scholarly journals Pathways of peroxynitrite oxidation of thiol groups

1997 ◽  
Vol 322 (1) ◽  
pp. 167-173 ◽  
Author(s):  
Celia QUIJANO ◽  
Beatriz ALVAREZ ◽  
Reynaldo M. GATTI ◽  
Ohara AUGUSTO ◽  
Rafael RADI

Peroxynitrite mediates the oxidation of the thiol group of both cysteine and glutathione. This process is associated with oxygen consumption. At acidic pH and a cysteine/peroxynitrite molar ratio of ≤ 1.2, there was a single fast phase of oxygen consumption, which increased with increasing concentrations of both cysteine and oxygen. At higher molar ratios the profile of oxygen consumption became biphasic, with a fast phase (phase I) that decreased with increasing cysteine concentration, followed by a slow phase (phase II) whose rate of oxygen consumption increased with increasing cysteine concentration. Oxygen consumption in phase I was inhibited by desferrioxamine and 5,5-dimethyl-1-pyrroline N-oxide, but not by mannitol; superoxide dismutase also inhibited oxygen consumption in phase I, while catalase added during phase II decreased the rate of oxygen consumption. For both cysteine and glutathione, oxygen consumption in phase I was maximal at neutral to acidic pH; in contrast, total thiol oxidation was maximal at alkaline pH. EPR spin-trapping studies using N-tert-butyl-α-phenylnitrone indicated that the yield of thiyl radical adducts had a pH profile comparable with that found for oxygen consumption. The apparent second-order rate constants for the reactions of peroxynitrite with cysteine and glutathione were 1290ŷ30 M-1ƃs-1 and 281ŷ6 M-1ƃs-1 respectively at pH 5.75 and 37 ŶC. These results are consistent with two different pathways participating in the reaction of peroxynitrite with low-molecular-mass thiols: (a) the reaction of the peroxynitrite anion with the protonated thiol group, in a second-order process likely to involve a two-electron oxidation, and (b) the reaction of peroxynitrous acid, or a secondary species derived from it, with the thiolate in a one-electron transfer process that yields thiyl radicals capable of initiating an oxygen-dependent radical chain reaction.

1993 ◽  
Vol 181 (1) ◽  
pp. 279-293
Author(s):  
J. Mallefet ◽  
F. Baguet

1. Basal oxygen consumption of isolated photophores from Porichthys sp. at rest, i.e. without light emission, increased significantly from 0.101+/− 0.021 nmol min-1 to 0.173+/−0.016 nmol min-1 in response to the addition of 5.5 mmol l-1 glucose. 2. 5.5 mmol l-1 glucose pretreatment modified the time course of the two phases of adrenaline-induced luminescence; an increase in oxygen consumption was observed during the fast phase of light production but a decrease occurred during the slow phase of luminescence. 3. Pretreatment of isolated photophores with 5.5 mmol l-1 glucose totally inhibited the light emission induced by 1 mmol l-1 potassium cyanide. With this treatment, the respiration rate decreased progressively and after 40 min reached a value not significantly different from zero. 4. Even after blockage of cellular respiration by cyanide, an increase in the rate of oxygen consumption was observed during the fast adrenaline- induced luminescence. 5. Glucose utilisation by glycolysis or by oxidative metabolism may provide energy to an inhibitory mechanism that maintains the photophores in a non- luminescent state. 6. We suggest that the oxygen consumed during the fast phase of adrenaline luminescence could represent the activity of an extramitochondrial oxidative pathway involved in the light reaction.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tanurup Das ◽  
Abhimanyu Harshey ◽  
Ankit Srivastava ◽  
Kriti Nigam ◽  
Vijay Kumar Yadav ◽  
...  

AbstractThe ex-vivo biochemical changes of different body fluids also referred as aging of fluids are potential marker for the estimation of Time since deposition. Infrared spectroscopy has great potential to reveal the biochemical changes in these fluids as previously reported by several researchers. The present study is focused to analyze the spectral changes in the ATR-FTIR spectra of three body fluids, commonly encountered in violent crimes i.e., semen, saliva, and urine as they dry out. The whole analytical timeline is divided into relatively slow phase I due to the major contribution of water and faster Phase II due to significant evaporation of water. Two spectral regions i.e., 3200–3400 cm−1 and 1600–1000 cm−1 are the major contributors to the spectra of these fluids. Several peaks in the spectral region between 1600 and 1000 cm−1 showed highly significant regression equation with a higher coefficient of determination values in Phase II in contrary to the slow passing Phase I. Principal component and Partial Least Square Regression analysis are the two chemometric tool used to estimate the time since deposition of the aforesaid fluids as they dry out. Additionally, this study potentially estimates the time since deposition of an offense from the aging of the body fluids at the early stages after its occurrence as well as works as the precursor for further studies on an extended timeframe.


Drug Research ◽  
2020 ◽  
Vol 70 (04) ◽  
pp. 145-150 ◽  
Author(s):  
Viviana Noriega ◽  
Hugo F. Miranda ◽  
Juan Carlos Prieto ◽  
Ramón Sotomayor-Zárate ◽  
Fernando Sierralta

AbstractThere are different animal models to evaluate pain among them the formalin hind paw assay which is widely used since some of its events appear to be similar to the clinical pain of humans. The assay in which a dilute solution of formalin is injected into the dorsal hindpaw of a murine produces two ‘phases’ of pain behavior separated by a inactive period. The early phase (Phase I) is probably due to direct activation of nociceptors and the second phase (Phase II) is due to ongoing inflammatory input and central sensitization. Mice were used to determine the potency antinociceptive of piroxicam (1,3,10,and 30 mg/kg), parecoxib (0.3, 1,3,10 and 30 mg/kg), dexketoprofen (3,10,30 and 100 mg/kg) and ketoprofen (3,10,30 and 100 mg/kg). Dose-response for each NSAIDs were created before and after 5 mg/kg of L-NAME i.p. or 5 mg/kg i.p. of 7-nitroindazole. A least-squares linear regression analysis of the log dose–response curves allowed the calculation of the dose that produced 50% of antinociception (ED50) for each drug. The ED50 demonstrated the following rank order of potency, in the phase I: piroxicam > dexketoprofen > ketoprofen > parecoxib and in the phase II: piroxicam > ketoprofen > parecoxib > dexketoprofen. Pretreatment of the mice with L-NAME or 7-nitroindazol induced a significant increase of the analgesic power of the NSAIDs, with a significant reduction of the ED50. It is suggested that NO may be involved in both phases of the trial, which means that nitric oxide regulates the bioactivity of NSAIDs.


2018 ◽  
Vol 33 (09) ◽  
pp. 1843004 ◽  
Author(s):  
◽  
M. Agostini ◽  
A. M. Bakalyarov ◽  
M. Balata ◽  
I. Barabanov ◽  
...  

The GERmanium Detector Array (GERDA) is a low background experiment at the Laboratori Nazionali del Gran Sasso (LNGS) of INFN designed to search for the rare neutrinoless double beta decay ([Formula: see text]) of [Formula: see text]Ge. In the first phase (Phase I) of the experiment, high purity germanium diodes were operated in a “bare” mode and immersed in liquid argon. The overall background level of [Formula: see text] was a factor of ten better than those of its predecessors. No signal was found and a lower limit was set on the half-life for the [Formula: see text] decay of [Formula: see text]Ge [Formula: see text] yr (90% CL), while the corresponding median sensitivity was [Formula: see text] yr (90% CL). A second phase (Phase II) started at the end of 2015 after a major upgrade. Thanks to the increased detector mass and performance of the enriched germanium diodes and due to the introduction of liquid argon instrumentation techniques, it was possible to reduce the background down to [Formula: see text]. After analyzing 23.2 kg[Formula: see text]⋅[Formula: see text]yr of these new data no signal was seen. Combining these with the data from Phase I a stronger half-life limit of the [Formula: see text]Ge [Formula: see text] decay was obtained: [Formula: see text] yr (90% CL), reaching a sensitivity of [Formula: see text] yr (90% CL). Phase II will continue for the collection of an exposure of 100 kg[Formula: see text]yr. If no signal is found by then the GERDA sensitivity will have reached [Formula: see text] yr for setting a 90% CL. limit. After the end of GERDA Phase II, the flagship experiment for the search of [Formula: see text] decay of [Formula: see text]Ge will be LEGEND. LEGEND experiment is foreseen to deploy up to 1-ton of [Formula: see text]Ge. After ten years of data taking, it will reach a sensitivity beyond 10[Formula: see text] yr, and hence fully cover the inverted hierarchy region.


Author(s):  
Hironobu Abe ◽  
Koichiro Hatanaka

The Horonobe URL project has been pursued by JAEA (Japan Atomic Energy Agency) to establish and demonstrate site characterization methodologies, engineering technologies, and safety assessment methodologies for HLW geological disposal in relevant geological environment with sedimentary rock and saline groundwater distributing in the Horonobe area, Hokkaido, Japan. In the Horonobe URL project, surface-based investigation phase (Phase I) has already completed in the fiscal year 2005, and then construction phase (Phase II) has initiated in the same year. Currently, construction of the underground facilities such as shafts/galleries which were designed in Phase I, investigations of the geological environment in the excavated shafts/galleries and confirmation of applicability of engineering technologies have been alternately carried out as Phase II activities of the project. During the construction so far, monitoring for the construction safety such as convergence measurements, tunnel wall observation, sampling of groundwater and rock, investigations for evaluating excavation damaged/disturbed zone (EDZ/EdZ) along shafts/galleries were carried out. In addition, a shotcrete construction test and a grout injection test by using low alkaline cement material were carried in the horizontal galleries. In this paper, status of the URL construction and research activities mentioned above are outlined as the current achievement of the Horonobe URL project.


Holzforschung ◽  
2010 ◽  
Vol 64 (1) ◽  
Author(s):  
Lili Yu ◽  
Jinzhen Cao ◽  
Guangjie Zhao

Abstract The reactions between constituents of alkaline copper quat (ACQ) and of wood were investigated by a tensile stress relaxation approach. Small samples were stressed and impregnated with various ACQ solutions, in which the ratios of monoethanolamine (MEA), ACQ, and didecyl dimethyl ammonium chloride (DDAC) were varied. The other parameters included temperature and concentration of the treating solutions. The stress relaxation curves of wood were recorded during the impregnation period and the effects of impregnation parameters were investigated by an orthogonal experimental design (OED). The effects of water, MEA, and DDAC on stress relaxation of the samples were also observed. The bulking effect of water was tested separately in samples treated with distilled water without stretching. The results showed that the stress relaxes dramatically in the initial period and then changes slightly over a long period, which is readily visible in double logarithmic plots of f (t)/f (0) versus time (t). There are complex interactions between the components of ACQ solutions and wood matrix: (1) in rapid phase I, the splitting of the easily accessible hydrogen bonds (mainly in the amorphous hemicelluloses) are prevalent by interaction with components of ACQ solution; (2) in slow phase II, Cu penetrates deeper in less accessible regions (e.g., in paracrystalline regions of cellulose) and renders possible further relaxation. The results of range and variance analysis reveal that the molar ratio of Cu to MEA and temperature of ACQ solution have significant effects on the rate of reaction during phase I, whereas in phase II only the temperature of ACQ solution has a significant effect. The stress relaxation curves of samples impregnated in water, MEA, and DDAC all showed a quasi one phase stress relaxation rate, which suggests that phase II is mostly related to Cu in ACQ formulations. It is concluded that the formation of complexes with Cu is still the major reaction in wood although there is competition among ACQ constituents for reaction sites.


2021 ◽  
Author(s):  
Tanurup Das ◽  
Abhimanyu Harshey ◽  
Ankit Srivast ◽  
Kriti Nigam ◽  
Vijay Yadav ◽  
...  

Abstract The ex-vivo biochemical changes of different body fluids are potential marker for the estimation of TSD. Infrared spectroscopy has great potential to reveal the biochemical changes in these fluids as previously reported by several researchers. Present study is focused to analyze the spectral changes in the ATR-FTIR spectra of three body fluids, commonly encountered in violent crimes i.e., Semen, Saliva and Urine as they dry out. The whole analytical timeline is divided into relatively slow phase I due to major contribution of water and faster Phase II due significant evaporation of water. Two spectral regions i.e., 3200-3400 cm-1 and 1600-1000 cm-1 are the major contributor to the spectra of these fluids. Several peaks in the spectral region between 1600-1000 cm-1 showed highly significant regression equation with higher coefficient of determination values in the Phase II in contrary to the slow passing Phase I. Principal component and Partial Least Square Regression analysis are the two chemometric tool used to estimate the TSD of the aforesaid fluids as they dry out. This study potentially estimates the TSD of an offence at the early stages after is occurrence as well as work as the precursor for further studies on extended timeframe.


1982 ◽  
Vol 53 (6) ◽  
pp. 1594-1602 ◽  
Author(s):  
L. E. Nery ◽  
K. Wasserman ◽  
J. D. Andrews ◽  
D. J. Huntsman ◽  
J. E. Hansen ◽  
...  

The influence of chronic obstructive pulmonary disease (COPD) on exercise ventilatory and gas exchange kinetics was assessed in nine patients with stable airway obstruction (forced expired volume at 1 s = 1.1 +/- 0.33 liters) and compared with that in six normal men. Minute ventilation (VE), CO2 output (VCO2), and O2 uptake (VO2) were determined breath-by-breath at rest and after the onset of constant-load subanaerobic threshold exercise. The initial increase in VE, VCO2, and VO2 from rest (phase I), the subsequent slow exponential rise (phase II), and the steady-state (phase III) responses were analyzed. The COPD group had a significantly smaller phase I increase in VE (3.4 +/- 0.89 vs. 6.8 +/- 1.05 liters/min), VCO2 (0.10 +/- 0.03 vs. 0.22 +/- 0.03 liters/min), VO2 (0.10 +/- 0.03 vs. 0.24 +/- 0.04 liters/min), heart rate (HR) (6 +/- 0.9 vs. 16 +/- 1.4 beats/min), and O2 pulse (0.93 +/- 0.21 vs. 2.2 +/- 0.45 ml/beat) than the controls. Phase I increase in VE was significantly correlated with phase I increase in VO2 (r = 0.88) and HR (r = 0.78) in the COPD group. Most patients also had markedly slower phase II kinetics, i.e., longer time constants (tau) for VE (87 +/- 7 vs. 65 +/- 2 s), VCO2 (79 +/- 6 vs. 63 +/- 3 s), and VO2 (56 +/- 5 vs. 39 +/- 2 s) and longer half times for HR (68 +/- 9 vs. 32 +/- 2 s) and O2 pulse (42 +/- 3 vs. 31 +/- 2 s) compared with controls. However, tau VO2/tau VE and tau VCO2/tau VE were similar in both groups. The significant correlations of the phase I VE increase with HR and VO2 are consistent with the concept that the immediate exercise hyperpnea has a cardiodynamic basis. The slow ventilatory kinetics during phase II in the COPD group appeared to be more closely related to a slowed cardiovascular response rather than to any index of respiratory function. O2 breathing did not affect the phase I increase in VE but did slow phase II kinetics in most subjects. This confirms that the role attributed to the carotid bodies in ventilatory control during exercise in normal subjects also operates in patients with COPD.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Hanjie Wang ◽  
Kenneth J. Hunt

Abstract Background Characterisation of heart rate (HR) dynamics and their dependence on exercise intensity provides a basis for feedback design of automatic HR control systems. This work aimed to investigate whether the second-order models with separate Phase I and Phase II components of HR response can achieve better fitting performance compared to the first-order models that do not delineate the two phases. Methods Eleven participants each performed two open-loop identification tests while running at moderate-to-vigorous intensity on a treadmill. Treadmill speed was changed as a pseudo-random binary sequence (PRBS) to excite both the Phase I and Phase II components. A counterbalanced cross-validation approach was implemented for model parameter estimation and validation. Results Comparison of validation outcomes for 22 pairs of first- and second-order models showed that root-mean-square error (RMSE) was significantly lower and fit (normalised RMSE) significantly higher for the second-order models: RMSE was 2.07 bpm ± 0.36 bpm vs. 2.27 bpm ± 0.36 bpm (bpm = beats per min), second order vs. first order, with $$p = 2.8 \times 10^{-10}$$ p = 2.8 × 10 - 10 ; fit was $$54.5\% \pm 5.2$$ 54.5 % ± 5.2 % vs. $$50.2\% \pm 4.8$$ 50.2 % ± 4.8 %, $$p = 6.8 \times 10^{-10}$$ p = 6.8 × 10 - 10 . Conclusion Second-order models give significantly better goodness-of-fit than first-order models, likely due to the inclusion of both Phase I and Phase II components of heart rate response. Future work should investigate alternative parameterisations of the PRBS excitation, and whether feedback controllers calculated using second-order models give better performance than those based on first-order models.


2008 ◽  
Vol 100 (6) ◽  
pp. 3105-3116 ◽  
Author(s):  
Christopher J. Bockisch ◽  
Stefan Hegemann

According to Alexander's law (AL), the slow phase velocity of nystagmus of vestibular origin is dependent on horizontal position, with lower velocity when gaze is directed in the slow compared with the fast phase direction. Adaptive changes in the velocity-to-position neural integrator are thought to cause AL. Although these changes have been described for the horizontal neural integrator, nystagmus often includes vertical and torsional components, but the adaptive abilities of the vertical and torsional integrators have not been investigated. We measured 11 patients with a peripheral vestibular asymmetry and used second-order equations to describe how velocity varied with position. Horizontal velocity changed with horizontal position in accordance with AL and the second-order term for horizontal position was also significant. Whereas velocity decreased in the slow phase direction, it was relatively unchanged >10° into the fast phase direction. Vertical velocity was also highest in the vertical fast phase direction and the second-order term for vertical position was also significant, in that vertical velocity increased in the vertical fast phase direction, but was unchanging in the slow phase direction. Torsional velocity varied linearly with horizontal, but not vertical, position. These results show that the horizontal and vertical oculomotor neural integrators react to altered vestibular input by maintaining different integrating time constants depending on gaze direction.


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