from 50 g to 300 g; this large working range is obtained by using a microcontroller that performs a digital control on the bridge of an oscillator containing the wire of which the tension has to be measured. The microcontroller automatically brings the system towards the oscillation condition and subsequently, measuring the frequency, it evaluates, displays and sends to a host computer the value of the mechanical tension of the wires. The system is precise and allows fast measurements. A description of the hardware and software design is given. (orig.)

  7. Breath ethane as a marker of reactive oxygen species during manipulation of diet and oxygen tension in rats.

    Science.gov (United States)

    Risby, T H; Jiang, L; Stoll, S; Ingram, D; Spangler, E; Heim, J; Cutler, R; Roth, G S; Rifkind, J M

    1999-02-01

    Breath ethane, O2 consumption, and CO2 production were analyzed in 24-mo-old female Fischer 344 rats that had been fed continuously ad libitum (AL) or restricted 30% of AL level (DR) diets since 6 wk of age. Rats were placed in a glass chamber that was first flushed with air, then with a gas mixture containing 12% O2. After equilibration, a sample of the outflow was collected in gas sampling bags for subsequent analyses of ethane and CO2. The O2 and CO2 levels were also directly monitored in the outflow of the chamber. O2 consumption and CO2 production increased for DR rats. Hypoxia decreased O2 consumption and CO2 production for the AL-fed and DR rats. These changes reflect changes in metabolic rate due to diet and PO2. A significant decrease in ethane generation was found in DR rats compared with AL-fed rats. Under normoxic conditions, breath ethane decreased from 2.20 to 1.61 pmol ethane/ml CO2. During hypoxia the levels of ethane generation increased, resulting in a DR-associated decrease in ethane from 2.60 to 1.90 pmol ethane/ml CO2. These results support the hypothesis that DR reduces the level of oxidative stress.

  8. Delayed Tension Pneumothorax - Identification and Treatment in Traumatic Bronchial Injury: An Interesting Presentation.

    Science.gov (United States)

    Gupta, Amit; Rattan, Amulya; Kumar, Sunil; Rathi, Vinita

    2017-09-01

    A 13-year-old girl, who did not receive any treatment for few hours following Road Traffic Injury (RTI), reported to the Casualty Department and found to have patent airway with clinically normal C spine, air-hunger (RR 42/minute), trachea deviated to left, distended neck veins and absent breath sounds on the right side. The chest X-ray she carried, done immediately after the injury, showed right sided tension pneumothorax. She was put on oxygen at 11 L/minute and an Intercostal chest tube drainage (ICD) was inserted on right side. Her oxygen saturation (40%) failed to improve. ICD bag showed continuous bubbling and air entry remained absent on the right side. An urgent right thoracotomy was done which revealed right main bronchus tear; the tear was repaired using interrupted Prolene ® sutures. Patient recovered well and was discharged 10 days later in a stable condition.

  9. Cavitation propagation in water under tension

    Science.gov (United States)

    Noblin, Xavier; Yip Cheung Sang, Yann; Pellegrin, Mathieu; Materials and Complex Fluids Team

    2012-11-01

    Cavitation appears when pressure decreases below vapor pressure, generating vapor bubbles. It can be obtain in dynamical ways (acoustic, hydraulic) but also in quasi-static conditions. This later case is often observed in nature, in trees, or during the ejection of ferns spores. We study the cavitation bubbles nucleation dynamics and its propagation in a confined microfabricated media. This later is an ordered array of microcavities made in hydrogel filled with water. When the system is put into dry air, it dehydrates, water leaves the cavities and tension (negative pressure) builds in the cavities. This can be sustained up to a critical pressure (of order -20 MPa), then cavitation bubbles appear. We follow the dynamics using ultra high speed imaging. Events with several bubbles cavitating in a few microseconds could be observed along neighboring cells, showing a propagation phenomenon that we discuss. ANR CAVISOFT 2010-JCJC-0407 01.

  10. Tension Tests of Copper Thin Films

    Energy Technology Data Exchange (ETDEWEB)

    Park, Kyung Jo; Kim, Chung Youb [Chonnam Nat’l Univ., Gwangju (Korea, Republic of)

    2017-08-15

    Tension tests for copper thin films with thickness of 12 μm were performed by using a digital image correlation method based on consecutive digital images. When calculating deformation using digital image correlation, a large deformation causes errors in the calculated result. In this study, the calculation procedure was improved to reduce the error, so that the full field deformation and the strain of the specimen could be accurately and directly measured on its surface. From the calculated result, it can be seen that the strain distribution is not uniform and its variation is severe, unlike the distribution in a common bulk specimen. This might result from the surface roughness introduced in the films during the fabrication process by electro-deposition.

  11. Tension Type Headache: Evaluation of Chronic Type

    Directory of Open Access Journals (Sweden)

    Ömer Karadaş

    2013-11-01

    Full Text Available Tension type headache(TTH which is a primary headache has episodic and chronic forms. Episodic TTH (ETTH can also be frequent-type and non-frequent-type. According to population-based studies, annual prevalence rates are 38.3% for ETTH and 2.2% for chronic TTH (CTTH. Patients can shift between the sub-groups of TTH. In particular, patients with ETTH are at risk of developing CTTH. Peripheral and central nociceptive mechanism are thought to be responsible in occurrence of TTH. Psychiatric disorders are frequently associated with TTH. Although basic and combined analgesics are used in acute treatment and antidepresants are used in prophylaxis, new treatment modalities are needed.

  12. Effective tension and fluctuations in active membranes.

    Science.gov (United States)

    Loubet, Bastien; Seifert, Udo; Lomholt, Michael Andersen

    2012-03-01

    We calculate the fluctuation spectrum of the shape of a lipid vesicle or cell exposed to a nonthermal source of noise. In particular, we take constraints on the membrane area and the volume of fluid that it encapsulates into account when obtaining expressions for the dependency of the membrane tension on the noise. We then investigate three possible origins of the nonthermal noise taken from the literature: A direct force, which models an external medium pushing on the membrane, a curvature force, which models a fluctuating spontaneous curvature, and a permeation force coming from an active transport of fluid through the membrane. For the direct force and curvature force cases, we compare our results to existing experiments on active membranes.

  13. Reduced muscle activation during exercise related to brain oxygenation and metabolism in humans

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Nielsen, Jannie; Overgaard, M

    2010-01-01

    Maximal exercise may be limited by central fatigue defined as an inability of the central nervous system to fully recruit the involved muscles. This study evaluated whether a reduction in the cerebral oxygen-to-carbohydrate index (OCI) and in the cerebral mitochondrial oxygen tension relate to th...... indicating that reduced cerebral oxygenation may play a role in the development of central fatigue and may be an exercise capacity limiting factor.......Maximal exercise may be limited by central fatigue defined as an inability of the central nervous system to fully recruit the involved muscles. This study evaluated whether a reduction in the cerebral oxygen-to-carbohydrate index (OCI) and in the cerebral mitochondrial oxygen tension relate...... of perceived exertion (RPE), arm maximal voluntary force (MVC), and voluntary activation of elbow flexor muscles assessed with transcranial magnetic stimulation. Low intensity exercise did not produce any indication of central fatigue or marked cerebral metabolic deviations. Exercise in hypoxia (0.10) reduced...

  14. Bone tumors

    International Nuclear Information System (INIS)

    Moylan, D.J.; Yelovich, R.M.

    1991-01-01

    Primary bone malignancies are relatively rare with less than 4,000 new cases per year. Multiple myeloma (more correctly a hematologic malignancy) accounts for 40%; osteosarcomas, 28%; chondrosarcomas, 13%; fibrosarcomas arising in bone, 4%; and Ewing's sarcoma, 7%. The authors discuss various treatments for bone tumors, including radiotherapy, chemotherapy and surgery

  15. Wilms Tumor

    Science.gov (United States)

    ... a child's general health and to detect any adverse side effects (such as low red or white blood cell ... medicine needed, which helps reduce long-term side effects. The most common ... can be completely removed by surgery. About 41% of all Wilms tumors are stage ...

  16. Nephrogenic tumors

    International Nuclear Information System (INIS)

    Wiesbauer, P.

    2008-01-01

    Nephroblastomas are the most common malignant renal tumors in childhood. According to the guidelines of the SIOP (Societe Internationale d'Oncologie Pediatrique) and GPOH (Gesellschaft fuer Paediatrische Onkologie und Haematologie) pre-operative chemotherapy can be started without histological confirmation and thus initial imaging studies, in particular ultrasound, play an outstanding role for diagnostic purposes

  17. Artificial oxygen transport protein

    Science.gov (United States)

    Dutton, P. Leslie

    2014-09-30

    This invention provides heme-containing peptides capable of binding molecular oxygen at room temperature. These compounds may be useful in the absorption of molecular oxygen from molecular oxygen-containing atmospheres. Also included in the invention are methods for treating an oxygen transport deficiency in a mammal.

  18. Hypoxia signaling pathways: modulators of oxygen-related organelles

    Science.gov (United States)

    Schönenberger, Miriam J.; Kovacs, Werner J.

    2015-01-01

    Oxygen (O2) is an essential substrate in cellular metabolism, bioenergetics, and signaling and as such linked to the survival and normal function of all metazoans. Low O2 tension (hypoxia) is a fundamental feature of physiological processes as well as pathophysiological conditions such as cancer and ischemic diseases. Central to the molecular mechanisms underlying O2 homeostasis are the hypoxia-inducible factors-1 and -2 alpha (HIF-1α and EPAS1/HIF-2α) that function as master regulators of the adaptive response to hypoxia. HIF-induced genes promote characteristic tumor behaviors, including angiogenesis and metabolic reprogramming. The aim of this review is to critically explore current knowledge of how HIF-α signaling regulates the abundance and function of major O2-consuming organelles. Abundant evidence suggests key roles for HIF-1α in the regulation of mitochondrial homeostasis. An essential adaptation to sustained hypoxia is repression of mitochondrial respiration and induction of glycolysis. HIF-1α activates several genes that trigger mitophagy and represses regulators of mitochondrial biogenesis. Several lines of evidence point to a strong relationship between hypoxia, the accumulation of misfolded proteins in the endoplasmic reticulum, and activation of the unfolded protein response. Surprisingly, although peroxisomes depend highly on molecular O2 for their function, there has been no evidence linking HIF signaling to peroxisomes. We discuss our recent findings that establish HIF-2α as a negative regulator of peroxisome abundance and suggest a mechanism by which cells attune peroxisomal function with O2 availability. HIF-2α activation augments peroxisome turnover by pexophagy and thereby changes lipid composition reminiscent of peroxisomal disorders. We discuss potential mechanisms by which HIF-2α might trigger pexophagy and place special emphasis on the potential pathological implications of HIF-2α-mediated pexophagy for human health. PMID:26258123

  19. Membrane tension regulates clathrin-coated pit dynamics

    Science.gov (United States)

    Liu, Allen

    2014-03-01

    Intracellular organization depends on close communication between the extracellular environment and a network of cytoskeleton filaments. The interactions between cytoskeletal filaments and the plasma membrane lead to changes in membrane tension that in turns help regulate biological processes. Endocytosis is thought to be stimulated by low membrane tension and the removal of membrane increases membrane tension. While it is appreciated that the opposing effects of exocytosis and endocytosis have on keeping plasma membrane tension to a set point, it is not clear how membrane tension affects the dynamics of clathrin-coated pits (CCPs), the individual functional units of clathrin-mediated endocytosis. Furthermore, although it was recently shown that actin dynamics counteracts membrane tension during CCP formation, it is not clear what roles plasma membrane tension plays during CCP initiation. Based on the notion that plasma membrane tension is increased when the membrane area increases during cell spreading, we designed micro-patterned surfaces of different sizes to control the cell spreading sizes. Total internal reflection fluorescence microscopy of living cells and high content image analysis were used to quantify the dynamics of CCPs. We found that there is an increased proportion of CCPs with short (<20s) lifetime for cells on larger patterns. Interestingly, cells on larger patterns have higher CCP initiation density, an effect unexpected based on the conventional view of decreasing endocytosis with increasing membrane tension. Furthermore, by analyzing the intensity profiles of CCPs that were longer-lived, we found CCP intensity decreases with increasing cell size, indicating that the CCPs are smaller with increasing membrane tension. Finally, disruption of actin dynamics significantly increased the number of short-lived CCPs, but also decreased CCP initiation rate. Together, our study reveals new mechanistic insights into how plasma membrane tension regulates

  20. Damage development in woven fabric composites during tension-tension fatigue

    DEFF Research Database (Denmark)

    Hansen, U.

    1999-01-01

    of the operating fatigue damage mechanism(s). Fatigue leads to a degradation of material properties. Consequently, in connection with impact induced local stress raisers, fatigue produces continuously changing non-uniform stress fields because of stress redistribution effects. Other models addressing evolution...... of fatigue damage in composite materials have not been able to simulate evolving nonuniform stress fields. Therefore. in the second part of this paper, an analytical/numerical approach capable of addressing these issues is also proposed.......Impacted woven fabric composites were tested in tension-tension fatigue. In contrast to results from static testing, the effects of low energy impact damage in a fatigue environment were found to be the critical element leading to failure of the specimen. This difference emphasizes the need...

  1. Validation of the protoporphyrin IX-triplet state lifetime technique for mitochondrial oxygen measurements in the skin

    NARCIS (Netherlands)

    F.A. Harms (Floor A.); S.I.A. Bodmer (Sander I. A.); N.J.H. Raat (Nicolaas); R.J. Stolker (Robert); E.G. Mik (Egbert)

    2012-01-01

    textabstractMitochondrial oxygen tension can be measured in vivo by means of oxygen-dependent quenching of delayed fluorescence of protoporphyrin IX (PpIX). Here we demonstrate that mitochondrial PO2 (mitoPO2) can be measured in the skin of a rat after topical application of the PpIX precursor

  2. Effects of Dissolved Oxygen Concentration and Iron Addition on Immediate-early Gene Expression of Magnetospirillum gryphiswaldense MSR-1

    DEFF Research Database (Denmark)

    Zhuang, Shiwen; Anyaogu, Diana Chinyere; Kasama, Takeshi

    2017-01-01

    in cultures at 0.5% O2 compared to those at higher oxygen tensions. Moreover, expression of katG (catalase-peroxidase gene) and feoB2 (ferrous transport protein B2 gene) was reduced markedly by iron addition, regardless of oxygen conditions. The data provides a greater understanding of molecular response...

  3. Simultaneous sampling of tissue oxygenation and oxygen consumption in skeletal muscle.

    Science.gov (United States)

    Nugent, William H; Song, Bjorn K; Pittman, Roland N; Golub, Aleksander S

    2016-05-01

    Under physiologic conditions, microvascular oxygen delivery appears to be well matched to oxygen consumption in respiring tissues. We present a technique to measure interstitial oxygen tension (PISFO2) and oxygen consumption (VO2) under steady-state conditions, as well as during the transitions from rest to activity and back. Phosphorescence Quenching Microscopy (PQM) was employed with pneumatic compression cycling to achieve 1 to 10 Hz sampling rates of interstitial PO2 and simultaneous recurrent sampling of VO2 (3/min) in the exteriorized rat spinotrapezius muscle. The compression pressure was optimized to 120-130 mmHg without adverse effect on the tissue preparation. A cycle of 5s compression followed by 15s recovery yielded a resting VO2 of 0.98 ± 0.03 ml O2/100 cm(3)min while preserving microvascular oxygen delivery. The measurement system was then used to assess VO2 dependence on PISFO2 at rest and further tested under conditions of isometric muscle contraction to demonstrate a robust ability to monitor the on-kinetics of tissue respiration and the compensatory changes in PISFO2 during contraction and recovery. The temporal and spatial resolution of this approach is well suited to studies seeking to characterize microvascular oxygen supply and demand in thin tissues. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Conducting Qualitative Data Analysis: Managing Dynamic Tensions within

    Science.gov (United States)

    Chenail, Ronald J.

    2012-01-01

    In the third of a series of "how-to" essays on conducting qualitative data analysis, Ron Chenail examines the dynamic tensions within the process of qualitative data analysis that qualitative researchers must manage in order to produce credible and creative results. These tensions include (a) the qualities of the data and the qualitative data…

  5. Tensions within Teaching: An Autoethnography of an American Teacher

    Science.gov (United States)

    Tuura, Brianne Marie

    2012-01-01

    This dissertation examines the personal transformation of an American teacher as she becomes aware of the social, political, and economic tensions that exist within the American school system and the affects these tensions have on her ability to teach. As the researcher becomes more aware of power structures surrounding her, the reader is enabled…

  6. Curvature dependence of the electrolytic liquid-liquid interfacial tension

    NARCIS (Netherlands)

    Bier, Markus; de Graaf, J.; Zwanikken, J.W.; van Roij, R.H.H.G.

    2009-01-01

    The interfacial tension of a liquid droplet surrounded by another liquid in the presence of microscopic ions is studied as a function of the droplet radius. An analytical expression for the interfacial tension is obtained within a linear Poisson–Boltzmann theory and compared with numerical results

  7. Measurement for Surface Tension of Aqueous Inorganic Salt

    Directory of Open Access Journals (Sweden)

    Jiming Wen

    2018-03-01

    Full Text Available Bubble columns are effective means of filtration in filtered containment venting systems. Here, the surface tension has a significant influence on bubble size distribution and bubble deformation, which have a strong impact on the behavior of the bubble column. The influence of aqueous inorganic compounds on the surface tension depends on the electrolytic activity, Debye length, entropy of ion hydration, and surface deficiencies or excess. In this work, the surface tensions of same specific aqueous solutions have been measured by different methods including platinum plate method, platinum ring method, and maximum bubble pressure method. The measured surface tensions of both sodium hydroxide and sodium thiosulfate are less than that of water. As solution temperature ranges from 20 to 75°C, the surface tension of 0.5 mol/L sodium hydroxide solution decreases from 71 to 55 mN/m while that of 1 mol/L solution decreases from 60 to 45 mN/m. Similarly during the same temperature range, the surface tension of 0.5 mol/L sodium thiosulfate decreases from 70 to 38 mN/m, and that of 1 mol/L sodium thiosulfate is between 68 and 36 mN/m. The analysis for the influence mechanism of aqueous inorganic on surface tension is provided. In addition, experimental results show that the surface tension of solid aerosol suspension liquid has no obvious difference from that of distilled water.

  8. The tension as perturbative parameter in string theory

    International Nuclear Information System (INIS)

    Gamboa, J.

    1990-01-01

    We propose an approach to string theory where the zero theory is the null string. We find an explicit form of the propagator for the null string in the momentum space. We show that considering the tension as perturbative parameter, the perturbative series is completely summable and we find the propagator of the bosonic open string with tension T. (author) [pt

  9. Corrosion resistance of grouted post-tensioning systems : [summary].

    Science.gov (United States)

    2013-08-01

    The increased popularity of post-tensioned bridge construction in the United States has led to concerns about corrosion and its impact on the life cycle of these bridges. Although the vast majority of post-tensioned bridges in the United States have ...

  10. The Tension between Justice and Freedom in Paulo Freire's Epistemology.

    Science.gov (United States)

    Joldersma, Clarence W.

    2001-01-01

    Explores how the concept of freedom in Paulo Freire's constructivist epistemology-constituted as agentive, spontaneity-based action-is in tension with his ethical project of a pedagogy for justice, one based on responsibility and non-indifference. Resolution of this tension means reconceptualizing the grounding notion of the subject beyond a…

  11. Rapid cable tension estimation using dynamic and mechanical properties

    Science.gov (United States)

    Martínez-Castro, Rosana E.; Jang, Shinae; Christenson, Richard E.

    2016-04-01

    Main tension elements are critical to the overall stability of cable-supported bridges. A dependable and rapid determination of cable tension is desired to assess the state of a cable-supported bridge and evaluate its operability. A portable smart sensor setup is presented to reduce post-processing time and deployment complexity while reliably determining cable tension using dynamic characteristics extracted from spectral analysis. A self-recording accelerometer is coupled with a single-board microcomputer that communicates wirelessly with a remote host computer. The portable smart sensing device is designed such that additional algorithms, sensors and controlling devices for various monitoring applications can be installed and operated for additional structural assessment. The tension-estimating algorithms are based on taut string theory and expand to consider bending stiffness. The successful combination of cable properties allows the use of a cable's dynamic behavior to determine tension force. The tension-estimating algorithms are experimentally validated on a through-arch steel bridge subject to ambient vibration induced by passing traffic. The tension estimation is determined in well agreement with previously determined tension values for the structure.

  12. Mimicking physiological O2 tension in the female reproductive tract improves Assisted Reproduction outcomes in pig.

    Science.gov (United States)

    García-Martínez, S; Sánchez-Hurtado, M A; Gutiérrez, H; Sánchez-Margallo, F M; Romar, R; Latorre, R; Coy, P; López-Albors, O

    2018-02-27

    48hpi, cleavage was evaluated under the stereomicroscope. Finally, at 180hpi, development to the blastocyst stage was quantified, blastocyst morphology was assessed, and embryos were fixed and stained to count the mean cell number per blastocyst. The mean O2 content within the pig oviduct and uterus was always lower than in ambient air. The average O2 percentage was higher in gilts (10.0%) than in sows (7.6%) (p number of cells in embryos cultured under the low O2 concentration (88.9 ± 5.9) was observed compared to those cultured under 20% O2 (59.0 ± 5.0) (p < 0.05). None. Although minimally invasive surgery was used the effect of anaesthesia and manipulations on O2 tension within the organs are unknown. Using physiological oxygen concentrations in IVF/EC could improve ART outcomes. This study was funded by Spanish Ministry of Economy and Competitiveness (MINECO) and European Regional Development Fund (FEDER). Grants AGL2012-40180-C03-01 and AGL2015-66341-R. The authors declare no conflict of interest.

  13. Planck and the local Universe: quantifying the tension

    CERN Document Server

    Verde, Licia; Protopapas, Pavlos

    2013-01-01

    We use the latest Planck constraints, and in particular constraints on the derived parameters (Hubble constant and age of the Universe) for the local universe and compare them with local measurements of the same quantities. We propose a way to quantify whether cosmological parameters constraints from two different experiments are in tension or not. Our statistic, T, is an evidence ratio and therefore can be interpreted with the widely used Jeffrey's scale. We find that in the framework of the LCDM model, the Planck inferred two dimensional, joint, posterior distribution for the Hubble constant and age of the Universe is in "strong" tension with the local measurements; the odds being ~ 1:50. We explore several possibilities for explaining this tension and examine the consequences both in terms of unknown errors and deviations from the LCDM model. In some one-parameter LCDM model extensions, tension is reduced whereas in other extensions, tension is instead increased. In particular, small total neutrino masses ...

  14. Myosin II dynamics are regulated by tension in intercalating cells.

    Science.gov (United States)

    Fernandez-Gonzalez, Rodrigo; Simoes, Sérgio de Matos; Röper, Jens-Christian; Eaton, Suzanne; Zallen, Jennifer A

    2009-11-01

    Axis elongation in Drosophila occurs through polarized cell rearrangements driven by actomyosin contractility. Myosin II promotes neighbor exchange through the contraction of single cell boundaries, while the contraction of myosin II structures spanning multiple pairs of cells leads to rosette formation. Here we show that multicellular actomyosin cables form at a higher frequency than expected by chance, indicating that cable assembly is an active process. Multicellular cables are sites of increased mechanical tension as measured by laser ablation. Fluorescence recovery after photobleaching experiments show that myosin II is stabilized at the cortex in regions of increased tension. Myosin II is recruited in response to an ectopic force and relieving tension leads to a rapid loss of myosin, indicating that tension is necessary and sufficient for cortical myosin localization. These results demonstrate that myosin II dynamics are regulated by tension in a positive feedback loop that leads to multicellular actomyosin cable formation and efficient tissue elongation.

  15. Animal studies using an oxygen-tension sensor for tissue viability monitoring

    NARCIS (Netherlands)

    Tanase, D.; Komen, N.; Draaijer, A.; Lange, J.F.; Kleinrensink, G.J.; Jeekel, J.; French, P.J.

    2008-01-01

    Leakage at the site of an anastomosis is the main, yet unsolved reason for mortality in abdominal surgery. Every year, a large number of patients die due to anastomotic leakage after surgery. An objective aid to monitor the anastomotic site pre- and postoperatively and detect leakage at an early

  16. Decreased mucosal oxygen tension in the maxillary sinuses in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Aanæs, Kasper; Rickelt, Lars Fledelius; Johansen, Helle Krogh

    2011-01-01

    Pseudomonas aeruginosa in the sinuses plays a role in the lungs in cystic fibrosis (CF) patients, but little is known about the sinus environment where the bacteria adapt. Anoxic areas are found in the lower respiratory airways but it is unknown if the same conditions exist in the sinuses....

  17. Metabolic programming of mesenchymal stromal cells by oxygen tension directs chondrogenic cell fate

    NARCIS (Netherlands)

    Leijten, Jeroen Christianus Hermanus; Georgi, Nicole; Moreira Teixeira, Liliana; van Blitterswijk, Clemens; Post, Janine Nicole; Karperien, Hermanus Bernardus Johannes

    2014-01-01

    Actively steering the chondrogenic differentiation of mesenchymal stromal cells (MSCs) into either permanent cartilage or hypertrophic cartilage destined to be replaced by bone has not yet been possible. During limb development, the developing long bone is exposed to a concentration gradient of

  18. Reference values of arterial oxygen tension in the middle-aged and elderly.

    Science.gov (United States)

    Cerveri, I; Zoia, M C; Fanfulla, F; Spagnolatti, L; Berrayah, L; Grassi, M; Tinelli, C

    1995-09-01

    The lack of available reference values of arterial PO2, particularly for elderly persons, led us to study a sample of 194 normal nonsmoking subjects, equally distributed over all age ranges from 40 to 90 yr. The radial artery was punctured and blood samples were taken and analyzed on an automated, computerized gas-analyzer. The trend of the mean values of PaO2 in the 5-yr class intervals of age showed a clear decline up to the 70- to 74-yr class, and then an inversion. The two regression lines intersecting at this point provided a better fit to the data than did a single regression line (R22 - R12 = 0.918 - 0.678 = 0.24; F = 20.49, p = 0.0027). The relationship of PaO2 with age was thus subsequently considered for the two subgroups (40 to 74 yr; > or = 75 yr) identified on the basis of this cutoff. Because of the significant influence on Pao2 of age, body-mass index (BMI), and PaCO2 in the group 40 to 74 yr of age, the following reference equation was constructed: Pao2 (mm Hg) = 143.6 - (0.39 . age) - (0.56 . BMI) - (0.57 . PaCO2); R2 = 0.28; SEE = 7.48; p or = 75 yr old, for whom there was no correlation with age, BMI, or PaCO2, only the mean +/- SD and 5th percentile of PaO2 were reported (83.4 +/- 9.15 mm Hg and 68.4 mm Hg, respectively). PaCO2 values were not correlated with either age or BMI; the mean +/- SD was 35.79 +/- 3.87 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. A noninvasive multimodal technique to monitor brain tumor vascularization

    Science.gov (United States)

    Saxena, Vishal; Gonzalez-Gomez, Ignacio; Laug, Walter E.

    2007-09-01

    Determination of tumor oxygenation at the microvascular level will provide important insight into tumor growth, angiogenesis, necrosis and therapeutic response and will facilitate to develop protocols for studying tumor behavior. The non-ionizing near infrared spectroscopy (NIRS) technique has the potential to differentiate lesion and hemoglobin dynamics; however, it has a limited spatial resolution. On the other hand, magnetic resonance imaging (MRI) has achieved high spatial resolution with excellent tissue discrimination but is more susceptible to limited ability to monitor the hemoglobin dynamics. In the present work, the vascular status and the pathophysiological changes that occur during tumor vascularization are studied in an orthotopic brain tumor model. A noninvasive multimodal approach based on the NIRS technique, namely steady state diffuse optical spectroscopy (SSDOS) along with MRI, is applied for monitoring the concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor region. The concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor vasculature are extracted at 15 discrete wavelengths in a spectral window of 675-780 nm. We found a direct correlation between tumor size, intratumoral microvessel density and tumor oxygenation. The relative decrease in tumor oxygenation with growth indicates that though blood vessels infiltrate and proliferate the tumor region, a hypoxic trend is clearly present.

  20. A noninvasive multimodal technique to monitor brain tumor vascularization

    International Nuclear Information System (INIS)

    Saxena, Vishal; Gonzalez-Gomez, Ignacio; Laug, Walter E

    2007-01-01

    Determination of tumor oxygenation at the microvascular level will provide important insight into tumor growth, angiogenesis, necrosis and therapeutic response and will facilitate to develop protocols for studying tumor behavior. The non-ionizing near infrared spectroscopy (NIRS) technique has the potential to differentiate lesion and hemoglobin dynamics; however, it has a limited spatial resolution. On the other hand, magnetic resonance imaging (MRI) has achieved high spatial resolution with excellent tissue discrimination but is more susceptible to limited ability to monitor the hemoglobin dynamics. In the present work, the vascular status and the pathophysiological changes that occur during tumor vascularization are studied in an orthotopic brain tumor model. A noninvasive multimodal approach based on the NIRS technique, namely steady state diffuse optical spectroscopy (SSDOS) along with MRI, is applied for monitoring the concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor region. The concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor vasculature are extracted at 15 discrete wavelengths in a spectral window of 675-780 nm. We found a direct correlation between tumor size, intratumoral microvessel density and tumor oxygenation. The relative decrease in tumor oxygenation with growth indicates that though blood vessels infiltrate and proliferate the tumor region, a hypoxic trend is clearly present

  1. "Cancer tumor".

    Science.gov (United States)

    Bronshtehn, V. A.

    The title is a phrase borrowed from a speech by a Leningrad pressman, V. E. Lvov, who called upon those attending a theoretical conference on ideological issues in astronomy held by the Leningrad Branch of the All-Union Astronomic and Geodetic Society (13 - 4 December 1948), "to make a more radical emphasis on the negative role of relativistic cosmology which is a cancer tumor disintegrating the contemporary astronomy theory, and a major ideological enemy of a materialist astronomy".

  2. Ethnography in community psychology: promises and tensions.

    Science.gov (United States)

    Case, Andrew D; Todd, Nathan R; Kral, Michael J

    2014-09-01

    Community psychology recognizes the need for research methods that illuminate context, culture, diversity, and process. One such method, ethnography, has crossed into multiple disciplines from anthropology, and indeed, community psychologists are becoming community ethnographers. Ethnographic work stands at the intersection of bridging universal questions with the particularities of people and groups bounded in time, geographic location, and social location. Ethnography is thus historical and deeply contextual, enabling a rich, in-depth understanding of communities that is aligned with the values and goals of community psychology. The purpose of this paper is to elucidate the potential of ethnography for community psychology and to encourage its use within the field as a method to capture culture and context, to document process, and to reveal how social change and action occur within and through communities. We discuss the method of ethnography, draw connections to community psychology values and goals, and identify tensions from our experiences doing ethnography. Overall, we assert that ethnography is a method that resonates with community psychology and present this paper as a resource for those interested in using this method in their research or community activism.

  3. Tension pneumothorax due to perforated colon.

    Science.gov (United States)

    Abdullah, Muhammad; Stonelake, Paul

    2016-05-31

    A very rare case of traumatic diaphragmatic hernia is reported in a 65-year-old woman who presented 46 years after her initial thoracoabdominal injury with tension faecopneumothorax caused by a perforated colon in the chest cavity. She presented in a critical condition with severe respiratory distress, sepsis and acute kidney injury. She had a long-standing history of bronchial asthma with respiratory complications and had experienced progressive shortness of breath for the past year. A recent CT scan had excluded the presence of a diaphragmatic hernia but showed a significantly raised left hemidiaphragm. On admission, chest X-rays showed a significantly raised left hemidiaphragm and mediastinal shift, but the possibility of a diaphragmatic hernia with strangulated bowel in the chest was not suspected until the patient was reviewed by the surgical and intensive care unit consultants the next morning and a repeat CT performed. She had a successful outcome after her emergency operation. 2016 BMJ Publishing Group Ltd.

  4. Muscle tension dysphonia in Vietnamese female teachers.

    Science.gov (United States)

    Nguyen, Duong Duy; Kenny, Dianna T; Tran, Ninh Duy; Livesey, Jonathan R

    2009-03-01

    There has been no published research on muscle tension dysphonia (MTD) in speakers who use a tonal language. Using a sample of 47 Northern Vietnamese female primary school teachers with MTD, we aimed to discover whether professional voice users of tonal languages presented with the same symptoms of MTD as speakers of nontonal languages and whether they presented with additional symptoms as a result of speaking a tonal language. The vocal characteristics were assessed by use of a questionnaire and expert perceptual evaluation. Laryngeal features were assessed by photolaryngoscopy. The results showed that MTD was associated with a larger number of vocal symptoms than previously reported. However, the participants did not have the same vocal symptoms reported in English speakers, for example, hard glottal attack, pitch breaks, unusual speech rate, and glottal fry. Factor analysis of the vocal symptoms revealed three factors: "vocal fatigue/hyperfunction," "physical discomfort," and "voice quality," all of which demonstrated high reliability. The major laryngeal characteristic was a glottal gap. The glottal shapes observed included: 44.7% had an incomplete closure, 29.8% a posterior gap, 12.8% an hourglass-shaped gap, 8.5% a spindle-shaped gap, and 4.3% had complete glottal closure. The findings implied a potential contribution of linguistic-specific factors and teaching-related factors to the presentation of this voice disorder in this group of teachers.

  5. BIOFEEDBACK TRAINING AND TENSION-TYPE HEADACHE.

    Science.gov (United States)

    Šecić, Ana; Cvjeticanin, Timon; Kes, Vanja Bašić

    2016-03-01

    Biofeedback is a training method, which connects physiological and psychological processes in a person for the purposes of improving his/her physical, emotional, mental and spiritual health. In biofeedback treatment, an active role of the patient is stressed for him/her to be able to actively control the physiological and emotional processes. The aim of biofeedback is to improve the conscious control of the individual's involuntary physiological activity. Research has shown that biofeedback, either applied alone or in combination with other behavioral therapies (techniques), is an effective treatment for various medical and psychological disorders, from headache and hypertension to temporomandibular and attention deficit disorders. More than 90% of adults experience headache once a year, which makes headache one of the most common symptoms and diagnoses in medicine. Tension-type headaches occur in at least 40% of the population and their impact on the health insurance costs and diminished productivity is significant. Studies have shown that clinical biofeedback training is effective in treating headaches. Moreover, the authors stress the need for additional research and further development of methodology for this kind of research.

  6. Updated constraints on the cosmic string tension

    International Nuclear Information System (INIS)

    Battye, Richard; Moss, Adam

    2010-01-01

    We reexamine the constraints on the cosmic string tension from cosmic microwave background (CMB) and matter power spectra, and also from limits on a stochastic background of gravitational waves provided by pulsar timing. We discuss the different approaches to modeling string evolution and radiation. In particular, we show that the unconnected segment model can describe CMB spectra expected from thin string (Nambu) and field theory (Abelian-Higgs) simulations using the computed values for the correlation length, rms string velocity and small-scale structure relevant to each variety of simulation. Applying the computed spectra in a fit to CMB and SDSS data we find that Gμ/c 2 -7 (2σ) if the Nambu simulations are correct and Gμ/c 2 -7 in the Abelian-Higgs case. The degeneracy between Gμ/c 2 and the power spectrum slope n S is substantially reduced from previous work. Inclusion of constraints on the baryon density from big bang nucleosynthesis (BBN) imply that n S 2 and loop production size, α, we find that Gμ/c 2 -7 for αc 2 /(ΓGμ) 2 -11 /α for αc 2 /(ΓGμ)>>1.

  7. Ocular Blood Flow and Normal Tension Glaucoma

    Directory of Open Access Journals (Sweden)

    Ning Fan

    2015-01-01

    Full Text Available Normal tension glaucoma (NTG is known as a multifactorial optic neuropathy characterized by progressive retinal ganglion cell death and glaucomatous visual field loss, even though the intraocular pressure (IOP does not exceed the normal range. The pathophysiology of NTG remains largely undetermined. It is hypothesized that the abnormal ocular blood flow is involved in the pathogenesis of this disease. A number of evidences suggested that the vascular factors played a significant role in the development of NTG. In recent years, the new imaging techniques, fluorescein angiography, color Doppler imaging (CDI, magnetic resonance imaging (MRI, and laser speckle flowgraphy (LSFG, have been used to evaluate the ocular blood flow and blood vessels, and the impaired vascular autoregulation was found in patients with NTG. Previous studies showed that NTG was associated with a variety of systemic diseases, including migraine, Alzheimer’s disease, primary vascular dysregulation, and Flammer syndrome. The vascular factors were involved in these diseases. The mechanisms underlying the abnormal ocular blood flow in NTG are still not clear, but the risk factors for glaucomatous optic neuropathy likely included oxidative stress, vasospasm, and endothelial dysfunction.

  8. Tension tests of concrete containment wall elements

    International Nuclear Information System (INIS)

    Schultz, D.M.; Julien, J.T.; Russel, H.G.

    1984-01-01

    Tension tests of concrete containment wall elements were conducted as part of a three-phase research program sponsored by the Electric Power Research Institute (EPRI). The objective of the EPRI experimental/analytical program is twofold. The first objective is to provide the utility industry with a test-verified analytical method for making realistic estimates of actual capacities of reinforced and prestressed concrete containments under internal over-pressurization from postulated degraded core accidents. The second objective is to determine qualitative and quantitative leak rate characteristics of typical containment cross-sections with and without penetrations. This paper covers the experimental portion to the EPRI program. The testing program for Phase 1 included eight large-scale specimens representing elements from the wall of a containment. Each specimen was 60-in (1525-mm) square, 24-in (610-mm) thick, and had full-size reinforcing bars. Six specimens were representative of prototypical reinforced concrete containment designs. The remaining two specimens represented prototypical prestressed containment designs. Various reinforcement configurations and loading arrangements resulted in data that permit comparisons of the effects of controlled variables on cracking and subsequent concrete/reinforcement/liner interaction in containment elements. Subtle differences, due to variations in reinforcement patterns and load applications among the eight specimens, are being used to benchmark the codes being developed in the analytical portion of the EPRI program. Phases 2 and 3 of the test program will examine leak rate characteristics and failure mechanisms at penetrations and structural discontinuities. (orig.)

  9. Oxygen sensing and conducted vasomotor responses in mouse cremaster arterioles in situ

    DEFF Research Database (Denmark)

    Ngo, Thuc Anh; Jensen, Lars Jørn; Riemann, Mads Achen

    2010-01-01

    .0 +/- 4.9 mum) when changing from high (PO(2) = 242.5 +/- 13.3 mm Hg) to low (PO(2) = 22.5 +/- 4.8 mm Hg) oxygen tension as seen in the intact cremaster circulation (DeltaD = 18.7 +/- 1.0 mum). Blockade of NO synthases by L: -NAME and adenosine receptors by DPCPX had no effects on vasomotor responses...... to low or high oxygen. Induction of localized low (PO(2) = 23.3 +/- 5.7 mmHg) or high (PO(2) = 300.0 +/- 25.7 mm Hg) oxygen tension caused vasodilatation or -constriction locally and at a site 1,000 mum upstream (distantly). Glibenclamide blocker of ATP-sensitive K(+) channels inhibited vasodilatation...... and -constriction to low (PO(2) = 16.0 +/- 6.4 mm Hg) and high (PO(2) = 337.4 +/- 12.8 mm Hg) oxygen tension. 1) ATP-sensitive K(+) channels seem to mediate, at least in part, vasodilatation and vasoconstriction to low and high oxygen tension; 2) Red blood cells are not necessary for inducing vasodilatation...

  10. Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen.

    Science.gov (United States)

    Mathiesen, Claus; Brazhe, Alexey; Thomsen, Kirsten; Lauritzen, Martin

    2013-02-01

    Glial calcium (Ca(2+)) waves constitute a means to spread signals between glial cells and to neighboring neurons and blood vessels. These waves occur spontaneously in Bergmann glia (BG) of the mouse cerebellar cortex in vivo. Here, we tested three hypotheses: (1) aging and reduced blood oxygen saturation alters wave activity; (2) glial Ca(2+) waves change cerebral oxygen metabolism; and (3) neuronal and glial wave activity is correlated. We used two-photon microscopy in the cerebellar cortexes of adult (8- to 15-week-old) and aging (48- to 80-week-old) ketamine-anesthetized mice after bolus loading with OGB-1/AM and SR101. We report that the occurrence of spontaneous waves is 20 times more frequent in the cerebellar cortex of aging as compared with adult mice, which correlated with a reduction in resting brain oxygen tension. In adult mice, spontaneous glial wave activity increased on reducing resting brain oxygen tension, and ATP-evoked glial waves reduced the tissue O(2) tension. Finally, although spontaneous Purkinje cell (PC) activity was not associated with increased glia wave activity, spontaneous glial waves did affect intracellular Ca(2+) activity in PCs. The increased wave activity during aging, as well as low resting brain oxygen tension, suggests a relationship between glial waves, brain energy homeostasis, and pathology.

  11. Understanding Brain Tumors

    Science.gov (United States)

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  12. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  13. Brain tumor - children

    Science.gov (United States)

    ... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

  14. Adrenal Gland Tumors: Statistics

    Science.gov (United States)

    ... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

  15. Pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Poussaint, Tina Y. [Department of Radiology, Boston, MA (United States); Panigrahy, Ashok [Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Department of Radiology, Pittsburgh, PA (United States); Huisman, Thierry A.G.M. [Charlotte R. Bloomberg Children' s Center, Johns Hopkins Hospital, Division of Pediatric Radiology and Pediatric Neuroradiology, Baltimore, MD (United States)

    2015-09-15

    Among all causes of death in children from solid tumors, pediatric brain tumors are the most common. This article includes an overview of a subset of infratentorial and supratentorial tumors with a focus on tumor imaging features and molecular advances and treatments of these tumors. Key to understanding the imaging features of brain tumors is a firm grasp of other disease processes that can mimic tumor on imaging. We also review imaging features of a common subset of tumor mimics. (orig.)

  16. Diltiazem enhances tumor blood flow: MRI study in a murine tumor

    International Nuclear Information System (INIS)

    Muruganandham, M.; Kasiviswanathan, A.; Jagannathan, N.R.; Raghunathan, P.; Jain, P.C.; Jain, V.

    1999-01-01

    Purpose: Diltiazem, a calcium-channel blocker, is known to differentially influence the radiation responses of normal and murine tumor tissues. To elucidate the underlying mechanisms, the effects of diltiazem on the radiation response of Ehrlich ascites tumor (EAT) in mice have been investigated, and the hemodynamic changes induced by diltiazem in tumor and normal muscle have been studied using magnetic resonance imaging (MRI) techniques. Methods and Materials: Ehrlich ascites tumors were grown subcutaneously in Swiss albino strain A mice. Dynamic gadodiamide and blood oxygen level dependent (BOLD) contrast enhanced 1 H MR imaging studies of EAT and normal muscle were performed after administration of diltiazem in mice using a 4.7 Tesla MR scanner. Tumor radiotherapy experiments (total dose = 10 Gy, 0.4-0.5 Gy/min, single fraction) were carried out with 30 min preadministration of diltiazem (27.5 or 55 mg/kg i.p.) to EAT-bearing mice using a teletherapy machine. Results: The diltiazem+ radiation treated group showed significant tumor regression (in congruent with 65% of the animals) and enhanced animal survival. MR-gadodiamide contrast kinetics revealed a higher magnitude of signal enhancement in diltiazem treated groups as compared to the controls. The observed changes in the magnitude of kinetic parameters were the same for both tumor and normal muscle. BOLD-MR images at 30 min after diltiazem administration showed a 25% and 8% (average) intensity enhancement from their basal values in tumor and normal muscle regions, respectively. The control group showed no significant changes. Conclusion: The present studies demonstrate the radiosensitization potential of diltiazem in the mice EAT model. The enhanced radiation response observed with diltiazem correlates with the diltiazem-induced increase in tumor blood flow (TBF) and tumor oxygenation. The present results also demonstrate the applications of BOLD-MR measurements in investigating the alterations in tumor

  17. Ultrasound Findings in Tension Pneumothorax: A Case Report.

    Science.gov (United States)

    Inocencio, Maxine; Childs, Jeannine; Chilstrom, Mikaela L; Berona, Kristin

    2017-06-01

    Delayed recognition of tension pneumothorax can lead to a mortality of 31% to 91%. However, the classic physical examination findings of tracheal deviation and distended neck veins are poorly sensitive in the diagnosis of tension pneumothorax. Point-of-care ultrasound is accurate in identifying the presence of pneumothorax, but sonographic findings of tension pneumothorax are less well described. We report the case of a 21-year-old man with sudden-onset left-sided chest pain. He was clinically stable without hypoxia or hypotension, and the initial chest x-ray study showed a large pneumothorax without mediastinal shift. While the patient was awaiting tube thoracostomy, a point-of-care ultrasound demonstrated findings of mediastinal shift and a dilated inferior vena cava (IVC) concerning for tension physiology, even though the patient remained hemodynamically stable. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case demonstrates a unique clinical scenario of ultrasound evidence of tension physiology in a clinically stable patient. Although this patient was well appearing without hypotension, respiratory distress, tracheal deviation, or distended neck veins, point-of-care ultrasound revealed mediastinal shift and a plethoric IVC. Given that the classic clinical signs of tension pneumothorax are not uniformly present, this case shows how point-of-care ultrasound may diagnose tension pneumothorax before clinical decompensation. Published by Elsevier Inc.

  18. Automated wireless monitoring system for cable tension using smart sensors

    Science.gov (United States)

    Sim, Sung-Han; Li, Jian; Jo, Hongki; Park, Jongwoong; Cho, Soojin; Spencer, Billie F.; Yun, Chung-Bang

    2013-04-01

    Cables are critical load carrying members of cable-stayed bridges; monitoring tension forces of the cables provides valuable information for SHM of the cable-stayed bridges. Monitoring systems for the cable tension can be efficiently realized using wireless smart sensors in conjunction with vibration-based cable tension estimation approaches. This study develops an automated cable tension monitoring system using MEMSIC's Imote2 smart sensors. An embedded data processing strategy is implemented on the Imote2-based wireless sensor network to calculate cable tensions using a vibration-based method, significantly reducing the wireless data transmission and associated power consumption. The autonomous operation of the monitoring system is achieved by AutoMonitor, a high-level coordinator application provided by the Illinois SHM Project Services Toolsuite. The monitoring system also features power harvesting enabled by solar panels attached to each sensor node and AutoMonitor for charging control. The proposed wireless system has been deployed on the Jindo Bridge, a cable-stayed bridge located in South Korea. Tension forces are autonomously monitored for 12 cables in the east, land side of the bridge, proving the validity and potential of the presented tension monitoring system for real-world applications.

  19. Photodynamic therapy of solid tumors

    Science.gov (United States)

    Jori, Giulio

    Some porphyrin compounds, which are characterized by a relatively large degree of hydrophobicity (n-octanol/water partition coefficient above 8), are accumulated in greater amounts and retained for longer periods of time by neoplastic as compared with normal tissues. The affinity of these dyes for tumors is partially a consequence of their in vivo transport by low-density lipoproteins, which are preferentially endocytosized by hyperproliferating tissues in a receptor-mediated process. In general, at 24-48 h after the systematic administration of porphyrin doses in the range of 2.5 mg/kg body weight, the ratio of drug concentration between the neoplastic and the surrounding tissues is sufficiently large to guarantee a selective photoexcitation of the porphyrin. Toward this aim, the porphyrin-containing tumor tissues are irradiated with light wavelengths longer than 600 nm, since the transmittance of biological tissues is maximal in this spectral region. The electronically excited porphyrin transfers its excitation energy to oxygen, thus generating activated oxygen species (mainly, singlet oxygen): as a consequence, the photooxidative modification of subcellular targets (e.g. the plasma membrane and mitochondria) is readily obtained leading to an irreversible necrosis of the cell. With the most frequently used porphyrins for clinical phototherapy (including hematoporphyrin and its derivatives HpD and Photofrin II), one observes the preferential photosensitized destruction of endothelial cells, hence the vascular damage is a major process involved in the necrosis of tumors. The optimization of the phototherapy of tumors is presently pursued by the definition of clinical protocols tailored to the optical properties of specific neoplastic tissues as well as by the use of porphyrin analogs, such as chlorins and phthalocyanines, having an extinction coefficient in the red spectral region larger than that typical of hematoporphyrin and HpD.

  20. Biogeochemistry: Oxygen burrowed away

    NARCIS (Netherlands)

    Meysman, F.J.R.

    2014-01-01

    Multicellular animals probably evolved at the seafloor after a rise in oceanic oxygen levels. Biogeochemical model simulations suggest that as these animals started to rework the seafloor, they triggered a negative feedback that reduced global oxygen.