The oxygen effect and therapeutic approaches to tumour hypoxia
Michael C. Joiner, Albert J. van der Kogel in Basic Clinical Radiobiology, 2018
It has been demonstrated from rapid-mix studies that the oxygen effect only occurs if oxygen is present either during irradiation or within a few milliseconds thereafter (22). The dependence of the degree of sensitization on oxygen tension is shown in Figure 17.1b. As the oxygen concentration increases from zero (anoxia), there is a relatively steep increase in radiosensitivity. The greatest change occurs from about 0.5 to 20 mm Hg (equivalent to about 0.05%–2.5% O2). A further increase in oxygen concentration, up to that seen in air (21% or 159 mm Hg) or even to 100% oxygen (760 mm Hg), produces a much smaller though definite increase in radiosensitivity. Oxygen tension typically found in arterial blood is between 75 and 100 mmHg and in venous blood between 30 and 40 mm Hg. Thus, from a radiobiological standpoint most normal tissues can be considered to be well oxygenated, although it is now recognized that moderate hypoxia is a feature of some normal tissues such as cartilage and skin. The average oxygen concentration in tumours, however, is typically much lower with many cells at intermediate oxygen concentrations between 0.5 and 20 mm Hg where there is the maximum change of radiosensitivity.
Physiology of the Neonate
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
Airway resistance decreases from about 90 cmH2O/L/s in the first minute to about 25 cmH2O/L/min at the end of the first day of life. The resistance of nasal passages in the neonate is about 50% of the total airway resistance. Significant ventilation–perfusion mismatch occurs in the newborn, with a ventilation–perfusion ratio of 0.4 due to small airway closure. This results in a lower normal arterial oxygen tension of 50–70 mmHg (6.7–9.3 kPa) in the neonate. The central and peripheral chemoreceptors are well developed in the neonate. The ventilatory response to carbon dioxide is mature, with the CO2 response curve shifted to the left compared with the adult, so that ventilatory increases take place at a lower level of CO2 tension (Figure 74.7). The increase in ventilation is mainly achieved by an increased TV. Hypoxaemia causes a transient increase in ventilation for about 2 minutes in the immediate post-natal period, but a sustained response is seen by the 10th day after birth. The respiratory centre of the neonate is depressed by hypothermia.
Unusual Inherited Pulmonary Diseases Which Provide Clues to Pulmonary Physiology and Function
Stephen D. Litwin in Genetic Determinants of Pulmonary Disease, 2020
The single most important etiologic factor is undoubtedly the decreased inspired oxygen tension at high altitudes leading to hypoxia and pulmonary hypertension. The disorder is unknown below 9000 ft (2700 m). Individual susceptibility may be related to the degree of pulmonary vascular reactivity. It has been shown that in subjects with a previous history of high altitude pulmonary edema, reexposure to altitude induces significantly higher increases in the pulmonary arterial pressure than normals [145]. There was also an abnormal increase in the alveolar-arterial oxygen gradient, especially on exercise. Acute relief of the hypoxia did not immediately bring the pulmonary arterial pressure to normal, suggesting factors other than hypoxic pulmonary vasoconstriction may play a part. Contributory factors in the etiology are rapid ascent without acclimatization, severe physical exertion, and exposure to cold [135,146,147].
Oxygen sensing; a stunningly elegant molecular machinery highjacked in cancer
Published in Upsala Journal of Medical Sciences, 2020
How is oxygen tension sensed, and what is the consequence of oxygen sensing? The oxygen-sensitive signal is generated by enzymes that catalyse hydroxylation of specific prolyl and asparaginyl residues in hypoxia-inducible factor (HIF). HIF is the key transcription factor that regulates transcriptional responses to hypoxia. Hydroxylation of HIF at different phylogenetically conserved sites targets it for degradation in normoxia. In hypoxia, HIF escapes destruction and forms active transcriptional complexes that control expression of thousands of genes in the human genome. HIF is a heterodimer consisting of one α (oxygen-sensitive) and one β (oxygen-insensitive) subunit. There are three α subunits with partly overlapping but also distinct functions. Many of the most prominent and well-characterized HIF-regulated genes have key functions in oxygen supply and utilisation via erythropoiesis, angiogenesis, haematopoiesis, and metabolic reprogramming (1). In order to coordinate the most efficient use of oxygen by the cell, HIFs activate genes that shift energy dependence away from high oxygen demand, towards glycolysis. The genes encoding essentially all glycolytic enzymes are directly upregulated by HIFs (2,3). In addition to pathways important for maintaining oxygen homeostasis, HIF targets are involved in autophagy, apoptosis, redox homeostasis, inflammation and immunity, stemness and self-renewal, and metastasis and invasion (Figure 1) (2,4–6).
Mathematical analysis of oxygen and carbon dioxide exchange in the human capillary and tissue system
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2023
Ahsan Ul Haq Lone, M. A. Khanday
Krogh (1919) laid the foundation of the theory of oxygen transport to tissue. He proposed that oxygen is transported in the tissue by passive diffusion driven by gradients of oxygen tension (PO2). He then formulated a simple geometrical model of the elementary tissue unit supplied by a single capillary. This geometrical model is commonly referred to as the Krogh tissue cylinder or simply Krogh’s model. Together with his colleague, the mathematician Erlang, Krogh formulated a differential equation governing oxygen diffusion and uptake in the tissue cylinder. The solution to this equation expresses oxygen tension in the tissue as a function of spatial position within the tissue cylinder. This simple equation, known as the Krogh or Krogh-Erlang equation, has been the basis of most physiological estimates for the last 70 years. This model was further extended and modified by Blum (1960), Salathe et al. (1980) and Reneau et al. (1967).
Bone marrow- and adipose tissue-derived mesenchymal stem cells from donors with coronary artery disease; growth, yield, gene expression and the effect of oxygen concentration
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2020
Emma Adolfsson, Gisela Helenius, Örjan Friberg, Ninos Samano, Ole Frøbert, Karin Johansson
Exposure to hypoxic conditions for a prolonged period of time results in environmental adaptation of cells by upregulation of pro-angiogenic genes such as VEGF and angiopoetin1/2 [12,16,33–35] and increased secretion of anti-apoptotic and proangiogenic factors [34]. Since MSCs are administrated into a hypoxic environment, the response of the cells to hypoxia might influence therapeutic response [3]. We expected exposure to 1% O2 to result in higher levels of target genes compared to exposure to 5% O2. However, the effect of oxygen concentration on target gene expression differed between BMSCs and ADSCs. In ADSCs, the response was more pronounced, with significantly higher levels of LIF in cells exposed to 5% O2 and significant higher levels of LIF as well as Angpt1 and TGF-β1 (although, the increases was non-significant) in cells exposed to 1% O2, whereas in BMSCs, only TGF-β1 increased in BMSCs exposed to the lower oxygen tension. The response to oxygen tension developed over time.
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