scholarly journals Oxygen Delivery as a Limiting Factor in Modelling Dicopper(II) Oxidase Reactivity

2017 ◽  
Vol 23 (29) ◽  
pp. 6941-6941
Author(s):  
Jana Gülzow ◽  
Gerald Hörner ◽  
Peter Strauch ◽  
Anika Stritt ◽  
Elisabeth Irran ◽  
...  
2006 ◽  
Vol 290 (1) ◽  
pp. E192-E198 ◽  
Author(s):  
Ken D. Sumida ◽  
Jerry H. Urdiales ◽  
Casey M. Donovan

The purpose of this study was to determine, using the isolated liver perfusion technique, whether the limiting factor for hepatic gluconeogenesis (GNG) from lactate was precursor delivery or oxygen availability during reduced flow rates of 0.85 or 0.60 ml·min−1·g liver−1. After a 24-h fast, three different experimental protocols were employed. Protocol 1 examined the impact on GNG when reservoir lactate concentration was maintained but oxygen delivery was elevated via increases in hematocrit (Hct). Elevating the Hct from 22.5 ± 0.8% to 30.9 ± 0.4% at a blood flow of 0.89 ± 0.01 ml·min−1·g liver−1 increased the oxygen consumption (V̇o2) but did not augment GNG. Similarly, when the Hct was elevated from 22.5 ± 0.8% to 41.5 ± 0.7% at 0.59 ± 0.04 ml·min−1·g liver−1, V̇o2 was increased, but GNG was unaffected. Protocol 2 examined the impact on GNG when Hct was maintained but precursor delivery was elevated via increases in reservoir lactate concentration ([LA]). Specifically, elevating the [LA] from 2.31 ± 0.07 to 3.61 ± 0.33 mM at a flow rate of 0.82 ± 0.04 ml·min−1·g liver−1 significantly increased GNG. Similarly, elevating the [LA] from 2.31 ± 0.07 to 4.24 ± 0.37 mM at a flow rate of 0.58 ± 0.02 ml·min−1·g liver−1 increased GNG. Finally, we examined the impact of increasing both the oxygen and lactate delivery ( Protocol 3). Again, V̇o2 was elevated with increased oxygen delivery, but GNG was not augmented beyond that observed with elevations in lactate delivery alone, i.e., Protocol 2. The results indicate that, during decrements in blood flow, GNG is limited primarily by precursor delivery, not oxygen availability.


2017 ◽  
Vol 15 (1) ◽  
pp. 43-47
Author(s):  
Robert T. Mankowski ◽  
Victor M. Niemeijer ◽  
Jasper P. Jansen ◽  
Lotte Spraakman ◽  
Henk J. Stam ◽  
...  

2019 ◽  
Vol 244 (8) ◽  
pp. 690-701 ◽  
Author(s):  
Victor A Convertino ◽  
Kristen R Lye ◽  
Natalie J Koons ◽  
Michael J Joyner

Based on evidence extracted from a cross-sectional review of the literature, we sought to advance a novel conceptual framework that the physiology of hemorrhagic shock from exsanguination and maximal oxygen uptake ([Formula: see text]O2max), induced by physical exercise, shares key common features. As such, this review focuses on the notion that intolerance to inadequate oxygen delivery (DO2) resulting from associated states of hypovolemia appears to be a common physiological link that “connects” hemorrhagic shock to the physiology that limits maximal aerobic capacity. Our approach focuses on the similarities in a complex cascade of cardiopulmonary, metabolic and autonomic compensatory responses during hemorrhage and maximal physical exertion that ultimately function to avoid critical levels of DO2 (DO2crit) and are manifested by elevation in blood lactate levels. We introduce a paradigm of absolute (i.e. hemorrhage) versus relative (i.e. exercise) hypovolemia as a primary physiological factor that contributes to reaching DO2crit, and define the concept of “O2 deficit” to replace the clinical concept of O2 debt. Using the peer-reviewed literature, we provide human data obtained from patients who suffered hemorrhagic shock from severe blood loss and compare it to healthy subjects who performed maximal exercise. We include a novel conceptual framework of the continuum of metabolic relationship between DO2 and [Formula: see text]O2 that is manifested as the final step during both progressive blood loss leading to hemorrhagic shock and at [Formula: see text]O2max. We present evidence to support the contribution of utilizing “O2 extraction reserve” as the initial mechanism for developing an O2 deficit, and the notion of individual variability in compensatory responses. In the absence of reversing inadequate DO2, an increased reliance on O2 extraction reserve, cellular anaerobic glycolysis, and phosphocreatine stores to supplement the energy required by the tissues for normal function will deplete a finite capacity for compensation. In the end, acidity reflected by a blood pH ≤ ∼7.0 leads to disturbance of normal cell functioning of metabolic machinery manifested by irreversible shock in the case of hemorrhage or physical exhaustion when [Formula: see text]O2max is reached. Impact statement Disturbance of normal homeostasis occurs when oxygen delivery and energy stores to the body’s tissues fail to meet the energy requirement of cells. The work submitted in this review is important because it advances the understanding of inadequate oxygen delivery as it relates to early diagnosis and treatment of circulatory shock and its relationship to disturbance of normal functioning of cellular metabolism in life-threatening conditions of hemorrhage. We explored data from the clinical and exercise literature to construct for the first time a conceptual framework for defining the limitation of inadequate delivery of oxygen by comparing the physiology of hemorrhagic shock caused by severe blood loss to maximal oxygen uptake induced by intense physical exercise. We also provide a translational framework in which understanding the fundamental relationship between the body’s reserve to compensate for conditions of inadequate oxygen delivery as a limiting factor to [Formula: see text]O2max helps to re-evaluate paradigms of triage for improved monitoring of accurate resuscitation in patients suffering from hemorrhagic shock.


2017 ◽  
Vol 23 (29) ◽  
pp. 7009-7023 ◽  
Author(s):  
Jana Gülzow ◽  
Gerald Hörner ◽  
Peter Strauch ◽  
Anika Stritt ◽  
Elisabeth Irran ◽  
...  

2017 ◽  
Vol 23 (29) ◽  
pp. 6939-6939
Author(s):  
Jana Gülzow ◽  
Gerald Hörner ◽  
Peter Strauch ◽  
Anika Stritt ◽  
Elisabeth Irran ◽  
...  

Author(s):  
J. N. Meador ◽  
C. N. Sun ◽  
H. J. White

The electron microscope is being utilized more and more in clinical laboratories for pathologic diagnosis. One of the major problems in the utilization of the electron microscope for diagnostic purposes is the time element involved. Recent experimentation with rapid embedding has shown that this long phase of the process can be greatly shortened. In rush cases the making of projection slides can be eliminated by taking dark field electron micrographs which show up as a positive ready for use. The major limiting factor for use of dark field micrographs is resolution. However, for conference purposes electron micrographs are usually taken at 2.500X to 8.000X. At these low magnifications the resolution obtained is quite acceptable.


Author(s):  
Zhifeng Shao

Recently, low voltage (≤5kV) scanning electron microscopes have become popular because of their unprecedented advantages, such as minimized charging effects and smaller specimen damage, etc. Perhaps the most important advantage of LVSEM is that they may be able to provide ultrahigh resolution since the interaction volume decreases when electron energy is reduced. It is obvious that no matter how low the operating voltage is, the resolution is always poorer than the probe radius. To achieve 10Å resolution at 5kV (including non-local effects), we would require a probe radius of 5∽6 Å. At low voltages, we can no longer ignore the effects of chromatic aberration because of the increased ratio δV/V. The 3rd order spherical aberration is another major limiting factor. The optimized aperture should be calculated as


Author(s):  
P. Pradère ◽  
J.F. Revol ◽  
R. St. John Manley

Although radiation damage is the limiting factor in HREM of polymers, new techniques based on low dose imaging at low magnification have permitted lattice images to be obtained from very radiation sensitive polymers such as polyethylene (PE). This paper describes the computer averaging of P4MP1 lattice images. P4MP1 is even more sensitive than PE (total end point dose of 27 C m-2 as compared to 100 C m-2 for PE at 120 kV). It does, however, have the advantage of forming flat crystals from dilute solution and no change in d-spacings is observed during irradiation.Crystals of P4MP1 were grown at 60°C in xylene (polymer concentration 0.05%). Electron microscopy was performed with a Philips EM 400 T microscope equipped with a Low Dose Unit and operated at 120 kV. Imaging conditions were the same as already described elsewhere. Enlarged micrographs were digitized and processed with the Spider image processing system.


Author(s):  
S.K. Aggarwal ◽  
J.M. Fadool

Cisplatin (CDDP) a potent antitumor agent suffers from severe toxic side effects with nephrotoxicity being the major dose-limiting factor, The primary mechanism of its action has been proposed to be through its cross-linking DNA strands. It has also been shown to inactivate various transport enzymes and induce hypocalcemia and hypomagnesemia that may be the underlying cause for some of its toxicities. The present is an effort to study its influence on the parathyroid gland for any hormonal changes that control calcium levels in the body.Male Swiss Wistar rats (Crl: (WI) BR) weighing 200-300 g and of 60 days in age were injected (ip) with cisplatin (7mg/kg in normal saline). The controls received saline injections only. The animals were injected (iv) with calcium (0.5 ml of 10% calcium gluconate/day) and were killed by decapitation on day 1 through 5. Trunk blood was collected in heparinized tubes.


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