Modeling pulmonary and CNS O2 toxicity and estimation of parameters for humans

2002 ◽  
Vol 92 (1) ◽  
pp. 248-256 ◽  
Author(s):  
R. Arieli ◽  
A. Yalov ◽  
A. Goldenshluger
Keyword(s):  
Vital Capacity ◽  
Oxygen Toxicity ◽  
Recovery Process ◽  
Likelihood Method ◽  
Estimation Of Parameters ◽  
Power Equation ◽  
Hyperoxic Exposure ◽  
Calculated Parameter ◽  
Hyperbaric Oxygen Exposure ◽  
Combined Data

10.1152/japplphysiol.00434.2001.—The power expression for cumulative oxygen toxicity and the exponential recovery were successfully applied to various features of oxygen toxicity. From the basic equation, we derived expressions for a protocol in which Po 2 changes with time. The parameters of the power equation were solved by using nonlinear regression for the reduction in vital capacity (ΔVC) in humans:  %ΔVC  = 0.0082 × t 2(Po 2/101.3)4.57, where t is the time in hours and Po 2is expressed in kPa. The recovery of lung volume is  ΔVC t  = ΔVCe × e −(−0.42 + 0.00379Po 2 ) t , where ΔVC t is the value at time tof the recovery, ΔVCe is the value at the end of the hyperoxic exposure, and Po 2 is the prerecovery oxygen pressure. Data from different experiments on central nervous system (CNS) oxygen toxicity in humans in the hyperbaric chamber ( n = 661) were analyzed along with data from actual closed-circuit oxygen diving ( n = 2,039) by using a maximum likelihood method. The parameters of the model were solved for the combined data, yielding the power equation for active diving: K = t 2(Po 2/101.3)6.8, where tis in minutes. It is suggested that the risk of CNS oxygen toxicity in diving can be derived from the calculated parameter of the normal distribution: Z = [ln( t) − 9.63 +3.38 × ln(Po 2/101.3)]/2.02. The recovery time constant for CNS oxygen toxicity was calculated from the value obtained for the rat, taking into account the effect of body mass, and yielded the recovery equation: Kt = K e × e −0.079 t , where Kt and K e are the values of K at time t of the recovery process and at the end of the hyperbaric oxygen exposure, respectively, and tis in minutes.

Effect of prenatal isoxsuprine on pulmonary oxygen toxicity in the newborn rat

1980 ◽  
Vol 48 (3) ◽  
pp. 505-510 ◽  
Author(s):  
L. Frank ◽  
J. Summerville ◽  
D. Massaro
Keyword(s):  
Enzyme Activities ◽  
Oxygen Toxicity ◽  
Fetal Lung ◽  
Antioxidant Enzyme Activities ◽  
Newborn Rats ◽  
Lung Maturation ◽  
Lung Weight ◽  
Pregnant Rats ◽  
Rat Pups ◽  
Hyperoxic Exposure

Isoxsuprine, a beta-sympathomimetic agent used clinically to delay premature parturition and to possibly accelerate fetal lung maturation, was administered to pregnant rats at 48 and 24 h prior to delivery. Newborn rats were placed in 96-98% O2 (or room air) to determine if the prenatal isoxsuprine treatment compromised their tolerance to prolonged hyperoxic exposure. (Exogenous catecholamines are known to exacerbate O2 toxicity in adult animals). Survival of the isoxsuprine-treated pups in O2 (52%) was no different than for control neonates exposed to hyperoxia for 7 days (57%) (P = 0.22). Body weight, lung weight, lung protein, and DNA content of the newborns were also not altered by the prenatal isoxsuprine treatment. Lung antioxidant enzyme activities for superoxide dismutase, catalase, and glutathione peroxidase were the same at birth in the isoxsuprine-treated and control rat pups, and the enzyme activities increased in response to hyperoxic exposure in each group to an equivalent degree. Thus, in utero treatment with isoxsuprine had no apparent adverse effect on newborn rats exposed to a prolonged O2 challenge.

Pulmonary oxygen toxicity in mice is characterized by alterations in ascorbate redox status

1995 ◽  
Vol 79 (5) ◽  
pp. 1769-1776 ◽  
Author(s):  
L. S. Rusakow ◽  
J. Han ◽  
M. A. Hayward ◽  
O. W. Griffith
Keyword(s):  
High Performance ◽  
Clinical Utility ◽  
Oxygen Toxicity ◽  
Redox Status ◽  
The Body ◽  
Antioxidant Defenses ◽  
Total Glutathione ◽  
Plasma Ascorbate ◽  
Hyperoxic Exposure ◽  
Reduced Forms

Pulmonary oxygen toxicity results from disruption of the usual antioxidant defenses of the body. We therefore investigated whether mice that suffer from oxygen toxicity show significant alterations in the redox status of ascorbate, an important antioxidant, as reflected by changes in the relative amounts of its oxidized and reduced forms. Mice were exposed to air or hyperoxia (> 97% O2, 760 mmHg). After 5 days, plasma and saline-perfused lungs were removed and levels of ascorbate (AA), oxidized ascorbate [dehydroascorbate (DHAA)], and total ascorbate species ([AA+DHAA]) were determined by a sensitive and specific high-performance liquid chromatography assay; lungs were also assayed for total glutathione and glutathione disulfide (GSSG), an established marker of oxidative stress. We found that with hyperoxic exposure plasma AA increased by 32%, plasma DHAA increased substantially from previously undetectable levels, and the DHAA-to-[AA+DHAA] ratio increased. In contrast, in lung, [AA+DHAA] decreased by 41%. Plasma AA, DHAA, and [AA+DHAA] each correlated inversely with lung [AA+DHAA] and directly with lung GSSC. We conclude that alterations in plasma ascorbate redox status reflect pulmonary oxygen toxicity in mice. Our results suggest that further investigations are warranted to determine whether similar findings occur in humans and have clinical utility.

Prediction of central nervous system oxygen toxicity in rats

1994 ◽  
Vol 77 (4) ◽  
pp. 1903-1906 ◽  
Author(s):  
R. Arieli ◽  
G. Hershko
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Exposure Time ◽  
Electrical Discharge ◽  
Oxygen Toxicity ◽  
Threshold Value ◽  
Power Equation ◽  
The Mean

Cumulative O2 toxicity (K) can be calculated using the expression K = t2 x PO2c, where t is exposure time and the power c is to be determined; the phenomenon is liable to occur when K reaches Kc, the threshold value of K at which a symptom is manifested. Six rats were each exposed six times to 6 ATA O2 at 2-day intervals until the first electrical discharge (FED) was noted in an electroencephalogram. There was no difference in latency to FED in the series of six exposures. Thirteen rats were exposed to O2 until FED was noted in an electroencephalogram. They were exposed to four constant PO2's of 5, 6, 7, and 8 ATA and to two combined profiles of 1) 5 min at 7 ATA followed by 5 ATA and 2) 15 min at 5 ATA followed by 7 ATA. The solution of the equation for each rat was used to predict its latency to FED on the combined profile. The correlation of predicted to measured latency was significant (P < 0.0001), and the slope was not different from 1. Solving for these parameters using the combination of all the data, we obtained Kc = 5.71 x 10(6) and c = 5.39, which correctly predicted the mean latency but failed to predict individual latency. It is preferable to use each rat as its own control. The significance of the correlation supports the validity of the power equation for calculating K.

Oxygen toxicity in neonatal and adult animals of various species

1978 ◽  
Vol 45 (5) ◽  
pp. 699-704 ◽  
Author(s):  
L. Frank ◽  
J. R. Bucher ◽  
R. J. Roberts
Keyword(s):  
Antioxidant Enzyme ◽  
Oxygen Toxicity ◽  
Antioxidant Enzyme Activities ◽  
Defense System ◽  
Exposure System ◽  
Hyperoxic Exposure ◽  
Respective Parent ◽  
Study Support

Neonatal and adult animals of five species were exposed to 95+% O2. Survival time and changes in lung antioxidant enzyme activity (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GP)) in response to hyperoxia were determined. Adult animals succumbed to O2 lung toxicity in 3--5 days. Neonatal rats, mice and rabbits showed minimal lung changes after 7 days of hyperoxic exposure and these same neonatal animals showed rapid and significant increases in lung antioxidant enzyme activities. In contrast, neonatal guinea pigs and hamsters had no lung antioxidant enzyme response to hyperoxia and these neonates died in 95+% O2 as readily as their respective parent animals. Results from an in vitro hyperoxic exposure system suggest that the lack of enzymic response of the guinea pig (and hamster) neonates to O2 challenge is due to an inherent pulmonary biochemical unresponsiveness rather than to a deficiency of a necessary “serum factor.” The results of this species and age study support the important role of the lung antioxidant enzyme defense system in protection of the lung from O2-induced injury.

scholarly journals A new Weibull Exponentiated Inverted Weibull Distribution for modelling positively-skewed data

2021 ◽  
Vol 27 (1) ◽  
pp. 43-53
Author(s):  
J.O. Braimah ◽  
J.A. Adjekukor ◽  
N. Edike ◽  
S.O. Elakhe
Keyword(s):  
Weibull Distribution ◽  
Failure Rate ◽  
Real Life ◽  
Rate Function ◽  
Likelihood Method ◽  
Estimation Of Parameters ◽  
Failure Rate Function ◽  
Lifetime Distributions ◽  
Increasing Failure Rate ◽  
Modeling Data

An Exponentiated Inverted Weibull Distribution (EIWD) has a hazard rate (failure rate) function that is unimodal, thus making it less efficient for modeling data with an increasing failure rate (IFR). Hence, the need to generalize the EIWD in order to obtain a distribution that will be proficient in modeling these types of dataset (data with an increasing failure rate). This paper therefore, extends the EIWD in order to obtain Weibull Exponentiated Inverted Weibull (WEIW) distribution using the Weibull-Generator technique. Some of the properties investigated include the mean, variance, median, moments, quantile and moment generating functions. The explicit expressions were derived for the order statistics and hazard/failure rate function. The estimation of parameters was derived using the maximum likelihood method. The developed model was applied to a real-life dataset and compared with some existing competing lifetime distributions. The result revealed that the (WEIW) distribution provided a better fit to the real life dataset than the existing Weibull/Exponential family distributions.

scholarly journals CONTINUOUS-TIME SEMI-MARKOV INFERENCE OF BIOMETRIC LAWS ASSOCIATED WITH A LONG-TERM CARE INSURANCE PORTFOLIO

2017 ◽  
Vol 47 (2) ◽  
pp. 527-561 ◽  
Author(s):  
Guillaume Biessy
Keyword(s):  
Continuous Time ◽  
Long Term Care ◽  
Likelihood Method ◽  
Estimation Of Parameters ◽  
Term Care ◽  
Insurance Portfolio ◽  
The Disabled ◽  
Reliable Knowledge ◽  
Access To Data

AbstractUnlike the mortality risk on which actuaries have been working for more than a century, the long-term care (LTC) risk is relatively new and as of today hardly mastered. Semi-Markov processes have been identified as an adequate tool to study this risk. Nevertheless, access to data is limited and the associated literature still scarce. Insurers mainly use discrete time methods directly inspired from the study of mortality in order to build experience tables. Those methods however are not perfectly suited for the study of competing risk situations. This article provides a theoretical framework to estimate biometric laws associated with a LTC insurance portfolio. The presented method relies on a continuous-time semi-Markov model with three states: autonomy, disability and death. The process describing the state of disability is defined through its transition intensities. We provide a formula to infer the mortality of autonomous people from the mortality of the whole portfolio, on which we have more reliable knowledge. We then propose a parametric expression for the remaining intensities of the model. In particular, incidence in LTC is described by a logistic formula. Under the assumption that the disabled population is a mixture of two latent populations with respect to the category of pathology that caused LTC, we show that the resulting intensity of mortality in LTC takes a very peculiar form and depends on time spent in the LTC state. Estimation of parameters relies on the maximum likelihood method. Our parametric approach, while inducing model uncertainty, eliminates issues related to segmentation in age categories, smoothing or extrapolation at higher ages and thus proves very convenient for the practitioner. Finally, we provide an application using data from a real LTC insurance portfolio.

scholarly journals Sustained hyperoxia-induced NF-κB activation improves survival and preserves lung development in neonatal mice

2014 ◽  
Vol 306 (12) ◽  
pp. L1078-L1089 ◽  
Author(s):  
Sarah McKenna ◽  
Katherine A. Michaelis ◽  
Fadeke Agboke ◽  
Thanh Liu ◽  
Kristie Han ◽  
...  
Keyword(s):  
Lung Development ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Growth Factor Receptor ◽  
Oxygen Toxicity ◽  
Vessel Density ◽  
Pulmonary Vessel ◽  
Neonatal Mice ◽  
Hyperoxic Exposure ◽  
Lung Structure

Oxygen toxicity contributes to the pathogenesis of bronchopulmonary dysplasia (BPD). Neonatal mice exposed to hyperoxia develop a simplified lung structure that resembles BPD. Sustained activation of the transcription factor NF-κB and increased expression of protective target genes attenuate hyperoxia-induced mortality in adults. However, the effect of enhancing hyperoxia-induced NF-κB activity on lung injury and development in neonatal animals is unknown. We performed this study to determine whether sustained NF-κB activation, mediated through IκBβ overexpression, preserves lung development in neonatal animals exposed to hyperoxia. Newborn wild-type (WT) and IκBβ-overexpressing (AKBI) mice were exposed to hyperoxia (>95%) or room air from day of life (DOL) 0–14, after which all animals were kept in room air. Survival curves were generated through DOL 14. Lung development was assessed using radial alveolar count (RAC) and mean linear intercept (MLI) at DOL 3 and 28 and pulmonary vessel density at DOL 28. Lung tissue was collected, and NF-κB activity was assessed using Western blot for IκB degradation and NF-κB nuclear translocation. WT mice demonstrated 80% mortality through 14 days of exposure. In contrast, AKBI mice demonstrated 60% survival. Decreased RAC, increased MLI, and pulmonary vessel density caused by hyperoxia in WT mice were significantly attenuated in AKBI mice. These findings were associated with early and sustained NF-κB activation and expression of cytoprotective target genes, including vascular endothelial growth factor receptor 2. We conclude that sustained hyperoxia-induced NF-κB activation improves neonatal survival and preserves lung development. Potentiating early NF-κB activity after hyperoxic exposure may represent a therapeutic intervention to prevent BPD.

scholarly journals Testing Procedure for Item Response Probabilities of 2Class Latent Model

2020 ◽  
Vol 39 (3) ◽  
pp. 657-667
Author(s):  
Bushra Shamshad ◽  
Junaid Sagheer Siddiqui
Keyword(s):  
Item Response ◽  
Latent Variable ◽  
Goodness Of Fit ◽  
Latent Class ◽  
Latent Class Model ◽  
Likelihood Method ◽  
Model Parameters ◽  
Estimation Of Parameters ◽  
Goodness Of Fit Test ◽  
Significant Difference

This paper presents Hotelling T2 as a procedure for the testing of significance difference between the item response probabilities (ωij′s) of classes in a Latent Class Model (LCM). Parametric bootstrap technique is used in order to generate samples for ωij′s. These samples are based on the estimated parameters of 2-class latent model. The estimation of parameters in either situation is done using the Expectation Maximization (EM) algorithm through Maximum likelihood method. The hypothesis under consideration is whether the response probabilities (ωij′s) are equal against each item in both the classes. { H0 : ωi1 = ωi2. against H1 : =ωi1 ≠ ωi2}. If the test exhibits significant difference between response probabilities in both classes, it will be a clear indication of a presence of latent variable. We consider both training and testing data sets to develop the test. In order to apply Hotelling T2 test the basic assumptions of normality and homogeneity of variance are also checked. Chi-square goodness of fit test is used for assessing normal distribution to be good fitted on the hypothesized (bootstrap samples) based on 2-class latent model parameters for each data and Bartlett test to check heterogeneity of variances in ωij′s. Moreover, our procedure produces a minimum standard error of estimates as compared to those obtained through the package in R.Gui environment

scholarly journals Development of pulmonary oxygen toxicity in rats after hyperoxic exposure

2014 ◽  
Vol 58 (2) ◽  
pp. 305-310 ◽  
Author(s):  
Piotr Siermontowski ◽  
Agnieszka Pedrycz ◽  
Maciej Konarski ◽  
Dorota Kaczerska ◽  
Katarzyna van Damme-Ostapowicz ◽  
...  
Keyword(s):  
Cross Sections ◽  
Prolonged Exposure ◽  
Oxygen Toxicity ◽  
Pure Oxygen ◽  
Hyperbaric Chamber ◽  
Qualitative And Quantitative ◽  
Hyperoxic Exposure ◽  
Pulmonary Parenchyma ◽  
Quantitative Examination ◽  
Animal Experimental Model

Abstract The aim of the study was to examine the effects of hyperbaric oxygen on lung aeration on an animal experimental model and compare the obtained results with the anticipated scope of damage to pulmonary parenchyma in humans under the same exposure conditions. The research was carried out on Black Hood rats that were kept in a hyperbaric chamber designed for animals in an atmosphere of pure oxygen and at overpressures of 0.15, 0.2, 0.3, 0.4, and 0.5 MPa for 1, 2 or 4 h. After sacrificing the animals, histopathological specimens were obtained encompassing cross-sections of entire lungs, which were subjected to qualitative and quantitative examination with the use of the 121-point Haug grid. A statistically significant decrease in pulmonary parenchyma was observed as a result of an increasing oxygen partial pressure as well as with prolonged exposure time. The intensification of changes observed was much higher than expected on the basis of calculations performed with the use of tables.

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