Tissue Oxygen Content Research Articles

Bayesian Modeling of NMR Data: Quantifying Longitudinal Relaxation in Vivo, and in Vitro with a Tissue-Water-Relaxation Mimic (Crosslinked Bovine Serum Albumin).

Recently, a number of MRI protocols have been reported that seek to exploit the effect of dissolved oxygen (O2, paramagnetic) on the longitudinal 1H relaxation of tissue water, thus providing image contrast related to tissue oxygen content. However, tissue water relaxation is dependent on a number of mechanisms, and this raises the issue of how best to model the relaxation data. This problem, the model selection problem, occurs in many branches of science and is optimally addressed by Bayesian probability theory. High signal-to-noise, densely sampled, longitudinal 1H relaxation data were acquired from rat brain in vivo and from a cross-linked bovine serum albumin (xBSA) phantom, a sample that recapitulates the relaxation characteristics of tissue water in vivo. Bayesian-based model selection was applied to a cohort of five competing relaxation models: (i) monoexponential, (ii) stretched-exponential, (iii) biexponential, (iv) Gaussian (normal) R1-distribution, and (v) gamma R1-distribution. Bayesian joint analysis of multiple replicate datasets revealed that water relaxation of both the xBSA phantom and in vivo rat brain was best described by a biexponential model, while xBSA relaxation datasets truncated to remove evidence of the fast relaxation component were best modeled as a stretched exponential. In all cases, estimated model parameters were compared to the commonly used monoexponential model. Reducing the sampling density of the relaxation data and adding Gaussian-distributed noise served to simulate cases in which the data are acquisition-time or signal-to-noise restricted, respectively. As expected, reducing either the number of data points or the signal-to-noise increases the uncertainty in estimated parameters and, ultimately, reduces support for more complex relaxation models.

Blood Oxygenation Level-Dependent MRI to Assess Renal Oxygenation in Renal Diseases: Progresses and Challenges.

BOLD-MRI (blood oxygenation-level dependent magnetic resonance imaging) allows non-invasive measurement of renal tissue oxygenation in humans, without the need for contrast products. BOLD-MRI uses the fact that magnetic properties of hemoglobin depend of its oxygenated state:: the higher local deoxyhemoglobin, the higher the so called apparent relaxation rate R2* (sec−1), and the lower local tissue oxygen content. Several factors other than deoxyhemoglobin (such as hydration status, dietary sodium intake, and susceptibility effects) influence the BOLD signal, and need to be taken into account when interpreting results. The last 5 years have witnessed important improvements in the standardization of these factors, and the appearance of new, highly reproducible analysis techniques of BOLD-images, that are reviewed in this article. Using these new BOLD-MRI analysis techniques, it has recently been shown that persons suffering from chronic kidney diseases (CKD) have lower cortical oxygenation than normotensive controls, thus confirming the chronic hypoxia hypothesis. The acute alterations in R2* after the administration of furosemide are smaller in CKD, and represent an estimate of the oxygen-dependent tubular transport of sodium. BOLD-MRI-alone or in combination with other functional MRI methods- can be used to monitor the renal effects of drugs, and is increasingly used in the preclinical setting. The near future will tell whether or not BOLD-MRI represents a new tool to predict renal function decline an adverse renal outcome.

Hyperbaric oxygen for the treatment of skin diseases

Hyperbaric oxygen (HBO) therapy is the inhalation of 100% oxygen at a pressure higher than one atmosphere absolute (ATA) , and has been used as an auxiliary therapy for various skin diseases. It has been proved that HBO can increase the oxygen content in skin tissues, accelerate aerobic metabolism of skin, promote epithelial regeneration and wound healing, relieve adverse stimuli on peripheral nerves and sensors in the skin, inhibit apoptosis of neurons, enhance the function of regulatory T cells, alleviate inflammation, and mobilize vascular stem/progenitor cells (SPCs) from the bone marrow to peripheral blood and ulcer tissues. At present, HBO has been widely applied in the auxiliary treatment of psoriasis, atopic dermatitis, postherpetic neuralgia, chronic refractory cutaneous ulcer, pyoderma gangrenosum, fungal infection, vascular embolization after cosmetic facial filling, and some other skin diseases. Key words: Skin diseases; Hyperbaric oxygenation; Therapeutic uses; Drug therapy, combination; Physical therapy modalities

First in situ TOF-PET study using digital photon counters for proton range verification

Positron emission tomography (PET) is the imaging modality most extensively tested for treatment monitoring in particle therapy. Optimal use of PET in proton therapy requires in situ acquisition of the relatively strong 15O signal due to its relatively short half-life (~2 min) and high oxygen content in biological tissues, enabling shorter scans that are less sensitive to biological washout. This paper presents the first performance tests of a scaled-down in situ time-of-flight (TOF) PET system based on digital photon counters (DPCs) coupled to Cerium-doped Lutetium Yttrium Silicate (LYSO:Ce) crystals, providing quantitative results representative of a dual-head tomograph that complies with spatial constraints typically encountered in clinical practice (2 × 50°, of 360°, transaxial angular acceptance). The proton-induced activity inside polymethylmethacrylate (PMMA) and polyethylene (PE) phantoms was acquired within beam pauses (in-beam) and immediately after irradiation by an actively-delivered synchrotron pencil-beam, with clinically relevant 125.67 MeV/u, 4.6 × 108 protons s−1, and 1010 total protons. 3D activity maps reconstructed with and without TOF information are compared to FLUKA simulations, demonstrating the benefit of TOF-PET to reduce limited-angle artefacts using a 382 ps full width at half maximum coincidence resolving time. The time-dependent contributions from different radionuclides to the total count-rate are investigated. We furthermore study the impact of the acquisition time window on the laterally integrated activity depth-profiles, with emphasis on 2 min acquisitions starting at different time points. The results depend on phantom composition and reflect the differences in relative contributions from the radionuclides originating from carbon and oxygen. We observe very good agreement between the shapes of the simulated and measured activity depth-profiles for post-beam protocols. However, our results also suggest that available experimental cross sections underestimate the production of 10C for in-beam acquisitions, which in PE results in an overestimation of the predicted activity range by 1.4 mm. The uncertainty in the activity range measured in PMMA using the DPC-based TOF-PET prototype setup equals 0.2 mm–0.3 mm.

Anti-Inflammatory Effects of Hyperbaric Oxygenation during DSS-Induced Colitis in BALB/c Mice Include Changes in Gene Expression of HIF-1α, Proinflammatory Cytokines, and Antioxidative Enzymes.

Reactive oxygen species (ROS) and nitrogen species have an indispensable role in regulating cell signalling pathways, including transcriptional control via hypoxia inducible factor-1α (HIF-1α). Hyperbaric oxygenation treatment (HBO2) increases tissue oxygen content and leads to enhanced ROS production. In the present study DSS-induced colitis has been employed in BALB/c mice as an experimental model of gut mucosa inflammation to investigate the effects of HBO2 on HIF-1α, antioxidative enzyme, and proinflammatory cytokine genes during the colonic inflammation. Here we report that HBO2 significantly reduces severity of DSS-induced colitis, as evidenced by the clinical features, histological assessment, impaired immune cell expansion and mobilization, and reversal of IL-1β, IL-2, and IL-6 gene expression. Gene expression and antioxidative enzyme activity were changed by the HBO2 and the inflammatory microenvironment in the gut mucosa. Strong correlation of HIF-1α mRNA level to GPx1, SOD1, and IL-6 mRNA expression suggests involvement of HIF-1α in transcriptional regulation of these genes during colonic inflammation and HBO2. This is further confirmed by a strong correlation of HIF-1α with known target genes VEGF and PGK1. Results demonstrate that HBO2 has an anti-inflammatory effect in DSS-induced colitis in mice, and this effect is at least partly dependent on expression of HIF-1α and antioxidative genes.

Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo.

Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG) of the hippocampus and the sub-ventricular zone (SVZ) of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCs)in vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr) and DG (approximately 10 Torr) were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr). Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.

An MRI Method To Map Tumor Hypoxia Using Red Blood Cells Loaded with a pO2-Responsive Gd-Agent.

Hypoxia is a typical hallmark of many solid tumors and often leads to therapy resistance and the development of a more aggressive cancer phenotype. Oxygen content in tissues has been evaluated using numerous different methods for several imaging modalities, but none has yet reached the required standard of spatial and temporal resolution. Magnetic Resonance Imaging (MRI) appears to be the technique of choice and several pO2-responsive probes have been designed for it over the years. In vivo translation is often hampered in Gd-relaxation agents as it is not possible to separate effects that arise from changes in local concentration from those associated with responsive properties. A novel procedure for the MRI based assessment of hypoxia is reported herein. The method relies on the combined use of Gd-DOTP- and Gd-HPDO3A-labeled red blood cells (RBCs) where the first probe acts as a vascular oxygenation-responsive agent, while the second reports the local labeled RBC concentration in a transplanted breast tumor mouse model. The MRI assessment of oxygenation state has been validated by photoacoustic imaging and ex vivo immunofluorescence. The method refines tumor staging in preclinical models and makes possible an accurate monitoring of the relationship between oxygenation and tumor growth.

The ability of cells to adapt to low-oxygen conditions is associated with glutathionylation of Na,K-ATPase

The decrease in the oxygen content of tissues, which is observed in a number of pathological processes, inevitably leads to damage. One of the main causes of cell damage and death in hypoxia is the failure of the systems that maintain the ionic balance. Na,K-ATPase is the main ion-transporting protein in the plasma membrane of animal cells, and its inhibition at low concentrations of oxygen is one of the earliest and most critical events for cell viability. Scientists are currently conducting an active search for regulators of Na,K-ATPase activity. Cardiac glycosides traditionally used for this purpose induce severe side effects, which necessitates the search for alternative inhibitors of Na,K-ATPase. We have previously found that glutathionylation of the Na,K-ATPase catalytic subunit leads to a complete inhibition of the enzyme. The present study demonstrates that the substances that increase the level of glutathionylation in Na,K-ATPase, namely, ethyl glutathione (et-GSH), oxidized glutathione (GSSG), and N-acetylcysteine (NAC), enhance cell survival under low-oxygen conditions, prevent ATP depletion, and normalize the redox status of the cells. The following concentration range in which these substances have the maximum protective effect and no pronounced cytotoxic properties was determined to be as follows: 0.2–0.5 mM et-GSH, 0.2–1 mM GSSG, and 10–15 mM NAC. These results demonstrate the prospects of developing methods of protecting tissues from damage under low-oxygen conditions that are based on changes in Na,K-ATPase glutathionylation.

Erythrocyte deformability and nitric oxide mobilization under pannexin-1 and PKC dependence

The erythrocyte adenosine triphosphate (ATP) is utilised for protein phosphorylation and exported through the pannexin 1 hemichannel (Px1) in the microcirculation. The physiological stimuli for ATP release are dependent of blood shear rate level and of the tissue oxygen content. The deoxygenated and oxygenated states of haemoglobin are respectively bound and unbound to N terminal domain of the protein band 3 of the erythrocyte membrane in dependence of its degree of phosphorylation. The protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) contribute to the phosphorylation degree of band 3 and are modulated by protein kinase C (PKC). Chelerythrine (Che) is a competitive inhibitor of ATP for PKC and a negative modulator of erythrocyte deformability. The aim of this study was to assess the mobilization of nitric oxide (NO) in erythrocyte in absence and presence of Che and Px1 inhibitor (carbenoxolone). Erythrocyte deformability was evaluated in presence of carbenoxolone (Carb). Regarding the effects observed in the erythrocyte by presence of Che or Carb, the values of efflux of NO and the concentration of nitrosogluthatione are similar and with no changes in relation to their absence. Px1inhibition by Carb 10 μM ameliorates the erythrocyte deformability at a shear force of 0.6 and 1.2 Pa. The PKC inhibitor shows similar effects to the Carb on the mobilization of nitric oxide in erythrocyte. The blockage of ATP release by Carb from erythrocytes suggests a possible benefit to develop in ischemia reperfusion or in inflammatory response where will be needed to rescue the excess of NO present and ameliorate the red blood cell deformability at low shear rates.

Synergistic inhibitory effect of hyperbaric oxygen combined with sorafenib on hepatoma cells.

ObjectivesHypoxia is a common phenomenon in solid tumors, associated with chemotherapy and radiotherapy resistance, recurrence and metastasis. Hyperbaric oxygen (HBO) therapy can increase tissue oxygen pressure and content to prevent the resistance, recurrence and metastasis of cancer. Presently, Sorafenib is a first-line drug, targeted for hepatocellular carcinoma (HCC) but effective in only a small portion of patients and can induce hypoxia. The purpose of this study is to investigate the effect of HBO in combination with sorafenib on hepatoma cells.MethodsHepatoma cell lines (BEL-7402 and SK-Hep1) were treated with HBO at 2 atmosphere absolute pressure for 80 min per day or combined with sorafenib or cisplatin. At different time points, cells were tested for cell growth, colony formation, apoptosis, cell cycle and migration. Finally, miRNA from the hepatoma cells was detected by microRNA array and validated by qRT-PCR.ResultsAlthough HBO, sorafenib or cisplatin alone could inhibit growth of hepatoma cells, HBO combined with sorafenib or cisplatin resulted in much greater synergistic growth inhibition (cell proliferation and colony formation) in hepatoma cells. Similarly, the synergistic effect of HBO and sorafenib on induction of apoptosis was also observed in hepatoma cells. HBO induced G1 arrest in SK-Hep1 not in BEL-7402 cells, but enhanced cell cycle arrest induced by sorafenib in BEL-7402 treated cells. However, HBO had no obvious effect on the migration of hepatoma cells, and microRNA array analysis showed that hepatoma cells with HBO treatment had significantly different microRNA expression profiles from those with blank control.ConclusionsWe show for the first time that HBO combined with sorafenib results in synergistic growth inhibition and apoptosis in hepatoma cells, suggesting a potential application of HBO combined with sorafenib in HCC patients. Additionally, we also show that HBO significantly altered microRNA expression in hepatoma cells.

Study the effect of hyperbaric oxygen therapy in Egyptian autistic children: A clinical trial

BackgroundNumerous studies of autistic individuals have revealed evidence of cerebral hypoperfusion, neuroinflammation, gastrointestinal inflammation, immune dysregulation, oxidative stress, relative mitochondrial dysfunction, and neurotransmitter abnormalities. Many of these findings have been correlated with core autistic symptoms. For example, cerebral hypoperfusion in autistic children has been correlated with repetitive, self-stimulatory and stereotypical behaviors, and impairments in communication. Specifically, hyperbaric oxygen therapy (HBOT) has been used and can compensate for decreased blood flow by increasing the oxygen content of plasma and body tissues. The aim of this work was to study the effect of hyperbaric oxygen therapy in autistic Egyptian children. Patients and methodsThis prospective clinical trial study was conducted on 20 children diagnosed as autism based on DSM-IV-TR criteria (diagnostic and statistical manual of mental disorders, 4th edition criteria, text revised). All patients received at least 20 sessions of hyperbaric oxygen therapy. Sessions were done at pressure 1.5 ATA (atmosphere absolute) with 100% oxygen concentration each lasting for 1–1.5h either in multiplace chamber or monoplace chamber. MRI Perfusion of the brain was done before and after at least 20 HBOT sessions only for 6 cases. ResultsThere was a statistically significant increase in the ratio of regional cerebral blood flow (RCBF) to white matter after HBOT in different brain regions when compared to their levels before HBOT. ConclusionHBOT is a treatment that has recently become quite popular in the autism spectrum disorder (ASD) community. Its benefits cross a wide range of autistic traits as: improved language, increased awareness, behavior and socialization by affecting the pathophysiological findings in autism.

The Oxygen Paradox of Neurovascular Coupling

The coupling of cerebral blood flow (CBF) to neuronal activity is well preserved during evolution. Upon changes in the neuronal activity, an incompletely understood coupling mechanism regulates diameter changes of supplying blood vessels, which adjust CBF within seconds. The physiologic brain tissue oxygen content would sustain unimpeded brain function for only 1 second if continuous oxygen supply would suddenly stop. This suggests that the CBF response has evolved to balance oxygen supply and demand. Surprisingly, CBF increases surpass the accompanying increases of cerebral metabolic rate of oxygen (CMRO2). However, a disproportionate CBF increase may be required to increase the concentration gradient from capillary to tissue that drives oxygen delivery. However, the brain tissue oxygen content is not zero, and tissue pO2 decreases could serve to increase oxygen delivery without a CBF increase. Experimental evidence suggests that CMRO2 can increase with constant CBF within limits and decreases of baseline CBF were observed with constant CMRO2. This conflicting evidence may be viewed as an oxygen paradox of neurovascular coupling. As a possible solution for this paradox, we hypothesize that the CBF response has evolved to safeguard brain function in situations of moderate pathophysiological interference with oxygen supply.

Hypoxia Drives Tenocyte Differentiation: Not a clinical study

Oxygen content in connective tissues varies. At the tendon–bone interface, oxygen levels are low.1 Interestingly, human tenocytes lose their phenotype when cultured repeatedly in normal (normoxic) oxygen tension in vitro.2 Given the low oxygen levels in the region of the tendon as it joins the enthesis in vivo,3 we hypothesized that oxygen content may be responsible for tendon cell differentiation in vitro. Furthermore, given that oxygen levels affect activity of the Rho family of small GTPases,4 we hypothesized that oxygen tension drives tenocyte differentiation through differential activity of RhoA and Rac1 GTPase.

Deriving concentrations of oxygen and carbon in human tissues using single- and dual-energy CT for ion therapy applications

Dedicated methods of in-vivo verification of ion treatment based on the detection of secondary emitted radiation, such as positron-emission-tomography and prompt gamma detection require high accuracy in the assignment of the elemental composition. This especially concerns the content in carbon and oxygen, which are the most abundant elements of human tissue. The standard single-energy computed tomography (SECT) approach to carbon and oxygen concentration determination has been shown to introduce significant discrepancies in the carbon and oxygen content of tissues. We propose a dual-energy CT (DECT)-based approach for carbon and oxygen content assignment and investigate the accuracy gains of the method. SECT and DECT Hounsfield units (HU) were calculated using the stoichiometric calibration procedure for a comprehensive set of human tissues. Fit parameters for the stoichiometric calibration were obtained from phantom scans. Gaussian distributions with standard deviations equal to those derived from phantom scans were subsequently generated for each tissue for several values of the computed tomography dose index (CTDIvol). The assignment of %weight carbon and oxygen (%wC,%wO) was performed based on SECT and DECT. The SECT scheme employed a HU versus %wC,O approach while for DECT we explored a Zeff versus %wC,O approach and a (Zeff, ρe) space approach. The accuracy of each scheme was estimated by calculating the root mean square (RMS) error on %wC,O derived from the input Gaussian distribution of HU for each tissue and also for the noiseless case as a limiting case. The (Zeff, ρe) space approach was also compared to SECT by comparing RMS error for hydrogen and nitrogen (%wH,%wN). Systematic shifts were applied to the tissue HU distributions to assess the robustness of the method against systematic uncertainties in the stoichiometric calibration procedure. In the absence of noise the (Zeff, ρe) space approach showed more accurate %wC,O assignment (largest error of 2%) than the Zeff versus %wC,O and HU versus %wC,O approaches (largest errors of 15% and 30%, respectively). When noise was present, the accuracy of the (Zeff, ρe) space (DECT approach) was decreased but the RMS error over all tissues was lower than the HU versus %wC,O (SECT approach) (5.8%wC versus 7.5%wC at CTDIvol = 20 mGy). The DECT approach showed decreasing RMS error with decreasing image noise (or increasing CTDIvol). At CTDIvol = 80 mGy the RMS error over all tissues was 3.7% for DECT and 6.2% for SECT approaches. However, systematic shifts greater than ±5HU undermined the accuracy gains afforded by DECT at any dose level. DECT provides more accurate %wC,O assignment than SECT when imaging noise and systematic uncertainties in HU values are not considered. The presence of imaging noise degrades the DECT accuracy on %wC,O assignment but it remains superior to SECT. However, DECT was found to be sensitive to systematic shifts of human tissue HU.

Calf muscle stimulation with the Veinoplus device results in a significant increase in lower limb inflow without generating limb ischemia or pain in patients with peripheral artery disease

Increase in arterial inflow to the lower limbs is important to obtain functional improvement in peripheral artery disease (PAD) patients with claudication. The aim of this study was to assess the effect of electrical stimulation of calf muscles on arterial inflow and tissue oxygen content in PAD in the area of stimulation. Fifteen adult patients [mean (standard deviation) age, 62 (12 ) years; height, 165 (8)cm; weight, 76 (13) kg; lowest ankle-brachial index 0.66 (0.19)] with stable arterial claudication were recruited. All patients performed a treadmill test (3.2 km/h, 10% slope) associated with a transcutaneous oximetry test expressed as decrease from rest of oxygen pressure (DROP) index values (calf changes minus chest changes from rest) with a maximum walking distance (median [25th/75th percentiles]) of 295[133-881] m. The DROP index on the symptomatic side was -25 [-18/-34] mm Hg. On another daythe patients underwent electrical stimulation in the seated position on the leg that was the most symptomatic on the treadmill. After resting values were recorded, the gastrocnemius was stimulated for 20minutes at increasing contraction rates at 5-minute steps of 60, 75, 86, and 100bpm on the most symptomatic side. Arterial blood inflow with duplex Doppler ultrasound scanning of the femoral artery, DROP transcutaneous oxygen pressure value, and oxygen concentration (O2Hb) from the near-infrared spectroscopic signal of the calf were recorded on both sides. Patients were instructed to report eventual contraction-induced pain in the stimulated calf. Results are given as mean (standard deviation) or median [25th/75th percentiles] according to distribution, and the level of statistical significance was set at P< .05 on two-tailed tests. Lower limb inflow (mL/min) was 64 [48/86] vs 63 [57/81] (P> .05) before stimulation, 123 [75/156] vs 57 [44/92] (P< .01) at 60bpm, 127 [91/207] vs 49 [43/68] (P< .01) at 75bpm, 140 [84/200] vs 57 [45/71] (P< .01) at 86bpm, and 154 [86/185] vs 55 [46/94] (P< .01) at 100bpm on the stimulated vs nonstimulated limb, respectively. No apparent decrease or significant leg difference was observed in DROP index or O2Hb values. None of the patients reported contraction-induced pain in the leg. Electrical stimulation of calf muscle with the Veinoplus device results in a significant increase of arterial inflow without measurable muscle ischemia or pain. Potential use of this device as an adjuvant treatment to improve walking capacity in PAD patients remains to be evaluated.

Potential Utility of Near-Infrared Spectroscopy in Out-of-Hospital Cardiac Arrest: An Illustrative Case Series

Objective. We evaluated the measurement of tissue oxygen content (StO2) by continuous near-infrared spectroscopy (NIRS) during and following cardiopulmonary rescuscitation (CPR) and compared the changes in StO2 and end-tidal carbon dioxide (ETCO2) as a measure of return of spontaneous circulation (ROSC) or rearrest. Methods. This was a case series of five patients who experienced out-of hospital cardiac arrest. Patients included those who had already experienced ROSC, who were being transported to the hospital, or who were likely to have a reasonable amount of time remaining in the resuscitation efforts. Patients were continuously monitored from the scene using continuous ETCO2 monitoring and a NIRS StO2 monitor until they reached the hospital. The ETCO2 and StO2 values were continuously recorded and analyzed for comparison of the time points when patients were clinically identified to have ROSC or rearrest. Results. Four of five patients had StO2 and EtCO2 recorded during an episode of CPR and all were monitored during the postarrest period. Three patients experienced rearrest en route to the hospital. Downward trends were noted in StO2 prior to each rearrest, and rapid increases were noted after ROSC. The StO2 data showed less variance than the ETCO2 data in the periarrest period. Conclusions. This preliminary study in humans demonstrates that StO2 dynamically changes during periods of hemodynamic instability in postarrest patients. These data suggest that a decline in StO2 level may correlate with rearrest and may be useful as a tool to predict rearrest in post–cardiac arrest patients. A rapid increase in StO2 was also seen upon ROSC and may be a better method of identifying ROSC during CPR than pauses for pulse checks or ETCO2 monitoring. Key words: resuscitation; hemodynamics; tissue oxygen content; near-infrared spectroscopy; cardiopulmonary resuscitation; return of spontaneous circulation; rearrest

Ascorbate oxidase: The unexpected involvement of a ‘wasteful enzyme’ in the symbioses with nitrogen-fixing bacteria and arbuscular mycorrhizal fungi

Ascorbate oxidase (AO, EC 1.10.3.3) catalyzes the oxidation of ascorbate (AsA) to yield water. AO over-expressing plants are prone to ozone and salt stresses, whereas lower expression apparently confers resistance to unfavorable environmental conditions. Previous studies have suggested a role for AO as a regulator of oxygen content in photosynthetic tissues. For the first time we show here that the expression of a Lotus japonicus AO gene is induced in the symbiotic interaction with both nitrogen-fixing bacteria and arbuscular mycorrhizal (AM) fungi. In this framework, high AO expression is viewed as a possible strategy to down-regulate oxygen diffusion in root nodules, and a component of AM symbiosis. A general model of AO function in plants is discussed.

Measurement of three gamma annihilation by lanthanum-based crystals compared with NaI(Tl) and HPGe

The relative yield of 3γ to 2γ annihilation was measured for a positron emitter, 22Na, with the new scintillator detectors lanthanum chloride (LaCl3:Ce) and lanthanum bromide (LaBr3:Ce), which had been characterised for comparison with high-purity germanium (HPGe) and sodium iodide (NaI(Tl)) detectors. The information obtained from the ortho-positronium 3γ decay in positron emission tomography (PET) can be a measure of the oxygen content in biological tissues by determination of this relative yield. However, it requires high resolution spectroscopy and detection efficiency. Characterisation of the new generation of scintillator detectors determines whether they could replace conventional scintillators and semiconductors. A series of experiments was carried out with different samples in order to study the effect of ortho-positronium formation. The peak-to-peak and the peak-to-valley methods were compared in the measurement of the relative yield of 3γ to 2γ annihilation.

Evaluation of Intrarenal Oxygenation by Blood Oxygen Level-Dependent Magnetic Resonance Imaging in Living Kidney Donors and Their Recipients: Preliminary Results

Objective Blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) is a noninvasive tool to measure modifications in tissue oxygen content. Lower deoxyhemoglobin concentrations due to increased tissue oxygenation induce a longer transverse relaxation time (T2*), thus a stronger MRI signal. We have studied the changes in the kidney oxygenation profiles of living donors and their recipients by BOLD-MRI associated with transplantation and nephrectomy. Materials and Methods Two donor/recipient couples were selected for this preliminary study. BOLD-MRI was performed on the donor on the day prior to surgery, on day 4, and 1 month thereafter, and on the recipient on day 4 and 1 month postsurgery. Mean T2* values were measured in specific target regions in the cortical and medullary regions of each kidney using the T2StarMappingTool (Philips, Eindhoven, Netherlands). Modifications of tissue oxygen profiles were then compared considering the proportionality between T2* values and tissue oxygen content. Results The clinical courses posttransplantation were uneventful throughout the study; kidney function resumed rapidly. All MRI examinations showed a significantly higher T2* level in the cortex than in the medulla, confirming the notion that the medulla is hypoxic compared to the cortex. Nephrectomy and transplantation induced a significant rise in cortical T2* values in the remnant and transplanted kidney at day 4 and 1 month. Medullary T2* level only increased in the transplanted kidney. Conclusions Profound modifications in renal oxygenation intervene following transplantation and nephrectomy. BOLD-MRI may be a useful tool to explore these modifications and possibly identify pathological patterns.

Cellular preservation therapy in acute myocardial infarction

the past decade has been characterized by unprecedented progress in cardiac cell biology and pathophysiology. The dogma of the heart being a terminally differentiated organ has been challenged by compelling evidence generated in several different laboratories around the world ([6][1]). These