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Sample records for tumor oxygen tension

  1. 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; Liu, Hanli

    2007-01-01

    Objective/Hypothesis: By monitoring global and local vascular oxygenation and tissue oxygen tension in breast tumors under HBO exposure with several different gas interventions, we wish to prove the following two hypotheses: that 1...

  2. 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

  3. 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

    ... spectroscopy and FOXY oxygen sensor simultaneously. The results show that the fitted tumor blood flow and metabolic rate of oxygen showed different responses between oxygen and carbogen interventions by applying our model...

  4. 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...

  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....

  6. 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....

  7. 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...

  8. 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 block...

  9. 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

  10. 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 ].

  11. Changes in tumor oxygen tension during radiotherapy of uterine cervical cancer: relationships to changes in vascular density, cell density, and frequency of mitosis and apoptosis

    International Nuclear Information System (INIS)

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

    2000-01-01

    Purpose: Changes in oxygen tension (pO 2 ) during the early phase of fractionated radiotherapy were studied in 22 patients with uterine cervical cancer. The aims were to investigate (a) whether possible changes in pO 2 differed among and within tumors and (b) whether the changes could be attributed to changes in vascular density, cell density, and frequency of mitosis and apoptosis. Methods and Materials: The pO 2 was measured polarographically in four regions of the tumors before treatment and after 2 weeks of radiotherapy. The vascular density, cell density, and frequency of mitosis and apoptosis were determined from biopsies taken from the tumor regions after each pO 2 measurement. Results: The changes in pO 2 during therapy differed among the tumors and were correlated to pO 2 before treatment (p 2 and vice versa. The tumors with increased pO 2 (n = 10) had a large decrease in cell density and a significant increase in apoptotic frequency. In contrast, the tumors with decreased pO 2 (n = 10) had a smaller decrease in cell density (p = 0.014) and no significant increase in apoptotic frequency. Vascular density and mitotic frequency showed no change during therapy; however, vascular damage other than decreased vascular density was observed. Conclusion: These results indicate that the oxygenation of cervix tumors generally changes during the early phase of radiotherapy. The change depends on the balance between the factor leading to an increase and that leading to a decrease in oxygenation; i.e., decreased cell density and vascular damage, respectively. Increased apoptotic frequency may contribute to a large decrease in cell density and hence increased oxygenation during therapy

  12. 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.

  13. Oxygen tension affects lubricin expression in chondrocytes.

    Science.gov (United States)

    Hatta, Taku; Kishimoto, Koshi N; Okuno, Hiroshi; Itoi, Eiji

    2014-10-01

    We assessed the effects of oxygen tension on lubricin expression in bovine chondrocytes and cartilage explants and a role for hypoxia-inducible transcription factor (HIF)-1α in regulating lubricin expression was investigated using a murine chondroprogenitor cell line, ATDC5, and bovine chondrocytes isolated from superficial and middle/deep zones of femoral cartilage. ATDC5 cells and bovine chondrocytes were cultured in micromass under different oxygen tensions (21%, 5%, and 1%). ATDC5 cells and middle/deep zone chondrocytes that initially had low lubricin expression levels were also cultured with or without transforming growth factor (TGF)-β1. Quantitative reverse transcription (RT)-PCR was used to determine lubricin and chondrogenic marker gene mRNA levels and immunohistochemistry was used to assess lubricin protein expression. Explant cartilage plugs cultured under different oxygen tensions were also subjected to immunohistological analysis for lubricin. HIF-1α gene silencing was achieved by electroporatic transfer into ATDC5 cells. A low oxygen tension reduced lubricin gene expression levels in bovine superficial chondrocytes, TGF-β1-treated middle/deep zone chondrocytes, and TGF-β1-treated ATDC5 cells. Lubricin expression in explant cartilage was also suppressed under hypoxia. HIF-1α gene silencing in ATDC5 cells attenuated the lubricin expression response to the oxygen tension. These results corroborate with previous studies that the oxygen tension regulates lubricin gene expression and suggest that HIF-1α plays an important role in this regulation. The normal distribution of lubricin in articular cartilage may be due to the hypoxic oxygen environment of cartilage as it is an avascular tissue. An oxygen tension gradient may be a key factor for engineering cartilage tissue with a layered morphology.

  14. Tissue oxygen tension in the stria vascularis.

    Science.gov (United States)

    Nagahara, K; Miyake, Y; Aoyama, T; Ogino, F

    1988-01-01

    Tissue oxygen tension in the stria vascularis was successfully measured in cats using the polarographic technique. A correlation study using the differential coefficient between oxygen tension in the stria vascularis and systemic blood pressure proved that vascular autoregulation is present in the mean systemic blood pressure range between 40 and 80 mmHg. The anatomical findings and the response patterns to different gas inhalations indicated that the type of vascular regulation present is more closely related to chemical control than to auto-regulation.

  15. 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...

  16. "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.

  17. Ail expression in Yersinia enterocolitica is affected by oxygen tension.

    OpenAIRE

    Pederson, K J; Pierson, D E

    1995-01-01

    We investigated several environmental factors for their abilities to regulate ail gene expression and found that ail transcript levels are regulated by oxygen tension. Bacteria growing under anaerobiosis at 37 degrees C repress ail mRNA and Ail expression, resulting in a loss of Ail-mediated serum resistance and cell invasion.

  18. Ail expression in Yersinia enterocolitica is affected by oxygen tension.

    Science.gov (United States)

    Pederson, K J; Pierson, D E

    1995-10-01

    We investigated several environmental factors for their abilities to regulate ail gene expression and found that ail transcript levels are regulated by oxygen tension. Bacteria growing under anaerobiosis at 37 degrees C repress ail mRNA and Ail expression, resulting in a loss of Ail-mediated serum resistance and cell invasion.

  19. Measuring microvascular and mitochondrial oxygen tension: novel techniques for studying tissue oxygenation

    NARCIS (Netherlands)

    Mik, E.G.

    2011-01-01

    This thesis describes the implementation of novel approaches for measuring tissue oxygenation based on oxygen-dependent quenching of the triplet-state lifetime of porphyrins. Ultimately we created a tool for assessment of mitochondrial oxygen tension in vivo. The first measurements indicate much

  20. 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

  1. 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...

  2. 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...

  3. 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

  4. 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

  5. Predicting scleral GP lens entrapped tear layer oxygen tensions.

    Science.gov (United States)

    Jaynes, Jared M; Edrington, Timothy B; Weissman, Barry A

    2015-02-01

    Over the past decade, utilization of scleral gas permeable (GP) contact lenses has steadily increased. Scleral GP lenses offer yet another option for patients suffering from visually debilitating corneal and tear conditions. Oxygen delivery to the cornea in the presence of a contact lens system continues to be a subject of interest, and scleral GP lenses are no exception. This paper utilizes an existing model based on simultaneous two lens systems (piggyback lenses) as a resistance to oxygen in series, and applies this model to scleral GP lens systems. Theoretical oxygen tensions are calculated for tear layers trapped beneath scleral contact lens systems and the anterior corneal surface with a simple single chamber corneal model using a computer software spreadsheet. Only the best case scenario for current scleral gas permeable lenses (thickness and Dk)/tear layer values allow sufficient tear layer oxygen tension (approximately 100 mmHg) to preclude corneal hypoxia. The results of the spreadsheet model suggest that clinicians would be prudent to prescribe scleral GP lenses manufactured in the highest Dk materials available and to fit without excessive corneal clearance to minimize anterior segment hypoxia. Copyright © 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  6. 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.

  7. 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.

  8. 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

    The effect of carbon ion radiotherapy on hypoxic tumors has recently been questioned because of low linear energy transfer (LET) values in the spread-out Bragg peak (SOBP). The aim of this study was to investigate the role of hypoxia and local oxygenation changes (LOCs) in fractionated carbon ion...... radiotherapy. Three-dimensional tumors with hypoxic subvolumes were simulated assuming interfraction LOCs. Different fractionations were applied using a clinically relevant treatment plan with a known LET distribution. The surviving fraction was calculated, taking oxygen tension, dose and LET into account...... 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...

  9. 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 pig retina and optic nerve before and after dorzolamide injection. Also the retinal vessel diameters during carbonic anhydrase inhibition were studied....

  10. 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.

  11. 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.

  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. 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....

  14. 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...

  15. 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....

  16. 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.

  17. 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

  18. Chronically decreased oxygen tension in rat pancreatic islets transplanted under the kidney capsule.

    Science.gov (United States)

    Carlsson, P O; Palm, F; Andersson, A; Liss, P

    2000-03-15

    A factor of potential importance in the failure of islet grafts is poor or inadequate engraftment of the islets in the implantation organ. This study measured the oxygen tension and blood perfusion in 1-, 2-, and 9-month-old islet grafts. The partial pressure of oxygen was measured in pancreatic islets transplanted beneath the renal capsule of diabetic and nondiabetic recipient rats with a modified Clark electrode (outer tip diameter 2-6 microm). The size of the graft (250 islets) was by purpose not large enough to cure the diabetic recipients. The oxygen tension in islets within the pancreas was also recorded. Blood perfusion was measured with the laser-Doppler technique. Within native pancreatic islets, the partial pressure of oxygen was approximately 40 mm Hg (n=8). In islets transplanted to nondiabetic animals, the oxygen tension was approximately 6-7 mm Hg 1, 2, and 9 months posttransplantation. No differences could be seen between the different time points after transplantation. In the diabetic recipients, an even more pronounced decrease in graft tissue oxygen tension was recorded. The mean oxygen tension in the superficial renal cortex surrounding the implanted islets was similar in all groups (approximately 15 mm Hg). Intravenous administration of glucose (0.1 gxkg(-1)x min(-1)) did not affect the oxygen tension in any of the investigated tissues. The islet graft blood flow was similar in all groups, measuring approximately 50% of the blood flow in the kidney cortex. The oxygen tension in islets implanted beneath the kidney capsule is markedly lower than in native islets up to 9 months after transplantation. Moreover, persistent hyperglycemia in the recipient causes an even further decrease in graft oxygen tension, despite similar blood perfusion. To what extent this may contribute to islet graft failure remains to be determined.

  19. 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

  20. Effects of Oxygen Partial Pressure on the Surface Tension of Liquid Nickel

    Science.gov (United States)

    SanSoucie, Michael P.; Rogers, Jan R.; Gowda, Vijaya Kumar Malahalli Shankare; Rodriguez, Justin; Matson, Douglas M.

    2015-01-01

    The NASA Marshall Space Flight Center's electrostatic levitation (ESL) laboratory has been recently upgraded with an oxygen partial pressure controller. This system allows the oxygen partial pressure within the vacuum chamber to be measured and controlled, theoretically in the range from 10-36 to 100 bar. The oxygen control system installed in the ESL laboratory's main chamber consists of an oxygen sensor, oxygen pump, and a control unit. The sensor is a potentiometric device that determines the difference in oxygen activity in two gas compartments (inside the chamber and the air outside of the chamber) separated by an electrolyte, which is yttria-stabilized zirconia. The pump utilizes coulometric titration to either add or remove oxygen. The system is controlled by a desktop control unit, which can also be accessed via a computer. The controller performs temperature control for the sensor and pump, PID-based current loop, and a control algorithm. Oxygen partial pressure has been shown to play a significant role in the surface tension of liquid metals. Oxide films or dissolved oxygen may lead to significant changes in surface tension. The effects of oxygen partial pressure on the surface tension of undercooled liquid nickel will be analyzed, and the results will be presented. The surface tension will be measured at several different oxygen partial pressures while the sample is undercooled. Surface tension will be measured using the oscillating drop method. While undercooled, each sample will be oscillated several times consecutively to investigate how the surface tension behaves with time while at a particular oxygen partial pressure.

  1. Continuous assessment of oxygen saturation and subcutaneous oxygen tension after abdominal operations

    DEFF Research Database (Denmark)

    Rosenberg, J; Ullstad, T; Larsen, P N

    1990-01-01

    stimulation test (10 l/min by face mask) was carried out in eight of the 10. Median SpO2 was 91% (range 82-95) on the second, and 91% (86-95) on the third, postoperative nights, respectively. Six patients had intermittent episodes of desaturation to less than 80%, each of less than one minute's duration. PtcO......Ten patients undergoing abdominal operations had oxygen saturation (SpO2) and transcutaneous (PtcO2) and subcutaneous (PscO2) oxygen tensions monitored continuously during the second and third postoperative nights from 11 pm to 7 am. At the end of the second postoperative night an oxygen......2, but not PscO2, followed the episodic variations in SpO2. PscO2 was 58 mmHg (46-69) on the second postoperative night and 61 mmHg (48-71) on the third postoperative night. PscO2 correlated with SpO2 in all but one patient who had lower PscO2 than expected from the measured SpO2 and estimated PaO2...

  2. Decreased oxygen tension lowers reactive oxygen species and apoptosis and inhibits osteoblast matrix mineralization through changes in early osteoblast differentiation.

    Science.gov (United States)

    Nicolaije, Claudia; Koedam, Marijke; van Leeuwen, Johannes P T M

    2012-04-01

    Accumulating data show that oxygen tension can have an important effect on cell function and fate. We used the human pre-osteoblastic cell line SV-HFO, which forms a mineralizing extracellular matrix, to study the effect of low oxygen tension (2%) on osteoblast differentiation and mineralization. Mineralization was significantly reduced by 60-70% under 2% oxygen, which was paralleled by lower intracellular levels of reactive oxygen species (ROS) and apoptosis. Following this reduction in ROS the cells switched to a lower level of protection by down-regulating their antioxidant enzyme expression. The downside of this is that it left the cells more vulnerable to a subsequent oxidative challenge. Total collagen content was reduced in the 2% oxygen cultures and expression of matrix genes and matrix-metabolizing enzymes was significantly affected. Alkaline phosphatase activity and RNA expression as well as RUNX2 expression were significantly reduced under 2% oxygen. Time phase studies showed that high oxygen in the first phase of osteoblast differentiation and prior to mineralization is crucial for optimal differentiation and mineralization. Switching to 2% or 20% oxygen only during mineralization phase did not change the eventual level of mineralization. In conclusion, this study shows the significance of oxygen tension for proper osteoblast differentiation, extra cellular matrix (ECM) formation, and eventual mineralization. We demonstrated that the major impact of oxygen tension is in the early phase of osteoblast differentiation. Low oxygen in this phase leaves the cells in a premature differentiation state that cannot provide the correct signals for matrix maturation and mineralization. Copyright © 2011 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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 hypoxia. Lewis rats underwent syngenic renal transplantation (TX) and contralateral nephrectomy. Controls were uninephrectomized (1K-CON) or left untreated (2K-CON). After 7 days, urinary excretion of protein and thiobarbituric acid-reactive substances were measured, and after 14 days glomerular filtration rate (GFR), renal blood flow, whole kidney Qo2, cortical Po2, kidney cortex mitochondrial uncoupling, renal oxidative damage, and tubulointerstitial injury were assessed. TX, compared with 1K-CON, resulted in mitochondrial uncoupling mediated via uncoupling protein-2 (16 ± 3.3 vs. 0.9 ± 0.4 pmol O2 · s(-1)· mg protein(-1), P < 0.05) and increased whole kidney Qo2 (55 ± 16 vs. 33 ± 10 μmol O2/min, P < 0.05). Corticomedullary Po2 was lower in TX compared with 1K-CON (30 ± 13 vs. 47 ± 4 μM, P < 0.05) whereas no significant difference was observed between 2K-CON and 1K-CON rats. Proteinuria, oxidative damage, and the tubulointerstitial injury score were not significantly different in 1K-CON and TX. Treatment of donors for 5 days with mito-TEMPO reduced mitochondrial uncoupling but did not affect renal hemodynamics, Qo2, Po2, or injury. Collectively, our results demonstrate increased mitochondrial uncoupling as an early event after experimental renal transplantation associated with increased oxygen consumption and kidney hypoxia in the absence of increases in markers of damage. Copyright © 2015 the American Physiological Society.

  4. 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

  5. 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

  6. 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.

  7. Tissue oxygen tensions under physiological and pathological conditions

    NARCIS (Netherlands)

    M. Fennema (Michael)

    1988-01-01

    textabstractThe aims of this thesis are twofold: One - to describe a reliable micro-electrode system for determination of oxygen partial pressures in the micro-area of the tissue and to demonstrate that it is applicable in exxerimental and clinical situations. Two - to demonstrate that

  8. 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

  9. 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...

  10. 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

    OBJECTIVES: Most cell culture studies have been performed at atmospheric oxygen tension of 21%, however the physiological oxygen tension is much lower and is a factor that may affect skeletal muscle myoblasts. In this study we have compared activation of G0 arrested myoblasts in 21% O2 and in 1% ...

  11. 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...

  12. Comparison of the transcutaneous oxygen and carbon dioxide tension in different electrode locations during general anaesthesia.

    Science.gov (United States)

    Nishiyama, T; Nakamura, S; Yamashita, K

    2006-12-01

    The best place for the electrode of transcutaneous measurement of oxygen tension (tcPO2) and carbon dioxide tension (tcPCO2) during general anaesthesia was investigated in three different locations. Fifteen patients for major abdominal surgery in the supine position were studied. The electrode of the TCM4 (Radiometer, Copenhagen, Denmark) was put on the chest, upper arm or forearm. TcPO2, tcPCO2, end-tidal carbon dioxide tension (etCO2), percutaneous oxygen saturation (SaO2), arterial oxygen tension (PaO2 ) and arterial carbon dioxide tension (PaCO2) were simultaneously measured at four different etCO2 concentrations and inhaled oxygen percentages and the location of the electrode was changed to other places to repeat the same measurement. In total, 12 measurements for each patient and 60 measurements for each place were performed. TcPO2 correlated better than SaO2 (R2 = 0.58) with PaO2 (R2 = 0.76), and tcPCO2 correlated well with PaCO2 (R2 = 0.76) and etCO2 (R2 = 0.74) when the electrode was put on the chest, while not on the upper arm or forearm (R2 tcPCO2 (bias, -0.47; limits of agreement, 8.7, -9.64) as surrogate measures of PaO2 and PaCO2, respectively even when the electrode was put on the chest. When the electrode was put on the chest, tcPO2 and tcPCO2 might be available as non-invasive monitors of oxygenation and CO2 status during general anaesthesia, while the absolute values were not interchangeable with PaO2 and PaCO2, respectively.

  13. 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

  14. 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

    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...... 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...

  15. Mitochondrial bioenergetics of metastatic breast cancer cells in response to dynamic changes in oxygen tension: effects of HIF-1α.

    Directory of Open Access Journals (Sweden)

    Anne R Diers

    Full Text Available Solid tumors are characterized by regions of low oxygen tension (OT, which play a central role in tumor progression and resistance to therapy. Low OT affects mitochondrial function and for the cells to survive, mitochondria must functionally adapt to low OT to maintain the cellular bioenergetics. In this study, a novel experimental approach was developed to examine the real-time bioenergetic changes in breast cancer cells (BCCs during adaptation to OT (from 20% to <1% oxygen using sensitive extracellular flux technology. Oxygen was gradually removed from the medium, and the bioenergetics of metastatic BCCs (MDA-MB-231 and MCF10CA clones was compared with non-tumorigenic (MCF10A cells. BCCs, but not MCF10A, rapidly responded to low OT by stabilizing HIF-1α and increasing HIF-1α responsive gene expression and glucose uptake. BCCs also increased extracellular acidification rate (ECAR, which was markedly lower in MCF10A. Interestingly, BCCs exhibited a biphasic response in basal respiration as the OT was reduced from 20% to <1%. The initial stimulation of oxygen consumption is found to be due to increased mitochondrial respiration. This effect was HIF-1α-dependent, as silencing HIF-1α abolished the biphasic response. During hypoxia and reoxygenation, BCCs also maintained oxygen consumption rates at specific OT; however, HIF-1α silenced BCC were less responsive to changes in OT. Our results suggest that HIF-1α provides a high degree of bioenergetic flexibility under different OT which may confer an adaptive advantage for BCC survival in the tumor microenvironment and during invasion and metastasis. This study thus provides direct evidence for the cross-talk between HIF-1α and mitochondria during adaptation to low OT by BCCs and may be useful in identifying novel therapeutic agents that target the bioenergetics of BCCs in response to low OT.

  16. 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

  17. Transcutaneous oxygen tension monitoring after successful revascularization in diabetic patients with ischaemic foot ulcers.

    Science.gov (United States)

    Caselli, A; Latini, V; Lapenna, A; Di Carlo, S; Pirozzi, F; Benvenuto, A; Uccioli, L

    2005-04-01

    To monitor transcutaneous oxygen tension (TcPO2) after percutaneous transluminal angioplasty (PTA) in diabetic patients with ischaemic foot ulcers. Twenty-three diabetic patients with ischaemic foot ulcers who underwent successful revascularization by PTA (SR group) were retrospectively selected. Twenty diabetic patients who underwent unsuccessful revascularization (UR group) were also included. Transcutaneous oxygen tension was measured at the dorsum of the foot before and 1 (+/- 1), 7 (+/- 1), 14 (+/- 1), 21 (+/- 1) and 28 (+/- 1) days after the surgical procedure. After PTA, TcPO2 progressively improved in the SR group, reaching its peak 4 weeks after angioplasty. A concomitant decrease of cutaneous carbon dioxide tension (TcPCO2) was also observed immediately after PTA which reached the lowest levels 3 weeks later. In the UR group, TcPO2 showed a slight improvement immediately after PTA but remained stable throughout the observation, while TcPCO2 levels did not change. Finally, the percentage of SR patients with a TcPO2 > or = 30 mmHg was 38.5% 1 week after PTA, while it increased to 75% 3 weeks later. Transcutaneous oxygen tension monitoring showed that after successful revascularization it takes 3-4 weeks for cutaneous oxygenation to improve and reach the optimal levels for wound healing. Transcutaneous carbon dioxide tension monitoring may be more useful to identify the negative outcome of a revascularization procedure. Our findings suggest that, when the surgical approach can be delayed, the best timing to perform a more aggressive debridement or minor amputations is 3-4 weeks after successful revascularization.

  18. 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.

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

    Science.gov (United States)

    2016-10-01

    HLNL and DHLNL (Suppl. Figure 2). These data not only demonstrated a direct positive relationship between changes in stromal Lox expression, collagen...Force Microscopy (AFM). (Months 11-15 for Task 1B and 15-19 for Task 1C) Task 1G. Immunofluorescence analyses will be done using marker for...role for STAT3 activity in tumor-initiating cells (TICs) is well-known in mouse models of breast cancer; and 3) we have evidence that there is a direct

  20. 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.

  1. 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.)

  2. 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....

  3. 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

  4. 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.

  5. 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

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

    OpenAIRE

    Pedersen, D B; Eysteinsson, T; Stefánsson, E; Kiilgaard, J F; la Cour, M; Bang, K; Jensen, P K

    2004-01-01

    Background/aims: Prostaglandins are important in blood flow regulation. Carbon dioxide (CO2) 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 (ONPO2), the authors investigated how indomethacin affects ONPO2 and the ONPO2 increases caused by CO2 breathing and carbonic anhydrase inhibition in the pig.

  7. 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....

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

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, Pia [Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Winslowparken 21, DK-5000 Odense C (Denmark); Department of Neurosurgery, University of Bern, CH-3010 Bern (Switzerland); Gramsbergen, Jan-Bert; Zimmer, Jens [Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Winslowparken 21, DK-5000 Odense C (Denmark); Widmer, Hans R. [Department of Neurosurgery, University of Bern, CH-3010 Bern (Switzerland); Meyer, Morten, E-mail: MMeyer@health.sdu.dk [Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Winslowparken 21, DK-5000 Odense C (Denmark)

    2011-07-15

    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 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 in high oxygen cultures. Low oxygen during FGF2-mediated expansion resulted also in a significant increase in tyrosine hydroxylase-immunoreactive (TH-ir) dopaminergic neurons as compared to high oxygen tension, but no corresponding effect was observed for dopamine release into the culture medium. However, 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 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.

  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. 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

  11. Reprogramming metabolism with metformin improves tumor oxygenation and radiotherapy response.

    Science.gov (United States)

    Zannella, Vanessa E; Dal Pra, Alan; Muaddi, Hala; McKee, Trevor D; Stapleton, Shawn; Sykes, Jenna; Glicksman, Rachel; Chaib, Selim; Zamiara, Paul; Milosevic, Michael; Wouters, Bradly G; Bristow, Robert G; Koritzinsky, Marianne

    2013-12-15

    Tumor hypoxia is a negative prognostic factor in multiple cancers, due in part to its role in causing resistance to radiotherapy. Hypoxia arises in tumor regions distal to blood vessels as oxygen is consumed by more proximal tumor cells. Reducing the rate of oxygen consumption is therefore a potential strategy to reduce tumor hypoxia. We hypothesized that the anti-diabetic drug metformin, which reduces oxygen consumption through inhibition of mitochondrial complex I, would improve radiation response by increasing tumor oxygenation. Tumor hypoxia was measured in xenografts before and after metformin treatment using 2-nitroimidazole hypoxia markers quantified by immunohistochemistry (IHC), flow cytometry, and positron emission tomography (PET) imaging. Radiation response was determined by tumor growth delay and clonogenic survival in xenografts with and without administration of metformin. The impact of metformin use on outcome was assessed in 504 patients with localized prostate cancer treated with curative-intent, image-guided radiotherapy (IGRT) from 1996 to 2012. Three-year biochemical relapse-free rates were assessed using the Kaplan-Meier method. Metformin treatment significantly improved tumor oxygenation in two xenograft models as measured by IHC, flow cytometry, and PET imaging. Metformin also led to improved radiotherapy responses when mice were administered metformin immediately before irradiation. Clinically, metformin use was associated with an independent and significant decrease in early biochemical relapse rates (P = 0.0106). Our data demonstrate that metformin can improve tumor oxygenation and response to radiotherapy. Our study suggests that metformin may represent an effective and inexpensive means to improve radiotherapy outcome with an optimal therapeutic ratio. ©2013 AACR.

  12. Are tumor-to-tumor differences in oxygenation responsible for the heterogeneity in the response of tumors to therapy

    International Nuclear Information System (INIS)

    Rockwell, S.; Moulder, J.E.; Martin, D.F.

    1984-01-01

    Individual tumors from the same transplanted tumor line often show very different responses to the same treatments, even when the tumors are implanted into similar sites in similar hosts and studied at the same time. The cause of this heterogeneity is unknown; either tumor or host factors could be responsible. Solid tumors contain large numbers of viable hypoxic cells, which are resistant to both radiotherapy and chemotherapy and limit the response of tumors to intensive treatments. To determine whether differences in the proportion of hypoxic cells in the tumors produce the observed variability in therapeutic sensitivity, the authors compared the radiation responses of normally-aerated tumors and tumors made artificially hypoxic. If large tumor-to-tumor differences in oxygenation exist, data from normally-aerated tumors should be more variable than data from hypoxic tumors (which should all be brought to uniform hypoxia and uniform radioresistance). Analysis of data from several tumor systems revealed the variability in the radiation responses of hypoxic tumors to be at least as great as that for aerobic tumors. Thus, factors other than differences in oxygenation must produce the heterogeneity in tumor radiation response

  13. 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...... nutritional support to tumor cells. As a consequence the expanding neoplastic cell population initiates its own vascular network which is both structurally and functionally abnormal. This aberrant vasculature impacts all aspects of the tumor microenvironment including the cells, extracellular matrix......, and extracellular molecules which together are essential for the initiation, progression and spread of tumor cells. The physical conditions that arise are imposing and manifold, and include elevated interstitial pressure, localized extracellular acidity, and regions of oxygen and nutrient deprivation. No less...

  14. Oxygenation of spontaneous canine tumors during fractionated radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Achermann, R.E.; Ohlerth, S.M.; Bley, C.R.; Inteeworn, N.; Schaerz, M.; Wergin, M.C.; Kaser-Hotz, B. [Section of Diagnostic Imaging and Radiation Oncology, Veterinary School, Univ. of Zurich (Switzerland); Gassmann, M. [Inst. for Veterinary Physiology, Univ. of Zurich (Switzerland); Roos, M. [Inst. for Social and Preventive Medicine, Univ. of Zurich (Switzerland)

    2004-05-01

    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{sub 2}) measurements were performed with the eppendorf-pO{sub 2}-Histograph. The measurements were done under general anesthesia, and probe tracks were guided with ultrasound. pO{sub 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{sub 2} {<=} 10 mmHg. The pO{sub 2} values appeared to be quite variable in individual tumors during fractionated radiation therapy. The pO{sub 2} of initially hypoxic tumors (pretreatment median pO{sub 2} {<=} 10 mmHg) remained unchanged during fractionated radiotherapy, whereas in initially normoxic tumors the pO{sub 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.)

  15. 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))

  16. 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...... 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...

  17. Oxygen tension in mouse mammary carcinomas and osteosarcomas after irradiation with reactor fission neutrons; Pression en oxygene dans les carcinomes mammaires et les osteosacomes de la souris apres irradiation par neutrons de fission

    Energy Technology Data Exchange (ETDEWEB)

    Weissfloch, L.; Auberger, T.; Molls, M. [Clinic and Policlinic for Radiotherapy and Radiological Oncology, Ismaninger, Munich (Germany); Senekowitsch-Schmidtke, R. [Clinic and Policlinic for Nuclear Medicine, Klinikum Rechts der Isar, Munich (Germany); Wagner, F.M. [Reactor Station Garching, Munich (Germany); Tempel, K. [Institute for Pharmacology, Veterinary Faculty, Munich (Germany)

    1996-12-31

    Investigations were made on intratumoral oxygen tension after irradiations with reactor fission neutrons using the Eppendorf - pO{sub 2} -Histograph{sup R}. Iso-transplanted AT17-mammary carcinomas on C3H-mice and osteosarcomas OTS-64 on Balb c-mice received 2 or - Gy neutrons single dose. Before and at certain points of time after treatment the pO{sub 2}-values were evaluated. Some tumors with initially low median pO{sub 2}-values showed a short-lasting increase between 2 and 24 hours after irradiation. In the tumors with relatively high median pO{sub 2}-values before irradiation the pO{sub 2} decreased to hypoxic range. third group of tumors showed no significant changes after irradiation. None of the tumors stopped growth during the observation period. (author). 19 refs.

  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. Abnormal retinal vascular oxygen tension response to light flicker in diabetic rats.

    Science.gov (United States)

    Blair, Norman P; Wanek, Justin M; Mori, Marek; Shahidi, Mahnaz

    2009-11-01

    To test the hypothesis that the intravascular oxygen response to light flicker is abnormal in diabetes. Ten eyes of normal rats and 10 eyes of rats made diabetic with streptozotocin were examined. Oxygen tension (PO(2)) was measured noninvasively in the retinal arteries and veins on optical section retinal images. PO(2) was estimated based on the quenching by oxygen of the phosphorescence of an intravenously injected palladium porphyrin molecular probe. Measurements were conducted with and without light flicker at 10 Hz. Oxygen saturation (SO(2)) was calculated with adjustment for the arterial pH. In the normal rats flicker induced an increase in arterial PO(2) and in the difference in arterial and venous (A-V difference) PO(2) from 51 +/- 5 (mean and SD) to 55 +/- 7 mm Hg and from 22 +/- 3 to 26 +/- 5 mm Hg, respectively (P Flicker induced an increase of arterial SO(2) and A-V SO(2) difference from 64% +/- 8% to 68% +/- 7% and from 34% +/- 4% to 38% +/- 6%, respectively (P flicker in the veins. In the diabetic rats, no significant flicker-induced changes were seen in PO(2) or SO(2) in the retinal arteries, veins, or A-V differences. The diabetic rats lacked the flicker induced increase in arterial PO(2) and SO(2) and also the A-V difference in PO(2) and SO(2) observed in the normal rats. The best explanation appeared to be that diabetes impairs the increase in oxygen consumption normally provoked by light flicker.

  20. Low oxygen tension maintains multipotency, whereas normoxia increases differentiation of mouse bone marrow stromal cells.

    Science.gov (United States)

    Berniakovich, Ina; Giorgio, Marco

    2013-01-22

    Optimization of mesenchymal stem cells (MSC) culture conditions is of great importance for their more successful application in regenerative medicine. O(2) regulates various aspects of cellular biology and, in vivo, MSC are exposed to different O(2) concentrations spanning from very low tension in the bone marrow niche, to higher amounts in wounds. In our present work, we isolated mouse bone marrow stromal cells (BMSC) and showed that they contained a population meeting requirements for MSC definition. In order to establish the effect of low O(2) on cellular properties, we examined BSMC cultured under hypoxic (3% O(2)) conditions. Our results demonstrate that 3% O(2) augmented proliferation of BMSC, as well as the formation of colonies in the colony-forming unit assay (CFU-A), the percentage of quiescent cells, and the expression of stemness markers Rex-1 and Oct-4, thereby suggesting an increase in the stemness of culture when exposed to hypoxia. In contrast, intrinsic differentiation processes were inhibited by 3% O(2). Overall yield of differentiation was dependent on the adjustment of O(2) tension to the specific stage of BMSC culture. Thus, we established a strategy for efficient BMSC in vitro differentiation using an initial phase of cell propagation at 3% O(2), followed by differentiation stage at 21% O(2). We also demonstrated that 3% O(2) affected BMSC differentiation in p53 and reactive oxygen species (ROS) independent pathways. Our findings can significantly contribute to the obtaining of high-quality MSC for effective cell therapy.

  1. 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.

  2. 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...... or high oxygen superfusate. This indicates that adenosine and NO- release are not involved in the regulation of blood flow induced by changes in tissue oxygen tension. The roles of prostaglandins and 20-HETE were also tested. While application of indomethacin (inhibitor of cyclooxygenase...... (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...

  3. Oxygen Sensitivity of Reporter Genes: Implications for Preclinical Imaging of Tumor Hypoxia

    Directory of Open Access Journals (Sweden)

    Ivana Cecic

    2007-07-01

    Full Text Available Reporter gene techniques have been applied toward studying the physiologic phenomena associated with tumor hypoxia, a negative prognostic indicator. The purpose of this study was to assess the potential adverse effects of hypoxic conditions on the effectiveness of four commonly used reporter genes: Renilla luciferase, monomeric red fluorescent protein, thymidine kinase, and lacZ. Tumor-forming A375 cells expressing a trifusion reporter consisting of Renilla luciferase, monomeric red fluorescent protein, and thymidine kinase were subjected to decreasing oxygen tensions and assayed for reporter expression and activity. A375 cells expressing β-galactosidase were similarly exposed to hypoxia, with activity of the reporter monitored by cleavage of the fluorescent substrate 7-hydroxy-9H-(1, 3-dichloro-9, 9-dimethylacridin-2-one-β-galactoside (DDAOG. Generation of signal in in vivo tumor models expressing bioluminescent or β-galactosidase reporters were also examined over the course of hypoxic stresses, either by tumor clamping or the antivascular agent 5, 6-dimethylxanthenone-4-acetic acid (DMXAA. Our findings indicate that bioluminescent and fluorescent reporter activity are decreased under hypoxia despite minimal variations in protein production, whereas β-galactosidase reporter activity per unit protein was unchanged. These results demonstrate that combining β-galactosidase with the DDAOG optical probe may be a robust reporter system for the in vivo study of tumor hypoxia.

  4. DHP-derivative and low oxygen tension effectively induces human adipose stromal cell reprogramming.

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    Min Ki Jee

    Full Text Available BACKGROUND AND METHODS: In this study, we utilized a combination of low oxygen tension and a novel anti-oxidant, 4-(3,4-dihydroxy-phenyl-derivative (DHP-d to directly induce adipose tissue stromal cells (ATSC to de-differentiate into more primitive stem cells. De-differentiated ATSCs was overexpress stemness genes, Rex-1, Oct-4, Sox-2, and Nanog. Additionally, demethylation of the regulatory regions of Rex-1, stemnesses, and HIF1alpha and scavenging of reactive oxygen species were finally resulted in an improved stem cell behavior of de-differentiate ATSC (de-ATSC. Proliferation activity of ATSCs after dedifferentiation was induced by REX1, Oct4, and JAK/STAT3 directly or indirectly. De-ATSCs showed increased migration activity that mediated by P38/JUNK and ERK phosphorylation. Moreover, regenerative efficacy of de-ATSC engrafted spinal cord-injured rats and chemical-induced diabetes animals were significantly restored their functions. CONCLUSIONS/SIGNIFICANCE: Our stem cell remodeling system may provide a good model which would provide insight into the molecular mechanisms underlying ATSC proliferation and transdifferentiation. Also, these multipotent stem cells can be harvested may provide us with a valuable reservoir of primitive and autologous stem cells for use in a broad spectrum of regenerative cell-based disease therapy.

  5. 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

  6. Low Oxygen Tension Maintains Multipotency, Whereas Normoxia Increases Differentiation of Mouse Bone Marrow Stromal Cells

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    Marco Giorgio

    2013-01-01

    Full Text Available Optimization of mesenchymal stem cells (MSC culture conditions is of great importance for their more successful application in regenerative medicine. O2 regulates various aspects of cellular biology and, in vivo, MSC are exposed to different O2 concentrations spanning from very low tension in the bone marrow niche, to higher amounts in wounds. In our present work, we isolated mouse bone marrow stromal cells (BMSC and showed that they contained a population meeting requirements for MSC definition. In order to establish the effect of low O2 on cellular properties, we examined BSMC cultured under hypoxic (3% O2 conditions. Our results demonstrate that 3% O2 augmented proliferation of BMSC, as well as the formation of colonies in the colony-forming unit assay (CFU-A, the percentage of quiescent cells, and the expression of stemness markers Rex-1 and Oct-4, thereby suggesting an increase in the stemness of culture when exposed to hypoxia. In contrast, intrinsic differentiation processes were inhibited by 3% O2. Overall yield of differentiation was dependent on the adjustment of O2 tension to the specific stage of BMSC culture. Thus, we established a strategy for efficient BMSC in vitro differentiation using an initial phase of cell propagation at 3% O2, followed by differentiation stage at 21% O2. We also demonstrated that 3% O2 affected BMSC differentiation in p53 and reactive oxygen species (ROS independent pathways. Our findings can significantly contribute to the obtaining of high-quality MSC for effective cell therapy.

  7. 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

  8. 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

  9. Reactive oxygen species as mediator of tumor radiosensitivity

    Directory of Open Access Journals (Sweden)

    Renu Dayal

    2014-01-01

    Full Text Available In normal functioning of the cell, there is a balance between generation and neutralization of reactive oxygen species (ROS by endogenous cellular defense machinery. Low levels of ROS inside the cells are required for normal functioning of the cell, which regulate signaling mechanisms involved in mitosis and apoptosis; excess of ROS production may cause oxidative stress leading to damage in vital cellular molecules, namely cytosolic lipids, proteins, and DNA. In the situation of intracellular redox imbalance, molecules of cells are altered by ROS leading to pathogenic state. It is to be noted that ROS is not only known to be involved in tumor induction and progression processes but also enhances tumor cell radiosensitivity. The level of ROS-mediated oxidative stress is linked to cellular radiosensitivity. In general, cancer cells exhibit high levels of ROS, which forms a target for selectively killing them by radiation. In this paper, we have reviewed how oxidative stress determines the radiosensitivity of tumor cells involving ROS in the mechanism of radiation induced tumor cell killing. It is suggested that radiation-induced ROS play a key role in the mechanism of tumor cell killing by altering the signaling network and triggering of apoptosis. Furthermore, it is pointed out that combined use of plant-derived antioxidants and radiation enhance overproduction of ROS in tumor cells leading to enhanced radiosensitivity, which may find practical applications in clinic.

  10. 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

  11. Computational Model for Tumor Oxygenation Applied to Clinical Data on Breast Tumor Hemoglobin Concentrations Suggests Vascular Dilatation and Compression.

    Directory of Open Access Journals (Sweden)

    Michael Welter

    Full Text Available We present a computational model for trans-vascular oxygen transport in synthetic tumor and host tissue blood vessel networks, aiming at qualitatively explaining published data of optical mammography, which were obtained from 87 breast cancer patients. The data generally show average hemoglobin concentration to be higher in tumors versus host tissue whereas average oxy-to total hemoglobin concentration (vascular segment RBC-volume-weighted blood oxygenation can be above or below normal. Starting from a synthetic arterio-venous initial network the tumor vasculature was generated by processes involving cooption, angiogenesis, and vessel regression. Calculations of spatially resolved blood flow, hematocrit, oxy- and total hemoglobin concentrations, blood and tissue oxygenation were carried out for ninety tumor and associated normal vessel networks starting from various assumed geometries of feeding arteries and draining veins. Spatial heterogeneity in the extra-vascular partial oxygen pressure distribution can be related to various tumor compartments characterized by varying capillary densities and blood flow characteristics. The reported higher average hemoglobin concentration of tumors is explained by growth and dilatation of tumor blood vessels. Even assuming sixfold metabolic rate of oxygen consumption in tumorous versus host tissue, the predicted oxygen hemoglobin concentrations are above normal. Such tumors are likely associated with high tumor blood flow caused by high-caliber blood vessels crossing the tumor volume and hence oxygen supply exceeding oxygen demand. Tumor oxy- to total hemoglobin concentration below normal could only be achieved by reducing tumor vessel radii during growth by a randomly selected factor, simulating compression caused by intra-tumoral solid stress due to proliferation of cells and extracellular matrix. Since compression of blood vessels will impede chemotherapy we conclude that tumors with oxy- to total

  12. Correlation of brain tissue oxygen tension with cerebral near-infrared spectroscopy and mixed venous oxygen saturation during extracorporeal membrane oxygenation.

    Science.gov (United States)

    Tyree, Kreangkai; Tyree, Melissa; DiGeronimo, Robert

    2009-09-01

    The aim of this prospective, animal study was to compare brain tissue oxygen tension (PbtO(2)) with cerebral near infrared spectroscopy (NIRS) and mixed venous oxygen saturation (SVO(2)) during venoarterial extracorporeal membrane oxygenation (VA ECMO) in a porcine model. This was accomplished using twelve immature piglets with surgically implanted catheters placed in the superficial cerebral cortex to measure brain PbtO(2) and microdialysis metabolites. The NIRS sensor was placed overlying the forehead to measure cerebral regional saturation index (rSO(2)i) while SVO(2) was measured directly from the ECMO circuit. Animals were placed on VA ECMO followed by an initial period of stabilization, after which they were subjected to graded hypoxia and recovery. Our results revealed that rSO(2)i and SVO(2) correlated only marginally with PbtO(2) (R(2)=0.32 and R(2)=0.26, respectively) while the correlation between rSO(2)i and SVO( 2) was significantly stronger (R(2)=0.59). Cerebral metabolites and rSO(2)i were significantly altered during attenuation of PbtO( 2), p<0.05). A subset of animals, following exposure to hypoxia, experienced markedly delayed recovery of both rSO(2)i and PbtO( 2) despite rapid normalization of SVO(2). Upon further analysis, these animals had significantly lower blood pressure (p=0.001), lower serum pH (p=0.01), and higher serum lactate (p=0.02). Additionally, in this subgroup, rSO(2)i correlated better with PbtO(2) (R(2)=0.76). These findings suggest that, in our ECMO model, rSO(2)i and SVO( 2) correlate reasonably well with each other, but not necessarily with brain PbtO(2) and that NIRS-derived rSO(2)i may more accurately reflect cerebral tissue hypoxia in sicker animals.

  13. 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.

  14. Oxygen tension and formation of cervical-like tissue in two-dimensional and three-dimensional culture.

    Science.gov (United States)

    House, Michael; Daniel, Jennifer; Elstad, Kirigin; Socrate, Simona; Kaplan, David L

    2012-03-01

    Cervical dysfunction contributes to a significant number of preterm births and is a common cause of morbidity and mortality in newborn infants. Cervical dysfunction is related to weakened load bearing properties of the collagen-rich cervical stroma. However, the mechanisms responsible for cervical collagen changes during pregnancy are not well defined. It is known that blood flow and oxygen tension significantly increase in reproductive tissues during pregnancy. To examine the effect of oxygen tension, a key mediator of tissue homeostasis, on the formation of cervical-like tissue in vitro, we grew primary human cervical cells in both two-dimensional (2D) and three-dimensional (3D) culture systems at 5% and 20% oxygen. Immunofluorescence studies revealed a stable fibroblast phenotype across six passages in all subjects studied (n=5). In 2D culture for 2 weeks, 20% oxygen was associated with significantly increased collagen gene expression (p<0.01), increased tissue wet weight (p<0.01), and increased collagen concentration (p=0.046). 3D cultures could be followed for significantly longer time frames than 2D cultures (12 weeks vs. 2 weeks). In contrast to 2D cultures, 20% oxygen in 3D cultures was associated with decreased collagen concentration (p<0.01) and unchanged collagen gene expression, which is similar to cervical collagen changes seen during pregnancy. We infer that 3D culture is more relevant for studying cervical collagen changes in vitro. The data suggest that increased oxygen tension may be related to significant cervical collagen changes seen in pregnancy.

  15. 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.

  16. 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

  17. Influence of oxygen tension on dopaminergic differentiation of human fetal stem cells of midbrain and forebrain origin.

    Directory of Open Access Journals (Sweden)

    Christina Krabbe

    Full Text Available Neural stem cells (NSCs constitute a promising source of cells for transplantation in Parkinson's disease (PD, but protocols for controlled dopaminergic differentiation are not yet available. Here we investigated the influence of oxygen on dopaminergic differentiation of human fetal NSCs derived from the midbrain and forebrain. Cells were differentiated for 10 days in vitro at low, physiological (3% versus high, atmospheric (20% oxygen tension. Low oxygen resulted in upregulation of vascular endothelial growth factor and increased the proportion of tyrosine hydroxylase-immunoreactive (TH-ir cells in both types of cultures (midbrain: 9.1 ± 0.5 and 17.1 ± 0.4 (P<0.001; forebrain: 1.9 ± 0.4 and 3.9 ± 0.6 (P<0.01 percent of total cells. Regardless of oxygen levels, the content of TH-ir cells with mature neuronal morphologies was higher for midbrain as compared to forebrain cultures. Proliferative Ki67-ir cells were found in both types of cultures, but the relative proportion of these cells was significantly higher for forebrain NSCs cultured at low, as compared to high, oxygen tension. No such difference was detected for midbrain-derived cells. Western blot analysis revealed that low oxygen enhanced β-tubulin III and GFAP expression in both cultures. Up-regulation of β-tubulin III was most pronounced for midbrain cells, whereas GFAP expression was higher in forebrain as compared to midbrain cells. NSCs from both brain regions displayed less cell death when cultured at low oxygen tension. Following mictrotransplantation into mouse striatal slice cultures predifferentiated midbrain NSCs were found to proliferate and differentiate into substantial numbers of TH-ir neurons with mature neuronal morphologies, particularly at low oxygen. In contrast, predifferentiated forebrain NSCs microtransplanted using identical conditions displayed little proliferation and contained few TH-ir cells, all of which had an immature appearance. Our data may reflect

  18. 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

  19. Postocclusive Hyperemia Measured with Laser Doppler Flowmetry and Transcutaneous Oxygen Tension in the Diagnosis of Primary Raynaud's Phenomenon: A Prospective, Controlled Study

    Science.gov (United States)

    Maga, Paweł; Henry, Brandon Michael; Kmiotek, Elizabeth K.; Gregorczyk-Maga, Iwona; Kaczmarczyk, Paweł; Niżankowski, Rafał

    2016-01-01

    The aim of this study was to measure the sensitivity and specificity of transcutaneous oxygen tension and postocclusive hyperemia testing using laser Doppler flowmetry in patients with primary Raynaud's phenomenon. One hundred patients and one hundred controls were included in the study. Baseline microvascular blood flow and then time to peak flow following occlusion were measured using laser Doppler flowmetry. Afterwards, the transcutaneous oxygen tension was recorded. The sensitivities of baseline microvascular blood flow, postocclusive time to peak flow, and transcutaneous oxygen tension were 79%, 79%, and 77%, respectively. The postocclusive time peak flow had a superior specificity of 90% and area under the curve of 0.92 as compared to 66% and 0.80 for baseline microvascular flow and 64% and 0.76 for transcutaneous oxygen tension. Time to postocclusive peak blood flow measured by laser Doppler flowmetry is a highly accurate test for differentiating patients with primary Raynaud's phenomenon from healthy controls. PMID:28101516

  20. 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

  1. Noninvasive near-infrared hemoglobin spectroscopy for in vivo monitoring of tumor oxygenation and response to oxygen modifiers

    Science.gov (United States)

    Hull, Edward L.; Foster, Thomas H.

    1997-08-01

    The shift in optical absorption of hemoglobin upon binding of oxygen provides a basis for near-infrared monitoring of hemoglobin oxygen saturation, which is an important indicator of tissue oxygenation. Tumor oxygenation has long been studied, because hypoxic cells exhibit resistance to ionizing radiation therapy. The ability to measure noninvasively the oxygenation status of tumors and their response to oxygen modifiers is important in research and clinical settings. We have implemented a steady-state diffuse reflectance method of optical spectroscopy in scattering systems based on the theory of Farrell et al. (Med. Phys., 1992). In scattering phantoms containing erythrocytes, the method recovers the hemoglobin absorption spectrum (650 - 820 nm) and accurately monitors hemoglobin oxygen saturation. We have implemented a probe that individually positions several detection fibers normal to the surface of subcutaneous rodent tumors. Near-infrared absorption spectra reconstructed from diffuse reflectance measurements indicate a hemoglobin oxygen saturation of approximately 50% in R3230AC rat mammary adenocarcinomas when the anesthetized animal breathes room air. Administration of carbogen (95% oxygen, 5% carbon dioxide) via a nose cone produces a rapid and readily detectable increase in the saturation to 75% with no increase in tumor blood volume. Several methods of determining hemoglobin oxygen saturation from absorption spectra obtained by diffuse reflectance spectroscopy are compared, including singular value decomposition, which provides the ability to reconstruct the non-hemoglobin absorbing background without a priori knowledge of its structure or absolute magnitude.

  2. Tumor Oxygen Dynamics as a Prognostic Indicator of Effective Antiangiogenic Therapy

    National Research Council Canada - National Science Library

    Zhao, Dawen

    2002-01-01

    ...) MR, our results showed that significantly better oxygenation was found in the well differentiated and slower growing H and HI tumors, compared with anaplastic or metastatic, faster growing ATl and MAT-Lu tumors...

  3. Inhaled nitric oxide and arterial oxygen tension in patients with chronic obstructive pulmonary disease and severe pulmonary hypertension

    Science.gov (United States)

    Katayama, Y.; Higenbottam, T. W.; d Diaz; Cremona, G.; Akamine, S.; Barbera, J. A.; Rodriguez-Roisin, R.

    1997-01-01

    BACKGROUND: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator which can improve gas exchange in acute lung injury. However, it is uncertain that this effect on arterial oxygenation can be generalised to all lung diseases. METHODS: The effects of inhaled NO on gas exchange were studied in nine patients with chronic obstructive pulmonary disease (COPD), 11 patients with severe pulmonary hypertension, and 14 healthy volunteers. A randomized sequence of 40 ppm of NO or air was inhaled for 20 minutes through an orofacial mask. RESULTS: Inhaled NO reduced mean (SE) transcutaneous arterial oxygen tension (TcPO2) from 9.6 (0.3) to 8.9 (0.4) kPa in healthy volunteers and from 7.4 (0.6) to 7.0 (0.5) kPa in patients with COPD. There was no change in TcPO2 in patients with severe pulmonary hypertension. During inhalation of NO and air no change occurred in transcutaneous arterial carbon dioxide tension (TcPCO2), arterial oxygen saturation (SaO2) measured by pulse oximeter, or cardiac output determined by the transthoracic impedance method. CONCLUSIONS: Inhaled NO does not improve TcPO2 nor increase cardiac output in normal subjects and patients with COPD, suggesting that inhaled NO worsens gas exchange. This could represent inhaled NO overriding hypoxic pulmonary vasoconstriction in COPD. The finding that TcPO2 also fell when normal subjects inhaled NO suggests that a similar mechanism normally contributes to optimal gas exchange. Whilst inhaled NO can improve oxygenation, this effect should not be considered to be a general response but is dependent on the type of lung disease. 


 PMID:9059470

  4. Effects of oxygen on the metabolism of murine tumors using in-vivo P-31 NMR

    International Nuclear Information System (INIS)

    Okunieff, P.; Willett, C.; Suit, H.D.; McFarland, E.; Neuringer, L.; Hitzig, B.

    1987-01-01

    The effect of 100% inspired oxygen on in vivo tumor metabolism was examined using /sup 31p/. Isotransplants of murine tumors, MCaIV (mammary adenocarcinoma) and FSaII, (fibrosarcoma), were used. Tumor volumes ranged from 30 to 1800 mm/sup 3/. Both tumors have a high hypoxic cell fraction at >250mm/sup 3/. NMR spectra were obtained using a narrow bore superconducting magnet operating at 145.587 MHz for Phosphorus-31. Tumors were implanted in the hind food dorsum to assure all detected mobile phosphates were of tumor origin. PCr/Pi ratios of tumors >250mm/sup 3/ were reduced compared with tumors <250mm/sup 3/ of the same histology. Response to 100% inspired oxygen was greater for large tumors, and for tumors with lower baseline PCr/Pi ratios. Respiration of 10% oxygen increased Pi and decreased PCr and ATP. The response to 10% oxygen was observed in both large and small tumors of both histologies. The fractional increase in PCr/Pi ratio after 100% oxygen breathing appears to be a non-invasive method of detecting tumor hypoxia

  5. 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...... differentiation and survival of a human ventral mesencephalic stem cell line (hVM1). hVM1 cells and a Bcl-x(L) over-expressing subline (hVMbcl-x(L)) were differentiated by sequential treatment with fibroblast growth factor-8, forskolin, sonic hedgehog, and glial cell line-derived neurotrophic factor. After 10......-PCR-analysis revealed expression of several dopaminergic markers besides of TH just as dopamine was detected in the culture medium by HPLC analysis. Although Bcl-x(L)-over-expression reduced cell death in the cultures, it did not alter the relative content of GABAergic, neurons, while the content of astroglial cells...

  6. Low Oxygen Tension Maintains Multipotency, Whereas Normoxia Increases Differentiation of Mouse Bone Marrow Stromal Cells

    OpenAIRE

    Berniakovich, Ina; Giorgio, Marco

    2013-01-01

    Optimization of mesenchymal stem cells (MSC) culture conditions is of great importance for their more successful application in regenerative medicine. O2 regulates various aspects of cellular biology and, in vivo, MSC are exposed to different O2 concentrations spanning from very low tension in the bone marrow niche, to higher amounts in wounds. In our present work, we isolated mouse bone marrow stromal cells (BMSC) and showed that they contained a population meeting requirements for MSC defin...

  7. 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

  8. 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

  9. Effect of magnetic field on oxygen pressure, radiosensitivity and growth of some experimental tumors

    Energy Technology Data Exchange (ETDEWEB)

    Lyu, B.N.; Kauashev, S.K.

    The effect of variation of partial oxygen pressure in liquid media and directly in living tumors was investigated to determine the effect of a permanent magnetic field on these changes. Partial oxygen pressure increases significantly in Pliss lymphosarcoma and RS-1 tumors when exposed to a magnetic field and decreases after the magnetic field is removed. The variation of partial oxygen pressure is similar in Walker carcinosarcoma, but is different for living and killed rats. The growth rate of tumors decreases appreciably after each session of combination magnetic and radiation effects with an increase of partial oxygen pressure in magnetized tumors. Periodic one-hour magnetic exposure preceding irradiation causes a marked zigzag growth of tumors, while 5- and 30- minute exposure to a permanent magnetic field has essentially no effect on tumor growth.

  10. Influence of pretreatment polarographically measured oxygenation levels in spontaneous canine tumors treated with radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Bley, C.R.; Ohlerth, S.; Wergin, M.; Achermann, R.; Kaser-Hotz, B. [Section of Diagnostic Imaging and Radiation Oncology, Vetsuisse Faculty, Univ. of Zurich (Switzerland); Roos, M. [Biostatistics, ISPM, Univ. of Zurich (Switzerland)

    2006-09-15

    Background and purpose: the level of hypoxia in primary tumors has been described to influence response to treatment. The aim of the present study was to investigate the impact of pretreatment oxygen level measurements in spontaneous canine tumors on treatment outcome. Material and methods: data of pretreatment tumor oxygenation status and local tumor response after primary radiation therapy in a group of spontaneously occurring tumors in dogs (n = 52) was collected. Radiation therapy was given with curative (14-17 x 3-3.5 Gy) or palliative intent (3 x 8 Gy or 4-5 x 6 Gy). Progression-free interval and overall survival were correlated to polarographically measured tumor oxygenation status. Results: in the curatively irradiated group, tumors with median p0{sub 2} values {<=} 10 mmHg tended to have shorter median progression-free interval compared to better oxygenated tumors (246 vs. 739 days). The same trend could be shown for overall survival (330 vs. 745 days), indicating a cutoff value in this region. In the group treated with lower doses of radiation, the level of oxygen was no longer found to be of prognostic value; however, in this group hemoglobin had a significant impact on outcome. Conclusion: in curatively irradiated spontaneous canine tumors, tumor hypoxia was found to be a prognostic indicator, independent of tumor histologies and volume. (orig.)

  11. 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.

  12. Phosphorescent ruthenium complexes with a nitroimidazole unit that image oxygen fluctuation in tumor tissue.

    Science.gov (United States)

    Son, Aoi; Kawasaki, Atsushi; Hara, Daiki; Ito, Takeo; Tanabe, Kazuhito

    2015-02-02

    Understanding oxygen fluctuation in a cancerous tumor is important for effective treatment, especially during radiotherapy. In this paper, ruthenium complexes bearing a nitroimidazole group are shown to report the oxygen status in tumor tissue directly. The nitroimidazole group was known to be accumulated in hypoxic tumor tissues. On the other hand, the ruthenium complex showed strong phosphorescence around 600 nm. The emission of ruthenium is quenched instantaneously by molecular oxygen due to energy transfer between triplet states of oxygen and ruthenium complex, but the emission is then recovered by the removal of oxygen. Thus, we could observe oxygen fluctuation in tumor tissue in a real-time manner by monitoring the phosphorescence of the ruthenium complex. The versatility of the probe is demonstrated by monitoring oxygen fluctuation in living cells and tumor tissue planted in mice. The ruthenium complex promptly penetrated plasma membrane and accumulated in cells to emit its oxygen-dependent phosphorescence. In vivo experiments revealed that the oxygen level in tumor tissue seems to fluctuate at the sub-minute timescale. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Controlling the Effective Oxygen Tension Experienced by Cells Using a Dynamic Culture Technique for Hematopoietic Ex Vivo Expansion.

    Science.gov (United States)

    Tiwari, Abhilasha; Wong, Cynthia S; Nekkanti, Lakshmi P; Deane, James A; McDonald, Courtney; Li, Jingang; Pham, Yen; Sutherland, Amy E; Jenkin, Graham; Kirkland, Mark A

    2018-02-28

    Clinical hematopoietic stem/progenitor cell (HSPC) transplantation outcomes are strongly correlated with the number of cells infused. Hence, to generate sufficient HSPCs for transplantation, the best culture parameters for expansion are critical. It is generally assumed that the defined oxygen (O 2 ) set for the incubator reflects the pericellular O 2 to which cells are being exposed. Studies have shown that low O 2 tension maintains an undifferentiated state, but the expansion rate may be constrained because of limited diffusion in a static culture system. A combination of low ambient O 2 and dynamic culture conditions has been developed to increase the reconstituting capacity of human HSPCs. In this unit, the protocols for serum-free expansion of HSPCs at 5% and 20% O 2 in static and dynamic nutrient flow mode are described. Finally, the impact of O 2 tension on HSPC expansion in vitro by flow cytometry and colony forming assays and in vivo through engraftment using a murine model is assessed. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

  14. 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...

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

    DEFF Research Database (Denmark)

    Booth, Paul J; Holm, Peter; Callesen, Henrik

    2005-01-01

    Reducing oxygen concentration from atmospheric levels during in vitro culture generally, but not invariably, improves embryonic development across a range of species. Since the few published reports of such an action in the pig are contradictory--perhaps a consequence of the derivation of the emb...

  16. 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

  17. 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.

  18. 2-Deoxy-D-glucose Restore Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia via Modification of N-Linked Glycosylation in an Oxygen Tension-Independent Manner

    Directory of Open Access Journals (Sweden)

    Zaira Leni

    2017-01-01

    Full Text Available In childhood acute lymphoblastic leukemia, treatment failure is associated with resistance to glucocorticoid agents. Resistance to this class of drugs represents one of the strongest indicators of poor clinical outcome. We show that leukemic cells, which are resistant to the glucocorticoid drug methylprednisolone, display a higher demand of glucose associated with a deregulation of metabolic pathways, in comparison to sensitive cells. Interestingly, a combinatorial treatment of glucocorticoid and the glucose analog 2-deoxy-D-glucose displayed a synergistic effect in methylprednisolone-resistant cells, in an oxygen tension-independent manner. Unlike solid tumors, where 2-deoxy-D-glucose promotes inhibition of glycolysis by hexokinase II exclusively under hypoxic conditions, we were able to show that the antileukemic effects of 2-deoxy-D-glucose are far more complex in leukemia. We demonstrate a hexokinase II-independent cell viability decrease and apoptosis induction of the glucose analog in leukemia. Additionally, due to the structural similarity of 2-deoxy-D-glucose with mannose, we could confirm that the mechanism by which 2-deoxy-D-glucose predominantly acts in leukemia is via modification in N-linked glycosylation, leading to endoplasmic reticulum stress and consequently induction of the unfolded protein response.

  19. Easy to use and reliable technique for online dissolved oxygen tension measurement in shake flasks using infrared fluorescent oxygen-sensitive nanoparticles.

    Science.gov (United States)

    Flitsch, David; Ladner, Tobias; Lukacs, Mihaly; Büchs, Jochen

    2016-02-24

    Despite the progressive miniaturization of bioreactors for screening purposes, shake flasks are still widespread in biotechnological laboratories and industry as cultivation vessels. Shake flasks are often applied as the first or second step in applications such as strain screening or media optimization. Thus, there are ongoing efforts to develop online measurement techniques for shake flasks, to gain as much information as possible about the cultured microbial system. Since dissolved oxygen tension (DOT) is a key experimental parameter, its accurate determination during the course of experiment is critical. Some of the available DOT measurement techniques can lead to erroneous measurements or are very difficult to handle. A reliable and easy to use DOT measurement system, based on suspended oxygen-sensitive nanoparticles, is presented in this work. In a cultivation of Kluyveromyces lactis, a new DOT measurement technique via suspended oxygen-sensitive nanoparticles was compared with the conventional DOT measurement via fixed sensor spots. These experiments revealed the main disadvantage of applying sensor spots. With further cultivations of Escherichia coli and Hansenula polymorpha, the new measurement technique was successfully validated. In combination with a RAMOS device, kLa values were determined during the presented cultivations. The determined kLa values are in good agreement with a correlation recently found in the literature. The presented DOT measurement technique via suspended oxygen-sensitive nanoparticles in shake flasks turned out to be easy to use, robust and reliable under all applied combinations of shaking frequencies and filling volumes. Its applicability as an online monitoring system for cultivations was shown by means of four examples. Additionally, in combination with a RAMOS device, the possibility of experimental kLa determination was successfully demonstrated.

  20. Oxygen-generating hybrid nanoparticles to enhance fluorescent/photoacoustic/ultrasound imaging guided tumor photodynamic therapy.

    Science.gov (United States)

    Gao, Shi; Wang, Guohao; Qin, Zainen; Wang, Xiangyu; Zhao, Guoqing; Ma, Qingjie; Zhu, Lei

    2017-01-01

    Photodynamic therapy (PDT) is a promising tumor treatment modality that can convert oxygen into cytotoxic singlet oxygen (SO) via photosensitizer to ablate tumor growth. However, the uncontrolled cancer cell proliferation during tumor development and the oxygen consumption during PDT always result in an insufficient oxygen level in tumors, which can adversely affect the PDT efficiency in turn. We designed an oxygen-generating PDT nanocomplex by encapsulating a manganese dioxide nanoparticle (MnO 2 NP) in an indocyanine green (ICG) modified hyaluronic acid nanoparticle (HANP) to overcome this limitation. Because of the excellent fluorescent and photoacoustic properties, the tumor accumulation of the ICG-HANP/MnO 2 (IHM) nanocomplex was monitored by fluorescent imaging and photoacoustic imaging after intravenous administration into the SCC7 tumor-bearing mouse model. Both high fluorescent and photoacoustic signals were detected and found peak at 6 h post-injection (tumor-muscle ratio: 4.03 ± 0.36 for fluorescent imaging and 2.93 ± 0.13 for photoacoustic imaging). In addition, due to the high reactivity of MnO 2 NP to H 2 O 2 , an unfavorable tumor cell metabolic, the oxygen content in the tumor is elevated 2.25 ± 0.07 times compared to that without IHM treatment as ultrasound imaging confirmed. After laser irradiation, significant tumor growth inhibition was observed in the IHM-treated group compared to the ICG-HANP-treated group, attributed to the beneficial oxygen-generating property of IHM for PDT. It is expected that the design of IHM will provide an alternative way of improving clinical PDT efficacy and will be widely applied in cancer theranostics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Oxygen consumption can regulate the growth of tumors, a new perspective on the Warburg effect.

    Science.gov (United States)

    Chen, Yijun; Cairns, Rob; Papandreou, Ioanna; Koong, Albert; Denko, Nicholas C

    2009-09-15

    The unique metabolism of tumors was described many years ago by Otto Warburg, who identified tumor cells with increased glycolysis and decreased mitochondrial activity. However, "aerobic glycolysis" generates fewer ATP per glucose molecule than mitochondrial oxidative phosphorylation, so in terms of energy production, it is unclear how increasing a less efficient process provides tumors with a growth advantage. We carried out a screen for loss of genetic elements in pancreatic tumor cells that accelerated their growth as tumors, and identified mitochondrial ribosomal protein L28 (MRPL28). Knockdown of MRPL28 in these cells decreased mitochondrial activity, and increased glycolysis, but paradoxically, decreased cellular growth in vitro. Following Warburg's observations, this mutation causes decreased mitochondrial function, compensatory increase in glycolysis and accelerated growth in vivo. Likewise, knockdown of either mitochondrial ribosomal protein L12 (MRPL12) or cytochrome oxidase had a similar effect. Conversely, expression of the mitochondrial uncoupling protein 1 (UCP1) increased oxygen consumption and decreased tumor growth. Finally, treatment of tumor bearing animals with dichloroacetate (DCA) increased pyruvate consumption in the mitochondria, increased total oxygen consumption, increased tumor hypoxia and slowed tumor growth. We interpret these findings to show that non-oncogenic genetic changes that alter mitochondrial metabolism can regulate tumor growth through modulation of the consumption of oxygen, which appears to be a rate limiting substrate for tumor proliferation.

  2. Oxygen consumption can regulate the growth of tumors, a new perspective on the Warburg effect.

    Directory of Open Access Journals (Sweden)

    Yijun Chen

    Full Text Available The unique metabolism of tumors was described many years ago by Otto Warburg, who identified tumor cells with increased glycolysis and decreased mitochondrial activity. However, "aerobic glycolysis" generates fewer ATP per glucose molecule than mitochondrial oxidative phosphorylation, so in terms of energy production, it is unclear how increasing a less efficient process provides tumors with a growth advantage.We carried out a screen for loss of genetic elements in pancreatic tumor cells that accelerated their growth as tumors, and identified mitochondrial ribosomal protein L28 (MRPL28. Knockdown of MRPL28 in these cells decreased mitochondrial activity, and increased glycolysis, but paradoxically, decreased cellular growth in vitro. Following Warburg's observations, this mutation causes decreased mitochondrial function, compensatory increase in glycolysis and accelerated growth in vivo. Likewise, knockdown of either mitochondrial ribosomal protein L12 (MRPL12 or cytochrome oxidase had a similar effect. Conversely, expression of the mitochondrial uncoupling protein 1 (UCP1 increased oxygen consumption and decreased tumor growth. Finally, treatment of tumor bearing animals with dichloroacetate (DCA increased pyruvate consumption in the mitochondria, increased total oxygen consumption, increased tumor hypoxia and slowed tumor growth.We interpret these findings to show that non-oncogenic genetic changes that alter mitochondrial metabolism can regulate tumor growth through modulation of the consumption of oxygen, which appears to be a rate limiting substrate for tumor proliferation.

  3. 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.)

  4. 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.

  5. 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

  6. Variations in tumour oxygen tension (pO{sub 2}) during accelerated radiotherapy of head and neck carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Guichard, M. [Laboratory of Radiobiology, Institut Gustave Roussy, 94800 Villejuif (France); Eschwege, F. [Department of Radiotherapy, Institut Gustave Roussy, 94800 Villejuif (France); Luboinski, B. [Department of Head and Neck Surgery, Institut Gustave Roussy, 94800 Villejuif (France); Wibault, P. [Department of Radiotherapy, Institut Gustave Roussy, 94800 Villejuif (France); Weeger, P. [Department of Head and Neck Surgery, Institut Gustave Roussy, 94800 Villejuif (France); Lusinchi, A.; Lartigau, E. [Department of Radiotherapy, Institut Gustave Roussy, 94800 Villejuif (France)

    1998-05-01

    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{sub 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{sub 2} was measured using a polarographic technique. For pooled normal tissues, median pO{sub 2} was 38 mmHg before treatment and 46 mmHg after 2 weeks. For tumours, very low values (<2 mmHg) represented 20% of the recorded values before treatment and 10% after 2 weeks. The relative increase in tumour oxygenation was more pronounced for primary tumours (median pO{sub 2} 12 mmHg before treatment versus 26 mmHg after 2 weeks, P<0.05) than for metastatic nodes (respectively, 20 and 27 mmHg P=0.1). For the 5 patients who breathed carbogen during accelerated radiotherapy, the median pO{sub 2} was 44 mmHg at 2 weeks, compared with 13.5 mmHg before treatment (P=0.05). Very low pO{sub 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{sub 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.)

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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...... which can characterize such features non-invasively and repeatedly will be of significant value in planning treatment as well as monitoring response to treatment. The three techniques based on magnetic resonance imaging (MRI) are reviewed here. Tumor pO2 can be measured by two MRI methods requiring...... an exogenous contrast agent: electron paramagnetic resonance imaging (EPRI) and Overhauser magnetic resonance imaging (OMRI). Tumor metabolic profile can be assessed by a third method, hyperpolarized metabolic MR, based on injection of hyperpolarized biological molecules labeled with 13C or 15N and MR...

  13. Modeling the Interplay Between Tumor Volume Regression and Oxygenation in Uterine Cervical Cancer During Radiotherapy Treatment.

    Science.gov (United States)

    Belfatto, Antonella; Riboldi, Marco; Ciardo, Delia; Cattani, Federica; Cecconi, Agnese; Lazzari, Roberta; Jereczek-Fossa, Barbara Alicja; Orecchia, Roberto; Baroni, Guido; Cerveri, Pietro

    2016-03-01

    This paper describes a patient-specific mathematical model to predict the evolution of uterine cervical tumors at a macroscopic scale, during fractionated external radiotherapy. The model provides estimates of tumor regrowth and dead-cell reabsorption, incorporating the interplay between tumor regression rate and radiosensitivity, as a function of the tumor oxygenation level. Model parameters were estimated by minimizing the difference between predicted and measured tumor volumes, these latter being obtained from a set of 154 serial cone-beam computed tomography scans acquired on 16 patients along the course of the therapy. The model stratified patients according to two different estimated dynamics of dead-cell removal and to the predicted initial value of the tumor oxygenation. The comparison with a simpler model demonstrated an improvement in fitting properties of this approach (fitting error average value <5%, p < 0.01), especially in case of tumor late responses, which can hardly be handled by models entailing a constant radiosensitivity, failing to model changes from initial severe hypoxia to aerobic conditions during the treatment course. The model predictive capabilities suggest the need of clustering patients accounting for cancer cell line, tumor staging, as well as microenvironment conditions (e.g., oxygenation level).

  14. 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.

  15. Effect of a topical vasodilator on tumor hypoxia and tumor oxygen guided radiotherapy using EPR oximetry.

    Science.gov (United States)

    Hou, Huagang; Abramovic, Zrinka; Lariviere, Jean P; Sentjurc, Marjeta; Swartz, Harold; Khan, Nadeem

    2010-05-01

    We sought to reduce tumor hypoxia by topical application of a vasodilator, benzyl nicotinate (BN), and investigated its effect on the growth of tumors irradiated at times when tumor pO(2) increased. EPR oximetry was used to follow the changes in the tissue pO(2) of subcutaneous radiation-induced fibrosarcoma (RIF-1) tumors during topical applications of 1.25-8% BN formulations for 5 consecutive days. The RIF-1 tumors were hypoxic with a tissue pO(2) of 4.6-7.0 mmHg. A significant increase in tumor pO(2) occurred 10-30 min after BN application. The formulation with the minimal BN concentration that produced a significant increase in tumor pO(2) was used for the radiation study. The tumors were irradiated (4 Gy x 5) at the time of the maximum increase in pO(2) observed with the 2.5% BN formulation. The tumors with an increase in pO(2) of greater than 2 mmHg from the baseline after application of BN on day 1 had a significant growth inhibition compared to the tumors with an increase in pO(2) of less than 2 mmHg. The results indicate that the irradiation of tumors at the time of an increase in pO(2) after the topical application of the 2.5% BN formulation led to a significant growth inhibition. EPR oximetry provided dynamic information on the changes in tumor pO(2), which could be used to identify responders and non-responders and schedule therapy during the experiments.

  16. 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.

  17. 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

  18. 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

  19. Noninvasive tumor oxygen imaging by photoacoustic lifetime imaging integrated with photodynamic therapy

    Science.gov (United States)

    Shao, Qi; Biel, Merrill A.; Ashkenazi, Shai

    2014-03-01

    Oxygen plays a major role in cancer biology and tumor progression. In PDT, the reduction in efficacy is directly related to lack of oxygen because its molecular mechanism relies on oxygen as an energy mediator. Measuring tumor oxygenation can provide physicians with better diagnosis and optimization of treatment plans. However, clinical tools for directly assessing tissue oxygenation are limited. The gold standard is oxygen needle electrode, which is invasive and measures oxygen level at a single location. We present our work on developing a combined treatment-imaging modality that integrates PDT and photoacoustic oxygen imaging. We propose a system designed for clinical treatments of cancer of the oral cavity. Tissue oxygen imaging is performed by applying Photoacoustic Lifetime Imaging (PALI). This technology relies on photoacoustic probing of oxygen-dependent excitation lifetime of Methylene Blue. The dye is excited by the same wavelength of illumination source for PDT. Once excited, the population of photosensitizer molecules at triplet state has a lifetime depending on the oxygen level. The transition from excited triplet state to ground state can be probe by another laser, which generate photoacoustic signal that is used to map the lifetime. The lifetime map is then converted to pO2 distribution. We expect that PDT efficacy can be improved by applying PALI imaging feedback in real-time to determine, and individually optimize, O2-enriched gas breathing parameters and PDT light-dose during treatment. Successful implementation of PALI in PDT can also drive its application in guiding other cancer treatments that are affected by hypoxia.

  20. 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

  1. 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...

  2. 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

  3. 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.

  4. 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

  5. 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

  6. Optical monitoring of singlet oxygen generation during photodynamic treatment of tumors

    International Nuclear Information System (INIS)

    Optical detection of singlet oxygen production accompanying continuous-wave (CW) laser irradiation of subcutaneous murine tumors at 630 nm following prior intraperitoneal injection of a Photofrin II sensitizer has been demonstrated. In order to separate the spectrally discrete, time-delayed, singlet oxygen emission from the dominant, spectrally diffuse, coherent background provided by the combination of sensitizer infrared fluorescence and tissue-related autofluorescence, chopping of the incident laser beam was required. Using the infrared fluorescence to provide a reference, the singlet oxygen emission is shown to be given directly by the frequency-dependent quadrature component of the detector output. Maximum detector quadrature output for the in vivo case was obtained for a chopping frequency between 10 and 20 kHz. The spectral variation of the emission from the tumor was obtained and identified as that characteristic of singlet oxygen. This demonstration provides the rationale for the development of a clinically useful electro-optical system to provide a realistic means for monitoring treatment effectiveness during the photodynamic therapy of tumors as well as the establishment of much-needed dosimetry standards. It is expected that, in the future, development of this capbility will provide an analytical, quantitative means to remove some of the mysteries now impeding progress in this important area of medicine

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

    Science.gov (United States)

    Truong, Grace; Guanzon, Dominic; Kinhal, Vyjayanthi; Elfeky, Omar; Lai, Andrew; Longo, Sherri; Nuzhat, Zarin; Palma, Carlos; Scholz-Romero, Katherin; Menon, Ramkumar; Mol, Ben W.; Rice, Gregory E.; Salomon, Carlos

    2017-01-01

    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 (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. PMID:28350871

  8. 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.

  9. 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.)

  10. 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

  11. 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.

  12. 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

    2018-03-02

    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 diet might improve microvascular health. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. 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.

  14. Mapping of oxygen tension and cell distribution in a hollow-fiber bioreactor using magnetic resonance imaging.

    Science.gov (United States)

    Williams, S N; Callies, R M; Brindle, K M

    1997-10-05

    We mapped the distribution of dissolved oxygen and mammalian cells in a hollow-fiber bioreactor (HFBR) using (19)F NMR T(1) relaxation time imaging measurements on an infused perfluorocarbon probe molecule and diffusion-weighted (1)H NMR imaging of water. This study shows how cell density influences dissolved oxygen concentration in the reactor and demonstrates that NMR can play an important role in defining the biochemical engineering parameters required for optimization of HFBR design and operation.

  15. 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)

  16. Photoacoustic signal characterization of cancer treatment response: Correlation with changes in tumor oxygenation

    Directory of Open Access Journals (Sweden)

    Eno Hysi

    2017-03-01

    Full Text Available Frequency analysis of the photoacoustic radiofrequency signals and oxygen saturation estimates were used to monitor the in-vivo response of a novel, thermosensitive liposome treatment. The liposome encapsulated doxorubicin (HaT-DOX releasing it rapidly (<20 s when the tumor was exposed to mild hyperthermia (43 °C. Photoacoustic imaging (VevoLAZR, 750/850 nm, 40 MHz of EMT-6 breast cancer tumors was performed 30 min pre- and post-treatment and up to 7 days post-treatment (at 2/5/24 h timepoints. HaT-DOX-treatment responders exhibited on average a 22% drop in oxygen saturation 2 h post-treatment and a decrease (45% at 750 nm and 73% at 850 nm in the slope of the normalized PA frequency spectra. The spectral slope parameter correlated with treatment-induced hemorrhaging which increased the optical absorber effective size via interstitial red blood cell leakage. Combining frequency analysis and oxygen saturation estimates differentiated treatment responders from non-responders/control animals by probing the treatment-induced structural changes of blood vessel.

  17. 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

  18. 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

  19. 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

    of DDMS (inhibitor of 20-HETE production) inhibited vasoconstriction to high oxygen superfusates, indicating that 20-HETE is involved in hyperoxic vasoconstriction. Using a custom-built gas exchange chamber with a small aperture covered by a gas-permeable membrane, we were able to induce highly localized...... localized hypoxia or hyperoxia is able to induce a conducted vasomotor response in mouse cremaster arterioles in situ. In anesthetized C57BL/6J male mice, cremaster arterioles (~30 μm) where examined during superfusion with a Krebs’ buffer equilibrated with gas mixtures containing 0% (low oxygen superfusate....... In a separate study we examined if low or high oxygen caused any change in the intracellular Ca2+ concentration of isolated mouse cremaster arterioles using fluorescent microscopy. Cremaster arterioles were isolated by gentle microdissection, loaded with Fura-PE3 (calcium fluorescent dye) and placed in a small...

  20. Expression of the Fanconi anemia gene FAC in human cell lines : Lack of effect of oxygen tension

    NARCIS (Netherlands)

    Joenje, H; Youssoufian, H; Kruyt, FAE; dosSantos, CC; Wevrick, R; Buchwald, M

    1995-01-01

    Fanconi anemia (FA) is a recessively inherited disease characterized by bone marrow failure, congenital anomalies, chromosomal instability and hypersensitivity to crosslinking agents. Some of the cellular defects of FA defect are known to be responsive to the ambient oxygen concentration. We

  1. 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.

  2. [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.

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

    Science.gov (United States)

    1988-07-01

    perception during oxygen deficiency provided by Rose (1950a), Heinke (1942) used Koch’s depth percegtion testing apparatus on 11 subjects who were familiar ...1955), and ten Doesschate (1955) which were described above. Ohlbaum’s subjects were highly familiar with decompression and this may have been a...Richerche comparative sull’azione dell’anossta e dell’alcool da soli o associati. BRivisa 1 Medicina Aeronautica,. 12:198-210. Bietti, G. B., and Giardini, A

  4. 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

  5. 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.)

  6. Impact of Hyperglycemia and Low Oxygen Tension on Adipose-Derived Stem Cells Compared with Dermal Fibroblasts and Keratinocytes: Importance for Wound Healing in Type 2 Diabetes.

    Directory of Open Access Journals (Sweden)

    Aurore Lafosse

    Full Text Available Adipose-derived stem cells (ASC are currently proposed for wound healing in those with type 2 diabetes mellitus (T2DM. Therefore, this study investigated the impact of diabetes on adipose tissue in relation to ASC isolation, proliferation, and growth factor release and the impact of hyperglycemia and low oxygen tension (found in diabetic wounds on dermal fibroblasts, keratinocytes, and ASC in vitro.Different sequences of hypoxia and hyperglycemia were applied in vitro to ASC from nondiabetic (n = 8 or T2DM patients (n = 4 to study cell survival, proliferation, and growth factor release. Comparisons of dermal fibroblasts (n = 8 and keratinocytes (primary lineage were made.No significant difference of isolation and proliferation capacities was found in ASC from nondiabetic and diabetic humans. Hypoxia and hyperglycemia did not impact cell viability and proliferation. Keratinocyte Growth Factor release was significantly lower in diabetic ASC than in nondiabetic ASC group in each condition, while Vascular Endothelial Growth Factor release was not affected by the diabetic origin. Nondiabetic ASC exposition to hypoxia (0.1% oxygen combined with hyperglycemia (25mM glucose, resulted in a significant increase in VEGF secretion (+64%, p<0.05 with no deleterious impact on KGF release in comparison to physiological conditions (5% oxygen and 5 mM glucose. Stromal cell-Derived Factor-1α (-93%, p<0.001 and KGF (-20%, p<0.05 secretion by DF decreased in these conditions.A better profile of growth factor secretion (regarding wound healing was found in vitro for ASC in hyperglycemia coupled with hypoxia in comparison to dermal fibroblasts and keratinocytes. Interestingly, ASC from T2DM donors demonstrated cellular growth rates and survival (in hypoxia and hyperglycemic conditions similar to those of healthy ASC (from normoglycemic donors; however, KGF secretion was significantly depleted in ASC obtained from T2DM patients. This study demonstrated the impact of

  7. Tension Headache

    Science.gov (United States)

    ... your head Tenderness on your scalp, neck and shoulder muscles Tension headaches are divided into two main categories — ... that monitor and give you feedback on body functions such as muscle tension, heart rate and blood pressure. You then ...

  8. 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...

  9. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.

    2005-01-01

    oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer......oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer...

  10. 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

  11. Signal transduction pathway mediated by the novel regulator LoiA for low oxygen tension induced Salmonella Typhimurium invasion.

    Science.gov (United States)

    Jiang, Lingyan; Feng, Lu; Yang, Bin; Zhang, Wenwen; Wang, Peisheng; Jiang, Xiaohan; Wang, Lei

    2017-06-01

    Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major intestinal pathogen of both humans and animals. Salmonella pathogenicity island 1 (SPI-1)-encoded virulence genes are required for S. Typhimurium invasion. While oxygen (O2) limitation is an important signal for SPI-1 induction under host conditions, how the signal is received and integrated to the central SPI-1 regulatory system in S. Typhimurium is not clear. Here, we report a signal transduction pathway that activates SPI-1 expression in response to low O2. A novel regulator encoded within SPI-14 (STM14_1008), named LoiA (low oxygen induced factor A), directly binds to the promoter and activates transcription of hilD, leading to the activation of hilA (the master activator of SPI-1). Deletion of loiA significantly decreased the transcription of hilA, hilD and other representative SPI-1 genes (sipB, spaO, invH, prgH and invF) under low O2 conditions. The response of LoiA to the low O2 signal is mediated by the ArcB/ArcA two-component system. Deletion of either arcA or arcB significantly decreased transcription of loiA under low O2 conditions. We also confirmed that SPI-14 contributes to S. Typhimurium virulence by affecting invasion, and that loiA is the virulence determinant of SPI-14. Mice infection assays showed that S. Typhimurium virulence was severely attenuated by deletion of either the entire SPI-14 region or the single loiA gene after oral infection, while the virulence was not affected by either deletion after intraperitoneal infection. The signal transduction pathway described represents an important mechanism for S. Typhimurium to sense and respond to low O2 conditions of the host intestinal tract for invasion. SPI-14-encoded loiA is an essential element of this pathway that integrates the low O2 signal into the SPI-1 regulatory system. Acquisition of SPI-14 is therefore crucial for the evolution of S. Typhimurium as an intestinal pathogen.

  12. Signal transduction pathway mediated by the novel regulator LoiA for low oxygen tension induced Salmonella Typhimurium invasion.

    Directory of Open Access Journals (Sweden)

    Lingyan Jiang

    2017-06-01

    Full Text Available Salmonella enterica serovar Typhimurium (S. Typhimurium is a major intestinal pathogen of both humans and animals. Salmonella pathogenicity island 1 (SPI-1-encoded virulence genes are required for S. Typhimurium invasion. While oxygen (O2 limitation is an important signal for SPI-1 induction under host conditions, how the signal is received and integrated to the central SPI-1 regulatory system in S. Typhimurium is not clear. Here, we report a signal transduction pathway that activates SPI-1 expression in response to low O2. A novel regulator encoded within SPI-14 (STM14_1008, named LoiA (low oxygen induced factor A, directly binds to the promoter and activates transcription of hilD, leading to the activation of hilA (the master activator of SPI-1. Deletion of loiA significantly decreased the transcription of hilA, hilD and other representative SPI-1 genes (sipB, spaO, invH, prgH and invF under low O2 conditions. The response of LoiA to the low O2 signal is mediated by the ArcB/ArcA two-component system. Deletion of either arcA or arcB significantly decreased transcription of loiA under low O2 conditions. We also confirmed that SPI-14 contributes to S. Typhimurium virulence by affecting invasion, and that loiA is the virulence determinant of SPI-14. Mice infection assays showed that S. Typhimurium virulence was severely attenuated by deletion of either the entire SPI-14 region or the single loiA gene after oral infection, while the virulence was not affected by either deletion after intraperitoneal infection. The signal transduction pathway described represents an important mechanism for S. Typhimurium to sense and respond to low O2 conditions of the host intestinal tract for invasion. SPI-14-encoded loiA is an essential element of this pathway that integrates the low O2 signal into the SPI-1 regulatory system. Acquisition of SPI-14 is therefore crucial for the evolution of S. Typhimurium as an intestinal pathogen.

  13. 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.

  14. 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)

  15. Immunohistochemical detection of HIF-1α and CAIX in advanced head-and-neck cancer. Prognostic role and correlation with tumor markers and tumor oxygenation parameters

    International Nuclear Information System (INIS)

    Kappler, M.; Reddemann, R.; Rot, S.; Becker, A.; Kuhnt, T.; Dellas, K.; Haensgen, G.; Bache, M.; Taubert, H.; Holzhausen, H.J.; Dunst, J.; Vordermark, D.

    2008-01-01

    Background: tumor hypoxia has an impact on the outcome of cancer patients treated with radiotherapy. The validity of endogenous markers such as hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase isozyme IX (CAIX) to detect therapeutically relevant levels of hypoxia within tumors is controversially discussed. Furthermore, the association of these hypoxia markers with tumor markers or tumor oxygenation parameters is of importance for understanding the relationship between the different factors. Patients and methods: tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radio(chemo)therapy were assessed by immunohistochemistry for the expression of HIF-1α and CAIX. The relationships of both markers with tumor oxygenation parameters, molecular factors like P53, OPN, VEGF, VHL, survivin, and Ki67 levels, and clinical parameters were studied. Results: bivariate analysis showed a significant correlation of HIF-1α expression with high P53 and high OPN expression, high serum VEGF levels, and low VHL and low Ki67 expression. The CAIX expression was inversely correlated with pH value and directly correlated with T-stage. However, no correlation was found between HIF-1α and CAIX expression. Neither in a univariate Cox proportional hazard regression nor in a Kaplan-Meier analysis did expression of HIF-1α or CAIX have a significant impact on clinical outcome. However, in a Kaplan-Meier analysis, the combination of both factors showed that patients with intratumoral overexpression of either HIF-1α or CAIX or both markers died on average 2 years earlier than patients whose tumors had low expression of both factors (p < 0.05). Conclusion: expression of HIF-1α and CAIX was correlated with different tumor parameters. Only combined HIF-1α and CAIX expression was significantly predictive of patients' overall survival. (orig.)

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

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    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.

  17. Effects of low oxygen tension on gene profile of soluble growth factors in co-cultured adipose-derived stromal cells and chondrocytes.

    Science.gov (United States)

    Shi, Sirong; Xie, Jing; Zhong, Juan; Lin, Shiyu; Zhang, Tao; Sun, Ke; Fu, Na; Shao, Xiaoru; Lin, Yunfeng

    2016-06-01

    Moving towards development of optimized cartilage regeneration with adipose-derived stromal cells (ASCs), the focus of this study was on investigating the influence of hypoxia on soluble factors secreted by ASCs and chondrocytes after crosstalk. We established direct contact co-culture and non-contact co-culture systems by using red or green fluorescent protein (R/GFP)-labelled mice and SD rats respectively. Gene variation of growth factors of the two cell types, in both hypoxic and normoxic conditions, were screened using semi-quantitative polymerase chain reaction (PCR). Co-culture with ASCs and chondrocytes under hypoxia was shown to successfully induce or enhance ASC to chondrogenic differentiation. To be specific, chondrogenic maker genes: AGC, COL II and SOX9 were remarkably enhanced in both ASCs and chondrocytes after crosstalk under low oxygen tension. Subsequently, screening growth factors in ASCs and chondrocytes under hypoxia showed that HIF-1α, VEGF-A/B, BMP-2/-4/-6, FGF-2 and IGF-1 were significantly increased, but not TGF-β1. These results revealed that both hypoxia and co-culture systems can notably enhance chondrogenesis of ASCs as well as increase proliferation of ASCs and chondrocytes. © 2016 John Wiley & Sons Ltd.

  18. 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.

    Science.gov (United States)

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

    2011-04-01

    To assess postprocedural angiograms, the ankle-brachial index (ABI), and transcutaneous oxygen tension (TcPO₂) to predict outcome after infrageniculate angioplasty (PTA) in diabetic patients with critical limb ischemia (CLI) scheduled for amputation. 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 TcPO₂ of the foot. 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. TcPO₂ 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, TcPO₂ was capable of reliably predicting the outcome. 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. TcPO₂ was a valid predictor for limb salvage, even when angiographic outcome criteria failed.

  19. Monitoring of tumor oxygenation changes in head-and-neck carcinoma patients breathing a hyperoxic hypercapnic gas mixture with a noninvasive MRI technique

    International Nuclear Information System (INIS)

    Kotas, Markus; Flentje, Michael; Schmitt, Markus; Jakob, Peter M.

    2009-01-01

    Purpose: to implement and evaluate a noninvasive functional MRI technique for measuring tumor tissue oxygenation changes in head-and-neck carcinoma patients. Patients and methods: tissue oxygenation changes were determined quantitatively in 13 patients with head-and-neck cancer. The MR examinations were performed on a clinical MR scanner at 1.5 T. Different breathing gases (air, 2% CO 2 and 98% O 2 , 100% oxygen) were administered to induce oxygenation changes. A multigradient echo sequence was used for quantification of the apparent transverse relaxation time T2*. Results: pixel-by-pixel analysis of the T2* values in tumors showed a shift toward higher values corresponding to oxygenation increase and correlated with a median shift toward positive values in the ΔT2* fraction under carbogen and oxygen breathing in most but not all patients. A slightly pronounced T2* increase breathing oxygen compared with 2% CO 2 /98% O 2 was found. Furthermore, a statistically significant difference in the heterogeneity of oxygenation changes induced by oxygen or 2% CO 2 /98% O 2 breathing was seen. Conclusion: measurement of oxygenation changes in head-and-neck tumor patients is feasible by the presented MRI technique. Tumor oxygenation and oxygenation changes were heterogeneous among the investigated patients. To the authors' knowledge, they are the first to describe a statistically significant difference in the heterogeneity of oxygenation changes induced by oxygen or 2% CO 2 /98% O 2 breathing using a noninvasive MRI technique. (orig.)

  20. Studies of radiosensitizing effects of oxygen and/or perfluorochemical emulsion on 10 species of transplanted tumors in mice

    International Nuclear Information System (INIS)

    Nishikawa-Itoh, Youko

    1992-01-01

    We have previously reported that perfluorochemical emulsion in combination with breathing carbogen (95% O 2 +5% CO 2 ) showed to enhance the response of several solid rodent tumors to single dose and fractionated radiation treatment. In the present experiment, radiation-effect, oxygen-effect and radiosensitizing-effect of FDAS (one of the preparations of perfluorochemical emulsion, Fluosol-DA saline) were examined and compared in 10 kinds of murine experimental tumor (EMT6, FM3A, LLC, Meth-A, MH134, MM46, RIF1, S-180, SCCVII and Y-83). All of the tumors were found to be radiosensitive and the growth of them were delayed by radiation itself. The growth of tumors derived from RIF1, Y-83, LLC, S-180 were significantly delayed by radiation under breathing carbogen. The administration of FDAS to tumor-bearing mice and exposure of the mice to an atmosphere of carbogen significantly enhanced the radiation-induced suppression of the growth of EMT6, Y-83, MM46, MH134, FM3A, LLC, SCCVII and S-180 tumor. Radiosensitizing-effects of FDAS were more sensitive in carcinomas than in fibrosarcomas. It is suggested that FDAS may play effectively as a radiosensitizer in many tumors. The reason why various tumors showed different responses may be ascribed to the difference in type and proportion of hypoxic cells in each tumor. (author)

  1. 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.

  2. Low-dose candesartan improves renal blood flow and kidney oxygen tension in rats with endotoxin-induced acute kidney dysfunction.

    Science.gov (United States)

    Nitescu, Nicoletta; Grimberg, Elisabeth; Guron, Gregor

    2008-08-01

    Sepsis is associated with an activation of the renin-angiotensin system and causes acute kidney injury. The aim was to examine the effects of a low, nondepressor dose of the selective angiotensin II type 1 receptor antagonist candesartan on renal hemodynamics and function in endotoxemic rats. Endotoxemia was induced in Sprague-Dawley rats by a dose of LPS (Escherichia coli O127:B8; 7.5 mg kg(-1), i.p.). At 16 h after endotoxin administration, renal clearance experiments were performed in thiobutabarbital anesthetized rats. Study groups (1) sham-saline, (2) LPS-saline, and (3) LPS-candesartan received isotonic saline or candesartan (10 microg kg(-1), i.v.) after baseline measurements. Kidney function, renal blood flow (RBF), and cortical and outer medullary perfusion (laser-Doppler flowmetry) and oxygen tension (P(O2); Clark-type microelectrodes) were analyzed during 2 h after drug administration. At baseline, endotoxemic rats showed an approximately 50% reduction in glomerular filtration rate and RBF (P < 0.05), a decline in cortical and outer medullary perfusion, and Po2 (P < 0.05), but no significant alterations in MAP compared with saline-injected controls. Candesartan treatment significantly improved RBF (+40% +/- 6% vs. baseline), cortical perfusion (+18% +/- 3% vs. baseline), and cortical (+19% +/- 7% vs. baseline) and outer medullary (+22% +/- 10% vs. baseline) P(O2) in endotoxemic rats (P < 0.05 vs. LPS-saline). Candesartan did not significantly influence MAP or glomerular filtration rate, whereas filtration fraction was reduced by 27% +/- 5% vs. baseline (P < 0.05 vs. LPS-saline). In conclusion, candesartan, in a dose that did not significantly decrease MAP, caused renal vasodilation and markedly improved RBF and intrarenal P(O2) in endotoxemic rats. These findings suggest renoprotective effects of candesartan in sepsis.

  3. 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 <=100 mm3, for the four dose metrics light fluence, photosensitizer photobleaching rate, PDT dose and [1O2]rx. PDT dose is 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.

  4. Polymeric micelles of zinc protoporphyrin for tumor targeted delivery based on EPR effect and singlet oxygen generation.

    Science.gov (United States)

    Iyer, Arun K; Greish, Khaled; Seki, Takahiro; Okazaki, Shoko; Fang, Jun; Takeshita, Keizo; Maeda, Hiroshi

    2007-01-01

    Polymeric micelles of zinc protoporphyrin (ZnPP) with water soluble biocompatible and amphiphilic polymer, polyethylene glycol (PEG) demonstrated unique characteristics to target tumor tissues selectively based on the enhanced permeability and retention (EPR) effect. The micellar macromolecular drug of ZnPP (SMA-ZnPP and PEG-ZnPP) previously showed notable anticancer activity as a consequence of selective tumor targeting ability and its potent HO-1 inhibitory potential, resulting in suppressed biliverdin/bilirubin production in tumors thereby leading to oxystress induced tumor cell killing. Furthermore, recent findings also showed that ZnPP efficiently generated reactive singlet oxygen under illumination of visible light, laser, or xenon light source, which could augment its oxystress induced cell killing abilities. In the present paper, we report the synergistic effects of light induced photosensitizing capabilities and HO-1 inhibitory potentials of these unique micelles when tested in vitro and in vivo on tumor models under localized, mild illumination conditions using a tungsten-xenon light source. The results indicate that these water soluble polymeric micelles of ZnPP portend to be promising candidates for targeted chemotherapy as well as photodynamic therapy against superficial tumors as well as solid tumors located at light penetrable depths.

  5. NADPH oxidase subunit 4-mediated reactive oxygen species contribute to cycling hypoxia-promoted tumor progression in glioblastoma multiforme.

    Directory of Open Access Journals (Sweden)

    Chia-Hung Hsieh

    Full Text Available Cycling and chronic tumor hypoxia are involved in tumor development and growth. However, the impact of cycling hypoxia and its molecular mechanism on glioblastoma multiforme (GBM progression remain unclear.Glioblastoma cell lines, GBM8401 and U87, and their xenografts were exposed to cycling hypoxic stress in vitro and in vivo. Reactive oxygen species (ROS production in glioblastoma cells and xenografts was assayed by in vitro ROS analysis and in vivo molecular imaging studies. NADPH oxidase subunit 4 (Nox4 RNAi-knockdown technology was utilized to study the role of Nox4 in cycling hypoxia-mediated ROS production and tumor progression. Furthermore, glioblastoma cells were stably transfected with a retroviral vector bearing a dual reporter gene cassette that allowed for dynamic monitoring of HIF-1 signal transduction and tumor cell growth in vitro and in vivo, using optical and nuclear imaging. Tempol, an antioxidant compound, was used to investigate the impact of ROS on cycling hypoxia-mediated HIF-1 activation and tumor progression.Glioblastoma cells and xenografts were compared under cycling hypoxic and normoxic conditions; upregulation of NOX4 expression and ROS levels were observed under cycling hypoxia in glioblastoma cells and xenografts, concomitant with increased tumor cell growth in vitro and in vivo. However, knockdown of Nox4 inhibited these effects. Moreover, in vivo molecular imaging studies demonstrated that Tempol is a good antioxidant compound for inhibiting cycling hypoxia-mediated ROS production, HIF-1 activation, and tumor growth. Immunofluorescence imaging and flow cytometric analysis for NOX4, HIF-1 activation, and Hoechst 3342 in glioblastoma also revealed high localized NOX4 expression predominantly in potentially cycling hypoxic areas with HIF-1 activation and blood perfusion within the endogenous solid tumor microenvironment.Cycling hypoxia-induced ROS via Nox4 is a critical aspect of cancer biology to consider for

  6. The role of reactive oxygen species in tumor cells apoptosis induced by landomycin A

    Directory of Open Access Journals (Sweden)

    L. V. Lehka

    2015-10-01

    Full Text Available Landomycin A (LA is a new antitumor antibiotic of angucycline group, possessing high antitumor activity against cancer cells of different origin, which induces early apoptosis in target cells. It was shown that under LA action the level of reactive oxygen species (ROS in human T-leukemia cells had increased 5.6 times in comparison to control already at the 1st hour after the addition of studied antibiotic to the culture medium. At the 6th hour after incubation of cells with LA the nucleosomal DNA cleavage, chromatin condensation and nucleus fragmentation were observed, indicating apoptotic cell death. Catalase (scavenger of hydrogen peroxide, mannitol (scavenger of hydroxyl radicals and superoxide dismutase (scavenger of superoxide radicals reduced the level of ROS production under LA, suggesting the generation of H2O2, OH• and O2– radicals, respectively. It was revealed that catalase and mannitol effectively inhibited LA-mediated tumor cell death, increasing 2.5 times the percentage of alive cells in comparison to LA. However, superoxide dismutase had no significant inhibitory effect on cytotoxic activity of LA, indicating the minor role of superoxide anions in the implementation of antitumor activity of this antibiotic. Combination of catalase, mannitol and superoxide dismutase with LA increased 4-fold the percentage of alive cells in comparison to the action of LA. Dynamics of ROS formation confirms that the increase of ROS is a very rapid process, but at the same time it is not a direct consequence of apoptosis triggering, mediated by mitochondria

  7. In vivo determination of tumor oxygenation during growth and in response to carbogen breathing using 15C5-loaded alginate capsules as fluorine-19 magnetic resonance imaging oxygen sensors

    International Nuclear Information System (INIS)

    Noeth, Ulrike; Rodrigues, Loreta M.; Robinson, Simon P.; Jork, Anette; Zimmermann, Ulrich; Newell, Barry; Griffiths, John R.

    2004-01-01

    Purpose: The objective was to present a method for the repeated noninvasive measurement of tumor oxygenation (PO 2 ) over the whole period of tumor growth. Methods and materials: A mixture of tumor homogenate (GH3 prolactinoma) and alginate capsules loaded with perfluoro-15-crown-5-ether (15C5) was injected into the flanks of Wistar Furth rats. The temporal behavior of tumor PO 2 was monitored between Day 1 and 26 after injection using fluorine-19 ( 19 F) magnetic resonance imaging (MRI). In addition, the response of tumor PO 2 to modifiers of the tumor microenvironment (carbogen [95% O 2 /5% CO 2 ], nicotinamide, and hydralazine) was investigated. Results: An initial increase of tumor PO 2 , probably reflecting neovascularization, followed by a decrease after Week 2, probably indicating tumor hypoxia or necrosis, were observed. The minimum and maximum average PO 2 ± SEM observed were 3.3 ± 2.0 mm Hg on Day 2 and 25.7 ± 3.8 mm Hg on Day 13, respectively. Carbogen increased the tumor PO 2 , whereas nicotinamide caused no significant change and hydralazine induced a significant decrease in tumor oxygenation. Conclusions: A preclinical method for the repeated noninvasive determination of tumor PO 2 was presented. It might help to investigate tumor physiology and the mechanisms of modifiers of the tumor microenvironment and their role in different therapeutic approaches

  8. Role of endothelin ET(A) and ET(B) receptor subtypes in the regulation of intrarenal blood flow and oxygen tension in rats.

    Science.gov (United States)

    Nitescu, Nicoletta; Grimberg, Elisabeth; Herlitz, Hans; Guron, Gregor

    2008-10-01

    The aim of the present study was to investigate the role of endothelin ET(A) and ET(B) receptors in the regulation of intrarenal blood flow and oxygen tension in normotensive Sprague-Dawley rats. Thiobutabarbital anaesthetized rats were divided into four groups (n = 6-9 per group): (i) saline (4 mL/kg per h); (ii) BQ123; (iii) BQ788; and (iv) BQ123 + BQ788. After baseline measurements, the ET(A) receptor antagonist BQ-123 (30 nmol/kg per min, i.v.) and/or the ET(B) receptor antagonist BQ-788 (30 nmol/kg per min, i.v.), was administered for a period of 60 min. Total renal blood flow (RBF), cortical and outer medullary perfusion (laser-Doppler flowmetry) and Po(2) (Clark-type microelectrodes) were analysed throughout. At baseline, there were no significant differences between groups in mean arterial pressure (MAP), RBF, cortical and outer medullary perfusion and Po(2). Infusion of BQ-788 reduced RBF, cortical perfusion and outer medullary Po(2) (P < 0.05) and increased renal vascular resistance (P < 0.05) compared with saline-treated and BQ123 + BQ788-infused groups. BQ-123 and coinfusion of BQ-123 + BQ-788 increased outer medullary perfusion compared with the saline-treated group (P < 0.05) without significantly affecting outer medullary Po(2) and MAP. Neither selective nor combined ET(A) and ET(B) receptor antagonism significantly affected renal cortical Po(2). In conclusion, in normotensive rats, ET(B) receptor antagonism caused renal vasoconstriction and reduced RBF and cortical perfusion. Furthermore, ET(B) receptor antagonism decreased outer medullary Po(2). These effects were mediated by ET(A) receptor activation and are not due to a lack of ET(B) receptor activation per se. Finally, BQ-123 increased renal outer medullary perfusion, suggesting a tonic vasoconstrictor effect of ET(A) receptors in the medulla of normotensive rats.

  9. 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

  10. Correlation of pretreatment polarographically measured oxygen pressures with quantified contrast-enhanced power doppler ultrasonography in spontaneous canine tumors and their impact on outcome after radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Rohrer Bley, Carla; Laluhova, Dagmar [Section of Radiooncology, Vetsuisse Faculty, Univ. of Zurich (Switzerland); Roos, Malgorzata [Inst. for Social and Preventive Medicine, Medical Faculty, Univ. of Zurich (Switzerland); Kaser-Hotz, Barbara [Section of Radiooncology, Vetsuisse Faculty, Univ. of Zurich (Switzerland); Section Imaging Diagnostics, Vetsuisse Faculty, Univ. of Zurich (Switzerland); Ohlerth, Stefanie [Section Imaging Diagnostics, Vetsuisse Faculty, Univ. of Zurich (Switzerland)

    2009-11-15

    Purpose: to evaluate the use of noninvasive quantified contrast-enhanced power Doppler ultrasonography as a surrogate in the estimation of tumor hypoxia measured by invasive pO{sub 2} histography in canine tumors. Material and methods: data of pretreatment tumor oxygenation status, tumor vascularity and blood volume, and tumor response after radiation therapy was collected in 48 spontaneous malignant oral tumors (Table 1). Tumor oxygenation status was correlated to vascularity and blood volume, and influences on outcome after treatment were analyzed. Results: although vascularity and blood volume correlated moderately with median pO{sub 2} (r = 0.51 and 0.61; p = 0.001 and < 0.0001) and percentage of pO{sub 2} readings {<=} 2.5, 5, and 10 mmHg (r = -0.37 to -0.42; p < 0.01-0.03) for all tumors, they did not correlate within the different histology groups (p = 0.06-0.9). For all tumors, pretreatment oxygenation status, vascularity and blood volume were not found to be of prognostic value. Conclusion: these analyses show that quantified contrast-enhanced power Doppler ultrasonography does not represent a non-invasive indirect method to assess tumor hypoxia measured by invasive pO{sub 2} histography. Both technologies were nonprognostic indicators in spontaneous malignant canine oral tumors. (orig.)

  11. 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 <= 100 mm3 using four dose metrics: light fluence, photosensitizer photobleaching rate, PDT dose, and [1O2]rx. PDT dose was 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.

  12. 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.

  13. 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.

  14. 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...

  15. 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.

  16. Tumor Oxygen Dynamics as a Prognostic Indicator of Effective Antiangiogenic Therapy

    National Research Council Canada - National Science Library

    Zhao, Dawen

    2003-01-01

    ...: so called angiogenesis. One major goal of this project is to fully understand and precisely assess the dynamic changes in blood perfusion and oxygenation, both during normal growth and following anti-angiogenic therapy...

  17. Tumor Oxygen Dynamics as a Prognostic Indicator of Effective Antiangiogenic Therapy

    National Research Council Canada - National Science Library

    Zhao, Dawen

    2002-01-01

    ...: so called angiogenesis. One major goal of this project is to fully understand and precisely assess the dynamic changes in blood perfusion and oxygenation, both during normal growth and following anti-angiogenic therapy...

  18. 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

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

    Science.gov (United States)

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

    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 5mg·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 2.5mg·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. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. 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

  1. 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

  2. [Effect of solcoseryl on oxygen metabolism and growth of experimental tumors].

    Science.gov (United States)

    Mosienko, V S; Zagoruĭko, L I; Todor, I N; Khasanova, L T

    1987-01-01

    Antihypoxant and antitumour properties of solcoseryl were studied on intact and tumour-bearing rats and mice. By the polarographic method it is found that solcoseryl increases the oxygen metabolism only in animal hypoxic tissues and improves, probably, energy production of their mitochondria. On many tumour strains it is shown that the injections of solcoseryl decelerate the growth of some tumours, inhibit the metastatic process and produce no toxic effect on the animals.

  3. 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.)

  4. 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

  5. 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)

  6. Experimental studies on radiation effects under high pressure oxygen

    International Nuclear Information System (INIS)

    Fujimura, Eisuke

    1974-01-01

    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 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. (author)

  7. 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

  8. Evaluation and Immunohistochemical Qualification of Carbogen-Induced ΔR2* as a Noninvasive Imaging Biomarker of Improved Tumor Oxygenation

    International Nuclear Information System (INIS)

    Baker, Lauren C.J.; Boult, Jessica K.R.; Jamin, Yann; Gilmour, Lesley D.; Walker-Samuel, Simon; Burrell, Jake S.; Ashcroft, Margaret; Howe, Franklyn A.; Griffiths, John R.; Raleigh, James A.; Kogel, Albert J. van der; Robinson, Simon P.

    2013-01-01

    Purpose: To evaluate and histologically qualify carbogen-induced ΔR 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 2 * during air breathing. With the mouse remaining positioned within the magnet bore, the gas supply was switched to carbogen (95% O 2 , 5% CO 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 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 2 were further validated using the Oxylite fiberoptic probe. Results: Carbogen challenge significantly reduced mean tumor R 2 * from 116 ± 13 s −1 to 97 ± 9 s −1 (P 2 * and Δhypoxic fraction (r=0.55, P 2 during carbogen breathing significantly increased from 6.3 ± 2.2 mm Hg to 36.0 ± 7.5 mm Hg (P 2 * as a noninvasive imaging biomarker of increased tumor oxygenation

  9. 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.

  10. 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."

  11. Oxygen sensitive microwells.

    Science.gov (United States)

    Sinkala, Elly; Eddington, David T

    2010-12-07

    Oxygen tension is critical in a number of cell pathways but is often overlooked in cell culture. One reason for this is the difficulty in modulating and assessing oxygen tensions without disturbing the culture conditions. Toward this end, a simple method to generate oxygen-sensitive microwells was developed through embossing polystyrene (PS) and platinum(ii) octaethylporphyrin ketone (PtOEPK) thin films. In addition to monitoring the oxygen tension, microwells were employed in order to isolate uniform clusters of cells in microwells. The depth and width of the microwells can be adapted to different experimental parameters easily by altering the thin film processing or embossing stamp geometries. The thin oxygen sensitive microwell substrate is also compatible with high magnification modalities such as confocal imaging. The incorporation of the oxygen sensor into the microwells produces measurements of the oxygen tension near the cell surface. The oxygen sensitive microwells were calibrated and used to monitor oxygen tensions of Madin-Darby Canine Kidney Cells (MDCKs) cultured at high and low densities as a proof of concept. Wells 500 µm in diameter seeded with an average of 330 cells exhibited an oxygen level of 12.6% whereas wells seeded with an average of 20 cells per well exhibited an oxygen level of 19.5%, a 35.7% difference. This platform represents a new tool for culturing cells in microwells in a format amenable to high magnification imaging while monitoring the oxygen state of the culture media.

  12. 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

  13. 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.

  14. 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.

  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. 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.

  17. 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.

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

    Science.gov (United States)

    Shipp, Christopher; Derhovanessian, Evelyna; Pawelec, Graham

    2012-01-01

    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.

  19. 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.

  20. 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.

  1. Skin tension related to tension reduction sutures.

    Science.gov (United States)

    Hwang, Kun; Kim, Han Joon; Kim, Kyung Yong; Han, Seung Ho; Hwang, Se Jin

    2015-01-01

    The aim of this study was to compare the skin tension of several fascial/subcutaneous tensile reduction sutures. Six upper limbs and 8 lower limbs of 4 fresh cadavers were used. At the deltoid area (10 cm below the palpable acromion) and lateral thigh (midpoint from the palpable greater trochanter to the lateral border of the patella), and within a 3 × 6-cm fusiform area of skin, subcutaneous tissue defects were created. At the midpoint of the defect, a no. 5 silk suture was passed through the dermis at a 5-mm margin of the defect, and the defect was approximated. The initial tension to approximate the margins was measured using a tensiometer.The tension needed to approximate skin without any tension reduction suture (S) was 6.5 ± 4.6 N (Newton). The tensions needed to approximate superficial fascia (SF) and deep fascia (DF) were 7.8 ± 3.4 N and 10.3 ± 5.1 N, respectively. The tension needed to approximate the skin after approximating the SF was 4.1 ± 3.4 N. The tension needed to approximate the skin after approximating the DF was 4.9 ± 4.0 N. The tension reduction effect of approximating the SF was 38.8 ± 16.4% (2.4 ± 1.5 N, P = 0.000 [ANOVA, Scheffé]). The tension reduction effect of approximating the DF was 25.2% ± 21.9% (1.5 ± 1.4 N, P = 0.001 [ANOVA, Scheffé]). The reason for this is thought to be that the SF is located closely to the skin unlike the DF. The results of this study might be a basis for tension reduction sutures.

  2. Optical imaging for monitoring tumor oxygenation response after initiation of single-agent bevacizumab followed by cytotoxic chemotherapy in breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Shigeto Ueda

    Full Text Available PURPOSE: Optical imaging techniques for measuring tissue hemoglobin concentration have been recently accepted as a way to assess tumor vascularity and oxygenation. We investigated the correlation between early optical response to single-agent bevacizumab and treatment outcome. METHODS: Seven patients with advanced or metastatic breast cancer were treated with single-agent bevacizumab followed by addition of weekly paclitaxel. Optical imaging of patient's breasts was performed to measure tumor total hemoglobin concentration (tHb and oxygen saturation (stO2 at baseline and on days 1, 3, 6, 8, and 13 after the first infusion of bevacizumab. To assess early metabolic response, 2-deoxy-2-(18F-fluoro-D-glucose (FDG positron emission tomography/computed tomography (PET/CT, 18F-fluoromisonidazole (FMISO-PET/CT, and magnetic resonance imaging were performed at baseline and after two cycles of the regimen. RESULTS: Seven patients were grouped as responders (n = 4 and nonresponders (n = 3 on the basis of metabolic response measured by FDG-PET/CT. The responders showed remarkable tumor shrinkage and low accumulations of FMISO tracer relative to those of the nonresponders at the completion of two cycles of chemotherapy. Tumors of both groups showed remarkable attenuation of mean tHb as early as day 1 after therapy initiation. The nonresponders had lower baseline stO2 levels compared with adjacent breast tissue stO2 levels along with a pattern of steadily low stO2 levels during the observation window. On the other hand, the responders appeared to sustain high stO2 levels with temporal fluctuation. CONCLUSIONS: Low tumor stO2 level after single-agent bevacizumab treatment was characteristic of the nonresponders. Tumor stO2 level could be a predictor of an additional benefit of bevacizumab over that provided by paclitaxel.

  3. 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)

  4. 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

  5. Selective Induction of Tumor Cell Apoptosis by a Novel P450-mediated Reactive Oxygen Species (ROS) Inducer Methyl 3-(4-Nitrophenyl) Propiolate*

    Science.gov (United States)

    Sun, Xiaoxiao; Ai, Midan; Wang, Ying; Shen, Shensi; Gu, Yuan; Jin, Yi; Zhou, Zuyu; Long, Yaqiu; Yu, Qiang

    2013-01-01

    Induction of tumor cell apoptosis has been recognized as a valid anticancer strategy. However, therapeutic selectivity between tumor and normal cells has always been a challenge. Here, we report a novel anti-cancer compound methyl 3-(4-nitrophenyl) propiolate (NPP) preferentially induces apoptosis in tumor cells through P450-catalyzed reactive oxygen species (ROS) production. A compound sensitivity study on multiple cell lines shows that tumor cells with high basal ROS levels, low antioxidant capacities, and p53 mutations are especially sensitive to NPP. Knockdown of p53 sensitized non-transformed cells to NPP-induced cell death. Additionally, by comparing NPP with other ROS inducers, we show that the susceptibility of tumor cells to the ROS-induced cell death is influenced by the mode, amount, duration, and perhaps location of ROS production. Our studies not only discovered a unique anticancer drug candidate but also shed new light on the understanding of ROS generation and function and the potential application of a ROS-promoting strategy in cancer treatment. PMID:23382387

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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…

  11. 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...

  12. Imaging hypoxia after oxygenation-modification: comparing [18F]FMISO autoradiography with pimonidazole immunohistochemistry in human xenograft tumors.

    NARCIS (Netherlands)

    Troost, E.G.C.; Laverman, P.; Kaanders, J.H.A.M.; Philippens, M.E.P.; Lok, J.; Oyen, W.J.G.; Kogel, A.J. van der; Boerman, O.C.; Bussink, J.

    2006-01-01

    PURPOSE: Hypoxia is one of the reasons for radiation therapy resistance. Positron emission tomography using (18)F-labeled misonidazole ([(18)F]FMISO) is a non-invasive method of imaging tumor hypoxia. Aim of this study was to validate [(18)F]FMISO against the clinically most widely used hypoxic cell

  13. 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.

  14. 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...

  15. 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.

  16. Strings with zero tension

    Energy Technology Data Exchange (ETDEWEB)

    Amorim, R.; Barcelos-Neto, J.

    1988-05-01

    We describe bosonic strings by using a kind of Lagrangian compatible with the zero tension limit. The work is developed on an extended configuration space and the quantization is carried out with details.

  17. 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...

  18. 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.

  19. Obesity Decreases Perioperative Tissue Oxygenation

    Science.gov (United States)

    Kabon, Barbara; Nagele, Angelika; Reddy, Dayakar; Eagon, Chris; Fleshman, James W.; Sessler, Daniel I.; Kurz, Andrea

    2005-01-01

    Background: Obesity is an important risk factor for surgical site infections. The incidence of surgical wound infections is directly related to tissue perfusion and oxygenation. Fat tissue mass expands without a concomitant increase in blood flow per cell, which might result in a relative hypoperfusion with decreased tissue oxygenation. Consequently, we tested the hypotheses that perioperative tissue oxygen tension is reduced in obese surgical patients. Furthermore, we compared the effect of supplemental oxygen administration on tissue oxygenation in obese and non-obese patients. Methods: Forty-six patients undergoing major abdominal surgery were assigned to one of two groups according to their body mass index (BMI): BMI < 30 kg/m2 (non-obese) and BMI ≥ 30 kg/m2 (obese). Intraoperative oxygen administration was adjusted to arterial oxygen tensions of ≈150 mmHg and ≈300 mmHg in random order. Anesthesia technique and perioperative fluid management were standardized. Subcutaneous tissue oxygen tension was measured with a polarographic electrode positioned within a subcutaneous tonometer in the lateral upper arm during surgery, in the recovery room, and on the first postoperative day. Postoperative tissue oxygen was also measured adjacent to the wound. Data were compared with unpaired two tailed t-tests and Wilcoxon rank-sum tests; P < 0.05 was considered statistically significant. Results: Intraoperative subcutaneous tissue oxygen tension was significantly less in the obese patients at baseline (36 vs. 57 mmHg, P = 0.002) and with supplemental oxygen administration (47 vs. 76 mmHg, P = 0.014). Immediate postoperative tissue oxygen tension was also significantly less in subcutaneous tissue of the upper arm (43 vs. 54 mmHg, P = 0.011) as well as near the incision (42 vs. 62 mmHg, P = 0.012) in obese patients. In contrast, tissue oxygen tension was comparable in each group on the first postoperative morning. Conclusion: Wound and tissue hypoxia were common in obese

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

    Science.gov (United States)

    Chen, Guozhu; Zhang, Xuhui; Zhao, Ming; Wang, Yan; Cheng, Xiang; Wang, Di; Xu, Yuanji; Du, Zhiyan; Yu, Xiaodan

    2011-05-14

    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. 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. 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. Moreover, the inhibition of MRC complex I activity

  1. 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

  2. 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.

  3. 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

  4. 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

  5. Responses of Solid Tumor Cells in DMEM to Reactive Oxygen Species Generated by Non-Thermal Plasma and Chemically Induced ROS Systems

    Science.gov (United States)

    Kaushik, Neha; Uddin, Nizam; Sim, Geon Bo; Hong, Young June; Baik, Ku Youn; Kim, Chung Hyeok; Lee, Su Jae; Kaushik, Nagendra Kumar; Choi, Eun Ha

    2015-02-01

    In this study, we assessed the role of different reactive oxygen species (ROS) generated by soft jet plasma and chemical-induced ROS systems with regard to cell death in T98G, A549, HEK293 and MRC5 cell lines. For a comparison with plasma, we generated superoxide anion (O2-), hydroxyl radical (HO.), and hydrogen peroxide (H2O2) with chemicals inside an in vitro cell culture. Our data revealed that plasma decreased the viability and intracellular ATP values of cells and increased the apoptotic population via a caspase activation mechanism. Plasma altered the mitochondrial membrane potential and eventually up-regulated the mRNA expression levels of BAX, BAK1 and H2AX gene but simultaneously down-regulated the levels of Bcl-2 in solid tumor cells. Moreover, a western blot analysis confirmed that plasma also altered phosphorylated ERK1/2/MAPK protein levels. At the same time, using ROS scavengers with plasma, we observed that scavengers of HO. (mannitol) and H2O2 (catalase and sodium pyruvate) attenuated the activity of plasma on cells to a large extent. In contrast, radicals generated by specific chemical systems enhanced cell death drastically in cancer as well as normal cell lines in a dose-dependent fashion but not specific with regard to the cell type as compared to plasma.

  6. Superstrings with zero tension

    Energy Technology Data Exchange (ETDEWEB)

    Barcelos-Neto, J.; Ruiz-Altaba, M. (European Organization for Nuclear Research, Geneva (Switzerland). Theory Div.)

    1989-09-14

    The superstring in the limit of vanishing tension is analyzed with the help of a phase space lagrangian. We show that our formulation is the supersymmetric extension of Schild's null string and that all the symmetries of the standard Green-Schwarz theory are maintained. The null superstring thus arises as a new theoretical laboratory, its complexity between the usual superstring and the massless superparticle. Its canonical quantization is carried through in detail. (orig.).

  7. 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.

  8. Intratumoral oxygen gradients mediate sarcoma cell invasion

    Science.gov (United States)

    Lewis, Daniel M.; Park, Kyung Min; Tang, Vitor; Xu, Yu; Pak, Koreana; Eisinger-Mathason, T. S. Karin; Simon, M. Celeste; Gerecht, Sharon

    2016-01-01

    Hypoxia is a critical factor in the progression and metastasis of many cancers, including soft tissue sarcomas. Frequently, oxygen (O2) gradients develop in tumors as they grow beyond their vascular supply, leading to heterogeneous areas of O2 depletion. Here, we report the impact of hypoxic O2 gradients on sarcoma cell invasion and migration. O2 gradient measurements showed that large sarcoma mouse tumors (>300 mm3) contain a severely hypoxic core [≤0.1% partial pressure of O2 (pO2)] whereas smaller tumors possessed hypoxic gradients throughout the tumor mass (0.1–6% pO2). To analyze tumor invasion, we used O2-controllable hydrogels to recreate the physiopathological O2 levels in vitro. Small tumor grafts encapsulated in the hydrogels revealed increased invasion that was both faster and extended over a longer distance in the hypoxic hydrogels compared with nonhypoxic hydrogels. To model the effect of the O2 gradient accurately, we examined individual sarcoma cells embedded in the O2-controllable hydrogel. We observed that hypoxic gradients guide sarcoma cell motility and matrix remodeling through hypoxia-inducible factor-1α (HIF-1α) activation. We further found that in the hypoxic gradient, individual cells migrate more quickly, across longer distances, and in the direction of increasing O2 tension. Treatment with minoxidil, an inhibitor of hypoxia-induced sarcoma metastasis, abrogated cell migration and matrix remodeling in the hypoxic gradient. Overall, we show that O2 acts as a 3D physicotactic agent during sarcoma tumor invasion and propose the O2-controllable hydrogels as a predictive system to study early stages of the metastatic process and therapeutic targets. PMID:27486245

  9. 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.

  10. 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...

  11. Immunomodulatory effect of oxygen and pressure

    NARCIS (Netherlands)

    van den Blink, B.; van der Kleij, A. J.; Versteeg, H. H.; Peppelenbosch, M. P.

    2002-01-01

    The immunomodulatory effect of hyperbaric oxygen, involving altered cytokine release by macrophages. is well described. Importantly, however, it is not known what the relative contribution is of the hyperbaric environment of the cells vs. increased oxygen tension on these hyperbaric oxygen-dependent

  12. 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.

  13. 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.

  14. 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)

  15. Hyperbaric oxygen and perfluorochemicals in radiotherapy

    International Nuclear Information System (INIS)

    Fischer, J.J.

    1987-01-01

    Malignant tumors are thought to contain radioresistant hypoxic cells which limit curability with radiation therapy. Attempts to improve tumor oxygenation by breathing oxygen under increased pressure have been only marginally successful. To improve oxygenation, the partial pressure must be increased throughout the capillary bed and must remain elevated as oxygen is consumed. Theoretical calculations predict that the combination of perfluorochemical micelles and hyperbaric oxygen could provide the necessary amount of oxygen at sufficiently high partial pressure to meet these requirements. Fluosol-DA (Alpha Therapeutic Corporation) and hyperbaric oxygen significantly reduce the hypoxic fraction in experimental rodent tumors

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

    International Nuclear Information System (INIS)

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

    1997-01-01

    To determine appropriate use of 2-[ 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 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

  17. 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....

  18. 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.

  19. Combined MR and Optical Imaging System for Noninvasive Tumor Characterization and Quantification of Oxygenation Gain Factor in a Breast Cancer Animal Model

    National Research Council Canada - National Science Library

    Shafiiha, Roshanak

    2007-01-01

    This study proposes to modify and improve an existing MR-compatible optical tomography system that is used for non-invasive tumor characterization and provides higher sensitivity and specificity for cancer imaging...

  20. Modeling Corneal Oxygen with Scleral Gas Permeable Lens Wear.

    Science.gov (United States)

    Compañ, Vicente; Aguilella-Arzo, Marcel; Edrington, Timothy B; Weissman, Barry A

    2016-11-01

    The main goal of this current work is to use an updated calculation paradigm, and updated boundary conditions, to provide theoretical guidelines to assist the clinician whose goal is to improve his or her scleral gas permeable (GP) contact lens wearing patients' anterior corneal oxygen supply. Our model uses a variable value of corneal oxygen consumption developed through Monod equations that disallows negative oxygen tensions within the stroma to predict oxygen tension at the anterior corneal surface of scleral GP contact lens wearing eyes, and to describe oxygen tension and flux profiles, for various boundary conditions, through the lens, tears, and cornea. We use several updated tissue and boundary parameters in our model. Tear exchange with GP scleral lenses is considered nonexistent in this model. The majority of current scleral GP contact lenses should produce some levels of corneal hypoxia under open eye conditions. Only lenses producing the thinnest of tear vaults should result in anterior corneal surface oxygen tensions greater than a presumed critical oxygen tension of 100 mmHg. We also find that corneal oxygen tension and flux are each more sensitive to modification in tear vault than to changes in lens oxygen permeability, within the ranges of current clinical manipulation. Our study suggests that clinicians would be prudent to prescribe scleral GP lenses manufactured from higher oxygen permeability materials and especially to fit without excessive corneal clearance.

  1. Oxygen Therapy

    Science.gov (United States)

    ... best for you. Oxygen is usually delivered through nasal prongs (an oxygen cannula) or a face mask. Oxygen equipment can attach to other medical equipment such as CPAP machines and ventilators. Oxygen therapy can help you ...

  2. Oxygen consumption of Callianassa kraussi Stebbing ...

    African Journals Online (AJOL)

    Oxygen consumption experiments were performed on the thalassinid prawn, Callianassa kraussi Stabbing, using an open flow system coupled to a Radiometer electrode and a continuous recorder. The effect of starvation, sex, body size, salinity, temperature, seasons and reduced oxygen tensions on the respiratory rates of ...

  3. Monitoring Cancer Oxygenation Changes Induced by Ultrasound

    National Research Council Canada - National Science Library

    Piao, Daqing

    2004-01-01

    ...) The oxygenation changes can be detected by optical measurements. Preliminary studies with 5 tumor-bearing rats demonstrate that ultrasonic vibrations can either generate significant effects (early stage tumors...

  4. Abolishing the maximum tension principle

    Directory of Open Access Journals (Sweden)

    Mariusz P. Da̧browski

    2015-09-01

    Full Text Available We find the series of example theories for which the relativistic limit of maximum tension Fmax=c4/4G represented by the entropic force can be abolished. Among them the varying constants theories, some generalized entropy models applied both for cosmological and black hole horizons as well as some generalized uncertainty principle models.

  5. Portfolios: Assumptions, Tensions, and Possibilities.

    Science.gov (United States)

    Tierney, Robert J.; Clark, Caroline; Fenner, Linda; Herter, Roberta J.; Simpson, Carolyn Staunton; Wiser, Bert

    1998-01-01

    Presents a discussion between two educators of the history, assumptions, tensions, and possibilities surrounding the use of portfolios in multiple classroom contexts. Includes illustrative commentaries that offer alternative perspectives from a range of other educators with differing backgrounds and interests in portfolios. (RS)

  6. 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 ...

  7. CALCULATION OF TENSION FORCE OF BELT CONVEYOR

    OpenAIRE

    Ismet Ibishi; Ahmet Latifi; Gzim Ibishi; Kadri Sejdiu; Melihate Shala-Galica; Bekim Latifi

    2012-01-01

    In this paper is done the explanation on tension fashion of the belt conveyor which is employed in Kosovo Energy Corporation – KEK, for coal transportation to provide electric power plant. The aim of the paper enables to recognize tension forces not to pass with deformation of belt so that this problem will damage the workingprocess. Work principle is based on initial tension and tension during working process. The fact is known that the tension starts from the carriage on the way to tension ...

  8. 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

  9. Tensions of Corporate Social Responsibility

    DEFF Research Database (Denmark)

    Strand, Robert

    I engaged with the top management team (TMT) and employees of American Cafes Corporation as an action/intervention researcher in the 20 months immediately following the TMT’s decision to formalize the company’s corporate social responsibility (CSR) activities. This led to the establishment...... CSR agenda is considered, which brings with it a multiplicity of substantively rational ends for which the corporation could pursue. I show the CSR bureaucracy can create a space for reflection in which the multiplicity of substantively rational ends can be considered, negotiated, and selected...... for reflection within the corporation. But I also show tensions can arise from the establishment of the CSR bureaucracy itself. This suggests the CSR bureaucracy itself resides in a tension....

  10. 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.

  11. Mediastinal tumor

    Science.gov (United States)

    Thymoma - mediastinal; Lymphoma - mediastinal ... mediastinal tumors in adults occur in the anterior mediastinum. They are usually cancerous (malignant) lymphomas, germ cell tumors, or thymomas. These tumors are ...

  12. Intraoperative Magnetic Resonance Imaging of Cerebral Oxygen Metabolism During Resection of Brain Lesions.

    Science.gov (United States)

    Stadlbauer, Andreas; Merkel, Andreas; Zimmermann, Max; Sommer, Björn; Buchfelder, Michael; Meyer-Bäse, Anke; Rössler, Karl

    2017-04-01

    Tissue oxygen tension is an important parameter for brain tissue viability and its noninvasive intraoperative monitoring in the whole brain is of highly clinical relevance. The purpose of this study was the introduction of a multiparametric quantitative blood oxygenation dependent magnetic resonance imaging (MRI) approach for intraoperative examination of oxygen metabolism during the resection of brain lesions. Sixteen patients suffering from brain lesions were examined intraoperatively twice (before craniotomy and after gross-total resection) via the quantitative blood oxygenation dependent technique and a 1.5-Tesla MRI scanner, which is installed in an operating room. The MRI protocol included T2*- and T2 mapping and dynamic susceptibility weighted perfusion. Data analysis was performed with a custom-made, in-house MatLab software for calculation of maps of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) as well as of cerebral blood volume and cerebral blood flow. Perilesional edema showed a significant increase in both perfusion (cerebral blood volume +21%, cerebral blood flow +13%) and oxygen metabolism (OEF +32%, CMRO 2  +16%) after resection of the lesions. In perilesional nonedematous tissue only, however, oxygen metabolism (OEF +19%, CMRO 2  +11%) was significantly increased, but not perfusion. No changes were found in normal brain. Fortunately, no neurovascular adverse events were observed. This approach for intraoperative examination of oxygen metabolism in the whole brain is a new application of intraoperative MRI additionally to resection control (residual tumor detection) and updating of neuronavigation (brain shift detection). It may help to detect neurovascular adverse events early during surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. 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.

  14. [Role of tumor microenvironment in the formation and progression of skin melanoma].

    Science.gov (United States)

    Olbryt, Magdalena

    2013-05-14

    Melanoma develops from melanocytes localized mainly in skin, to a lesser extent in uvea and mucosal tissue. It is one of the most aggressive tumors, resistant to standard therapies. It is caused mainly by UV radiation. Approximately 10% of melanomas have a familial background. Transformation of melanocytes is driven mainly by mutations in genes coding for proteins regulating proliferation, cell growth, cell cycle, and death. Although genetic changes are indisputable causes of melanoma formation, the key role of the skin microenvironment is becoming more and more acknowledged. Normal cells of the skin, such as keratinocytes, fibroblasts, endothelial, and immune cells, alongside melanocytes constitute a special microenvironment in which disturbed homeostasis may facilitate melanoma development. The process of transformation is initiated by aberrant interaction of keratinocytes and melanocytes. Proliferation and invasive growth of the developing neoplasm may be further facilitated by myofibroblasts as well as macrophages residing within the tumor. They are able to stimulate angiogenesis and suppress the immune response. Macrophages may, additionally, create aggressive hybrid cells through fusion with melanoma cells. Indispensable in the process of metastasis are endothelial cells which co-form blood vessels, the main routes of tumor cells' seeding. All of the aforementioned processes take place in a tumor growth-promoting atmosphere of low oxygen tension in the skin, further decreasing during tumor growth. Probably the tumor growth-promoting microenvironment is one of the main factors responsible for melanoma aggressiveness.

  15. Origen de la Cefalea Tensional

    OpenAIRE

    Romero Godoy, Rosalinda; Romero Godoy, Sara Raquel

    2010-01-01

    Introducción y objetivos: La cefalea es una de las causas de consulta médica más comunes y el síntoma más frecuente consultado en neurología. La prevalencia según estudios estadísticos nacionales es de un 62% en hombres y un 86% en mujeres. De todas las cefaleas la cefalea tensional es la más común, pero la menos estudiada y conocida. Nos hemos propuesto hacer una revisión actual sobre la etiopatogenia en las cefaleas tensionales que nos pueda orientar a futuras investigaciones. ...

  16. Oxygen Therapy

    Science.gov (United States)

    ... oxygen at very high altitudes (like in the mountains or in an airplane) even if you do ... an arterial blood gas (ABG) measurement. The ABG measures your oxygen level directly from your blood and ...

  17. 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.

  18. Adipose tissue oxygenation: Effects on metabolic function

    OpenAIRE

    Hodson, Leanne

    2013-01-01

    With the increasing prevalence of obesity there is a concomitant increase in white adipose tissue dysfunction, with the tissue moving toward a proinflammatory phenotype. Adipose tissue hypoxia has been proposed as a key underlying mechanism triggering tissue dysfunction but data from human, in vivo studies, to support this hypothesis is limited. Human adipose tissue oxygenation has been investigated by direct assessment of tissue oxygen tension (pO2) or by expression of hypoxia-sensitive gene...

  19. 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.

  20. 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

  1. The Plastic Tension Field Method

    DEFF Research Database (Denmark)

    Hansen, Thomas

    2005-01-01

    . The emphasis is attached to the presentation of a design method based on the diagonal tension field theory. Also, how to determine the load-carrying capacity of a given steel plate girder with transverse web stiffeners, is briefly presented. The load-carrying capacity may be predicted by applying both...... 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......, but the method presented differs from these theories by incorporating the strength of the transverse stiffeners and by the assumption that the tensile bands may pass the transverse stiffeners, which often is observed in tests. Other methods have only dealt with a single web field between two stiffeners...

  2. 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....

  3. 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.

  4. 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

  5. Endogenous Bone Regeneration Is Dependent Upon a Dynamic Oxygen Event

    Science.gov (United States)

    2014-01-01

    exogenous induction. This makes P3 amputation an excellent model in which to study the effects of oxygen during regeneration. That oxygen tensions fluctuate...mechanisms to drug development. Antioxid Redox Signal. 2010; 13: 1593-616. 39. Ruiz JC, Walker SD, Anderson SA, Eisenstein RS and Bruick RK. F-box

  6. Oxygen consumption and responses of the freshwater snail Bulinus ...

    African Journals Online (AJOL)

    A gradient or choice apparatus, based on the 'fluvarium' principle and suitable for testing the responses of the freshwater snail Bulinus (Physopsis) globosus to different partial oxygen tensions was used. In a gradual oxygen gradient established with this apparatus, B. (P.) globosus shows a significant preference for ...

  7. Tumor necrosis factor-alpha and apoptosis signal-regulating kinase 1 control reactive oxygen species release, mitochondrial autophagy, and c-Jun N-terminal kinase/p38 phosphorylation during necrotizing enterocolitis.

    Science.gov (United States)

    Baregamian, Naira; Song, Jun; Bailey, C Eric; Papaconstantinou, John; Evers, B Mark; Chung, Dai H

    2009-01-01

    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 (TNF)-alpha 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 TNF-alpha/ROS on mitochondrial function, ASK1-JNK/p38 cascade activation in intestinal epithelial cells during NEC. We found (a) abundant tissue TNF-alpha and ASK1 expression throughout all layers of the intestine in neonates with NEC, suggesting that TNF-alpha/ASK1 may be a potential source (indicators) of intestinal injury in neonates with NEC; (b) TNF-alpha-induced rapid and transient activation of JNK/p38 apoptotic signaling in all cell lines suggests that this may be an important molecular characteristic of NEC; (c) TNF-alpha-induced rapid and transient ROS production in RIE-1 cells indicates that mitochondria are the predominant source of ROS, demonstrated by significantly attenuated response in mitochondrial DNA-depleted (RIE-1-rho) intestinal epithelial cells; (d) further studies with mitochondria-targeted antioxidant PBN supported our hypothesis that effective mitochondrial ROS trapping is protective against TNF-alpha/ROS-induced intestinal epithelial cell injury; (e) TNF-alpha induces significant mitochondrial dysfunction in intestinal epithelial cells, resulting in increased production of mtROS, drop in mitochondrial membrane potential (MMP) and decreased oxygen consumption; (f) although the significance of mitochondrial autophagy in NEC has not been unequivocally shown, our studies provide a strong preliminary indication that TNF-alpha/ROS-induced mitochondrial autophagy may play a role in NEC, and this process is a

  8. 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…

  9. 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

    2017-11-01

    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 of surface tension through simple experiments.

  10. Intraoperative Development of Tension Pneumocephalus in a ...

    African Journals Online (AJOL)

    Rapid buildup of gas within the cranial vault can result in a life‑threatening condition known as “tension pneumocephalus,” necessitating immediate surgical intervention. Nitrous oxide (N2O), a commonly used inhaled anesthetic, is associated with the development of tension pneumocephalus and its role in neurosurgical ...

  11. 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 ...

  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. 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.

  14. 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.

  15. 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.

  16. 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.

  17. No oxygen delivery limitation in hepatic encephalopathy

    DEFF Research Database (Denmark)

    Gjedde, Albert; Keiding, Susanne; Vilstrup, Hendrik

    2010-01-01

    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...... declined in all gray matter regions of the brain in patients with HE but not significantly in patients with CL. Analysis of flow-metabolism coupling indicated that blood flow declined in HE as a consequence of reduced brain energy metabolism implied by the calculation of increased mitochondrial oxygen...... tensions that patients with HE were unable to utilize. We ascribe the inability to use the delivered oxygen of patients with HE to a specific inhibition associated with oxidative metabolism in mitochondria....

  18. 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

  19. Tension-related activity in the orbitofrontal cortex and amygdala: an fMRI study with music.

    Science.gov (United States)

    Lehne, Moritz; Rohrmeier, Martin; Koelsch, Stefan

    2014-10-01

    Tonal music is characterized by a continuous flow of tension and resolution. This flow of tension and resolution is closely related to processes of expectancy and prediction and is a key mediator of music-evoked emotions. However, the neural correlates of subjectively experienced tension and resolution have not yet been investigated. We acquired continuous ratings of musical tension for four piano pieces. In a subsequent functional magnetic resonance imaging experiment, we identified blood oxygen level-dependent signal increases related to musical tension in the left lateral orbitofrontal cortex (pars orbitalis of the inferior frontal gyrus). In addition, a region of interest analysis in bilateral amygdala showed activation in the right superficial amygdala during periods of increasing tension (compared with decreasing tension). This is the first neuroimaging study investigating the time-varying changes of the emotional experience of musical tension, revealing brain activity in key areas of affective processing. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  20. 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

  1. Tumor vaccines

    International Nuclear Information System (INIS)

    Frank, M.; Ihan, A.

    2006-01-01

    Tumor vaccines have several potential advantages over standard anticancer regiments. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tumor vaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which immune tolerance exists. That is why the population of tumor-specific lymphocytes is represented by a small number of low-affinity T-lymphocytes that induce weak antitumor immune response. Simultaneously, tumors evolve many mechanisms to actively evade immune system, what makes them poorly immunogenic or even tolerogenic. Novel immunotherapeutic strategies are directed toward breaking immune tolerance to tumor antigens, enhancing immunogenicity of tumor vaccines and overcoming mechanisms of tumor escape. There are several approaches, unfortunately, all of them still far away from an ideal tumor vaccine that would reject a tumor. Difficulties in the activation of antitumor immune response by tumor vaccines have led to the development of alternative immunotherapeutic strategies that directly focus on effector mechanisms of immune system (adoptive tumor- specific T-lymphocyte transfer and tumor specific monoclonal antibodies). (author)

  2. 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.

  3. Foundation design for high tension cable guardrails.

    Science.gov (United States)

    2010-06-01

    High tension cable guardrail is becoming increasing popular in median and roadside applications due to the promise of reduced deflections upon impact and reduced maintenance. As the performance of these systems is observed in service, there is a grow...

  4. Modelling Tension Stiffening in Reinforced Concrete Structures

    DEFF Research Database (Denmark)

    Christiansen, Morten Bo; Nielsen, Mogens Peter

    1997-01-01

    Part I of the present thesis deals with crack formation in reinforced concrete and the phenomenon of tension stiffening in concrete tension rods reinforced with deformed bars.Two physical models are presented for uniaxial tension, and they are modified for application on beams subjected to pure...... predicted by the models are compared with experimental data from tests on tension rods as well as flexural beams.In the light of the simple assumptions made and the random nature of cracking, the accordance between the models and the test data is quite good.Part II of the present thesis deals...... flexure.In the first model, the yield zone model, it is assumed that the mean crack distance is a descending function of the reinforcement stress in a crack. Furthermore it is assumed that in certain zones between the cracks the concrete is carrying its full effective tensile strength, i.e. the concrete...

  5. 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

  6. 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.

  7. Oxygen diffusion and consumption in extracellular matrix gels: implications for designing three-dimensional cultures.

    Science.gov (United States)

    Colom, Adai; Galgoczy, Roland; Almendros, Isaac; Xaubet, Antonio; Farré, Ramon; Alcaraz, Jordi

    2014-08-01

    Three-dimensional (3D) cultures are increasingly used as tissue surrogates to study many physiopathological processes. However, to what extent current 3D culture protocols provide physiologic oxygen tension conditions remains ill defined. To address this limitation, oxygen tension was measured in a panel of acellular or cellularized extracellular matrix (ECM) gels with A549 cells, and analyzed in terms of oxygen diffusion and consumption. Gels included reconstituted basement membrane, fibrin and collagen. Oxygen diffusivity in acellular gels was up to 40% smaller than that of water, and the lower values were observed in the denser gels. In 3D cultures, physiologic oxygen tension was achieved after 2 days in dense (≥3 mg/mL) but not sparse gels, revealing that the latter gels are not suitable tissue surrogates in terms of oxygen distribution. In dense gels, we observed a dominant effect of ECM composition over density in oxygen consumption. All diffusion and consumption data were used in a simple model to estimate ranges for gel thickness, seeding density and time-window that may support physiologic oxygen tension. Thus, we identified critical variables for oxygen tension in ECM gels, and introduced a model to assess initial values of these variables, which may short-cut the optimization step of 3D culture studies. © 2013 Wiley Periodicals, Inc.

  8. Porphyromonas gingivalis-induced production of reactive oxygen species, tumor necrosis factor-α, interleukin-6, CXCL8 and CCL2 by neutrophils from localized aggressive periodontitis and healthy donors: modulating actions of red blood cells and resolvin E1.

    Science.gov (United States)

    Damgaard, C; Kantarci, A; Holmstrup, P; Hasturk, H; Nielsen, C H; Van Dyke, T E

    2017-04-01

    Porphyromonas gingivalis is regarded as a significant contributor in the pathogenesis of periodontitis and certain systemic diseases, including atherosclerosis. P. gingivalis occasionally translocates from periodontal pockets into the circulation, where it adheres to red blood cells (RBCs). This may protect the bacterium from contact with circulating phagocytes without affecting its viability. In this in vitro study, we investigated whether human peripheral blood neutrophils from 10 subjects with localized aggressive periodontitis (LAgP) and 10 healthy controls release the proinflammatory cytokines interleukin (IL)-6, tumor necrosis factor α (TNF-α), the chemokine (C-X-C motif) ligand 8 (CXCL8; also known as IL-8) and chemokine (C-C motif) ligand 2 (CCL2; also known as monocyte chemotactic protein-1) and intracellular reactive oxygen species (ROS) in response to challenge with P. gingivalis. In addition, the impact of RBC interaction with P. gingivalis was investigated. The actions of resolvin E1 (RvE1), a known regulator of P. gingivalis induced neutrophil responses, on the cytokine and ROS responses elicited by P. gingivalis in cultures of neutrophils were investigated. Upon stimulation with P. gingivalis, neutrophils from subjects with LAgP and healthy controls released similar quantities of IL-6, TNF-α, CXCL8, CCL2 and intracellular ROS. The presence of RBCs amplified the release of IL-6, TNF-α and CCL2 statistically significant in both groups, but reduced the generation of ROS in the group of healthy controls, and showed a similar tendency in the group of subjects with LAgP. RvE1 had no impact on the production of intracellular ROS, TNF-α, IL-6, CXCL8 and CCL2 by neutrophils from either group, but tended to reduce the generation of ROS in subjects with LAgP in the absence of RBCs. Our data support that binding to RBCs protects P. gingivalis from ROS and concomitantly enhances neutrophil release of proinflammatory cytokines providing a selective

  9. 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.

  10. 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.)

  11. Mammary tumors

    International Nuclear Information System (INIS)

    Weller, R.E.

    1988-10-01

    Mammary neoplasia is one of the more common malignancies affecting domestic species. Despite their importance, they are often over- diagnosed, undertreated and subject to several misconceptions propagated by veterinarians and pet owners alike. Mammary neoplasia is the most frequent tumor type encountered in the female accounting for almost half of all malignancies reported. The canine has the highest incidence of mammary tumors of all domestic species. In the dog, about 65 percent of mammary tumors are benign mixed tumors, and 25 percent are carcinomas. The rest are adenomas, myoepitheliomas, and malignant mixed tumors. The age distribution of mammary tumors closely follows the age distribution of most tumors in the dog. Mammary tumors are rare in dogs 2 years old, but incidence begins to increase sharply at approximately 6 years of age. Median age at diagnosis is about 10 years. No breed predilection has been consistently reported

  12. Tensile mechanical behavior of hollow and filled carbon nanotubes under tension or combined tension-torsion

    Science.gov (United States)

    Jeong, Byeong-Woo; Lim, Jang-Keun; Sinnott, Susan B.

    2007-01-01

    The tensile mechanical behavior of hollow and filled single-walled carbon nanotubes under tension or combined tension-torsion is examined using classical molecular dynamics simulations. These simulations indicate that the tensile strength under combined tension-torsion can be increased by filling the carbon nanotubes, and the amount of this increase depends on the kind of filling material. They also predict that the tensile strength under combined tension-torsion decreases linearly under applied torsion. The tensile strength can be modified by adjusting the system temperature and through chemical functionalization to the carbon nanotube walls.

  13. 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

  14. Hyperoxia does not affect oxygen delivery in healthy volunteers while causing a decrease in sublingual perfusion.

    Science.gov (United States)

    Smit, Bob; Smulders, Yvo M; Eringa, Etto C; Gelissen, Harry P M M; Girbes, Armand R J; de Grooth, Harm-Jan S; Schotman, Hans H M; Scheffer, Peter G; Oudemans-van Straaten, Heleen M; Spoelstra-de Man, Angelique M E

    2018-02-01

    To determine the human dose-response relationship between a stepwise increase in arterial oxygen tension and its associated changes in DO 2 and sublingual microcirculatory perfusion. Fifteen healthy volunteers breathed increasing oxygen fractions for 10 minutes to reach arterial oxygen tensions of baseline (breathing air), 20, 40, 60 kPa, and max kPa (breathing oxygen). Systemic hemodynamics were measured continuously by the volume-clamp method. At the end of each period, the sublingual microcirculation was assessed by SDF. Systemic DO 2 was unchanged throughout the study (P slope  = .8). PVD decreased in a sigmoidal fashion (max -15% while breathing oxygen, SD18, P slope  = .001). CI decreased linearly (max -10%, SD10, P slope  fashion. All hemodynamic changes appear negligible up to an arterial oxygen tension of 20 kPa. © 2017 The Authors. Microcirculation Published by John Wiley & Sons Ltd.

  15. 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

  16. 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.

  17. 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 ...

  18. Intraoperative monitoring of brain tissue oxygen and carbon dioxide pressures reveals low oxygenation in peritumoral brain edema

    NARCIS (Netherlands)

    Pennings, Frederik A.; Bouma, Gerrit J.; Kedaria, Mohan; Jansen, Gerard F. A.; Bosch, D. Andries

    2003-01-01

    Brain edema and swelling often complicate surgery for brain tumors. Its pathophysiology is unclear, as is the relationship with brain tissue oxygenation. Our hypothesis was that brain edema around tumor is cytotoxic type caused by impaired local tissue oxygenation due to increased local tissue

  19. 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.

  20. 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

  1. Needle Decompression of Tension Pneumothorax Tactical Combat Casualty Care Guideline Recommendations

    Science.gov (United States)

    2012-07-06

    pleural space at either the second ICS at the MCL or the fourth or fifth ICS AAL and is not suitable for optimal use in ND. 1, 4 The majority of...Consider chest tube insertion if no improvement and/or long transport is anticipated. c. Most combat casualties do not require supplemental oxygen...JG, Kerr ST, et al.: Needle versus tube thoracostomy in a swine model of traumatic tension hemopneumpothorax Prehosp Emerg Care. 2009; 13:18-27 3

  2. Tension Distribution in a Tendon-Driven Robotic Finger

    Science.gov (United States)

    Abdallah, Muhammad E. (Inventor); Platt, Robert (Inventor); Wampler, II, Charles W. (Inventor)

    2013-01-01

    A method is provided for distributing tension among tendons of a tendon-driven finger in a robotic system, wherein the finger characterized by n degrees of freedom and n+1 tendons. The method includes determining a maximum functional tension and a minimum functional tension of each tendon of the finger, and then using a controller to distribute tension among the tendons, such that each tendon is assigned a tension value less than the maximum functional tension and greater than or equal to the minimum functional tension. The method satisfies the minimum functional tension while minimizing the internal tension in the robotic system, and satisfies the maximum functional tension without introducing a coupled disturbance to the joint torques. A robotic system includes a robot having at least one tendon-driven finger characterized by n degrees of freedom and n+1 tendons, and a controller having an algorithm for controlling the tendons as set forth above.

  3. TBK1 duplication is found in normal tension and not in high tension ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 95; Issue 2. TBK1 duplication is found in normal tension and not in high tension glaucoma patients of Indian origin. LALIT KAURANI MANSI VISHAL JHARNA RAY ABHIJIT SEN KUNAL RAY ARIJIT MUKHOPADHYAY. RESEARCH NOTE Volume 95 Issue 2 June 2016 pp 459- ...

  4. TBK1 duplication is found in normal tension and not in high tension ...

    Indian Academy of Sciences (India)

    Supplementary data: TBK1 duplication is found in normal tension and not in high tension glaucoma patients of Indian origin. Lalit Kaurani, Mansi Vishal, Jharna Ray, Abhijit Sen, Kunal Ray and Arijit Mukhopadhyay. J. Genet. 95, 459–461. Table 1. Intraocular pressure of NTG and HTG patients. Total. Mean IOP. Mean IOP ...

  5. Percutaneous tension band wiring for patellar fractures.

    Science.gov (United States)

    Rathi, Akhilesh; Swamy, M K S; Prasantha, I; Consul, Ashu; Bansal, Abhishek; Bahl, Vibhu

    2012-08-01

    To evaluate outcome of percutaneous tension band wiring for transverse fractures of the patella. 16 men and 7 women aged 27 to 65 (mean, 40) years underwent percutaneous tension band wiring for transverse fractures of the patella with a displacement of >3 mm. Pain, operating time, mobility, functional score, and complications were evaluated. 20 patients underwent successful percutaneous tension band wiring. The remaining 3 patients in whom closed reduction failed underwent open reduction and tension band wiring. The mean operating time was 46 (range, 28-62) minutes. The mean follow-up period was 20 (range, 15-30) months. At the latest follow-up, all patients had regained full extension. The objective score was excellent in 20 patients and good in 3, whereas the subjective score was excellent in 17, good in 5, and fair in one. All patients had radiological union at week 8. One patient had patellofemoral arthritis (secondary to a postoperative articular step). Two patients developed superficial infections, which resolved after antibiotic therapy. Mean thigh muscle wasting was 0.7 (range, 0.4-1) cm. Three patients encountered hardware problems (impingement/irritation of the skin over the knee) necessitating implant removal. Percutaneous tension band wiring is a viable option for transverse fractures of the patella.

  6. 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.

  7. 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 ...

  8. 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.

  9. Role of tumor microenvironment in the formation and progression of skin melanoma

    Directory of Open Access Journals (Sweden)

    Magdalena Olbryt

    2013-05-01

    Full Text Available Melanoma develops from melanocytes localized mainly in skin, to a lesser extent in uvea and mucosal tissue. It is one of the most aggressive tumors, resistant to standard therapies. It is caused mainly by UV radiation. Approximately 10�0of melanomas have a familial background. Transformation of melanocytes is driven mainly by mutations in genes coding for proteins regulating proliferation, cell growth, cell cycle, and death. Although genetic changes are indisputable causes of melanoma formation, the key role of the skin microenvironment is becoming more and more acknowledged. Normal cells of the skin, such as keratinocytes, fibroblasts, endothelial, and immune cells, alongside melanocytes constitute a special microenvironment in which disturbed homeostasis may facilitate melanoma development. The process of transformation is initiated by aberrant interaction of keratinocytes and melanocytes. Proliferation and invasive growth of the developing neoplasm may be further facilitated by myofibroblasts as well as macrophages residing within the tumor. They are able to stimulate angiogenesis and suppress the immune response. Macrophages may, additionally, create aggressive hybrid cells through fusion with melanoma cells. Indispensable in the process of metastasis are endothelial cells which co-form blood vessels, the main routes of tumor cells’ seeding. All of the aforementioned processes take place in a tumor growth-promoting atmosphere of low oxygen tension in the skin, further decreasing during tumor growth. Probably the tumor growth-promoting microenvironment is one of the main factors responsible for melanoma aggressiveness.

  10. 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

  11. 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.

  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. Reactive oxygen species in cancer: a dance with the devil.

    Science.gov (United States)

    Schumacker, Paul T

    2015-02-09

    Reactive oxygen species (ROS) can initiate cancer, but oxidant generation in tumors leaves them vulnerable to further stresses. In this issue of Cancer Cell, Harris and colleagues show that augmenting oxidant stress in normal cells limits tumor initiation and progression. Hence, strategic targeting of antioxidant systems may undermine survival of new tumor cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Tumor vaccines:

    OpenAIRE

    Frank, Mojca; Ihan, Alojz

    2006-01-01

    Tumor vaccines have several potential advantages over standard anticancer regirrcents. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tccmor aaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which imrrtune tol...

  15. 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...

  16. El metamodelo meditativo y cefalea tensional. The meditative metamodel and tensional headache.

    OpenAIRE

    Bestard Bizet, Rafael; Batista González, Antonio; Escobar de la Torre, José Carlos; Bestard Silva, Dalia Del Carmen

    2014-01-01

    El metamodelo meditativo y cefalea tensional. The meditative metamodel and tensional headache. Resumen. La cefalea tensional se ha convertido en un verdadero fustigador de la sociedad moderna ocasionando verdaderos estragos en la salud y en la economía colectiva e individual. Aunque se hacen ingentes esfuerzos por paliar sus nefastos efectos, estos todavía resultan insuficientes e ineficientes. El presente trabajo constituye el primer intento en nuestro país de evaluar la efectividad de la me...

  17. 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.

  18. On the role of the string tension

    Energy Technology Data Exchange (ETDEWEB)

    Amorim, R.; Barcelos-Neto, J. (Universidade Federal do Rio de Janeiro, RJ (Brazil). Inst. de Fisica)

    1991-01-10

    We study in detail the role played by the tension in the quantum algebra of constraints for bosonic and spinning strings, from the point of view of the BRST/BFV formalism. We observe why the well-known critical dimensions D=10 and D=26 can survive in the tensionless case. (orig.).

  19. Five tensions between science and democracy

    Energy Technology Data Exchange (ETDEWEB)

    Guston, D.J.

    1995-12-31

    The historical aspects of dialogue between the scientific establishments and the congress are used to illustrate and define the continuing tensions between these parties since 1880. Five areas are addressed as how best to cope and deal with the issues which in all probability will not go away. 1 ref.

  20. 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.

  1. 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…

  2. Multiple Intelligences: Its Tensions and Possibilities

    Science.gov (United States)

    Eisner, Elliot W.

    2004-01-01

    This article explores the tensions between Howard Gardner's theory of multiple intelligences and current educational policies emphasizing standardized and predictable outcomes. The article situates Gardner's theory within the historical interests among psychometricians in identifying those core processes that constitute human intelligence.…

  3. The tension nose: open structure rhinoplasty approach.

    Science.gov (United States)

    Johnson, C M; Godin, M S

    1995-01-01

    The term tension nose is known to many rhinoplastic surgeons, yet confusion exists as to its precise meaning. We define the tension deformity as excessive growth of the quadrilateral cartilage, resulting in a high nasal dorsum and anterior and sometimes inferior displacement of the nasal tip cartilages. A review of the surgical literature shows that little attention has been given to the evaluation and management of this problem. We reviewed 50 consecutive primary rhinoplasty candidates and found that 46 percent had some manifestation of tension deformity that required correction at the time of surgery. The techniques of open structure rhinoplasty are ideally suited to manage the tension nose. The essence of correction is a deprojection-reprojection process. First, excessive elements of the septal cartilage and anterior nasal spine, which comprise what we have termed the nasal pedestal, are reduced, resulting in tip deprojection. Open structure methods are then employed to achieve reprojection of the domes by using cartilage grafts and suturing techniques to build strength, support, and elegance into the nasal tip.

  4. Tenure Tensions: Out in the Enchanted Forest

    Science.gov (United States)

    Tyler, Jo A.

    2010-01-01

    The tenure track in higher education represents a path shrouded in a fair degree of mystery. This essay provides the perspective of a middle-aged, second-career tenure track faculty member on the vagaries of progressing down the track as an out lesbian. Three dialectics that build tension into the process--covering-creating, evaluation-liberation,…

  5. Influence of colour symmetry on string tension

    International Nuclear Information System (INIS)

    Yukalov, V.I.; Yukalova, E.P.; Shanenko, A.A.

    1994-01-01

    The ratio of the fundamental string tension in the SU(3) pure (quarkless) gauge theory to that in the SU(2) gluonic system is estimated within a statistical model approach to the description of the QCD thermodynamics. The obtained estimation is in agreement with the lattice evaluation of the ratio. 9 refs

  6. Surface tension of aqueous electrolyte solutions. Thermodynamics

    NARCIS (Netherlands)

    Drzymala, J.; Lyklema, J.

    2012-01-01

    A thermodynamic theory is developed for obtaining the enthalpic and entropic contributions to the surface excess Gibbs energy of electrolyte solutions from the dependence of the surface tension on concentration and temperature. For elaboration, accurate activity coefficients in solution as functions

  7. Normal tension glaucoma and Alzheimer disease

    DEFF Research Database (Denmark)

    Bach-Holm, Daniella; Kessing, Svend Vedel; Mogensen, Ulla

    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...

  8. 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…

  9. 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…

  10. 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.

    Science.gov (United States)

    Song, Changhoon; Hong, Beom-Ju; Bok, Seoyeon; Lee, Chan-Ju; Kim, Young-Eun; Jeon, Sang-Rok; Wu, Hong-Gyun; Lee, Yun-Sang; Cheon, Gi Jeong; Paeng, Jin Chul; Carlson, David J; Kim, Hak Jae; Ahn, G-One

    2016-07-01

    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. 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 [(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. 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. 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 slightly by day 6. Our results indicate that single

  11. 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

    International Nuclear Information System (INIS)

    Song, Changhoon; Hong, Beom-Ju; Bok, Seoyeon; Lee, Chan-Ju; Kim, Young-Eun; Jeon, Sang-Rok; Wu, Hong-Gyun; Lee, Yun-Sang; Cheon, Gi Jeong; Paeng, Jin Chul; Carlson, David J.

    2016-01-01

    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 [ 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

  12. 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

  13. 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

  14. Carcinoid Tumors

    Science.gov (United States)

    ... spread to other parts of the body. Doctors don't know what causes the mutations that can lead to carcinoid tumors. But they know that carcinoid tumors develop in neuroendocrine cells. Neuroendocrine cells are found in various organs throughout the body. They perform some nerve cell ...

  15. Magnetic Resonance Spectroscopic Imaging of Tumor Metabolic Markers for Cancer Diagnosis, Metabolic Phenotyping, and Characterization of Tumor Microenvironment

    OpenAIRE

    He, Qiuhong; Xu, Ray Z.; Shkarin, Pavel; Pizzorno, Giuseppe; Lee-French, Carol H.; Rothman, Douglas L.; Shungu, Dikoma C.; Shim, Hyunsuk

    2004-01-01

    Cancer cells display heterogeneous genetic characteristics, depending on the tumor dynamic microenvironment. Abnormal tumor vasculature and poor tissue oxygenation generate a fraction of hypoxic tumor cells that have selective advantages in metastasis and invasion and often resist chemo- and radiation therapies. The genetic alterations acquired by tumors modify their biochemical pathways, which results in abnormal tumor metabolism. An elevation in glycolysis known as the “Warburg effect” and ...

  16. 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...... is to enhance the initial failure stress of the glass and to obtain ductile (post-breakage) performance. From four-point bending tests on the post-tensioned glass beam specimens it is observed that these goals are reached. From the test results it is concluded that post-tensioning glass beams is a feasible...

  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. 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.

  19. Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen

    DEFF Research Database (Denmark)

    Mathiesen, Claus; Brazhe, Alexey; Thomsen, Kirsten Joan

    2013-01-01

    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....

  20. Tension pneumocephalus following suboccipital sitting craniotomy in the pediatric population.

    Science.gov (United States)

    Daszkiewicz, P; Dziedzic, D

    Sitting craniotomy often results in entrapment of air in fluid-filled intracranial cavities. Gas under pressure exerts a deleterious effect on adjacent nervous tissue, resulting in clinical deterioration. To assess the incidence of tension pneumocephalus (TP) and to define risk factors associated therewith. Analysis included 100 consecutive patients (57 boys, 43 girls, mean age 9.7 y) undergoing suboccipital sitting craniotomy since 2012 to 2014. In our material (n=100) TP was seen in 7 cases, asymptomatic pneumocephalus (AP) in 77 and no pneumocephalus (NP) in 16. Tumor types encountered were typical for pediatric population. In the TP group (n=7) the ratio of low-grade to high-grade tumors was 5:2, in the AP group (n=77) 2:1 and in the NP group (n=16) 1:1. Preoperative hydrocephalus was present in 21 cases (21%, mean incidence), thereof 3 in the TP group (3/7; 42.8%), 12 in AP group (12/77; 15.5%) and 6 in the NP group (6/16; 37.5%). All TP patients received an emergency external drainage, thereof 4 required a permanent ventriculo-peritoneal shunt (57.1%), while AP and NP patients combined (n=93) required a permanent shunt in 4 cases only (4.3%). TP-associated morbidity (n=2) consisted in a significant deterioration of neurological condition. TP is a relatively rare but potentially serious complication of suboccipital sitting craniotomy. Risk factors for TP are low-grade tumor and pre-existing long-standing hydrocephalus. TP requires emergency decompression by temporary external drainage. TP patients significantly more often require a permanent CSF shunt. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

  1. 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.

  2. Static tensioning promotes hamstring tendons force relaxation more reliably than cycling tensioning.

    Science.gov (United States)

    Piedade, Sérgio Rocha; Dal Fabbro, Inácio Maria; Mischan, Martha Maria; Piedade, Cezar; Maffulli, Nicola

    2017-08-01

    Graft elongation might be a major reason for increased anterior laxity after anterior cruciate ligament (ACL) reconstruction. This study analyzed the force relaxation values and their stabilization when single strands of the gracilis and semitendinosus tendons underwent cyclic and static tensioning at 2.5% strain level, and compared the efficiency of static and cyclic tensioning in promoting force relaxation. Eighteen gracilis tendons and 18 semitendinosus tendons from nine male cadavers (mean age: 22.44years) were subjected to 10 in vitro cyclic loads at 2.5% strain level, or to a static load at 2.5% strain level. During cyclic loading, the reduction in force values tended to stabilize after the sixth cyclic load, while, in the case of static loading, this stabilization occurred by the second minute. Comparing static and cyclic loading, the gracilis tendon had similar mechanical responses in both conditions, while the semitendinosus tendon showed greater force relaxation in static compared with cyclic loading. Considering that the semitendinosus tendon is the main component of the hamstring graft, its biomechanical response to loading should guide the tensioning protocol. Therefore, static tensioning seems more effective for promoting force relaxation of the semitendinosus tendon than cyclic tensioning. The gracilis tendon showed a similar mechanical response to either tensioning protocols. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. 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.'

  4. 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.

  5. 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

  6. Surface and interfacial tension measurement, theory, and applications

    CERN Document Server

    Hartland, Stanley

    2004-01-01

    This edited volume offers complete coverage of the latest theoretical, experimental, and computer-based data as summarized by leading international researchers. It promotes full understanding of the physical phenomena and mechanisms at work in surface and interfacial tensions and gradients, their direct impact on interface shape and movement, and their significance to numerous applications. Assessing methods for the accurate measurement of surface tension, interfacial tension, and contact angles, Surface and Interfacial Tension presents modern simulations of complex interfacial motions, such a

  7. 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...

  8. 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.

  9. Tumor Markers

    Science.gov (United States)

    ... only a small number of people will test positive for the disease who do not have it—in other words, it will result in very few false-positive results. Although tumor markers are extremely useful in ...

  10. Tumor Grade

    Science.gov (United States)

    ... Peer Review and Funding Outcomes Step 4: Award Negotiation & Issuance Manage Your Award Grants Management Contacts Monitoring ... may require immediate or more aggressive treatment. The importance of tumor grade in planning treatment and determining ...

  11. Tending the tensions in co-creation

    DEFF Research Database (Denmark)

    Phillips, Louise Jane

    -creation as a process of mutual learning to be valued at least as much as the outcome AND the neoliberal instrumentalisation of creativity in the service of social innovation and economic growth. The papers build on the themes of Knowledge and Power in Collaborative Research: A Reflexive Approach (Phillips, Kristiansen......Across fields of social practice, the harnessing of creativity in collaborative, dialogic processes of knowledge production is championed as a means to empower participants as agents and generate practice change. ‘Collaboration’, ‘dialogue’ and ‘participation’ have become buzzwords with a taken......-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...

  12. Surface tension and deformation in soft adhesion

    Science.gov (United States)

    Jensen, Katharine

    Modern contact mechanics was originally developed to account for the competition between adhesion and elasticity for relatively stiff deformable materials like rubber, but much softer sticky materials are ubiquitous in biology, engineering, and everyday consumer products. In such soft materials, the solid surface tension can also play an important role in resisting shape change, and significantly modify the physics of contact with soft matter. We report indentation and pull-off experiments that bring small, rigid spheres into adhesive contact with compliant silicone gel substrates, varying both the surface functionalization of the spheres and the bulk elastic properties of the gels. We map the resulting deformation profiles using optical microscopy and image analysis. We examine the substrate geometry in light of capillary and elastic theories in order to explore the interplay of surface tension and bulk elasticity in governing soft adhesion.

  13. Tensions of Teaching Media Literacy in Teacher Education

    Science.gov (United States)

    Ngomba-Westbrook, Nalova Elaine

    2013-01-01

    This study investigates the tensions a teacher educator faces in facilitating a media literacy teacher education course at the university level. Teaching tensions are conceptualized as a three-tier framework. At the first level, tensions may arise in the selection and application of pedagogies associated with critical and new/21st century…

  14. Line tension and the shape of nanodroplets.

    Science.gov (United States)

    Schimmele, L; Dietrich, S

    2009-12-01

    Various factors are discussed which might influence the equilibrium contact angle of nanodroplets placed on a solid substrate. Special emphasis is put on the possible role of the dependence of the solid-liquid interface tension [Formula: see text] on the pressure in the liquid, which in nanodrops considerably exceeds the saturation pressure. We show that certain published data regarding that dependence are meaningless because these have been deduced based on an inconsistent data analysis.

  15. 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....

  16. 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)

  17. 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.

  18. 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

  19. Tumor Types: Understanding Brain Tumors

    Science.gov (United States)

    Search Menu Facebook Twitter YouTube Flickr Instagram LinkedIn Brain Tumor Information | News & Blog Our Mission Our History Mission Leadership & Staff Financials Careers News & Blog Contact Us Donate Now Our Impact Our Impact Recent News News & ...

  20. Mitochondrial reactive oxygen species accelerate gastric cancer cell invasion.

    Science.gov (United States)

    Tamura, Masato; Matsui, Hirofumi; Tomita, Tsutomu; Sadakata, Hisato; Indo, Hiroko P; Majima, Hideyuki J; Kaneko, Tsuyoshi; Hyodo, Ichinosuke

    2014-01-01

    Tumor invasion is the most important factor to decide patient's prognosis. The relation between reactive oxygen species and tumor invasion is mainly reported that nicotinamide adenine dinucleotide phosphate oxidase in the cell membrane is a reactive oxygen species producer for formulating an invadopodia. On the other hand, mitochondrion was known as one of the most important reactive oxygen species-producer in the cell via an energy transfer system. However, the relation between mitochondrial reactive oxygen species and the tumor invasion was not well clarified. In this study, we evaluated the relation between mitochondrial reactive oxygen species and tumor invasion using a normal gastric mucosal cell-line (RGM-1) and a cancerous mutant RGM-1 cell-line (RGK-1). Manganese superoxide dismutase-expressing RGK-1 cell-lines were used for a scavenging mitochondrial reactive oxygen species. The cells have been evaluated their movement ability as follows; cellular ruffling frequencies, wound healing assay to evaluate horizontal cellular migration, and invasion assay using matrigel to analyze vertical cellular migration. All cellular movement abilities were inhibited by scavenging mitochondrial reactive oxygen species with manganese superoxide dismutase. Therefore mitochondrial reactive oxygen species was one of factors enhancing the tumor invasion in gastric cancer.

  1. Mediastinal tumors

    International Nuclear Information System (INIS)

    Canizares, Claudio; Araujo, Ivan; Rodriguez, Amparo; Robles, Wilson; Simba, Catalina

    2005-01-01

    In our practice the mediastinal tumors are infrequent. The mediastinum is the portion of the thoracic cavity that contains numerous organs and structures which makes a crossroad for the diagnostic process. Within which congenital cysts, inflammatory and benign tumors, malignant neoplasms may develop. In the superior compartment are found: thymoma and thymic cysts, germ cell tumors, thyroid lesions, parathyroid adenomas, malignant lymphomas, paragangliomas, hemangiomas, lipomas, and inflammatory lesions such as fibrosing mediastinitis. In the middle portion: pericardial cysts, bronchial cysts, malignant lymphomas. In the posterior region: neurogenic tumors such as Shawnomas, neurofibromas, ganglioneuroblastomas, neuroblastomas, paragangliomas, and gastro enteric cysts. We describe two cases. One of a female patient with a prominent tumor in the anterior compartment of the mediastinum, detected by the x-ray films. Initially a cardiac lesion was excluded by echographic, angiographic studies. The biopsy exhibited a prominent fibrosis that suggested fibrosing mediastinitis (sclerosing). Whoever the immunohistochemical phenotype was positive for lambda chains, determining the diagnosis of lymphoma. The other case is of a young male with a thymoma associated to a pure red cell aplasia, which was the initial clinical symptom. Computerized tomography and thyroid scintigraphy was used. (The author)

  2. Actomyosin tension as a determinant of metastatic cancer mechanical tropism

    Science.gov (United States)

    McGrail, Daniel J.; Kieu, Quang Minh N.; Iandoli, Jason A.; Dawson, Michelle R.

    2015-04-01

    Despite major advances in the characterization of molecular regulators of cancer growth and metastasis, patient survival rates have largely stagnated. Recent studies have shown that mechanical cues from the extracellular matrix can drive the transition to a malignant phenotype. Moreover, it is also known that the metastatic process, which results in over 90% of cancer-related deaths, is governed by intracellular mechanical forces. To better understand these processes, we identified metastatic tumor cells originating from different locations which undergo inverse responses to altered matrix elasticity: MDA-MB-231 breast cancer cells that prefer rigid matrices and SKOV-3 ovarian cancer cells that prefer compliant matrices as characterized by parameters such as tumor cell proliferation, chemoresistance, and migration. Transcriptomic analysis revealed higher expression of genes associated with cytoskeletal tension and contractility in cells that prefer stiff environments, both when comparing MDA-MB-231 to SKOV-3 cells as well as when comparing bone-metastatic to lung-metastatic MDA-MB-231 subclones. Using small molecule inhibitors, we found that blocking the activity of these pathways mitigated rigidity-dependent behavior in both cell lines. Probing the physical forces exerted by cells on the underlying substrates revealed that though force magnitude may not directly correlate with functional outcomes, other parameters such as force polarization do correlate directly with cell motility. Finally, this biophysical analysis demonstrates that intrinsic levels of cell contractility determine the matrix rigidity for maximal cell function, possibly influencing tissue sites for metastatic cancer cell engraftment during dissemination. By increasing our understanding of the physical interactions of cancer cells with their microenvironment, these studies may help develop novel therapeutic strategies.

  3. 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.)

  4. Tension Pneumocephalus Related to Radiotherapy for Nasopharyngeal Carcinoma

    Directory of Open Access Journals (Sweden)

    Esther Jimenez-Jimenez

    2014-01-01

    Full Text Available Introduction. Tension pneumocephalus (TP is a very rare complication related to radiotherapy for nasopharyngeal carcinoma (NPC. Case Presentation. A 46-year-old man was admitted to the hospital with an altered mental status and aqueous rhinorrhea for several hours of evolution. The computed tomography (CT scan showed TP, a defect in the skull base and nasocranial fistula. The patient was receiving a second course of radiotherapy for local relapse. With medical treatment the patient recovered neurological status but died two days later. Discussion. In our knowledge, only 4 cases with similar characteristics have been reported in the literature. This is the first case report of TP during radiotherapy. TP was an abrupt and rapid process with neurological impairment for hours of evolution without suspicious osteoradionecrosis (OR in previous scan images. The defect in the skull base could be due to a rapid disappearance of the tumor. The appearance of aqueous rhinorrhea and neurological symptoms must be viewed as signs of alarm.

  5. 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.

  6. 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.

  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. Incorporating Oxygen-Enhanced MRI into Multi-Parametric Assessment of Human Prostate Cancer.

    Science.gov (United States)

    Zhou, Heling; Hallac, Rami R; Yuan, Qing; Ding, Yao; Zhang, Zhongwei; Xie, Xian-Jin; Francis, Franto; Roehrborn, Claus G; Sims, R Douglas; Costa, Daniel N; Raj, Ganesh V; Mason, Ralph P

    2017-08-24

    Hypoxia is associated with prostate tumor aggressiveness, local recurrence, and biochemical failure. Magnetic resonance imaging (MRI) offers insight into tumor pathophysiology and recent reports have related transverse relaxation rate (R₂*) and longitudinal relaxation rate (R₁) measurements to tumor hypoxia. We have investigated the inclusion of oxygen-enhanced MRI for multi-parametric evaluation of tumor malignancy. Multi-parametric MRI sequences at 3 Tesla were evaluated in 10 patients to investigate hypoxia in prostate cancer prior to radical prostatectomy. Blood oxygen level dependent (BOLD), tissue oxygen level dependent (TOLD), dynamic contrast enhanced (DCE), and diffusion weighted imaging MRI were intercorrelated and compared with the Gleason score. The apparent diffusion coefficient (ADC) was significantly lower in tumor than normal prostate. Baseline R₂* (BOLD-contrast) was significantly higher in tumor than normal prostate. Upon the oxygen breathing challenge, R₂* decreased significantly in the tumor tissue, suggesting improved vascular oxygenation, however changes in R₁ were minimal. R₂* of contralateral normal prostate decreased in most cases upon oxygen challenge, although the differences were not significant. Moderate correlation was found between ADC and Gleason score. ADC and R₂* were correlated and trends were found between Gleason score and R₂*, as well as maximum-intensity-projection and area-under-the-curve calculated from DCE. Tumor ADC and R₂* have been associated with tumor hypoxia, and thus the correlations are of particular interest. A multi-parametric approach including oxygen-enhanced MRI is feasible and promises further insights into the pathophysiological information of tumor microenvironment.

  9. Pituitary Tumors

    Science.gov (United States)

    ... nursing, or cause a man to lose his sex drive or lower his sperm count. Pituitary tumors often go undiagnosed because their symptoms resemble those of so many other more common diseases. × Definition The pituitary is a small, bean-sized gland ...

  10. 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

  11. Interpreting expressive performance through listener judgments of musical tension.

    Science.gov (United States)

    Farbood, Morwaread M; Upham, Finn

    2013-01-01

    This study examines listener judgments of musical tension for a recording of a Schubert song and its harmonic reduction. Continuous tension ratings collected in an experiment and quantitative descriptions of the piece's musical features, include dynamics, pitch height, harmony, onset frequency, and tempo, were analyzed from two different angles. In the first part of the analysis, the different processing timescales for disparate features contributing to tension were explored through the optimization of a predictive tension model. The results revealed the optimal time windows for harmony were considerably longer (~22 s) than for any other feature (~1-4 s). In the second part of the analysis, tension ratings for the individual verses of the song and its harmonic reduction were examined and compared. The results showed that although the average tension ratings between verses were very similar, differences in how and when participants reported tension changes highlighted performance decisions made in the interpretation of the score, ambiguity in tension implications of the music, and the potential importance of contrast between verses and phrases. Analysis of the tension ratings for the harmonic reduction also provided a new perspective for better understanding how complex musical features inform listener tension judgments.

  12. 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.

  13. TBK1 duplication is found in normal tension and not in high tension ...

    Indian Academy of Sciences (India)

    Duplication in TANK-binding kinase 1 (TBK1) gene has been shown to be associated with normal tension glaucoma. (NTG), a subtype of the neurodegenerative disease glau- coma, which is the largest cause of irreversible blindness. A specific Taqman assay was used in exploring the genetic contribution of the duplication ...

  14. Nitinol Fatigue Investigation on Stent-Finish Specimens Using Tension-Tension Method

    Science.gov (United States)

    Lin, Z.; Pike, K.; Zipse, A.; Schlun, M.

    2011-07-01

    Nitinol fatigue strain limit versus both strain amplitude (range 0.25-1.25%) and mean strain (1.0, 2.0, and 4.0%) was investigated using a tension-tension method. In order to apply the fatigue testing results to a nitinol stent and evaluate stent fatigue performance, the dog-bone style specimens were processed from the same raw material common to implantable stent manufacturing, i.e., similar nitinol tubing, surface quality, and electropolished surface. To simulate a physiological environment, the tension-tension fatigue tests were conducted in water at 37 °C. This strain-controlled fatigue test was conducted with a run-out set at 106 cycles. The fatigue strain limit at 106 cycles as well as the mean strain effect and the effects of inclusions are discussed. Fatigue results appeared in a bi-modal pattern when the strain amplitude was at a level between too high, which made all specimens to fail, and too low, which allowed all specimens to survive.

  15. 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.

  16. Tension-type headache: pain, fatigue, tension, and EMG responses to mental activation.

    Science.gov (United States)

    Bansevicius, D; Westgaard, R H; Sjaastad, O M

    1999-06-01

    Twenty patients with tension-type headache (14 chronic and 6 episodic) and 20 group-matched controls were selected for this study. They participated in a 1-hour, complex, two-choice, reaction-time test, as well as 5-minute pretest and 20-minute posttest periods. Subjects reported any pain in the forehead, temples, neck, and shoulders, as well as any feelings of fatigue and tension during the pretest, and every 10 minutes during the test and posttest by visual analog scales. Superficial electromyography was recorded simultaneously from positions representing the frontal and temporal muscles, neck (mostly splenius), and trapezius muscles. The location of pain corresponded to the position of the electrodes, but extended over a larger area. The test provoked pain in the forehead, neck, and shoulders of patients, i.e., pain scores from these regions increased significantly during the test. The pain scores continued to increase posttest. In patients, the EMG response of the trapezius (first 10 minutes of the test) was elevated relative to pretest. In controls, only the frontal muscles showed an EMG test response. Patients showed significantly higher EMG responses than controls in the neck (whole test period) and trapezius (first 10 minutes of the test period). There were significant differences in pain and fatigue scoring between patients and controls in all three periods and in tension scoring posttest. Fatigue correlated with pain, with increasing significance for all locations examined, while tension was mainly associated with the neck pain. The meaning of the variables "tension" and "fatigue" in headache, and their association with recorded muscle activity in various regions is discussed. The EMG response of the trapezius muscle to the test is discussed in comparison with similar responses observed in patients with other pain syndromes.

  17. 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.

  18. Effect of oxygen on multidrug resistance in term human placenta.

    Science.gov (United States)

    Javam, M; Audette, M C; Iqbal, M; Bloise, E; Gibb, W; Matthews, S G

    2014-05-01

    The placenta contains efflux transporters, including P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), that limit the passage of xenobiotics, certain hormones and nutrients from the maternal to the fetal circulation. The expression of these transporters changes with gestational age, yet the mechanisms involved remain unknown. However, the changes in P-gp and BCRP transporter expression coincide with those of oxygen tension in the placenta, and oxygen tension has been shown to modulate P-gp and BCRP expression in other tissues. The objective of this study was to investigate the effects of oxygen tension on P-gp and BCRP expression in the term human placenta. Following equilibration in culture (96 h), term placental explants (n = 7) were cultured in 3% or 20% oxygen for 24 and 48 h. Culture medium was collected every 24 h to measure lactate dehydrogenase (LDH; explant viability) and human chorionic gonadotropin (hCG; syncytiotrophoblast function). P-gp (encoded by ABCB1) and BCRP (encoded by ABCG2) protein and mRNA, as well as VEGFA mRNA were measured using western blot and qRT-PCR. P-gp localization was determined using immunofluorescence. Oxygen tension had a significant effect on P-gp expression, with ABCB1/P-gp mRNA and protein levels increased in the hypoxic condition (3% O2) after 48 h (p placenta in the third trimester may alter levels of placental P-gp, and in doing so alter fetal exposure to P-gp substrates, including xenobiotics and certain hormones. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Modification of Upper Thread Tensioner of Sewing Machine

    Science.gov (United States)

    Klouček, P.; Škop, P.

    Standard mechanical upper thread tensioner of sewing machines is more and more limited in use for industrial sewing machines due to increasing requests for quality and raising velocity of machines. If we omit mostly manual settings of force made only by sense, the most problematic things are influence of different friction coefficient of the different batch of threads and strong relation between thread tension and sewing machine velocity. The article describes the development focused to the elimination of the most significant disadvantages of a standard tensioner and mainly finding of new conception of the tensioner with electromagnetic brake, development and testing of its prototype.

  20. STRENGTH SHRINKAGE AND CREEP OF CONCRETE IN TENSION AND COMPRESSION

    Directory of Open Access Journals (Sweden)

    S A Kristiawan

    2006-01-01

    Full Text Available Strength, shrinkage and creep of concrete in tension and compression have been determined and the relationship between those properties was studied. Direct tensile tests were applied to measure those properties in tension. The relationship of creep in tension and compression was determined based on the measurement of creep at similar stress and similar stress/strength ratio. It is found that concrete deforms more in tension than in compression. Except for concrete with a higher water/cement ratio, the use of pulverised fuel ash, ground granulated blast furnace slag, superplasticizer and shrinkage reducing admixture has no effect on strength. However, they affect creep and shrinkage of concrete.

  1. Origin of line tension for a Lennard-Jones nanodroplet

    Science.gov (United States)

    Weijs, Joost H.; Marchand, Antonin; Andreotti, Bruno; Lohse, Detlef; Snoeijer, Jacco H.

    2011-02-01

    The existence and origin of line tension has remained controversial in literature. To address this issue, we compute the shape of Lennard-Jones nanodrops using molecular dynamics and compare them to density functional theory in the approximation of the sharp kink interface. We show that the deviation from Young's law is very small and would correspond to a typical line tension length scale (defined as line tension divided by surface tension) similar to the molecular size and decreasing with Young's angle. We propose an alternative interpretation based on the geometry of the interface at the molecular scale.

  2. 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...... in drawing of stainless steel showing the influence of varying process conditions and the performance of different lubricants....

  3. 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.

  4. 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

  5. Neurotrophic factors in tension-type headache

    Directory of Open Access Journals (Sweden)

    Renan B. Domingues

    2015-05-01

    Full Text Available Neurotrophic factors (NF are involved in pain regulation and a few studies have suggested that they may play a pathophysiological role in primary headaches. The aim of this study was to investigate NF levels in patients with tension type headache (TTH. We carried out a cross sectional study including 48 TTH patients and 48 age and gender matched controls. Beck Depression and Anxiety Inventories, and Headache Impact Test were recorded. Serum levels of NF were determined by ELISA. There were not significant differences between NF levels between TTH patients and controls. Patients with chronic and episodic TTH had not significant differences in NF levels. The presence of headache at the time of evaluation did not significantly alter the levels of NF. Depression and anxiety scores as well as headache impact did not correlate with NF levels. Our study suggest that the serum levels of NF are not altered in TTH.

  6. Cognitive functions and normal tension glaucoma.

    Science.gov (United States)

    Daveckaite, Akvile; Grusauskiene, Evelina; Petrikonis, Kestutis; Vaitkus, Antanas; Siaudvytyte, Lina; Januleviciene, Ingrida

    2017-10-01

    Only a few studies have analyzed the potential link between glaucoma and cognitive function impairment. They have found controversial results. This study aims to perform quick cognitive function assessment with clock drawing test (CDT) using two different scoring systems and compare between normal tension glaucoma (NTG) and cataract patients. Totally, 30 NTG and 30 patients with cataracts were included in a prospective, pilot study. The predrawn circle was given, and patients were asked to draw the clock showing a time of 11:10. The test was evaluated using two methods - Freund method using a 7-point scoring scale (optimal cutoff ≤4) and Rakusa using a 4-point scoring scale (optimal cutoff ≤3). The level of significance was set at P drawing. Further prospective studies are needed to investigate the CDT reliability as fast screening test of cognitive function impairment in glaucoma patients.

  7. Evolving spacetimes with purely radial tension

    Directory of Open Access Journals (Sweden)

    B. Nasre Esfahani

    2000-12-01

    Full Text Available   In this study time-dependent and spherically symmetric solutions of the Einstein field equations in an anisotropic background with a purely radial tension are presented. There exist three classes of solutions,1 An open spacetime with a wormhole at its center. 2 A conical spacetime. 3 A closed spacetime. These inhomogeneous solutions are reduced to FRW spacetimes in matter-dominated era, asymptotically. Therefore, they can be used to describe local inhomogeneities that are not considered in the standard model. For the wormhole solution. it is explicity shown that the considered matter is non-exotic, that is, it does not violate the energy conditions. Also, static solutions are studied. There is only one static solution,a conical spacetime. In this case, the matter satisfies the energy condition critically.

  8. Biaxial tension on polymer in thermoforming range

    Directory of Open Access Journals (Sweden)

    Billon N.

    2010-06-01

    Full Text Available This paper presents an experimental characterization of mechanical properties of a polyethylene terephtalate (PET resin classically used in stretch blow moulding process. We have applied on such a material a well established experimental protocol at CEMEF, including new and relevant biaxial tensile tests. The experimental set-up relative to biaxial tension will be presented and described in a first part of the paper. Furthermore, we will focus on the experimental DMTA preliminary tests which are required to estimate the resin sensibility to temperature and strain rate in linear viscoelasticity domain. Finally, we will be interested in the material large strain behaviour: biaxial tensile results are presented and discussed. Finally, such an experimental approach should allow a relevant modelling of polymer physics and mechanics; this point will not be discussed here because of a lack of time.

  9. 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 ...

  10. Brain Tumor Symptoms

    Science.gov (United States)

    ... Brain Anatomy Brain Tumor Symptoms Headaches Seizures Memory Depression Mood Swings & Cognitive Changes Fatigue Other Symptoms Diagnosis Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning About Us ...

  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. 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.

  13. 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......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...... to identify and understand the fatigue damage mechanism. A relatively new non-destructive inspection technique using infrared thermography was found to be a very useful tool in detecting damage initiation and growth. Furthermore, this technique supplies valuable information to the characterization...

  14. 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

  15. Oxygen-enhanced combustion

    CERN Document Server

    Baukal, Charles E

    2013-01-01

    Combustion technology has traditionally been dominated by air/fuel combustion. However, two developments have increased the significance of oxygen-enhanced combustion-new technologies that produce oxygen less expensively and the increased importance of environmental regulations. Advantages of oxygen-enhanced combustion include less pollutant emissions as well as increased energy efficiency and productivity. Oxygen-Enhanced Combustion, Second Edition compiles information about using oxygen to enhance industrial heating and melting processes. It integrates fundamental principles, applications, a

  16. 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.

  17. 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 ...

  18. 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.

  19. Tension band wiring fi xation is associated with good functional ...

    African Journals Online (AJOL)

    Background: Tension band wiring (TBW) is a widely accepted technique for olecranon fractures. Various investigators have reported a significant rate of complications especially hardware prominence. The purpose of this study was to determine the clinical and radiological outcome after tension band wiring of olecranon ...

  20. College Learning and Teaching: Struggling with/in the Tensions.

    Science.gov (United States)

    Child, Mark; Williams, David D.

    1996-01-01

    Tensions arising in the college classroom when a teacher attempts to change instructional practice and meets resistance are examined. It is suggested that the common response is for both teacher and students to struggle to overcome tensions entirely, which tends to reproduce the original instructional problems. Alternative approaches that can…

  1. 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…

  2. Surface tension of ionic liquids and ionic liquid solutions.

    Science.gov (United States)

    Tariq, Mohammad; Freire, Mara G; Saramago, Benilde; Coutinho, João A P; Lopes, José N Canongia; Rebelo, Luís Paulo N

    2012-01-21

    Some of the most active scientific research fronts of the past decade are centered on ionic liquids. These fluids present characteristic surface behavior and distinctive trends of their surface tension versus temperature. One way to explore and understand their unique nature is to study their surface properties. This critical review analyses most of the surface tension data reported between 2001 and 2010 (187 references).

  3. Creative tensions in youth ministry in a congregational context ...

    African Journals Online (AJOL)

    congregational approach to youth ministry could lead to certain creative tensions in youth ministry as an integral part of congregational ministry. Therefore the article identifies and discusses specific creative tensions that could be present in youth ministry where the inclusive congregational approach to youth ministry is ...

  4. Managing Tensions Between New and Existing Business Models

    DEFF Research Database (Denmark)

    Sund, Kristian J.; Bogers, Marcel; Villarroel, J. Andrei

    2016-01-01

    The search for new business models forces established companies to experiment with organizational designs — and leads to tensions that should be anticipated and carefully managed.......The search for new business models forces established companies to experiment with organizational designs — and leads to tensions that should be anticipated and carefully managed....

  5. 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…

  6. 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…

  7. 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.

  8. Tissue Force Programs Cell Fate and Tumor Aggression.

    Science.gov (United States)

    Northey, Jason J; Przybyla, Laralynne; Weaver, Valerie M

    2017-11-01

    Biomechanical and biochemical cues within a tissue collaborate across length scales to direct cell fate during development and are critical for the maintenance of tissue homeostasis. Loss of tensional homeostasis in a tissue not only accompanies malignancy but may also contribute to oncogenic transformation. High mechanical stress in solid tumors can impede drug delivery and may additionally drive tumor progression and promote metastasis. Mechanistically, biomechanical forces can drive tumor aggression by inducing a mesenchymal-like switch in transformed cells so that they attain tumor-initiating or stem-like cell properties. Given that cancer stem cells have been linked to metastasis and treatment resistance, this raises the intriguing possibility that the elevated tissue mechanics in tumors could promote their aggression by programming their phenotype toward that exhibited by a stem-like cell. Significance: Recent findings argue that mechanical stress and elevated mechanosignaling foster malignant transformation and metastasis. Prolonged corruption of tissue tension may drive tumor aggression by altering cell fate specification. Thus, strategies that could reduce tumor mechanics might comprise effective approaches to prevent the emergence of treatment-resilient metastatic cancers. Cancer Discov; 7(11); 1224-37. ©2017 AACR. ©2017 American Association for Cancer Research.

  9. 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.

  10. 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 ...

  11. Maximizing aesthetics in lateral-tension abdominoplasty and body lifts.

    Science.gov (United States)

    Lockwood, Ted E

    2004-10-01

    The high-lateral-tension abdominoplasty addresses the practical and theoretic faults of standard abdominoplasty design. Key features include limited direct undermining, increased lateral skin resection with highest-tension wound closure along lateral limbs, two-layer superficial fascial system repair, and significant truncal liposuction when needed. The high-lateral-tension design limits the unfavorable features of standard abdominoplasty and produces balanced natural aesthetic contours. The high-lateral-tension abdominoplasty is the foundation for treatment of more generalized relaxation problems in the circumferential trunk and thighs. For more significant thigh laxity and buttock ptosis, the lateral-tension abdominoplasty is combined with the transverse thigh/buttock lift to produce the lower body lift #2.

  12. Exploratory experimental investigations on post-tensioned structural glass beams

    Directory of Open Access Journals (Sweden)

    Christian Louter

    2015-05-01

    Full Text Available The mechanical response of post-tensioned glass beams is explored in this paper. This is done through bending experiments on post-tensioned glass beam specimens with either mechanically anchored or adhesively bonded steel tendons by which a beneficial pre-stress is inflicted on the glass beams. In addition, reference beams with identical geometry but without tendons are tested. From the results of the bending experiments it can be seen that the post-tensioned glass beams reach higher initial fracture loads than the reference glass beams. Furthermore, the post-tensioned glass beams develop a significant post-fracture reserve. From this it is concluded that post-tensioning a glass beam is a feasible concept, which provides increased initial fracture strength and enhanced post-fracture performance.

  13. 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....

  14. 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)

  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. 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...

  17. 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.

  18. 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.

  19. 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.)

  20. [Prozac treatment of chronic tension headache].

    Science.gov (United States)

    Voznesenskaia, T G

    1999-01-01

    The paper summarizes the experience of therapy of chronic tension type headache (TTH) with prozac (fluoxetine)--a selective serotonine reuptake inhibitor. The data are presented concerning clinical psychologic examination of 20 outpatients with chronic TTH both before and after therapy with prozac in daily dose of 20 mg during 6 weeks. Background study of the patients revealed severe depression (according to Beck's and SCL-90 scales), anxiety (Spilberger scale) and alexitimia (Toronto scale). Before the treatment, a frequency of TTH attacks was at least four times a week, the intensivity was equal to 8.9 scores according to visual analogous scale. Together with a headache there were psychopathologic and psychoautonomic manifestations. After the course of therapy the headaches disappeared completely in 25%, while considerable improvement was observed in 75% of the patients. The levels of depression, anxiety, somatization have decreased significantly too. Side effects as well as withdrawal syndrome weren't found. The role of depression in formation of chronic TTH, as well as the role of alixetimia in formation of somatizated variation of the depression were considered.

  1. India: environmental degradation, urban slums, political tension.

    Science.gov (United States)

    Chhabra, R

    1985-09-01

    This article presents an overview of stresses facing Indian society, including population pressures on land and agriculture, topsoil erosion, deforestation, flooding, unemployment, urban slums, and political unrest. Over 60% of India's arable land is estimated to suffer from environmental degradation. This has been caused both by a rapidly growing poor population seeking subsistence and by the misappropriation of natural resources by the wealthy for luxury consumption. Although deforestation is officially cited at 0.37 million acres/year, more sensitive estimates put it at 2.5 million acres/year. Deforestation and massive soil erosion have further created silting, flooding, and pollution in the plains areas of the country. Moreover, the urban population of India is expected to double in the next 15 years to reach a level of 350-400 million. At present, 20-33% of the urban population lives in slums without basic facilities. The employment crisis precipitated by increasing urbanization and migration is expected to be a major problem in the decades ahead. By the year 2000, 7.5 million people will enter the labor force annually. Demographic tension has been a major factor in recent political unrest. Language differences, inequitable access to resources, and the lack of job opportunities have been central issues in these conflicts. Unless more effective means can be found to cope simultaneously with the need to speed up development and meet the needs of a rapidly expanding population, the social and environmental fabric of India is in danger of further erosion.

  2. 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.

  3. Pathophysiological Basis for the Formation of the Tumor Microenvironment

    DEFF Research Database (Denmark)

    Horsman, Michael R; Vaupel, Peter

    2016-01-01

    Poor microenvironmental conditions are a characteristic feature of solid tumors. Such conditions occur because the tumor vascular supply, which develops from the normal host vasculature by the process of angiogenesis, is generally inadequate in meeting the oxygen and nutrient demands of the growing...

  4. Characterization of positron emission tomography hypoxia tracer uptake and tissue oxygenation via electrochemical modeling.

    Science.gov (United States)

    Bowen, Stephen R; van der Kogel, Albert J; Nordsmark, Marianne; Bentzen, Søren M; Jeraj, Robert

    2011-08-01

    Unique uptake and retention mechanisms of positron emission tomography (PET) hypoxia tracers make in vivo comparison between them challenging. Differences in imaged uptake of two common hypoxia radiotracers, [(61)Cu]Cu-ATSM and [(18)F]FMISO, were characterized via computational modeling to address these challenges. An electrochemical formalism describing bioreductive retention mechanisms of these tracers under steady-state conditions was adopted to relate time-averaged activity concentration to tissue partial oxygen tension (PO(2)), a common metric of hypoxia. Chemical equilibrium constants of product concentration to reactant concentration ratios were determined from free energy changes and reduction potentials of pertinent reactions reported in the literature. Resulting transformation functions between tracer uptake and PO(2) were compared against measured values in preclinical models. Additionally, calculated PO(2) distributions from imaged Cu-ATSM tracer activity concentrations of 12 head and neck squamous cell carcinoma (HNSCC) patients were validated against microelectrode PO(2) measurements in 69 HNSCC patients. Both Cu-ASTM- and FMISO-modeled PO(2) transformation functions were in agreement with preclinical measured values within single-deviation confidence intervals. High correlation (r(2)=0.94, Ptracers. Comprehensive and robust assessment of tumor hypoxia prior to as well as in response to therapy may be best provided by imaging of multiple hypoxia markers that provide complementary rather than interchangeable information. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. A reason for intermittent fasting to suppress the awakening of dormant breast tumors.

    NARCIS (Netherlands)

    Lankelma, J.; Kooi, B.W.; Krab, K.; Dorsman, J.C.; Joenje, H.; Westerhoff, H.V.

    2015-01-01

    For their growth, dormant tumors, which lack angiogenesis may critically depend on gradients of nutrients and oxygen from the nearest blood vessel. Because for oxygen depletion the distance from the nearest blood vessel to depletion will generally be shorter than for glucose depletion, such tumors

  6. A reason for intermittent fasting to suppress the awakening of dormant breast tumors

    NARCIS (Netherlands)

    Lankelma, J.; Kooi, B.; Krab, K.; Dorsman, J.C.; Joenje, H.; Westerhoff, H.V.

    2015-01-01

    For their growth, dormant tumors, which lack angiogenesis may critically depend on gradients of nutrients and oxygen from the nearest blood vessel. Because for oxygen depletion the distance from the nearest blood vessel to depletion will generally be shorter than for glucose depletion, such tumors

  7. Aerobic Glycolysis as a Marker of Tumor Aggressiveness: Preliminary Data in High Grade Human Brain Tumors

    Directory of Open Access Journals (Sweden)

    Andrei G. Vlassenko

    2015-01-01

    Full Text Available Objectives. Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG, is a hallmark of active cancer cells that is not directly measured with standard 18F-fluorodeoxyglucose (FDG positron emission tomography (PET. In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucose and oxygen metabolism. Methods. Fourteen individuals with high-grade brain tumors underwent structural MR scans and PET measurements of cerebral blood flow (CBF, oxygen (CMRO2 and glucose (CMRGlu metabolism, and AG, using 15O-labeled CO, O2 and H2O, and FDG, and were compared to a normative cohort of 20 age-matched individuals. Results. Elevated AG was observed in most high-grade brain tumors and it was associated with decreased CMRO2 and CBF, but not with significant changes in CMRGlu. Elevated AG was a dramatic and early sign of tumor growth associated with decreased survival. AG changes associated with tumor growth were differentiated from the effects of nonneoplastic processes such as epileptic seizures. Conclusions. Our findings demonstrate that high-grade brain tumors exhibit elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas of active tumor growth that are not evident on conventional FDG PET.

  8. Blood Outgrowth Endothelial Cells Increase Tumor Growth Rates and Modify Tumor Physiology: Relevance for Therapeutic Targeting

    International Nuclear Information System (INIS)

    Pagan, Jonathan; Przybyla, Beata; Jamshidi-Parsian, Azemat; Gupta, Kalpna; Griffin, Robert J.

    2013-01-01

    Endothelial cell precursors from human peripheral blood have been shown to home to areas of neovascularization and may assist tumor growth by increasing or fortifying blood vessel growth. In the present study, the influence of these cells on tumor growth and physiology was investigated and the role of these cells as a therapeutic target or in determining treatment sensitivity was tested. After isolation from human blood and expansion in vitro, actively growing cells with verified endothelial phenotype (Blood Outgrowth Endothelial Cell, BOEC) were injected i.v. into tumor bearing mice for three consecutive days. The growth rate was significantly enhanced in relatively small RERF human lung tumors (i.e., less than 150 mm 3 ) grown in immunocompromised mice by an average of 1.5-fold while it had no effect when injections were given to animals bearing larger tumors. There were no signs of toxicity or unwanted systemic effects. We also observed evidence of increased perfusion, vessel number, response to 15 Gy radiation and oxygenation in RERF tumors of animals injected with BOECs compared to control tumors. In addition, FSaII murine fibrosarcoma tumors were found to grow faster upon injection of BOECs. When FSaII tumors were subjected to a partial thermal ablation treatment using high intensity focused ultrasound (HIFU) there was consistently elevated detection of fluorescently labeled and i.v. injected endothelial precursors in the tumor when analyzed with optical imaging and/or histological preparations. Importantly, we also observed that BOECs treated with the novel anti-angiogenic peptide anginex in-vitro, show decreased proliferation and increased sensitivity to radiation. In vivo, the normal increase in FSaII tumor growth induced by injected BOECs was blunted by the addition of anginex treatment. It appears that endothelial precursors may significantly contribute to tumor vessel growth, tumor progression and/or repair of tumor damage and may improve the

  9. Inhibition of hypoxia-inducible factor 1 with acriflavine sensitizes hypoxic tumor cells to photodynamic therapy with zinc phthalocyanine-encapsulating cationic liposomes

    NARCIS (Netherlands)

    Broekgaarden, Mans; Weijer, Ruud; Krekorian, Massis; van den IJssel, Bas; Kos, Milan; Alles, Lindy K.; van Wijk, Albert C.; Bikadi, Zsolt; Hazai, Eszter; van Gulik, Thomas M.; Heger, Michal

    2016-01-01

    Photodynamic therapy (PDT) is a tumor treatment modality in which a tumorlocalized photosensitizer is excited with light, which results in local production of reactive oxygen species, destruction of tumor vasculature, tumor hypoxia, tumor cell death, and induction of an anti-tumor immune response.

  10. 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.

  11. Surface tension of Nanofluid-type fuels containing suspended nanomaterials.

    Science.gov (United States)

    Tanvir, Saad; Qiao, Li

    2012-04-18

    The surface tension of ethanol and n-decane based nanofluid fuels containing suspended aluminum (Al), aluminum oxide (Al2O3), and boron (B) nanoparticles as well as dispersible multi-wall carbon nanotubes (MWCNTs) were measured using the pendant drop method by solving the Young-Laplace equation. The effects of nanoparticle concentration, size and the presence of a dispersing agent (surfactant) on surface tension were determined. The results show that surface tension increases both with particle concentration (above a critical concentration) and particle size for all cases. This is because the Van der Waals force between particles at the liquid/gas interface increases surface free energy and thus increases surface tension. At low particle concentrations, however, addition of particles has little influence on surface tension because of the large distance between particles. An exception is when a surfactant was used or when (MWCNTs) was involved. For such cases, the surface tension decreases compared to the pure base fluid. The hypothesis is the polymer groups attached to (MWCNTs) and the surfactant layer between a particle and the surround fluid increases the electrostatic force between particles and thus reduce surface energy and surface tension.

  12. Oxygen transport membrane

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention relates to a novel composite oxygen transport membrane as well as its preparation and uses thereof.......The present invention relates to a novel composite oxygen transport membrane as well as its preparation and uses thereof....

  13. Miniature oxygen resuscitator

    Science.gov (United States)

    Johnson, G.; Teegen, J. T.; Waddell, H.

    1969-01-01

    Miniature, portable resuscitation system is used during evacuation of patients to medical facilities. A carrying case contains a modified resuscitator head, cylinder of oxygen, two-stage oxygen regulator, low pressure tube, and a mask for mouth and nose.

  14. Cryptococcus neoformans and oxygen

    OpenAIRE

    Vladislav,Raclavsky

    2006-01-01

    Oxygen is essential to life of all organisms except for obligate anaerobic species, because it is necessary for energy generation and also for some biosynthetic pathways. However, sensitivity to low oxygen levels can vary widely in different organisms and cell types. The pathogenic yeast species Cryptococcus neoformans is known to love oxygen. In response to the lack of oxygen (hypoxia), this yeast delays budding without resigning DNA replication, which eventually results in unique cell cycle...

  15. Proterozoic atmospheric oxygen

    DEFF Research Database (Denmark)

    Canfield, Donald Eugene

    2014-01-01

    This article is concerned with the evolution of atmospheric oxygen concentrations through the Proterozoic Eon. In particular, this article will seek to place the history of atmospheric oxygenation through the Proterozoic Eon in the context of the evolving physical environment including the history...... of continental growth and volcanic outgassing, as well as biogeochemical processing of elements within the oceans. The author will seek to explore constraints on the history of oxygenation and understand which processes have regulated oxygen through this eon....

  16. Oxygen evolution reaction catalysis

    Science.gov (United States)

    Haber, Joel A.; Jin, Jian; Xiang, Chengxiang; Gregoire, John M.; Jones, Ryan J.; Guevarra, Dan W.; Shinde, Aniketa A.

    2016-09-06

    An Oxygen Evolution Reaction (OER) catalyst includes a metal oxide that includes oxygen, cerium, and one or more second metals. In some instances, the cerium is 10 to 80 molar % of the metals in the metal oxide and/or the catalyst includes two or more second metals. The OER catalyst can be included in or on an electrode. The electrode can be arranged in an oxygen evolution system such that the Oxygen Evolution Reaction occurs at the electrode.

  17. An ultrasonically powered implantable micro-oxygen generator (IMOG).

    Science.gov (United States)

    Maleki, Teimour; Cao, Ning; Song, Seung Hyun; Kao, Chinghai; Ko, Song-Chu Arthur; Ziaie, Babak

    2011-11-01

    In this paper, we present an ultrasonically powered implantable micro-oxygen generator (IMOG) that is capable of in situ tumor oxygenation through water electrolysis. Such active mode of oxygen generation is not affected by increased interstitial pressure or abnormal blood vessels that typically limit the systemic delivery of oxygen to hypoxic regions of solid tumors. Wireless ultrasonic powering (2.15 MHz) was employed to increase the penetration depth and eliminate the directional sensitivity associated with magnetic methods. In addition, ultrasonic powering allowed for further reduction in the total size of the implant by eliminating the need for a large area inductor. IMOG has an overall dimension of 1.2 mm × 1.3 mm × 8 mm, small enough to be implanted using a hypodermic needle or a trocar. In vitro and ex vivo experiments showed that IMOG is capable of generating more than 150 μA which, in turn, can create 0.525 μL/min of oxygen through electrolytic disassociation. In vivo experiments in a well-known hypoxic pancreatic tumor models (1 cm (3) in size) also verified adequate in situ tumor oxygenation in less than 10 min.

  18. Temperature and oxygenation during organ preservation: friends or foes?

    Science.gov (United States)

    Gilbo, Nicholas; Monbaliu, Diethard

    2017-06-01

    The liberalization of donor selection criteria in organ transplantation, with the increased use of suboptimal grafts, has stimulated interest in ischemia-reperfusion injury prevention and graft reconditioning. Organ preservation technologies are changing considerably, mostly through the reintroduction of dynamic machine preservation. Here, we review the current evidence on the role of temperature and oxygenation during dynamic machine preservation. A large but complex body of evidence exists and comparative studies are few. Oxygenation seems to support an advantageous effect in hypothermic machine preservation and is mandatory in normothermic machine preservation, although in the latter, supraphysiological oxygen tensions should be avoided. High-risk grafts, such as suboptimal organs, may optimally benefit from oxygenated perfusion conditions that support metabolism and activate mechanisms of repair such as subnormothermic machine preservation, controlled oxygenated rewarming, and normothermic machine preservation. For lower risk grafts, oxygenation during hypothermic machine preservation may sufficiently reduce injuries and recharge the cellular energy to secure functional recovery after transplantation. The relationship between temperature and oxygenation in organ preservation is more complex than physiological laws would suggest. Rather than one default perfusion temperature/oxygenation standard, perfusion protocols should be tailored for specific needs of grafts of different quality.

  19. Tension in the recent Type Ia supernovae datasets

    International Nuclear Information System (INIS)

    Wei, Hao

    2010-01-01

    In the present work, we investigate the tension in the recent Type Ia supernovae (SNIa) datasets Constitution and Union. We show that they are in tension not only with the observations of the cosmic microwave background (CMB) anisotropy and the baryon acoustic oscillations (BAO), but also with other SNIa datasets such as Davis and SNLS. Then, we find the main sources responsible for the tension. Further, we make this more robust by employing the method of random truncation. Based on the results of this work, we suggest two truncated versions of the Union and Constitution datasets, namely the UnionT and ConstitutionT SNIa samples, whose behaviors are more regular.

  20. Bending Under Tension Test with Direct Friction Measurement

    DEFF Research Database (Denmark)

    Andreasen, Jan Lasson; Olsson, David Dam; Chodnikiewicz, K.

    2004-01-01

    A special 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 in drawing of stainless steel...

  1. First-principles prediction of liquid/liquid interfacial tension

    DEFF Research Database (Denmark)

    Andersson, Martin Peter; Bennetzen, M.V.; Klamt, A.

    2014-01-01

    of groundwater aquifers contaminated by chlorinated solvents to drug delivery and a host of industrial processes. Here, we present a model for predicting interfacial tension from first principles using density functional theory calculations. Our model requires no experimental input and is applicable to liquid/liquid......The interfacial tension between two liquids is the free energy per unit surface area required to create that interface. Interfacial tension is a determining factor for two-phase liquid behavior in a wide variety of systems ranging from water flooding in oil recovery processes and remediation...

  2. Percutaneous Relief of Tension Pneumomediastinum in a Child

    International Nuclear Information System (INIS)

    Chau, Helen Hoi-lun; Kwok, Philip Chong-hei; Lai, Albert Kwok-hung; Fan, Tsz Wo; Chan, Susan Chi-hum; Miu, Ting Yat; Chan, Grace Lai-har

    2003-01-01

    The purpose of this article was to describe the experience of relieving tension pneumomediastinum by a fluoroscopic-guided percutaneous method. We inserted a percutaneous drainage catheter with a Heimlich valve under fluoroscopic guidance to relieve the tension pneumomediastinum in a 2-year-old girl who suffered from dermatomyositis with lung involvement. This allowed immediate relief without the need for surgery. The procedure was repeated for relapsed tension pneumomediastinum. Good immediate results were achieved in each attempt. We conclude that percutaneous relief of pneumomediastinum under fluoroscopic guidance can be performed safely and rapidly in patients not fit for surgery

  3. [Domiciliary oxygen therapy].

    Science.gov (United States)

    Abdel Kafi, S

    2010-09-01

    In Belgium, oxygen therapy is becoming more and more accessible. When oxygen is needed for short periods or for special indications as palliative care, an agreement between mutual insurance companies and pharmacists allows the practitioner the home installation of gazeous oxygen cylinder or of oxygen concentrator. When long term oxygen therapy (LTOT) is indicated for patients with respiratory insufficiency, the pneumologist must first ask the INAMI the authorization to install one of the following modalities: oxygen concentrator with or without demand oxygen delivery cylinder and liquid oxygen. The goal of LTOT is to increase survival and quality of life. The principal and well accepted indication for LTOT is severe hypoxemia. The beneficial effects of oxygen therapy limited at night or on exertion are controversial. In order to increase patient's autonomy, oxygen can be prescribed for ambulation, respecting prescription's rules. At each step of oxygen therapy implementing (indication, choice of the device and follow-up) the patient under oxygen may benefit from a joint approach between the general practitioner and the chest specialist.

  4. Climate-derived tensions in Arctic security.

    Energy Technology Data Exchange (ETDEWEB)

    Backus, George A.; Strickland, James Hassler

    2008-09-01

    Globally, there is no lack of security threats. Many of them demand priority engagement and there can never be adequate resources to address all threats. In this context, climate is just another aspect of global security and the Arctic just another region. In light of physical and budgetary constraints, new security needs must be integrated and prioritized with existing ones. This discussion approaches the security impacts of climate from that perspective, starting with the broad security picture and establishing how climate may affect it. This method provides a different view from one that starts with climate and projects it, in isolation, as the source of a hypothetical security burden. That said, the Arctic does appear to present high-priority security challenges. Uncertainty in the timing of an ice-free Arctic affects how quickly it will become a security priority. Uncertainty in the emergent extreme and variable weather conditions will determine the difficulty (cost) of maintaining adequate security (order) in the area. The resolution of sovereignty boundaries affects the ability to enforce security measures, and the U.S. will most probably need a military presence to back-up negotiated sovereignty agreements. Without additional global warming, technology already allows the Arctic to become a strategic link in the global supply chain, possibly with northern Russia as its main hub. Additionally, the multinational corporations reaping the economic bounty may affect security tensions more than nation-states themselves. Countries will depend ever more heavily on the global supply chains. China has particular needs to protect its trade flows. In matters of security, nation-state and multinational-corporate interests will become heavily intertwined.

  5. Cognitive functions and normal tension glaucoma

    Directory of Open Access Journals (Sweden)

    Akvile Daveckaite

    2017-01-01

    Full Text Available Purpose: Only a few studies have analyzed the potential link between glaucoma and cognitive function impairment. They have found controversial results. This study aims to perform quick cognitive function assessment with clock drawing test (CDT using two different scoring systems and compare between normal tension glaucoma (NTG and cataract patients. Methods: Totally, 30 NTG and 30 patients with cataracts were included in a prospective, pilot study. The predrawn circle was given, and patients were asked to draw the clock showing a time of 11:10. The test was evaluated using two methods – Freund method using a 7-point scoring scale (optimal cutoff ≤4 and Rakusa using a 4-point scoring scale (optimal cutoff ≤3. The level of significance was set at P < 0.05. Results: CDT result was significantly better in cataract group than in NTG group: 3.5 (2 versus 2 (2 by Freund, (P = 0.003 and 6.5 (1 versus 4.5 (2.75 by Rakusa, respectively (P = 0.004. Sixty percent (n = 18 of NTG group and 10% (n = 3 of cataract group patients completed the CDT in the specific picture manner (the short hand on 11 and the long hand between 11 and 12, (P = 0.001. Conclusions: Lower CDT results were seen in NTG patients according to two different scoring systems. NTG patients showed a specific manner of drawing. Further prospective studies are needed to investigate the CDT reliability as fast screening test of cognitive function impairment in glaucoma patients.

  6. Diffuse brain damage in normal tension glaucoma.

    Science.gov (United States)

    Giorgio, Antonio; Zhang, Jian; Costantino, Francesco; De Stefano, Nicola; Frezzotti, Paolo

    2018-01-01

    Brain changes within and beyond the visual system have been demonstrated in primary open angle glaucoma (POAG), the most common type of glaucoma. These changes have been often interpreted as a neurodegenerative process due, at least partially, to the raised intraocular pressure (IOP). In this context, normal tension glaucoma (NTG), a form of POAG with IOP acquired multimodal brain MRI in NTG patients (n = 17) and compared them with demographically matched groups of POAG patients with raised IOP (n = 17) and normal controls (NC, n = 29). Voxelwise statistics was performed with nonparametric permutation testing. Both NTG and POAG patients showed, compared to NC, significantly more gray matter atrophy in both the visual system and in nonvisual brain regions and altered diffusion tensor imaging-derived anatomical connectivity (AC; lower fractional anisotropy and/or higher diffusivities). Compared with NTG, POAG had both more atrophic visual cortex and higher axial diffusivity in nonvisual regions. Functional connectivity (FC) with respect to NC was altered in NTG at short-range level [visual network (VN), ventral attention network] and in POAG at long-range level (between secondary VN and limbic network). FC of POAG was higher than NTG in both VN and executive network. This study provides further evidence that diffuse structural and functional abnormalities across glaucoma brain may be, at least partially, independent of raised IOP and the consequent retinal degeneration. This further defines glaucoma as a condition with neurodegeneration spreading. Hum Brain Mapp 39:532-541, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Hyperpolarized magnetic resonance spectroscopy for assessing tumor hypoxia.

    Science.gov (United States)

    Iversen, Ane B; Ringgaard, Steffen; Laustsen, Christoffer; Stødkilde-Jørgensen, Hans; Bentzen, Lise; Busk, Morten; Horsman, Michael R

    2015-01-01

    Hypoxic tumor cells are radioresistant, therefore, identification of hypoxia is crucial. Hyperpolarized magnetic resonance spectroscopy (HPMRS) allows real time measurements of the conversion of pyruvate to lactate, the final step of anaerobic energy production, and may thus allow non-invasive identification of hypoxia or treatment-induced changes in oxygenation. The aim of the study was to investigate the usefulness of HPMRS as a means to assess tumor hypoxia and its dynamics during intervention. C3H mammary carcinomas grown in CDF1 mice were used. To manipulate with tumor oxygenation, non-anaesthetized mice were gassed with air, 10% or 100% oxygen prior to administration of hyperpolarized [1-¹³C]pyruvate and HPMRS analysis. A direct assessment of tumor oxygen partial pressure (pO2) distributions were made using the Eppendorf oxygen electrode in a separate, but similarly treated, group of mice. Even though breathing 100% oxygen improved tumor oxygenation as evidenced by pO2 measurements, the mean (with 1 S.E.) [1-¹³C]lactate/[1-¹³C]pyruvate ratio was unaffected by this intervention, being 34 (30-37) in mice breathing air and 37 (33-42) in mice breathing 100% oxygen. In contrast, and in accordance with pO2 measurements, a significant increase in the [1-¹³C]lactate/[1-¹³C]pyruvate ratio was seen in 10% oxygen-breathing mice with a ratio of 46 (42-50). Although, no metabolic change was observed during 100% O2 breathing using HPMRS, the significant increase in the [1-¹³C]lactate/[1-¹³C]pyruvate ratio during 10% oxygen breathing suggests, that HPMRS can detect hypoxia-driven changes in the metabolic fate of pyruvate. To what extent and for what purposes HPMRS may best supplement or complement established techniques like hypoxia PET needs to be unraveled in future research.

  8. Differences of optic disc appearance between normal tension and high tension glaucoma patients

    Directory of Open Access Journals (Sweden)

    Stojčić Milan

    2011-01-01

    Full Text Available Introduction. The term glaucoma is used to cover a wide range of diseases, whose main feature is optic neuropathy. According to the level of intraocular pressure (IOP, the open angle glaucoma is arbitrarily divided into high tension glaucoma (HTG and normal tension glaucoma (NTG. Objective. The aim of this study was to investigate the differences of optic disc cup appearance between patients with NTG and HTG. Methods. Prospective study included 30 patients (60 eyes with NTG and 30 patients (60 eyes with HTG. IOP was measured by Goldmann applanation tonometry. Examination of optic disc head was performed by indirect ophthalmoscopy with Volk 90 D superfield lens through a dilated pupil to observe qualitative and quantitative parameters. Visual fields were examined in all patients with the Octopus program G1, full threshold strategy (Octopus 500 EZ, Interzeag, Switzerland. Results. Vertical form of optic disc cup was present in 11 eyes with NTG (18.3% and three eyes with HTG (5% (p<0.05. A disc with localized tissue loss (polar notching on the inferior pole was observed in eight eyes with NTG (13.3% and in one eye with HTG (1.7% (p<0.01. Uniformly enlarged, round cup was more frequent in patients with HTG than NTG: 93.3% and 68.3% respectively (p<0.05. Conclusion. The perceived differences indicate a complex multifactorial nature of glaucoma disease and a possible existence of two pathophysiological ways of optic disc changes within the same basic disease.

  9. Neuroendocrine Tumor: Statistics

    Science.gov (United States)

    ... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 11/ ... the body. It is important to remember that statistics on the survival rates for people with a ...

  10. Tumors and Pregnancy

    Science.gov (United States)

    Tumors during pregnancy are rare, but they can happen. Tumors can be either benign or malignant. Benign tumors aren't cancer. Malignant ones are. The most common cancers in pregnancy are breast cancer, cervical cancer, lymphoma, and melanoma. ...

  11. DCB - Tumor Metastasis Research

    Science.gov (United States)

    Tumor metastasis research examines the mechanisms that allow cancer cells to leave the primary tumor and spread to another part of the body. Learn about recent tumor metastasis research studies supported by the Division of Cancer Biology.

  12. Childhood Brain Tumors

    Science.gov (United States)

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  13. Pediatric Brain Tumor Foundation

    Science.gov (United States)

    ... navigate their brain tumor diagnosis. WATCH AND SHARE Brain tumors and their treatment can be deadly so ... Pediatric Central Nervous System Cancers Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  14. Ghrelin and gastrointestinal stromal tumors.

    Science.gov (United States)

    Zhu, Chang-Zhen; Liu, Dong; Kang, Wei-Ming; Yu, Jian-Chun; Ma, Zhi-Qiang; Ye, Xin; Li, Kang

    2017-03-14

    Ghrelin, as a kind of multifunctional protein polypeptide, is mainly produced in the fundus of the stomach and can promote occurrence and development of many tumors, including gastrointestinal tumors, which has been proved by the relevant researches. Most gastrointestinal stromal tumors (GISTs, about 80%), as the most common mesenchymal tumor, also develop in the fundus. Scientific research has confirmed that ghrelin, its receptors and mRNA respectively can be found in GISTs, which demonstrated the existence of a ghrelin autocrine/paracrine loop in GIST tissues. However, no reports to date have specified the mechanism whether ghrelin can promote the occurrence and development of GISTs. Studies of pulmonary artery endothelial cells in a low-oxygen environment and cardiac muscle cells in an ischemic environment have shown that ghrelin can activate the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. Moreover, some studies of GISTs have confirmed that activation of the PI3K/AKT/mTOR pathway can indeed promote the growth and progression of GISTs. Whether ghrelin is involved in the development or progression of GISTs through certain pathways remains unknown. Can we find a new target for the treatment of GISTs? This review explores and summaries the relationship among ghrelin, the PI3K/AKT/mTOR pathway and the development of GISTs.

  15. Machine for winding under tension a prestressing wire

    International Nuclear Information System (INIS)

    Perez, M.A.; Thillet, Georges.

    1975-01-01

    This invention concerns a machine for winding under tension a prestressing wire or cable. It is used in the wrapping of cylindrical structures, particularly concrete vessels, for the purpose of achieving radial prestressing in them [fr

  16. System and Method for Tensioning a Robotically Actuated Tendon

    Science.gov (United States)

    Reiland, Matthew J. (Inventor); Diftler, Myron A. (Inventor)

    2013-01-01

    A tendon tensioning system includes a tendon having a proximal end and a distal end, an actuator, and a motor controller. The actuator may include a drive screw and a motor, and may be coupled with the proximal end of the tendon and configured to apply a tension through the tendon in response to an electrical current. The motor controller may be electrically coupled with the actuator, and configured to provide an electrical current having a first amplitude to the actuator until a stall tension is achieved through the tendon; provide a pulse current to the actuator following the achievement of the stall tension, where the amplitude of the pulse current is greater than the first amplitude, and return the motor to a steady state holding current following the conclusion of the pulse current.

  17. Corrosion characteristics of unprotected post-tensioning strands under stress.

    Science.gov (United States)

    2014-05-01

    An investigation was conducted to determine the effect of stress condition : and environmental exposure on corrosion of post-tensioned strands during ungrouted periods. : Exposures for periods of up to 4 weeks of stressed, as-received strand placed i...

  18. Fracture analysis of composites in high-speed tension

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Chiping; Cao, Li; Zou, Zhenzhu; Wang, Duo; Yao, Zhongkai (Harbin Institute of Technology (China))

    1989-12-01

    The fracture mechanism of composites in high-speed tension is investigated using a simplified theoretical model and results of a high-speed tension experiment on a sample of SiC-whisker-reinforced Al composite. Particular attention is given to the influence of microcracks and faults which may exist along the interfaces between the matrix and reinforcers of the composite on the strength of the composite. Results of the experimental observations show that, in high-speed tension (at 500 mm/min tensile rate), the effect of microcracks and faults along the interfaces on the composite's strength decreases in comparison with samples under conventional tension (i.e., at 0.5 mm/min tensile rate), and thus, the fracture strength of composites increases. 5 refs.

  19. Molecular dynamics calculation of the surface tension of aluminum nanodrops

    International Nuclear Information System (INIS)

    Gubin, A.S.; Botyachkova, A.I.; Dubrovskij, A.V.

    2012-01-01

    A method has been proposed for calculating the surface tension coefficient of liquid drops. The density and normal and tangential components of the stress tensor have been calculated as functions of the distance to the center of a nanodrop [ru

  20. Quantifying the BICEP2-Planck tension over gravitational waves.

    Science.gov (United States)

    Smith, Kendrick M; Dvorkin, Cora; Boyle, Latham; Turok, Neil; Halpern, Mark; Hinshaw, Gary; Gold, Ben

    2014-07-18

    The recent BICEP2 measurement of B-mode polarization in the cosmic microwave background (r = 0.2(-0.05)(+0.07)), a possible indication of primordial gravity waves, appears to be in tension with the upper limit from WMAP (r < 0.13 at 95% C.L.) and Planck (r < 0.11 at 95% C.L.). We carefully quantify the level of tension and show that it is very significant (around 0.1% unlikely) when the observed deficit of large-scale temperature power is taken into account. We show that measurements of TE and EE power spectra in the near future will discriminate between the hypotheses that this tension is either a statistical fluke or a sign of new physics. We also discuss extensions of the standard cosmological model that relieve the tension and some novel ways to constrain them.

  1. Bathing Trunk Inevus Associated with Neurofibromatosis and Raised Intracranial Tension

    Directory of Open Access Journals (Sweden)

    T.V.S Arya

    1988-01-01

    Full Text Available A 17-year-old boy had bathing trunk nevus with multiple large neurofibromata on the nevus and raised intracranial tension presenting with bilateral papilloedema and pyramidal tract sings. This combination, of features is extremely rare.

  2. CASE SERIES Traumatic tension pneumocephalus: a series of 4 ...

    African Journals Online (AJOL)

    Test

    ABSTRACT. Tension pneumocephalus is the accumulation of air in the intracranial cavity with attendant neurological changes. ... differentiated from intracranial haemorrhage. The presentation may include headache, ..... evacuation of chronic subdural hematoma : Is it a serious complication? Asian J Neurosurg. 2012 ...

  3. Study on the makinq of Cockroft Walton high tension

    International Nuclear Information System (INIS)

    Hutapea, Sumihar.

    1976-01-01

    A prototype of a generator is being developed at the GAMA Research Center. Experience in working with some components, high voltage capacitor, column, and potential divider is discussed. High voltage diode, the type which is usually used in television, is used. The tension of the generator is measured by using the high ohmic resistence of 4000 megaohm. The maximum tension can be reached no more than 150000 volts. (author)

  4. Nonzero Ideal Gas Contribution to the Surface Tension of Water.

    Science.gov (United States)

    Sega, Marcello; Fábián, Balázs; Jedlovszky, Pál

    2017-06-15

    Surface tension, the tendency of fluid interfaces to behave elastically and minimize their surface, is routinely calculated as the difference between the lateral and normal components of the pressure or, invoking isotropy in momentum space, of the virial tensor. Here we show that the anisotropy of the kinetic energy tensor close to a liquid-vapor interface can be responsible for a large part of its surface tension (about 15% for water, independent from temperature).

  5. Concentric and eccentric time-under-tension during strengthening exercises

    DEFF Research Database (Denmark)

    Skovdal Rathleff, Michael; Thorborg, Kristian; Bandholm, Thomas

    2013-01-01

    Total, single repetition and contraction-phase specific (concentric and eccentric) time-under-tension (TUT) are important exercise-descriptors, as they are linked to the physiological and clinical response in exercise and rehabilitation.......Total, single repetition and contraction-phase specific (concentric and eccentric) time-under-tension (TUT) are important exercise-descriptors, as they are linked to the physiological and clinical response in exercise and rehabilitation....

  6. Observer-based fault diagnosis for trucks belt tensioner

    OpenAIRE

    Dubuc , Donatien; Sename , Olivier; Bresch-Pietri , Delphine; Gauthier , Christophe

    2017-01-01

    International audience; This paper deals with the monitoring of a serpentine belt tensioner performance, a critical automotive engine component guaranteeing the cooling system efficiency. A belt tensioner fault will affect the transmission, deteriorate the water pump efficiency, and eventually, lead the engine to stall. Monitoring this component is thus a key to design predictive or corrective maintenance. In this paper, we propose to estimate a parameter which is shown to be characteristic o...

  7. Surface tension and related thermodynamic quantities of aqueous electrolyte solutions

    CERN Document Server

    Matubayasi, Norihiro

    2013-01-01

    Surface tension provides a thermodynamic avenue for analyzing systems in equilibrium and formulating phenomenological explanations for the behavior of constituent molecules in the surface region. While there are extensive experimental observations and established ideas regarding desorption of ions from the surfaces of aqueous salt solutions, a more successful discussion of the theory has recently emerged, which allows the quantitative calculation of the distribution of ions in the surface region. Surface Tension and Related Thermodynamic Quantities of Aqueous Electrolyte Solutions provides a d

  8. Queer feminist international relations: uneasy alliances, productive tensions

    OpenAIRE

    Leigh, Darcy

    2017-01-01

    This article examines the ‘uneasy alliance’ between Feminist IR and Queer IR. The article focusses on three areas of tension and continuity between the fields: (1) sexuality, sexual deviance and gender variance; (2) the roles of liberalism in gendered, sexualized and racialized violence; and (3) binaries relating to sex, gender and sexuality. The article argues that it is around tensions between Queer and Feminist IR that a Queer Feminist IR can be productively articulated. In particular, a Q...

  9. The spatial string tension and dimensional reduction in QCD

    Science.gov (United States)

    Cheng, M.; Datta, S.; van der Heide, J.; Huebner, K.; Karsch, F.; Kaczmarek, O.; Laermann, E.; Liddle, J.; Mawhinney, R. D.; Miao, C.; Petreczky, P.; Petrov, K.; Schmidt, C.; Soeldner, W.; Umeda, T.

    2008-08-01

    We calculate the spatial string tension in (2+1) flavor QCD with physical strange quark mass and almost physical light quark masses using lattices with temporal extent Nτ=4, 6 and 8. We compare our results on the spatial string tension with predictions of dimensionally reduced QCD. This suggests that also in the presence of light dynamical quarks dimensional reduction works well down to temperatures 1.5Tc.

  10. Managing Tensions Between New and Existing Business Models

    DEFF Research Database (Denmark)

    Sund, Kristian J.; Bogers, Marcel; Villarroel Fernandez, Juan Andrei

    2016-01-01

    Exploring new business models may be a good way to stay competitive, but doing so can create tensions internally, in areas such as organizational structure and competition for resources. Companies exploring business model innovation may not recognize the inevitability of these tensions and thus b...... be poorly prepared to manage them. But understanding these issues may lessen some of the organizational challenges associated with business model innovation....

  11. Development of Fabric-Type of Tensional Force Sensor

    OpenAIRE

    Suzuki, Y; Ogura, D; Shikida, M; Hasegawa, Y; Sato, K

    2009-01-01

    We developed a tensional force sensor by applying artificial tetrafluoroethylene-perfluoroalkylvinyl ether copolymer (PFA) hollow fibers. The fibers were fabricated by depositing thin metal and an insulation layer on the PFA tube, and the fabric sensor was made by weaving the decorated PFA tube and the conventional cotton yarns together. The sensor was 57.0 times 4.0 mm. The sensor output linearly increased with the increase of the tension. We confirmed that the sensor output increased with a...

  12. Central and peripheral mechanisms in chronic tension-type headache

    OpenAIRE

    Lipchik, Gay L.; Holroyd, Kenneth A.; France, Christopher R.; Kvaal, Steven A.; Segal, David; Cordingley, Gary E.; Rokicki, Lori A.; McCool, Heidi R.

    1996-01-01

    The second exteroceptive suppression of masseter muscle activity (ES2) and tenderness in pericranial muscles were evaluated in 112 young adults who met IHS criteria in the following diagnostic classifications: 31 chronic tension headache, 31 episodic tension headache, 33 migraine without aura and 17 migraine with aura. An additional 31 subjects served as controls. Pericranial muscle tenderness better distinguished diagnostic subgroups and better distinguished recurrent headache sufferers from...

  13. The role of muscles in tension-type headache

    DEFF Research Database (Denmark)

    Bendtsen, Lars; Fernández-de-la-Peñas, César

    2011-01-01

    The tenderness of pericranial myofascial tissues and number of myofascial trigger points are considerably increased in patients with tension-type headache (TTH). Mechanisms responsible for the increased myofascial pain sensitivity have been studied extensively. Peripheral activation or sensitizat......The tenderness of pericranial myofascial tissues and number of myofascial trigger points are considerably increased in patients with tension-type headache (TTH). Mechanisms responsible for the increased myofascial pain sensitivity have been studied extensively. Peripheral activation...

  14. MDT WIRE TENSION MEASUREMENT USING AN ELECTROSTATIC METHOD

    CERN Document Server

    Balla, A; Esposito, B; Felici, G; Nedosekin, A; Ponzio, B; Russo, V; Spitalieri, M C

    1998-01-01

    An automated system to measure wire tension in MDT tubes is presented.The method uses electrostatic forces between wire and tube to excite mechanical oscillation around the wire harmonic resonance. A LC oscillating circuit is used to measure capacitance variation due towire oscillation. Wire tension is determined by the frequency at which the wirereaches the maximum oscillation amplitude. Both the excitation and measuring circuits are controlled by a computer.

  15. Contact angle control of sessile drops on a tensioned web

    Science.gov (United States)

    Park, Janghoon; Kim, Dongguk; Lee, Changwoo

    2018-04-01

    In this study, the influence of the change of tension applied to flexible and thin web substrate on the contact angle of sessile drop in roll-to-roll system was investigated. Graphene oxide and deionized water solutions were used in the experiments. Tension was changed to 29, 49, and 69 N, and the casting distance of the micropipette and the material was set to 10, 20, and 40 mm, and the droplet volume was set to 10, 20, and 30 μL, respectively. Statistical analysis of three variables and analysis of the variance methodology showed that the casting distance was most significant for the contact angle change, and the most interesting tension variable was also affected. The change in tension caused the maximum contact angle to change by 5.5°. The tension was not uniform in the width direction. When the droplet was applied in the same direction in the width direction, it was confirmed that the tension unevenness had great influence on the contact angle up to 11°. Finally, the casting distance, which has a large effect on the contact angle, was calibrated in the width direction to reduce the width direction contact angle deviation to 1%. This study can be applied to fine patterning research using continuous inkjet printing and aerosol jet printing, which are roll-to-roll processes based on droplet handling.

  16. Tension-Enhanced Hydrogen Evolution Reaction on Vanadium Disulfide Monolayer.

    Science.gov (United States)

    Pan, Hui

    2016-12-01

    Water electrolysis is an efficient way for hydrogen production. Finding efficient, cheap, and eco-friendly electrocatalysts is essential to the development of this technology. In the work, we present a first-principles study on the effects of tension on the hydrogen evolution reaction of a novel electrocatalyst, vanadium disulfide (VS2) monolayer. Two electrocatalytic processes, individual and collective processes, are investigated. We show that the catalytic ability of VS2 monolayer at higher hydrogen coverage can be efficiently improved by escalating tension. We find that the individual process is easier to occur in a wide range of hydrogen coverage and the collective process is possible at a certain hydrogen coverage under the same tension. The best hydrogen evolution reaction with near-zero Gibbs free energy can be achieved by tuning tension. We further show that the change of catalytic activity with tension and hydrogen coverage is induced by the change of free carrier density around the Fermi level, that is, higher carrier density, better catalytic performance. It is expected that tension can be a simple way to improve the catalytic activity, leading to the design of novel electrocatalysts for efficient hydrogen production from water electrolysis.

  17. Patients with tension-type headaches feel stigmatized

    Directory of Open Access Journals (Sweden)

    Sanjay Prakash

    2016-01-01

    Full Text Available The author, a sufferer of tension-type headache (TTH, believes that the word "tension" in "tension-type headache" carries a social stigma and that patients do not accept a diagnosis of TTH readily. TTH is the most common primary headache disorder. The disability of TTH as a burden of society is greater than that of migraine. Absenteeism because of TTH is higher than that due to migraine. However, patients with TTH do not go for consultation. Even the prevalence of new daily persistent headache (NDPH is 12 times higher at the headache clinic than that of chronic TTH (CTTH. These points hint that TTH patients probably do not want to visit the clinic. The author believes that it could be because of the stigma attached to "tension." Herein, the author has noted the first responses given by 50 consecutive patients with TTH when they were told that they had been suffering from TTH. The first answer of 64% of patients with TTH was "I do not have any tension/stress ." This denial is similar to the denial declared by patients with depression. Depression and tension are similar in the sense that both are considered as a signs of personal weakness. Such a preconception in the society creates a stigma, and patients deny the diagnosis, conceal symptoms, and become reluctant to seek help and treatment.

  18. Dynamic interplay between the collagen scaffold and tumor evolution

    DEFF Research Database (Denmark)

    Egeblad, Mikala; Rasch, Morten G; Weaver, Valerie M

    2010-01-01

    and remodeling of the ECM network regulate tissue tension, generate pathways for migration, and release ECM protein fragments to direct normal developmental processes such as branching morphogenesis. Collagens are major components of the ECM of which basement membrane type IV and interstitial matrix type I...... are the most prevalent. Here we discuss how abnormal expression, proteolysis and structure of these collagens influence cellular functions to elicit multiple effects on tumors, including proliferation, initiation, invasion, metastasis, and therapy response....

  19. Superficial urinary bladder tumors treatment results: A 10-year experience

    Directory of Open Access Journals (Sweden)

    Stanković Jablan

    2007-01-01

    Full Text Available Background/Aim. The most common urinary bladder tumors are superficial tumors. Due to their tension to relapse and progress towards deeper layers after surgical therapy, an adequate therapy significantly contributed to the improvement of the results of urinary bladder tumors treatment. Staging and gradus of the tumor, presence of the carcinoma in situ (CIS or relapses significantly influenced the choice of the therapy. The aim of this study was to ascertain the effectiveness of the intravesicelly applied BCG (Bacille Colmette - Guerin vaccine or chemiotherapy in the prevention of the relapses and further progression of superficial urinary bladder tumors. Methods. All of the diagnosed superficial tumors of bladder were removed by transurethral resection (TUR. After receiving the patohistological finding they were subjected to adjuvant therapy, immune BCG vaccine or chemiotherapy (epirubicin, doxorubicin, mitomycin-C. The third group did not accept adjuvant therapy, but had regularly scheduled cystoscopic controls. The appearance of relapses, progression of stage and grades of the tumor, as well as possible unwanted effects of adjuvant therapy were registered. Results. The applied immunotherapy (BCG influenced decreased tumor relapses (7% and statistically important difference between patients who had taken adjuvant chemotherapy (relapses 18.4% and those without this therapy was acknowledged. Grades of tumor did not show statistically significant difference on tumor relapse. A significantly longer period of time in the appearance of tumor relapse after BCG (29.33 months, had significant importance comparing to chemio (9.44 months or non-taken adjuvant therapy (9.84 months. Very small number of unwanted effects suggested an obligatory undertaking adjuvant therapy after TUR of superficial tumors. Conclusion. A significant decrease of relapses as well as avoidance of further progression of urinary bladder tumors, has introduced adjuvant therapy in

  20. Perceiving the affordance of string tension for power strokes in badminton: expertise allows effective use of all string tensions.

    Science.gov (United States)

    Zhu, Qin

    2013-01-01

    Affordances mean opportunities for action. These affordances are important for sports performance and relevant to the abilities developed by skilled athletes. In racquet sports such as badminton, different players prefer widely different string tension because it is believed to provide opportunities for effective strokes. The current study examined whether badminton players can perceive the affordance of string tension for power strokes and whether the perception of affordance itself changed as a function of skill level. The results showed that string tension constrained the striking performance of both novice and recreational players, but not of expert players. When perceptual capability was assessed, perceptual mode did not affect perception of the optimal string tension. Skilled players successfully perceived the affordance of string tension, but only experts were concerned about saving energy. Our findings demonstrated that perception of the affordance of string tension in badminton was determined by action abilities. Furthermore, experts could adjust the action to maintain a superior level of performance based on the perception of affordance.