There now seems to be intense interest in EBO2 techniques. Copious volumes of research have provided evidence that Ozone’s dynamic resonance structures facilitate physiological interactions useful in treating a myriad of pathologies. The comment of Ozone opponents is that ozone therapy looks like a panacea for all diseases. Indeed, it seems so, but in reality, this is due to the multitude of compounds originated at first from the reaction of ozone with body fluids, and eventually able to display pleiotropic effects delivered by different organs.
Ozone can be considered a “PRODRUG”. What exactly is a Prodrug? A prodrug is a medication or compound that, after administration, is metabolized into a pharmacologically active drug. Instead of administering a drug directly. The following illustration shows how a prodrug works:
One of the issues raised by the scientific community is: how does Ozone really acts on Humans? Ozone is quite different from a drug and its action is not a consequence of a binding reaction between one molecule (drug) and one receptor (cellular membrane protein). For this reason, we cannot look at Ozone in the classical terms of pharmacology.
Ozone like other agents, and unlike the common drugs that act on a specific receptor, induces small stress to the whole cell when used at adequate doses. This, in turn, triggers a series of intracellular metabolic processes and promotes a myriad of intracellular activities. Because of these reactions, the defense mechanisms of the cell are alarmed and pushed to improve cell activity, explaining in part the surprising therapeutic actions of Ozone. By the same token Ozone is not truly a prodrug since it can have direct effects on phospholipids, lipoproteins, the cell membrane envelopes of bacteria and viruses. These bioactivities can eradicate bacteria and viruses.
In order to fully understand the biochemical basis underlying the pharmacological effects of ozone, it is important to illustrate its effects on various coenzymes. These coenzymes are responsible for ozone cell metabolism regulation. These effects on metabolism have profound effects on many aspects in the body. One of the significant effects of ozone is the acceleration of glycolysis. Glycolysis results in breaking glucose into pyruvate and getting a very valuable H+ hydrogen ion. The free energy released in this process is used to form the high-energy molecules ATP (adenosine triphosphate) and NADH (reduced nicotinamide adenine dinucleotide). ATP is cellular energy that all cells depend upon. Ozone will allow the ratio of NAD/NADH to be about 700/1. A fundamental condition for guaranteeing the continuity of this process is the reoxidation of NADH as it occurs following ozone exposure. The NADH is converted to NAD+.
The above diagram shows some important relationships. The ratio of NAD/NADH should be about 700/1. Ozone will stimulate the NQO1 gene which has profound effects on this ratio. NQO1 also stimulates the Sirtuin genes which are very significant in anti-aging and general well-being.
As far as protein metabolism, ozone intervenes mainly due to its remarkable affinity towards sulfhydryl groups. A sulfhydryl is a functional group consisting of a sulfur bonded to a hydrogen atom.
The sulfhydryl group is one of the most reactive and ubiquitous binding molecules in biological systems. It is found in most proteins and also in a few low molecular-weight substances such as glutathione, CoA (Coenzyme A, notable for its role in the synthesis and oxidation of fatty acids), lipoate, thioglycolate, and free cysteine. It is the most studied of chemical groups, particularly in relation to its role in enzymatic activity and properties of proteins.
Similarly, ozone reacts with essential amino acids such as methionine, tryptophan, and other amino acids containing sulfur (i.e., cysteine). In this case, the amino acids are protected from ozone inactivation by two reactions that prevent their degradation: first the oxidation of glutathione and then the oxidation of the coenzymes NADH and NADPH, which are key reactions in the biochemical mechanism of ozone. Nicotinamide adenine dinucleotide, or NAD, is in all living cells, where it functions as a coenzyme. It exists in either an oxidized form, NAD+, which can accept a hydrogen atom (i.e., a proton), or a reduced form, NADH, which can donate a hydrogen atom. Note that "donate a proton" and "accept a pair of electrons" translates to the same thing in biochemistry. Nicotinamide adenine dinucleotide phosphate, or NADP+, is a similar molecule with a similar function, differing from NAD+ in that it contains an additional phosphate group. The oxidized form is NADP+, while the reduced form is NADPH.
Finally, ozone reacts directly with unsaturated fatty acids, which have a double carbon bond and are therefore available for an oxidative reaction, leading to the formation of peroxides following cleavage of the lipid chains. In addition to the direct contributions to cellular metabolism described above, both NADH and NADPH may take part in other important physiological processes, including mitochondrial functions, calcium regulation, antioxidation and its counterpart (the generation of oxidative stress), gene expression, immune functions, the aging process and cell death. As a result, some biochemistry researchers have proposed that further investigation
Ozone dissolved in the plasma reacts immediately with a number of biomolecules producing two compounds. There are two compounds Reactive Oxygen Species (ROS) and Lipid Oxidative Products (LOPS). They represent the “ozone messengers” and are responsible for many of the biological and therapeutic effects attributed to ozone. ROS are produced immediately in the early phase (mainly Hydrogen peroxide or H2O2) and are responsible for the early biological effects on blood (erythrocytes, leucocytes, platelets). Hydrogen peroxide, now universally recognized as one of the main intracellular signaling molecules, acts on the different blood cells. Hydrogen peroxide is one of the most significant cytokine inducers in white blood cells. The mass of erythrocytes mops up the bulk of hydrogen peroxide. H2O2 diffuses easily from the plasma into the cells and its sudden appearance in the cytoplasm represents a triggering stimulus. This stimulus depends upon the cell types. Different biochemical pathways can be concurrently activated in erythrocytes, leukocytes and platelets resulting in numerous biological effects.
On the other hand, Lipid Oxidative Products (LOPS), which are simultaneously produced at the same time as ROS have a far longer half-life. They reach the vascular system and interact with several organs, where they trigger late effects. Some of these real targets are liver, vascular system, while other organs are probably involved in restoring normal homeostasis including the central nervous system, gastrointestinal tract, mucosal associated lymphoid tissue. The LOPS molecules can elicit the upregulation of antioxidant enzymes such as superoxide dismutase (SOD), GSH-peroxidases (GSH-Px), GSH-reductase (GSH-Rd) and catalase (CAT). Moreover, LOPS exert a neuroimmunomodulatory effect highlighted by a feeling of well-being reported by patients during ozone therapy.
OZONE THE WONDER DRUG
Ozone is a wonder drug because it can produce four extraordinary phenomena: 1) the induction of Oxidative Shock Proteins (OSP) 2) the upregulation of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase) 3) the reduction and/or normalization of oxidative stress; and 4) the release of bone marrow stem cells.
Ozone mobilizes bone marrow stem cells (BMSC) and produces LOPS, which induce Nitric Oxide synthase (NOs). This produces inhibition of platelet-leukocyte aggregation.NO is responsible for producing neovascularization and neoangiogenisis. Also, NO activates MMP-9 (matrix metalloproteinase 9) which is indispensable for stem cell mobilization. MMP-9 actually releases the bond that holds stem cells in the bone marrow and releases them to the circulation. The production of Nitric Oxide is one of the main mechanisms by which hyperbaric oxygen will increase stem cell output from the bone marrow. These numbers will include a wide variety of the stem cells that are released from the marrow including Hematopoietic and Mesenchymal Stem cells. Ozone forms lipid oxidative products which in turn produce nitric oxide which makes proteases which release stem cells from the bone marrow into the circulation. The release of stem cells from the marrow is a multi-step process dependent on many different factors.
We can see from the following diagram the very process of how Ozone affects stem cell release:
The above diagram shows release of stem cells (HSC) from the bone marrow to the circulation. This is very dependent upon the production of MMP-9. This stimulation releases the stem cells from the bone marrow and allows them to go into circulation.
The fact that Ozone releases stem cells from the bone marrow is very important. It should be mentioned that this concept is similar to the mechanism of hyperbaric oxygen. In the above diagram it is demonstrates that LOPS, throughout the treatments, act as acute oxidative stressors in the bone marrow microenvironments activate the release of metalloproteinases, of which MP-9 particularly may favor the detachment of stem cells. These cells, once in the blood circulation, may be attracted and home at sites where a previous injury (a trauma or an ischemic-degenerative event) has taken place. The potential relevance of such an event would have a huge practical importance and will avoid the unnatural, costly and scarcely effective practice of the bone marrow collection with the need of the successive and uncertain re-infusion.
OZONE AND OXIDATIVE STRESS
One of the most important aspects of Ozone therapy is activation the Nuclear Factor Erythroid 2 Related Factor 2 commonly known as NrF2. NrF2 is like the body’s “missile defense system”. It helps keep oxidative stress under control. Oxidative stress arises from free radicals. Free radicals are compounds which have free electrons. These rogue molecules can cause havoc by “stealing” electrons from other molecules. Some free radicals are capable of damaging the DNA or crippling the proteins and lipids that make up various tissues. As a result, these crucial molecules become damaged, weak, dysfunctional, or otherwise incapable of fulfilling their roles. Produced deep within cells as a byproduct of ordinary energy-producing processes, free radicals are thought to be responsible for aging and disease, including even cancer. How does NrF2 protect us from free radicals?
NrF2 is basically like a thermostat. But instead of regulating temperature, it regulates stress levels known as oxidative stress. It responds by binding with the DNA, signaling the cells to make thousands of molecules to shield the cells. They will later activate a new response to form a new barrier. This “barrier” will protect the cells from future stress. Furthermore, Nrf2 will remove the toxins that cause cell damage and boost the normal function. Both of these functions will return the stress levels to normal, minimizing the negative effects.
We must realize that we do not want to constantly have NrF2 activated. Ozone is a selective NrF2 activator. How does this work? Ozone produces Antioxidant Responsive Elements (ARE). Antioxidant responsive elements (AREs) mediate the transcriptional induction of a battery of genes which comprise much of this chemoprotective response system and ultimately the NrF2 pathway.
Under normal conditions, Nrf2 is expressed at very low levels, and is mainly sequestered in the cytoplasm by its specific inhibitor called Kelch-like ECH associated protein-1 (Keap-1) that also promotes its rapid degradation. The effectiveness of this mechanism allows a rapid turnover of Nrf2, which displays a half-life of a few minutes. Under specific stimuli, Nrf2 dissociates from Keap1 and translocates into the nucleus and transactivates the ARE-driven genes. These genes encode for proteins involved in a multitude of vital biological functions which include protein homeostasis, oxidative stress response, detoxication, DNA repair, proliferation, autophagy (body's way of cleaning out damaged cells), mitochondrial biogenesis and function, inflammation, and the metabolism of lipids, carbohydrates and amino acids. When you stimulate NrF2 you have a healthier patient.
The following illustration shows these concepts:
NrF2 goes on to control a wide variety of processes in the body including proper formation of proteins, control of inflammation, healthy mitochondrial function, and healthy adipose tissue.
WHAT ARE SOME OF THE OTHER EFFECTS OF OZONE THERAPY
The oxidation chemistry of ozone is known to produce Hydrogen Peroxide (H2O2) that enters cells where it has various effects. In red blood cells (RBCs), it shifts the hemoglobin dissociation curve to the right and facilitates release of oxygen, while in leukocytes (WBCs) and endothelial cells it can stimulate the production of interleukins, interferons, growth factors and nitric oxide production. In platelets it favors release of growth factors. As a further aspect of the therapeutic action of ozone, there is the capacity to regulate the cell antioxidant network positively. This aspect is of key relevance in all those conditions in which an imbalance between production and neutralization of ROS (Reactive Oxygen Species) may develop, resulting in oxidative stress. Again, this relates to the implications of the NrF2 pathway and its activation or inactivation. These events may turn into a self-feeding cycle in which oxidative stress is sustained by micro- and macro-inflammatory reactions that lead to cell and tissue degeneration and necrosis. This scenario features the pathogenetic role of oxidative stress in several chronic, degenerative disease states such as chronic viral infections, atherosclerosis, tumor growth, neurodegenerative diseases and accelerated aging. Ozone can help stop these problems in their tracks.
HEAT SHOCK PROTEINS
Another aspect of Ozone therapy is the production of HEAT SHOCK PROTEINS (HSPS). Shock proteins are a family of proteins that are produced by cells in response to exposure to stressful conditions. They were first described in relation to actual heat shock, but are now known to also be expressed during other stresses including exposure to cold, UV light (this is one of the reasons we are utilizing a UVA light to stress the blood cells) and during wound healing or tissue remodeling. We can also stimulate Heat Shock Proteins by using a sauna or by subjecting our body to very cold temperatures.
Many members of the Heat Shock Protein group perform chaperone functions by stabilizing new proteins to ensure correct folding or by helping to refold proteins that were damaged by the cell stress. This increase in expression is genetically regulated. In the packed, busy confines of a living cell, hundreds of chaperone proteins vigilantly monitor and control protein folding. From the moment proteins are generated in and then exit the ribosome until their demise by degradation, chaperones act like helicopter parents, jumping in at the first signs of bad behavior to nip misfolding in the bud or to sequester problematically folded proteins before their aggregation causes disease. People often mistakenly think that proteins are free to live out their lives in a cell. As it becomes increasingly clear that folding is not a once-in-a-lifetime event for proteins but instead a part of day-to-day life in the cell. Scientists are discovering that problems in this sophisticated system of protein folding are implicated in diseases as diverse as cancer, diabetes, and Alzheimer’s. As time goes on we are finding more and more diseases associated with misfolded proteins. This will open up a new realm in medicine in which Ozone therapy and Photo modulation may be integral players on taking the science of Heat Shock Proteins to the next level. Not only is Heat Shock Proteins important in disease control but it seems to have a place in improving athletic performance.
The dramatic upregulation of the heat shock proteins is a key part of the heat shock response and is induced primarily by heat shock factor (HSF). The following illustrations demonstrate the very important work of the Heat Shock proteins:
HSPs are found in virtually all living organisms, from bacteria to humans. HSPs are known to modulate the effects of inflammation cascades leading to the generation of ROS and intrinsic apoptosis through inhibition of pro-inflammatory factors, thereby playing crucial roles in the pathogenesis of human inflammatory diseases and cancer. There is a scientific push for studying the HSPs for the treatment of various inflammatory diseases and cancer. Also, it appears that a safe and effective method of stimulating HSPs is by the use of Ozone in blood. Heat shock proteins may play a critical role in reducing recovery time and boosting muscle development.
The following illustration shows the mechanism of HSPs:
We can see that the HSPs can have profound implications for a person’s well-being. This is a field where more research will certainly be needed. We can see that when we have an altered expression of Heat Shock proteins many bad things happen. It appears that many autoimmune diseases are related to altered Heat Shock proteins. The following diagram is a good illustration of this.
Chronic inflammatory conditions are accompanied by a partial or sometimes large resetting of the immune system to a pro-inflammatory and pro-oxidant state. This response has gross implications also in the integrity of vascular components and may represent a sensitive therapeutic target of chronic, degenerative conditions. On the basis of these theoretical foundations, reported therapeutic applications for ozone therapy were the activation of the immune system in infectious diseases and cancer, and an improved oxygen utilization and release of growth factors that can reduce the extent of ischemic lesions in vascular diseases.
- Dr. P
This is a question that, when I give a lecture to either doctors or the lay public, most everyone gets it wrong. I am not talking about the chocolate one finds in a Hershey’s kiss or chocolate bar, because the problem with these is that they contain too much sugar. I would consider them a very unhealthy food. Ah, but chocolate with no sugar, that is a whole different story. What I would like to do is introduce everyone to the science of chocolate. First off, where does chocolate come from? It comes from the tropical Cacao tree, where it is found in pods.
Here we see a picture of the beans that are found in the pod. They are roasted and ground up, then turned into chocolate:
When one adds the sugar to these products, that is when the damage occurs. Dark chocolate has both cocoa butter and cacao fiber, both of which science has proven to have health benefits. The cacao fiber is the part of the cocoa bean where most antioxidants are found. This is why dark chocolate with high cocoa solids, and thus more cacao fiber, is considered healthy chocolate. So, now let us get to the science.
Dark chocolate is rich in minerals, such as iron, magnesium, and zinc (think anti-viral). The cocoa in the dark chocolate contains some amazing compounds called flavonoids and antioxidants, which have many health benefits. Chocolate is considered one of the best antioxidant foods known to man.
The following chart clearly shows this:
Antioxidants will neutralize free radicals. Free radicals are highly unstable molecules that are naturally formed when you exercise and when your body converts food into energy. Your body can also be exposed to free radicals from a variety of environmental sources, such as cigarette smoke, air pollution, and sunlight. Free radicals can cause “oxidative stress,” a process that can trigger cell damage. Oxidative stress is thought to play a role in a variety of diseases including cancer, cardiovascular diseases, diabetes, Alzheimer’s disease, Parkinson’s disease, and eye diseases, such as cataracts and age-related macular degeneration. Remember that oxidative stress is one of the major causes of the failure of the immune system (again think virus infections). There is no question that dark chocolate is a superb antioxidant. In a study published in the October 2017 Journal of Community and Hospital Internal Medicine Perspectives, the antioxidants in dark chocolate were found to reduce oxidative stress, which scientists think is the primary cause of insulin resistance and subsequently diabetes. By improving your body’s sensitivity to insulin, resistance is reduced and, in turn, the risk of diseases like diabetes decreases.
Also, at the center of chocolate’s health benefits are flavonoids. Most dark chocolate is high in flavonoids, particularly a subtype called flavanols, which are associated with a lower risk of heart disease and a variety of other conditions. As I have already said, some studies suggest chocolate or cocoa consumption is associated with a lower risk of both insulin resistance and high blood pressure in adults. These plant pigments are responsible for many of the health benefits of many fruits and medicinal plants, but chocolate may be a much more sensually pleasing vehicle. In addition, there is evidence that not only is chocolate rich in flavonoids, but that factors in chocolate somehow dramatically increase absorption of these compounds. The key flavonoids are procyanidins, which are similar to those found in grape seed extract, apples, berries, and pine bark extract. There are a few of these flavonoids that garner attention, such as PQQ.
PQQ (pyrroloquinoline quinone) restores youthful cellular function and can extend the lifespan. PQQ helps generate and restore mitochondria, especially in aging cells. It allows the mitochondria powerhouses to work more efficiently. Dysfunctional mitochondria contribute to body-wide degeneration. Many of the diseases of aging have one thing in common; namely, they involve mitochondrial degeneration. Remember that mitochondrial degeneration leads to shortening of our telomeres. Shorter telomeres lead to aging. But it turns out PQQ has many other beneficial aspects.
A team of researchers from China and Italy found that when PQQ was applied to human cells in culture, it delayed cellular senescence. A growing body of research suggests that reducing cellular senescence may lead to increased health and lifespan. Remember that a senescent cell is a cell that should have died but did not. These cells are like zombies, in that they attack normal cells. A senescent cell will increase inflammatory factors in various areas of the body. There is now a new name for this inflammation; it is called inflammaging. ‘Inflammaging’ refers to the chronic, low-grade inflammation that characterizes aging. We see that inflammation and aging are more or less synonymous. One causes the other to take hold. Recent studies have shown a way that PQQ may be able to slow aging even more, by reducing the activity of certain age-accelerating signaling pathways.
The following is a chart shows different foods and the amounts of PQQ they have:
Another important bioactive compound found in chocolate is Epicatechin, which is classed as a flavanol. Epicatechin is a natural flavonoid. It has been reported to possess an immense antioxidant effect, which contributes to its therapeutic effect against a handful of ailments. Epicatechin has many different functions. It will increase Nitric Oxide for increased vascularity and blood flow. It will lower cholesterol levels due to its natural antioxidant properties, while improving endurance and insulin sensitivity, regulating blood sugar levels, and stimulating muscle protein synthesis. A very fascinating property of Epicatechin is that it is a myostatin blocker.
Myostatin is a type of protein called a myokine, which limits the level of muscle growth. Animals lacking myostatin, either due to a defective gene or because they have been treated with compounds that inhibit production, show huge increases in muscularity. In other words, the brakes on muscle growth are removed by the inhibition or absence of myostatin.
Myostatin became famous within the bodybuilding community. It has been considered the holy grail of muscle building.
Below is an example of a cow which has a gene that blocks myostatin. If you block myostatin in a human, a similar result will be obtained:
A number of supplements have been designed to inhibit myostatin production over the past 20 years, but these have all been discarded as not working well. What is the exact epicatechin/myostatin connection? Research with epicatechin indicates that it increases levels of Follistatin, a special type of protein found in the muscles. Follistatin binds to and thereby inhibits the actions of myostatin in the body. In a nutshell, more Follistatin equals less myostatin, which in turn means more muscle mass and less fatty tissue.
A study conducted on males of an average age of 40 showed that approximately 170mg of epicatechin per day, dosed at 2mg per kg of bodyweight, resulted in almost a 50% increase in Follistatin and a 16.6% decrease in myostatin, alongside a strength increase of 7%. In a second study, researchers provided participants with 50-200mg of epicatechin a day and were amazed to find that their Follistatin levels were 250% higher after just 5 days! In a study performed on mice, researchers found increases in nitric oxide and endurance that persisted even in the absence of exercise. In other words, epicatechin supplementation offers bodybuilders the potential for better muscle pumps and endurance even when they are not training. The same may hold true for the average person.
As one can see, chocolate is one of the best health foods one can eat. Just remember to leave the sugar out. Do as I do, buy unsweetened chocolate and melt it in the microwave. When it is melted, then add some cinnamon (another great supplement) and Stevia as a sweetener. Sometimes we will add a bit of rum to spice up the flavor. I will typically buy my chocolate in bulk. Also remember that chocolate is much like wine; it can vary in taste by where it is grown and the growing conditions.
- Dr. P
Just exactly what is the novel Coronavirus and how is it different from the regular flu? Seasonal flu is an “all human virus”. The DNA/RNA chains that make up the virus are recognized by the human immune system. This means that your body has some immunity to it before it comes around each year. Immunity is obtained in one of two ways. You obtain it through exposure to a virus, or by getting a flu shot. Novel viruses typically come from animals. Usually these viruses only transfer from animal to animal (pigs in the case of H1N1) (birds in the case of the Spanish flu). But once, one of these animal viruses mutates, and starts to transfer from animals to humans then it’s a problem. Why? Because we have no natural or acquired immunity. The RNA sequencing of the genes inside the virus isn’t human, and the human immune system doesn’t recognize it so, we can’t fight it off. Many times, when the virus jumps from an animal to a human it does not have the ability to jump and infect another human. However, when the virus mutates then jumps from a human to a human we have a contagion phase which is what we are now experiencing with the Covid-19 virus. This seems to be the mechanism of the Covid-19 virus that began in an animal market in Wuhan China. Humans have no known immunity to this virus and thus initially no medicines have effectiveness with Covid-19. We now have some knowledge of the Covid-19 virus. The good news is that it still behaves similar to other viruses so we have some basis for treatment. I have covered some of these techniques in some of my other blogs so please excuse the redundancy.
WHAT ARE THE COMPONENTS OF OUR IMMUNE SYSTEM
Becoming symptomatic from the Covid-19 virus depends on how our immune system responds to the problem. One may only have the sniffles or one could end up in the ICU and be gravely ill. Our immune system consists of two main parts. One is called the innate immunity while the other is called adaptive immunity. The following illustrations show the differences between these two systems.
In the first diagram we see the two types of immune systems. The innate system is immunity that is naturally present and is not due to prior sensitization to an antigen from, for example, an infection or vaccination. While adaptive immunity is activated by exposure to pathogens such as the Covid-19, and uses an immunological memory to learn about the threat and enhance the immune response accordingly. The second diagram shows the innate immune response and adaptive immune responses of a Covid-19 infection. The Covid-19 infects macrophages (a form of white blood cell), and then macrophages present Covid-19 antigens to T cells (an immune cell). This process leads to T cell activation and differentiation, including the production of cytokines associated with the different T cell subsets followed by a massive release of cytokines for immune response amplification.
WHERE DO THE PROBLEMS START ARISING ESPECIALLY IN THE ELDERLY?
Let us discuss immunity more in lay terms. Our immune systems have two sets of defenses against viruses and other pathogens. Our first-line army of cells are called leukocytes (WBCs). They attack invading microbes within minutes to hours, and a second-line force of precisely targeted antibodies and T cells that surge to the battle front as late as several days after. The problems start arising when either the patient has some predisposing condition which weakens his immunity or age is catching up to him. We call the phenomena of aging of the immune system Immunosenescence.
With advancing age, the body has fewer T cells, which produce virus-fighting chemicals called cytokines. By puberty, the thymus gland is producing tenfold fewer T cells than it did in childhood. By age 40 or 50, there is another tenfold drop. That leaves the body depleted of T cells that have not yet been programmed to defend against a specific microbe. Fewer such “naïve T cells” means fewer able to be deployed against a never-before-seen microbe such as the Covid -19. These T cells are battle hardened soldiers but they are exposed to an enemy they have no experience with. It was as if our army were to wage battle against aliens. Complicating the problem, there are fewer soldiers that are dealing with attackers that they never experienced before, namely the coronavirus. The body does retain the “memory T cells” that learned to fight attackers in youth, which is why immunization against smallpox and many other viral diseases lasts decades. Even before T cells enter the fray, other cells recognize invaders and dispatch natural killer cells and other soldiers to destroy as many as possible in the first few hours after infection. Then these same front-line cells literally show the virus to T cells, saying in essence, this is the enemy and instructing them to produce virus-killing compounds. But this communication doesn’t work as well as we get older. The instructor cells grow scarce and start giving garbled messages. T cells response is too little and too late. Antibodies are made by B cells, and their decline is less precipitous than the fall-off in T cells. But older B cells can’t produce as much of the antibodies as when they were new. Specifically, they have lower levels of the molecules that rearranges their genome so as to produce never-before-seen antibodies to a never-before-seen virus. THE BOTTOM LINE IS THAT NOT CHRONOLOGICAL AGE ALONE DETERMINES HOW ONE DOES IN THE FACE OF A LIFE-THREATENING INFECTION SUCH AS COVID-19. Having multiple chronic diseases and frailty is in many ways as or more important than chronological age. An 80-year-old who is otherwise healthy and not frail might be more resilient in fighting off infection than a 50-year-old with many chronic conditions. The reason is that the older person may have a younger immune system.
OZONE: ONE OF THE ALLIES TO STRENGTHEN THE IMMUNE SYSTEM AND FIGHT THE VIRUS
We are very fortunate to have one of the only EBO2 machines available on the east coast. EBO2 stands for Extracorporeal Blood Oxygenation Therapy. This machine is essentially a dialysis machine that utilizes ozone rather than water to perform a “dialysis” procedure. We are not targeting kidney patients but rather a wide variety of the population from professional athletes to the average citizen. Typically, we perform EBO2 to enhance general health and for anti-aging principles. But with the current situation our emphasis has shifted a bit but in the long run the goals are still the same. We are looking for methods to boost our immune system and medical Ozone is one way to do this.
There is much scientific literature on the use of medical ozone to help eliminate viruses. For more than 100 years, ozone has been considered a virus killer in the nature. It has been widely used by people for disinfection, sterilization, deodorization, detoxification, storage, and bleaching tanks due to its strong ozonating properties.
The virus found in Wuhan and SARS (which respond well to Ozone therapy) virus both belong to the Coronavirus family. Researchers found that the Covid-19 virus is 80% similar to the SARS virus in their genome sequences. It is reasonable to predict that ozone is equally effective in preventing and controlling the new Coronavirus. Most research efforts on ozone's viricidal effects have centered upon ozone's propensity to break apart lipid molecules at sites of multiple bond configuration. Once Ozone interacts with these compounds it produces compounds called Ozonides. Indeed, once the lipid envelope of the virus is fragmented, its DNA or RNA core cannot survive. The following diagram shows this quite well.
There are a number of different methods of utilizing medical ozone. However, we only utilize the intravenous method. We utilize a machine called the EBO2 machine. I wrote a detailed blog about the EBO2 machine and its mode of action (blog is found in website stemcellorthopedic.com). The EBO2 has a variety of benefits for the body but for now we will limit out comments to its anti-viral abilities. With EBO2 the entire blood supply passes a number of times thru a dialysis filter after the blood is automatically mixed with ozone gas. Not only are we stimulating the immune system with the ozone but we are also killing viruses in the blood. The unit allows extracorporeal blood oxygenation, ozone exposure and blood filtration. The Ozonides also seem to have a significant effect on cytokine production. Cytokines are messenger molecules that seem to have a significant effect especially on cells of the immune system. The importance of cytokines cannot be understated. Essentially all medical conditions are a result of an imbalance of cytokines. The reaction of the immune cells to the Ozonides causes an increase in cytokine production enabling the body to kill viral cells, kill microbes including the dreaded Lyme’s disease, and potentially cancer cells. Ozone is a potent regulator of the immune system. This means that when the immune system is activated (autoimmunity), ozone will calm it down. Also, when the immune system is depleted (infections, cancer, etc.), ozone will stimulate it. This occurs by ozone’s unique interaction with white blood cells to release immune messenger cytokines. These cytokines are ultimately produced by cells of the immune system. The Ozone therapy stimulates various pathways in the body that specifically deal with oxidative stress and its ramifications. Most of the serious pulmonary and other health problems caused by the Covid-19 virus develop from a phenomenon called a “CYTOKINE STORM”. A cytokine storm occurs when there is excessive immune response between cytokines and immune cells. The symptoms are high fever, redness, swelling, extreme fatigue and nausea, which can be fatal in some cases. The following two illustrations show aspects of a cytokine storm. The second diagram shows the damage that occurs in the body.
The goal of our Institute is to prevent the patient from ever reaching the point where they are close to a cytokine storm. This is accomplished by a sort of balancing act. If the immune system is stimulated too much the storm will develop. There is too much inflammation which is causing oxidative damage which results in tissue damage. Many infections including the Covid-19 virus overwhelm the body by the production of Reactive Oxygen Species (ROS) which are very similar to free radicals. The reactive oxygen species are the contributors of oxidative stress which lead to various diseases and disorders such as cardiovascular disease, cancer, aging, and various neurodegenerative diseases. In the case of Covid-19 we see mainly pulmonary and kidney problems. The best way to prevent oxidative damage is to fight it with powerful anti-oxidants. This is where EBO2 therapy shines. Most battles in the body are a result of a tug of war in various pathways in the body.
One very important pathway is called the NRF2 pathway (nuclear factor-erythroid 2-related factor 2). The NRF2 pathway is the master regulator of antioxidant, detoxification and cell defense gene expression. It regulates over 600 genes involved in cellular protection and anti-oxidant defenses. It modulates numerous genes responsible for cognitive processes, inflammatory responses, rebuilding tissue, immune system response. The Nrf2-mediated antioxidant system is essential to protect the lungs from oxidative injury and inflammation. Furthermore, NrF2 stimulates another pathway called the NQ01 pathway. The Nq01 is intimately involved with NAD production and insures a proper NAD/NADH ratio. of antioxidant, detoxification and cell defense gene expression. Considering the significant impact of the Nrf2 pathway on the pathophysiology of both host cell and virus, Nrf2 modulators may be able to serve as a promising supplement for viral diseases by therapeutic modulation of virus-induced oxidative stress in the near future. Well the future is here in that EBO2 is a potent stimulator of the NrF2 pathway. The NrF2 pathway seems to inhibit another very important pathway called the NF-κB-r pathway. NF-κB has long been recognized as a point of convergence of inflammation, aging and disease. Remember, all diseases including the Covid-19 virus really either get eliminated or get a foothold by their effects on various pathways in the body. Below is an illustration of the NrF2 pathway and its’ relationships to other pathways.
As we can see, the EBO2 machine and Ozone can work in two distinct ways. First, there is the ability to actually kill viruses in the body by destroying their protective coating. Secondly, and perhaps more importantly they remove the “stranglehold of oxidative stress” on the immune system thus allowing it to more efficiently perform its job.
One final note on Ozone therapy. On March 24 the following letter was written. “After evaluating possible insights, the letter signed by Dr. Luigi Bertinato, Head of the President's Scientific Secretariat, says that since the proposal to use oxygen ozone "is supported by clinical centers experienced in the treatment of viral pneumonia, the Istituto Superiore di Sanità considers it appropriate that the treatment itself can be carried out, after acquiring the patient's informed consent. Essentially, the Italian government feels Medical Ozone seems to have great promise in the treatment of Covid19.
NAD, AN IMMUNE BOOSTER
Another very important aspect of EBO2 is the effect it has on NAD production and subsequent stimulation of the Sirtuin genes. We take this one step further by supplanting the NAD produced by the EBO2 with intra venous delivery of NAD. Mounting evidence points to NAD+ as one of the major modulators of immuno-metabolic circuits, thus regulating immune responses and functions. Recent studies show impaired host NAD+ metabolism during chronic infections and inflammation, suggesting NAD+ replenishment as an avenue to ameliorate deleterious inflammatory responses. Besides playing key roles in various cellular enzymatic reactions and signaling pathways, mounting evidence suggests that NAD+ dictates the host’s innate and adaptive immune responses. Thus, the evidence is fairly convincing that NAD+ may have significant beneficial effects on our immune system. For this reason, it is one of our weapons in boosting immunity.
NIH has a clinical study that has been completed but not yet published to study NR's positive effects on healthy peoples innate immune systems. There are two types of immune systems the body uses to combat viral infections. Let us review it one more time. The first is the innate system which offers a first line of defense by preventing pathogens from taking hold if they enter the body. This is what can prevent you from being infected in the first place. The second system is the adaptive system where once a pathogen has taken hold, the body develops a specific response to the pathogen. This includes both antibody responses as well as cell-mediated responses. Boosting NAD has shown benefits in both the innate system as well as the adaptive system. As adults get older both immune systems decline along the same time frame that NAD declines in the body. The bottom line is that the NAD has direct effects on the Sirtuin Pathways which seem to influence most of the other pathways in the body. We must also remember that NAD+ is of prime importance in the production of ATP. All cells need ATP as a source of energy. NAD+ itself is also used by various enzymes to repair DNA damage. Here is an illustration of NAD benefits.
GENERAL INTRAVENOUS THERAPY
At most of the med-spas, when you ask the employees about how various IV therapies work they state that it improves the immune system and makes one feel better. But when pressed as to how it improves the immune system they are hard pressed to give an answer. We give the answers below.
We have a wide variety of intravenous methods to boost immunity. I will mention a few of them. We have already mentioned NAD given via an IVroute. NAD has far ranging impacts on various functions in the body including our immune system. Another type of intravenous therapy is called Myers cocktail. Myers’ Cocktail is a formula of intravenous vitamins and minerals that was pioneered by the late Dr. John Myers, MD. The “Cocktail” includes magnesium, calcium, B-vitamins (including B12), and Vitamin C and is given by a slow IV push or slow infusion to achieve concentrations of nutrients that are not obtainable with oral administration. It appears that this cocktail will hopefully increase one ability to respond to immune challenges. The vitamin C is especially important. It is a potent antioxidant and a cofactor for a family of biosynthetic and gene regulatory enzymes. Vitamin C contributes to immune defense by supporting various cellular functions of both the innate and adaptive immune system. Vitamin C deficiency results in impaired immunity and higher susceptibility to infections. We always hear Vitamin C is helpful but what is the real mechanism of action? Vitamin C supports epithelial barrier function against pathogens and promotes the oxidant scavenging activity of the skin, thereby potentially protecting against environmental oxidative stress. Vitamin C accumulates in phagocytic cells, such as neutrophils (WBCs), and can enhance chemotaxis, phagocytosis, generation of reactive oxygen species, and ultimately microbial and viral killing. We have other similar intravenous therapies that seem to boost immunity. These are more or less variations of the Myers cocktail but seem to have more effects on the immune system.
Another type of intravenous formula is called Immune Boost. This is somewhat similar but yet different than Myers cocktail. One thing they all have in common is Vitamin C. The following shows the multitude of Vitamin C benefits. We must realize that when you are sick you need a good bit more Vitamin C. The best benefit from Vitamin C is when it is in your blood, hence IV route. There are some studies in China that seem to support the use of Vitamin C in Covid 19 virus. Will Vitamin C cure the Covid -19 probably not, but it should be able to alter its course for the better. I have a diagram on the various aspects Vitamin C has upon the body’s immune system.
Another aspect of our IV therapy involves Glutathione. This powerful antioxidant is one of most protective molecules in the human body. There are two different forms of glutathione: reduced glutathione (GSH, or L-glutathione), which is the active form, and oxidized glutathione (GSSG), the inactive form. As GSH patrols the cellular environment and puts out oxidative “free radical” fires, it becomes oxidized itself and inactive, thus turning into GSSG. Fortunately, inactive GSSG can be recycled back into the active GSH form, thanks to an enzyme called glutathione reductase. When this enzyme is overwhelmed and too much oxidized GSSG accumulates (as compared to the active GSH), your cells become susceptible to damage. Glutathione is such an important antioxidant to the human body that a scientific study suggests that the abundance of glutathione in the cells can help predict the life expectancy of that human. Glutathione has also been shown to be a powerful anti-inflammatory agent because it inhibits the production of most inflammatory cytokines. Glutathione can also help repair cells that were damaged by radiation, pollutants, stress, infection, and a range of other ailments. Surprisingly enough, glutathione can also slow the process of aging in the cells. As we age, our cells begin to lose their ability to self-repair and to produce strong antioxidants. Increasing our intake of glutathione can help replenish or replace the antioxidants lost from aging and slow down the aging and deterioration of our cells and aid in the self-repair of the cells to prolong their functionality and lifespan. As an antioxidant, glutathione removes oxygen radicals from the body which can harm other cells in the body and cause disease and deterioration. While vitamins C and E are also antioxidants, glutathione has the added benefit of already living within each of your cells allowing it to perfectly placed to do its job. One problem with glutathione is that it has a poor oral absorption rate. It is well absorbed when given via an intravenous route.
WHY IS OUR IV THERAPY UNIQUE?
What will make our IV therapy unique is that we will add some unique products to our IV formulas. We will include some cytokines in very small dosages. For instance, one of these is GCSF. GCSF is called granulocyte colony stimulating factor. GCSF acts in a similar method as to a medicine called Neupogin. Neupogin is a medicine given to patients who have taken chemotherapy and their blood count became low. It especially helps to build up their white blood cell count (WBCs). Remember, WBCs fight viruses. We will give the GCSF in a few different ways. We have an oral form that is absorbed under the tongue, we can deliver it via a patch which utilizes a weak electrical current and is called iontophoresis. Lastly, we will give some low dose intra venous therapy.
Another addition is IFNγ, or type II interferon. It is a cytokine that is critical for innate and adaptive immunity against viral, some bacterial and protozoal infections. IFNγ is an important activator of macrophages. The importance of IFNγ in the immune system stems in part comes from its ability to inhibit viral replication directly, and most importantly from its immunostimulatory and immunomodulatory effects. IFNγ is produced predominantly by natural killer (NK) and natural killer T (NKT) cells as part of the innate immune response, and by CD4 Th1 and CD8 cytotoxic T lymphocyte (CTL) effector T cells once antigen-specific immunity develops. Again, we can deliver this a few different ways to the patient.
The last product I would to mention is one called Immunexx. Like some of the other cytokines, this is a compound made by the Canadian company we are working directly with called Viatrexx. Immunexx is an interesting compound. It has a number of interesting components that seem to be significant immune boosters. Again, this can be delivered to the patient in a number of different ways. We also produce our own blend of cytokines that seem to promote healing etc. We have been using this for uyears with excellent success.
MEDICATIONS AND SUPPLEMENTS
We certainly recommend good multi-vitamins. However, we have some specific recommendations when it comes to immune boosting. Luckily, we have access to some of these.
VITAMIN C 5g/day (25mg/pound
VITAMIN D 5000IU/day
ZINC is a mineral that's commonly added to supplements and other healthcare products like lozenges that are meant to boost your immune system. This is because zinc is essential for immune system function. Zinc is needed for immune cell development. A deficiency in Zinc significantly affects your immune system's ability to function properly, resulting in an increased risk of infection and disease, including pneumonia.
Oral NAD 600mg/day
ELDERBERRY SYRUP 1 tsp/day
UMCKA (Pelargonium sidoides) An herbal remedy of a species of South African geranium, Umcka plays a role in the production of a specialized protein, called cytokines, that may protect the body’s cells from viral infection.
BETA GLUCANS effects are caused by stimulation of both cellular and humoral immune reaction resulting in lower viral load.
RED MARINE ALGAE: seems to have antiviral properties. Dosages depends upon the brand.
CURCUMIN. Curcumin is the main active compound in turmeric. It has powerful anti-inflammatory properties, and animal studies indicate that it may help improve immune function
LICORICE contains more than 20 triterpenoids and nearly 300 flavonoids. Triterpenoids are widely found in plants. It is found that triterpenoids have a variety of pharmacological activities including anti-inflammatory, anti-diabetic, anti-cancer, regulation of immune function, etc. Among them, only two triterpenes, GL and GA have been reported to have antiviral effects. They can weaken virus activities by inhibiting virus gene expression and replication, reducing adhesion force and stress, and reducing HMGB1 binding to DNA.
Medicinal mushrooms have been used since ancient times to prevent and treat infection and disease. Many types of medicinal mushrooms have been studied for their immune-boosting potential. Over 270 recognized species of medicinal mushrooms are known to have immune-enhancing properties.
I am sure that I can more to the list but this should suffice for now. The above is in addition to the supplements that one takes to maintain general health. For instance, mine would include Neo-40 (nitric oxide supplement), Resveratrol, Pterostilbene, Green tea extract, and StemXcell, and some other supplements.
SENSECENT CELLS AND SENOLYTIC AGENTS
Cellular senescence is a phenomenon characterized by the cessation of cell division. A senescent cell is one that should have died but did not. It can act like a zombie in the body. Cellular senescence can be initiated by a wide variety of stress inducing factors. These stress factors include both environmental and internal damaging events, abnormal cellular growth, oxidative stress, autophagy factors, among many other things. Aging and senescent cells have a great impact in both innate and adaptive immune systems. This is a process known as immunosenescence which I have already spoken about. Immunity declines during aging, as shown by the increased susceptibility to infection by both previously encountered and new pathogens and by the decreased efficacy of vaccination. We are aware that induction of senescence alters leukocyte, and specifically T cell, function. An effective immune response against viral infections depends on the activation of cytotoxic T cells that can clear infection by killing virus-infected cells. So, the bottom line is if we can eliminate some senescent cells it would probably make our immune systems function better. Remember, our immune system is responsible for removing senescent cells. If we can take away some of this burden than our immune system will function more efficiently. However, it is important to retain some senescent cells. I strongly advise people to take at least an over the counter senolytic agent on a temporary basis. Make sure these compounds contain Fisetin, Quercetin, and Piperlongumine. In our office we use some very powerful senolytic agents. These include quercetin and a medication which we are using off label.
The FDA has issued an emergency authorization of the anti-malaria drug Hydroxychloroquine for Covid-19 virus. Although the evidence seems to be anecdotal, there does appear to be efficacy. I ordered the dosages for myself and my family. I have also included a dosage of a Z-pack (Azithromycin). I would recommend the Hydroxychloroquine to be taken if one tests positive or if one has symptoms of Covid -19 virus. The dosage should be two tabs twice a day on the first day followed by one tablet twice a day for five days. The Z pack should be started at the same time.
Another aspect of medications includes certain peptides. Peptides are naturally occurring biological molecules. Peptides are found in all living organisms and play a key role in all manner of biological activity. Some of the peptides we will utilize include Thymosin alpha-1 and Thymosin Beta 4. Thymosin alpha-1 is the most recommend peptide for immune stimulation. This should be used as a treatment adjuvant and a prophylactic aid that can help with many conditions beyond viral illness! Most will dose it at 450mcg daily. Thymosin Beta-4 stimulates Natural killer (NK) cells which are essential for defense against tumors and virus-infected cells. These cells are activated in by INF-Gamma. IFN-gamma is activated by IL-18 which TB4 upregulates. Thus, TB4 has been studied for many immune related diseases. One other peptide to consider is LL-37. This is a peptide made by mesenchymal stem cells. It is a very strong bactericidal and viricidal agent.
There are some biologics that are currently under consideration. Remdesivir is a broad-spectrum antiviral drug that interferes with a virus’ ability to replicate. It was originally developed to treat Ebola but had only limited success. However, a study from 2017 showed that remdesivir was able to successfully stop SARS and MERS — sister coronaviruses to the new strain — in both human cells and animal models. In February, Chinese scientists found that remdesivir successfully blocked the novel coronavirus, SARS-CoV-2, from replicating in human cells. Lopinavir and ritonavir, an antiviral drug combination was initially developed to treat HIV, but it turns out it works on other viruses as well. The drugs are given together because lopinavir breaks down very quickly on its own, and it lasts longer when paired with ritonavir. Similar to chloroquine and remdesivir, scientists discovered in 2004 that lopinavir was moderately effective at stopping the original SARS virus from replicating in human cells. When given in combination, lopinavir and ritonavir also helped treat SARS in human patients. There is also talk of utilizing some of the biologics that are used for autoimmune diseases.
A simple and promising treatment which is being considered is the use of the Contrad anti-inflammatory patches (AI). I use these in my stem cell practice on a daily basis. These patches are revolutionary. They are registered with the FDA. They have very powerful anti-inflammatory agents which can be of great importance in the face of pulmonary problems resulting from a cytokine storm. These are patches which will have the gel placed on a patch and then they are placed on the lung and left for about 6-8 hours. The gel contains penetrating molecules which drive the cytokines down deep. There are currently some studies going on the Milan Italy using these patches. From what I am hearing there seems to be some promising results.
PERIPHERAL BLOOD STEM CELLS
This is a type of stem cell coming from the patient. It is found in the blood and is prepared in a propriety method. What is of significance here is that these cells seem to make the immune system younger and healthier. Remember, the reason why some people exposed to the virus never get ill is because of their immune system. As I said earlier a healthy immune system is a healthy patient. One major effect that these cells have on the immune system is that they will make the telomeres of the immune system cells longer. Remember, the telomeres are found at the end of the DNA strand. The shorter the telomere the less effective the cell would be in performing its tasks. Longer telomers will most of the time either prevent or ameliorate many different health issues including viral infections by virtue of making the immune system healthier. Remember what we said about immunosenescence. Short telomeres cause senescent cells to form. So, these peripheral blood stem cells can certainly be a potent weapon in the battle against the Covid-19 virus. The process is quite simple. First, on day one we stimulate the bone marrow to release large number of the cells into the circulation. On day two the blood is taken from the patient and is processed. On day three the cells are given back to the patient and hopefully perform their magic behind the scenes.
WHAT HAVE I DONE, WHAT AM I DOING, WHAT WILL I DO???
I am faithful in doing my exercises everyday
I practice the precautions recommended by the CDC including wearing a mask and gloves whenever leaving home. Also follow social distancing
I take my supplements including a number on the list. It is about a handful every day. I will make sure that I take extra CURCUMIN.
I have recently received IV vitamin C, NAD, and GLUTATHIONE. I will probably get more of the same. It is probably not a bad idea to get IV Vitamin C on a weekly basis for the next few weeks
I have done an EBO2 and Peripheral blood stem cell treatment within the last few weeks. I intend to give myself another EBO2 in the near future.
A few weeks ago, I took my senolytic agents so we are good there.
If I become symptomatic or I suspect an exposure. I will take Hydroxychloroquine and a Z pack, take higher doses of vitamin C and NAD including intravenous delivery. I will perform another EBO2.
I will take Berberine to help control my blood sugar.
If I become symptomatic in chest area will use the AI patches. The results from Milan seem to be very promising
CUT OUT ALL SUGARS!!!! All they will do is add to the inflammation of the immune system.
I will go on the oral cytokine formula that we give to most of our patients
Also, it would not be a bad idea to pray.
HOW ABOUT IMMUNITY??
How well a person’s immune system remembers SARS-CoV-2 is called immune memory. It helps our bodies avoid reinfection by a bug we’ve had before. Immune memory influences the potency of life-saving treatments and vaccines. For now, in people who have had the Covid-19 virus, it appears unlikely that they will get it again. But, and this is a big but, we cannot say for sure. When a pathogen breaches the body’s barriers, the immune system will churn out a variety of immune molecules to fight it. One subset of these molecules, called antibodies, recognizes specific features of the bug in question and mounts repeated attacks until the invader is purged from the body. Antibodies can also be a way for clinicians to tell if a patient has been recently infected with a given pathogen, even when the microbe itself can no longer be detected.
COVID-19 packs a stronger punch than the common cold, so antibodies capable of fending off this new coronavirus may have a shot at lingering longer. Typically, the more severe the disease, the more resources the body will dedicate to memorizing that pathogen’s features resulting in a stronger and longer lasting the immune response. Complicating matters further is the biology of SARS-CoV-2 itself. Viruses aren’t technically alive. They contain genetic instructions to make more copies of themselves but they lack the molecular tools to execute the steps to reproduce. Therefore, they must hijack living cells to complete the replication process. After these pathogens infect cells, their genomes (genetic material) often duplicate sloppily, leading to frequent mutations that persist in the new copies. Most of these changes are inconsequential or lead to revolutionary dead ends. Occasionally, however, mutations will alter a viral strain so substantially that the immune system can no longer recognize it and subsequently sparking an outbreak even in populations that have seen a previous version of the virus before. Viruses in the influenza family are the poster children for these transformations which is in part of why scientists create a new flu vaccine every year.
WHERE DOES THE ANSWER TO CONQUERING THE COVID-19 LIE?
These next two diagrams most likely hold the solution to defeating the Covid-19 virus. The solution to the virus lies in one or more of these pathways. These diagrams represent the stem cell aging pathways. REMEMBER HOW STEM CELLS AGE IS HOW WE AND OUR IMMUNE SYSTEM AGES.
MORE IMPORTANTLY, I HAVE A SAYING I USE IN MY LECTURES “CELLS NOT DOCTORS HEAL PATIENTS”. We can manipulate the cells in methods I have already mentioned but ultimately, THE CELL WILL HEAL THE BODY.
No one knows for sure which pathways are involved. Most all of the techniques and procedures mentioned in this report will affect certain of these pathways. The answer is right before our eyes in these two diagrams. These diagrams represent the cause and solution to the Covid-19 virus. How these pathways are stimulated can mean health or sickness!!
Manipulate these pathways and you will manipulate the immune system. Some food for thought!!
This is another scheme of the pathways.
The next diagram gives a view of the various subpopulations that are affected by the Covid-19 virus.
A FINAL COMMENT OR TWO.
We have been practicing telemedicine for a number of years now so we are still a phone call away to discuss concerns and questions.
IN THE BIT OF LEVITY, there is a good song that seems to sum up times: THIS IS THE OLD CHUCK BERRY SONG The title of it is “RIDDING AROUND IN MY AUTOMOBILE, LISTENING TO THE RADIO, WITH NO PARTICULAR PLACE TO GO” Seems to be a good song for the times where we have stay at home orders with no place to go !!!!
Stay safe and practice CDC RECOMMENDATIONS and consider some of these other options. Please realize that these statements have not been evaluated by the FDA.
- DR. P
Many in the chiropractor community wish to be involved in Regenerative Medicine. Unfortunately, there are some that are exposing themselves to a variety of potential problems both legally and professionally by choosing to use umbilical cord products, amniotic products, and exosomes.
First off, these products typically do not have any stem cells -- yet these same doctors are touting the fact that the product does have stem cells. That leaves the Chiropractic physician open to claims of fraud.
Secondly, the FDA has stated unequivocally that if these products are to be used in the United States, they need either a Biologics license or an Investigational new drug application. Both entities are costly and time consuming, and currently none of these products have this classification. Thus, these products are in violation of the existing FDA guidance.
Fortunately, we now have We now have SIGMOLECS® Technology, which is an alternative that can allow the Chiropractor to become involved in Regenerative Medicine in keeping with the current guidance regulations and local state chiropractic boards. I, myself, have used this technology for the past several years on thousands of patients with superb results and essentially no side effects.
SIGMOLECS technology is an advanced chemical profiling through structural assembling of key molecules, mostly proteins and peptides, that form actuated molecules. It accomplishes this by specifically improving their bio-activity in solution and in vivo by increasing their transmembrane penetration. This creates precise specificity of action, particularly in intracellular signaling. This is essentially the method that the body uses to heal itself and is the essential basis of Regenerative Medicine and cytokine therapy.
SIGMOLECS molecules induce signals to key amino acid sensors that govern gene expression of amino acid metabolism that then trigger specific physiological and metabolic activity. The nuts and bolts of Sigmolecs molecules is quite simple. Sigmolecs® molecules are really like microchips carrying the information we want to program into the patient. So, once designed and synthesized Sigmolecs are put into a proprietary gel that delivers them trans-dermally, while at the same time causing essentially no reaction in the skin. We must also be cognizant of the fact that if you don’t have the right delivery system for your clinical application, even the most potent medicine will not work.
These SIGMOLECS molecules are structured according to key amino acid sensors to trigger specific regenerative tasks. This is done by grafting bioactive peptides or amino acid (AA) sequences onto a source molecule, usually a natural source of protein like Soy protein or Collagen peptides. This becomes the template for the Sigmolecs molecule that will be structured to have very specific bioactivity. Many of the mini-proteins found in plants are desirable for this work because of the resistance they contribute to enzymatic degradation, and their native structure provides a chemical template conducive to various sequence designs. Overall, this allows the synthesis of specific bioactive peptides while silencing signals and gene expression encoding undesirable processes; such as, proteinase secretion and expression of associated catabolic cytokines.
Sigmolecs® molecules are configured and assembled to mirror highly specific intracellular signaling factors. These are the same factors that stem cells and other regenerative cells utilize to accomplish repair of damaged tissue. They are essentially clones of what the body produces.
SIGMOLECS designer molecules are part of the delivery package; that is, the gel carrier. It contains Sigmolecs® Technology in that it designs scaled molecules that can easily penetrate the skin and enter deep tissue. The molecules are fashioned according to sequences that are ‘skin friendly’ and can facilitate navigation through cell membranes. For example, when using native peptides from suis collagen peptides the molecules provide a chemical template to structure therapeutic specificity in a repair combination. The basic gel amalgam provides structural molecules conducive to crossing skin and cell barriers, and in this sense, is a completely functional product that is both a carrier and a therapeutic gel in one. This gel enables the transfer of large molecules and solutes through cutaneous channels that normal dermal formulation or patches could not deliver. It allows penetration of large molecular weight molecules to cross the Stratum Corneum, deeply penetrating the epidermis and dermis, reaching vascular and cellular targets through tissue permeability akin to injection, but without any invasive needling.
There are two different type of products which are available in gel monodoses to be used with a patch. The first gel monodose is called the AI (ANTI-INFLAMMATORY) monodose which is upgraded to code for IL-10 and IRAP. These two entities are considered master anti-inflammatory cytokines. The raw material used to design the therapeutic Sigmolecs P3 AI gel is Soybean protein. This plant contains several small proteins that are already anti-inflammatory in nature, but more importantly, that are conducive to structural modification. Many drugs have been fashioned from plant molecules; most are proteins such as cytokines. Many come from Tobacco plant cell cultures, such as IL-2, IL-4 and the famed Neupogen otherwise known as G-CSF! Even Human Interferons have been successfully produced from plants, and many more human synthesized cytokines originate from plants.
The Anti-Inflammatory sequence provides vascular support, regulation of blood flow and platelet function, and very importantly, inhibition of inflammatory cytokines specifically, IL-6, IL-8 and TNF. It mediates the inflammatory response to prevent and reduce edema and pain while also contributing considerable analgesic effect without invasive pain procedures.
The RG REGENERATIVE MONODOSE GEL invokes cell differentiation especially to chondrocytes and keratinocytes. The raw material used to design the therapeutic SIGMOLECS® P3 RG gel is suis collagen. The peptides extracted from this source naturally regulate neutrophils especially in stem cell procedures while at the same time they stimulate and induce mobilization of transplanted adult stem cells. The SIGMOLECS® combination of structures in the P3 RG gel regulates the cell cycle particularly by signaling resting phase cells to migrate to areas of repair. It combats oxidative reactions in synovial fluid while stimulating chondrocytes to repopulate decellularized tissue at the site of injury. It also provides the extracellular matrix with signals, such as those that mimic hematopoietic cytokines, which reinforce procedures such as PRP and stem cells treatments. Furthermore, in Regenerative Medicine, the use of RG gel monodose post regenerative therapy will enhance the treatments by sustaining stem cell niches enhancing the success of clinical treatments.
Moreover, suis collagen peptides, in particular, are structured cleaner than other types of collagen which allows for a larger spectrum of sequencing for specific therapeutic action. These actions include sequences that mimic growth factor signaling such as Insulin Like Growth Factor (IGF) and Fibroblast Growth Factor (FGF.) The suis collagen peptides have more affinity for human synthesized growth factors than other collagen sources. The RG gel is particularly good to apply after a stem cell treatment. It will enhance treatment protocols by providing the regenerative cytokine signals and also provides the needed elements to the extracellular stem cell niche. It signals repair pathways while inhibiting TNF-override that often occurs during repair processes.
Please notice that the opinions in this article are solely my own professional opinions intended for professionals only.
Dr. Joseph Purita
These gel monodoses are now available for sale in the U.S.A to health care providers.
For details please contact:
Bob Colucci, at PuRxCell
Phone number: 561-350-4465
Email: [email protected]
Many people know me from my blogs that I write on the website. Unlike most people, I do not use ghost writers. I write my own material. There is another group of people who know me from my comments on LinkedIn. The above represents one of the articles I recently commented upon on LinkedIn. What I find interesting is that the above article gives a glimpse into my journey in Regenerative Medicine. As I stated, many years ago when I became involved in Regenerative Medicine, it was the dogma that Mesenchymal Stem Cells were the only cells that accomplished repair. Well, that certainly has changed, as can be seen by the 1900+ hits this short article has gotten. We now know that a symphony of cells accomplish repair.
This article reminded me of my journey into the field of Regenerative Medicine. The groundwork for my journey began as a typical Orthopedic surgeon. I was seeing patients in the office, and at the same time having a very busy operative practice. My week would consist of performing total joint replacements, performing arthroscopies, and doing spinal laminectomies. Of course, my occasional weekend was involved in repairing hip fractures and a variety of other fractures. In those days, there was not the specialization in Orthopedics as there is today. I did many of these surgeries, but at the same time I thought that these were rather barbaric operations. I was basically doing carpentry on patients. When I finished my residency, the field of Arthroscopic Surgery was just getting started. I remember some of the more “seasoned” orthopedic surgeons that I met in private practice said to me that arthroscopy was just a fad that would die out in a few years. Initially, they looked at me in scorn thinking I was doing some type of quackery surgery. Well, I guess they were wrong! I became very proficient with the arthroscope, and did many surgeries, as did the rest of the Orthopedic community. Although the initial results in arthroscopic surgery were excellent, later on in my career I realized that these surgeries were actually causing patients to develop osteoarthritis at a young age, and this concept is now supported in the literature. I started to become disillusioned with this treatment protocol, but at the time did not know what could be a better option.
I would go to conferences to learn the latest techniques which, when all was said-and-done, was not much different from older techniques. One thing I was always drawn to was the cutting-edge techniques. I was at one time involved with injecting chymopapin into herniated discs. Chymopapin is the enzyme found in meat tenderizers. In this case, it would disolve the herniated disc. The results we obtained were very good. After this technique, I moved on to laser discectomies. Both of these methods gave excellent success in the right patient. I would call these episodes my springboard for regenerative medicine.
Total joint replacements were my formal indoctrination to the world of Regenerative Medicine. I was doing joint replacements, and I went to a conference where they discussed a “new technique” called PRP or Platelet Rich Plasma. They said that this helps the joint replacement patient heal quicker and, in general, have less pain. I started using this “new technique” with excellent success. I started studying more about PRP, and realized that this is the way nature heals itself. This was my “A-ha!” moment. I realized that the PRP technique could be used in many other applications besides total joints. My second “A-ha!” moment was that perhaps this might eventually replace the joint replacement itself.
I was now at the fork in the road. I could continue doing everyday orthopedics, or I could get more involved in the path that led to the use of biologics for orthopedic conditions. I went down this path when few people even knew what a PRP was. Those that knew about a PRP typically did not know much about bone marrow aspirate or adipose tissue. Bone marrow and adipose were my next targets to learn and study. They fell into place quickly. This time period reminded me of the time when I first went into private practice, and began doing arthroscopic surgery. The more established orthopedists said this was a fad and recommended against it. Well, fast-forward twenty years and the same comments were being made by the Orthopedic community about PRP. They said that PRP and Regenerative medicine was “Hocus Pocus Surgery.” They said that it was a fad with no scientific basis, and the talk behind my back was causing my ears to burn.
I stood steadfast in my convictions and I am so happy I did. Slowly, more acceptance crept into the field. I was eventually lecturing all over the world, and continue to do so. As a matter of fact, I leave tonight for a quick teaching trip to Brazil. I will be there for about a day and a half and then return to the USA. In that time, I will talk about the basic science of stem cells and regenerative medicine. This is interesting, in that, most clinicians try to disregard basic science and usually are not involved in teaching. Well, low and behold, I now find myself teaching of all things about the basic science of stem cells and Regenerative Medicine. As a matter of fact, I have taught on all six continents. If someone would have told me this twenty years ago, I would have bet the farm against it. It is interesting how life takes some unexpected turns. I realized that in order to become proficient in anything, one must learn to master the basics.
Every day, I try to learn more basic science in the field of Regenerative Medicine. It reminds me of one of my slides in my talks, “the more you know the more you don’t know.” That is actually a profound statement because of its simplicity. Using this knowledge of basic science has allowed me to expand the horizons and successes of our clinics. We are involved in cutting-edge aspects of anti-aging medicine that down the road will become building blocks of mainstream medicine. I have learned that the way stem cells age is how we age. These aging pathways include eliminating senescent zombie cells and stimulating gene pathways to improve the health of our mitochondria. I have realized that Anti-Aging, Stem cells and Regenerative Medicine have a strong bond that ties all of them together. It has been an exciting journey that I look forward to continuing.
- Dr. P
I would like to present a series of blogs that will address the future of Regenerative Medicine. I found the above picture and found it fascinating. It brought memories as to when I was a child. I grew up watching the Three Stooges on TV. Above we see the stooges looking at the eight-ball trying to tell the future. Well hopefully I can do a better job than the stooges as far as Regenerative medicine is concerned
THE FIRST TOPIC TO DISCUSS IS CRISPR:
The first topic I would like to address is what is known as Crispr. This is not to be confused with the section of your refrigerator that keeps salads and leafy vegetables fresh. We now have technology available that will hopefully change the face of medicine and potentially other aspects of our daily lives. Crisper technology will have far reaching effects in our lives. It can help us make bio fuels, eliminate cancer and other debilitating diseases, and possibly slow down or reverse aging. Until Crispr came along, biologists lacked the tools to force specific genetic changes across an entire population. But the system, which is essentially a molecular scalpel, makes it possible to alter or delete any sequence in a genome of billions of nucleotides. By placing it in an organism’s DNA, scientists can insure that the new gene will copy itself in every successive generation.
This gene-editing technique called Crispr-Cas9. This is a powerful new tool to control what genes get expressed in plants, animals, and even humans. The ability to delete undesirable traits and, potentially, add desirable traits with more precision than ever before. Until now, researchers had the tools to genetically manipulate only a small selection of animals, and the process was often inefficient and laborious. The following is a complicated diagram of this concept.
With the arrival of CRISPR, we can alter the genes of a wide range of organisms with relative precision and ease. In the past two years alone, the prospect of gene-edited monkeys, mammoths, mosquitoes and more have made headlines as scientists attempt to put CRISPR to use for applications as varied as agriculture, drug production and bringing back lost species. This seems to remind us of the movie Jurassic Park.
Interestingly, if we want to understand CRISPR, we should go back to 1987, when Japanese scientists studying the bacteria E. coli first came across some unusual repeating sequences in the bacteria’s DNA. Over time, other researchers found similar clusters in the DNA of other bacteria. They gave these sequences a name: Clustered Regularly Interspaced Short Palindromic Repeats — or CRISPR. Yet these CRISPR sequences were mostly a mystery until 2007. In 2007, food scientists studying the streptococcus bacteria used to make yogurt showed how these odd clusters actually served a vital function a living organism. They’re part of the bacteria’s immune system. In the past five years, scientists have figured out how to exploit a quirk in the immune systems of bacteria to edit genes in other organisms — plant genes, mouse genes, even human genes.
With CRISPR, they can now make these edits quickly and cheaply, in days rather than weeks or months. There are multiple gene-editing "tools," but CRISPR is by far the most cost-effective and precise. It works by injecting a DNA construct with three major components into the Cas9 to the correct location to cut, and a new DNA template to repair the cut with. It works by injecting a DNA construct with three major components into a living organism. The components are the Cas9 enzyme that cuts or deletes a segment of DNA, a sequence of RNA that guides the Cas9 to the correct location to cut, and a new DNA template to repair the cut with. What we are able to do is eliminate the possible genetic problems that arose by a random chance. The possibilities of what can be accomplished by Crispr are almost endless. Think of a world where Alzheimer’s is a forgotten scourge that at one time robbed people of their lives. Again, we can use this technology to improve food crops, produce supplies of energy, eliminate much of the worlds suffering. Pesticides will be a footnote in history since food crops will be genetically resistant to pests.
We need to also remember that there is both good and bad that can be accomplished with Crispr. There is no question that we will make dramatic improvements with Crispr technology. There is also the potential that we might encounter some major unforeseen problems. There is a possibility of creating a new super bacterium that can ravage the entire human population. There is the potential of making the bacterium a weapon of mass destruction. Do we want to make a super human race where intelligence is fostered? These are all questions that will arise in the not too distant future. We must approach Crispr technology with an approving eye since it may be the next quantum leap for mankind. But at the same time, we need also display some trepidation of what we may create. One example I will give is nuclear power. The devil was in the details. Give it some thought. Thanks Dr. P
Lately I have encountered a number of patients who tell me they have seen a physician who is beginning to perform Regenerative Medicine procedures such as PRP and stem cell injections. They are starting to "dabble" in this field. Their reasons are many fold. What they are doing is not fair to the patient or for that matter the entire field of regenerative medicine. I have seen a similar phenomenon in the past. Many years ago I was involved in some work where physicians used collaganase and chymopapain to reduce the size of a herniated disc. When we looked at the result of this technique a definite pattern emerged. Those doctors who were properly trained in the field and understood what they were doing had in general very good results. When this technique was released to the general medical public than the results suffered significantly.
I suspect that same thing might happen with Regenerative Medicine. Some doctors think just using a PRP or placenta growth factors will be the panacea for many musculoskeletal problems. They do not realize that many times there is much more to a successful result than just preforming a PRP or using off the shelf growth factors. Do these doctors know and utilize various growth factors. For instance in our clinic we deliver growth factors into the joint and we give them orally where they are absorbed under the tongue. The newest means that we are utilizing these growth factors is by means of a patch. Our clinic and some others that I am affiliated with are the only facilities in the world that are delivering a proprietary blend of amino acids that mimic the growth factors that the body makes. These amino acid growth factors are essential to a successful result and are sometimes lacking in a typical PRP regardless of its concentration. These factors are delivered by an iontophoresis patch (please see my previous blog on iontophoresis). Sometimes these growth factors are injected and they are many times used orally. We sometimes use placenta growth factors but these are neither new or game changers to us. We laugh at the thought that some physicians are utilizing these growth factors from placenta tissue and calling it a stem cell treatment.
Typically the "Dabblers" will not have other methods to stimulate the regenerative cells. We make extensive use of lasers and other types of lights which have a significant positive effect on stem cells and other regenerative cells. If you ask other physicians about these aspects I suspect they would have little to say due to their lack of knowledge of these subjects.
A question to ask these these physicians is if they utilize extracorporeal shock wave therapy. This is a very important modality which we extensively use in our office. It releases growth factors, causes stem cell homing to the area, and increases micro-circulation.
Another trait of the Dabblers is that they typically only use one type of treatment. Most of the time it could be a PRP injection. The more bolder ones will utilize some fat with that. Rarely will they use Bone Marrow. I suspect few of these docs will be using V cells or as they are also called Very Small Embryonic Like Stem Cells or Adult Pluripotent Stem Cells. I believe these cells will be game changers. These are our own cells yet they are similar to embryonic stem cells. We have had tremendous results when using these cells for auto immune diseases such as Rheumatoid arthritis. The other intriguing aspect of these cells is that they appear to have a profound effect on osteoporosis. We have had some patients have a 14% increase in bone density in less than six months! As you can see there are many aspects in Regenerative Medicine that separate the Dabblers from the real deal. Hopefully, this blog gives you some pointers and questions to ask.
Thanks Dr. P
Here is the Wikipedia definition of an urban legend:” An urban legend, urban myth, urban tale, or contemporary legend is a form of modern folklore. It usually consists of fictional stories, often presented as true, rooted in local popular culture. These legends can be used for entertainment purposes, as well as semi-serious explanations for random events such as disappearances and strange objects”. This seems to describe some of the thoughts that are found in the stem cell field. Things that I at one time assumed to be the gospel turned out to not be true or had no actual scientific studies to back up many of these concepts. I often wondered where these ideas came from. I would like to discuss a few of these “legends” to at least put a different spin on things. No one can say for sure where the truth lies but hopefully this will provoke some critical thinking!
One aspect in the stem cell field that is often overlooked but is of paramount importance is the individual cell and its environment and how they are related. We should all bear in mind what happens in vitro (the lab) does not always translate to what happens in the real world (in vivo). Any attempt to analyze a cell necessarily alters the nature of the cell at the time of isolation, thereby altering outcomes of subsequent differentiation events. The implications of this fact are enormous. I have read many studies that have shown that certain compounds are toxic to cells. Yet when used in clinical practice these compounds do not seem to make a difference. A good example of this is lidocaine, a common local anesthetic. In the lab, lidocaine seems to be toxic to cells yet we have used lidocaine on our patients for years with no deleterious effects. Realize of course that we still use lidocaine judiciously. What this all boils down to is the fact that when we study a cell we are taking it out of its native environment. Out of this environment it is missing its niche and the possible paracrine effect of neighboring cells. These aspects may dramatically affect the behavior of the cell. Clinical will always trump the lab. So, Urban Legend #1 is that in vitro is the same as vivo.
Another legend is the we are performing “stem cell therapy”. We should realize that we may be utilizing a small number of stem cells in our treatment but the majority of cells utilized are not stem cells. When we are typically utilizing bone marrow aspirate we are using the “soup” of the bone marrow. To say that we are doing a stem cell transplant is not really accurate. Granted there are stem cells in the aspirate but the majority of cells we are transplanting are not stem cells. These cells include a host of many different types of cells which work in concert to achieve regeneration. These cells would include macrophages and a whole array of other blood products including platelets. I, myself, am guilty of calling these procedures stem cell transplants but in reality, they are Regenerative Medicine procedures. Urban Legend #2 is that we are performing “stem cell” treatments.
Another Legend is the fact the one cannot take anti-inflammatories when utilizing Platelet Rich Plasma (PRP) injections. This idea came about from the premise that the anti-inflammatories (NSAIDs) will interfere with the platelet function and the inflammatory response. This is simply not the case. A number of years ago I spoke with Dr. Sherwin Kevy of Mass. General and Harvard. Dr. Kevy was one the early pioneers and giants in PRP therapy. I asked him his opinion on anti-inflammatories. He responded that they should not make any difference. When we are dealing with PRP injections and utilize NSAIDs this may affect the clotting of the platelets but not the release of growth factors which is what we desire. We must realize when we are doing a PRP injection we are not concerned with clotting, but the release of growth factors. The growth factors are released when the platelets come in contact with collagen which is found in most tissue. For several years now we have utilized anti-inflammatories around the time of the procedure and have seen no drop-off in results. So, at least in our hands anti-inflammatories will have no significant effect in the function of the platelet response in a PRP injection. So, Urban Legend #3 is the effect of NSAIDS on PRP function.
There is another concept out there that red and white blood cells cause significant inflammation in the joint, tendon, or soft tissue. There really are not many good clinical (in vivo) studies that back up this misconception. There is a perception that a “pure PRP” may be best in certain clinical situations. A pure PRP is one which has been centrifuged and has a significantly decreased numbers of red and white cells. The idea is that these cells lead to inflammation and possible damage. But then again, these studies were in vitro. I guess someone forget to tell the body about this. When I last checked most bodies don’t have their own centrifuge built in. The idea is that a pure PRP causes less of an inflammatory response thus the patient has less pain. I suspect the reason for less pain is that the PRP is probably less effective. If we look at the literature we realize it is probably best to take full advantage of the complete array of the components in the blood. Given the right environment most components of the blood can actually produce anti-inflammatory cytokines. Some excellent papers on using all components of the blood come from Dr. William Parrish. I strongly advise everyone to read his papers.
I am not a proponent of just using whole blood. I feel it is essential to concentrate platelets in higher numbers by centrifugation but it is not necessary to remove all red cells. There are several good clinical examples on how red cells do not seem to make a difference. One striking example on how this is not that significant comes from an orthopedic procedure called a micro-fracture technique. This is an arthroscopic technique used in the treatment of osteoarthritis. In this technique holes are made in the joint surface when there is no longer any cartilage (bare bone). The idea is that some stem cells will “leak out” from the bone marrow and help to grow new cartilage. This is the precursor to many modern day “stem cell” procedures that are performed for musculoskeletal joint conditions. The significance of the micro-fracture is that the bleeding from the holes will fill up the joint with whole blood which has a large number of red blood cells. The blood in the joint does not typically cause an inflammation. Another example of red blood cells not causing inflammation is when a patient suffers an injury such as a torn anterior cruciate in the knee. This will produce a good bit of bleeding in the knee resulting in what is called a hemarthrosis. This blood in the knee does not cause an inflammation. Furthermore, when the blood is removed the pain (caused by pressure) goes away. The last example is when someone has a spinal tap and they continue to have a headache from a spinal leak. The method to eliminate this problem is to take blood from a vein and inject it into the spinal canal so that it is in direct contact with the spinal cord. It plugs the hole but it does not cause an inflammation to the spinal cord (dura)skin. Would it make sense to put something that causes inflammation next to something as delicate as the spinal cord? As can be seen there is some good clinical evidence that red blood cells cause no inflammation yet little if any studies that show otherwise. Thus Urban Legend #4 concerns the benefits of a pure PRP.
Another myth concerns supplements. When I first become involved in performing PRP and “Stem Cell” injections I had enough ridicule from the fact that I was involved in this science. Even more ridicule was laid upon me from the fact that I was advising the use of supplements. Like usual, I took a look toward the world of science to see the true value of supplements. One need to look no further than certain supplements that we advise to our patients. There is solid science behind these supplements. One supplement which we use is StemXcell. This is a supplement that was born out of the laboratories of the Univ. of South Florida. It was devised by Drs. Bickford and Sandberg, two prominent researchers. This supplement was shown to significantly increase the number of stem cells released from bone marrow. Actually, in the lab it seemed to perform better than Granulocyte Colony Stimulating Factor (GCSF). GCSF is expensive and not without potentially serious side effects. StemXcell is the exact opposite.
Another supplement is Neo-40 which hails from the labs of the Univ. of Texas. Neo-40 has been shown to dramatically increase nitric oxide levels in the body. Taking this one step further we know that increased levels of nitric oxide (NO) have many different effects including the release of stem cells. We must realize that there are a few different forms of NO. But this product is all good since it releases the form of NO which helps reduce inflammation and stimulates stem cells. As time goes on we will see more and more information concerning the use of NO as an adjunct in Regenerative therapies. The use of NO is one of the basics of hyperbaric oxygen therapy. There is still a misconception that hyperbaric oxygen works mainly by donating extra amounts of oxygen to the cells. This is not really the case. The true mechanism of hyperbaric oxygen is that it will dramatically increase nitric oxide release which in turn significantly increases stem cell release from the bone marrow. The stem cell release is what heals the diabetic foot ulcer or other problem that is being treated. The list of supplements and their effects goes on and on. The fact that supplements are not needed represents Urban Legend #5.
I have saved perhaps the most important Urban Legend for last. In the field of Regenerative Medicine there is a perception that “doctors heal the patients”. Actually, this perception seems to permeate all of medicine. As much as I hate to admit it, this perception is dead wrong. When I first heard this, I was disturbed and angry. After spending years studying the “healing arts” in medical school and post graduate training in orthopedics how could I not heal patients? The real answer is very simple: “CELLS NOT DOCTORS HEAL PATIENTS”. As a physician, I can help direct the cells and give them some guidance and aid but ultimately, they will repair and heal the problem not me. The concept that “physicians heal patients” is Urban Legend #6.
I am sure there will be some disagreement with some of these premises but it should provoke some thought. One thing I can safely say, Regenerative Medicine is not an Urban Legend! It is here to stay and will eventually permeate most medical specialties.
It seems in the last few weeks I have seen a number of patients that have consulted with me after they have been treated “Amniotic Stem Cells” but still continued to be symptomatic. Occasionally, I will also see a patient who claims that they were treated by “Cord Stem Cells”. The real question to ask was if these patients were actually treated with stem cells? I feel that I can say with good conviction that they were not! For those of us that have been involved in Regenerative Medicine for a while this is something that rubs us the wrong way. Regenerative Medicine is a newly emerging field where there are many different opinions and sometimes heated discussions and disagreements among the various professionals as to a variety of aspects of the science. However, the opinion on Amniotic stem cells has almost unanimous support by those professionals who are involved in this field. We all feel that there is no such thing as live amniotic or cord stem cells in these products. These products at best have growth factors which may give patients some temporarily relief of pain.
Let us look at the nuts and bolts of the matter. The cord and amniotic products are registered as a 361 product with the FDA. This is a very simple product registration. It is a registration that involves tissues. It does not involve live cells! When a product has live cells, it is designated as a 351 by the FDA. There is a world of difference between a 351 and a 361.
Many times, I have been approached by the sales persons telling me that these products contain live cells but they cannot say this publicly. Their pitch is “hey doc do not tell anyone but there are 10 million stem cells here”. Well, if indeed what they say is true than they just crossed the line and have become a 351 with the FDA. This is a very significant departure from a 361. The claim of live cells has crossed the line. The FDA regulation 21 CFR 1271.1 at section 4 part 2 states that if you claim that your cells are alive and have metabolic activity and they’re a donor tissue, that’s considered a drug. Once the FDA considers something a drug it will require what is called an IND. IND stands for “Investigational New Drug”. A 351 designation with an IND is a very lengthy process which requires many years, usually millions of dollars and lengthy clinical trials. As one can see it is not an easy task. Furthermore, if the physician is aware that these products contain live cells than he is also breaking the law.
I decided to take the bull by the horns and actually call the FDA and get an opinion from them on these products. I called the following number (240) 402-8055. Within less than two minutes I was able to talk with an FDA specialist and I ask them if an amniotic product that had live cells was a 361. classification. I was told that it was not. It would be a 351 and requires an IND application. There is no grey area here. They had other concerns about these products but that will be the topic of another blog. I suspect it is only a matter of time before these products are significantly restricted. Now if a physician is using these products as a “stem cell procedure” to treat patients there arise some serious problems. He is either telling the patient a lie and deceiving them and committing fraud; or he is using a product that has no FDA approval as a drug. Furthermore, there is some question as to the indications of these products. This potentially exposes the physician to serious legal ramifications. In any case not a good situation. It can lead to problems on a variety of levels. Unfortunately, it also gives the entire field of Regenerative Medicine a black eye.
I strongly advise all patients who have a physician telling them that they will use these products as a stem cell procedure to do the following. Call the number (240-402-8055) I have listed and ask the FDA about the status of these products. When they get the correct answer, they need to educate their uninformed doctor. They need to let the doctor know that they are being treated only with growth factors not stem cells. The prices that the patients are being charged for these products are outrageous. Remember, these products are essentially growth factors similar to what is found in a PRP. Unlike a PRP, they lack other components (monocytes etc.) that can be essential in generating repair. Furthermore, in the processing of these products many of the growth factors may be damaged and not have a great efficiency. Those of us in the know will favor a PRP over these products any day. In general, I think it is safe to say that the more experienced a physician is in this field the less likely he is inclined to depend only on these amniotic growth factor products as a treatment. I should like to mention that one company out there seems to be doing things the right way. They are involved in some FDA trials. This company is Mimedix.
Thanks Dr. P
In the diagram, we see one aspect on how we can increase stem cell numbers in some of our procedures in a safe and efficient way. We are constantly looking for ways to increase the stem cell output from the bone marrow. We know all too well that most of the regenerative cells that we inject into the joint typically survive for only a short period of time. Their release of growth factors is what gives the various signals for more cells to visit the area or, just as importantly, for some of the neighboring cells to help accomplish repair. It becomes a numbers game. The more cells we have in circulation the better chance we have to achieve success. Now, if we are able to find a medication that can increase stem cell numbers and at the same time have an effect on the health of the cartilage than we have something special. Parathyroid hormone (PTH) may be just the ticket.
For a number of years now we have been using a clone of Parathyroid hormone (PTH). Another PTH clone is known as Forteo. Forteo is used in the treatment of Osteoporosis. We are actually using another analog clone of PTH which has given us considerable cost savings and at the same time may work better. We first started using PTH as a stimulator of Very Small Embryonic Like Stem Cells (you can read about these cells on a previous blog). There is still some controversy to these cells but that controversy is on the wane. There is a receptor on the V cell surface that seems to stimulate these cells when the PTH binds to the cell membrane. It appeared to activate these V cells.
When we investigated PTH we were very intrigued by a number of scientific articles that show PTH can have some interesting effects on articular cartilage. The Univ. of Rochester is studying PTH for its ability to inhibit chondrocyte hypertrophy and induce cartilage matrix production. Chondrocyte hypertrophy is the beginning of the death spiral for chondrocytes which produce and maintain cartilage. Chondrocyte hypertrophy-like changes play a role in early and late stage Osteoarthritis (OA). Since not all cells in an OA joint are synchronized in their stage of the cell cycle, inhibition of hypertrophy-like changes might be a therapeutic target to slow down further OA progression. There are a number of studies that show that PTH is chondro-regenerative. There were many preclinical findings providing proof-of-concept that (PTH) may be useful for decelerating cartilage degeneration and inducing matrix regeneration in osteoarthritis patients. In addition to bone as a target, signaling downstream of the type I parathyroid hormone receptor (PTHR1) regulates chondrocyte differentiation. Parathyroid hormone-related peptide (PTHrP) a clone, is a potent stimulator of proliferation and collagen synthesis and suppressor of maturation. One classic article on this effect of PTH comes from the work of Dr. Eric Sampson and his group from Univ. of Rochester. They were able to show the chondro-regenerative properties of PTH. So, we can see that PTH may have some powerful effects on improving the status of articular cartilage and its underlying bone.
Another aspect of Parathyroid hormone is that it increases Prg4 expression which has been reported to inhibit articular cartilage degeneration in arthropathic joints. Lubricin is present in synovial fluid and on the surface (superficial layer) of articular cartilage and therefore plays an important role in joint lubrication and synovial homeostasis. Lubricin is the most lubricating and anti-adhesive molecule in the human body. Lubricin biosynthesis and bio distribution are mostly regulated by cytokines and growth factors. When first isolated, cartilage lubricin was called "superficial zone protein" (SZP) Lubricin, MSF, and SZP are now collectively known as Proteoglycan 4. Lubricin was originally identified as a lubricating glycoprotein present in the synovial fluid, specifically synthesized and expressed by articular chondrocytes (cells that makes cartilage) of the superficial zone. It is recognized to have a major protective role in preventing cartilage wear, synovial cell adhesion and proliferation and reducing the coefficient of friction of the articular cartilage surface. The best way to think of lubricin is that it is a very high-powered hyaluronic acid. Hyaluronic acid has been used for years as a treatment for symptomatic osteoarthritis of the knees. We are looking into getting a bioengineered form of Lubricin and Hyaluronic acid. Both Lubricin and Hyaluronic acid are more than lubricating agents. Lubricin and Hyaluronic acid as a biologically active molecules that regulates tissue repair process on multiple levels. They are signaling agents affecting many different cell processes. Hyaluronic acid (HA), one of the main components of the extracellular matrix, is considered a key player in the tissue regeneration process. It has been proven to modulate, via specific HA receptors that are located on cell membranes, inflammation, stem cell migration, and angiogenesis (formation of blood vessels). These are the main phases of healing. We typically use Hyaluronic acid in our treatment protocols. It is a very specialized form we are using. Unfortunately, many offices performing stem cell treatments do not go to this length and utilize Hyaluronic acid.
This is not where the story about the benefits of PTH stops. One of the missions of the regenerative medicine doctor is to come up with ways in which we are able to increase stem cell output from the bone marrow. We are aware that certain supplements may help in this endeavor. On such supplement that comes to mind is StemXcell which is licensed by the Univ. of South Florida. In some lab studies StemXcell was found to have similar effects as granulocyte colony stimulating factor (GCSF). GCSF is sometimes called Neupogen. Neupogen is used in cancer treatment to increase the numbers of white blood cells after for instance chemotherapy. GCSF will increase the number of white blood cells released into the system. At the same time, it will increase the number of other blood components released from the bone marrow including stem cells into the circulation. The problem with these medications is that they are very expensive and at the same time do present some substantial risks. Another product which increases stem cell output is Procrit. Procrit increases the number of red blood cells released into the circulation. Procrit and GCSF are manufactured by recombinant DNA technology meaning it is produced by Escherichia coli (E coli) which are bioengineered. Many of our medicines are produced by bio-engineered E. coli. We have utilized some of these recombinant DNA products in our lab.
What initially got our attention with PTH was the effect it has upon bone marrow. PTH has been demonstrated to influence and expand the bone marrow stem cell niche where hematopoietic stem cells, capable of both self-renewal and differentiation, reside. Moreover, intermittent PTH treatment is capable to induce mobilization of progenitor cells from the bone marrow into the bloodstream. This is what has wet our appetite. We now have a safe method of increasing the number of circulating stem cells in the circulation. This is similar to the effect of hyperbaric oxygen. Thru the work of Dr. Thom of the University of Pennsylvania we have discovered that hyperbaric oxygen will increase the number of circulating stem cells in the circulation. Dr. Thom discovered that hyperbaric oxygen works on a nitric oxide (NO) mechanism. The enzyme responsible for the production of NO in this case is endothelial nitric oxide synthase. The NO will stimulate the marrow to release large numbers of stem cells. We will give a NO supplement to increase the effects on bone marrow. This supplement is called Neo-40. We have used it for years to help increase the marrow stem cell output. However, PTH seems to have a more profound effect on marrow stem cell release. The PTH is given in intermittent doses. Stimulation with PTH showed a significant increase of all characterized subpopulations of bone marrow-derived progenitor cells (BMCs) in peripheral blood (1.5- to 9.8-fold) similar to GCSF. Luckily, PTH has a much better safety profile than GCSF. Also, our source is much more reasonably priced. This is a piece of our Advanced Cellular Repair Division.
On doing research we find one more important aspect of PTH. PTH seems to increase the amount of a chemokine called SDF-1 also known to many PHDs as CXCL-12. The major role of chemokines is to act as a chemoattractant to guide the migration of cells. The receptor on the cells that attracts the SDF-1 is called CXCR-4. The CXCR-4 is expressed on many circulating progenitor cells. The CXCL-12 and the CXCR-4 axis is one of themain axis of stem cell migration and homing. SDF-1 acts as a “tractor beam” on stem cells much in the spirit of Star Wars.
We continue to expand our uses of PTH. Luckily, we have an excellent source of a clone of PTH which is both effective and cost efficient. We are using the PTH on an intermittent basis. As time goes on we will find other medications and supplements to complement our use of PTH. We are ever pushing the envelope. Thanks DR. P
There are no results that match your search criteria