Harry Demopoulos
Encyclopedia
Harry B. Demopoulos, MD is an pioneer in the medical aspects of free radicals, especially in the areas of ischaemic injury, the toxicity of anticancer drugs, and in spinal cord injury
. He has also been a film actor and is currently a member of the Board of Trustees of the Doris Duke Charitable Foundation.
and heart attack
are secondary to ischaemic injury, a consequence of the ischemic cascade
. Thus, much research has been done into the causes and treatment of ischaemic injury. One important thread involves the essential role of free radicals (reactive oxygen species
and the like) as modulators of ischaemic injury. This has resulted in important therapeutic advances, such as the radical-scavenging neuroprotective agent NXY-059
, which was under development for the treatment of stroke.
Harry B. Demopoulos and his coworkers played a key role this research. The opening sentence of J.Cell. Mol.Med. Vol 5, No 2, 2001 pp. 163-170 Oxidative damage following cerebral ischemia depends on reperfusion D. Al. Nita, et al. states:
Has worked with:
Clint Eastwood
, Burt Reynolds
, Sylvester Stallone
, Liam Neeson
, Jim Carrey
, Sondra Locke
, Anthony Charnota, George Orrison, Irene Cara
, and George Fisher
Charitable Foundation, founded upon the death of the billionaire tobacco heiress. When Duke died in 1993 at the age of 80, legal documents revealed she had previously assigned Demopoulos - a longtime friend - co-executor of her estate. However, a controversial change to her will near her death put her vast fortune in the control of her Irish-born butler, Bernard Lafferty, who Demopoulos described in a subsequent lawsuit as "an illiterate, unstable and even dangerous person."
But the real bombshell came when the litigants produced an affidavit
from Tammy Payette, 28, a nurse who had attended to Duke in her final weeks. Payette maintained that Kivowitz (one of Duke's doctors) and Lafferty had conspired to murder Duke through the use of "massive sedation", including morphine and Demerol." This lawsuit resulted in Lafferty's being discharged.
Spinal cord injury
A spinal cord injury refers to any injury to the spinal cord that is caused by trauma instead of disease. Depending on where the spinal cord and nerve roots are damaged, the symptoms can vary widely, from pain to paralysis to incontinence...
. He has also been a film actor and is currently a member of the Board of Trustees of the Doris Duke Charitable Foundation.
Free Radical Research
Ischaemic injury (injury to cells due to oxygen deprivation) is an important cause of morbidity and mortality in humans. For example, most deaths in strokeStroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
and heart attack
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
are secondary to ischaemic injury, a consequence of the ischemic cascade
Ischemic cascade
The ischemic cascade is a series of biochemical reactions that are initiated in the brain and other aerobic tissues after seconds to minutes of ischemia . This is typically secondary to stroke, injury, or cardiac arrest due to heart attack. Most ischemic neurons that die do so due to the...
. Thus, much research has been done into the causes and treatment of ischaemic injury. One important thread involves the essential role of free radicals (reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
and the like) as modulators of ischaemic injury. This has resulted in important therapeutic advances, such as the radical-scavenging neuroprotective agent NXY-059
NXY-059
Disufenton sodium is the disulfonyl derivative of the neuroprotective spin trap phenylbutynitrone or "PBN". It was under development at the drug company AstraZeneca. A 2005 phase-3 clinical trial called "SAINT-1" reported some efficacy in the acute treatment of ischemia injury due to stroke...
, which was under development for the treatment of stroke.
Harry B. Demopoulos and his coworkers played a key role this research. The opening sentence of J.Cell. Mol.Med. Vol 5, No 2, 2001 pp. 163-170 Oxidative damage following cerebral ischemia depends on reperfusion D. Al. Nita, et al. states:
Works
- Flamm ES, Demopoulos HB, Seligman ML, Poser RG, Ransohoff J., Free radicals in cerebral ischemia, Stroke. 1978 Sep-Oct;9(5):445-7. http://stroke.ahajournals.org/cgi/content/abstract/9/5/445
- Generally-acknowledged as the first experimental demonstration of a role for reactive oxygen speciesReactive oxygen speciesReactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
in strokeStrokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
. http://scholar.google.com/scholar?q=link:http%3A%2F%2Fstroke.ahajournals.org%2Fcgi%2Fcontent%2Fabstract%2F9%2F5%2F445 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Display&itool=abstractplus&dopt=pubmed_pubmed&from_uid=705824- Demopoulos, H. B,, Flamm, E. S., Pietronegro, D. D., and Seligman, M. L., The free radical pathology and the microcirculation in the major central nervous system disorders, Acta Physiol. Scand. Suppl., 492, 91, 1980.
- This paper first suggests that free radical pathogenesis in strokeStrokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
may be at least partially-mediated through damage to the microcirculationMicrocirculationThe microcirculation is a term used to describe the small vessels in the vasculature which are embedded within organs and are responsible for the distribution of blood within tissues; as opposed to larger vessels in the macrocirculation which transport blood to and from the organs...
. The neuroprotective antistroke agents NXY-059NXY-059Disufenton sodium is the disulfonyl derivative of the neuroprotective spin trap phenylbutynitrone or "PBN". It was under development at the drug company AstraZeneca. A 2005 phase-3 clinical trial called "SAINT-1" reported some efficacy in the acute treatment of ischemia injury due to stroke...
, TirilazadTirilazadTirilazad is a drug proposed for use in the treatment of stroke, though results so far have been mixed....
, Superoxide dismutaseSuperoxide dismutaseSuperoxide dismutases are a class of enzymes that catalyze the dismutation of superoxide into oxygen and hydrogen peroxide. As such, they are an important antioxidant defense in nearly all cells exposed to oxygen...
/CatalaseCatalaseCatalase is a common enzyme found in nearly all living organisms that are exposed to oxygen, where it catalyzes the decomposition of hydrogen peroxide to water and oxygen...
, and uric acidUric acidUric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
all likely work at this level, rather than interneuronally.- Demopoulos, H., Flamm, E., Seligman, M. L., Poser, R., Pietronegro, D., and Ransohoff, J., Molecular pathology of lipids in CNS membranes, in Oxygen and Physiological Function, Volsis, F. F., Ed., Professional Information Library, Dallas, Tex., 1977, 491.
- Demopoulos, H. B., Flamm, E., Seligman, M,, and Pietronigro, D. D., Oxygen free radicals in central nervous system ischaemia and trauma, in Pathology of Oxygen, Autor, A. P., Ed., Academic Press, New York, 1982, 127.
- "Large doses of methohexital protect the microcirculation in regional cerebral ischaemia models". This is the first well-defined example of an antistroke neuroprotective agent working outside the blood-brain barrier. NXY-059NXY-059Disufenton sodium is the disulfonyl derivative of the neuroprotective spin trap phenylbutynitrone or "PBN". It was under development at the drug company AstraZeneca. A 2005 phase-3 clinical trial called "SAINT-1" reported some efficacy in the acute treatment of ischemia injury due to stroke...
, Superoxide dismutaseSuperoxide dismutaseSuperoxide dismutases are a class of enzymes that catalyze the dismutation of superoxide into oxygen and hydrogen peroxide. As such, they are an important antioxidant defense in nearly all cells exposed to oxygen...
, catalaseCatalaseCatalase is a common enzyme found in nearly all living organisms that are exposed to oxygen, where it catalyzes the decomposition of hydrogen peroxide to water and oxygen...
, uric acidUric acidUric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
, and TirilazadTirilazadTirilazad is a drug proposed for use in the treatment of stroke, though results so far have been mixed....
are others.- John McGinnessJohn McGinnessJohn Edward McGinness , is an American physicist and physician. McGinness worked as a in the field of Organic electronics and Nanotechnology.-Education:McGinness studied physics at the University of Houston and after his B.S...
, Proctor, P.H., Demopoulos, H.B., Hokansen, J.A. and Kirkpatrick, D. S. Amelioration of cis-platinum nephrotoxicity by orgotein (superoxide dismutase). Physiol. Chem. and Phys. 10: 267-277, 1978. - John McGinness, Proctor, P.H., Demopoulos, H.B., Hokansen, J.A. and Van, N.T. In vivo evidence for superoxide and peroxide production by adriamycin and cis-platinum. In: Pathology of Oxygen. A. Autor, (Ed.). Academic Press, New York, 1982, pp. 191-202.
- John McGinness
Filmography
- The Dead PoolThe Dead PoolThe Dead Pool is a 1988 American action thriller film about the manipulation of a "dead pool" game by a serial killer, whose efforts are foiled by a hardened detective. It is the fifth and final film in the Dirty Harry series, set in San Francisco, California and starring Clint Eastwood as...
(1988) - Cobra (1986)
- City HeatCity HeatCity Heat is a 1984 American action-comedy film starring Clint Eastwood and Burt Reynolds. The film was released in North America in December 1984. The pairing of Eastwood and Reynolds in a Prohibition-era action-comedy seemed to give the film the potential to be a hit...
(1984) - Sudden ImpactSudden ImpactSudden Impact is a 1983 American crime thriller and the fourth film in the Dirty Harry series, directed by and starring Clint Eastwood...
(1983) (as Dr Barton)
Has worked with:
Clint Eastwood
Clint Eastwood
Clinton "Clint" Eastwood, Jr. is an American film actor, director, producer, composer and politician. Eastwood first came to prominence as a supporting cast member in the TV series Rawhide...
, Burt Reynolds
Burt Reynolds
Burton Leon "Burt" Reynolds, Jr. is an American actor. Some of his memorable roles include Bo 'Bandit' Darville in Smokey and the Bandit, Lewis Medlock in Deliverance, Bobby "Gator" McCluskey in White Lightning and sequel Gator, Paul Crewe and Coach Nate Scarborough in The Longest Yard and its...
, Sylvester Stallone
Sylvester Stallone
Michael Sylvester Gardenzio Stallone , commonly known as Sylvester Stallone, and nicknamed Sly Stallone, is an American actor, filmmaker, screenwriter, film director and occasional painter. Stallone is known for his machismo and Hollywood action roles. Two of the notable characters he has portrayed...
, Liam Neeson
Liam Neeson
Liam John Neeson, OBE is an Irish actor who has been nominated for an Oscar, a BAFTA and three Golden Globe Awards.He has starred in a number of notable roles including Oskar Schindler in Schindler's List, Michael Collins in Michael Collins, Peyton Westlake in Darkman, Jean Valjean in Les...
, Jim Carrey
Jim Carrey
James Eugene "Jim" Carrey is a Canadian-American actor and comedian. He has received two Golden Globe Awards and has also been nominated on four occasions. Carrey began comedy in 1979, performing at Yuk Yuk's in Toronto, Ontario...
, Sondra Locke
Sondra Locke
Sondra Locke is an American actress, singer and film director.She made her film debut in The Heart Is a Lonely Hunter , for which she was nominated for an Academy Award for Best Supporting Actress...
, Anthony Charnota, George Orrison, Irene Cara
Irene Cara
Irene Cara is an American singer and actress. Cara won an Academy Award in 1984 in the category of Best Original Song for co-writing "Flashdance... What a Feeling." She is also known for her recording of the song "Fame", and she also starred in the 1980 film Fame.She married Hollywood stuntman...
, and George Fisher
Doris Duke Estate
Harry Demopoulos is a trustee of the Doris DukeDoris Duke
Doris Duke was an American heiress, horticulturalist, art collector, and philanthropist.-Family and early life:...
Charitable Foundation, founded upon the death of the billionaire tobacco heiress. When Duke died in 1993 at the age of 80, legal documents revealed she had previously assigned Demopoulos - a longtime friend - co-executor of her estate. However, a controversial change to her will near her death put her vast fortune in the control of her Irish-born butler, Bernard Lafferty, who Demopoulos described in a subsequent lawsuit as "an illiterate, unstable and even dangerous person."
But the real bombshell came when the litigants produced an affidavit
Affidavit
An affidavit is a written sworn statement of fact voluntarily made by an affiant or deponent under an oath or affirmation administered by a person authorized to do so by law. Such statement is witnessed as to the authenticity of the affiant's signature by a taker of oaths, such as a notary public...
from Tammy Payette, 28, a nurse who had attended to Duke in her final weeks. Payette maintained that Kivowitz (one of Duke's doctors) and Lafferty had conspired to murder Duke through the use of "massive sedation", including morphine and Demerol." This lawsuit resulted in Lafferty's being discharged.