Hypoxia (medical)

Summary

Hypoxia is a condition in which the body or a region of the body is deprived of adequate oxygen supply at the tissue level. Hypoxia may be classified as either generalized, affecting the whole body, or local, affecting a region of the body. Although hypoxia is often a pathological condition, variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise. Hypoxia differs from hypoxemia and anoxemia, in that hypoxia refers to a state in which oxygen present in a tissue or the whole body is insufficient, whereas hypoxemia and anoxemia refer specifically to states that have low or no oxygen in the blood. Hypoxia in which there is complete absence of oxygen supply is referred to as anoxia. Hypoxia can be due to external causes, when the breathing gas is hypoxic, or internal causes, such as reduced effectiveness of gas transfer in t

Official source

https://en.wikipedia.org/wiki/Hypoxia_(medical)

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Radiotherapy is successfully used to treat cancer. Emerging evidence, however, indicates that recurrences after radiotherapy are associated with increased local invasion, metastatic spreading and poor prognosis. Radiation-induced modifications of the tumor microenvironment have been proposed to contribute to increased aggressive tumor behavior, an effect also referred to as tumor bed effect, but the putative mechanisms involved have remained largely elusive. We have recently demonstrated that irradiation of the prospective tumor stroma impairs de novo angiogenesis through sustained inhibition of proliferation, migration and sprouting of endothelial cells. Experimental tumors growing within a pre-irradiated field have reduced tumor angiogenesis and tumor growth, increased hypoxia, necrosis, local invasion and distant metastasis. Mechanisms of progression involve adaptation of tumor cells to local hypoxic conditions as well as selection of cells with invasive and metastatic capacities. The matricellular protein CYR61 and integrin alpha V beta 5 emerged as molecules that cooperate to mediate lung metastasis. Cilengitide, a small molecular inhibitor of alpha V integrins prevented lung metastasis formation. These results represent a conceptual advance to the understanding of the tumor bed effect and indicate that alpha V integrin inhibition might be a potential therapeutic approach for preventing metastasis in patients at risk for post-radiation recurrences.

2011

JNK Inhibition Reduced Retinal Ganglion Cell Death after Ischemia/Reperfusion In Vivo and after Hypoxia In Vitro

Tatiana Favez

Mitogen-activated protein kinases (MAPKs) are key regulators that have been linked to cell survival and death. Among the main classes of MAPKs, c-jun N-terminal kinase (JNK) has been shown to mediate cell stress responses associated with apoptosis. In Vitro, hypoxia induced a significant increase in 661W cell death that paralleled increased activity of JNK and c-jun. 661W cells cultured in presence of the inhibitor of JNK (D-JNKi) were less sensitive to hypoxia-induced cell death. In vivo, elevation in intraocular pressure (IOP) in the rat promoted cell death that correlated with modulation of JNK activation. In vivo inhibition of JNK activation with D-JNKi resulted in a significant and sustained decrease in apoptosis in the ganglion cell layer, the inner nuclear layer and the photoreceptor layer. These results highlight the protective effect of D-JNKi in ischemia/reperfusion induced cell death of the retina.

Springer Int Publishing Ag2016

In vivo measurement of tissue oxygenation by time-resolved luminescence spectroscopy: advantageous properties of dichlorotris(1, 10-phenanthroline)-ruthenium(II) hydrate

Sandrine Gay, Veronika Huntosova, Patrycja Nowak-Sliwinska, Senthil Kumar Rajendran, Hubert van den Bergh, Georges Wagnières, Matthieu Zellweger

Measuring tissue oxygenation in vivo is of interest in fundamental biological as well as medical applications. One minimally invasive approach to assess the oxygen partial pressure in tissue (pO(2)) is to measure the oxygen-dependent luminescence lifetime of molecular probes. The relation between tissue pO(2) and the probes' luminescence lifetime is governed by the Stern-Volmer equation. Unfortunately, virtually all oxygen-sensitive probes based on this principle induce some degree of phototoxicity. For that reason, we studied the oxygen sensitivity and phototoxicity of dichlorotris(1, 10-phenanthroline)-ruthenium(II) hydrate [Ru(Phen)] using a dedicated optical fiber-based, time-resolved spectrometer in the chicken embryo chorioallantoic membrane. We demonstrated that, after intravenous injection, Ru(Phen)'s luminescence lifetime presents an easily detectable pO(2) dependence at a low drug dose (1 mg/kg) and low fluence (120 mJ/cm(2) at 470 nm). The phototoxic threshold was found to be at 10 J/cm(2) with the same wavelength and drug dose, i.e., about two orders of magnitude larger than the fluence necessary to perform a pO(2) measurement. Finally, an illustrative application of this pO(2) measurement approach in a hypoxic tumor environment is presented. (C) 2014 Society of Photo-Optical Instrumentation Engineers (SPIE)

Spie-Soc Photo-Optical Instrumentation Engineers2014