Random mtDNA deletions and functional consequence in aged human skeletal muscle

Mitochondrial respiratory chain deteriorates with age, mostly in tissues with high energy requirements. Damage to mitochondrial DNA (mtDNA) by reactive oxygen species is thought to contribute primarily to this impairment. However, the overall extent of random mtDNA mutations has still not been evaluated. We carried out molecular and biochemical analyses in muscle biopsies from healthy young and aged subjects. Deleted mtDNA accumulation was followed by both quantitative PCR analysis to quantify total mtDNA, and Southern-blotting, to determine deleted to full length mtDNA ratio. Enzymatic activities of the mitochondrial respiratory chain were measured in all subjects. Randomly deleted mtDNA appeared mainly in the oldest subjects (beyond 80 years old), affecting up to 70% of mtDNA molecules. The activities of complexes III and IV of the respiratory chain, complexes with mtDNA encoded subunits, are lower in the aged subjects. Physical activity could be one major parameter modulating the mitochondrial respiratory chain activity in aged muscle.     

Antisense strategies for glycosylation engineering of Chinese hamster ovary (CHO) cells

The amount of acid or base consumed in yeast cultures has been recently assigned to the pathway of nitrogen assimilation under respiratory conditions with no contribution by carbon metabolism (Castrillo et al., 1995). In this investigation, experiments under respirofermentative conditions have shown that production or consumption of ethanol does not contribute significantly to the specific rate of proton production (qH+), thus extending the previously obtained relationships for all aerobic conditions in which other major acid/base contributions are not involved. Tests in batch and chemostat culture confirm the validity of qH+ as a formal control parameter in aerobic fermentations.     

Reshaping of bulbar odor response by nasal flow rate in the rat

Background

The impact of respiratory dynamics on odor response has been poorly studied at the olfactory bulb level. However, it has been shown that sniffing in the behaving rodent is highly dynamic and varies both in frequency and flow rate. Bulbar odor response could vary with these sniffing parameter variations. Consequently, it is necessary to understand how nasal airflow can modify and shape odor response at the olfactory bulb level.

Methodology and Principal Findings

To assess this question, we used a double cannulation and simulated nasal airflow protocol on anesthetized rats to uncouple nasal airflow from animal respiration. Both mitral/tufted cell extracellular unit activity and local field potentials (LFPs) were recorded. We found that airflow changes in the normal range were sufficient to substantially reorganize the response of the olfactory bulb. In particular, cellular odor-evoked activities, LFP oscillations and spike phase-locking to LFPs were strongly modified by nasal flow rate.

Conclusion

Our results indicate the importance of reconsidering the notion of odor coding as odor response at the bulbar level is ceaselessly modified by respiratory dynamics.     

Addition of inspiratory resistance increases the amplitude of the slow component of O2 uptake kinetics.

The contribution of respiratory muscle work to the development of the O(2) consumption (Vo(2)) slow component is a point of controversy because it has been shown that the increased ventilation in hypoxia is not associated with a concomitant increase in Vo(2) slow component. The first purpose of this study was thus to test the hypothesis of a direct relationship between respiratory muscle work and Vo(2) slow component by manipulating inspiratory resistance. Because the conditions for a Vo(2) slow component specific to respiratory muscle can be reached during intense exercise, the second purpose was to determine whether respiratory muscles behave like limb muscles during heavy exercise. Ten trained subjects performed two 8-min constant-load heavy cycling exercises with and without a threshold valve in random order. Vo(2) was measured breath by breath by using a fast gas exchange analyzer, and the Vo(2) response was modeled after removal of the cardiodynamic phase by using two monoexponential functions. As anticipated, when total work was slightly increased with loaded inspiratory resistance, slight increases in base Vo(2), the primary phase amplitude, and peak Vo(2) were noted (14.2%, P < 0.01; 3.5%, P > 0.05; and 8.3%, P < 0.01, respectively). The bootstrap method revealed small coefficients of variation for the model parameter, including the slow-component amplitude and delay (15 and 19%, respectively), indicating an accurate determination for this critical parameter. The amplitude of the Vo(2) slow component displayed a 27% increase from 8.1 +/- 3.6 to 10.3 +/- 3.4 ml. min(-1). kg(-1) (P < 0.01) with the addition of inspiratory resistance. Taken together, this increase and the lack of any differences in minute volume and ventilatory parameters between the two experimental conditions suggest the occurrence of a Vo(2) slow component specific to the respiratory muscles in loaded condition.     

Estimation of the mechanical parameters of the human respiratory system

A numerical algorithm has been developed for the estimation of the mechanical parameters of the human respiratory system. In order to estimate the pulmonary resistance and the dynamic pulmonary elastance, the transpulmonary pressure and the airflow at the mouth or nose are expanded in Chebyshev series. The nonlinear mathematical lung model and a set of measurements for airflow and pressure are then handled by the numerical technique. The lung model includes a component to account for turbulent flow in the larynx and trachea. This contribution presents an alternative method for lung parameter estimation and differs from most existing methods in that it does not need measurements for the tidal volume. It therefore eliminates the use of a body plethysmograph. The method may also find potential application to various other parameter identification problems.     

Modeling the electron transport chain of purple non‐sulfur bacteria

Purple non‐sulfur bacteria (Rhodospirillaceae) have been extensively employed for studying principles of photosynthetic and respiratory electron transport phosphorylation and for investigating the regulation of gene expression in response to redox signals. Here, we use mathematical modeling to evaluate the steady‐state behavior of the electron transport chain (ETC) in these bacteria under different environmental conditions. Elementary‐modes analysis of a stoichiometric ETC model reveals nine operational modes. Most of them represent well‐known functional states, however, two modes constitute reverse electron flow under respiratory conditions, which has been barely considered so far. We further present and analyze a kinetic model of the ETC in which rate laws of electron transfer steps are based on redox potential differences. Our model reproduces well‐known phenomena of respiratory and photosynthetic operation of the ETC and also provides non‐intuitive predictions. As one key result, model simulations demonstrate a stronger reduction of ubiquinone when switching from high‐light to low‐light conditions. This result is parameter insensitive and supports the hypothesis that the redox state of ubiquinone is a suitable signal for controlling photosynthetic gene expression.     

Acute respiratory viral infections and bronchial asthma. Cellular and molecular aspects of the problem

In this review information on relationships between acute respiratory viral infections (ARVI) and attacks of bronchial asthma is presented. The mechanisms of the appearance of virus induced attacks and bronchial hyperreactiveness have been analyzed. The role of the immune response of the body as well as anti-inflammatory and chemotaxic cytokines in the development of bronchial obstruction and hyperreactiveness has been substantiated. The conclusion on the role of ARVI especially induced by respiratory syncytial virus and rhinoviruses, in the development of immune response facilitating allergic sensitization and provoking attacks of bronchial asthma has been made.     

Pressure oscillation delivery to the lung: Computer simulation of neonatal breathing parameters

Preterm newborn infants may develop respiratory distress syndrome (RDS) due to functional and structural immaturity. A lack of surfactant promotes collapse of alveolar regions and airways such that newborns with RDS are subject to increased inspiratory effort and non-homogeneous ventilation. Pressure oscillation has been incorporated into one form of RDS treatment; however, how far it reaches various parts of the lung is still questionable. Since in-vivo measurement is very difficult if not impossible, mathematical modeling may be used as one way of assessment. Whereas many models of the respiratory system have been developed for adults, the neonatal lung remains essentially ill-described in mathematical models. A mathematical model is developed, which represents the first few generations of the tracheo-bronchial tree and the 5 lobes that make up the premature ovine lung. The elements of the model are derived using the lumped parameter approach and formulated in Simulink? within the Matlab? environment. The respiratory parameters at the airway opening compare well with those measured from experiments. The model demonstrates the ability to predict pressures, flows and volumes in the alveolar regions of a premature ovine lung.     

蝇蛹呼吸角的研究

本文首次研究了我国13种蝇蛹的呼吸角形态(8种有角,5种无),运用统计学方法论证了角参数的分类学价值,描述了光学显微镜和扫描电子显微镜下的显微结构。发现呼吸角呈管腔结构,它借呼吸角内导管将蛹内虫体的前气门与外界沟通。     

Sensitivity analysis for an improved estimation of respiratory mechanics parameters

In this paper a respiratory mechanics model is considered, which is characterized by a biquadratic input impedance, and a sensitivity analysis has been carried out to determine the influence of experimental conditions on parameter estimation. This analysis was effected with data obtained experimentally, in three different patients under intermittent positive pressure ventilation. In all three cases, the model's input impedance demonstrated a maximum sensitivity in relation to the various parameters included in the field of frequencies from 0 to 10 Hz. This seems to suggest therefore, that the use of a low-pass filter with a cut-off frequency equal to 10 Hz could improve the signal/noise ratio and, consequently, the accuracy of the estimation of the parameters. Furthermore, the use of a system input with a bandwidth of 0–10 Hz provides the experimental conditions, under which good estimates of the parameters can be obtained. This conclusion has also been confirmed by simulation studies which have been conducted with different types of input signals.     

Influence of phospholipids on the respiratory activity of embryonal heart cells cultured in vitro in presence of different ethanol concentrations

The influence of phospholipids on respiratory activity of embryonal heart cells, trated with certainly harmful concentrations of ethanol, has been discussed. It has been concluded that when the cell is deeply impaired the administration of phospholipids does not seem to have positive effects. In this condition an irreversible morphological alteration has been induced.     

Iterative Integral Parameter Identification of a Respiratory Mechanics Model

ABSTRACT: BACKGROUND: Patient-specific respiratory mechanics models can support the evaluation of optimal lung protective ventilator settings during ventilation therapy. Clinical application requires that the individual's model parameter values must be identified with information available at the bedside. Multiple linear regression or gradient-based parameter identification methods are highly sensitive to noise and initial parameter estimates. Thus, they are difficult to apply at the bedside to support therapeutic decisions. METHODS: An iterative integral parameter identification method is applied to a second order respiratory mechanics model. The method is compared to the commonly used regression methods and error-mapping approaches using simulated and clinical data. The clinical potential of the method was evaluated on data from 13 Acute Respiratory Distress Syndrome (ARDS) patients. RESULTS: The iterative integral method converged to error minima 350 times faster than the Simplex Search Method using simulation data sets and 50 times faster using clinical data sets. Established regression methods reported erroneous results due to sensitivity to noise. In contrast, the iterative integral method was effective independent of initial parameter estimations, and converged successfully in each case tested. CONCLUSION: These investigations reveal that the iterative integral method is beneficial with respect to computing time, operator independence and robustness, and thus applicable at the bedside for this clinical application.     

The energetics of bacterial growth: a reassessment

The growth yield of microbial cultures can be used to estimate the efficiency of energy generation during a fermentation or respiration, in the past, the assessment of this efficiency in organisms carrying out a respiration has been the subject of many heated debates. This has partly been caused by the complexity of microbial respiratory chains. Strains of Escherichia coli specifically modified in their respiratory chain have been used recently to re-evaluate the energetic efficiency of the bacterial respiration using chemostat cultures. The different strains indeed show different growth efficiencies. The physiological significance of energetically less-efficient branches of the respiratory chain is discussed.     

Etiologic Diagnosis of Lower Respiratory Tract Infections

Decision as to the role of infection in lower respiratory tract disease requires examination by culture of specimens known to be derived from the infra-laryngeal respiratory tract. Methods that involve the upper respiratory tract in collection of specimens entail the hazard of contamination by microbiota resident in the upper respiratory tract.The extrapulmonary approaches of cutting-needle biopsy and needle aspiration of intrathoracic disease have not been impressively productive of etiologic diagnosis of infections. While open-chest surgical biopsy has been a highly effective means to diagnosis, this approach does have special requirements in facilities and technical skills.Percutaneous transtracheal aspiration of tracheo-broncho-pulmonary secretions-exudates has been productive of useful information. Because of inherent simplicity and safety, transtracheal aspiration should precede resort to more demanding, difficult, dangerous procedures.     

Animal model of acute respiratory insufficiency by HCl aspiration in Lewe mini-pigs

Acute respiratory insufficiency or adult respiratory distress syndrome is a common medical emergency in intensive medicine complicated by high mortality. To study the acute respiratory insufficiency under standardized conditions an animal model in Lewe-mini-pigs has been developed. This model is based on aspiration pneumonitis produced by intrabrochial atomisation of 0.2 N hydrochloric acid. General anesthesia was performed by neuroleptanalgesia. In all animals the profound changes in gas exchange, pulmonary mechanics and hemodynamics as well as quasi-static volume-pressure relationships after hydrochloric acid aspiration were described. The results suggest that this model is suitable to outline the profound changes in pulmonary function in this type of acute respiratory insufficiency.     

The biological age of the respiratory system]

A model of the biological age of the respiratory system is described. The following biological age determinants are used: vital lung capacity, maximal breathing capacity, mid-expiratory flow rate, oxygen consumption. They commonly meet the requirements of the biological age measurement tests as well as reflect main symptoms of the respiratory system ageing. The proposed model has been used to study the peculiarities of the respiratory system ageing in the Abkhasian population and to assess the effect of smoking on this process.     

Mitochondrial membrane potential and aging

The mitochondrial membrane potential (or protonmotive force) is the central bioenergetic parameter that controls respiratory rate, ATP synthesis and the generation of reactive oxygen species, and is itself controlled by electron transport and proton leaks. As a consequence of extensive research, there has emerged a consensus as to how these parameters integrate. Despite this consensus, the literature contains contradictory reports on the extent to which these parameters are modified in animal models of aging. This article critically examines the basis for a number of these reports.     

Colonization of denture plaque by respiratory pathogens in dependent elderly

Objectives: Recently, there has been a resurgence of interest in the interactions between oral conditions and a number of prevalent systemic diseases. The morbidity and mortality of the dependent elderly that result from aspiration pneumonia have been recognized as a major geriatric health problem. The purpose of this study was to gain more information on the microflora of plaque on dentures and to assess the existence of oral infectious pathogens potentially causing the respiratory disease in the dependent elderly. Subjects and Methods: The denture bacterial flora of 50 dependent elderly were examined to identify microorganisms by the culture method. Results: 18 species of microorganisms were detected in denture plaque in this study. A variety of pathogens with the potential to cause respiratory infection pathogens colonized on the dentures of dependent elderly. Conclusion: The results of the present study revealed that bacteria that commonly cause respiratory infection colonized on the dentures of dependent elderly, suggesting that denture plaque may function as a reservoir of potential respiratory pathogens to facilitate colonization on the oropharynx.     

Does the respiratory system limit the aerobic working capacity of humans?

The question concerning respiratory function reserves among the factors determining the maximal power of muscular work is considered. Even in strenuous physical exercise, pulmonary ventilation does not exceed a rather constant level for every individual. Studies conducted using the programmed isocapnic hyperpnea method developed by the authors demonstrated that this level precisely reflects the functional respiratory reserve that is one of the factors limiting maximal work performance intensity. Under normal conditions, the functional respiratory reserve is 20 to 40% less than the so-called maximal breathing capacity (MBC) determined in a test, which requires voluntarily forcing respiratory efforts and exorbitant energy expenditure for the respiratory muscles performance. Therefore, the MBC should be regarded only as a parameter of ventilatory forced capacity used in extreme situations such as competitive athletic loading or in more resistive breathing when decreased respiratory system reserves become a leading factor rigidly limiting aerobic working capacity. A scheme is given that illustrates the ambiguous role of the respiratory system in this aspect.     

Regulation of respiration: visceral and behavioural components

The review segregates two aspects of respiration regulation: autonomous respiration regulation as a visceral function ensuring metabolic needs of a body by maintaining stability of own respiratory environment, on the one hand, and behavioural regulation of respiration under control of the volitional sphere, on the other hand. The authors focus on respiratory rythmogenesis, the problem that has not yet been resolved, and on the mechanism of precise correlation of lung ventillation with the metabolic level, in case of muscular exercise, in particular. The authors discuss interaction of visceral and behavioural mechanisms of respiratory regulation. The substance of the phenomenon of respiratory embarrassment is considered in this connection as a visceral signal addressed to the behavioural sphere. Reasonableness of introduction of a new breathing system in a healthy person is doubted. The article justifies the pracice of bioregulation of the respiratory function.