Figure 12.5 Schematic of the trauma shown in Figures 12.2 and 12.3. The spine starts in a neutral position (NP). The 50 to 75 ms time period illustrates the neck forming an S-shaped curvature (Phase I). During this phase, the lower cervical spine intervertebral joints exhibit hyper-extension, exceeding their physiological limits. In the later phase (Phase II), the spine transforms to a C-shape with complete extension. This phase is associated with a lesser degree of the lower level hyper-extension, and thus a lesser potential for injury.

1999 ◽  
pp. 277-284
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):  
Franz Mlynek ◽  
Markus Himmelsbach ◽  
Wolfgang Buchberger ◽  
Christian W. Klampfl

AbstractThe aim of this study was to investigate the uptake of four beta-blockers by the model plant Lepidium sativum (garden cress) and their possible metabolization over a time period of 8 days. Therefore, cress was grown hydroponically in tap water for a week until they were matured, following irrigation with drug-containing water over the course of another 8 days. Samples were taken at days 1, 2, 4, and 8 after irrigation started. All four beta-blockers were taken up by the plants and the different octanol-water coefficients (log P) of the drugs have an influence on the uptake speed in the roots of the plants. The log P seems to have no influence on the translocation of the drugs from the root to the shoots. Furthermore, neither phase I nor phase II metabolization occurred inside the plants.


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.


2002 ◽  
Vol 282 (4) ◽  
pp. H1320-H1326 ◽  
Author(s):  
Cristian Dumitrescu ◽  
Prakash Narayan ◽  
Igor R. Efimov ◽  
Yuanna Cheng ◽  
M. Judith Radin ◽  
...  

We examined mechanical alternans and electromechanical restitution in normal and failing rat hearts. Alternans occurred at 5 Hz in failing versus 9 Hz in control hearts and was reversed by 300 nM isoproterenol, 6 mM extracellular Ca2+, 300 nM −BAY K 8644, or 50 nM ryanodine. Restitution curves comprised phase I, which was completed before relaxation of the steady-state beat, and phase II, which occurred later. Phase I action potential area and developed pressure ratios were significantly reduced in the failing versus control hearts. Phase II was a monoexponential increase in relative developed pressure as the extrasystolic interval was increased. The plateau of phase II was significantly elevated in failing hearts. Thapsigargin (3 μM) plus ryanodine (200 nM) potentiated phase I to a significantly greater extent in control versus failing hearts and abolished phase II in both groups. The results suggest that both regulation of Ca2+ influx across the sarcolemma and Ca2+ release by the sarcoplasmic reticulum may contribute to altered excitation-contraction coupling in the failing spontaneously hypertensive heart failure prone rat heart.


1985 ◽  
Vol 65 (2) ◽  
pp. 275-311 ◽  
Author(s):  
Francis Pryor ◽  
Charles French ◽  
Maisie Taylor

This interim report is principally concerned with waterlogged lower ditch deposits of the Etton causewayed enclosure. The site is situated near the eastern edge of the Maxey complex of cropmarks, and owes its remarkable preservation to a high local water table and a blanket deposit of clayey alluvium which has protected the archaeological deposits from plough-damage. The description of the causewayed enclosure includes interim discussions of woodworking, the use of cattle as draught animals, and outlines of the environmental succession. Short statements on pottery and other finds are also included. Brief mention is also made of the earlier (Phase I) and later (Phase II) Neolithic sites at Etton Woodgate, immediately to the west of the causewayed enclosure. These sites, which were also partially waterlogged, were discovered during a watching brief of topsoil-removal work in the adjacent quarry. Etton Woodgate II produced very early evidence for textiles and for possible charcoal manufacture. The Discussion outlines recent research in the region and offers provisional explanations for the roles of lowland causewayed enclosures.


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.


2002 ◽  
Vol 282 (4) ◽  
pp. H1311-H1319 ◽  
Author(s):  
Cristian Dumitrescu ◽  
Prakash Narayan ◽  
Yuanna Cheng ◽  
Igor R. Efimov ◽  
Ruth A. Altschuld

We examined the contributions of the Ca2+ channels of the sarcolemma and of the sarcoplasmic reticulum to electromechanical restitution. Extrasystoles (F1) were interpolated 40–600 ms following a steady-state beat (F0) in perfused rat ventricles paced at 2 or 3 Hz. Plots of F1/F0 versus the extrasystolic interval consisted of phase I, which occurred before relaxation of the steady-state beat, and phase II, which occurred later. Phase I exhibited a period of enhanced left ventricular pressure development that coincided with action potential prolongation. Phase I was eliminated by −BAY K 8644 (100 nM) and FPL 64176 (150 nM), augmented by 3 μM thapsigargin plus 200 nM ryanodine and unaffected by KN-93 and KB-R7943. Phase II was accelerated by the Ca2+channel agonists and by isoproterenol but was eliminated by thapsigargin plus ryanodine. The results suggest that phase I of electromechanical restitution is caused by a transient L-type Ca2+ current facilitation, whereas phase II represents the recovery of the ability of the sarcoplasmic reticulum to release Ca2+.


2021 ◽  
Vol 288 (1945) ◽  
pp. 20203207
Author(s):  
Maiki K. Wakai ◽  
Mitsuru J. Nakamura ◽  
Satoshi Sawai ◽  
Kohji Hotta ◽  
Kotaro Oka

Marine invertebrate larvae are known to begin metamorphosis in response to environmentally derived cues. However, little is known about the relationships between the perception of such cues and internal signalling for metamorphosis. To elucidate the mechanism underlying the initiation of metamorphosis in the ascidian, Ciona intestinalis type A ( Ciona robusta ), we artificially induced ascidian metamorphosis and investigated Ca 2+ dynamics from pre- to post-metamorphosis. Ca 2+ transients were observed and consisted of two temporally distinct phases with different durations before tail regression which is the early event of metamorphosis. In the first phase, Phase I, the Ca 2+ transient in the papillae (adhesive organ of the anterior trunk) was coupled with the Ca 2+ transient in dorsally localized cells and endoderm cells just after mechanical stimulation. The Ca 2+ transients in Phase I were also observed when applying only short stimulation. In the second phase, Phase II, the Ca 2+ transient in papillae was observed again and lasted for approximately 5–11 min just after the Ca 2+ transient in Phase I continued for a few minutes. The impaired papillae by Foxg -knockdown failed to induce the second Ca 2+ transient in Phase II and tail regression. In Phase II, a wave-like Ca 2+ propagation was also observed across the entire epidermis. Our results indicate that the papillae sense a mechanical cue and two-round Ca 2+ transients in papillae transmits the internal metamorphic signals to different tissues, which subsequently induces tail regression. Our study will help elucidate the internal mechanism of metamorphosis in marine invertebrate larvae in response to environmental cues.


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