Multiple Lumiphore-Bound Nanoparticles for in vivo Quantification of Localized Oxygen Levels

Author(s):  
J. L. Van Druff ◽  
W. Zhou ◽  
E. Asman ◽  
J. B. Leach
Keyword(s):  
Author(s):  
Junchao Qian ◽  
Xiang Yu ◽  
Bingbing Li ◽  
Zhenle Fei ◽  
Xiang Huang ◽  
...  

Background:: It was known that the response of tumor cells to radiation is closely related to tissue oxygen level and fractionated radiotherapy allows reoxygenation of hypoxic tumor cells. Non-invasive mapping of tissue oxygen level may hold great importance in clinic. Objective: The aim of this study is to evaluate the role of oxygen-enhanced MR imaging in the detection of tissue oxygen levels between fractionated radiotherapy. Methods: A cohort of 10 patients with brain metastasis was recruited. Quantitative oxygen enhanced MR imaging was performed prior to, 30 minutes and 22 hours after first fractionated radiotherapy. Results: The ΔR1 (the difference of longitudinal relaxivity between 100% oxygen breathing and air breathing) increased in the ipsilateral tumor site and normal tissue by 242% and 152%, respectively, 30 minutes after first fractionated radiation compared to pre-radiation levels. Significant recovery of ΔR1 in the contralateral normal tissue (p < 0.05) was observed 22 hours compared to 30 minutes after radiation levels. Conclusion: R1-based oxygen-enhanced MR imaging may provide a sensitive endogenous marker for oxygen changes in the brain tissue between fractionated radiotherapy.


2001 ◽  
Vol 2001 ◽  
pp. 100-100
Author(s):  
J. Periz ◽  
K. Hillman

Lactobacillus probiotics have consistently shown in vitro properties of key importance in the prevention of diarrhoea at weaning. However, these probiotics have shown variable results in pigs in vivo, and it is important to determine the reasons for this variability if the efficacy of the preparations is to be improved. Hillman et al. (1993) reported that there are significant oxygen levels along the piglet intestine. As Lactobacillus spp. are primarily anaerobic bacteria, and are isolated and examined in vitro under anaerobic conditions, it is possible that the presence of oxygen along the piglet intestine could be exerting a detrimental action on their probiotic effectiveness. This experiment was set up to examine the influence of oxygen on two porcine Lactobacillus spp which have been previously demonstrated to inhibit the growth of Escherichia coli K88 in vitro (Hillman and Fox, 1994).


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. SCI-25-SCI-25 ◽  
Author(s):  
Matthew Vander Heiden

Abstract Abstract SCI-25 Many cancer cells metabolize glucose by aerobic glycolysis, a phenomenon characterized by increased glycolysis with lactate production and decreased oxidative phosphorylation. We have argued that alterations in cell metabolism associated with cancer may be selected by cancer cells to meet the distinct metabolic needs of proliferation. Unlike metabolism in differentiated cells, which is geared toward efficient ATP generation, the metabolism in cancer cells must be adapted to facilitate the accumulation of biomass. Cancer cells divert a larger fraction of their nutrient metabolism to pathways other than mitochondrial respiration regardless of oxygen availability. Nevertheless, oxygen levels still influence how nutrients are metabolized. We have found that the source of carbon used in various anabolic processes varies based on oxygen levels. Furthermore, the enzymes used to metabolize nutrients can also differ based on the cellular context. This includes regulation of isocitrate dehydrogenase, an enzyme that is mutated in some cancers. There is also strong selection for use of the M2 isoform of pyruvate kinase (PK-M2) to metabolize glucose in cancer cell lines. However, evidence from mouse models suggests that PK-M2 is dispensable for glucose metabolism by many tumors in vivo, suggesting an alternate pathway to convert phosphoenolpyruvate to pyruvate can be used to metabolize glucose. This regulation of pyruvate kinase also plays an important role in hematopoietic stem cell biology. Together, these findings argue that distinct metabolic phenotypes exist among proliferating cells, and both environmental and genetic factors influence how metabolism is regulated to support cell growth. Disclosures: Vander Heiden: Agios Pharmaceuticals: Consultancy, Equity Ownership.


2005 ◽  
Vol 98 (4) ◽  
pp. 1177-1184 ◽  
Author(s):  
Paul C. Johnson ◽  
Kim Vandegriff ◽  
Amy G. Tsai ◽  
Marcos Intaglietta

Repeated exposure to brief periods of hypoxia leads to pathophysiological changes in experimental animals similar to those seen in sleep apnea. To determine the effects of such exposure on oxygen levels in vivo, we used an optical method to measure Po2 in microcirculatory vessels and tissue of the rat cremaster muscle during a 1-min step reduction of inspired oxygen fraction from 0.21 to 0.07. Under control conditions, Po2 was 98.1 ± 1.9 Torr in arterial blood, 52.2 ± 2.8 Torr in 29.0 ± 2.7-μm arterioles, 26.8 ± 1.7 Torr in the tissue interstitium near venous capillaries, and 35.1 ± 2.6 Torr in 29.7 ± 1.9-μm venules. The initial fall in Po2 during hypoxia was significantly greater in arterial blood, being 93% complete in the first 10 s, whereas it was 68% complete in arterioles, 47% at the tissue sites, and 38% in venules. In the 10- to 30-s period, the fall in normalized tissue and venular Po2 was significantly greater than in arterial Po2. At the end of hypoxic exposure, Po2 at all measurement sites had fallen very nearly in proportion to that in the inspired gas, but tissue oxygen levels did not reach critical Po2. Significant differences in oxyhemoglobin desaturation rate were also observed between arterial and microcirculatory vessels during hypoxia. In conclusion, the fall in microcirculatory and tissue oxygen levels in resting skeletal muscle is significantly slower than in arterial blood during a step reduction to an inspired oxygen fraction of 0.07, and tissue Po2 does not reach anaerobic levels.


2019 ◽  
Author(s):  
Kamaleldin B Said ◽  
Xin Zhao ◽  
Marcus B Jones ◽  
Rosslyn Maybank ◽  
Scott Peterson

Abstract Background Mastitis-specialized lineages of Staphylococcus aureus are important pathogens in the dairy industry. The molecular mechanisms underlying host- and organ-specialization in these lineages are still not fully understood. Recent findings suggested that differential expression of genes may have contributed to the evolution of strains with enhanced virulence. However, studies on gene expressions under key intra-mammary conditions are quite limited for mastitis S. aureus . The purpose of the study was to investigate the influence of low oxygen levels on the transcriptome profiles of bovine matitis S. aureus , using high-throughput whole genome qRT-PCR.Results Results showed that under normal oxygenation, a mastitis-isolate expressed subsets of genes for adaptation, environmental-sensing, and binding including merR, sigB , vraS , yycG/yycF , araC , and tetR . In addition, coupling of fermentative metabolism to virulence was indicated by accumulated transcripts for catabolite control protein A ( ccpA) and pentose-monophosphate operon and depleted transcripts for tricaroxylic acid cycle. Furthermore, sarU mediated agr activation was evidented by transcripts for toxins, adaptation, and in-vivo viability factors as staphopains and gntR operon. On the other hand, reduced oxygenation increased transcription of fibrinogen-binding genes, isd- operon, and sdrH showing aggressive adherence phenotype. While normal oxygenation produced gene activities for quick and aggressive responses, low-oxygenation induced phenotypes for persistence, binding, and metabolic inactivity.Conclusion Significant differences in the transcriptional profiles were observed for mammary alveolar cell-T (MAC-T) internalized S. aureus under low oxygen levels compared to that at normal levels. This indicated that low oxygen is an important key mammary factor that influence transcriptome profiles of intra-mammary-specific phenotypes of S. aureus . These findings will help in understanding the effect of oxygen on the differentiation and evolution of intramammary S. aureus .


2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Yousef K. Al-Mutawa ◽  
Anne Herrmann ◽  
Catriona Corbishley ◽  
Paul D. Losty ◽  
Marie Phelan ◽  
...  

Hypoxia episodes and areas in tumours have been associated with metastatic dissemination and poor prognosis. Given the link between tumour tissue oxygen levels and cellular metabolic activity, we hypothesised that the metabolic profile between metastatic and non-metastatic tumours would reveal potential new biomarkers and signalling cues. We have used a previously established chick embryo model for neuroblastoma growth and metastasis, where the metastatic phenotype can be controlled by neuroblastoma cell hypoxic preconditioning (3 days at 1% O2). We measured, with fibre-optic oxygen sensors, the effects of the hypoxic preconditioning on the tumour oxygenation, within tumours formed by SK-N-AS cells on the chorioallantoic membrane (CAM) of chick embryos. We found that the difference between the metastatic and non-metastatic intratumoural oxygen levels was small (0.35% O2), with a mean below 1.5% O2 for most tumours. The metabolomic profiling, using NMR spectroscopy, of neuroblastoma cells cultured in normoxia or hypoxia for 3 days, and of the tumours formed by these cells showed that the effects of hypoxia in vitro did not compare with in vivo tumours. One notable difference was the high levels of the glycolytic end-products triggered by hypoxia in vitro, but not by hypoxia preconditioning in tumours, likely due to the very high basal levels of these metabolites in tumours compared with cells. In conclusion, we have identified high levels of ketones (3-hydroxybutyrate), lactate and phosphocholine in hypoxic preconditioned tumours, all known to fuel tumour growth, and we herein point to the poor relevance of in vitro metabolomic experiments for cancer research.


2020 ◽  
Author(s):  
Chao Li ◽  
Mouhita Humayun ◽  
Glenn M Walker ◽  
Keon Young Park ◽  
Bryce Connors ◽  
...  

Oxygen levels in vivo are autonomously regulated by a supply-demand balance, which can be altered in disease states. However, the oxygen levels of in vitro cell culture systems, particularly microscale cell culture, are typically dominated by either supply or demand. Further, the oxygen microenvironment in these systems are rarely monitored or reported. Here, we present a method to establish and dynamically monitor autonomously regulated oxygen microenvironments (AROM) using an oil overlay in an open microscale cell culture system. Using this method, the oxygen microenvironment is dynamically regulated via a supply-demand balance of the system. We simulate the kinetics of oxygen diffusion in multiliquid-phase microsystems on COMSOL Multiphysics and experimentally validate the method using a variety of cell types including mammalian, fungal and bacterial cells. Finally, we demonstrate the utility of this method to establish a co-culture between primary intestinal epithelial cells and a highly prevalent human gut species Bacteroides uniformis.


Author(s):  
Daan Adriaan Weits

Abstract Oxygen is essential for multicellular aerobic life due to its central role in energy metabolism. The availability of oxygen can drop below the level to sustain oxidative phosphorylation when plants are flooded, posing a severe threat to survival. However, under non-stressful conditions, the internal oxygen concentrations of most plant tissue is not in equilibrium with the environment, which is attributed to cellular respiration and diffusion constrains imposed by O2 barriers and bulky tissue. This is exemplified by the observations of steep oxygen gradients in roots, fruits, tubers, anthers and meristems. In order to adapt to a varying availability of oxygen, plants sense O2 via the conditional proteolysis of transcriptional regulators. This mechanism acts to switch oxidative metabolism to anaerobic fermentation, but it was also shown to play a role in plant development and pathogen defense. To investigate how dynamic and spatial distribution of O2 impacts on these processes, accurate mapping of its concentration in plants is essential. Physical oxygen sensors have been employed for decades to profile internal oxygen concentrations in plants, while genetically encoded oxygen biosensors have only recently started to see use. Driven by the critical role of hypoxia in human pathology and development, several novel oxygen sensing devices have also been characterized in cell lines and animal model organisms. This review aims to provide an overview of available oxygen biosensors, and to discuss their potential application to image oxygen levels in plants.


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