Biomedical subjects

J L Zweier

Publications and source records attributed to J L Zweier.

At least 91 records · Page 5Linked to original sources

PubMed1996

Hydrogen peroxide and superoxide modulate leukocyte adhesion molecule expression and leukocyte endothelial adhesion.

While endothelial oxidant generation and subsequent leukocyte chemotaxis and activation are important mechanisms of tissue damage in ischemic organs, it is not known if oxidant generation may be involved in triggering the subsequent leukocyte-mediated injury which occurs. Questions remain whether particular oxidants and oxygen-free radicals are capable of modulating the expression of leukocyte adhesion molecules and effecting leukocyte endothelial adhesion. Studies were performed to determine the effect of different biologically occurring oxidant molecules and oxygen free radicals including: .O2-, .OH, and H2O2 on the expression of integrin and selectin adhesion molecules on the surface of human PMNs and to determine the effect of these alterations on PMN adhesion to the endothelium. Adhesion molecule expression on the surface of human PMNs was measured by immunofluorescence flow cytometry. Electron paramagnetic resonance spectroscopy was applied to characterize the presence of exogenous free radical generation as well as that from activated PMNs. It was observed that these oxidants can cause up-regulation of CD11b and CD18 expression with shedding of L-selectin. The kinetics and dose-response of these effects were analyzed and their functional significance determined by measuring PMN adhesion to cultured human aortic endothelial monolayers. These studies demonstrate that oxygen free radicals and non-radical oxidants can directly trigger PMN activation and adhesion to vascular endothelium.

Antigens, CD↗

PubMed1996

A forward-subtraction procedure for removing hyperfine artifacts in electron paramagnetic resonance imaging.

The potential for using electron paramagnetic resonance (EPR) imaging in biological applications has been limited by the lack of ideal single-line imaging probes. The commonly used nitroxides exhibit multiple lines, causing either hyperfine-based limitations in the maximum obtainable image resolution or hyperfine-based artifacts in the reconstructed image. The application of a numerical method, based on forward-subtraction principles for removing hyperfine artifacts in the measured projections is reported. It is demonstrated by using computer simulations, imaging of phantoms, and imaging of rat hearts, that marked enhancement in image quality and resolution can be obtained by removing the hyperfine-imposed limit on the gradient magnitude and performing postacquisition corrections for removing hyperfine artifacts in the image.

Animals↗

PubMed1996

Three-dimensional gated EPR imaging of the beating heart: time-resolved measurements of free radical distribution during the cardiac contractile cycle.

In vivo or ex vivo EPR imaging, EPRI, has been established as a powerful technique for determining the spatial distribution of free radicals and other paramagnetic species in living organs and tissues. While instrumentation capable of performing EPR imaging of free radicals in whole tissues and isolated organs has been previously reported, it was not possible to image rapidly moving organs such as the beating heart. Therefore instrumentation was developed to enable the performance of gated-spectroscopy and imaging on isolated beating rat hearts at L-band. A synchronized pulsing and timing system capable of gated acquisitions of up to 256 images per cycle, with rates of up to 16 Hz was developed. The temporal and spatial accuracy of this instrumentation was verified using a specially designed beating heart-shaped isovolumic phantom with electromechanically driven sinusoidal motion at a cycle rate of 5 Hz. Gated EPR imaging was performed on a series of isolated rat hearts perfused with nitroxide spin labels. These hearts were paced at a rate of 6 Hz with either 16 or 32 gated images acquired per cardiac contractile cycle. The image enabled visualization of the time-dependent alterations in the free radical distribution and anatomical structure of the heart that occur during the cardiac cycle.

Animals↗

PubMed1996

Spatial mapping of nitric oxide generation in the ischemic heart using electron paramagnetic resonance imaging.

Recently, it has been shown that rat hearts subjected to global ischemia generate nitric oxide (NO) and that a significant portion of it is generated by the reduction of nitrite under the acidic and reducing conditions that occur during myocardial ischemia [Zweier, Wang, Samouilov, Kuppusamy, Nature Med. 1, 804-809 (1995)]. In the present study it is further attempted to map the spatial distributions of the NO generation in the ischemic myocardium using L-band electron paramagnetic resonance imaging. Rat hearts were loaded with 10 mM nitrite and subjected to global no-flow ischemia, during which time a series of three-dimensional spatial electron paramagnetic resonance (EPR) images of the distribution of NO were obtained using the NO trap bis(N-methyl-D-glucamine dithiocarbamate)iron(II). The images clearly showed that NO is formed throughout the myocardium. Kinetic experiments showed that maximum NO generation and trapping occur at the midmyocardium and spread out to endocardium and epicardium of the left ventricle. The magnitude of generation in the RV myocardium is four- to fivefold lower than in the LV.

Animals↗

PubMed1996

Induction of hepatic heme oxygenase-1 and ferritin in rats by cancer chemopreventive dithiolethiones.

Treatment of rats with the cancer chemopreventive agent 1,2-dithiole-3-thione (D3T) resulted in a significant increase in hepatic heme oxygenase (HO) activity, which corresponded to increased protein levels of HO-1. Upon further analysis of proteins related to heme metabolism, the level of ferritin, the major iron storage protein in liver, was also found to be elevated. Diminished levels of intracellular free iron were monitored by EPR spectroscopy at times after administration of D3T that suggested that increased ferritin content sequesters intracellular iron. The increased levels of protein were associated with increased levels of steady-state RNA of HO-1 and the light (FL) and heavy (FH) subunits of ferritin. A direct relationship between enhanced rates of gene transcription and elevated levels of HO-1 and ferritin RNA was found. The inductions of FL and FH, but not HO-1, were sensitive to cycloheximide, suggesting that in vivo these genes are regulated by distinct D3T-responsive transcriptional mechanisms. The known protective roles for induced HO-1 and ferritin in cellular stress have been suggested to include increased levels of the antioxidant bilirubin and enhanced sequestration of intracellular iron into ferritin, which can effectively reduce iron-mediated reactive oxygen generation. Thus, protective actions of D3T against the cytotoxic and carcinogenic consequences of chemicals that exert electrophilic or oxidative stresses may be mediated, in part, by the induction of HO-1, FL and FH.

Animals↗

PubMed1996

pH dependence of neutrophil-endothelial cell adhesion and adhesion molecule expression.

Neutrophil adhesion to the vascular endothelium is enhanced during tissue ischemia and/or inflammation, conditions that are associated with tissue acidosis. This study examined the effects of hypercarbic acidosis (10 or 20% CO2) and of hypocarbic alkalosis (0% CO2) on human neutrophil CD18 and human aortic endothelial cell intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin expression quantified by flow cytometry. Acidosis with 20% CO2 for 4 h decreased ICAM-1 to 60.6 +/- 9.7% of control. In contrast, alkalosis with 0% CO2 for 4 h enhanced ICAM-1 expression to 143.8 +/- 10.1% of control. There was no pH dependence of VCAM-1 or E-selectin expression. Tumor necrosis factor-alpha (TNF-alpha; 10 ng/ml) increased endothelial ICAM-1, E-selectin, and VCAM-1; under these conditions, acidosis with 20% CO2 blunted both ICAM-1 and E-selectin surface expression compared with 5% CO2-, TNF-alpha-treated cells. Hypercarbic acidosis with 20% CO2 increased neutrophil CD18 expression and enhanced neutrophil adhesion. This latter effect was inhibited by neutrophil pretreatment with an anti-CD18 monoclonal antibody. In contrast, when only endothelial cells were preincubated with the hypercarbic buffer, neutrophil adhesion diminished to 55.6 +/- 7.8% of control. The results suggest that acidosis generated during tissue ischemia/inflammation may induce CD18-mediated neutrophil adhesion despite a decrease in ICAM-1 expression.

Cell Adhesion↗

PubMed1996

Role of Cu/Zn-superoxide dismutase in xenobiotic activation. I. Chemical reactions involved in the Cu/Zn-superoxide dismutase-accelerated oxidation of the benzene metabolite 1,4-hydroquinone.

Cu/Zn-superoxide dismutase (Cu/Zn-SOD) has been shown to modulate the autoxidation of a variety of phenoic compounds, including 1,4-hydroquinone (HQ), a benzene-derived metabolite. The acceleration of autoxidation of HQ by Cu/Zn-SOD results in the production of 1,4-benzoquinone (BQ). It has been proposed that the chemical mechanism involved in the Cu/Zn-SOD-catalyzed autoxidation of HQ may be occur through either its conventional activity as a superoxide:superoxide oxidoreductase or as a semiquinone:superoxide oxidoreductase. However, Cu/Zn-SOD-accelerated oxidation of HQ has not been resolved experimentally. In this study, with ESR spectroscopy we investigated further the chemical reactions involved in the SOD-accelerated oxidation of HQ. In phosphate-buffered saline (PSB), HQ underwent a slow autoxidation to BQ, which was accelerated by Cu/Zn-SOD, Mn-SOD, or Fe-SOD with similar efficiency. In contrast, among free metals, only Cu(II) strongly mediated the oxidation of HQ to BQ. Mn(II) exhibited a slight capacity to oxidize HQ, whereas neither FE(II) nor FE(III) was capable of modulating the autoxidation of HG. The presence of either form of SOD also dramatically enhanced the formation of semiquinone anion radicals SQ-. from HQ. The SOD-accelerated oxidation of HQ was also accompanied by the generation of H202. In PBS containing bovine serum albumin (BSA) (PBS/BSA), HQ did not undergo autoxidation to SQ-., and as such the presence of SOD was unable to induce the formation of either SQ-. or BQ or the consumption of O2. The addition of 10 microM BQ to HQ (100 or 1000 microM) in PBS/BSA resulted in the formation of SQ-. and initiated a slow rate of oxidation of HQ to BQ. In this case, the presence of Cu/Zn-SOD strongly accelerated the oxidation of HQ to SQ-. and BQ and the utilization of O2. Furthermore, the enhancement by Cu/Zn-SOD of the generation of SQ-. or BQ from HQ in PBS/BSA was extensively inhibited under anaerobic conditions. The enhancement of SQ-. generation from HQ by all three forms of SOD does not support the possibility that Cu/Zn-SOD can oxidize SQ-. to BQ. Taken together, this study demonstrates that unlike free copper, Cu/Zn-SOD does not directly interact with HQ to cause its oxidation to BQ. Rather, the autoxidation of HQ to SQ-. is a prerequisite for the enhancing capacity of Cu/Zn-SOD, and the dismutation of superoxide anion radicals generated from the SQ-. in the presence of O2 appears to be the underlying mechanism responsible for the enhancement by Cu/Zn-SOD of the oxidation of HQ.

Anaerobiosis↗

PubMed1996

Effects of afterload on regional left ventricular torsion.

OBJECTIVE: To determine if left ventricular torsion, as measured by magnetic resonance tissue tagging, is afterload dependent in a canine isolated heart model in which neurohumoral responses are absent, and preload is constant. METHODS: In ten isolated, blood perfused, ejecting, canine hearts, three afterloads were studied, while keeping preload constant: low afterload, high afterload (stroke volume reduced by approx. 50% of low afterload), and isovolumic loading (infinite afterload). RESULTS: There were significant effects of afterload on both torsion (P < 0.05) and circumferential shortening (P < 0.0005). Between low and high afterloads, at the anterior region of the endocardium only, where torsion was maximal, there was a significant reduction in torsion (15.1 +/- 2.2 degrees to 7.8 +/- 1.8 degrees, P < 0.05). Between high afterload and isovolumic loading there was no significant change in torsion (7.8 +/- 1.8 degrees to 6.2 +/- 1.5 degrees, P = NS). Circumferential shortening at the anterior endocardium was significantly reduced both between low and high afterload (-0.19 +/- 0.02 to -0.11 +/- 0.02, P < 0.0005), and also between high afterload and isovolumic loading (-0.11 +/- 0.02 to 0.00 +/- 0.02, P < 0.05). Plots of strains with respect to end-systolic volume demonstrated a reduction in both torsion and shortening with afterload-induced increases in end-systolic volume. Torsion, but not circumferential shortening, persisted at isovolumic loading. CONCLUSIONS: Maximal regional torsion of the left ventricle is afterload dependent. The afterload response of torsion appears related to the effects of afterload on end-systolic volume.

Animals↗

PubMed1995

Substrate control of free radical generation from xanthine oxidase in the postischemic heart.

While the free radical-generating enzyme xanthine oxidase is a central mechanism of injury in postischemic tissues, questions remain regarding how xanthine oxidase-mediated radical generation is triggered during ischemia and reperfusion. There is controversy regarding whether radical generation is caused by enzyme formation of that of its substrates xanthine and hypoxanthine. Therefore, studies were performed in isolated rat hearts correlating the magnitude and time course of radical generation with alteration in xanthine oxidase and its substrates. Radical generation was measured by electron paramagnetic resonance spectroscopy and correlated with spectrophotometric assays of tissue xanthine oxidase activity and chromatographic measurements of tissue and effluent concentrations of xanthine oxidase substrates and products. Xanthine oxidase was present in preischemic hearts and slightly increased during 30-min global ischemia. Hypoxanthine and xanthine were not present prior to ischemia but accumulated greatly during ischemia due to ATP degradation. These substrate concentrations rapidly declined over the first 5 min of reperfusion matching the observed time course of radical generation, whereas xanthine oxidase activity was largely unchanged. Both substrates were also observed in the coronary effluent during the first 5 min of reflow along with the product uric acid. Thus, the burst of xanthine oxidase-mediated free radical generation upon reperfusion is triggered and its time course controlled by a large increase in substrate formation that occurs secondary to the degradation of ATP during ischemia.

Adenosine Triphosphate↗

PubMed1995

Direct measurement of nitric oxide generation in the ischemic heart using electron paramagnetic resonance spectroscopy.

Nitric oxide, NO., exerts numerous important regulatory functions in biological tissues and has been hypothesized to have a role in the pathogenesis of cellular injury in a number of diseases. It has been suggested that alterations in NO. generation are a critical cause of injury in the ischemic heart. However, the precise alterations in NO. generation which occur are not known, and there is considerable controversy regarding whether myocardial ischemia results in increased or decreased NO. formation. Therefore, electron paramagnetic resonance studies were performed to directly measure NO. in isolated rat hearts subjected to global ischemia, using the direct NO. trap Fe(2+)-N-methyl-D-glucamine dithiocarbamate, which specifically binds NO. giving rise to a characteristic triplet EPR spectrum with g = 2.04 and aN = 13.2 G. While only a small triplet signal was observed in normally perfused hearts, a 10-fold increase in this triplet EPR spectrum was observed after 30 min of ischemia indicating a marked increase in NO. formation and trapping. Measurements were performed as a function of the duration of ischemia, and it was determined that with increased duration of ischemia NO. formation and trapping was also increased. NO. generation was inhibited by the nitric oxide synthase blocker, N-nitro-L-arginine methyl ester (L-NAME), suggesting that NO. was generated via nitric oxide synthase. Blockade of NO. generation with L-NAME resulted in more than a 2-fold increase in the recovery of contractile function in hearts reperfused after 30 min of global ischemia. Thus, ischemia causes a marked duration-dependent increase of NO. in the heart which may in turn mediate postischemic injury.

Animals↗

PubMed1995

Prognostic significance of right ventricular dysfunction in patients with acute inferior myocardial infarction and right ventricular involvement.

Little is known about the influence of right ventricular (RV) dysfunction on prognosis of patients with acute inferior myocardial infarction (IMI) and RV involvement. Therefore, 99 consecutive patients (mean age 56.6 +/- 3.4 years) with RV involvement during acute IMI were followed for a 12-month period to clarify the influence of acute RV dysfunction on short- and long-term survivals. Forty-one patients with IMI evolved with severe arterial hypotension due to RV dysfunction, while 58 patients had no hemodynamic impairment due to RV involvement. Basal hemodynamic data (mean +/- SD) for patients with RV dysfunction were blood pressure (BP) 92/59 +/- 22/20 mmHg, systemic vascular resistance (SVR) 2314 +/- 252 dynes.s.cm-5, and cardiac index (CI) 1.3 +/- 0.3 l/min/m2. Patients without RV dysfunction demonstrated BP 113/74 +/- 20/16 mmHg (p < or = 0.05), SVR 1324 +/- 354 dynes.s.cm-5 (p < or = 0.01), and CI 2.6 +/- 0.5 l/min/m2 (p < or = 0.05). Angiographic differences noted were that hemodynamically compromised patients showed lower RV ejection fractions (0.27 +/- 0.08) than patients without hemodynamic disturbance [0.41 +/- 0.11 (p < or = 0.05)]; however, left ventricular ejection fractions were 0.48 +/- 0.10 and 0.52 +/- 0.12, respectively. Short- and long-term mortality rates were assessed during the follow-up period. Patients with hemodynamic impairment due to RV infarction had a higher mortality rate for the first month and for 11 subsequent months post MI than patients without hemodynamic impairment, that is 24.4 vs. 6.9 and 14.6 (p <or = 0.05) vs. 3.4 (p < or = 0.05), respect ively.(ABSTRACT TRUNCATED AT 250 WORDS)

Creatine Kinase↗

PubMed1995

Three-dimensional spatial EPR imaging of the rat heart.

While instrumentation capable of performing three-dimensional EPR imaging of free radicals in whole tissues and isolated organs has been developed at L-band, important questions remain regarding the resolution and image quality that can be obtained in practice using the presently available free radical labels. Therefore, studies were performed applying three-dimensional spatial EPR imaging at L-band to image the distribution of free radical labels in the isolated heart and in phantoms of similar size. With nitroxide labels the obtainable resolution is limited by the presence of hyperfine structure in the EPR absorption function that in turn limits the maximum applicable gradient. The authors observed that with the nitroxide labels, resolutions in the range of 1-2 mm are possible, while with a single line glucose char label, resolutions of 0.2 mm are obtained. With the nitroxides, images were of sufficient resolution to resolve the overall global shape of the heart and the location of the left and right ventricular cavities; however, finer structures could not be resolved. With the glucose char much finer resolution could be obtained enabling visualization of the ventricles, aortic root, and proximal coronary arteries.

Animals↗

PubMed1995

Development and optimization of three-dimensional spatial EPR imaging for biological organs and tissues.

The development and optimization procedures for obtaining high-quality three-dimensional spatial electron-paramagnetic-resonance images of large lossy samples at L band are described. Strategies for selecting optimized parameters for projection acquisition, instrumentation, and algorithms for correcting drifts in microwave frequency and inaccuracies in the static and gradient magnetic fields are described. Image reconstruction was performed using a two-stage filtered back-projection method with spectral deconvolution. With this instrumentation, correction algorithms, and image reconstruction method, spatially accurate 3D images of radical distribution were observed in complex phantoms using 0.5 mM nitroxide labels. The results indicate that high-quality images of lossy samples, including biological organs and tissues of up to 25 mm in size, could be obtained in a reasonable time with submillimeter resolution.

Algorithms↗

PubMed1995

Mapping the spin-density and lineshape distribution of free radicals using 4D spectral-spatial EPR imaging.

The development and application of four-dimensional spectral-spatial electron paramagnetic resonance imaging (EPRI) techniques for unambiguous determination of spectral shape and spin distribution of paramagnetic samples are described. Strategies for optimizing acquisition and computation times, image resolution, and data presentation are described. The feasibility of studying small linewidth differences of approximately 0.1 G in samples of up to 25 mm in size was tested by computer simulations and by measurements on phantoms containing 0.5 mM nitroxide spin label. One thousand projections were used to reconstruct 32 x 32 x 32 x 32 pixel images. Similar 4D imaging experiments were performed on an isolated rat heart infused with a suspension of glucose char. The 4D image of the rat heart clearly showed the three-dimensional spatial structure of the heart and the spectral shape at each spatial point. Thus, we have demonstrated, for the first time, that 4D spectral-spatial EPRI could be performed on lossy biological samples or tissues at L-band frequencies, enabling the mapping of spectral information over the entire three-dimensional spatial structure of the object.

Animals↗

PubMed1995

Development of an electronically tunable L-band resonator for EPR spectroscopy and imaging of biological samples.

While interest in the EPR spectroscopy and imaging of biological samples triggered the development of numerous resonator and microwave-bridge designs operating at high RF and L-band frequencies, a number of important technical problems remain. Two of these problems are the occurrence of sample-induced drifts in resonance frequency of the resonator and the intrinsic limitations in sensitivity of low-frequency EPR measurements. In an effort to address these problems, an approach was developed for obtaining fixed-frequency EPR measurements, utilizing a low-phase-noise fixed-frequency oscillator as a microwave source and an electronically tunable ceramic re-entrant L-band resonator, which was locked to the oscillator via automatic frequency control (AFC). The tunable microwave resonator described in this paper employs a voltage-controlled piezoelectric actuator for adjustment of the resonance frequency via variations of the equivalent capacitance of the resonator. Design considerations and data, as well as schematic drawings and test results, are presented. The reported approach provides true fixed-frequency operation under a wide range of sample and environment conditions and over prolonged periods of time. The use of this tunable resonator design in conjunction with an ultra-low-noise fixed-frequency oscillator should enable enhanced sensitivity in EPR measurements of large lossy biological samples.

Algorithms↗

PubMed1995

Measurement of nitric oxide with a solid-state-char EPR probe.

Recently, highly oxygen-sensitive solid-state paramagnetic probes have been developed from glucose chars which are capable of providing measurements of very low, millitorr, oxygen concentrations in biological cells and tissues. With the increased interest and recognition of the presence and importance of the free-radical gas nitric oxide, NO., in biology, studies were performed aimed at characterizing the effect of NO. on this probe. It was observed that NO. exerts a similar concentration-dependent broadening as does molecular oxygen, O2. In anaerobic solutions, concentrations of NO. could be detected down to 10-100 nM levels. Measurements of NO. formation in aqueous solution were performed from a pharmacological NO. donor, which produced micromolar concentrations of NO.. This technique, however, was not sufficiently sensitive to measure physiological 1-10 nM concentrations. Thus, the glucose-char EPR probe could be used to detect pharmacological levels of NO. but was not significantly affected by the low physiological levels which occur in normal biological tissues. These results indicate that, under normal physiological conditions, the linewidth alterations measured using the glucose-char EPR probe are solely caused by oxygen.

Electron Spin Resonance Spectroscopy↗

PubMed1995

ESR evidence for the generation of reactive oxygen species from the copper-mediated oxidation of the benzene metabolite, hydroquinone: role in DNA damage.

In previous studies, we observed that Cu(II) strongly induces the oxidation of hydroquinone (HQ), producing benzoquinone and H2O2 through a Cu(II)/Cu(I) redox cycle mechanism. The oxidation of HQ by Cu(II) also results in plasmid DNA cleavage. In this study, using ESR spectroscopy we have investigated whether this chemical-metal redox system can generate reactive oxygen species which induce DNA damage. In order to set the stage for the ESR experiments and the inhibitors to be used in these experiments, some preliminary O2 consumption and plasmid DNA cleavage experiments were performed. Mixing 100 microM HQ with 10 microM Cu(II) in phosphate-buffered saline (PBS) resulted in a marked consumption of O2 and the concomitant generation of H2O2, and extensive DNA degradation in chi X-174 RF I DNA. The presence of superoxide dismutase (SOD) or mannitol did not affect either the O2 consumption, H2O2 generation or DNA damage. In contrast, the Cu(I) chelators, bathocuproinedisulfonic acid (BCS) and glutathione (GSH), extensively inhibited the HQ/Cu(II)-mediated O2 consumption and DNA damage. The presence of catalase also prevented the DNA damage. Although the HQ/Cu(II)-mediated O2 consumption increased in the presence of azide, azide markedly inhibited the HQ/Cu(II)-induced DNA degradation, resulting in primarily open circles. Using ESR spectroscopy, it was observed that Cu(II) strongly mediated the formation of semiquinone anion radicals from HQ in PBS, which could be blocked by BCS. alpha-(4-Pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN)-spin trapping experiments showed that the interaction of HQ with Cu(II) produced 4-POBN-CH3 and 4-POBN-CH(OH)CH3 adducts in the presence of dimethyl sulfoxide (DMSO) and ethanol, respectively, suggesting that hydroxyl radical or an equivalent reactive intermediate is generated from the HQ/Cu(II) system. The presence of catalase, BCS or GSH but not SOD completely prevented the formation of 4-POBN-CH3 adduct from the HQ/Cu(II) plus 4-POBN/DMSO system. This indicates that both H2O2 and Cu(I) are critical for the formation of reactive oxygen from the HQ/Cu(II) system. Anaerobic conditions induced an approximately 85% decrease in the formation of 4-POBN-CH3 adduct. Reactive oxygen scavenger experiments showed that the formation of the 4-POBN-CH3 adduct was significantly inhibited by azide but not by mannitol. Overall, the above results indicate that through a copper-redox cycling mechanism the copper-mediated oxidation of HQ generates reactive oxygen species which may participate in DNA damage.

Animals↗

PubMed1995

Three-dimensional imaging of nitric oxide production in the rat brain subjected to ischemia-hypoxia.

By the systemic administration of diethyldithiocarbamate and iron into the rat, nitric oxide radicals produced in the brain during ischemia-hypoxia were trapped. The right hemisphere of the brain was then removed and frozen with liquid nitrogen. With use of recently developed electron paramagnetic resonance imaging instrumentation and techniques, three-dimensional imaging of the production of the nitric oxide radicals in several brains was performed. The results suggest that nitric oxide radicals were produced and trapped in the areas that are known to have high nitric oxide synthase activity, such as cortex, hippocampus, hypothalamus, amygdala, and substantia nigra. In this ischemia-hypoxia model, which did not interrupt the posterior circulation, the production and trapping of nitric oxide in the cerebellum were approximately 30% of those in the cerebrum.

Anaerobiosis↗