Disturbances In Oxygen Supply Research Articles

Oxygen diffusion: an enzyme-controlled variable parameter.

Previous oxygen microelectrode studies have shown that the oxygen diffusion coefficient (DO₂) increases during extracellular PO₂ decreases, while intracellular PO₂ remained unchanged and thus cell function (spike activity of neurons). Oxygen dependency of complex multicellular organisms requires a stable and adequate oxygen supply to the cells, while toxic concentrations have to be avoided. Oxygen brought to the tissue by convection diffuses through the intercellular and cell membranes, which are potential barriers to diffusion. In gerbil brain cortex, PO₂ and DO₂ were measured by membrane-covered and by bare gold microelectrodes, as were also spike potentials. Moderate respiratory hypoxia was followed by a primary sharp drop of tissue PO₂ that recovered to higher values concomitant with an increase of DO₂. A drop in intracellular PO₂ recovered immediately. Studies on the abdominal ganglion of aplysia californica showed similar results.Heterogeneity is a feature of both normal oxygen supply to tissue and supply due to a wide range of disturbances in oxygen supply. Oxygen diffusion through membranes is variable thereby ensuring adequate intracellular PO₂. Cell-derived glucosamine oxidase seems to regulate the polymerization/depolymerisation ratio of membrane mucopolysaccharides and thus oxygen diffusion.Variability of oxygen diffusion is a decisive parameter for regulating the supply/demand ratio of oxygen supply to the cell; this occurs in highly developed animals as well as in species of a less sophisticated nature. Autoregulation of oxygen diffusion is as important as the distribution/perfusion ratio of the capillary meshwork and as the oxygen extraction ratio in relation to oxygen consumption of the cell. Oxygen diffusion resistance is the cellular protection against luxury oxygen supply (which can result in toxic oxidative species leading to mutagenesis).

Expression profiling of the cerebral ischemic and hypoxic response

In mammals, the major component in energy production is molecular oxygen. This has led to the development of several elaborate strategies that tightly regulate oxygen homeostasis in order to allow appropriate cell function and survival. However, a sustained drop in oxygen supply to neuronal tissue has detrimental consequences to cell functioning and survival. Disturbances in oxygen supply have been implicated in a number of CNS disorders that can be related to hypoxia or ischemia. On a cellular level, oxygen-deprived stress induces a multitude of spatially and temporally regulated responses, ranging from adapted channel activity to altered gene expression. Global analysis of expression changes over several time points and tissue regions or cells has already shed light on previous known and unknown biological processes and molecules. By combining knowledge from several different expression-profiling studies into one database, the first steps are made in unifying and categorizing the molecular response to oxygen-deprived conditions, such as stroke. In this review, some of the queries that can be extracted from the database are discussed in regard to the biological context.

Clinical aspects and biological bases of drug-resistant epilepsies.

The definition of drug-resistant epilepsy (DRE) is elusive and still controversial owing to some unresolved questions such as: how many drugs should be tried before a patient is considered intractable; to which extent side-effects may be acceptable; how many years are necessary before establishing drug resistance. In some cases, the view of epilepsy as a progressive disorder constitutes another important issue. Despite the use of new antiepileptic drugs (AEDs), intractable epilepsy represents about 20-30% of all cases, probably due to the multiple pathogenetic mechanisms underlying refractoriness. Several risk factors for pharmacoresistance are well known, even if the list of clinical features and biological factors currently accepted to be associated with difficult-to-treat epilepsy is presumably incomplete and, perhaps, disputable. For some of these factors, the biological basis may be common, mainly represented by mesial temporal sclerosis or by the presence of focal lesions. In other cases, microdysgenesis or dysplastic cortex, with abnormalities in the morphology and distribution of local-circuit (inhibitory) neurons, may be responsible for the severity of seizures. The possible influence of genes in conditioning inadequate intraparenchimal drug concentration, and the role of some cytokines determining an increase in intracellular calcium levels or an excessive growth of distrophic neurites, constitute other possible mechanisms of resistance. Several hypotheses on the mechanisms involved in the generation of DRE have been indicated: (a) ontogenic abnormalities in brain maturation; (b) epilepsy-induced alterations in network, neuronal, and glial properties in seizure-prone regions such as the hippocampus; (c) kindling phenomenon; (d) reorganization of cortical tissue in response to seizure-induced disturbances in oxygen supply. Such hypotheses need to be confirmed with suitable experimental models of intractable epilepsy that are specifically dedicated, which have until now been lacking.

The optimality concept and its clinical value.

To verify the clinical usefulness of the optimality concept in general and its prognostic value for later outcome, all babies born at all 14 maternity hospitals in Slovenia in the period from 1987 to 1991 (124,759 newborns) have been screened. In order to get an estimate of their condition Prechtl's original list of optimality has been adapted to 51 items representing mostly obstetric variables. The median of perinatal optimality scores for all newborns was 45 (six negative points) in mature, and 41 (10 negative points) in premature infants. Girls born at term scored better than mature boys, whereas there was no sex difference in the median score in prematures. Analysis of the data has shown that the majority of items which were non-optimal and which were associated with the greatest number of other non-optimal factors had to do with disturbances in oxygen supply. Children who developed cerebral palsy had a lower optimality score at birth than the remainder of the newborns. In these children the difference between the sexes is even more pronounced, to the advantage of the girls. Prematurely born children with spastic diplegia had a lower optimality score than mature children with diplegia. The opposite was noticed in children born prematurely and at term who developed spastic tetraparesis or dyskinesia. The present follow-up study has shown that predictions of disability were most accurate in the group of newborns who were clinically at risk at birth and who also had a low optimality score. The combination of both appraisals is the best way to identify newborns who need special attention.

Oxygen supply of skeletal muscle in experimental endotoxic shock.

In our model of hypodynamic endotoxic shock systemic pulmonary and metabolic alterations such as -hypotension, tachycardia, low output syndrome -pulmonary hypertension -pulmonary failure with arterial hypoxemia and - lactacidosis developed earlier than disturbances in oxygen supply of skeletal muscle. This points to the different responses of the organ systems in endotoxic shock.