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 hypoventilation training or strenuous physical exercise.
Necrosis is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated digestion of cell components. In contrast, apoptosis is a naturally occurring programmed and targeted cause of cellular death. While apoptosis often provides beneficial effects to the organism, necrosis is almost always detrimental and can be fatal.
Cerebrovascular disease includes a variety of medical conditions that affect the blood vessels of the brain and the cerebral circulation. Arteries supplying oxygen and nutrients to the brain are often damaged or deformed in these disorders. The most common presentation of cerebrovascular disease is an ischemic stroke or mini-stroke and sometimes a hemorrhagic stroke. Hypertension is the most important contributing risk factor for stroke and cerebrovascular diseases as it can change the structure of blood vessels and result in atherosclerosis. Atherosclerosis narrows blood vessels in the brain, resulting in decreased cerebral perfusion. Other risk factors that contribute to stroke include smoking and diabetes. Narrowed cerebral arteries can lead to ischemic stroke, but continually elevated blood pressure can also cause tearing of vessels, leading to a hemorrhagic stroke.
Carotenoids, also called tetraterpenoids, are yellow, orange, and red organic pigments that are produced by plants and algae, as well as several bacteria, and fungi. Carotenoids give the characteristic color to pumpkins, carrots, parsnips, corn, tomatoes, canaries, flamingos, salmon, lobster, shrimp, and daffodils. Carotenoids can be produced from fats and other basic organic metabolic building blocks by all these organisms. The only land dwelling arthropods known to produce carotenoids are aphids, and spider mites, which acquired the ability and genes from fungi. It is also produced by endosymbiotic bacteria in whiteflies. Carotenoids from the diet are stored in the fatty tissues of animals, and exclusively carnivorous animals obtain the compounds from animal fat. In the human diet, absorption of carotenoids is improved when consumed with fat in a meal. Cooking carotenoid-containing vegetables in oil and shredding the vegetable both increase carotenoid bioavailability.
Tumor hypoxia is the situation where tumor cells have been deprived of oxygen. As a tumor grows, it rapidly outgrows its blood supply, leaving portions of the tumor with regions where the oxygen concentration is significantly lower than in healthy tissues. Hypoxic microenvironements in solid tumors are a result of available oxygen being consumed within 70 to 150 μm of tumour vasculature by rapidly proliferating tumor cells thus limiting the amount of oxygen available to diffuse further into the tumor tissue. In order to support continuous growth and proliferation in challenging hypoxic environments, cancer cells are found to alter their metabolism. Furthermore, hypoxia is known to change cell behavior and is associated with extracellular matrix remodeling and increased migratory and metastatic behavior.
In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 60% of total body weight; women and the obese typically have a lower percentage than lean men. Extracellular fluid makes up about one-third of body fluid, the remaining two-thirds is intracellular fluid within cells. The main component of the extracellular fluid is the interstitial fluid that surrounds cells.
Ischemia or ischaemia is a restriction in blood supply to any tissues, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism. Ischemia is generally caused by problems with blood vessels, with resultant damage to or dysfunction of tissue i.e. hypoxia and microvascular dysfunction. It also means local hypoxia in a given part of a body sometimes resulting from constriction. Ischemia comprises not only insufficiency of oxygen, but also reduced availability of nutrients and inadequate removal of metabolic wastes. Ischemia can be partial or total blockage. The inadequate delivery of oxygenated blood to the organs must be resolved either by treating the cause of the inadequate delivery or reducing the oxygen demand of the system that needs it. For example, patients with myocardial ischemia have a decreased blood flow to the heart and are prescribed with medications that reduce chronotrophy and ionotrophy to meet the new level of blood delivery supplied by the stenosed so that it is adequate.
Hypovolemia, also known as volume depletion or volume contraction, is a state of abnormally low extracellular fluid in the body. This may be due to either a loss of both salt and water or a decrease in blood volume. Hypovolemia refers to the loss of extracellular fluid and should not be confused with dehydration.
Infarction is tissue death (necrosis) due to inadequate blood supply to the affected area. It may be caused by artery blockages, rupture, mechanical compression, or vasoconstriction. The resulting lesion is referred to as an infarct (from the Latin infarctus, "stuffed into").
Hypovolemic shock is a form of shock caused by severe hypovolemia. It could be the result of severe dehydration through a variety of mechanisms or blood loss. Hypovolemic shock is a medical emergency; if left untreated, the insufficient blood flow can cause damage to organs, leading to multiple organ failure.
Cerebral hypoxia is a form of hypoxia, specifically involving the brain; when the brain is completely deprived of oxygen, it is called cerebral anoxia. There are four categories of cerebral hypoxia; they are, in order of increasing severity: diffuse cerebral hypoxia (DCH), focal cerebral ischemia, cerebral infarction, and global cerebral ischemia. Prolonged hypoxia induces neuronal cell death via apoptosis, resulting in a hypoxic brain injury.
Histotoxic hypoxia is the inability of cells to take up or use oxygen from the bloodstream, despite physiologically normal delivery of oxygen to such cells and tissues. Histotoxic hypoxia results from tissue poisoning, such as that caused by cyanide and certain other poisons like hydrogen sulfide.
Crocetin is a natural apocarotenoid dicarboxylic acid that is found in the crocus flower together with its glycoside, crocin, and Gardenia jasminoides fruits. It forms brick red crystals with a melting point of 285°C.
A radiosensitizer is an agent that makes tumor cells more sensitive to radiation therapy. It is sometimes also known as a radiation sensitizer or radio-enhancer.
An oxygen diffusion-enhancing compound is any substance that increases the availability of oxygen in body tissues by influencing the molecular structure of water in blood plasma and thereby promoting the movement (diffusion) of oxygen through plasma. Oxygen diffusion-enhancing compounds have shown promise in the treatment of conditions associated with hypoxia and ischemia. Such conditions include hemorrhagic shock, myocardial infarction, and stroke.
Diffusion Pharmaceuticals Inc (NASDAQ:DFFN) is a publicly traded biotechnology and drug development company based in Charlottesville, Virginia, U.S. It was co-founded in 2001 by American life sciences entrepreneur David Kalergis and University of Virginia Chemical Engineering Professor John L. Gainer. Gainer is the inventor of the company's platform technology of oxygen diffusion-enhancing compounds and its lead drug, trans sodium crocetinate (TSC). TSC acts to increase the rate at which oxygen moves through blood plasma by the process of diffusion, a phenomenon that forms the basis for the company's name. On January 8, 2016, the formerly privately held company merged with Restorgenex Cororation to become a publicly traded NASDAQ-listed company with the trading symbol DFFN. TSC and other oxygen diffusion-enhancing compounds, including bipolar trans carotenoid salts, have been investigated by Diffusion Pharmaceuticals for treatment of conditions associated with reduced oxygen availability in tissues (hypoxia). Most recently, Diffusion has begun the initiation of clinical trials in the U.S. and Eastern Europe for the use of trans sodium crocetinate in the treatment of COVID-19 patients with respiratory distress-related oxygen deficiency and the risk of multiple organ failure.
David Kalergis is an American life sciences entrepreneur and the Co-founder, Chairman and Chief Executive Officer of Diffusion Pharmaceuticals Inc, a Charlottesville, Virginia, U.S.-based biotechnology and pharmaceutical company. He co-founded the company in 2001 with American chemical engineer John L. Gainer. Kalergis became Diffusion's CEO in 2004, a position in which he has drawn extensively on his career in law, business, and clinical trials implementation. Under Kalergis' leadership, Diffusion Pharmaceuticals has been cited for advancing improved cancer treatments and is currently conducting multicenter clinical trials of a novel therapeutic for brain cancers, including glioblastoma multiforme. Diffusion Pharmaceuticals is also currently conducting clinical trials for the treatment of oxygen deficiencies associated with COVID-19 and acute stroke.
Carotenoid complexes are physical associations of carotenoids with other molecules.
Andre Francis Palmer, Ph.D. is the Associate Dean for research in the College of Engineering and the Fenburr Ohio Eminent Scholar and Professor of Chemical and Biomolecular Engineering at Ohio State University. He is an expert on hemoglobin-based oxygen carriers and biomaterials used in transfusion medicine.
