Nitric oxide molecuul als toevoeging aan hemoglobine verbetert effect van ozontherapie en vermindert risico's van te veel zuurstof in bloed

16 februari 2012: klik hier voor een uitleg over ozontherapie. Dit is de website van een van de klinieken in Nederland die ozontherapie toepast, maar we hebben geen enkele binding met deze kliniek en ozontherapie is ook elders in Nederland verkrijgbaar. Maar hier wordt helder uitgelegd wat ozontherapie is en hoe het wordt toegepast

31 mei 2005: Bron: Met dank aan Marijke die ons deze informatie toestuurde. Science Daily en Duke Universiteit

Onderzoekers aan Duke University Medical Center , met deelname van Belgisch onderzoekersteam uit Leuven hebben een methode gevonden om meer zuurstof toe te voegen aan het bloed en daarmee de kankercellen te doden terwijl daarmee ook het risico op hartklachten en andere bijwerkingen sterk worden beperkt..De onderzoekers voegden het molecuul nitric oxide toe aan het hemoglobine (rode bloedlichaampjes), die de zuurstofdragers zijn in het menselijk bloed en bereikten daarmee dat het zuurstofgehalte toenam. Dit lijkt belangrijk voor vooral wondgenezing, maar voor kankerpatiënten kan deze vinding ook belangrijk zijn. Bv. kankercellen gaan dood in een zuurstofrijke omgeving en chemo en bestraling hebben groter dodend effect op kankercellen als die meer zuurstof bevatten. Ook bij ozontherapie wordt gewerkt met toevoeging van oxygen - zuurstof aan het bloed en kan deze vondst een positief effect hebben. Achtereenvolgens het originele artikel van de Duke Universiteit en daaronder artikel uit Science Daily over deze ontdekking

DURHAM, N.C. –Duke University Medical Center researchers have demonstrated how to safely deliver more oxygen to oxygen-deprived tissues in the body, a finding that could lead to more effective blood substitutes, wound healing therapies and cancer treatments.

Oxygen is critical to proper functioning and healing of all tissues in the body, but altering its levels with current therapies can elevate blood pressure and constrict blood vessels – serious risks for heart disease. Additionally, such effects reduce the efficacy of many cancer therapies, including radiation and some forms of chemotherapy.

The Duke team showed that simply adding a molecule called nitric oxide to the blood's hemoglobin can make it deliver more oxygen to tissues -- without boosting heart rate or constricting blood vessels. Hemoglobin is the blood's oxygen-carrying component.

Results of the study by Duke and Howard Hughes Medical Institute researchers are reported in the May 27, 2005, issue of Circulation Research. The study was led by Mark Dewhirst, D.V.M., Ph.D., the Gustavo S. Montana Professor of radiation oncology; and Jonathan Stamler, M.D., Howard Hughes Medical Institute investigator and professor of medicine.

"Hemoglobin needs its natural partner in the blood, nitric oxide, to do its job of delivering oxygen to tissues, but current treatments deliver hemoglobin without nitric oxide," said Dewhirst. "Hemoglobin by itself actually reduces oxygenation to tissue because it constricts blood vessels, reducing blood flow." Thus, when delivered alone, hemoglobin may cause potentially fatal side effects and limit the effectiveness of radiation and chemotherapy.

The Duke researchers were seeking ways to improve oxygen levels inside tumors, which are often "hypoxic" or low in oxygen. These tumors are more resistant to treatment with chemotherapy or radiation, said Dewhirst.

"If we could raise the level of tumor oxygenation before radiation, we would have a better chance of killing more of the cancer cells," added Dewhirst.

The team hypothesized that hemoglobin containing nitric oxide would hold onto its oxygen until reaching the hypoxic environment of the tumor. Once there, it would release nitric oxide and dilate blood vessels to increase oxygen delivery.

The researchers confirmed this scenario by comparing the effects in animals of pure oxygen versus injections of combined hemoglobin and nitric oxide. The pure oxygen, breathed in naturally, raised the level of circulating oxygen, but not oxygen levels in the arteries feeding the tumor. The hemoglobin plus nitric oxide, by contrast, raised oxygen levels in the tumors.

The result supports the theory that hemoglobin senses oxygen levels and holds on to its nitric oxide and oxygen when oxygen levels in tissue are high, but releases oxygen and nitric oxide when oxygen levels are low, said Pierre Sonveaux, Ph.D., a post-doctoral fellow in Dewhirst's laboratory.

"This is the strongest proof yet that hemoglobin senses oxygen levels and unloads nitric oxide when oxygen levels are low," said Sonveaux. "These results open up the possibility of using nitrosohemoglobin therapeutically in patients where there is not adequate oxygen perfusion to tissue." Nitrosohemoglobin (SNO) is the combination of nitric oxide and hemoglobin.

The team's finding is the strongest evidence to date supporting Stamler's theory, first developed in 1996, that nitric oxide is an innate part of the body's oxygen delivery system. In previous studies, Stamler and his colleagues demonstrated that nitric oxide in blood cells is an active regulatory molecule that senses the oxygen level in tissue and causes hemoglobin to undergo subtle shape changes to release its oxygen in tissues when levels are low.

The study was funded by grants from the National Institutes of Health. Sonveaux is a fellow of the Belgian American Educational Foundation (BAEF) and a "Fonds National de la Recherche Scientifique" (FNRS) post-doctoral fellow detached from the University of Louvain Medical School, Belgium.

contact sources : Mark Dewhirst DVM, PhD , (919) 684-4180
dewhirst@radonc.duke.edu
Jonathan Stamler , (919) 684-6933
Staml001@mc.duke.edu

Nitric Oxide Finding May Yield Better Cancer Treatments And Blood Substitutes

DURHAM, N.C. -- Duke University Medical Center researchers have demonstrated how to safely deliver more oxygen to oxygen-deprived tissues in the body, a finding that could lead to more effective blood substitutes, wound healing therapies and cancer treatments.

Oxygen is critical to proper functioning and healing of all tissues in the body, but altering its levels with current therapies can elevate blood pressure and constrict blood vessels -- serious risks for heart disease. Additionally, such effects reduce the efficacy of many cancer therapies, including radiation and some forms of chemotherapy.

The Duke team showed that simply adding a molecule called nitric oxide to the blood's hemoglobin can make it deliver more oxygen to tissues -- without boosting heart rate or constricting blood vessels. Hemoglobin is the blood's oxygen-carrying component.

Results of the study by Duke and Howard Hughes Medical Institute researchers are reported in the May 27, 2005, issue of Circulation Research. The study was led by Mark Dewhirst, D.V.M., Ph.D., the Gustavo S. Montana Professor of radiation oncology; and Jonathan Stamler, M.D., Howard Hughes Medical Institute investigator and professor of medicine.

"Hemoglobin needs its natural partner in the blood, nitric oxide, to do its job of delivering oxygen to tissues, but current treatments deliver hemoglobin without nitric oxide," said Dewhirst. "Hemoglobin by itself actually reduces oxygenation to tissue because it constricts blood vessels, reducing blood flow." Thus, when delivered alone, hemoglobin may cause potentially fatal side effects and limit the effectiveness of radiation and chemotherapy.

The Duke researchers were seeking ways to improve oxygen levels inside tumors, which are often "hypoxic" or low in oxygen. These tumors are more resistant to treatment with chemotherapy or radiation, said Dewhirst.

"If we could raise the level of tumor oxygenation before radiation, we would have a better chance of killing more of the cancer cells," added Dewhirst.

The team hypothesized that hemoglobin containing nitric oxide would hold onto its oxygen until reaching the hypoxic environment of the tumor. Once there, it would release nitric oxide and dilate blood vessels to increase oxygen delivery.

The researchers confirmed this scenario by comparing the effects in animals of pure oxygen versus injections of combined hemoglobin and nitric oxide. The pure oxygen, breathed in naturally, raised the level of circulating oxygen, but not oxygen levels in the arteries feeding the tumor. The hemoglobin plus nitric oxide, by contrast, raised oxygen levels in the tumors.

The result supports the theory that hemoglobin senses oxygen levels and holds on to its nitric oxide and oxygen when oxygen levels in tissue are high, but releases oxygen and nitric oxide when oxygen levels are low, said Pierre Sonveaux, Ph.D., a post-doctoral fellow in Dewhirst's laboratory.

"This is the strongest proof yet that hemoglobin senses oxygen levels and unloads nitric oxide when oxygen levels are low," said Sonveaux. "These results open up the possibility of using nitrosohemoglobin therapeutically in patients where there is not adequate oxygen perfusion to tissue." Nitrosohemoglobin (SNO) is the combination of nitric oxide and hemoglobin.

The team's finding is the strongest evidence to date supporting Stamler's theory, first developed in 1996, that nitric oxide is an innate part of the body's oxygen delivery system. In previous studies, Stamler and his colleagues demonstrated that nitric oxide in blood cells is an active regulatory molecule that senses the oxygen level in tissue and causes hemoglobin to undergo subtle shape changes to release its oxygen in tissues when levels are low.

The study was funded by grants from the National Institutes of Health. Sonveaux is a fellow of the Belgian American Educational Foundation (BAEF) and a "Fonds National de la Recherche Scientifique" (FNRS) post-doctoral fellow detached from the University of Louvain Medical School, Belgium.