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Pain and ROx Clinical Study

Rutgers University School of Medicine performed an independent clinical study on Pain and ROx levels and have identified ROx, a Reserve of Oxygen in blood, which is required by the body to generate the energy for proper functioning of muscles, nerves, and other needs.

Technical Information

Test Subjects

Fifty-eight subjects were asked to choose one of three pain levels to describe their pain. The first group (the control group) had essentially no pain (pain = 0 to 2). The second group had pain that could be controlled with medication (pain = 3 to 6). The third group had pain, not controllable with medication (pain = 7 to 10).

Please note that for the control group (no pain), the average ROX measured in venous blood is 348.8 mg/liter of oxygen. The group with the highest pain had 270.1 mg/liter ROX— a 78.7 mg/liter depletion of ROX as compared to the control group.

Therefore, we have established norms using ROX to measure the intensity of pain in individuals. We hypothesize that supplying a sufficient amount of nutritional ROX Supplement to an individual, pain relief will be experienced. For example, a person with high pain with a blood ROX level of 270.1 will find that a ROX Supplement elevating his or her blood ROX level by 78.7, to 348.8 will experience relief.

The ROx Hypothesis

A special mechanism exists that uses white blood cells (WBCs) to encapsulate oxygen from red blood cells (RBCs) and transports it to all the cells in the body. For example, the volume of a large motor neuron is about 1,000 times the volume of a single RBC. For this neuron to fire, it requires a 30% increase in oxygen delivery to the mitochondria inside the neuron, within 1/1000th of a second. Oxygen is essentially not soluble in the water or plasma and cytosol. Simple diffusion of oxygen from the RBC, through the plasma and capillary walls, past other tissue, through the neuron wall, and into the mitochondria of the neuron is an unreasonable mechanism for four reasons: (1) huge amounts of oxygen delivery are required, (2) the delivery must be made within milliseconds, (3) the oxygen needs to be signaled when needed for firing, and (4) it cannot be diluted on the way to the neuron.

This means that each of us has a limited amount of ROx that can be tapped into. Healthy amounts of ROx deliver oxygen to the mitochondria inside our cells, and the oxygen is used properly and efficiently—where it is needed and when it is needed. But, when ROx is in disarray, it prematurely bursts before reaching the cell’s mitochondria and generates unwanted radical oxygen species and can cause neuronal damage (i.e., ALS). Plausibly, then, when stress causes ROx depletion, disease can happen.

What is ROx? What is known about ROx?

To observe the behavior of ROx, consider the following experiments. A small sample of blood is placed in a closed cell and exposed to stress. Oxygen is measured as a function of time. In the two example runs shown below, the concentration of oxygen remains at essentially zero for hours after being stressed, and then suddenly and spontaneously goes way up, and then comes back down. Where does this oxygen suddenly come from? We define this oxygen peak as a reservoir of oxygen, or ROx, which suddenly and spontaneously breaks open to release its oxygen when it is stressed.

ROx happens when blood is stressed
Figure 2: Whole blood cell

Figure 2 shows the oxygen released when whole blood is stressed with mechanical shear (vigorous mixing), bacteria, and a chemical toxin. Note that at the start of the run, there is no oxygen in the hemoglobin of the red blood cells (RBCs), because the oxygen starts at zero concentration. The release of oxygen comes from ROx.

Figure 3: White blood cell

Figure 3 is a run for white blood cells (WBCs), stressed with mechanical shear and chemical toxin. The oxygen released by the WBCs is 7,880 micrograms per ml of cells as compared to 650 for saturated RBCs. The difference is significant—ROx from WBCs can store at least ten times as much oxygen as RBCs.

 

After several hundred runs(1-5), we have determined that these oxygen peaks from ROx happen more at higher levels of induced stress. Also, the higher the concentration of white blood cells, the more likely it becomes that spontaneous bursts of oxygen from ROx appear.

 

To summarize, blood contains reservoirs of oxygen, ROx, that are released when the blood is exposed to physical, chemical, or biological stress. ROx does not behave like hemoglobin, which is in equilibrium with oxygen partial pressure. In hemoglobin, when oxygen partial pressure is low, hemoglobin releases oxygen until equilibrium is observed. When oxygen partial pressure is high, hemoglobin absorbs oxygen. ROx does not release or absorb oxygen as a function of partial pressure.

 

Stress, not partial pressure causes the release of oxygen from ROx. This release can take place in the absence of red cells. The ROx oxygen is far more concentrated than red cell oxygen. ROx has been measured at 35,000 micrograms of oxygen per ml, as compared to 650 micrograms per ml for packed red cells. This is 54 times as much as RBCs can carry. It is impossible to pack that much oxygen into hemoglobin.

Why has ROx not been identified earlier?

Unlike hemoglobin, which has a well-defined equilibrium curve with the partial pressure of oxygen, and which attains that equilibrium relatively quickly, ROx can stay hidden for many hours, and will not break open unless exposed to a systematic stress.

ROx Analyzer

We have developed the ROx Analyzer (RA), an instrument that measures ROx. The RA exposes blood to a programmable stress profile made up of mechanical shear stress, followed by chemical or other stresses. The RA produces reproducible and uniform data which measure the amount of ROx available, and the rate at which WBCs produce new ROx—how much ROx we have, and how much ROx we can make.

Supplemental ROx

We can produce ROx supplements for those who lack sufficient amounts. We can measure how much ROx one can produce and how much ROx one already stores, in order to supply the correct amount.

Why ROx is important

Medical emergencies and serious accidents can lead to stress, which reduces both the available ROx, and the capability to make new ROx. ROx depletion can be caused by the stresses due to over-exhaustion, air pollution, and emotional pressures, all of which consume large amounts of oxygen. Depletion of ROx leads to inhibition of physical and muscular mobility, interference with good decision-making, and vulnerability to diseases such as ALS, PTSD, cancer, diabetes, and inflammation. Keeping ROx in balance will greatly improve mental and physical performance.

Planned Clinical Studies

Additional clinical studies are planned for ALS; Alzheimer’s, Huntington’s, MS, and other neurodegenerative diseases; Cancer; Complex Regional Pain Syndrome; Diabetes; HIV/AIDs; Parkinson’s Disease; and Rheumatoid Arthritis and other auto-immune diseases.

ALS: Imbalanced ROx at the motor neuron leads to oxidative damage to the motor neuron and surrounding tissue.

Alzheimer’s, Huntington’s, MS, and other neurodegenerative diseases: Imbalanced ROx, for nervous system operation and signaling, leads to oxidative damage of nerve tissue and surrounding tissue..

Cancer: A tumor cannot be contained if there is insufficient ROx. A cancer patient with sufficient ROx can prevent a tumor from spreading by destroying any metastasized cancer cells.

Complex Regional Pain Syndrome (CRPS): Out of balance ROx allows free radicals to send unexplained pain signals to the brain.

Diabetes: If not enough ROx is delivered for glucose to be converted to energy, more insulin will be required to control a person’s sugar level.

HIV/AIDs: When a T-cell recognizes a virus, it recruits a critical mass of ROx to destroy the virus. Insufficient ROx leads to the premature release of oxygen, destroying T-cells and surrounding tissues.

Parkinson’s Disease: Only about 30% of people with the gene for Parkinson’s Disease (PD) actually get the disease. If less than a critical mass of ROx exists, radicals will be released in the brain and the surrounding tissues, resulting in widespread damage and causing a chain of events that leads to PD.

Rheumatoid Arthritis (RA) and other auto-immune diseases: Insufficient ROx allows for the indiscriminate spread of radical oxygen species, thus damaging surrounding tissues.

Contributors

Principal Investigator: John Bach, MD, Rutgers NJMS, Department of Physical Medicine and Rehabilitation

Co-investigators: Zamir Brelvi, MD, PhD, Michael Demyen, MD, Rutgers New Jersey Medical School, Gastroenterology and Hepatology; Samyadev Datta, MD, Center for Pain Management; Andrew Kaufman, MD, Rutgers Comprehensive Pain Center

Study Coordinator: Sam Sofer, PhD, PE, Solmedx

Study Performance Sites: Apollo Medical Center, Parsippany, NJ; Center for Pain Management, Hackensack, NJ; Immedicenters, Bloomfield, Clifton, and Totowa, NJ; Rutgers University Hospital, Newark, NJ

References

  1. A Method for Quantitation of Molecular Oxygen Peaks (MOPs) in Blood and Comparison with Hemoglobin-bound Oxygen C. McKenna and S. Sofer, Acta Toxicol. Ther., Vol. XX, n. 1 (1999)
  2. A potential rapid in vitro Assay to Quantitate Chemical Stress in Mammalian Blood C. McKenna and S. Sofer, Emerging Therapeutic Targets 3(2) 365-374 (1999).
  3. Molecular Oxygen Peaks (MOPs) in Blood: Their Discovery, Investigation and Implications C. McKenna and S. Sofer, Comparative Haematology International 9:68-71(1999).
  4. The Initial Oxygraphic Response of Bovine Blood as the Basis for a Rapid Assay for Drug Toxicity”; (S. Sofer, C. McKenna), Comparative Haematology International 9:72-75 (1999).
  5. An investigation of the oxidative response of stressed bovine blood C. McKenna, PhD Dissertation, New Jersey Institute of Technology (1997)
  6. The structure of scientific revolutions Thomas S. Kuhn (Chicago: University of Chicago Press, 1962)
  7. The innovator’s DNA J. Dyer, H. Gregerson, and C. Christensen (Boston: Harvard Business Review Press, 2011)
  8. Three known unknowns [fundamental holes in understanding cancer] K. Bourzac Nature VXXX, Cancer Outlook Suppl. xx-xxx page s23, 2014)

Keywords

Rutgers University School of Medicine; Rutgers IRB Protocol No: 2011001111; Interferon treatment; patient blood samples; ROX (reservoir oxygen capacity); Cancer, innate immune viability; AIDs; BOX; blood cell oxygen capacity; adaptive immune system strength; proper medication dosage; clinical studies; Hepatitis C; Diabetes; patient injury and drug toxicity Alzheimer’s; ALS; neurodegenerative diseases; Cancer; Diabetes; HIV/AIDS; Huntington’s Disease; Parkinson’s Disease (PD); Rheumatoid Arthritis (RA) and other auto-immune diseases; and Complex Regional Pain Syndrome (CRPS)]

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