Autism marked by Brain Inflammation. HBO reduces inflammation!

Autism Marked by Widespread Brain Inflammation

HBOT reduces the inflammation and restores circulation!

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NEW YORK (Reuters Health) Nov 18 - Brains obtained at autopsy from autism patients show widespread neuroglial activation and inflammation, according to a report in the November 15th online edition of Annals of Neurology.

Despite suggestions that immune dysfunction plays a role in the pathogenesis of autism, the authors explain, neuropathological studies have given little attention to immune and neuroglial activity in autism.

Dr. Carlos A. Pardo from Johns Hopkins University School of Medicine, Baltimore, and colleagues studied brain tissues obtained at autopsy from 11 autistic patients and cerebrospinal fluid from 6 living autistic patients.  Neuropathological examination of autistic brains revealed extensive neuroglial responses, along with patchy loss of neurons in the Purkinje cell layer and granular cell layer of the cerebellum.  "The marked neuroglial activity in the cerebellum is consistent with previous observations that the cerebellum is one focus of pathological abnormalities in morphological and neuroimaging studies of patients with autism," Dr. Pardo commented.  There was, however, no evidence of adaptive immune reactions in autistic brains, the authors report.

Brain tissues from autistic patients showed increased levels of proinflammatory cytokines, the results indicate, particularly in the region of the anterior cingulate gyrus. Cytokines originated principally from reactive astrocytes.

Cerebrospinal fluid from living autistic patients showed significant increases in MCP-1, IL-6, IFN-gamma, IL-8, MIP-1beta, and other proinflammatory cytokines and modulatory cytokines.

"These cytokines play important roles in immune mediated processes, and their presence in the CSF in autistic patients may reflect an ongoing stage of inflammatory reactions likely associated with neuroglial activation and/or neuronal injury," Dr. Pardo explained.  "At present, there is no indication for using anti-inflammatory medications in patients with autism," Dr. Pardo cautioned. "There are ongoing experimental studies to examine the effect of drugs that limit the activation of microglia and astrocytes, but their use in humans must await further evidence of their efficacy and safety."

Hyperbaric Oxygen Therapy is known for its ability to dramatically reduce inflammation!

Ann Neurol 2004.

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oxygen

Oxygen is transported across the alveolar membrane and enters plasma. Some is then taken up by hemoglobin and some remains in plasma. Under normal conditions - that is at a standard atmosphere, which is defined as 1013 hPa or 760 mm Hg - 100 ml of arterial blood carries about 19 ml of oxygen as oxyhaemoglobin and only 0.3 ml in solution. Hence, the latter is often ignored. However only the oxygen in the plasma is available for transport through the capillary wall into the tissues and the concentration or tension determines the rate.

Oxygen has to dissociate from hemoglobin to be available. The plasma oxygen tension breathing air with oxygen at a partial pressure (Dalton's Law) of 2 tenths of an atmosphere (21% of 1 atm abs) is about 95 mm Hg. Increasing the oxygen inspired to 100% multiplies the amount in solution by a factor of 5 - hence (Henrys Law) the amount Carried in solution is multiplied by five to 1.5 ml at 3 atm abs it is 4.5 ml per 100 ml blood, which is the normal arterial - venous difference at rest. Hence, all the requirements of the body can be met by the oxygen in the plasma. However, the gradient is what is so important in therapy - over 2000 mm Hg can be achieved - a more than twenty fold increase. Consequently, life can be supported with Blood for a short time and the paper was published in 1959. Used Properly oxygen is the most powerful therapeutic tool in medicine. We Need to ensue our medical students are taught properly but after 25 Years in this school, we have only just established oxygen therapy in the curriculum.

Philip James M.D.
Wolfson Hyperbaric Medicine Unit
University of Dundee
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OXYGEN UPTAKE IN MITOCHONDRIA

OXYGEN UPTAKE IN MITOCHONDRIA

If there's one thing that mitochondria thrive on, its oxygen. All of it is consumed by cytochrome oxidase, the last enzyme in the electron transport chain which drives ATP production. If cells relied on diffusion alone to supply them with their oxygen needs, then there would not be enough to keep up with demand. So oxygen carrying molecules, such as haemoglobin and myoglobin, evolved to transport oxygen to where it is needed. However as Jonathan and Beatrice Wittenberg explain, researchers know very little about the conditions necessary for oxygen to reach cytochrome oxidase (p. 2082).

As oxygen travels through the body it exerts a pressure in the mixture of gases in the lungs, or in solution, known as the partial pressure. Oxygen bound to haemoglobin in the blood diffuses down a steep pressure gradient into tissues as blood travels through capillaries. Next oxygen diffuses into the mitochondria. By reducing the oxygen pressure to levels below which mitochondria would not get enough oxygen without the help of haemoglobins, the Wittenbergs hoped to find the oxygen partial pressure necessary for oxygen uptake by mitochondria from hard working pigeon hearts. Also, would myoglobin in the heart muscle need to bind to mitochondria to deliver oxygen? To extract mitochondria for their study, the team delicately ground up the heart muscle tissue with a homogeniser and dissolved away the toughest tissue with enzymes; then, they released the mitochondria from the cell fragments and put them in a nourishing solution.

To show that myoglobin doesn't need to bind to the surface of mitochondria to deliver its oxygen, they used six different haemoglobins in the solution to deliver the oxygen: one each from horse, an insect, and soy bean, and three from molluscs. Each binds and releases oxygen at very different rates. Using a method called spectrophotometry, where a light is shone through biological samples and the light absorbed at each wavelength is measured, the team could tell how oxygenated the haemoglobins were since they absorb different light wavelengths depending on how much oxygen they are carrying. Despite differences in the speed with which oxygen bound to and was released from the haemoglobins, the mitochondria still took up oxygen at the same rate, showing that the haemoglobins didn't bind to the surface to deliver their cargo.

To find what oxygen partial pressure kept cytochrome oxidase functioning normally, they measured the saturation of each of the haemoglobins with oxygen and how it decreased as the mitochondria used oxygen up. From this they calculated oxygen pressure, which is directly related to haemoglobin saturation. When oxygen uptake was half its maximal rate, they found that the oxygen pressure at the surface of the mitochondria was very similar for all the haemoglobins, around 0.0053 kPa, despite their different reaction kinetics. This is much smaller than the pressure measured previously in working hearts, around 0.32 kPa. This means that even when a heart muscle is working flat out, such as during flight, the mitochondria will still have plenty of oxygen available to generate ATP.

Because oxygen uptake also levelled out as they increased the concentrations of the haemoglobins, the team suspect that there is just enough myoglobin present to support the cell, but not more, indicating that cells optimise oxygen delivery. `The results were not unexpected', Jonathan Wittenberg explains. Despite this, he says, `there is still a lot we don't understand about oxygen transport in heart and muscle'.

References

Wittenberg, J. B. and Wittenberg, B. A. (2007). Myoglobin-enhanced oxygen delivery to isolated cardiac mitochondria. J. Exp. Biol. 210,2082 -2090.[Abstract/Free Full Text]

Oxygen; the new growth factor?

Oxygen; the new growth factor?

In recent years our understanding of the intercellular communication of healing has increased considerably. Cells within a wound receive a myriad of signals from their environment – the sum of which govern the activity of a cell. The term “cytokine” is applied to those substances which function as cellular signals. Growth factors are a subclass of cytokines that specifically stimulate the proliferation of cells. This stimulation may occur through several different mechanisms. For example, some growth factors have chemo-tactic activities that attract fibroblasts and inflammatory cells, some act as mitogens, stimulating cell division, and some effect the production and degradation of the extra-cellular matrix. All of these phenomena are the end result of a cytokine (growth factor) signaling the cell nucleus to produce proteins, which account for the observed activities. A clear understanding of growth factor physiology carries the promise of clinical advances in wound management. Currently one cytokine, Platelet Derived Growth Factor, is in clinical use for the management of problem wounds. As our knowledge of these substances expands, other growth factors will be added to our clinical armamentarium for the management of non-healing wounds.

Non-healing wounds can also be managed by optimizing the metabolic requirements of healing, e.g. protein, trace elements, and oxygen. The most frequent common denominator in non-healing wounds is inadequate tissue oxygenation, which impairs healing and host defenses. Correction of such hypoxia by means of revascularization or hyperbaric oxygen therapy results in healing for most patients. Conventional wisdom suggests that oxygen is just a metabolite and therefore healing, in these circumstances, is simply a reflection of having sufficient oxygen to meet the energy demands of wound repair. However, some exciting evidence is now emerging to suggest that oxygen serves a dual role as both a metabolite and a growth factor. The conceptualization of oxygen as a growth factor has considerable relevance to the field of hyperbaric oxygen therapy.

The idea of oxygen acting as a cell signal has already been established in the setting of hypoxia. As an example, gene expression for erythropoietin production is largely proportional to the pO2 level in the kidney. It has been proposed that cells in a non-healing wound may respond to hyperbaric therapy because the supra-physiologic elevation of tissue oxygen serves as a trigger signaling that enough oxygen is in the environment to proceed with normal healing.1 Subsequent daily exposure to the threshold oxygen level reinforces this signal and results in gene expression of the protein building blocks required for healing. Teleologically, it makes sense for cells to conserve resources until the environmental signals are strong enough and consistent enough to activate the cell nucleus and begin the healing process.

This past year two separate groups of investigators have published findings that support this concept of oxygen as a growth factor. Following a single one-hour exposure to hyperbaric oxygen, Hehenberger, et al. (1997) demonstrated a dose dependent stimulation of normal in vitro fibroblasts with a peak increase in cell proliferation at 2.5 ATA O2. The dose-dependent effect of a single 1-hour exposure to oxygen suggests a pharmacologic effect of oxygen on cells, as opposed to an increased metabolic availability of oxygen. These findings suggest, therefore, that a single brief exposure to hyperbaric oxygen on a daily basis provides a strong initiating signal for the intracellular events that culminate in cell proliferation, while sustained hyperoxia has the opposite effect.

In a study of in vitro fibroblast proliferation using tritium-labeled thymidine, Tompach, et al., found that a single dose of HBO (2.4 ATA for 120 minutes) produced a sustained stimulation of fibroblasts for 72 hours.3 If a second exposure to HBO was given on the same day there was no additional increase in cell proliferation. Similarly, cultured endothelial cells remained stimulated for 72 hours following a single 15-minute exposure to HBO. Again, these findings suggest that we must reconsider oxygen as being more than just a metabolite.

This new paradigm of oxygen as a growth factor is consistent with the clinical observation that a BID dosing of HBO appears to offer no clear benefit over a QD dosing schedule for the treatment of chronic wounds. As our understanding of oxygen physiology increases, we will be in a better position to determine the optimal dosing of oxygen in both its metabolic and stimulatory roles.

References:

1. Siddiqui A, Davidson JD, Mustoe TA. Ischemic tissue oxygen capacitance after hyperbaric oxygen therapy: A new physiologic concept. Plastic Reconstructive Surgery 1997; 99:148-69.

2. Hehenberger K, Brismar K, Folke L, Gunnar K. Dose-dependent hyperbaric oxygen stimulation of human fibroblast proliferation. Wound Rep Reg 1997; 5:147-50.

3. Tompach PC, Lew D, Stoll JL. Cell response to hyperbaric oxygen treatment. Int J Oral Maxillofac Surgery 1997; 26: 82-86.

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Scan Detects Oxygen Levels in Tumors

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Scan Detects Oxygen Levels in Tumors

April 23, 2009 (HealthDay News) -- New research suggests that scientists are close to developing a simple way to measure oxygen levels in tumors, giving doctors a heads-up about what kind of treatment is best for individual patients.

The findings fit into an emerging trend of individualized treatment for patients with cancer instead of treating people the same way, said Dr. Mark Dewhirst, a professor of radiation oncology at Duke University Medical Center.

"If successful, [the trend] will revolutionize the way that we treat cancer," said Dewhirst, who co-wrote a commentary accompanying the new study, published April 22 in the Journal of Clinical Investigation.

Scientists began realizing the important role of oxygen in tumors about 50 years ago, said study co-author James Mitchell, branch chief of radiation biology at the U.S. National Cancer Institute's Center for Cancer Research. The scientists discovered that tumors with higher concentrations of oxygen were more susceptible to radiation, he said.

"Radiation damages cells by causing damage to DNA, and one particular type of damage renders the DNA molecule non-reparable," Mitchell said. But less oxygen in the tumor allows tumor cells to survive more easily by making the DNA destruction process more difficult, he said.

According to Dewhirst, the same is true for chemotherapy drugs, which also don't work as well when tumors have less oxygen.

Lower levels of oxygen create other problems, Dewhirst. "One would think at first that lack of oxygen would make tumors unhealthy and easy to kill," he said. "But actually, the opposite happens -- tumor cells that lack oxygen become more aggressive and more difficult to kill."

Tumors with lower oxygen levels even spread more easily through the body, he said.

Doctors can check oxygen levels in patients by inserting a needle. But doctors can't insert needles into some patients, and. in others, it's difficult to insert the needle deep enough, Mitchell said.

In the new study, the researchers tested a scanning technique called pulsed electron paramagnetic resonance imaging and used it in tandem with magnetic resonance imaging. The study authors said they were able to successfully measure oxygen levels in tumors in mice by using the non-invasive technology.

"The imaging that is described in this study provides all of the information necessary to evaluate oxygen levels in tumors as well as to examine underlying causes for the lack of oxygen," Dewhirst said. "The fact that all of the imaging is completely non-invasive provides the ability to perform this measurement more than once, (meaning) this could be used to monitor the effectiveness of cancer therapy."

There are caveats, however. The research hasn't reached the human testing level yet, and it may not work in people. "Scaling up the method to make it suitable for use in humans will be a significant challenge, but not impossible," Dewhirst said.

For now, the plan is to launch more studies with animals to see if the technique works as a way to test cancer drugs.

SOURCES: Mark W. Dewhirst, DVM, Ph.D., Gustavo S. Montana professor of radiation oncology and professor of pathology and biomedical engineering, Duke University Medical Center, Durham, N.C.; James Mitchell, Ph.D., branch chief, radiation biology, Center for Cancer Research, U.S. National Cancer Institute, Bethesda, Md.; April 22, 2008, Journal of Clinical Investigation

Hypoxia and Oxygen Free Radical Damage

Hypoxia and Oxygen Free Radical Damage

Hyperbaric oxygen therapy does not cause free radical damage but this is a frequently raised objection. Fridovich

(1) was the first to publish that it is LACK of oxygen that creates the conditions for free radical damage. He discussed three possible scenarios.

1. The formation of free radicals increases when the level of oxygen in the tissue actually reduces.

2. The accumulation of substances when there is an insufficient level of oxygen causes free radical formation when normal levels of oxygen are restored.

3. White cells are programmed and congregate in the brain during hypoxia and activate the 'respiratory burst' normally responsible for microbial killing.

All three are probably valid and are interlinked, but the white cell effects can be seen. Fridovitch predicted the effects link free radical injury to inflammation. In infection white cells stick to the lining of blood vessels at the infection site (2) by detecting changes due to lack of oxygen. In both inflammation and reperfusion injury white cells stick to the lining of blood vessels and then pass through into the tissues to generate a burst of oxygen free radicals to kill the invaders. (3) This defense mechanism is wrongly activated when blood flow is restored in an organ after a period of arrest. Zamboni et al (4) stopped the blood flow in muscle for four hours and on restoring flow found white cells sticking to the wall of veins and then passing through, leading to the death of the muscle tissue. A high level of oxygen stopped the cells sticking and death of the muscle tissue was prevented.

The relevance to the practice of Medicine? The use of high dosage oxygen to treat ANY condition where blood flow is significantly reduced or stopped, especially organ transplantation and to protect the brain when the circulation is restored after cardiac arrest.

1. Fridovich I. Hypoxia and oxygen toxicity. Adv Neurol 1979;26:255-59.

2. Clark ER, Clark EL. Amer J Anat 1936;59;123

3. Babior BM Oxygen dependent microbial killing of phagocytes N Engl J Med 1978;298:721-725.

4. Zamboni WA et al.Morphologic analysis of the microcirculation during reperfusion of ischemic skeletal muscle and the effect of hyperbaric oxygen.

Plast Reconstr Surg 1993;91:1110-1123

Best wishes to all

Philip James

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HBOT relieves hypoxia

Hyperbaric Oxygen Therapy relieves the oxygen starvation of the brain known as hypoxia. Since full blood circulation to specific areas of the brain is impaired, increasing the rate at which oxygen diffuses into all of the body's fluids increases the amount of oxygen carried to the hypoxic brain tissues. Oxygen enriched cerebrospinal fluid will help to repair any recoverable brain tissue that is intact but not functioning normal. In many cases, HBOT has shown these idling neurons have started to function more efficiently, producing long-term improvements in both brain and clinical function. With the improvement of micro circulation and the relief of any brain swelling, a patient can experience a reduction in spasticity and an improvement in cognitive ability, vision, gross and fine motor skills, hearing and speech.

The brain now has the ability to learn and to process thought into actions. Depending on the age at the time of injury, many times the therapies now are able to be put into action. The patient may also now be able to go through the many stages of neurological steps. This steps may be skipping, crawling, standing, reactions as the brain now is going through a catch up stage of learning. With the permanent new blood supply the effects of HBOT will go on and on.

Some patients will suddenly be able to put into action a certain physical therapy or neuro-therapy, which never seemed to have an influence before.

In some, the most significant improvements are often seen when the HBOT is over; in some cases weeks later. Sadly, sometimes HBOT does not get the life-saving recognition, acknowledgment, and credit it so well deserves.

Patrick and Susan Rodriguez CHT, EMT, DMT

Parents of Susie, Danielle, Renee

Recovered

Asthma and HBOT Opinion By Dr. James M.D. U.K.

Oxygen is a powerful anti-inflammatory agent and asthma has been successfully treated by oxygen, especially at increased atmospheric pressure. The Russians presented data on the successful treatment of asthma in the International Congress Moscow 1981. Over the last 19 years operating high dosage oxygen therapy in the community many patients with MS in our charity have also had asthma and have found a much-reduced requirement for inhalers. NONE of the patients have had chest radiographs but of course all have had gas trapping in the lung. (It is not possible to remove it all by exhalation) We do advise patients if they have severe colds to use a decongestant, but the inflammation is considerably helped by oxygen.

Dr P B James MB ChB DIH PhD FFOM
Wolfson Hyperbaric Medicine Unit
University of Dundee

Bronchitis
K.K. Jain
Text Book of Hyperbaric Oxygen Medicine, Vol. 3

Efuni (1984) used HBOT in 92 patients with dust induced bronchitis. There was improvement in 88.9% of the patients as determined by tolerance to physical exercise and blood gas measurements. This is the only report from the USSR, and we find there are no studies in the Western Literature.

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Hypoxia

Hypoxia

Hypoxia is a state of oxygen deficiency in the body, which is sufficient to cause an impairment of function. Hypoxia is caused by the reduction in partial pressure of oxygen, inadequate oxygen transport, or the inability of the tissues to use oxygen.

In brief, being drunk is kind of the same as being exposed to high altitude. In both cases, oxygen to your brain and muscles is reduced.

Hypoxic Hypoxia is a reduction in the amount of oxygen passing into the blood. It is caused by a reduction in oxygen pressure in the lungs, by a reduced gas exchange area, exposure to high altitude, or by lung disease. [This is the hypoxia that is a hazard to aviators.]

Pemic Hypoxia is defined as a reduction in the oxygen carrying capacity of the blood. It is caused by a reduction in the amount of hemoglobin in the blood or a reduced number of red blood cells. A reduction in the oxygen transport capacity of the blood occurs through blood donation, hemorrhage, or anemia. A reduction in the oxygen carrying capacity of the blood occurs through drugs, chemicals, or carbon monoxide. [This hypoxia usually experienced by smokers.]

Stagnant Hypoxia is an oxygen deficiency due to poor circulation of the blood or poor blood flow. Examples of this condition are high "G" forces, prolonged sitting in one position or hanging in a harness, cold temperatures, and positive pressure breathing. [This hypoxia usually experienced when sitting for hours in a boring class.]

Histotoxic Hypoxia is defined as the inability of the tissues to use oxygen. Examples are carbon monoxide and cyanide poisoning. Certain narcotics, chewing tobacco, and alcohol will prevent oxygen use by the tissues. [This hypoxia usually experienced after drinking too much.]

Dr James MD

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Hypoxia
Hypoxia is a state of oxygen deficiency in the body, which is sufficient to cause an impairment of function. Hypoxia is caused by the reduction in partial pressure of oxygen, inadequate oxygen transport, or the inability of the tissues to use oxygen.
In brief, being drunk is kind of the same as being exposed to high altitude. In both cases, oxygen to your brain and muscles is reduced.
Hypoxic Hypoxia is a reduction in the amount of oxygen passing into the blood. It is caused by a reduction in oxygen pressure in the lungs, by a reduced gas exchange area, exposure to high altitude, or by lung disease. [This is the hypoxia that is a hazard to aviators.]
Pemic Hypoxia is defined as a reduction in the oxygen carrying capacity of the blood. It is caused by a reduction in the amount of hemoglobin in the blood or a reduced number of red blood cells. A reduction in the oxygen transport capacity of the blood occurs through blood donation, hemorrhage, or anemia. A reduction in the oxygen carrying capacity of the blood occurs through drugs, chemicals, or carbon monoxide. [This hypoxia usually experienced by smokers.]
Stagnant Hypoxia is an oxygen deficiency due to poor circulation of the blood or poor blood flow. Examples of this condition are high "G" forces, prolonged sitting in one position or hanging in a harness, cold temperatures, and positive pressure breathing. [This hypoxia usually experienced when sitting for hours in a boring class.]
Histotoxic Hypoxia is defined as the inability of the tissues to use oxygen. Examples are carbon monoxide and cyanide poisoning. Certain narcotics, chewing tobacco, and alcohol will prevent oxygen use by the tissues. [This hypoxia usually experienced after drinking too much.]
Dr James MD
Reprinted with Permission