A Novel Strategy Combining the Benefits of an Original Vegetal GcMAF with the Benefits of Hemp Fermentation and the Presence of a Unique Array of Probiotics and Phages

Talk from Autism One 2020 given by Dr. Marco Ruggiero

The product described here, Edestiny, is available here

It is well assessed that Gc protein-derived Macrophage Activating Factor (GcMAF), an immune stimulant molecule, shows promising therapeutic efficacy in autism thus highlighting the role of the immune system in the disease. It was also recently demonstrated that fecal transplant reduces the symptoms of autism thus underlining the role of the gut microbiota; fecal transplant involves transfer of phages that constitute an abundant form of life of the microbiota and contribute to its immune modulating features.

In this study, we present a novel approach that combines the efficacy of GcMAF and microbiota/phage reconstitution in one single and easy solution that does not involve human or animal derivatives. Our approach is based on fermentation of a unique Swiss hemp extract by microbes and phages that are known to reconstitute the healthy human microbiota and balance the immune system. Fermentation of this hemp extract determines the formation of a GcMAF vegetal analogue through glycosylation of edestin, a globular protein that shares significant similarity with the precursor of GcMAF. Immune system stimulation by vegetal GcMAF is complemented by the presence of fermenting probiotics and phages that show properties of interest for autism such as: reduction of inflammation, DNA repair in the nucleus and the mitochondria, repair of damages inflicted by electromagnetic radiations, suppression of retroviral infections, and detoxification.

This novel approach combines the benefits of an original vegetal GcMAF with the benefits of hemp fermentation and the presence of a unique array of probiotics and phages in a tool free of human or animal derivatives.

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How someone got their blood work to come into balance

https://www.bravocoop.com/so/6dNQEff_1?languageTag=en&cid=b77191d6-5c33-4b4a-9486-e8e0c00a3910#/main

Imuno and Cancer – Hope through Science

New and exciting results

A man and his wife traveled for hours to see their doctor.  Phil’s research genuinely is innovative.  He literally helped his doctors to get to the information they needed to get to the bottom of his wife’s cancer condition.  He studied hard and knows all the details of many technologies.  He came to me with questions about imuno.  He said that it “sounds good” but he had to vet it and see its effectiveness before he would allow himself to get hopeful.  

Phil wanted to see his wife’s immune system get better and fast. More specifically, they were testing neutrophils which are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans.  They form an essential part of the innate immune system which is the first line of defense against invading pathogens and is particularly important in warding off bacterial and viral infections presenting at the mucosal cell surface.  (hmmm sounds like this is the same system that fights Covid-19)

After two weeks of using imuno in a nebulizer, his wife visited her doctor again and they tested her.  Her neutrofils came up from “low” to “normal”.  Phil would have been happy with results that rose 10% but the results showed that the neutrofils rose 15.3% which made Phil very happy because this improvement showed only 2 weeks from the start of first use and we expect to see consistent support for her to come. 

Read more about imuno 

What Phil’s wife used was 5 droplets (from a 20 gauge syringe) of imuno 2x per week.  The imuno was placed in the medicine cup of a nebulizer and inhaled which Phil said took only one breath.  We suggest breathing in the imuno into your nose, up into your sinuses and then holding it in the lungs until the gas exchange happens.  As we hold and slowly breathe out, turn off the nebulizer to save product.  Sometimes, when the amount of drops is higher, it will require more than one breath.  With the nebulizer off, catch your breath, get ready for the next imuno breathe and then when you are ready, let the air all the way out and slowly breathe in the imuno until your lungs are full.

The Europeans say that the “otis” is cancer and the “itis” is infection.  The “otis” relates to scanning the end of the exhaled breath.  The itis has to do with breathing all the way in to the top of the inhalation.  They feel that the breath itself is a scanner that can scan the whole body inside the range of a full breath.  If we consistently skip part of the breath/scan, trouble can brew. Practice full breaths all the time to help your body scan intentionally.

Imuno works by cleaning with phosphatidylcholine.  It holds its boundaries around this clean space and penetrates deep into the cells with its low molecular weight chondroitin sulfate.  Then it turns on the power of the cell with Vitamin D3.  imuno does this by being small enough that it can penetrate through everything, including bone.    It’s like someone flipped the switch in a giant factory and brought it back to life.

The immune system has a way of marking what it needs removed.  Just like in our lives, when the project doesn’t have resources, it goes inactive but it is not forgotten.  The immune systems prioritizes and often clears out its list as it can.   imuno provides access to all the body with its nano sized particles and molecularly bonded ingredients.  It gives the body tremendous resource by tapping into and turning on the power within the cell. That’s why imuno has been rated 100 times more effective than other GcMAF products on the market today.

To Buy imuno

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How EMFs Impact Your Microbiome

How EMFs Impact Your Microbiome 

A talk given 2/23/32 by Dr. Marco Ruggiero 

Dr. Schaffner: Welcome, everyone, to The Body Electric 2.0. I’m so excited to have my colleague and friend, Dr. Marco Ruggiero, talk to us about a really important topic. And Marco always has these really innovative, cutting-edge ideas on how to approach the diseases and the stressors of our modern time. 

And we’re going to be talking about a novel natural way to protect our body from EMFs. So, welcome, Dr. Ruggiero. I’m so excited to have you on The Body Electric 2.0. 

Dr. Ruggiero: Thank you, Christine. This is a great opportunity. One of the many that you’re giving me to share the results of my research. So, thank you so much. 

I hope that this talk about electromagnetic fields and the damage that they may inflict to the human body and how can we protect ourselves will be interesting for everybody. I know you have a number of questions for me, and I’m ready to answer your questions. 

Dr. Schaffner: Right. And I’m so grateful you prepared a slide presentation to really bring these concepts to life. And you’re always a wonderful presenter. So, thank you for being so thorough. 

And this is such an important topic, and we have people discussing EMF, which we’ll get into why we need to be concerned, but you also have some really innovative ideas of how we can increase our resilience to the exposures we have. 

And many people might not know that you are a trained radiologist, and obviously, being a radiologist, you learn a lot about radiation, of course, how that applies to diagnostics in the body. 

But from that perspective, and from that point of view, what is your opinion about EMF and the increase in exposure that surround us and how it impacts the human body? 

Dr. Ruggiero: Well, thank you so much for pointing that I have been trained as a radiologist. Radiations, electromagnetic fields ranging from ionizing radiation, like the x-rays that we use in diagnostic radiology, and also radio waves and all types of EMF are bread and butter of my training. 

Going into the specifics, I’d like to show what my specific training on mobile telecommunication, electromagnetic fields, and human cells has been. We began working when I was at the University of Florence, Italy, on these topics in the late nineties. 

So we published two papers in 1999 describing the effects of EMFs on human breast cancer cells, as well as on human neurons. So, these two topics, cancer and neurology or neurosciences, and how they are affected by EMFs, will be discussed in this presentation or interview or talk. I don’t mind the way you want to call it. 

Then in 2002, we explored specifically the effects of those mobile phones of those days. They were called global system for mobile communication, GSM, specifically on skin cells, human skin cells. You may wonder why human skin cells. 

Well, we knew then, and we know now that human skin cells or the skin, in general, behaves like an antenna, like an antenna that receives electromagnetic signals. 

So this is an excerpt from a paper that I will be discussing later on that clearly says we showed that the 5G, in this case, millimeter waves, could be absorbed by the dermatologic cells, the cells of the skin acting like antennas. 

Now, we knew that in 2002, that’s why we decided to study the effects of those old cellphones — they are old by now. They were top-notch in those days — on the human cells. 

Then in 2001, we were invited to write a chapter on electromagnetic fields and cancer in the most respected and most famous encyclopedia of cancer that is published in Heidelberg, Germany. 

And this chapter on electromagnetic fields and cancer has been reprinted several times and, of course, updated. So the latest update is in 2017. And it’s interesting. 

At least, I think it is because for the very first time, we describe the effects of EMFs not only on the human cells, that is, the human cells that have our DNA, but also on those cells that are inside us, the microbiome. 

Now, we know that about 90% of our cells are microbial cells. We are only 10% human if we look at the number of cells, and we know a lot about the effects of EMFs on a human cell. So, as I said, we began studying on human breast cancer cells, then on human neurons, and then on skin cells. 

But we knew little about the effects of the EMFs on the microbiome, the microbial cells. As we wrote in this chapter, considering that the human microbiome is involved in development and function of, I would say, all the systems and organs and most notably the immune system, in this chapter, we hypothesized that the effects on the microbiome may be one of the mechanisms to which the electromagnetic fields, both endogenous and exogenous fields exert their biological effects. 

In other words, the effects of EMFs on the human microbiome open a new perspective in assessing the risk for health and in preventing that. Why? Because 

until now, people are focusing, including ourselves, of course, on the effects of EMFs on the human cells. And we know a lot about that. 

But little has been done to focus on the effects on the friendly microbes
that contribute so much to our wellbeing. So we have a number of different perspectives to study when we want to assess the effects of EMFs on the whole body. That is not only on the human cells but also on the microbial cells. 

Now, 20-some years later, if we go and look at the literature that you can find in the US National Library of Medicine in the database called PubMed, you find a number of papers confirming those early observation of ours. 

This paper was published quite recently, November 02, 2020. So just a few days ago. And it is also by researchers from US and Korea, and they did an enormous work. Essentially, they studied 46 different articles that they found in the literature. And they conclude that cellular phone use with cumulative call time of more than 1000 hours statistically significantly increases the risk of tumors. 

So it’s a confirmation of what we had observed 20-some years ago. This comprehensive meta-analysis of case-control studies– So, we’re talking about not an ecological observation, but serious case-control studies found evidence that links cellular phone use to increased tumor risk. 

Now, just to give you an idea of the numbers, they studied more than 66,000 participants and 46 case-control studies. 

And the studies came from all over the world, from Sweden, Denmark, United Kingdom, Finland, Norway, Germany, United States, Israel, Japan, Italy, New Zealand, France, Brazil, China, South Korea, and Thailand. So from all over the world, just to rule out any limit of observation. 

So, I would say that this is a clear demonstration that those observations of ours 20-some years ago were on the right path. And there is no doubt as of today that EMFs they affect our body, both our human cells and our microbial cells. 

I’d like to pinpoint also this study that was published a few months ago in April 2020. Again, you can find it in the National Library of Medicine of the US. 

And here, the author goes a little bit further because, in addition to these effects, they claim that official documents show that the impact of electromagnetic waves is not only physical and biological. 

Indeed, the climate and the behavior of the population are also targeted. So, essentially, we are immersed in EMFs. These EMFs are not in our calls. We know a lot, but still, there is a lot to be known. So that’s the best I could do in a few minutes to answer this question of yours. 

Dr. Schaffner: Yeah, no, that’s excellent. And I have seen some of those recent publications that I haven’t seen yet, so that’s great that this information knowledge base is growing, and the data continues to point and say the same story. And no, that’s really great, Dr. Ruggiero. 

And then it reminds me, too, as you’re studying the EMF and the microbiome, it’s kind of the same parallel how we look at glyphosate, but we really look at glyphosate’s effect on the microbiome. 

And the story of these things and their interactions with the microbiome has a lot to do in determining our health because we are more microbial cells than human cells. 

So it has to have an impact. So I appreciate you bringing all of those great points together. And as we expand our knowledge about 5G and we also expand our knowledge to this increase in exposure of EMFs and how this can impact our immune system, how do you feel that these might be related to, as we record this in 2020, really the evolution and the pandemic of COVID-19? 

[10:00] 

Dr. Ruggiero: Well, this is a very hot topic. And let me tell you that all the information I am giving today is supported by scientific articles that you can retrieve and you can study. So you don’t have to trust my words, but I am providing scientific proof for what is worth of what I’m saying. 

Now, this is not scientific proof, but if you want to learn a little bit about some alternative views on 5G, I recommend that you go to YouTube and look at this 5G APOCALYPSE – The Extinction Event. It’s a film made by a good friend of mine, Mr. Sasha Stone. 

And I, together with a number of other experts or so-called experts, participate in this film. So, I think it could be very interesting. But besides this, if you go to the US National Library of Medicine and you look for 5G and COVID-19, you end up with articles that describe very clearly and with no ambiguous terms that this is a conspiracy theory. 

So there is a no link between 5G and COVID-19. It’s a conspiracy theory. One of the craziest. The same level as a flat earth, or the earth is ruled by giant lizards or things like that. 

So these are a couple of articles that explain in very clear terms that this is only a conspiracy theory, not worth even discussing. And they might be right. 

However, I found this that might also be interesting, if nothing else, for the sake of curiosity. This is a study that, again, you can find in the US National Library of Medicine. 

Or actually, you could find the past tense. And this study produced by scientists from the Guglielmo Marconi University of Italy — Guglielmo Marconi is the one who invented the radio — Central Michigan University, and First Moscow State Medical University claims that 5G millimeter waves stimulate human DNA in a way that causes cell nuclei to produce, to create coronavirus. 

So that’s a kind of a strange and interesting. The authors, I will talk about the senior author a little bit later. So you could retrieve this paper, this article from PubMed. If you still can’t, if you want, I can give you some copies and the article is very complex, very technical. So let me just read the first lines. 

In this research, we show that 5G millimeter waves could be absorbed by dermatologic cells, cells of the skin, acting like antennas, transfer to other cells, and play the main role in producing Coronaviruses in biological cells. 

And then it goes on. It explains everything. Again, very technical, very complicated. Now, I personally know the senior author. I don’t know if you’re familiar with this convention, but in scientific articles in the field of biology and medicine, the last author is the senior author. The one who supervises the group. 

Doctor, actually, Professor Torreira Lotti used to work University of Florence, Italy, when I also was working over there as a full professor. He was a full professor of dermatology and is highly respected in the field of dermatology. He is president of the world health Academy of Dermatology. He has a number of awards. 

He is a honorary professor in China, in Russia. He has been a chair of dermatology at Rome’s Marconi University. And so, he is a scientist with hundreds and hundreds of peer-reviewed articles, very respected with extremely high reputation in the field of dermatology. 

And here, dermatology is involved because, again, the skin works like an antenna. So what happened then? It happened that this article was taken by some websites that are kind of controversial, like InfoWars. They deal with a number of controversial topics. 

And actually, this was the title: NIH ADMITS 5G CAN ACTUALLY CREATE CORONAVIRUS WITHIN HUMAN CELLS. Also, celebrities, they took these articles. This popstar suggested 5G link to coronavirus. Whatever the case, after all of this probably unwanted publicity, the editors of the journal retracted the paper. 

So the paper is no longer available, not because the data were fabricated and not at all but for not better-specified manipulation in the peer review. So the paper is no longer available. And again, if you wish, I can send you and the audience some copies. 

But let’s say that the controversy still exists. I found very interesting this Ph.D. from Canada, Dr. Magda Havas, who did some very simple study that I think everybody could do that is to compare the incidence and the mortality of COVID-19 in states of the United States that have already implemented the 5G and compared with states that have not yet implemented 5G. 

So, as you see, same number of tests per million population, number of cases, number of deaths. She observed that the COVID-19 cases per million are 95% higher and 126% higher the deaths for COVID-19 in those states that have already implemented 5G. 

Of course, we know very well that association doesn’t mean causation. There could be hundreds of different causes explaining this observation. Now the data is real, but the interpretation, of course, is subject to a number of variables. 

And as the doctor very honestly writes, whether these results are due to some factor other than 5G and whether this association will proceed as time goes on remains to be seen. 

However, I would say that controversy aside, it is something interesting to monitor because we never know. COVID-19 is something completely new. 5G is something completely new. So at least for the sake of scientific curiosity, it is something worth monitoring. 

Dr. Schaffner: Yeah. That’s amazing. Dr. Havas does incredible work. So, I didn’t realize she put that together, and yeah, as you said, it just continues to pose the question, and we have to look at this relationship with all the information you shared. 

So, no, that’s really interesting, Dr. Ruggiero. And as we’ve mentioned with your radiology training, you had to learn a lot about protection against x-rays and other forms of radiation in general. 

And so, from that knowledge base, and then all of your research, how can we protect ourselves from really the ubiquitous EMFs that surround us right now? 

Dr. Ruggiero: Well, this is something very difficult because to protect ourselves against the x-rays is relatively simple. You put some lead between yourself and the x-rays, and you’re protected. Much more difficult is to protect ourselves from the ubiquitous EMFs. 

We even have satellites that send EMF signals for communication. So even if you go to this beautiful place, which is the petrified forest in Northern Arizona, still, you have a very strong cellphone signal. So it means that even there, you have EMFs. So how can we do? 

We have to find some other way. Now, we described this new approach of ours in this article that can be freely retrieved from my archive, the preprint server for biology from the Cold Spring Harbor Laboratory, where we describe a novel method to protect ourselves using or, let’s say, exploiting microbes that are part or may become part of our microbiome. 

But first, let me talk about 5G again because, in this article, we describe the effects or the results of this approach of ours on a number of EMFs, including 5G. So, now I should be talking about 5G, not in relation with COVID-19, but in general. 

Now, this is a very interesting article that was published in May 2020 by authors from United States, Canada, and Russia, and also Greece. 

So, a multinational effort and in no ambiguous terms, they write: this article also presents evidence that the nascent 5G mobile networking technology will affect not only the skin — again, the skin because the skin is an antenna — and eyes, as commonly believed, but will have adverse systemic effects as well. Systemic means on the whole body. And most likely, the microbes are part of these systemic effects. 

Now, this concern has also been taken also by a non-technical scientific publication like Scientific America. Scientific American is probably the most respected journal for divulging scientific topics. Even Albert Einstein, as you can see from Wikipedia, has contributed to Scientific American

[20:05] 

So I think we’re not talking about the fringes, the conspiracy fringes of the internet. We are talking about what is called mainstream science. And in Scientific American, in October of last year, they write again, very clearly, we have no reason to believe that 5G is safe. 

Now, if this is the case, then what we can do? Can we do something we think we can? And we even filed a patent application at the United States patent trademark office describing this technology of ours. 

Now the title of this invention, if you want to call it so, is composition, methods, and rationale for the formula of a pre-probiotic dietary supplement. 

So this tells you where we are. We want to develop a supplement, pre-probiotic, that is aimed at protecting the human body from the harmful effects of electromagnetic radiation through quantum entanglement of DNA repair genes. 

So now it becomes complicated, but it’s a patent application. We have to use technical terms. That are elicited by natural superluminal — superluminal means they travel faster than light particles — inducing photosynthesis through or via the Cherenkov effect. 

What happens is sort of a light radiation that happens when particles travel faster than light in water, and this induces photosynthesis. So, I know it’s very complicated. Again, it’s a patent application. It is not something– It is not a novel. So it has to be very technical. 

Let’s hope that the abstract is more clear. Now, the invention is related to a 

product called — the name is still classified — that is formulated with the goal of protecting the human body from the harmful effects of ionizing and non-ionizing electromagnetic radiations. 

Examples of ionizing radiation targeted by this invention include, but are
not limited to—[legalize]—gamma- and x-rays. Non-ionizing electromagnetic radiation includes but are not limited to radio waves such as those used for mobile telecommunication comprising the fifth-generation technology standard for cellular networks, also known as 5G. 

So, essentially, we have developed a technology where we can exploit the ability of certain types of microbes to withstand enormous amounts of damage inflicted by EMFs, whether ionizing radiation or non-ionizing radiation, 5G, radio waves, whatever. 

And then these microbes, they transfer this ability of theirs to quantum entanglement of DNA to the microbes of our microbiome, and in turn, these transfer this acquired resistance or ability to repair the damage to our human cells. 

So, in this very indirect or [inaudible] way, our human cells become capable
of withstanding the damage inflicted by EMFs. Did you know that some microbes can withstand enormous amount of radiations? That’s something very interesting. 

Dr. Schaffner: Yeah, no, absolutely. And that’s really, as you are sharing a really unique approach that we can harness the power of these microbes that are resistant to these high amounts of EMF exposures and the harms of them. And we can use the microbes to basically — again, I’m oversimplifying — kind of educate and share that resistance knowledge to our own microbes so then we can be more resilient to EMFs. 

And so, I’m sure everyone’s wondering how’s it possible that these microbes are up to thousands of times more resistant to the lethal effects of radiation? 

Dr. Ruggiero: Well, thank you for asking because this is– No, for me being a radiologist is particularly fascinating. We found that some microbes that are called cyanobacteria. 

And the cyanobacteria are interesting because they perform photosynthesis. That’s why we use them in our approach. They are extremely resistant to the killing effects of ionizing radiation. 

So these words, they come from that article of mine that I showed that is published in bioRxiv. Arthrospira platensis is currently used by the NASA or maybe even the Russian astronauts because when you are up in space, you are exposed to a lot of radiations because you’re not protected by atmosphere. 

And actually, the astronauts, they use these microbes. Now, this bacterium survives exposure to gamma rays — gamma rays are the worst, even worse than x-rays — up to 6,400 grays. Grays is a unit of measurement of radiations. 

Now, to give you an example. The lethal dose that was computed from data on occupants of reinforced concrete structures in Nagasaki, Japan, that as we know tragically was bombed with the second nuclear bomb. Now, the lethal dose for humans is 3 grays. 

Now, these microbes, they can withstand radiations up to 6,400 grays, so they are not even comparable to our human ability to withstand radiation. How can they do this? They have a number of molecular mechanisms that have been 

429 

studied in detail. 

First of all, they can reduce significantly the production of those reactive oxygen species or ROS that are responsible for the damage to DNA. Secondly, they are subjected to DNA damage, of course, radiation. 

So they penetrate into these bacteria, and they cause a number of damages to the DNA, but they are incredibly efficient in DNA repair mechanisms. 

So, they have the same repair mechanism that we have, but theirs are much more efficient. Now, this is what they do. I mean, they can live closer to the volcanoes. They can withstand the worst radiations, and they survive. Now, the point is, how can we transfer this ability of theirs to our cells? 

That’s why we developed a technology that is based on phages. Phages or bacteriophages are viruses of bacteria. In most cases, they are not good for them because they kill them. But in other cases, they behave like the microbiome of the bacteria. 

We have in our gut microbes and the bacteria, they don’t have a gut, but inside them, they have viruses that can be very beneficial. And they’re very important for them to transfer the information. This is an article published in Science that highlights the importance of viruses for our health of these bacteriophages, these healthy viruses. 

So let’s not make confusion. There are some viruses that are very bad. We don’t want to meet them, but there are many more viruses that are truly important for our health. 

As a matter of fact, these viruses called bacteriophages or phages have been used in therapy of human disease for more than a hundred years. That is soon after their discovery in 1915 when it was enthusiastically thought that they could cure almost any disease, in particular, infectious disease. 

In those days, there were no antibiotics, and these viruses they killed the bad bacteria, the pathogenic bacteria, and saved the healthy microbiome. Now, phage therapy is only now in these past few years being rediscovered in Western countries, but it has been used continuously with no interruption in the country of Georgia, a former Soviet Union, and the Russian Federation. 

And actually, they do sell commercial phage cocktails for decades, and they belong to the armamentarium of a common practitioner. So, essentially, we have developed a technology that has been published. This is one of our most recent articles describing the phage composition of this pre-probiotic of ours. 

Now, these phages they are instrumental in transferring the resistance to
the killing effects of ionizing and non-ionizing radiation from the Arthrospira platensis to the microbes of the microbiome and then to our cells. So, we have a kind of a talk towards way to exploit or harness the abilities of these microbes and to transfer this resistance to our cells. 

Dr. Schaffner: It’s a brilliant way. It’s a very brilliant way. So these phages from the cyanobacteria are basically teaching our microbes of the microbiome how to protect us. Is that correct? 

Dr. Ruggiero: That’s correct. And then the phages, they also transfer the information to our human cells. 

Dr. Schaffner: Is there anything else you want to share with us about that mechanism or how we can really create a more resistant or resilient microbiome to these EMFs? 

[29:50] 

Dr. Ruggiero: Well, yes, there is something that is a fairly new, and actually, we have not discussed this far. But first, let me go a little bit back on the effects of EMFs on neurology because we have discussed about cancer. We have discussed about viruses, but what about neurology? Do EMFs somehow cause damage to our neurological functions? 

Unfortunately, the answer is yes. Again, all these are scientific articles you can retrieve from PubMed. For example, this one published in 2019 describes the effects of chronic exposure to extremely low-frequency EMFs, those that are used for mobile telecommunication, on sleep quality, stress, depression, and anxiety. 

I think we all know that we shouldn’t sleep with our cellphone next to our bed. And I mean, there is ample scientific proof that EMFs, they have very negative effects on neurology, in particular, on stress, depression, anxiety, and sleep quality. 

However, something that is not very well known, at least not by the general public, is that they also affect our ability of dreaming. And you may think, well, in these days with COVID-19 and cancer and all these things, who cares about dreaming? 

Actually, that’s important, more important than most people think. Also, this is an interesting article published in the New Scientist describing our sweet dreams, that is, good dreams, not nightmares, are made of geomagnetic activity. Even the magnetic field of the earth is able to influence our dreams. 

So think about those artificial EMFs that we are surrounded by. Now, again, you may think, well, who cares about dreams? We have many more dangerous, many more important things to deal with. 

Well, if you ask Carl Gustav Jung, one of the two fathers of psychology, the general function of dreams is to try to restore our psychological balance by producing dream material that re-establishes in a subtle way the total psychic equilibrium. 

So, according to Jung, and not only to him, dreams are essential for our psychic equilibrium. And if you want to go a little bit farther, again, according to Jung, we have forgotten the age-old fact that God speaks chiefly through dreams and visions. 

So, dreams are an essential part of our psychological well-being. And the fact that dreams are negatively affected by EMFs is not a good thing. And this might reflect in a number of stressors. But in addition to sleep, anxiety, dreams, also EMFs, they affect memory. 

And this is not a surprise because, in our brains, all these functions are closely connected. Now, this is another article published five years ago, where they described how EMFs seriously damage the physical and psychological health. And they propose electromagnetic fields as environmental contaminants. And in particular, in this study, they focus on the effects of EMFs on memory. 

Now, memory is located in this area of the brain that is called the hippocampus. The hippocampus is a very small area of the brain that has been known for many years is where in particular long-term memories are formed and stored. 

This is another article published in 2017 describing again the effects of short and long-term EMFs exposure on the human hippocampus. Why do I mention hippocampus? Because hippocampus is an organ, or let’s say the part of
the brain that I have been studying for many years. This article of mine was published in 1987. 

So several years ago, in the most respected journal, a European Journal of Molecular Biology. EMBO stands for European Molecular Biology Organization. It is the most respected in Europe and one of the most respected in the world. 

And here, we described the effects of a particular neurotransmitter that is called GABA, gamma-Aminobutyric acid, on the hippocampus as related with long-term memory. 

So now we put together two or three things, a neurotransmitter, which is called GABA, which is an inhibitory neurotransmitter. The hippocampus that is where memory is formed and stored. Actually, I didn’t publish only one article. I published two articles. This one was published in the same year in Brain Research

Now, the GABA is the trade union because GABA is produced by the microbes of the microbiome, in particular, by certain microbes that we took care to integrate in our pre-probiotic approach. So, now we have microbes producing GABA. 

And what can we do with all this information? Well, let’s go back a little bit to the skin as antenna because if it is true that EMFs they work primarily through the skin and the skin is like an antenna, maybe the skin is an important organ to target with this approach of ours. 

Now, who does say that the skin is an antenna? Well, we have already read in the paper by Lotti and colleagues that they hypothesized– They show actually. They don’t hypothesize. 

They have data showing that 5G millimeter waves can be absorbed by skin cells acting like antennas, but we know this paper has been retracted part of the conspiracy theory. So let’s forget about that. 

But amazingly, they are not the only ones because, in 2008, this is long before any COVID-19, long before any InfoWars or conspiracy theories. These authors from the Hebrew University of Jerusalem in Israel, they published this paper clearly describing how the human skin is arranged in an array of helical antennas in the millimeter and sub-millimeter wave range. 

And they are not the only ones. Again, New Scientist, that is a journal to divulge complex scientific concepts, clearly writes sweat ducts in the skin may act as giveaway antennas. 

Our skin may contain millions of tiny antennas in the form of microscopic sweat ducts, says researchers in Israel. And then they go on. You can read the article. And again, the article was dated 2008, so no controversy here. 

Skin cells, skin structures are antennas. This is more recent, 2018. In science, when you have a concept that stays there for 10 years or more, it means that it is true. Otherwise, again, it is retracted. It is disproved. It is ridiculed. 

Now, this is still there because 10 years later, other researchers, again from Israel, they published this article entitled The human skin as a sub-THz receiver – Does 5G pose a danger to it or not? You read the article, but I think you can deduct from the title of what they mean. 

Therefore, our approach now is to target also the skin. So not only to teach the microbes but also to use these metabolites of the microbes, the gamma- aminobutyric acid, to target the skin because the skin is the antenna through which we receive the EMF. 

In particular, the millimeter, sub-millimeter waves, and our approach combines the well-known property of GABA that I will describe in the next slide with a proprietary blend of Allantoin and Ambuk butter. 

So we’re talking about completely natural substances. Microbial (non-animal- derived) Chondroitin sulfate that serves as a delivery system, creating a unique proprietary delivery system, and all these things are combined. And they’re designed to amplify each other’s efficacy and counteract the effects of EMFs on body, brain, and mind. 

Briefly, because you can find, you can read these things for yourself on Wikipedia or anywhere else, GABA is responsible for the calming relaxing effects of alcohol, barbiturates, benzodiazepine, Valerian, anesthetics. 

In other words, all of these substances that are known pharmacologically or as food to calm, to relieve stress, they all work because they mimic the effects of GABA. 

GABA is the real thing. Alcohol, barbiturates, tranquilizers are mimicking. GABA is also involved in synthesis of melatonin. So it affects the regulatory effects on sleep and reproductive functions. 

Modulators of GABA receptors have shown clinical proof of concept as novel anxiolytics that are superior to the classic tranquilizers because they lack sedation and they have a much reduced or absent dependence liability. GABA is essential for memory. We published that in 1987. GABA is essential for eyesight, the so-called supernatural eyesight that we have during solar eclipses. 

And besides the nervous system, GABA is also produced in insulin-producing cells of the pancreas, where it promotes replication and survival of the cells and has been proposed as a new treatment for diabetes. 

[40:00] 

And it has also been detected in other tissues of the GI tract, the reproductive system, the liver, and kidneys, where it participates in regulating physiological functions of these organs. 

Now, all these now we can target through the skin because, again, the skin is like the antenna that receives the signals from millimeter and sub-millimeter radio waves. 

And Allantoin, just briefly to describe another part of our approach is it synergizes with GABA because it protects against the induced cell damage by EMFs. 

It reduces free radical activity. Now, the free radical activity, reactive oxygen species are produced as consequence of EMF exposure, and they are associated, again, with a number of neurological disturbances that include anxiety, poor quality of sleep, poor quality of dreams. 

And so, Allantoin helps in this. It positively affects the cognitive functions, increases neuronal cell proliferation of immature neurons in the hippocampus, again, and thus, it contributes to learning and memory, and in this respect, it synergizes with GABA. It has memory-enhancing effects up to the point that it is 

433 

proposed as a treatment for Alzheimer’s disease. 

So, now, here we have a two-pronged approach. On one side, we teach the microbes of our microbiome, starting from the gut, to withstand the effects of EMFs and then to transfer these abilities to our cells. And then, we target the skin because the skin is where the antennas that receive these EMFs are located. 

And we target the skin. One of the products of the microbes that is GABA and this produces the incredible effects. We already have clinical evidence on the quality of sleep, on stress, anxiety, and most interesting on quality of dreams. 

Dreams have become more numerous, more vivid. People have reported to smell things, to see vivid colors, and according to Jung, these are very good positive signs because they direct towards psychological equilibrium. 

So to conclude, and then I’m open to discussion, we will love to live in some etheric place as this one far from 5G towers, far from Fukushima type of radioactive pollution, far from any type of environmental pollution, including EMFs. 

Unfortunately, we can’t. We live surrounded by cellphones, like the first cellphones that is kind of a protasis of mine. And all of us, we live surrounded by wireless. Otherwise, I couldn’t be talking with you right now. So we live in this environment. This is an environment that we have to live with. 

So, we cannot shield ourselves from all the EMFs. And therefore, the best thing to do, in my opinion, is to exploit what nature offers us to protect ourselves from the harmful effects of EMFs. And I hope I’ve been able to convey this message. And of course, I am open to any question you may have. 

Dr. Schaffner: Yeah, that was excellent, Dr. Ruggiero. And I love the beautiful pictures you’ve been putting throughout your presentation. They’re really lovely. And yes, not many of us can experience such a beautiful place. And I agree. 

I mean, I think it’s just the reality. There’s going to be just increase in exposure until potentially we look at other forms of technology to be more biocompatible with our biology. 

So we have to continue to figure out how to support our resilience to these things. And yeah, I think this is a really innovative solution, and yeah, my mind is really open to all of this. 

And one thing when you’re talking about GABA to all of the health improvements or the health effects of GABA, but in my little research around GABA too,
I’ve seen that it helps with the aquaporin channels in the astrocytes for the glymphatic system. 

So, you’ve done such incredible work with developing products around the glymphatic system and enhancing the lymphatic drainage in the brain. And I wonder if that’s also another effect of GABA. Have you thought about that? 

Dr. Ruggiero: Yes. We have thought about that mechanism. The technology with GABA was born out of the desire to counteract the effects of EMFs on sleep, anxiety, stress, and dreams. 

But then, as it opened up, since we used some concepts that we had successfully used in the past, we have noticed that it also helps a lot with detoxification, I would say. So through the lymphatic system, but not only through the lymphatic system, but also through the skin. 

So, it helps a lot, and it is a very good complement to other approaches that 

we have. However, this GABA approach is quite unique as far as these kinds of subtle psychological effects are concerned. So we’re talking about mood. We’re talking about waking up in the morning with good optimism that is truly needed in these days. 

And so, all these effects that to find something that mimics the effects of alcohol and tranquilizers without any of the side effects of those, I think it’s something very interesting. And again, we used, we exploited our expertise on-skin technologies. 

We had worked on skin electroporation that is using electric current through the skin to study skin impotence and all these technical things. So, we put all this expertise to work, and I think that we now have an approach that is truly unique and truly fascinating. 

We are even working on some fringe or, let’s say, border types of science to see whether this approach could truly open the doors of perception. And I won’t say anything more. 

Dr. Schaffner: That’s really exciting in that a lot of my community also explores those either through plant medicines or other natural substances to open our minds to understand. You just have a fresh perspective of how to navigate the stressors of our time. 

And I guess, one, I’d love for you to just maybe briefly because you’ve done such incredible work with us not only on the glymphatic system but also many people, it’s still a new concept to understand the role of the interstitium and how that is. 

We use something topically through the skin, and it has all of the powerful effects that you just shared because of all the mechanisms. 

But also, we can think of this like systemic effects through the absorption
and the delivery through the interstitium and then how that can also be a transportation highway to get these nutrients and these compounds in the body to create a systemic effect. Are you thinking about that mechanism as well as you use these topical treatments? 

Dr. Ruggiero: Yeah, absolutely. The interstitium has been dubbed a new organ. Actually, it’s not an organ like the liver or the heart, but it’s an important part
of our human anatomy. And this is a kind of a holistic approach, also very microscopic, very anatomic because it truly connects everything. 

So, essentially, all our tissues, all our organs, all our systems are interconnected physically by an incredible array of very small tubes or tubules that physically connect all organs and tissues, and this interstitium starts at the skin, at the skin level. 

So again, the skin is the interface, another big discovery. I mean, this has been known for millennia. The skin is the interface between our bodies and our minds, now we know, and the environment. 

So the interstitium begins at the level of the skin. And from there, it connects everything inside our bodies, from our brains to our kidneys and organs and systems you can denominate. 

Now, if you are able to penetrate the interstitium, and this can be done now thanks to this proprietary new delivery system, then you can reach all parts of our bodies. 

And so, that’s the concept that we use. We have already used with other 435 

technologies that you have been applying for the past two, three years. I hope we’ve good success from what I can hear. 

And of course, we use the same approach with this GABA approach. This GABA approach also works on the skin because, again, the skin is where the antennas are located, but then, of course, it diffuses all over the body. 

Also, working with the skin and skin impedance and all these technical things about skin, we have learned a lot in the past decades, and now we can truly use the skin to target the rest of the body. 

[50:00] 

Think of acupuncture. I mean, nobody doubts the acupuncture work. It works in a number of different ways, but it works through the skin, actually through the nerve termini in the skin, but still, it works from the outside, and it has enormous effect inside. 

Well, our approach is not as acupuncture. We don’t use needles, but we use a very similar concept. So I was mentioning The Doors of Perception. If you read the original writings, you will find out that at the end, everything is connected. 

Well, in our limited knowledge, everything is connected through the interstitium, these little tubes, and we have, let’s say, broken the key, or we have found a way to exploit these intricate nets of connections to re-establish balance, to re- establish equilibrium that quite often is disrupted by EMFs. 

Dr. Schaffner: Thank you for explaining that. When I try to continue to understand my knowledge base of how everything’s interconnected and travels in the body, I keep coming back to the interstitium and the extracellular matrix and how all of these things are interconnected. 

And so, no, you always give a great explanation about that, Marco. And this was an absolutely fabulous presentation. You gave people a lot to think about and a lot of resources where people can go and check out these ideas or this information and continue to form their own opinions. 

You’ve showed your first paper. It was 1999, right before the iPhone, before 5G. And so, it’s like, this is something that– I’m glad that you’ve had so much knowledge and understanding to now develop an empowering solution so people can have less fear and more resilience and sleep well and have less anxiety and depression. 

And we can still live a very beautiful full life even though it’s stressful out there. So, thank you so much, Dr. Ruggiero. Where can people find out more about you, your work, and all of these wonderful ideas? 

Dr. Ruggiero: Well, I think you can give people all my contacts. I’m not a very private person. And I think in the first slide, let me see if I still have it. Bravo- europe.com, but again they can contact you, and I should be happy to answer any questions that anybody might have. 

Dr. Schaffner: Great. Well, thank you so much for your time. It’s always an excellent presentation, and I will be digesting all this information as well. And again, I can’t thank you enough. 

Dr. Ruggiero: Thank you, Christine. It has been a pleasure, honor, and a privilege. And I hope that we shall have many more opportunities like this in the future. 

Dr. Schaffner: Absolutely. 

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Dr. Ruggiero on Deeper Sleep

In this audio presentation, Dr. Ruggiero talks about the quality of our sleep and how we can support our creativity.   (including a novel new, natural product that he is working on). He is suggesting a new  cream to restore psychological balance through dreams and REM sleep and getting deeper than our ego selves.  Dreams are the precursor to creativity and may help us get unstuck and solve our problems.  He shows us how to protect and deepen our dreams and our level of consciousness.  Scientific evidence shows how Lyme disease is vastly helped by deepening sleep.  Get the recording here.

Dr. Ruggiero and Dr. Schaftner discuss an upcoming collaboration.

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Potential role of GcMAF in suppressing the severity of COVID-19-induced immune responses: Lesson learned from HIV

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513798/

Med Hypotheses. 2020 Nov; 144: 110293. Published online 2020 Sep 24. doi: 10.1016/j.mehy.2020.110293PMCID: PMC7513798PMID: 33254486

Lucrezia Spaderaa,⁎ and  Maria SpaderabAuthor informationArticle notesCopyright and License information

Introduction

Over the last six months, there have been increasing numbers of reports that struggle to understand the pathogenesis of the coronavirus disease 2019 (COVID-19) pandemic.

As of August 16, 2020, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for more than 21 294 000 infections and about 760 000 deaths worldwide [1], but the mechanisms of virus-induced host damage remain a mystery. Understanding the pathways behind viral pathogenicity just like cellular and tissue tropism, counteracting host defence processes and immunological responses are crucial to find new therapeutic strategies. Based on clinical reports, it is noteworthy that COVID-19 causes various degree of illness ranging from asymptomatic or milder symptomatic cases to severe lung injury or even multi-organ dysfunction with liver and kidney impairment [2][3][4]. Even in not severe patients, the heterogeneity of symptoms is consistent with the increasing evidence that SARS-CoV-2 shows a broad tissue tropism, being able to attack almost anything in the body [2][3][4][5]. To date, the most commonly investigated hypothesis about the underlying mechanisms of multi-organ failure may be summarized into three main targets: microcirculation dysfunction, overwhelming inflammation and abnormal coagulation [7]. Radiologic and laboratory findings as well as preliminary autopsy studies seem to support this hypothesis. The most common patterns seen on chest CT were ground-glass opacity, interlobular septal thickening, air bronchogram, bilateral patchy shadowing, crazy-paving pattern, and thickening of the adjacent pleura, resembling an interstitial involvement in viral pneumonia [2][3][7][8]. Under the light of microscope, the lungs revealed diffuse alveolar damage with formation of numerous hyaline membranes, very patchy and sparse interstitial chronic inflammation composed mainly of lymphocytes, thrombi within a few small pulmonary artery branches, congestion of alveolar septal capillaries, focal edema fluid, and macrophage infiltration within the airspaces [9][10][11][12]. The more significant laboratory abnormalities were metabolic acidosis, lymphocytopenia, leukopenia, thrombocytopenia, elevated levels of C-reactive protein (CRP), interleukin-6 (IL-6), lactate dehydrogenase (LDH) and D-dimer [2][3][4][5][6][7]. As firstly suggested by Huang C et al. [4], the systemic cytokine storm could play a key role in the virus-induced tissue damage. However, the question “what the link for the overproduction of pro-inflammatory mediators and the immune suppression, on the hand, and microvascular injury and thromboembolism, on the other, is”, remains unclear.

Being the knowledge of this issue very scarce, lessons learned from other human pathogenic viruses, with specific reference to human immunodeficiency virus (HIV), could be diriment.Go to:

The hypothesis

Based on the aforementioned findings and on documented analogies between SARS-CoV-2 and HIV [13], we hypothesized that the reduced conversion activity of the Gc protein (human group-specific component (Gc)) into the macrophage activating factor (MAF) could have a key role in the dysregulate immune response induced by SARS-CoV-2, just like for HIV infected patients [14][15]. If this hypothesis is correct, it might help to set a valid strategy of immunotherapy also based on an off-label use of GcMAF in critically ill COVID-19 patients.

GcMAF and COVID-19: a literature review with a focus on the evaluation of the hypothesis

Gc globulin, DBP and GcMAF: three in one

Serum Gc protein, also known as vitamin D-binding protein (DBP), is a multifunctional protein present in plasma/serum at concentrations of 300–600 mg/L [16]. It carries a trisaccharide consisting of N-acetylgalactosamine with dibranched galactose and sialic acid termini at 420 threonine residue [17]. Stepwise hydrolysis of Gc protein by the inducible membranous β-galactosidase of stimulated B-lymphocytes, and by the Neu-1 sialidase of T-lymphocytes converts it into the active GcMAF [17][18][19]. On the contrary, deglycosilation of Gc protein by action of the enzyme alpha-N-acetylgalactosaminidase, named nagalase, secreted from HIV-infected cells leads to lack of macrophage activation and to immunosuppression, as a consequence [14][15]. It is remarkable that nagalase was demonstrated to be an intrinsic component not only of the envelope glycoproteins gp120 and gp160 of HIV but also of the hemagglutinin (HE) of influenza virus [15][20] and even produced by neoplastic cells [21][22][23]. Indeed, flu-like symptoms with serum nagalase activity similar to the influenza acute state were reported in the early stage of HIV-infection, so that the serum enzyme activity may be detectable at all phases of HIV-infection [14][15]. Similarly, most COVID-19 patients complained of flu-like symptoms in the early stages of the disease [2][3][4][5].

The role of GcMAF as a multifunctional immune modulator and possible implications in Covid-19.

It is now well known that DBP Gc-globulin plays a crucial role in immune system regulation as a primary defense against infections [14][15][16][17][18][19][20]. In addition to the storage and transport of active vitamin D3, GcMAF’s effects include macrophage modulation, osteoclast activation, facilitation of neutrophil chemotaxis mediated by C5 derived peptide, superoxide activity, scavenging of circulating G-actin, anti-angiogenetic and anti-tumor properties [24][25][26][27][28]. Thus, this multifunctional protein, released into the blood stream, acts as a systemic immune modulator without pro-inflammatory activities. This means that any function impairment of Gc-globulin could result in a state of both immunosuppression and uncontrolled inflammation, just like in severe COVID-19. Interestingly, HIV viremia was associated with higher level of biomarkers of inflammation (measured by IL-6), monocyte activation (soluble CD14), and coagulation (D-dimer), leading to increased mortality, as compared with uninfected people [29]. Meanwhile, in COVID-19 patients, in addition to the reduced peripheral lymphocyte counts, mainly CD4+ T and CD8+ T cells, there were found significant high levels of pro-inflammatory cytokines and chemokines [2][3][4][5][6][7]. Indeed, GcMAF is not only a simple potent activator for macrophages, but more specifically is able to turn macrophage activity on at the sites of infection/inflammation and then to induce their apoptosis by upregulating caspase activity via the p38 and JNK1/2 pathways when no longer needed [30]. Post-mortem lung observations of patients died of COVID-19 showed the presence of mononuclear cells and macrophages infiltrating air spaces by autopsy [9][10][11][12].

With regards to the anti-oxidant properties, it was assessed that GcMAF promotes the superoxide generating capacity of activated macrophages and the production of nitric oxide (NO) [31]. An article by Nozik-Grayck et al. [32] pertinently and interestingly showed that the expression of extracellular superoxide dismutase (EC-SOD) mRNA and protein is cell- and tissue-specific and is prominent in lung, heart, blood vessels, placenta and kidney. In particular, high levels of EC-SOD are present in lung macrophages, alveolar type II cells, fibroblasts, vascular smooth muscle cells, and endothelial cells. EC-SOD limits oxidative stress and preserves NO bioactivity, thus protecting against a number of lung and cardiovascular diseases [32]. Even though only in a minority of cases, COVID-19 may progress to life-threatening complications, including respiratory failure, acute cardiac injury, acute kidney injury, septic shock, disseminated intra-vascular coagulation (DIC), and multi-organ dysfunction [2][3][4][5]. Hypoxemia was found to be associated with interstitial pneumonia and, in 10% to 20% of cases, developed into acute respiratory distress syndrome (ARDS) [2][3][4][5].

In this connection, it was documented that ARDS as well as organ dysfunction and septic shock is characterized by actin release which is involved in microvascular impairment [33][34].

DBP has an additional function in binding monomeric globular (G)-actin with high affinity. Thereby, rapidly removing polymeric actin fibrils from the blood stream, it prevents actin polymers from clogging the micro vessels not unlike fibrinogen/fibrin and consequently platelet aggregation and micro thrombi formation [26][35]. What we postulated could also explain hypercoagulability with elevated concentrations of D-dimer, fibrin degradation products increase, PT and aPTT prolongation, observed in COVID-19 patients [36][37]. Tang N et al. [37] reported that 71.4% of the non survivors of COVID-19 matched the grade of overt‐DIC according to the International Society on Thrombosis and Haemostasis (ISTH) diagnostic criteria for DIC.

Murine models deficient in DBP showed lung damage caused by actin polymerization, developing severe acute lung inflammation with vascular leakage, hemorrhage and thickening of the vascular wall after actin injection [38]. Interestingly, the lung was the only organ that showed inflammatory injury after intravenous actin injection. The observed lung inflammation was consistent with alterations to lung microvascular endothelial cells. Indeed, when lung endothelial cells were exposed to DBP-actin complexes in vitro showed enhanced cell death [38]. Reduced levels of DBP were even observed in sepsis and organ dysfunction of trauma patients as well as complete depletion of free DBP in those affected by septic shock [33][34]. These data could provide support for pathogenic explanations of cellular and tissue damage by SARS-CoV-2 and, at the same time, for the therapeutic use of DBP to bind extracellular actin and counteract microcirculatory alterations.

Whereas DBP also binds free fatty acids, it was shown that the administration of GcMAF complexed with oleic acid (OA) via nebulisation or subcutaneous injection led to rapid decrease of blood pressure and increase in splenic blood flow, as a result of a verisimilar synergistic NO release by OA-GcMAF-activated alveolar and splenic macrophages [31]. Severe or critically ill COVID-19 patients developed clinical typical manifestations of shock, even in the absence of overt hypotension [7].

Furthermore, it was found that GcMAF can inhibit the angiogenesis induced by pro-inflammatory prostaglandin E1 [39], which serves roles in the promotion of vascular endothelial growth factor (VEGF) expression [40]. A key role of VEGF in acute lung injury and ARDS was confirmed [41].

Explaining the clinical heterogeneity of Covid-19 with DBP polymorphisms, estrogens and vitamin D

Reflecting the fact that clinical features and severity of symptoms vary widely between and within each COVID-19 patient, with older males more likely to be affected and in a more severe manner [42], we sought to relate it with some special feature of DBP. Several studies showed that the polymorphisms of DBP were associated with susceptibility or resistance to disease states including chronic obstructive pulmonary disease [43][44]. Moreover, whereas androgens were not found to have any effect on circulating levels of DBP, exposure to high levels of estrogens increased them by up to 50%, suggesting a potential protective role of estrogens against COVID-19 [28]. On the other hand, in relation to vitamin D status, advanced age was recognized as one of the major risk factors for vitamin D deficiency [45]. Animal-based studies also demonstrated that deficiencies in both dietary protein- and energy-intake decreased the concentration of DBP in the circulation [46]. These data seem to be in line with the growing evidence that vitamin D supplementation could reduce the risk of COVID-19 infections and deaths [47][48][49].

Towards the application of GcMAF as immunotherapy: from cancer to SARS-CoV-2 infection

To date, a pharmaceutical grade GcMAF agent that can be administered to patients with COVID-19 is not developed yet, but, as our hypothesis suggests that GcMAF, an activator of macrophage, a key player of innate immunity, may be effective in suppressing the severity of COVID-19-induced immune responses, it would be advisable to proceed in this way.

In the GcMAF development timeline, there have been three major types of GcMAF until now: purified (i.e. first-generation) GcMAF, serum (i.e. second-generation) GcMAF, and oral colostrum MAF (i.e. third-generation GcMAF).

The first-generation GcMAF is produced from Gc protein isolated from human serum by an artificial enzymatic method using an affinity column modified with 25-hydroxy-vitamin D3 [50].

The second-generation GcMAF is prepared from degalactosylated/desialylated human serum without isolation of Gc protein using vitamin D affinity chromatography, leading to a higher concentration, stability and activity of the final GcMAF, without the risk of cross-contamination between different serum samples [51]. In addition, the second-generation GcMAF has been shown to have increasing activity of macrophages, superoxide radical generation, anti-angiogenetic effects, and antitumor effects.

In 2014, Saisei Mirai clinics (cell processing center, clinic in Kobe, Osaka and Tokyo), in collaboration with Tokushima University, developed a new form of GcMAF made from bovine colostrum [52]. Colostrum MAF has the advantage that it can be orally administered, namely, in an acid-resistant enteric capsule to activate macrophages in the gut-associated lymphoid tissue (GALT) [53]. This is considered to be the largest macrophage pool in the body playing a very important role in maintaining and regulating mucosal immunity [53]. Macrophages in the gastrointestinal mucosa also could modulate the respiratory tract mucosal immunity through immune regulation, the so-called “gut-lung axis”. Additionally, colostrum MAF is administered as a powder in the mouth to activate macrophages in the lymphoid tissue of the Waldeyer’s tonsillar ring. In this regard, it is remarkable that Angiotensin Converting Enzyme 2 (ACE2), an Entry Receptor for SARS-CoV-2, was found to be highly expressed in gastrointestinal epithelial cells, providing a prerequisite for SARS-CoV-2 infection [54]. On this base, if we consider GcMAF as an off-label immunomodulating agent for the treatment of COVID-19, oral administration should be preferred to all the other ones.

Although the administration of GcMAF is a yet an unapproved therapy, data from previous studies and clinical practice reported its effectiveness in the treatment of many pathologies such as HIV infection [55]and other infectious diseases [53], some types of cancer [56][57][58][59][60], juvenile osteopetrosis [61], immunological (systemic erythematous lupus) [62] and neurological (multiple sclerosis, autism) diseases [57][63][64]. In the same conditions, it was found an inverse correlation between the MAF precursor activity and serum levels of nagalase (reference ranges from 0,32 to 0,65–0,95 nM/min/ng), therefore showing to be other than pathogenicity or cancer biomarkers, also good prognosticators of illness and response to therapy [54][55][56][57][58][59][60][61][62][63][64].

However, it’s clear that only well-designed clinical trials will be able to properly evaluate the therapeutic use of GcMAF.

The main targets of the pharmacologic approaches to COVID-19, especially for the complicated cases, are addressed to modulate the immune system and counteract the overwhelming inflammation.

Notably, the mechanisms we have hypothesized about the possible pathogenesis of the cell and tissue damage induced by SARS-CoV-2 seem to provide a common denominator in explaining the effects of most drugs currently considered for the treatment of COVID-19: these include antivirals (i.e. remdesivir, lopinavir/ritonavir, darunavir, cobicistat) and immunomodulating and/or anti-inflammatory drugs [65][66].

In particular, based on their antiviral activity [67], chloroquine and hydroxychloroquine, initially conceived as antimalarial therapeutics, were proposed to treat patients hospitalized with COVID-19, better if associated to azithromycin, showing promising efficacy in “inhibiting the exacerbation of pneumonia, improving lung imaging findings, promoting a virus negative conversion and shortening the disease course“ [68][69]. On the other hand, hydroxychloroquine is the cornerstone of medical therapy in lupus, where it acts as an immunomodulatory without immunosuppressive effects [70]. However, in light of ongoing serious cardiac adverse events [71] and other serious side effects, the known and potential benefits of chloroquine and hydroxychloroquine no longer outweigh the known and potential risks for the authorized use in COVID-19 patients. In addition, the COVID-19 Treatment Guidelines Panel recommends against using hydroxychloroquine plus azithromycin for the treatment of COVID-19, except in a clinical trial [72].

Tocilizumab, an IL-6 antagonist, approved for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis, also had therapeutic application in critical COVID-19 patients, providing encouraging results [73]. However, the phase III clinical trial (COVACTA) [74] for evaluating tocilizumab in hospitalized patients with severe COVID-19 pneumonia found no difference between tocilizumab versus placebo in intensive care requirements or mortality. Therefore, there are insufficient data for the Panel to recommend either for or against the use of the IL-6 inhibitors for the treatment of COVID-19 [72].

The rationale basis for the use of monoclonal antibodies in patients affected by SARS-CoV-2 seems to lie in the so-called systemic cytokine storm. Taking into account the key role of VEGF in enhancing angiogenesis in acute lung injury and ARDS [75], two trials, evaluating the efficacy of bevacizumab as VEGF antagonist in the treatment of COVID-19 (BEST-PC and BEST-RCT), were started [76][77].Go to:

Possible consequences of the hypothesis and conclusion

Less than two months after the declaration of pandemic state by the World Health Organization, every effort by the entire scientific community has been made to face this worldwide emergency of COVID-19 in the best possible way.

However, at the present days, the underlying mechanisms of pathophysiology remain unknown. Nowadays, although a number of preliminary clinical trials are underway and scientific evidence is growing on this topic, neither specific drugs nor effective preventive measures are yet available for the treatment of COVID-19. Anyway, it seems we still have a great deal of work to find the “miracle care”. However, due to the risk of serious drug-related adverse events, the immunomodulatory and anti-inflammatory drugs currently used for COVID-19, are still restricted to carefully selected and complicated cases [71][78][79][80][81].

So, in sight of this, given its multifunctional properties, we believe that GcMAF could have a very important role in the pathophysiology of organ damage induced by SARS-CoV-2, providing explanations which are consistent with the clinical, radiological and histopathological findings observed in patients with COVID-19.

Despite burgeoning data from case series of various pathological conditions demonstrated the potential clinical benefits of GcMAF as above mentioned [55][56][57][58][59][60][61][62][63][64], no randomized controlled clinical trials verifying these preliminary results have been made till now. So, there are still unresolved controversies about the possibility of an its therapeutic application. To date, no other researcher has investigated the possibility of a potential linkage between GcMAF and COVID-19.

However, in view of the immunomodulatory potential and the high safety profile of GcMAF and because COVID-19 remains a life-threatening condition in many cases, despite currently recommended therapies, we think it is worth explorating our hypothesis further by:

  • -detecting the MAF precursor activity of serum Gc protein and serum Nagalase activity in all COVID-19 patients;
  • -providing in a short time, in addition to currently used drugs, GcMAF to critically ill COVID-19 patients, requesting Institutional Review Board (IRB) approval for compassionate use protocols on an emergency basis;
  • -confirming, in prospective randomized controlled clinical trials, the efficacy and the safety of the proposed treatment, in order to allow the international scientific community to analyse the results and guide the future clinical practice.

According to the provided literature overview, we firmly believe that GcMAF deserves be tested as immune-therapeutic to increase macrophages functionality for earlier SARS-CoV-2 viral control, protection against COVID-19 progression by limiting epithelial damage, control local inflammation and prevent from the hyperinflammatory immune response. For this purpose, we planned a Phase-II interventional clinical trial evaluating the effectiveness and safety of Oral immunotherapy with Third Generation GcMAF in hospitalized patients with COVID-19 pneumonia (COral-MAF1 Trial) at the “Ospedale del Mare” Hospital, Naples, Italy. For the time being, we are waiting for clinical trial approval by local ethics Committee.

In conclusion, even though our hypothesis might be not fully correct, we still wanted to give our own contribution to the research on COVID-19 pandemic which had the only underserved merit to give all humans across the world a common goal.

So, as we still see life from a rosy perspective from this small Italian hospital facing the sea, our last thought and gratitude are for all the researchers and health care professionals which are committed to the forefront of the war against SARS-CoV-2.Go to:

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Go to:

References

1. World Health Organization. Coronavirus disease 2019 (COVID-19): situation report 209. (https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200816-covid-19-sitrep-209.pdf?sfvrsn=5dde1ca2_2).

2. Guan W.J., Ni Z.Y., Hu Y. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020 [Google Scholar]

3. Chen N, Zhou M, Dong X. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 15-21 February; 395(10223): 507–513. [PMC free article] [PubMed]

4. Huang C., Wang Y., Li X. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. [PMC free article] [PubMed] [Google Scholar]

5. Zhou M., Zhang X., Qu J. Coronavirus Disease 2019 (COVID-19): a clinical update. Front Med. 2020[PMC free article] [PubMed] [Google Scholar]

6. Liu J, Li S, Liu J, et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. medRxiv 2020; published online Feb 22. [PMC free article] [PubMed]

7. Li H., Zhang D., Xu J. SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet. 2020[PMC free article] [PubMed] [Google Scholar]

8. Shi H., Han X., Jiang N. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis. 2020;20(4):425–434. [PMC free article] [PubMed] [Google Scholar]

9. Barton LM, Duval EJ, Stroberg E. COVID-19 Autopsies, Oklahoma, USA. Am J Clin Pathol. 2020 Apr 10. pii: aqaa062. [PMC free article] [PubMed]

10. Tian S., Hu W., Niu L. Pulmonary pathology of early-phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer: special report. J Thorac Oncol. 2020 [PMC free article][PubMed] [Google Scholar]

11. Xu Z., Shi L., Wang Y. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 [PMC free article] [PubMed] [Google Scholar]

12. Tian S., Xiong Y., Liu H. Pathological study of the 2019 novel coronavirus disease (COVID-19) through post-mortem core biopsies. Mod Pathol. 2020 [PMC free article] [PubMed] [Google Scholar]

13. Fung S.Y., Yuen K.S., Ye Z.W. A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses. Emerg Microbes Infect. 2020;9(1):558–570. [PMC free article] [PubMed] [Google Scholar]

14. Yamamoto N., Naraparaju V.R., Srinivasula S.M. Structural modification of serum vitamin D3-binding protein and immunosuppression in AIDS patients. AIDS Res Hum Retroviruses. 1995;11(11):1373–1378.[PubMed] [Google Scholar]

15. Yamamoto N. Pathogenic significance of alpha-N-acetylgalactosaminidase activity found in the envelope glycoprotein gp160 of human immunodeficiency virus Type 1. AIDS Res Hum Retroviruses. 2006;22(3):262–271. [PubMed] [Google Scholar]

16. Kawakami M., Blum C.B., Ramakrishnan R. Turnover of the plasma binding protein for vitamin D and its metabolites in normal human subjects. J Clin Endocrinol Metab. 1981;53(6):1110–1116. [PubMed] [Google Scholar]

17. Yamamoto N., Homma S. Vitamin D3 binding protein (group-specific component) is a precursor for the macrophage-activating signal factor from lysophosphatidylcholine -treated lymphocytes. Proc Natl Acad Sci USA. 1991 [PMC free article] [PubMed] [Google Scholar]

18. Yamamoto N., Naraparaju V.R. Vitamin D3-binding protein as a precursor for macrophage activating factor in the inflammation-primed macrophage activation cascade in rats. CellImmunol. 1996;170(2):161–167. [PubMed] [Google Scholar]

19. Yamamoto N., Kumashiro R., Yamamoto M. Regulation of inflammation-primed activation of macrophages by two serum factors, vitamin D3-binding protein and albumin. Infect Immun. 1993;61(12):5388–5391. [PMC free article] [PubMed] [Google Scholar]

20. Yamamoto N., Urade M. Pathogenic significance of alpha-N-acetylgalactosaminidase activity found in the hemagglutinin of influenza virus. Microbes Infect. 2005 Apr;7(4):674–681. [PubMed] [Google Scholar]

21. Yamamoto N., Naraparaju V.R., Asbell S.O. Deglyco-sylation of serum vitamin D3-binding protein leads to immunosuppression in cancer patients. Cancer Res. 1996;56:2827–2831. [PubMed] [Google Scholar]

22. Saburi E, Tavakol-Afshari J, Biglari S, et al. Is α-N-acetylgalactosaminidase the key to curing cancer? A mini-review and hypothesis. J BUON. 2017 Nov-Dec;22(6):1372-1377. [PubMed]

23. Saburi E, Saburi A, Ghanei M. Promising role for Gc-MAF in cancer immunotherapy: from bench to bedside. Caspian J Intern Med. 2017 Fall;8(4):228-238. [PMC free article] [PubMed]

24. Nagasawa H, Uto Y, Sasaki H, et al. Anticancer Res. Gc protein (vitamin D-binding protein): Gc genotyping and GcMAF precursor activity. 2005 Nov-Dec;25(6A):3689-95. [PubMed]

25. Ruggiero M., Reinwald H., Pacini S. Is chondroitin sulfate responsible for the biological effects attributed to the GC protein-derived Macrophage Activating Factor (GcMAF)? Med Hypotheses. 2016;94:126–131. [PubMed] [Google Scholar]

26. Van Baelen H., Bouillon R., De Moor P. Vitamin D-binding protein (Gc-globulin) binds actin. J Biol Chem. 1980;255(6):2270–2272. [PubMed] [Google Scholar]

27. Kanda S., Mochizuki Y., Miyata Y. Effects of vitamin D(3)-binding protein-derived macrophage activating factor (GcMAF) on angiogenesis. J Natl Cancer Inst. 2002;94(17):1311–1319. [PubMed] [Google Scholar]

28. Haddad JG. Plasma vitamin D-binding protein (Gc-globulin): multiple tasks. J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):579-82. Review. [PubMed

]29. So-Armah K.A., Tate J.P., Chang C.-C. Do biomarkers of inflammation, monocyte activation, and altered coagulation explain excess mortality between HIV infected and uninfected people? J Acquir Immune Defic Syndr. 2016;72(2):206–213. [PMC free article] [PubMed] [Google Scholar]

30. Gumireddy K., Reddy C.D., Swamy N. Mitogen-activated protein kinase pathway mediates DBP-maf-induced apoptosis in RAW 264.7 macrophages. J Cell Biochem. 2003;90(1):87–96. [PubMed] [Google Scholar]

31. Ruggiero M., Ward E., Smith R. Oleic acid, deglycosylated vitamin D-binding protein, nitric oxide: a molecular triad made lethal to cancer. Anticancer Res. 2014;34(7):3569–3578. [PubMed] [Google Scholar]

32. Nozik-Grayck E., Suliman H.B., Piantadosi C.A. Extracellular superoxide dismutase. Int J Biochem Cell Biol. 2005;37(12):2466–2471. Epub 2005 Jul 21. [PubMed] [Google Scholar]

33. Dahl B., Schiødt F.V., Ott P. Plasma concentration of Gc-globulin is associated with organ dysfunction and sepsis after injury. Crit Care Med. 2003;31(1):152–156. [PubMed] [Google Scholar]

34. Lee W.M., Galbraith R.M. The extracellular actin-scavenger system and actin toxicity. N Engl J Med. 1992;326(20):1335–1341. [PubMed] [Google Scholar]

35. Vasconcellos C.A., Lind S.E. Coordinated inhibition of actin-induced platelet aggregation by plasma gelsolin and vitamin D-binding protein. Blood. 1993;82(12):3648–3657. [PubMed] [Google Scholar]

36. Terpos E., Ntanasis-Stathopoulos I., Elalamy I. Hematological findings and complications of COVID-19. Am J Hematol. 2020 [PMC free article] [PubMed] [Google Scholar]

37. Tang N., Li D., Wang X. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844–847. [PMC free article][PubMed] [Google Scholar]

38. Ge L., Trujillo G., Miller E.J. Circulating complexes of the vitamin D binding protein with G-actin induce lung inflammation by targeting endothelial cells. Immunobiology. 2014;219(3):198–207.[PMC free article] [PubMed] [Google Scholar]

39. Pacini S, Morucci G, Punzi T, et al. Effect of paricalcitol and GcMAF on angiogenesis and human peripheral blood mononuclear cell proliferation and signaling. J Nephrol. 2012 Jul-Aug;25(4):577-81. [PubMed]

40. Slevin M., Kumar P., Gaffney J. Can angiogenesis be exploited to improve stroke outcome? Mechanisms and therapeutic potential. Clin Sci (Lond) 2006;111:171–183. [PubMed] [Google Scholar]

41. Barratt S., Medford A.R., Millar A.B. Vascular endothelial growth factor in acute lung injury and acute respiratory distress syndrome. Respiration. 2014;87(4):329–342. doi: 10.1159/000356034. [PubMed] [CrossRef] [Google Scholar]

42. Gausman J., Langer A. Sex and gender disparities in the COVID-19 pandemic. J Womens Health (Larchmt) 2020;29(4):465–466. [PubMed] [Google Scholar]

43. Chen H., Zhang L., He Z. Vitamin D binding protein gene polymorphisms and chronic obstructive pulmonary disease: a meta-analysis. J Thorac Dis. 2015;7(8):1423–1440. [PMC free article] [PubMed] [Google Scholar]

44. Stakisaitis D., Lesauskaitė V., Girdauskaitė M. Investigation of vitamin D-binding protein polymorphism impact on coronary artery disease and relationship with longevity: own data and a review. Int J Endocrinol. 2016;2016:8347379. [PMC free article] [PubMed] [Google Scholar]

45. Lips P. Vitamin D physiology. Prog Biophys Mol Biol. 2006;92(1):4–8. [PubMed] [Google Scholar]

46. Laing C.J., Fraser D.R. Changes with malnutrition in the concentration of plasma vitamin D binding protein in growing rats. Br J Nutr. 2002 Aug;88(2):133–139. [PubMed] [Google Scholar]

47. Grant W.B., Lahore H., McDonnell S.L. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients. 2020;12(4) [PMC free article] [PubMed] [Google Scholar]

48. La Vignera S., Cannarella R., Condorelli R.A. Sex-specific SARS-CoV-2 mortality: among hormone-modulated ACE2 expression, risk of venous thromboembolism and hypovitaminosis D. Int J Mol Sci. 2020;21(8) [PMC free article] [PubMed] [Google Scholar]

49. Caccialanza R., Laviano A., Lobascio F. Early nutritional supplementation in non-critically ill patients hospitalized for the 2019 novel coronavirus disease (COVID-19): Rationale and feasibility of a shared pragmatic protocol. Nutrition. 2020;3 [PMC free article] [PubMed] [Google Scholar]

50. Swamy N., Roy A., Chang R. Affinity purification of human plasma vitamin D-binding protein. Protein Expr Purif. 1995;6(2):185–188. [PubMed] [Google Scholar]

51. Uto Y., Hori H., Kubo K. GcMAF: our next-generation immunotherapy. Nature. 2012;485:S67–S70.[Google Scholar]

52. Uto Y., Kawai T., Sasaki T. Degalactosylated/desialylated bovine colostrum induces macrophage phagocytic activity independently of inflammatory cytokine production. Anticancer Res. 2015;35:4487–4492. [PubMed] [Google Scholar]

53. Inui T., Kubo K., Kuchiike D. Oral colostrum macrophage-activating factor for serious infection and chronic fatigue syndrome: three case reports. Anticancer Res. 2015;35:4545–4549. [PubMed] [Google Scholar]

54. https://www.ncbi.nlm.nih.gov/gene/59272.55. Yamamoto N, Ushijima N, Koga Y. Immunotherapy of HIV-infected patients with Gc protein-derived macrophage activating factor (GcMAF). J Med Virol. 2009 Jan;81(1):16-26. Retraction in: J Med Virol. 2014 Nov;86(11):1998. [PubMed]

56. Yamamoto N., Suyama H. Immunotherapy for prostate cancer with Gc protein-derived macrophage-activating factor, GcMAF. Transl Oncol. 2008;1:65–72. [PMC free article] [PubMed] [Google Scholar]

57. Thyer L., Ward E., Smith R. Therapeutic effects of highly purified de-glycosylated GcMAF in the immunotherapy of patients with chronic diseases. Am J Immunol. 2013;9:78–84. [Google Scholar]

58. Inui T., Kuchiike D., Kubo K. Clinical experience of integrative cancer immunotherapy with GcMAF. Anticancer Res. 2013;33:2917–2919. [PubMed] [Google Scholar]

59. Inui T., Makita K., Miura H. Case report: A breast cancer patient treated with GcMAF, sonodynamic therapy and hormone therapy. Anticancer Res. 2014;34:4589–4593. [PubMed] [Google Scholar]

60. Chaiyasit K., Toshio I., Wiwanitkit V. The use of Gc protein-derived macrophage activating factor for management of thyroid cancer. J Cancer Res Ther. 2015;11:1041. [PubMed] [Google Scholar]

61. Yamamoto N., Naraparaju V.R., Orchard P.J. Defective lymphocyte glycosidases in the macrophage activation cascade of juvenile osteopetrosis. Blood. 1996;88:1473–1478. [PubMed] [Google Scholar]

62. Yamamoto N., Naraparaju V.R., Moore M., Brent L.H. Deglycosylation of serum vitamin D3-binding protein by alpha-N-acetylgalactosaminidase detected in the plasma of patients with systemic lupus erythematosus. Clin Immunol Immunopathol. 1997;82:290–298. [PubMed] [Google Scholar]

63. Inui T., Katsuura G., Kubo K. Case report: GcMAF treatment in a patient with multiple sclerosis. Anticancer Res. 2016;36:3771–3774. [PubMed] [Google Scholar]

64. Bradstreet J.J., Vogelaar E., Thyer L. Initial observations of elevated alpha-N-acetylgalactosaminidase activity associated with autism and observed reductions from Gc protein–macrophage activating factor injections. Autism Insights. 2012;4:31. [Google Scholar]

65. Scavone C., Brusco S., Bertini M. Current pharmacological treatments for COVID-19: what’s next? Br J Pharmacol. 2020 [PMC free article] [PubMed] [Google Scholar]

66. Jean S.S., Lee P.I., Hsueh P.R. Treatment options for COVID-19: the reality and challenges. J Microbiol Immunol Infect. 2020;53(3):436–443. [PMC free article] [PubMed] [Google Scholar]

67. Inglot A.D. Comparison of the antiviral activity in vitro of some non-steroidal anti-inflammatory drugs. J Gen Virol. 1969;4(2):203–214. doi: 10.1099/0022-1317-4-2-203. [PubMed] [CrossRef] [Google Scholar]

68. Touret F., de Lamballerie X. Of chloroquine and COVID-19. Antiviral Res. 2020;177 [Google Scholar]

69. Gao J., Tian Z., Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020;14(1):72–73.[PubMed] [Google Scholar]

70. Jordan N., D’Cruz D. Current and emerging treatment options in the management of lupus. Immunotargets Ther. 2016 [PMC free article] [PubMed] [Google Scholar]

71. Frisk-Holmberg M., Bergqvist Y., Englund U. Chloroquine intoxication. Br J Clin Pharmacol. 1983;15(4):502–503. [PMC free article] [PubMed] [Google Scholar]

72. https://files.covid19treatmentguidelines.nih.gov/guidelines/covid19treatmentguidelines.pdf.

73. Oldfield V., Dhillon S., Plosker G.L. Tocilizumab: a review of its use in the management of rheumatoid arthritis. Drugs. 2009;69(5):609–632. [PubMed] [Google Scholar]

74. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2020 Mar 25 – Identifier: NCT04320615, A Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia (COVACTA). (https://clinicaltrials.gov/ct2/show/NCT04320615).

75. Wang Y, Fei D, Vanderlaan M, Song A. Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro. Angiogenesis. [PubMed]

76. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2020 Feb 19 – Identifier NCT04275414, Bevacizumab in severe or critical patients with Covid-19 pneumonia (BEST-CP). (https://clinicaltrials.gov/ct2/show/ NCT04275414).

77. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2020 Mar 12 Identifier: NCT04305106, Bevacizumab in Severe or Critically Severe Patients With COVID-19 Pneumonia-RCT (BEST-RCT). (https://clinicaltrials.gov/ct2/show/NCT04305106).

78. Yam J.C., Kwok A.K. Ocular toxicity of hydroxychloroquine. Hong Kong Med J. 2006;12(4):294–304.[PubMed] [Google Scholar]

79. Radbel J, Narayanan N, Bhatt PJ. Use of tocilizumab for COVID-19 infection-induced cytokine release syndrome: A cautionary case report. Chest. 2020 Apr 25. pii: S0012-3692(20)30764-9.

80. Rubel A.R., Chong P.L., Abdullah M.S. Letter to the Editor: Lipemic serum in patients with COVID-19 undergoing treatment. J Med Virol. 2020;28 [Google Scholar]

81. Zhang S., Li L., Shen A. Rational use of tocilizumab in the treatment of novel coronavirus pneumonia. Clin Drug Investig. 2020 [PMC free article] [PubMed] [Google Scholar]

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imuno® is over 100 times more effective than pure GcMAF

imuno® is over 100 times more effective than pure GcMAF

19th February 2020: Dr Marco Ruggiero, MD. PhD.

Elevated serum alpha-N-acetylgalactosaminidase (nagalase) is associated with a number of life threatening and/or debilitating conditions ranging from cancer (Korbelik et al., 1998; Greco et al., 2009; Thyer et al., 2013) to viral infections caused by influenza virus and HIV (Yamamoto and Urade, 2005; Yamamoto, 2006), bacterial infections (Caines et al., 2008), alcoholism (Zoga et al., 2017), and autism (Bradstreet et al., 2012). Nagalase, an enzyme, was first proposed as a marker for cancer and viral infections and its increased serum activity in these conditions was associated with immune system deficiency because nagalase prevents formation of the Gc protein derived Macrophage Activating Factor (GcMAF), an immune stimulant cytokine (Yamamoto and Naraparaju, 1997; Yamamoto and Urade, 2005; Yamamoto, 2006). According to the original hypothesis proposed by Yamamoto and Colleagues, cancer cells and cells infected by viruses produced and released nagalase that caused immune deficiency that, in turn, favored the progression of cancer or viral infections. Therefore, elevated serum nagalase activity in cancer and viral infections was considered a consequence of cancer or viral-infected cells releasing nagalase. In apparent agreement with this hypothesis, successful immunotherapy of cancer with GcMAF was associated with a decrease of serum nagalase activity (Thyer et al., 2013; Schwalb et al., 2016) that was attributed to the effects of GcMAF on macrophages that, once activated, attacked cancer cells with consequent decrease of the number of cancer cells producing nagalase.

This interpretation, however, was contradicted by the observation that in autism, just like in cancer, successful immunotherapy with GcMAF was associated with significant decrease of serum nagalase activity (Bradstreet et al., 2012). Since the autistic subjects successfully treated with GcMAF had no signs of cancer cells producing nagalase, nor of any other concurrent disease or infections (Bradstreet et al., 2012), a novel hypothesis concerning the role of nagalase was proposed. According to this novel hypothesis, elevated nagalase activity has to be considered more a pathogenetic factor for cancer and other conditions rather than a simple marker. In simpler words, elevated nagalase activity may be one of the causative factors leading to cancer, autism or other diseases because elevated nagalase impairs the function of the immune system and immune deficiency plays a pivotal role in the onset and development of cancer and other diseases. Such a role for nagalase is now well established as exemplified by the title of a recent review that reads ” Is α-N-acetylgalactosaminidase the key to curing cancer?” (Saburi et al., 2017a). Based on these considerations, strategies aiming at reducing serum nagalase activity may prove useful in the fight against cancer, autism, viral infections and all other conditions associated with elevated serum nagalase activity.

Here we demonstrated for the first time that GcMAF directly binds to, and inhibits, human nagalase in vitro, thus elucidating the mechanism of action of GcMAF and explaining its effectiveness in a variety of conditions ranging from cancer to autism (Saburi et al., 2017a; Saburi et al., 2017b; Bradstreet et al., 2012; Greilberger and Herwig, 2020). In addition, we demonstrate that a novel supplement containing low-molecular-weight microbial chondroitin sulfate, ultrapure phosphatidylcholine, and vitamin D3, (imuno®, imuno Corporation, Vanuatu) shows more than 100 fold higher activity than purified GcMAF.

Human nagalase and GcMAF were purified at R.E.D. Laboratories (Zellik, Belgium). The
experiment was performed using microtiter plates coated with a specific antibody able to capture human nagalase. Samples were incubated with a standardized dilution of a pool of 300 human sera from healthy subjects and, after 1 h incubation and exhaustive washing, nagalase-GcMAF or nagalase-imuno® complexes were detected with a horse radish peroxidase conjugate of a rabbit antibody. In order to establish the kinetics of interaction between nagalase and GcMAF, or imuno®, the serum pool was mixed either with 200 ng of purified Gc-MAF, or with a 1:100 dilution of imuno® in phosphate buffered saline (PBS). Since preliminary experiments indicated that undiluted imuno® exceeded the binding capacity of nagalase in the test, imuno® was diluted 1:100 in PBS. The mixture was then incubated at room temperature for 4, 24, 48, 72 and 120 h. Values for nagalase binding activity in the absence of GcMAF or imuno®, with only PBS in the reaction mixture, were taken as

1.00. The experiment was repeated twice and the results reported in Fig. 1 are the means of the two experiments.

Untitled-2-300x168.jpg

As shown in Fig. 1, purified GcMAF bound human nagalase only after 4 h incubation, reached a peak at 48 h, and returned below baseline values at 120 h. imuno®, on the other hand, had an initial value (at 0 h) higher than PBS, thus demonstrating immediate, intrinsic GcMAF activity against human nagalase. At every time point, imuno® showed significantly higher activity in comparison with purified GcMAF and, at 120 h, imuno® activity was still well above baseline, thus indicating a stronger, more prolonged activity. It is worth noticing that imuno® was diluted 100 fold and, therefore, it may be argued that its activity against human nagalase is more than 100 fold higher than that of purified GcMAF.

It is also important to consider that these results were obtained in vitro, that is in the absence of any variable or confounding factor that may hamper interpretation of results observed in clinical settings. Direct interaction between imuno® and nagalase may help explaining the effectiveness of imuno® recently observed by Antonucci and Colleagues in those conditions where GcMAF had proven effective in the past (Antonucci et al., 2019a; Antonucci et al., 2019b) and lead to propose imuno® as a more potent and intrinsically safer substitute for human-blood-derived GcMAF. The significantly higher potency of imuno® is to be ascribed to its peculiar molecular design that was described in detail in two recent papers (Ruggiero and Pacini, 2018a; Ruggiero and Pacini, 2018b); in brief, imuno® reproduces that physical-chemical features of GcMAF at a much higher molecular efficiency and density. The N- acetylgalactosamine active site of GcMAF is present in much higher concentration in imuno® thanks to the presence of low-molecular-weight chondroitin sulfate, a sulfated polysaccharide that is composed by an alternating chain of Nacetylgalactosamine and glucuronic acid. The hydrophobic moieties of GcMAF, that are the regions binding vitamin D and fatty acids, are present in imuno® thanks to the binding of phosphatidylcholine to chondroitin sulfate. Vitamin D3, essential for increasing the potency of GcMAF as demonstrated by Greilberger and Herwig in 2020, is intercalated in the proto-cellular structure formed by the core of chondroitin sulfate surrounded by phosphatidylcholine (Ruggiero and Pacini, 2018a). In fact, imuno® was designed taking into account the physical-chemical features of GcMAF that were published 2013 when a molecular model of GcMAF interaction with the cell membrane was described (Thyer et al., 2013). In this model, optimal interaction was achieved when GcMAF was non-covalently bound to a fatty acid – in that example, oleic acid – and vitamin D3 that are the conditions reproduced, at a much higher molecular efficiency and density, in imuno.

Buy it here: www.healthyenergetics.com

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Sulfate’s Critical Role for Maintaining Exclusion Zone Water: Dietary Factors Leading to Deficiencies



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Rapid Complete Recovery From An Autism Spectrum Disorder After Treatment of Aspergillus With The Antifungal Drugs Itraconazole And Sporanox

https://pubmed.ncbi.nlm.nih.gov/33132781/

Case Study: Rapid Complete Recovery From An Autism Spectrum Disorder After Treatment of Aspergillus With The Antifungal Drugs Itraconazole And Sporanox

Case Reports

. 2020 Aug;19(4):20-27.

Affiliations

  • PMID: 33132781
  • PMCID: PMC7572136 (available on 2021-08-01)

Context: A child with symptoms placing him within the autism spectrum and with urine biochemical markers consistent with fungal (Aspergillus) colonization of the gastrointestinal tract was first treated with the antifungal probiotic Saccharomyces boulardii. A dramatic Herxheimer reaction provided strong clinical indications that mold colonization might be a factor in causing autism in this child.

Objective: The child’s physician (Baker) wished to try a more potent antifungal therapy, itraconazole, in an attempt to reverse the child’s autism since itraconazole is an especially effective agent against Aspergillus species.

Setting: The child was treated as an outpatient by the physician who had first diagnosed the child with an autism spectrum disorder.

Participant: A child with an autism spectrum disorder.

Intervention: The major intervention was increasing doses of the antifungal drug itraconazole. However, the Sporanox® brand of itraconazole gave the best results. The child was monitored twice weekly with liver function tests which remained normal throughout the therapy.

Results: The child had a complete recovery from all the symptoms of autism and in addition developed excellent academic, athletic, and musical skills. The recovery coincided with a marked reduction of urine markers of Aspergillus colonization.

Conclusions: Escalation of the dose of itraconazole resulted in a complete loss of all symptoms of autism over the course of three months. This rapid complete reversal of autism is consistent with several articles proposing mold in general and Aspergillus specifically as a potential major cause of autism.

From: https://www.medicinenet.com/aspergillus_infection_aspergillosis/article.htm

The cause of an Aspergillus infection is a fungus (mold) that may, if conditions are favorable, spread and damage tissue and human organs. However, most people breathe in Aspergillus spores (conidia) daily with no ill effects. In general, people who develop any type of Aspergillus infection have risk factors that have airway compromise and/or weak immune systems.

Complete reversal of autism achieved in a child by using anti-fungal medication 

In a recent case study, a child had a complete recovery from all the symptoms of autism and in addition, developed excellent academic, athletic, and musical skills.  The recovery coincided with a reduction of urine markers for Aspergillus colonization. (mold)   We all inhale mold spores on a daily basis.  The difference between us and someone who is sickened by it is the strength of our immune system.

We recently tested some children on how strong they were at resisting various diseases.  (Immunity) We found some small number of diseases that the kids were not strongly able to resist.   We then realized that this “cluster” of weaknesses were related to each other and an emotional suppression which affected the weaknesses.   Things like helplessness or anxiety but were different for each person.

We then found things to strengthen the emotional issues and the result was that the children’s ability to respond to the diseases also strengthened and they were ability to resist the diseases.

I use imuno cream on my skin around my nose and mouth to help keep my systems “clear and strong” to resist Covid-19.  When I do this, I have an unexpected benefit.  My tummy beginning to gurgle and churn.   I wasn’t hungry or digesting.  This gut noise meant that I was digesting emotionally!  I know if I can stick with it for a moment, it will be done, gone and wow!

Most of us don’t really like to process in this way because it is uncomfortable emotionally to review upsetting things.  But the evidence is clear that when we face them and let them work their way out, we feel way better.  We literally need to digest them.  When I lift the suppression or excessive behavior, my tummy does rumble and I do indeed process.  Its needed & liberating.

Now, I use Bravo Yogurt to “summon my guts” and face things and allow them to process without pushing.  I watch the body’s behavior for feedback.  No noise is no joy!  Imuno keeps my systems up and running even when I don’t know what those needs are.   I do know how not to suppress with excesses.  It is the edge of prevention!

More on autism case study

More on imuno Cream (See $25. sample on pull down bar)

More on Bravo Yogurt

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Study shows Bravo Yogurt removes dangerous Glyphosate in just 3 months

In this study the effects of consuming Bravo yogurt alone (without other nutritional or immunological interventions) are studied and quantified. The effects include reduction or elimination of the Glyphosate, nagalase serum, detoxification of heavy metals and organic toxicants, and restoration of the body’s healthy microbiome.

Toxins, heavy metals & Glyphosate are involved in onset and development of several diseases including cancer, autism, & neurodegenerative diseases.  

Bravo restores health as well by building a microbiome and restoring production of butyrate, a short-chain fatty acid that regulates multiple functions of human cells by optimizing gene expression, cell differentiation and tissue development, modulation of the immune system and reduction of oxidative stress.

All these positive changes are accompanied by a trend toward normalization of serum triglycerides and cholesterol.

For article, find the download button on the right side of abstract

More about Bravo’s Swiss Milk & Colostrum

Ask Dr Ruggiero questions @ mimi@bravocoop.com

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Bravo’s milk/colostrum

Cow milk and colostrum used for our Bravo products have certified organic quality – awarded with the Bio Suisse bud seal. It is wholesome and contains all naturally occurring ingredients.

In the pictures, G.C.K, one of our colostrum collectors supervising some herds and colostrum suppliers in Switzerland.

We take care of the wellbeing of the cows who make colostrum

All mammals make colostrum that is the so-called first and second milk secreted by the mammary gland within the first 12 hours after birth. Colostrum is essential for survival of the newborn calf not only because it provides nutrition but, more importantly, because it contributes to the build-up of the immune system. At variance with humans, calves do not receive any prenatal passive immunization through antibodies from the mother, and their immunity is absolutely dependent on colostrum that contains a number of immune-stimulating factors. Because of this, we can use only the surplus of colostrum that is available after the calf has received what it needs; since the wellbeing of the calf is the primary interest of the farmer, only colostrum that is in surplus is sold for further processing. It is a very rare raw material which we value and respect.page1image52543488

Why is there a surplus of colostrum?

Colostrum surplus only arises from breeding. This began thousands of years ago; today’s “high- performance” dairy cows produce a surplus of milk and colostrum, that is a quantity much greater than that needed by the calves. The milk yield of dairy cows has increased over decades – and the amount of colostrum too. The cows from our Swiss suppliers (average herd size of our farmers is 18 cows) give an average surplus of 5 liters of colostrum within the first 12 hours after birth. Every farmer knows that a calf can only survive if it gets its share of colostrum; it needs about 6 liters of colostrum in order to build up its own immune system. That’s why every responsible farmer feeds his calves in the first place before using or selling any surplus of colostrum.

So please rest assured that the calf always gets its share in the first place. We love our animals and we take great care of their wellbeing.

Our milk and colostrum are collected exclusively from certified farms

Thanks to the regulations of Swiss organic agriculture, the highest quality of our cow milk and colostrum is guaranteed. Organic agriculture produces milk and colostrum on the basis of environmentally friendly production methods, taking ecological and environmental issues into consideration: no synthetic pesticides, growth promoters, mineral fertilizers or genetic engineering are used. As a result, organic products are less contaminated.

Milk and colostrum used for Bravo products comes exclusively from farms certified by Bio Suisse and thus subject to the highest standards throughout Europe.

Bio Suisse certification stands for foods of the highest organic quality.page3image52525072

Bio Suisse has very strict agricultural guidelines. Feeding, fertilization, hygiene regulations and the use of drugs are regulated and checked regularly. These standards form the framework for our suppliers and they are approved by annual audits. As a manufacturer, we also demand that each cow must be absolutely free from antibiotic treatments for at least one year. Preventive administration of antibiotics as food additives in conventional farming is a major problem in the food chain. Bio Suisse strictly prohibits this detrimental use of antibiotics.

The entire milk production is strictly regulated and controlled. Milk and colostrum as by- products are totally safe. Organic agriculture in particular produces food on the basis of environmentally friendly production methods taking into consideration ecology and environmental protection.

As a result, these products are less polluted.

The use of hormones is strictly prohibited in Switzerland. Antibiotics may only be used on organic farms if prescribed by a veterinary doctor. The cows of our contractual partners must be free of antibiotics for at least one year. This requirement is a prerequisite for best colostrum quality.

Our cow milk and colostrum are obtained exclusively from certified organic and biodynamic agriculture

These two certificates stand for a sustainable agriculture that cares for our precious resources and takes the wellbeing of the animals seriously. All our suppliers are organic and Demeter-certified farmers who adhere to the guidelines and regulations of Bio Suisse which are the strictest in the world. Demeter-products are produced and processed in a holistic manner, in harmony with nature. This means that conditions are right for people, animals, plants and soils alike and their

life forces can unfold in an ideal way. Moreover, Demeter holdings rely on homoeopathic medication for the treatment of sick animals and in cropping they use their own special preparations. In processing, much emphasis is placed on ensuring that the products retain as many of their natural qualities as possible. The Demeter label is recognized worldwide.

Our colostrum suppliers

We visit our suppliers personally on a regular basis. We are always pleased to see how great their responsibility and seriousness is. It demonstrates an incredible down-to-earth attitude and authenticity of the farmers.

One of the Swiss farmers with his family supplying colostrum for Bravo products

This spirit gives confidence in the best quality of colostrum and a responsible consideration for the welfare of the young animals. They need enough first milk to build up a healthy, strong immune system. The farmer also knows that his cows could supply several calves with fresh colostrum. This is due to our ancestors who have bred dairy animals for centuries. With the increasing milk yield the amount of colostrum increased as well.

Today we can totally rely on our Swiss organic colostrum suppliers to collect a product of the highest quality.page4image52894208page4image52893792page5image52945024

G.C.K., one of our colostrum collectors, with a farmer supplying colostrum for Bravo products

How is our colostrum processed?

Colostrum is a sensitive agricultural product whose production and distribution are strongly regulated and controlled by Swiss law. We preserve colostrum by pasteurization, that is a process used to sterilize it. Low temperature pasteurization (LTP) gently sterilizes colostrum, preserving most of all of its bio-activity. Then, our colostrum is freeze-dried (that is, it is gently dried).

Whole cow milk and colostrum, with no further treatment, are used as main ingredients of our Bravo products.page5image52944816page5image52946480

The colostrum used for Bravo undergoes Thorough Quality Control Procedures

CGMP (certified Good Manufacturing Practices) and HACCP (Hazard Analysis and Critical Control Procedures) procedures are being followed throughout the entire colostrum production process.
The product is examined in a laboratory registered with the United States federal government as a clinical laboratory.

Each colostrum product batch is thoroughly analyzed prior to shipment to assure its quality, efficacy and safety. Analytical chemistry, microbiological and other necessary testing is performed using AOAC or other approved testing methods. Colostrum is tested and certified for the immunoglobulin G (IgG) and proline-rich polypeptides (PRPs) content using one of five in-house High Performance Liquid Chromatography (HPLC) units.

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