The aim of this thesis was to examine the effects of exercise on gas mixing in the lung during exercise. There were four major stages. Firstly, the existing equipment used with resting subjects was applied to the exercising subject and was found to be inappropriate. Secondly, an in-line system of measuring flow and gas concentration was devised. Thirdly this system was validated with the aid of a physical model and resting subjects. Finally, nitrogen wash-out data were collected from 24 subjects at rest and during progressive exercise at three standard exercise intensities. The dynamic response characteristics of the bag-in-box spirometer at high breathing frequencies (50 min-1) were such that tidal volume was underestimated by almost 50%. The box was too small and its response too a linear for adequate correction factors to be applied. The in-line system, based on a linear relationship between flow and several argon, oxygen, carbon dioxide and nitrogen mixtures ( r = + 0.99, p < 0.01 , Y = 0.2687 FAr + 0.995 ), measured tidal volumes reliably ( CV < 1% ) when expired flow was maintained at 35&deg; C. Thirty-six wash-outs of a 2.4 litre bell jar produced a mean value of 2.461 litres ( SD. 0.034, CV. 1.4% ). The capacity of the in-line system to measure gas mixing efficiency reliably was tested on resting subjects ( six trials each on two days ). Mean values were 76.7% ( SD. 7-5% ) and 76.8% ( SD 4.7% ); mean CV for all trials was 8%. Progressive exercise resulted in significant reduction in lung volume as measured by recovered nitrogen; there was evidence that at the greatest exercise intensity all the nitrogen was not recovered. Decreased diffusion time as a result of greater respiratory frequency may have been responsible. The significantly greater tidal volumes and respiratory frequencies observed on exercise resulted in bigger minute volumes. Both series and alveolar deadspaces increased, but the greater minute volume more than compensated for the growing dead spaces, and so the inspired volume available for mixing was increased. Ventilatory and gas mixing efficiency improved significantly as exercise progressed, but the greatest improvement occurred at the first power output of 50W; thereafter, there was very little change in gas mixing efficiency in spite of three-fold increase in ventilation. It is possible that gas mixing efficiency functions optimally at FRC and that, unlike some other physiological measures, there is little reserve capacity. However, the possibility of gas mixing deficiencies at maximal exercise leading to a ventilatory limit to maximal oxygen uptake remains, and this issue still needs to be investigated.

NADH:ubiquinone oxidoreductase (complex I) is the largest and most complicated enzyme in the mitochondrial electron transfer chain. It catalyses the oxidation of NADH and the reduction of ubiquinone, coupled to the translocation of protons across the mitochondrial inner membrane, maintaining the proton motive force used for ATP synthesis. Complex I is the least understood of the respiratory enzymes; although the mechanisms of NADH oxidation and intramolecular electron transfer are gradually becoming appreciated, the mechanisms of quinone binding and reduction and proton translocation remain unknown. Complex I dysfunction has been implicated in a wide range of pathologies including mitochondrial diseases such as Leigh's disease, as well as neurodegenerative diseases such as Alzheimer's and Parkinson's. The work described in the first part of this thesis is aimed at elucidating the structure of either a subcomplex of mitochondrial complex I, or of the intact enzyme itself. A comprehensive investigation revealed that hydrophilic subcomplexes of complex I from bovine heart mitochondria are not suitable for use as models of the intact enzyme. Attempts to prepare intact complex I of sufficient quality for structural work were successful; however, results from a large set of crystallization trials were disappointing. The second part of this thesis describes three studies of the function and mechanism of complex I from bovine heart mitochondria. First, the flavin mononucleotide, the site of NADH oxidation, was identified as the site of the 'inhibitor-insensitive' NADH:ubiquinone oxidoreduction reaction. The formation of semiquinones initiates redox cycling reactions with oxygen, producing vast amounts of reactive oxygen species; further studies revealed that other oxidants, such as paraquat, also react at the flavin site and initiate redox cycling reactions. Second, kinetic studies showed that the reaction between NADH and positively charged oxidants such as HAR (hexaammineruthenium (III)) proceeds by an unusual ternary reaction mechanism at the flavin site of complex I. Finally, double electron-electron resonance spectroscopy was used to show unambiguously that iron sulphur cluster 4Fe[TY]1 gives rise to electron paramagnetic resonance signal N4; the data provide an alternating potential energy profile for electron transfer along the cluster chain between the flavin and the quinone-binding site.

No description available.

The normal breathing pattern recorded in unanaesthetized, lightly re-strained turtles, Chrysemys picta, consisted of periods of continuous breathing interspersed with periods of breath holding. During each ventilatory period, respiratory frequency and tidal volume were controlled separately and independently of breath length, the total inspiratory interval, the active inspiratory interval and the expiratory interval. Increases in pulmonary minute ventilation during hypercapnia were caused by increases in respiratory frequency due solely to shortening of the intervals of breath holding. The frequency of breathing within each ventilatory period remained constant. There was a large variability in inspiratory and expiratory gas flow rates yet tidal volume was maintained within narrow limits by adjustment of the lengths of the active inspiratory and expiratory intervals. This mechanism was dependent upon lung volume information carried within the vagus nerve. Following vagotomy, changes in minute ventilation due to hypercapnia stemmed primarily from changes in tidal volume while changes in respiratory frequency were markedly reduced. Lung volume information carried within the vagus nerve arose from slowly adapting pulmonary stretch receptors. Single fibre nerve activity from pulmonary receptors was recorded from vagal slips in single-pithed tidally ventilated turtles. The major stimulus of these receptors was the change in lung volume throughout each breathing cycle. The rate and degree of change in transpulmonary pressure were without direct effect on receptor discharge. The functional characteristics of these receptors differed only quantitatively from those recorded in pulmonary stretch receptors of mammals and these differences probably stem from the lower body temperature of the turtle and the location of the receptors in the turtle lung. Most receptors were sensitive to CO₂, several sufficiently sensitive that both tonic and phasic receptor discharge were totally inhibited throughout the ventilatory cycle by 5 to 10% CO₂ in the inspired gas. Pulmonary mechanoreceptors in the frog were also shown to be sensitive to. The acute sensitivity to of a few receptors in turtles and frogs parallels that of the intrapulmonary receptors described-in birds and suggests that a pulmonary receptor with distinct mechano- and chemosensitive properties may represent the functional precursor of the variety of pulmonary receptor types which appear in modern day vertebrates. To examine the role of sensitivity of pulmonary receptors in the overall response of turtles to inhaled CO₂, ventilatory responses of unanaesthetized turtles to changes in the intrapulmonary CO₂ content of a vascularly isolated lung (constant PaCO₂ ) and an intact lung were measured during spontaneous breathing. The isocapnic hyperpnea associated with inhalation of CO₂ by the vascularly isolated lung was small and abolished by vagotomy. It is concluded that both inhibition of pulmonary stretch receptor discharge with increasing levels of FICO₂ and a functional increase in central inspiratory volume threshold contributed significantly to tidal volume increases during hypercapnia. The primary ventilatory response of intact turtles to increasing levels of FICO₂ was an increase in respiratory frequency and this response FICO₂ was greatly reduced when CO₂ was inspired only by the vascularly isolated lung. Thus the ventilatory response of turtles to increasing levels of FICO₂ is primarily dependent upon increased levels of arterial CO₂. The effect of vagotomy in producing apneusis in turtles supports suggestions they lack a pneumotaxic centre. The arrhythmic breathing pattern in turtles with intact vagal nerves, however, bears no similarity to the pattern of breathing in mammals with only the pneumotaxic centre ablated. It is concluded that the vagal input from pulmonary receptors to the respiratory centres in turtles is qualitatively similar to that in mammals yet the differences in central integration of lung volume information in turtles and mammals are not due solely to the absence of a pneumotaxic centre in the turtle. Many of the remaining differences may arise from the lower metabolic demand of turtles but how this affects central integration and respiratory pattern generation is unknown. / Science, Faculty of / Zoology, Department of / Graduate

Respiratory conditions causing poor performance in horses are usually as result of upper respiratory tract diseases or are of pulmonary origin. The tracheal is rarely a cause of primary respiratory problems in the horse, but tracheal dimensions, particularly height, may be useful in evaluating upper repiratory tract conditions cranial to the trachea and lung pathology, due to resultant change in differential pressures between these areas. The normal radiological equine tracheal height along its length has as yet not been reported. Standing lateral radiographs of the cervical and thoracic trachea of 15 clinically normal sedated Thoroughbred horses, 3-6 years old, were made at peak inspiration and end expiration. Maximum height of the larynx, and trachea at the level of the third and fifth cervical vertebra, at the level of the first thoracic vertebra, carina and the left and right primary bronchi were measured. Ratios of laryngeal height relative to the third cervical vertebral body length and tracheal heights relative to the vertebral body lengths of adjacent third and fifth cervical vertebrae and first thoracic vertebra, and carina heights relative to a mid-thoracic vertebra, respectively were made, as well as tracheal height at the fist thoracic vertebra ratio with the thoracic inlet height. Known size metallic markers were used to determine magnification corrected tracheal heights in the sagittal plane and effect of body mass and height at the withers on tracheal height was determined. The magnification corrected radiological airway heights at end expiration and peak inspiration were measured and respectively the mean values were found to be: laryngeal height: 5.89 cm and 5.86 cm, tracheal height at the third cervical vertebra: 4.17 cm and 4.04 cm, tracheal height at the fifth cervical vertebra: 3.62 cm and 3.59 cm, tracheal height at the first thoracic vertebra: 3.4 cm and 3.23 cm and carina height: 3.85 cm and 4.12 cm. The ratios of these measurements to nearby vertebral body lengths were respectively: laryngeal height at the third cervical vertebra: 0.56 and 0.56, tracheal height at the third cervical vertebra: 0.4 and 0.39, tracheal height at the fifth cervical vertebra: 0.37 and 0.37, tracheal height at the first thoracic vertebra: 0.59 and 0.59, and carina height: 0.91 and 0.94. The ratio tracheal height at the first thoracic vertebra to the thoracic inlet respectively 0.15 and 0.15. Although there was no statistical difference in the data, there was a trend towards a higher tracheal height at expiration. No correlation was found between tracheal height and body mass or tracheal height and height at the withers, and measured tracheal height was generally lower than predicted tracheal height, possibly as result of sedation used. The small range of body mass and height in this study as well as the relatively small number of horses evaluated may account for the lack of correlation to predicted tracheal height. This study in normal horses may serve as a reference when radiologically evaluating cases of upper respiratory tract and lung pathology, where the tracheal dimensions may differ significantly due to differences in airway resistance and biomechanics. Radiographs to evaluate tracheal height can be made independent of respiratory phase in sedated horses, and it is recommended that ratios of tracheal height to an adjacent vertebral body length are more reliable values to compare within and between horses. It is recommended to take tracheal height measured at the fifth cervical vertebra since this measurement showed a slightly smaller standard deviation than at other sites measured as well as a medium amount of clinical effect. If only thoracic radiographs are made, measurements of tracheal height at the thoracic inlet is the alternative (the standard cranioventral view), but it is recommended to include the distal aspect of the first rib if the thoracic inlet is to be measured. / Dissertation (MMedVet)--University of Pretoria, 2008. / Companion Animal Clinical Studies / unrestricted

Respiratory failure accounts for a large, if not the largest, percentage of deaths during the first 48 hours of life. During the last ten years a great deal of research has been devoted to this early respiratory failure. The syndrome has been known by different names at different times; hyaline membrane disease (because pulmonary hyaline membrane is a frequent autopsy finding), congestive pulmonary failure, vernix membrane disease, pulmonary syndrome, and more recently the respiratory distress syndrome. A vast literature on the subject has accumulated. Many new and interesting facts have come to light and although many new theories have been put forth to explain the syndrome, the cause is still unknown.

Respiratory tract infections are caused by different types of virus and bacteria and have become a global health issue. The detection and analysis of respiratory tract pathogens is nowadays performed commonly using PCR technology because of its high sensitivity. The aim of this study was to compare the performance of a new instrument, Starlet IVD with Maglead 12gC for extraction of nucleic acid from respiratory tract samples prior to real time PCR analysis. Frozen positive samples and fresh negative samples from patients were analyzed for respiratory viruses and respiratory bacteria. The samples were extracted on both Starlet IVD and Maglead 12gC. Real time PCR analysis was performed after the extraction to compare the performance between both instruments. A total of 44 virus samples were analyzed with Allplex respiratory panel 2 and 61 bacteria samples analyzed with Allplex respiratory panel 4. The result has shown an acceptable agreement of the PCR analysis (&gt; 95%) for both panels between instruments. Starlet IVD has a higher Ct value compared to Maglead 12gC which led to a variation of 7,1% ± 3,6% in Ct value for Respiratory panel 2 and 10,1 % ± 5,3 % for Respiratory panel 4.  In conclusion, Starlet IVD is an automated instrument that will reduce hand-on-time, the risk of errors and improve the work routine for a better quality of results. Regardless the poor Ct-value, the new instrument has been able to detect almost all respiratory pathogens in the samples.

A dissertation submitted to the Faculty of Medicine, University of the Witwatersrand, Johannesburg. in fulfilment of the requirements for the degree of Doctor of Philosophy / This thesis describes and discusses oxidants and anti-oxidants and their relation to human disease. Cigarette smoking is used as the model for the study of chronic inflammatory processes, firstly, to establish a causative link between oxidants and disease viz. lung function abnormalities in smokers, secondly to evaluate the interaction between hyperactive phagocytes and anti-oxidant defences and thirdly, to investigate the possibility that intervention with anti-oxidants may ameliorate the effects of chronic inflammation. / IT2018

No description available.

Radar-based respiration monitoring has been increasingly popular among researchers in biomedical fields during the last decades since it is a contactless monitoring technique. It is very convenient for subjects because it does not impose any restrictions on subjects or require their cooperation. Meanwhile, recognizing alternations in respiratory patterns is an important early clue of the diagnosis of several cardiorespiratory diseases. Thus, a study of biomedical radar-based respiration monitoring and respiratory pattern classification is carried out in this thesis. Radar-based respiration monitoring technology has a shortcoming that the collected respiratory signal will be easily distorted by the body movement of the monitoring subjects or disturbed by environment noise because of the contactless measurement attribute. This shortcoming limits the application of the respiratory pattern classification model, that is, the existing models cannot be applied automatically since the distorted respiratory signal needs to be manually filtered out ahead of the classification. In this study, a new respiratory pattern classification strategy, which can be implemented full-automatic, is proposed. In this strategy, a class “moving” is introduced to classify the distorted signal, and the sampling window length is shortened to reduce the effect caused by the signal distortion. A performance requirement for the continuous respiratory pattern classification is also proposed based on its expected function that can alert the occurrence of the abnormal breathing patterns. Several models which can meet the proposed performance requirement are developed in this thesis based on the state-of-the-art pattern classification technique and the time-series-based shapelet transform algorithm. The proposed models can classify four breathing patterns including eupnea, Cheyne Stokes respiration, Kussmaul breathing and apnea. A radar-collected respiratory signal database is built in this study, and a respiration simulation model which can generate breath samples for pattern classification is developed in this thesis. The proposed models were tested and validated in batch and stream processing manner with independently collected data and continuously collected data, respectively.