|Posted on December 30, 2020 at 9:00 AM||comments (0)|
In 2008, a curious find was discovered down a coal mine in the Ukrainian city of Donetsk. As it could not be safely or successfully cut out due to the nature of the sandstone in which it was embedded, the mysterious artifact looking much like an ancient wheel remains in situ down the mine. The following article is extracted from The Myth Of Man by J.P. Robinson.SMXL
Whilst drilling the coal coking stratum named J3 ‘Sukhodolsky’ at a depth of 900 meters (2952.76 feet) from the surface, workers were surprised to find what appears to be the imprint of a wheel above them in the sandstone roof of the tunnel that they had just excavated.
Thankfully, photographs of the unusual imprint were taken by the Deputy Chief V.V. Kruzhilin and shared with the mine foreman S. Kasatkin, who brought news of the find to light. Without being able to further explore the site and inspect the imprint at close hand, we are left with only the photographs as evidence of their existence (there was more than one imprint) and the word of a group of Ukrainian miners.
Without being able to definitively date the strata in which the fossilized wheel print was found, it has been noted that the Rostov region surrounding Donetsk is situated upon Carboniferous rock aged between 360-300 million years ago, and the widely distributed coking coals have derived from the middle to late Carboniferous; suggesting a possible age of the imprint at around 300 million years old. This would mean that an actual wheel became stuck millions of years ago and dissolved over time due to a process called diagenesis, where sediments are lithified into sedimentary rocks, as is common with fossil remains.
The following is an extract from a letter written by S. Kasatkin (translated from Ukrainian) in reference to his testimony of having been witness to the anomalous wheel imprint discovered by his team of miners in 2008:
‘This finding is not a PR action. In due time (2008), we as a team of engineers and workers asked the mine director to invite scientists for detailed examination of the object, but the director, following the instructions of the then owner of the mine, prohibited such talks and instead only ordered to accelerate work on passing through this section of lava and on fast ‘charging’ of the section with mining equipment.
Owing to that, this artifact and the smaller one found during further work came to be in a tunnel blockage and could not be taken out and studied. It is good that there were people, who in spite of the director’s prohibition, photographed this artifact.
I have connections with the people who first discovered these imprints and also with those who photographed them. We have more than a dozen witnesses. As you understand, the admission in the mine is strictly limited (it is dangerous on sudden emissions) and to obtain such permit is rather difficult.
The ‘wheel’ was printed on sandstone of the roof. Guys (drifters) tried to ‘cut away’ the find with pick hammers and to take it out to the surface, but sandstone was so strong (firm) that, having been afraid to damage a print, they have left it in place. At present the mine is closed (officially since 2009) and access to the ‘object’ is impossible - the equipment is dismantled and the given layers are already flooded.’
Evidence for the existence of wheeled vehicles in antiquity has surfaced in other parts of the world, as petrified ancient tracks found in France, Spain, Italy, Malta, Kazakhstan, Ukraine, and even North America reveal. A prehistoric site known formally as Misrah Ghar il-Kbir meaning the Great Cave in Maltese (and commonly referred to as Clapham Junction), is located at Siggiewi, near the Dingli Cliffs in Malta.
It is at this now famous site that what have been termed ‘cart ruts’ cut into the limestone have mystified all that have visited the area. Likewise, a number of unusual tracks in stone are also visible on the island of Sicily at the Greek amphitheater called the Great Theater of Syracuse. Interestingly, most archaeologists have suggested that the Maltese tracks were probably created by Sicilian settlers who traveled to Malta around 2000 BC at the start of the Bronze Age.SML
Yet more tracks are to be found in Turkey. Some at Sofca cover an area roughly 45 by 10 miles (72.42 by 16.09 km), and also in Cappadocia, where several pockets of tracks can be seen. The many ruts discovered around the world have caused a great deal of controversy as to their purpose, age, and origin. These mysterious factors remain up for debate, but due to the association and close proximity with megalithic structures, in Malta particularly, and due to the fact that many tracks are now submerged below the sea in that region, many researchers have concluded that the fossilized lines show signs of great antiquity.
Bizarrely, considering the anomalous wheel print discovered in Ukraine that we have just discussed, a medieval city-fortress in the Crimean Mountains of Ukraine called Chufut-Kale lies in ruins, but also plays host to a number of cart ruts in stone like those at the nearby site of Eski-Kermen.
Dr. Alexander Koltypin is a geologist and director of the Natural Science Research Center at Moscow’s International Independent University of Ecology and Politology. He has spent a great deal of time visiting these sites and comparing them to one another in search of similarities.
“I first saw tracks in stone - fossilized car or terrain vehicle traces (usually called cart ruts) on Neogen plantation surface (peneplene in Phrygian) plain in May 2014 (Central Anatolia Turkey). They were situated in the field of development of Middle and Late Miocene tuffs and tuffites and according to age analysis of nearby volcanic rocks, had middle Miocene age of 12-14 million years,” wrote Koltypin.
This particular region which Koltypin has researched further is relatively unknown and the guide books offer nothing in the way of information. Whilst orthodox researchers claim that the tracks are simply the remnants of old petrified cart ruts from the kind of wheeled vehicles which donkeys or camels would have pulled, Koltypin has other ideas. “I will never accept it,” he explained when confronted with the standard explanations. “I myself will always remember . . . many other inhabitants of our planet wiped from our history.”
Indexed and Archived from Ancient Origins by Dragonfly Kingdom Library
|Posted on December 30, 2020 at 8:55 AM||comments (0)|
The details of the story depicted in the cave art surprised the researchers. Previously, the oldest known cave art first appeared in Europe 40,000 years ago, showcasing abstract symbols. By 35,000 years ago, the art became more sophisticated, showing horses and other animals.
But detailed scenes that share a story and therianthropes didn’t appear until 20,000 years ago – until this discovery. It “suggests that there was no gradual evolution of Paleolithic art from simple to complex around 35,000 years ago – at least not in Southeast Asia,” Aubert said.
“The hunters represented in the ancient rock art panel are simple figures with human-like bodies, but they have been depicted with heads or other body parts like those from birds, reptiles and other faunal species endemic to Sulawesi,” said Adhi Agus Oktaviana, study co-author and a PhD student at Griffith University in Australia, who has also studied rock art in Borneo, Sumatra, Raja Ampat and Misool.
|Posted on December 30, 2020 at 8:50 AM||comments (0)|
A 100,000-year-old workshop used to mix and store the reddish pigment ochre has been discovered in Blombos Cave on the rugged southern coast near Cape Town. At the same site, scientists have found some of the earliest sharp stone tools, as well as evidence of fishing.
The latest find is reported in Friday's edition of the journal Science. It includes pieces of ochre, grinding bowls, shells for storage and bone and charcoal to mix with the pigment.
Lead researcher Christopher Henshilwood of the University of Bergen, Norway, said the find represents an important benchmark in the evolution of complex human mental processes.
The ochre could have been used for painting, decoration and skin protection, according to the researchers.
The discovery shows that even at that time "humans had the conceptual ability to source, combine and store substances that were then possibly used to enhance their social practices."
Two separate tool kits for working ochre were found at the site, the researchers said.
Henshilwood, who is also affiliated with the South Africa's University of Witwatersrand, said in a statement that researchers believe that pieces of ochre were rubbed on rock to make a fine red powder, and that was mixed with crushed bone, charcoal, stone chips and a liquid. The mixture was put into abalone shells and stirred with a bone.
|Posted on December 30, 2020 at 8:45 AM||comments (0)|
Rock art dated to a minimum age of almost 40,000 years has been discovered in the Maros region of southern Sulawesi, Indonesia. This is an incredible result, published in Nature today, because one of the biggest challenges in rock art research is dating.
Consequently, every time we get dates for rock art, wherever from and no matter how old or young, it is important. But when we get really old dates outside Europe it is both highly significant and very exciting.
Specifically, the earliest minimum age for a hand stencil was found to be at least 39,900 years at the site of Leang Timpuseng and the oldest animal painting, of a babirusa “pig-deer” at the same site, dates back to at least 35,400 years.
A second animal painting (probably a pig) at another site has a minimum age of 35,700 years.
Obtaining 36,000 to 40,000 year minimum ages for paintings of animals and hand stencils of Sulawesi is an especially important rock art dating result because it has long been argued that the origin of art began in the deep caves of Europe more than 30,000 years ago.
Rock art is found all over the world. It is an archive of Indigenous arts and history stretching back tens of thousands of years and in this sense is a major component of world art history.
Rock art typically consists of paintings, drawings, engravings, stencils, prints, bas-relief carvings and figures made of beeswax in rock shelters and caves, on boulders and platforms.
Rock art sites are special, often spectacular places that reflect ancient experience and sometimes spirituality. They are locations where aspects of ceremony, belief and history are recorded in visual form. They are a testament to thousands of years of Indigenous culture and cultural interaction with other peoples, other creatures and the environment.
Where does the first rock art come from?
The Sulawesi dates show that the making of rock art did not originate in Europe, that it is more likely a much older behaviour brought by the first humans to both Europe and Southeast Asia. Or that rock art practices of making hand stencils and skilfully executed depictions of wild animals were independently invented in far flung parts of the world many tens of thousands of years ago.
Both possibilities are equally exciting as they force us to rethink many things about our most ancient modern human ancestors. They significantly change debates about the origin of art, the behavioural practices modern humans brought with them when they left Africa more than 60,000 years ago and what it is to be human.
Certainly, it appears that when modern humans reached new lands in vastly different parts of the world they literally put a human stamp on the new landscapes.
From southwest China to Malaysia, from Indonesia to the north of Australia, research by all three of us indicates the oldest surviving rock art to invariably consist of naturalistic paintings of animals.
In many places we also find hand stencils among the oldest surviving art forms. All attempts to date this early art have indicated considerable antiquity with various minimum ages but the new results from Sulawesi show this early widespread practice may have begun almost 40,000 years ago right across the region.
Australian rock art
In Australia there are at least 100,000 rock art sites, most across the north of the continent. But unlike Sulawesi, the oldest paintings are mostly in sandstone shelters rather than limestone, making them much more difficult to date.
Many researchers have suggested the oldest paintings include depictions of long extinct animals but we can never be absolutely sure of this. Used pieces of ochre, “crayons”, are found in the lowest levels and throughout excavated rock shelter floor deposits in Australia.
At more than one location they have been dated to up to 50,000 years ago. Sulawesi is not far from northern Australia and the first people to reach Australia’s shores more than 50,000 years ago would have passed through that region of Southeast Asia.
The ochre crayons from sites in northern Australia combined with the new dates of similar-looking imagery from Sulawesi give us strong circumstantial evidence that the oldest naturalistic animal paintings and hand stencils from Australia may also rival those of Europe in terms of age.
|Posted on December 13, 2020 at 6:25 PM||comments (0)|
There is no way that you can get big and strong on a vegetarian diet! I used to hear this all the time from my meat-eating friends. I say, used to as I never hear it anymore from people that know me or from people that have seen my photos on my website. Yes my friends, you can in fact get bigger and stronger on a vegetarian diet. You can even do it on a vegan diet (no animal products whatsoever).
How To Get Started
When I was fifteen I read an interview with Harley Flannagan (lead singer of the legendary NYC hardcore band, the Cro-mags) in which he stated that he became a vegetarian to lead a more peaceful life and that one cannot talk about peace when they have a steak on their plate, as an animal died in agonizing pain to end up there. That really struck a cord with me and got me thinking about the thousands of animals that suffer daily on factory farms. Next, I visited Kenya with my parents and experienced a feeling of oneness with the animals over there.
I realized that I did not want to contribute to the unnecessary suffering of other beings and I knew that I needed to make some changes. Finally, I saw a movie called "The Fly II" in which a golden retriever is mutilated in an experiment gone bad. That got me thinking about how animals are abused in labs and further solidified the new direction that I was taking. In addition, to giving up meat, I decided that I would make sure to purchase products such as: toothpaste, shampoo, soap etc that were not tested on animals.
I gave up meat gradually. I stated off by giving up all meat except fish. Then I gave up fish, but continued to eat eggs and dairy. Once I realized that most eggs and dairy products came from animals that lived miserable lives on factory farms, I gave up all animal products. That was ten years ago and I have never looked back. While I am an ethical vegan, there is no doubt in mind that a vegan diet is healthy and that I can get everything that my body need for my intense lifestyle. Regardless, like any other diet, planning is required.
The number one thing that people always ask me is where do I get my protein. Many vegans that I have met make the mistake of thinking that you do not need much protein at all. I even had one guy tell me that only 5% of one's diet should come from protein. Of course this guy looked like Don Knots and would be blown off like kite if a strong wind came by. I had another guy tell me that I can get protein from a cucumber and that I should not even worry about it.
Of course, this guy was not in shape either and was in no position to give me nutrition advice. We have to be much more sensible than that. Especially, if we expect anyone to give up meat and adopt a vegetarian diet. Telling people that they can get all of the protein that they need from eating spinach and leafy green vegetables is impractical. Just because it works for the gorillas does not mean that it will work for us. Not getting enough protein and thinking that only 5% of your diet needs to be comprised of protein are sure fire ways to be spindly and weak for the rest of your life. Now I am not saying that you need two grams of protein per pound of bodyweight like the bodybuilding magazines state.
That is way too much protein and a case of overkill. For athletes, 0.7 to 1 gram of protein per pound of lean muscle is optimal for increasing strength and size. For example, if you weigh 180lb and have ten percent bodyfat, then you should shoot for 150-160 grams of protein to build more muscle. If you want to maintain your size, then 100-120 will probably be sufficient.
Next, vegans like anyone else need to load up on healthy sources of fat. Without enough fat in your diet, your skin will dry up, your energy will plummet, and you will look like death. Getting 20-30% of your calories from fat is a good way to go. Load up on healthy fats such as: flaxseed oil, olive oil, almonds, walnuts, almond butter, and avocadoes. Also, vegan diets are free of all saturated fats, which is great for the most part. However, some saturated fat is required for optimal health, so get some coconut oil or coconut milk in you diet as well.
Finally, make sure that you eat a variety of food to get a full array of muscle building amino acids. Some examples of good combinations include: black beans and quinoa, lentils and brown rice, almond butter sandwich, rice protein/soy milk shake, green peas and almonds. Have some veggie burgers and other fake meat products from time to time, but make sure that the majority of your diet comes from fresh organic food.
|Posted on December 13, 2020 at 6:15 PM||comments (0)|
As many of you know by now, I strongly recommend a whole food, plant-based diet to combat cancer. The question I continually get is, “where do you get your protein?”
If you review the protein recommendations of the US government you can use the following equation to get your protein requirement:
Pounds X 4 divided by 10.
My weight is 155 pounds. Therefore 155 X 4 = 620.
620 divided by 10 = 62 grams.
If you use the metric system use kilograms X 0.8.
I eat a strict whole food, plant-based diet (no animal products) and I have checked my protein intake on consecutive days for a whole week and I normally get over 100 grams per day, which in my view is more than my goal.
The average Westerner who eats a lot of meat and dairy products is easily getting 2-3 times the recommended about of protein and this can be harmful to one’s health and especially someone who is combatting cancer. For now, let’s look at some of the negatives of high meat, dairy and protein consumption.
One of the concerning aspects of high animal protein consumption is that it stimulates the liver to produce a growth promoting hormone called “Insulin-like Growth Factor-1 (IGF-1)” which at higher levels in adults has been shown to be a major instigator of cancer initiation and growth [1,2]. This does not happen when the liver is exposed to incomplete plant proteins. Apparently, because animal protein is a complete protein, it sends a signal to the liver that growth is about to occur, so IGF-1 is manufactured. In studies, meat eaters consistently are shown to have much higher IGF-1 levels compared to vegans.
When we are young our body needs IGF-1 for growth to allow us to become a full grown adult. Our levels normally peak in our late teens, then gradually decline every year as we age. This gradual decline is built into our bodies to help us stay alive, because as we age we also accumulate thousands of DNA mutations. We do not want a stimulus for high cellular growth and replication in the setting of high levels of DNA mutations. This is a device that Nature has built in to protect us from cancer initiation, growth and metastasis.
It is also important to note that since IGF-1 can promote muscle growth, growth hormone has been promoted and prescribed by anti-aging physicians as an anti-aging hormone. However, studies are finding that restoring growth hormone levels to youthful levels in adulthood is not beneficial; in fact it has been found to increase death rates in formerly healthy adults.
High mTOR Activation
Another promoter of cancer growth in the body is the mTOR gene . This gene is a potent promoter of cellular growth and replication (similar to IGF-1) and as we just learned we do not want a growth stimulator in the setting of increasing mutations. Through scientific study we have learned that the amino acid “leucine” is the most powerful stimulator of mTOR. And guess where leucine is found in high levels? You guessed it. There are high levels in all animal products and very low levels in plant foods. Therefore lowering animal products while increasing plant intake, lowers leucine levels, which lowers mTOR activity. This is an effective way to decrease cancer initiation and growth.
High animal protein intake also puts inordinate stress on the kidneys and after chronic exposure creates damage to the kidney micro-tubules. Animal protein, but not vegetable protein, causes what is called “kidney hyper-filtration” . This is an inflammatory response in the kidney caused by high levels of sulfur-containing amino acids that are present in animal proteins. When anti-inflammatory drugs are given at the time of animal protein ingestion the hyper-filtration does not occur. This hyper-filtration also does not occur with the ingestion of vegetable protein. Furthermore, high animal protein consumption is extremely acidic which puts additional stress on the kidney while also, in the cancer patient, creating a favorable pH for enzymes like “collagenase” to assist the cancer to progress and metastasize .
High Pesticide and Endotoxin Levels
Because all animals are high on the food chain, various retrospective studies always reveal much higher levels of pesticides and heavy metals in the blood and tissue of meat eaters versus vegans. To help you understand this concept, if a grasshopper ate a bunch of pesticide-laden grass, it would absorb those pesticides that would then be dissolved into its fat tissue....something we call “bioaccumulation”. A bird then eats many grasshoppers. The bird’s pesticide levels will now be greater than the grasshopper’s levels. If a human eats a lot of the birds, a chicken for example, the human’s levels will be higher than the chicken’s. A similar situation occurs in the oceans. If you analyze mercury and PCB levels in small fish versus large fish, like tuna, the larger fish will consistently have much higher mercury and PCB levels than the smaller fish.
One of many studies analyzing this bioaccumulation was published in the British Journal of Nutrition and it found that PCB levels were much higher in meat eaters compared to vegans . Similar studies routinely demonstrate this same result... pesticides and heavy metals blood and tissue levels are consistently much higher in meat and dairy consumers.
Animal products also carry viruses like bovine leukemia virus (implicated in 37% of all US breast cancers and also non-Hodgkins lymphoma) and bacterial endotoxins that cannot be destroyed by heat and create much inflammation and negative health issues in the body.
Animal products contain ZERO fiber! 97% of the US population does not get the 30 grams/day of fiber recommended by the US government. This is due to the fact that the average American consumes 50% processed foods, 40% animal products and 10% unrefined plant foods. In a 2010 study, it was found that the average American eats, on average, 1.8 servings of fruits and vegetables per day. And that was allowing French fries and ketchup to be counted as a vegetable!
Fiber has been shown to be critical to creating the right balance in the 30 trillion bacteria that grow in our intestinal tract. These bacteria are many times referred to as “the microbiome”. There are 2 primary groups of bacteria in our GI tract....good Prevotella probiotic bacteria and bad Bacteroides bacteria. There are approximately 500 subspecies in each group. When one is eating at least 30 grams of fiber per day, the good Prevotella probiotic bacteria feed on the fiber, proliferate, and produce short-chain fatty acids which are extremely anti-inflammatory and are said by many experts in the field of immunology to control up to 80% of our immune function.
These short-chain fatty acids also stimulate the FFAR2 receptors on our cells which have a profound control over our metabolism. In rat studies when you feed high concentrations of fiber rich plant food (with no meat) to the rats, they become slim. Conversely, when you feed them high concentrations of animal products (with no plants) they become obese. When we eat primarily processed and animal foods the bad Bacteroides bacteria proliferate and the good probiotic Prevotella bacteria decrease, causing many chronic diseases and weight gain. Conversely, when we eat lots of fruits, vegetables, whole grains, beans, nuts and seeds, the good probiotic Prevotella increase in numbers and the harmful Bacteroides decrease. This latter scenario puts us in a much better position to enjoy maximal health.
This is the most important factor that causes me to recommend limiting animal product consumption. Plants have over 25,000 phytonutrients that have profound antioxidant, anti-inflammatory and anti-tumor effects in the body. Animal products have none of these phytonutrients.
Because of this fact, plants foods have been found to have 63X the antioxidant power compared to animal products. ORAC (oxygen radical absorbance capacity) units are the units that we use to measure the ability of foods to neutralize health-damaging free radicals. For those of you who are unfamiliar with free radicals, they are molecules with unpaired electrons that are created daily by our cells in the trillions. These free radicals will seek out another electron to create a neutral electrical charge, however in the process of finding an electron mate, they create thousands of DNA mutations in our lifetime which are at the root of all cancers. Innate intracellular antioxidants (glutathione peroxidase, superoxide dismutase and catalase), along with the antioxidants that we eat, can neutralize most of these free radicals, but the Standard American Diet can easily create free-radical overload. Therefore we must complement our innate intracellular antioxidants with a healthy dose of antioxidants from our food intake.
To demonstrate the difference between plant foods and animal products let’s compare one food (a sweet potato) to a whole day of eating a Standard American Diet.
One sweet potato with a teaspoon of cinnamon and a pinch of clove is 246 ORAC units. On the other hand, a morning Egg McMuffin, an afternoon Big Mac and an evening steak with parsley would total 44 ORAC units for the entire day! Every morning I drink a morning smoothie with various fruits, freeze dried powders, ground flax seeds and kale. That smoothie has 2,000+ ORAC units. An analysis of 5 Standard American Diet breakfasts revealed anywhere from 8-25 ORAC units for each of these typical American breakfasts. The dissimilarity is mind blowing!
In an interview, Dr. Nikhil Munshi, a famous myeloma genomic scientist, stated that at the time of myeloma diagnosis, a myeloma patient’s cancer cell has approximately 5,000+ mutations at diagnosis and at relapse about 12,000+. Therefore minimizing the number of mutations is critical for any cancer patient to help them to stay in remission. It is also extremely important for those trying to avoid cancer in the first place.
We all know that eating high cholesterol foods leads to high cholesterol blood levels which then leads to cardiovascular disease. This fact has been validated in thousands of studies over the past 50 years. And what is the only kind of food that contains cholesterol? You guessed it....animal products.
Cholesterol, however, does not only affect the cardiovascular system, it also has a significant effect on cancer. Many of us have heard that cancer needs an enormous amount of sugar to maintain itself due to the fact that it uses a very crude fermentation method of energy production called “Warburg’s aerobic glycolysis”. This method of energy production takes one molecule of glucose and creates only 2 ATP energy molecules. Our normal cells, on the other hand, create 36 ATP molecules from one glucose molecule. Therefore, cancer needs a prodigious amount of glucose just to maintain itself.
There are, however, other nutritional pathways that cancer can use. In Jane McLelland’s excellent and heavily-researched book How to Starve Cancer she demonstrates, through careful analysis of the scientific literature, how cancer can also use a cholesterol pathway and a glutamine (amino acid) pathway for energy production. In fact, some cancers like prostate, colon and breast cancer may even prefer the cholesterol pathway. In fact, there are studies that demonstrate that individuals who take statin drugs have much lower rates of the aforementioned cancers. To understand this concept better, I would highly recommend viewing the 5 minute video on nutritionfacts.org entitled Cholesterol Feeds Breast Cancer Cells.
Therefore cancer patients need to keep their total cholesterol level below 150 and their LDL cholesterol below 80. The absolute best way to do that is with a whole food, plant-based diet. If additional help is needed I recommend Chinese Red Yeast. The product that I use is Beni Koji RYR (Douglas Labs) which can be purchased on Amazon. I take 2 in the morning and 2 in the evening. I also take Ubiquinol-QH (Douglas Labs) with it to keep the CoEnzyme Q10 levels from getting to low. This can also be purchased on Amazon. I take 2 in the morning and 2 in the evening.
Heterocyclic amines are potentially carcinogenic chemical compounds formed in cooked muscle tissue. Examples of heterocyclic amines include harmane, which may cause essential tremor and PhIP, considered an estrogenic carcinogen that may increase breast cancer risk. Poultry meat appears to have the highest concentration of heterocyclic amines, but muscles are not the only source of these toxins. These carcinogens may be present in eggs, cheese, creatine supplements and cigarette smoke.
There are some measures that those who eat meat can do to reduce the risk of developing cancer. Boiling appears to be the safest cooking method in terms of carcinogen levels. Other foods may also decrease the risk. For example, cruciferous vegetables have been shown to reduce the absorption of heterocyclic amines for as long as 2 weeks after consumption. White and green tea may also be protective. If you don’t eat meat for just one day your levels of PhIP and MelQx will drop to zero in just twenty-four hours. Veggie meat is a safe bet since it contains no muscle tissue.
You can see that meat consumption has many negative health effects. A good culmination of what I have just shared with you was extremely well presented in a study by the National Health Institute and The World Health Organization where they looked at the diets of different countries throughout the world. They studied the percentage of unrefined plant consumption in each country and how it correlated with the percentage of people dying from cancer and cardiovascular disease.
In the United States, for example, the average person eats 10% of their diet in unrefined plant foods and we find that 90% of Americans die of either cancer or heart disease. Conversely, in Laos the average person eats over 90% of their diet in unrefined plant foods and only 5% of people in that country die of cancer and heart disease. In Greece, the average person eats a diet that is 35% unrefined plants and 35% of people die of cancer or heart disease. In this study it is absolutely fascinating how the percentage of plant foods directly correlates with the percentage of people dying from cancer and heart disease. The more plants...the less cancer and heart disease.
1. Werner H, Bruchim I. The insulin-like growth factor-1 receptor as an oncogene. Arch Physiol Biochem 2009; 115:58-71.
2. Chitnis MM, Yuen JS, Protheroe AS et al. The type 1 insulin-like growth factor receptor pathway. Clin Cancer Res 2008; 14:6364-70.
3. Wang Z et al. mTOR co-targeting strategies for head and neck cancer therapy. Cancer Metastasis Rev 2012; Sept;36(3):491-502.
4. Helal I et al. Glomerular hyperfiltration:definitions, mechanisms and clinical implications. Nat Rev Nephrol 2012; Feb;21;8(5):293-300.
5. Huang S et al. Acidic extracellular pH promotes prostate cancer bone metastasis by enhancing PC-3 stem cell characteristics, cell invasiveness and VEGF-induced vasculogenesisof BM-EPCs. Oncol Rep 2016; Oct;36(4):2025-32.
6. Arguin H et al. Impact of adopting a vegan diet or an olestra supplementation on plasma organochlorine concentrations:results from two pilot studies. Br J Nutr 2010; May;103(10):1433-41.
|Posted on December 11, 2020 at 1:55 PM||comments (0)|
The “chemical obesogen” hypothesis conjectures that synthetic, environmental contaminants are contributing to the global epidemic of obesity. In fact, intentional food additives (e.g., artificial sweeteners and colors, emulsifiers) and unintentional compounds (e.g., bisphenol A, pesticides) are largely unstudied in regard to their effects on overall metabolic homeostasis. With that said, many of these contaminants have been found to dysregulate endocrine function, insulin signaling, and/or adipocyte function. Although momentum for the chemical obesogen hypothesis is growing, supportive, evidence-based research is lacking. In order to identify noxious synthetic compounds in the environment out of the thousands of chemicals that are currently in use, tools and models from toxicology should be adopted (e.g., functional high throughput screening methods, zebrafish-based assays). Finally, mechanistic insight into obesogen-induced effects will be helpful in elucidating their role in the obesity epidemic as well as preventing and reversing their effects.
Keywords: obesity, BPA, bisphenol A, food additives, preservatives, pesticides, plastics, pollutants, contaminants
Since the industrial revolution, the goals of food technology have predominately been maximizing palatability, optimizing process efficiency, increasing shelf life, reducing cost, and improving food safety (free from harmful viruses, bacteria, and fungi). As such, over 4,000 novel ingredients have entered the food supply, some intentionally (such as preservatives) and some inadvertently (such as bisphenol A, BPA), and there are 1,500 new compounds that enter the market every year . While food processing techniques are also constantly being optimized to minimize toxic compounds and toxicants such as lead, melamine, and aflatoxin, other “non-toxic” additives are not thoroughly tested for their chronic, additive, and/or cumulative effects on human physiology.
Obesity and related chronic disorders are increasing at alarming rates and it is estimated that 86% of Americans will be overweight by 2030 . This trend continues despite increases in awareness, nutritional and behavioral research, the amount of diet foods available, and even gym memberships . Unfortunately, the etiology of obesity and diabetes in regard to biochemical mechanisms is still largely not understood. Treatment and prevention of obesity hinges on our ability to 1) characterize the biochemical pathways that promote obesity, 2) identify what changes in our environment are promoting obesity, and 3) avoid and reverse the effects of the offensive agents and practices. It is crucial that clinicians understand and communicate that most novel food ingredients have not been evaluated for metabolic safety. In this review, we outline what agents have been identified that may be contributing to obesity, describe current methods being used to identify offensive compounds, and identify critical gaps in our methods and body of knowledge.
The importance of identifying agents that contribute to obesity
There is an abundance of research related to obesity etiology and prevention in regard to decreasing caloric intake and increasing energy expenditure. However, “non-traditional” risk factors are under increased scrutiny for their contributions to the obesity epidemic: emotional stress, sleep deprivation, disruption of normal circadian rhythm, composition of the gut microbiome, oxidative stress, medications such as antidepressants and oral contraceptives, average home temperature, and environmental toxicants [24••,36•,55]. Agents in our food supply have immense potential to affect metabolism due to continuous exposure and potential interactions among multiple compounds. A recently hypothesized factor contributing to the obesity epidemic is our exposure to obesogens, chemicals in our environment that can disrupt metabolism and lead to accumulation of excess fat mass (coined by Grün and Blumberg in 2006 ). It is critical that we identify these obesogens in our food supply in order to facilitate obesity prevention and treatment .
Unfortunately, many of the obesogenic compounds in our food supply were added deliberately to enhance production instead of being added to enhance nutrition. For example, pesticides are added to ward off insects during farming; BPA is a strong, clear plastic that has ideal properties for making bottles and coating cans; and mono- and diglycerides are added to emulsify the fat and water in foods to achieve a favorable texture. Simple exclusion of these compounds may not be possible until alternatives are developed, but then these novel compounds must be tested. Like pharmaceuticals, thorough testing is time-consuming and expensive.
Obesogen identification and characterization is in its infancy, and much of the scientific evidence supporting the relationship between synthetic compounds and the obesity epidemic is currently weak. Strong, evidence-based scientific support is derived from randomized, controlled trials, ideally cross-over design, that comprise four steps: 1) addition of the compound of interest, 2) observation of an effect, 3) removal of the compound of interest, and 4) disappearance of the effect. However, the bulk of evidence relating environmental contaminants and obesity is derived from epidemiological studies which are correlational by nature. While correlations are important, they are limited in that conclusions about causal relationships are impossible. Well-designed animal studies provide strong evidence within the animal model, but must be confirmed in humans. Cell studies are important for deriving mechanisms that may link certain compounds to obesity, yet provide only weak evidence for the global phenomenon (the obesity epidemic). Thus, we currently do not have any strong evidence that any contaminant, food additive, or ingredient that is “generally recognized as safe” (GRAS) causes obesity, which is essential for making confident recommendations and changes in public policy.
It is important to note that in evaluating foods for their contribution to obesity, we may identify ingredients that prevent obesity. For example, some hydrocolloids including guar gum and β-glucan may be able to increase satiety and reduce caloric intake with their bulking properties . Also, anthocyanins (potent color compounds from grapes, purple corn, blueberries, and other plants) may reduce oxidative stress, prevent obesity, and help control diabetes in cell culture, animal models, and humans . Again, not all compounds in a class are equal; for example, although the hydrocolloid guar gum may prevent obesity (mentioned above), another hydrocolloid called carrageenan, found commonly in chocolate milk and ice cream, may contribute to insulin resistance in mice .
What in our food is making us fat?
There are many aspects of the average Western diet that may promote obesity. The macronutrient ratio (fat:carbohydrate:protein), the characteristics of the fat (e.g., diets rich in palmitic acid vs. eicosapentaenoic acid), the characteristics of the carbohydrates (refined vs. whole grain carbohydrates) [2,59], and form of the protein  are major concerns and reviewed elsewhere [2,59-63]. In addition, advances in food processing have facilitated consumption of high caloric food that is low in other nutrients (e.g., edible oils, refined grains)  as well as increased the glycemic load of common meals . Increased consumption of nutrient-poor added fat, added sugar, added salt, and refined grains may also underlie obesity and co-morbidities in ways that extend beyond energy balance . Baillie-Hamilton announced a well-received hypothesis in 2002 highlighting the potential for environmental compounds in our food to contribute to the obesity epidemic . While the relationship between obesity and food structure is reviewed elsewhere [59-63], herein, we will focus on potential obesogens and obesity-promoting food additives in our foods supply (Table 1)......... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101898/
|Posted on December 11, 2020 at 1:40 PM||comments (0)|
Some free fatty acids derived from milk and vegetable oils are known to have potent antiviral and antibacterial properties. However, therapeutic applications of short to medium chain fatty acids are limited by physical characteristics such as immiscibility in aqueous solutions. We evaluated a novel proprietary formulation based on an emulsion of short chain caprylic acid, ViroSAL, for its ability to inhibit a range of viral infections in vitro and in vivo. In vitro, ViroSAL inhibited the enveloped viruses Epstein-Barr, measles, herpes simplex, Zika and orf parapoxvirus, together with Ebola, Lassa, vesicular stomatitis and SARS-CoV-1 pseudoviruses, in a concentration- and time-dependent manner. Evaluation of the components of ViroSAL revealed that caprylic acid was the main antiviral component; however, the ViroSAL formulation significantly inhibited viral entry compared with caprylic acid alone. In vivo, ViroSAL significantly inhibited Zika and Semliki Forest Virus replication in mice following the inoculation of these viruses into mosquito bite sites. In agreement with studies investigating other free fatty acids, ViroSAL had no effect on norovirus, a non-enveloped virus, indicating that its mechanism of action may be via surfactant disruption of the viral envelope. We have identified a novel antiviral formulation that is of great interest for prevention and/or treatment of a broad range of enveloped viruses.
The antimicrobial properties of fatty acids have been extensively reported in the literature (for review, see Thormar et al. (Thormar and Hilmarsson, 2007) and (Churchward et al., 2018). Previously, (Thormar et al., 1987) demonstrated the antiviral effects of 14 different free fatty acids and lipid extracts from human milk against vesicular stomatitis virus (VSV), herpes simplex virus (HSV) and visna virus revealed that short chain saturated fatty acids (butyric, caproic and caprylic) together with long chain saturated fatty acids (palmitic and stearic) had no or very little antiviral activity, whereas medium chain saturated entities including capric, lauric, myristic and long chain unsaturated oleic, linoleic and linolenic acids were anti-viral, albeit at different concentrations. Another study (Hilmarsson et al., 2005) reported similar trends in the antiviral activity of six medium chain fatty acids together with their alcohol and mono-glyceride derivatives against herpes simplex viruses 1 and 2. In contrast, Dichtelmuller et al (2002) reported that caprylic acid had antiviral activity against enveloped viruses including human immunodeficiency virus, bovine viral diarrhoea virus, Sindbis virus and pseudorabies virus (Dichtelmuller et al., 2002, Pingen et al., 2016). Studies investigating the antiviral properties of whole milk reported no antiviral properties of fresh human milk, whereas milk that had been stored at 4°C possessed potent antiviral activity against several viruses in vitro. Refrigeration disrupts the milk fat globule membrane allowing ingress of milk serum lipase which results in hydrolysis of milk fat triglyceride (Thormar et al., 1987, Isaacs et al., 1990). It was concluded that release of fatty acids from milk triglycerides in stored milk, and that recovered from neonatal (achlorhydric) stomachs, was responsible for generating antiviral factor(s) (Thormar et al., 1987).
We investigated the effect of a specifically formulated emulsion of free fatty acids, ViroSAL, on infectivity of enveloped and non-enveloped viruses. Caprylic acid delivered in the ViroSAL emulsion exhibited significant anti-viral effects. A range of enveloped viral infection systems was utilized, and complete inhibition of viral infection was observed without any evidence of cytotoxicity. ViroSAL had no effect on the infectivity of a non-enveloped virus, norovirus, which is in agreement with previous studies demonstrating that free fatty acids are ineffective against non-enveloped viruses (Thormar et al., 1987, Kohn et al., 1980). Furthermore, ViroSAL inactivated the enveloped mosquito-borne viruses Semliki Forest virus (SFV) and Zika virus (ZIKV) in vitro. Prophylactic topical treatment of viral infection in mosquito bites with ViroSAL inhibited local replication and dissemination of SFV and plasma levels of ZIKV in mice. Transmission electron microscopy analysis indicated that ViroSAL disrupts orf parapoxvirus envelope integrity, with higher concentrations completely disrupting virion morphology. These data indicate that ViroSAL has antiviral activity against a range of enveloped viruses in vitro and in vivo.
|Posted on December 11, 2020 at 1:35 PM||comments (0)|
Stubborn belly fat can make it hard to fit into your jeans and uncomfortable to carry around. Choosing to add monounsaturated fats into a balanced diet will help promote fat loss through your midsection. Include foods that are high in monounsaturated fats into your daily meal plan to help to burn unwanted fat.
VIDEO OF THE DAY
Burn Belly Fat
Belly fat can be banished when you fill your diet with monounsaturated fats. The March 2007 issue of the "Journal For Diabetes Care" explained that eating a source of monounsaturated fatty acids with each meal of your day will help your body burn fat from the stomach area. Monounsaturated fats help to increase your basal metabolic rate allowing your body to burn fat quicker.
The "American Journal of Clinical Nutrition" published a study in April 2009 that found eating monounsaturated fats increase satiety unlike saturated fats. Monounsaturated fats will help keep you full and satisfied longer. This will help prevent over-eating, which will help you restrict your calories for weight loss. Add olive oils to your pasta or avocados to your sandwich to help you include extra monounsaturated fats to your meals.
Almonds are a healthy source of monounsaturated fats. The Almond Board of California explains that including about 1 oz. of almonds daily will help to keep your metabolism elevated. Olive oil and avocado are also foods filled with monounsaturated fats. These fats will help you burn belly fat when eaten in moderation. Portion sizing is key because these foods can be high in calories. Limit the amounts you consume to 10 almonds or 1/2 an avocado for fat burning results.
Stubborn belly fat can be decreased when you incorporate exercise to your healthy eating plan. Cardio training most days of the week for 30 minutes will help you melt off body fat. Weight training should be done three days a week to increase your lean muscle, which will help your body burn more calories during the day. Also target training your midsection will help to whittle away your waistline.
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|Posted on December 11, 2020 at 1:25 PM||comments (0)|
Effects of Different Dietary Fatty Acids on Human Energy Balance, Body Weight, Fat Mass, and Abdominal Fat
Sze Yen Tan, in Nutrition in the Prevention and Treatment of Abdominal Obesity, 2014
The effects of increased MUFA intake on body weight and body composition were investigated using a within-subject crossover and a randomized controlled experimental design (Table 36.1). In one crossover study, 16 adults with type 2 diabetes mellitus (T2DM) received two test diets, one high in carbohydrate and another high in MUFA (from olive oil), for 3 months per diet (separated by a 1-month washout period). Total body fat mass decreased after the intervention periods but was not significantly different between the two diets. However, there appeared to be a trend of different fat mass loss patterns: participants lost upper body fat with the MUFA diet but gained upper body fat slightly during the high-carbohydrate diet. When examined as a ratio of upper-to-lower body fat mass, the high-carbohydrate diet induced a significantly higher ratio than the high-MUFA diet (P < 0.01) . A more recent crossover study that fed 11 insulin-resistant adults high-SFA, high-MUFA, and high-carbohydrate diets in a random order for 28 days each also failed to document additional effects of increased MUFA intake on body weight and fat mass loss. However, the MUFA-rich diet did prevent upper body fat accumulation that was induced by the high-carbohydrate diet. Consequently, the upper-to-lower body fat ratio was significantly higher in that diet group . Similar to the aforementioned studies, one study documented greater upper body fat loss after following a high-MUFA diet (vs. a high-SFA diet) for 4 weeks . This study also recorded significant losses in body weight and total body fat mass, which was not found in the other two studies. Differences in the study populations may explain the contradictory observations regarding total body fat mass loss: studies that included adults with T2DM or insulin resistance reported no additional benefits of MUFA on body weight and fat mass, while studies that recruited healthy male adults did. Impaired fatty acid oxidation has been previously reported in adults with T2DM [104,105].
The randomized controlled, parallel-arm studies that tested the effects of MUFA on body weight and body composition are limited, and were conducted using a weight loss paradigm. In one study, 57 overweight and obese adults were randomly assigned to follow a low-fat, high-protein (30% fat, 35% protein) or a high-fat, standard-protein (45% fat high in MUFA from mixed nuts and canola oil and 18% protein) diet . During the first 12 weeks of this trial, energy restriction was prescribed to promote weight loss; this was followed by an energy balance period of 4 weeks. This study did not find significant differences in body weight and fat mass loss between the two diets. The lack of effects of MUFA in this trial may be due to (1) the simultaneous manipulation of two dietary components (e.g. protein and fat); (2) the absence of a proper control group; (3) subtle acute physiological effects of MUFA that failed to translate into clinical observations; or (4) adaptation of the body to increased dietary MUFA during the study period. However, these possibilities are yet to be evaluated.
Another randomized controlled trial compared the weight- and fat-mass-reducing effects of a high-MUFA (from almonds) vs. a high-carbohydrate energy-restricted diet for 24 weeks . Like the previous study, the two intervention diets differed in more than one aspect: the MUFA diet contained higher total fat and lower carbohydrate (39% fat, 32% carbohydrate) than the high-carbohydrate diet (19% fat, 53% carbohydrate). In this study, greater reductions in weight (−18% vs. −11%), fat mass (−30% vs. 20%), and waist circumference (an indicator of abdominal fat; −14% vs. −9%) were observed in the high-MUFA group, although it should be pointed out that these superior clinical outcomes may not be attributable to MUFA alone. Almonds (the vehicle of MUFA used in this study) influence energy balance by promoting satiety [108,109] and dietary compensation [110–112], and the absorption of dietary fat from almonds is lower than previously thought . In summary, the presence of confounding factors in the intervention studies limits the ability to draw conclusions as to whether MUFA has therapeutic effects on body weight and total fat mass reduction. More longer-term and better-controlled intervention trials are therefore warranted.
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|Posted on December 11, 2020 at 1:10 PM||comments (0)|
OBJECTIVE— Central obesity is associated with insulin resistance through factors that are not fully understood. We studied the effects of three different isocaloric diets on body fat distribution, insulin sensitivity, and peripheral adiponectin gene expression.
RESEARCH DESIGN AND METHODS— Eleven volunteers, offspring of obese type 2 diabetic patients with abdominal fat deposition, were studied. These subjects were considered insulin resistant as indicated by Matsuda index values <4 after an oral glucose tolerance test, and they maintained A1C <6.5% without therapeutic intervention. All subjects underwent three dietary periods of 28 days each in a crossover design: 1) diet enriched in saturated fat (SAT), 2) diet rich in monounsaturated fat (MUFA) (Mediterranean diet), and 3) diet rich in carbohydrates (CHOs).
RESULTS— Weight, body composition, and resting energy expenditure remained unchanged during the three sequential dietary periods. Using dual-energy X-ray absorptiometry we observed that when patients were fed a CHO-enriched diet, their fat mass was redistributed toward the abdominal depot, whereas periphery fat accumulation decreased compared with isocaloric MUFA-rich and high-SAT diets (ANOVA P < 0.05). Changes in fat deposition were associated with decreased postprandial mRNA adiponectin levels in peripheral adipose tissue and lower insulin sensitivity index values from a frequently sampled insulin-assisted intravenous glucose tolerance test in patients fed a CHO-rich diet compared with a MUFA-rich diet (ANOVA P < 0.05).
CONCLUSIONS— An isocaloric MUFA-rich diet prevents central fat redistribution and the postprandial decrease in peripheral adiponectin gene expression and insulin resistance induced by a CHO-rich diet in insulin-resistant subjects.
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|Posted on December 11, 2020 at 1:05 PM||comments (0)|
Safflower oil have been reviewed for nutraceutical applications.
Good stability index allows encapsulation of safflower oil in functional foods.
Recently extraction techniques of safflower oil have been reviewed.
Summary of recent findings related to bone health is reviewed.
Applications of safflower oil towards functional foods development is reviewed.
Safflower is a multiple purpose crop generally grown for oil production. The safflower oil is considered to be a better oil since it contains higher amount of oleic and linoleic acids than other oil seed crops. Safflower oil has numerous applications in food, cosmetics, pharmaceutical and feed industry. An added advantage of safflower oil is lower cost of production thus can become an alternate option for those who cannot afford to buy olive and other functional oils.
Scope and approach
This manuscript provides a comprehensive review on critical aspects of pharmacological and nutritional applications of safflower oil. A higher antioxidant activity renders better stability of safflower seed oil over extended storage period. Moreover, a higher content of omega six fatty acids makes it a healthier choice for consumption especially where olive oil being the only but costly choice. There has been a surge in developing innovative and efficient methods to extract safflower oil including super critical fluid and enzymatic extraction techniques.
Key findings and conclusions
A higher stability index makes it possible to encapsulate safflower oil or used it as a carrier in bioactive functional ingredient delivery systems. The functional properties of safflower oil can be used to treat skin infections, bone related disorders, menopause and atherosclerosis. Composition and distribution of phenolic contents of safflower oil has not been explored to its full potential. There is a need to conduct exclusive research on exploring the role of phenolic compounds in food and pharma industrial applications.
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|Posted on December 11, 2020 at 1:05 PM||comments (0)|
FDA Approves New Qualified Health Claim for Oils High in Oleic Acid
That Cut Risk of Coronary Heart Disease
The FDA has determined that there's credible evidence to support a qualified health claim that consuming oleic acid in edible oils, such as olive oil, sunflower oil, safflower oil, canola oil, or soybean oil, may reduce the risk of coronary heart disease.
After conducting a systematic review of the available scientific evidence, the FDA now intends to exercise enforcement discretion over the use of two qualified health claims characterizing the relationship between consumption of oleic acid in edible oils (containing at least 70% of oleic acid per serving) and reduced risk of coronary heart disease. Oleic acid is a monounsaturated fat which, when substituted for fats and oils higher in saturated fat, may reduce the risk of coronary heart disease.
The science behind the new qualified health claim for oleic acid, while not conclusive, is promising. The FDA evaluated results from seven small clinical studies that evaluated the relationship between consumption of oils containing high levels of oleic acid (at least 70% per serving) and improved cholesterol levels, which indicates a reduced risk of coronary heart disease. Six of the studies found that those who were randomly assigned to consume diets containing oils with high levels of oleic acid as a replacement to fats and oils higher in saturated fat experienced a modest lowering in their total cholesterol and heart-damaging LDL cholesterol levels compared with those who ate a more Western-style diet that was higher in saturated fat. One study showed no significant effect. Importantly, and as noted in the health claim, none of the studies found that eating oleic acid-containing oils had beneficial heart effects unless they replaced other types of fats and oils higher in saturated fats in the diet.
The FDA intends to exercise enforcement discretion for the following qualified health claims:
"Supportive but not conclusive scientific evidence suggests that daily consumption of about 1½ tablespoons (20 grams) of oils containing high levels of oleic acid, when replaced for fats and oils higher in saturated fat, may reduce the risk of coronary heart disease. To achieve this possible benefit, oleic acid-containing oils should not increase the total number of calories you eat in a day. One serving of [x] oil provides [x] grams of oleic acid (which is [x] grams of monounsaturated fatty acid)."
"Supportive but not conclusive scientific evidence suggests that daily consumption of about 1 1/2 tablespoons (20 grams) of oils containing high levels of oleic acid may reduce the risk of coronary heart disease. To achieve this possible benefit, oleic acid-containing oils should replace fats and oils higher in saturated fat and not increase the total number of calories you eat in a day. One serving of [x] oil provides [x] grams of oleic acid (which is [x] grams of monounsaturated fatty acid)."
The qualified health claims respond to a petition filed by Corbion Biotech, Inc. Qualified health claims are supported by credible scientific evidence, but don't meet the more rigorous "significant scientific agreement" standard required for an authorized FDA health claim. As such, they must be accompanied by a disclaimer or other qualifying language so that the level of scientific evidence supporting the claim is accurately communicated. The FDA's intent to exercise enforcement discretion for the use of the qualified health claims means that the agency doesn't intend to object to its use, as long as the products bearing the claim are consistent with the factors FDA stated in the Letter of Enforcement Discretion that responds to the petition.
Oleic acid can be found naturally in numerous food sources, including edible oils, meat (such as beef, chicken, and pork), cheese, nuts, sunflower seeds, eggs, pasta, milk, olives, and avocados. Corbion Biotech's petition identified the following edible oils that contain at least 70% of oleic acid per serving: 1) high oleic sunflower oil, 2) high oleic safflower oil, 3) high oleic canola oil, 4) olive oil, and 5) high oleic algal oil.
— Source: FDA
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|Posted on December 9, 2020 at 8:45 AM||comments (0)|
HHS Public Access
Oxytocin for the treatment of drug and alcohol use disorders
Mary R. Lee and Elise M. Weerts
Additional article information
There is growing interest in the use of oxytocin (OT) as a potential treatment for alcohol and other substance use disorders. OT is a neuropeptide that modulates adaptive processes associated with addiction including reward, tolerance, associative learning, memory, and stress responses. OT exerts its effects via interactions with the hypothalamic–pituitary–adrenal (HPA) axis, and multiple neurotransmitter systems including the dopamine mesolimbic reward and corticotrophin-releasing factor stress systems. Oxytocin effects on stress systems are of high interest given the strong link between stress, drug use and relapse, and known dysregulation of HPA-axis activity associated with substance use disorders. At the same time, the oxytocin system is itself altered by acute or chronic drug exposure. This review summarizes the preclinical and clinical literature on the oxytocin system, and its relevance to drug and alcohol addiction. In addition, findings from recent clinical trials conducted in participants with cocaine, cannabis or alcohol use disorder are included and evidence that oxytocin may help to normalize blunted stress responses, and attenuate withdrawal associated hypercortisolism, negative mood and withdrawal symptoms are summarized.
Keywords: Oxytocin, addiction, dependence, substance use disorder, alcoholism, treatment
Oxytocin (OT) is a 9 amino acid polypeptide hormone that acts via a specific receptor and is widely distributed in the central nervous system (CNS) and peripheral tissues (Gimpl and Fahrenholz 2001). OT is involved in the regulation and release of adenohypophyseal hormones including prolactin, adrenocorticotropin (ACTH), gonadotropins, and corticotrophin-releasing factor (CRF). Initially, OT was thought to be primarily involved in sexual behaviors, female parturition and lactation. Subsequent research has determined that OT is also involved in emotional regulation, pain and stress, and modulates response to rewarding behaviors promoted by food, sex and drugs (Meyer-Lindenberg et al. 2011; Onaka et al. 2012). The co-modulation of both stress and motivational processes is believed to be due to the important role of OT to shift salience to social, affiliative processes, both by increasing the salience itself of rewarding stimuli and/or by reducing stress, allowing for attention to social bonding (Baskerville and Douglas 2010). This is obviously relevant to addiction, where salience of drug stimuli overshadows motivation for social affiliation, and where stress may trigger drug seeking and relapse (Sinha 2008). In the current review, we will focus on the role of the oxytocin system in drug and alcohol addiction and highlight key findings to date on the use of intranasal OT to treat substance use disorders.
Oxytocin and stress
The influence of OT to dampen stress responses is important. Neuroendocrine pathways that modulate the response to stress include three interconnecting circuits, the HPA axis, the adrenomedullary system, and the extra-hypothalamic CRF system. The HPA axis releases CRF from paraventricular neurons within the hypothalamus, stimulating the synthesis and release of adrenocorticotropin (ACTH) by the anterior pituitary, which in turn stimulates the synthesis and release of corticosteroids (CORT) (cortisol in human and nonhuman primates and corticosterone in rodents) via the adrenal cortex. The sympathetic adrenomedullary system, which releases norepinephrine and epinephrine, and CRF expression in the extra-hypothalamic brain regions including limbic regions, are key substrates involved in anxiety and other stress-related behaviors. Stress, defined as any stimulus that disrupts physiological homeostasis, triggers a cascade of adaptive responses involving any or all of these pathways to return the organism to homeostasis.
There is strong evidence from the preclinical literature that stress exposure is an important contributor to relapse. In rats and monkeys, acute stress enhances alcohol preference and reward (Funk et al. 2004), and increased alcohol intake is correlated with stress-induced increases in CORT levels (Fahlke et al. 2000; Fish et al. 2008). In addition, following repeated social stress exposure (e.g., defeat, low social rank, and maternal separation), rats and monkeys subsequently show greater alcohol intake when compared to non-stressed cohorts (Fahlke et al. 2000; Cruz et al. 2008; Fish et al. 2008). Current theories suggest that CORT release induced by stress augments drug reinforcement. Indeed, in rodents, CORT increases drug reward by increasing mesolimbic dopamine transmission (Piazza and Le Moal 1996), rats self-administer CORT itself at levels similar to those elicited by stress, and intracerebroventricular infusions of CORT enhance the reinforcing effects of alcohol (Fahlke et al. 1996).
Studies in laboratory animals have demonstrated that OT has marked anti-stress effects. When administered centrally, OT decreases stress-induced increases in CORT levels (Lang et al. 1983; Windle et al. 1997; Neumann et al. 2000) and reduces stress-induced behaviors in rodent models of anxiety and depression (Arletti and Bertolini 1987; Insel and Winslow 1991; Windle, et al. 1997; Neumann et al. 2000). At the same time, the endogenous OT system appears to be sensitive to stressors. In rats, exposure to acute stress increased OT levels in blood and in hypothalamic and extra-hypothalamic brain regions (Lang et al. 1983; Neumann et al. 1998; Ebner et al. 2000; Ondrejcakova et al. 2010) and increased OT mRNA levels (Jezova et al. 1995). Thus, OT appears to play a protective role in homeostatic regulation of stress responses, and OT administration may attenuate the effects of stress on drinking/drug use and relapse (Uhart and Wand 2009; Koob et al. 2014).
Investigations in human subjects are in line with the preclinical literature. When administered via the intranasal route, OT produces changes in measures of autonomic arousal and mood (MacDonald et al. 2011), increased positive communication during couples’ conflict discussions (Ditzen et al. 2009) and improved recognition and processing of positive facial expressions (Di Simplicio et al. 2009; Marsh et al. 2010; Lischke et al. 2012). The anti-stress effects of OT have been also been investigated using the Trier Social Stress Test, a well-validated laboratory procedure for induction of stress responses in human subjects (Foley and Kirschbaum 2010). This test, which includes components of public speaking component and oral mental arithmetic, produces a robust increase in CORT and self-reported psychological stress and these effects are attenuated by OT (Heinrichs et al. 2003; Quirin et al. 2011; Simeon et al. 2011; de Oliveira et al. 2012; Kubzansky et al. 2012). Consistent with an OT anti-stress hypothesis, a recent study that measured both OT and CORT after the TSST found that salivary OT levels increased immediately following social stress exposure, prior to increases in salivary CORT (Jong et al. 2015). Taken together, these data suggest that OT treatment may be useful to normalize the HPA-axis and reduce stress-related physiological and subjective responses (e.g., anxiety, craving) that increase drug and alcohol use and trigger relapse. ......
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|Posted on December 4, 2020 at 6:00 PM||comments (0)|
Natural triterpenes modulate immune-inflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis
R Martín,* M Hernández, C Córdova, and ML Nieto
Author information Article notes Copyright and License information Disclaimer
This article has been cited by other articles in PMC.
BACKGROUND AND PURPOSE
Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory demyelinating diseases that develop as a result of deregulated immune responses causing glial activation and destruction of CNS tissues. Oleanolic acid and erythrodiol are natural triterpenes that display strong anti-inflammatory and immunomodulatory activities. Oleanolic acid beneficially influences the course of established EAE. We now extend our previous observations to erythrodiol and address the efficacy of both compounds to protect against EAE, given under different regimens.
The utility of both triterpenes in disease prevention was evaluated at a clinical and molecular level: in vivo through their prophylactic administration to myelin oligodendrocyte protein-immunized C57BL/6 mice, and in vitro through their addition to stimulated-BV2 microglial cells.
These triterpenes protected against EAE by restricting infiltration of inflammatory cells into the CNS and by preventing blood–brain barrier disruption. Triterpene-pretreated EAE-mice exhibited less leptin secretion, and switched cytokine production towards a Th2/regulatory profile, with lower levels of Th1 and Th17 cytokines and higher expression of Th2 cytokines in both serum and spinal cord. Triterpenes also affected the humoral response causing auto-antibody production inhibition. In vitro, triterpenes inhibited ERK and rS6 phosphorylation and reduced the proliferative response, phagocytic properties and synthesis of proinflammatory mediators induced by the addition of inflammatory stimuli to microglia.
CONCLUSIONS AND IMPLICATIONS
Both triterpenes restricted the development of the characteristic features of EAE. We envision these natural products as novel helpful tools for intervention in autoimmune and neurodegenerative diseases including MS.
Keywords: encephalomyelitis, neuroimmunology, inflammation, microglia, pharmacology, triterpenes
Multiple sclerosis (MS) is an autoimmune demyelinating disease directed against myelin proteins of the brain and spinal cord, and is considered as one of the major neurological diseases in young adults (Noseworthy et al., 2000). The precise cause of MS is unknown, but one theory is that it might be triggered by exposure to a viral infection or environmental influences. The disease takes dissimilar courses in different people and can go into four main pathological subtypes, even leading to death in the very progressive form (Lassmann et al., 2001).
Experimental autoimmune encephalomyelitis (EAE) induced in susceptible strains of animals provides the best available model for understanding events in MS and to test new drugs that could lead to novel therapies (Steinman, 1999). MS/EAE pathogenesis is driven mostly by a Th1-mediated autoimmune response. The development of the disease includes breakdown of the blood–brain barrier (BBB), infiltration of the CNS – brain and spinal cord – by myelin-reactive T cells and macrophages, activation of resident CNS cells (microglia and astrocytes), demyelination and axonal loss (Merrill and Benveniste, 1996; Benveniste, 1997; Engelhardt, 2006).
Microglial cells are active participants throughout the MS disease process. ‘Activated’ microglia produces inflammatory cytokines, free radicals and attracts immune cells into the CNS. A diffuse activation of microglia throughout the brain serves as a source of inflammation inside the CNS in chronic MS/EAE, while at latter stages of the disease a chronically activated microglia is associated with impaired neural function (Rasmussen et al., 2007).
Other components of the immune system that play crucial roles in MS/EAE pathogenesis include dendritic and B cells, antibodies, as well as inflammation-related enzymes, cytokines and chemokines. Thus, COX-2 and inducible nitric oxide synthase (iNOS) enzymes and pro-inflammatory cytokines such as IFN-γ, TNF-α or IL-17 are considered to be pathogenic, while the Th2 cell-related cytokines IL-4 and IL-10 have been shown to down-regulate the immune response in acute EAE (Hafler, 2004; Imitola et al., 2005; Sospedra and Martin, 2005). Much progress has been made over the past decade in elucidating the causes and molecular basis of MS, but in spite of the extensive research performed to develop new pharmacotherapeutic approaches to slow down the disease progression, there are still no optimal therapies available, due to both unwanted side effects of the drugs and the clinical and immunopathological heterogeneity of this disease (Hemmer et al., 2006).
Oleanolic acid and erythrodiol are two natural triterpenes of the oleanane group present in many vegetables, including the leaves and fruits of Olea europea (the olive tree). They have been recognized to have hepatoprotective, anti-inflammatory and antihyperlipidemic properties. Indeed, oleanolic acid has been promoted in China as an oral drug for human liver disorders. Data correlated well with the traditional use of O. europea in African and European Mediterranean countries, where this plant has been utilized widely in folk medicine as a diuretic, hypotensive, hypoglycaemic, emollient, febrifuge and tonic, for urinary and bladder infections, for headaches, as well as a therapy for inflammatory pain (Dold and Cocks, 1999). Recently, a number of synthetic oleanane triterpenoid derivatives have been synthesized based on oleanolic acid with more potent activities, some of which are currently being developed for the treatment of chronic kidney diseases (Pergola et al., 2011) or as an attractive new therapeutic option for cancer patients by enhancing the effect of immunotherapy (Nagaraj et al., 2010). In the last years, a variety of novel pharmacological properties of triterpenoids have been reported: (i) beneficial effects on cardiovascular system due to antioxidant and vasorelaxant activities (Rodriguez-Rodriguez et al., 2006); (ii) interaction with cytochrome P450s; (iii) anti-proliferative activities on tumoural cells by activating apoptotic programmes (Martín et al., 2007; 2009); (iv) effects on intracellular redox balance and protective effects against lipid peroxidation; as well as (v) immunomodulatory effects (Marquez-Martin et al., 2006). Besides, we have shown that oleanolic acid has a therapeutic effect on an experimental model of MS (Martín et al., 2010), demonstrating that i.p. administration of oleanolic acid, in mice with established EAE, is capable of reducing important biomarkers related to EAE disease. However, the potential of these biologically active molecules on maintenance of health has not been addressed in depth, although disease prevention is a major goal on public health, particularly because of the shifting of the concept from ‘disease care’ to ‘health care’. Therefore, it has been of interest in the present study to assess the influence of early administration of oleanolic acid and erythrodiol, an intermediate from which oleanolic acid is formed and on which no previous data exist, on health promotion in our EAE model. Our findings confirmed that both erythrodiol and oleanolic acid markedly slowed the clinical manifestations of the disease and we were able to correlate the magnitude of improvement for EAE with the decrease of the immuno-inflammatory responses.
Disease induction and treatment
All animal care and experimental protocols were reviewed and approved by the Animal Ethics Committee of the University of Valladolid and complied with the European Communities directive 86/609/ECC and Spanish legislation (BOE 252/34367-91, 2005) regulating animal research. C57BL/J6 mice (from Charles River Laboratories, Barcelona, Spain) were housed in the animal care facility at the Medical School of the University of Valladolid and provided food and water ad libitum.
EAE was induced in 8 to 10-week-old female C57BL/J6 mice by subcutaneous immunization with 100 µg of myelin oligodendrocyte glycoprotein (MOG)35–55 peptide (MEVGWYRSPFSRVVHLYRNGK; from Dr F. Barahona, CBM, Madrid) emulsified in complete Freund's adjuvant containing 0.4 mg Mycobacterium tuberculosis (H37Ra; Difco, Detroit, MI, USA) on day 0. Additionally, mice received 300 ng of Pertussis toxin i.p. on days 0 and 2. Clinical signs of EAE were assessed daily in a double-blind manner on a scale of 0 to 5, with 0.5 points for intermediate clinical findings: grade 0, no abnormality; grade 0.5, partial loss/reduced tail tone, assessed by inability to curl the distal end of the tail; grade 1, tail atony; grade 1,5, slightly/moderately clumsy gait, impaired righting ability or combination; grade 2, hind limb weakness; grade 2,5, partial hind limb paralysis; grade 3, complete hind limb paralysis; grade 3,5, complete hind limb paralysis and fore limb weakness; grade 4, tetraplegic; grade 5, moribund state or death. Scores from two investigators, both unaware of the treatments, were averaged. Data were plotted as daily mean clinical score for all animals in a particular treatment group. Scores of asymptomatic mice (score = 0) were included in the calculation of the daily mean clinical score for each group. Mice scoring at level 4 for 2 days were automatically given a disease severity grade of 5 and killed.
Triterpene treatment procedure
MOG-Immunized mice were treated daily with 50 mg kg–1 day–1 of oleanolic acid or erythrodiol by i.p. injection beginning at different times.
Groups OA0 and ERY0: triterpene treatment started at the immunization day.
Groups OA-7 and ERY-7: triterpene treatment started on day -7, before EAE induction.
Groups OA12 and ERY12: triterpene treatment started on day 12 after EAE induction.
Control groups (without EAE induction):
Group control, C: treated daily with 0.2% w/v DMSO.
Groups OA and ERY: healthy mice treated with the triterpenes for the same time as the corresponding EAE mice.
Animals were studied at two different times:
30 days after immunization, when EAE mice showed hind limb paralysis, or
at the day when severe symptoms (score 5) in each animal group were apparent. This was at day 40 in untreated EAE mice and at day 110 for triterpene-treated EAE mice, after immunization.
Control mice (without EAE induction) were also injected daily with oleanolic acid or erythrodiol for an equivalent period of time.
Oleanolic acid and erythrodiol (Extrasynthese, Genay Cedex, France) were first dissolved in 2% w/v DMSO and then diluted with PBS for each experiment (the final concentration of DMSO was 0.2%, w/v).
Spinal cord tissue was obtained from five representative animals of the different experimental groups on day 30 after immunization. Tissues were fixed and embedded in paraffin, cut on a microtome (5 µm thicknesses), stained with eosin-haematoxylin. Histological examination was performed with a Nikon Eclipse 90i (Nikon Instruments, Inc., Amstelveen, the Netherlands) connected to a DXM1200C digital camera (Nikon Instruments Inc). Sections from 4–10 segments per mouse were examined by one investigator, without knowledge of the treatments.
Intravital microscopy in mouse brain
Intravital microscopy of the mouse cerebromicrovasculature was performed as previously described (Martín et al., 2010). Briefly, mice were anaesthetized at day 30 post-immunization by i.p. injection of a mixture of 100 mg·kg−1 ketamine and 10 mg·kg−1 xylazine, and the tail vein was cannulated for administration of fluorescent dyes. A craniotomy was performed using a high-speed drill (Dremel, Madrid, Spain) and the dura matter was removed to expose the underlying pial vasculature. The mouse was maintained at 37°C throughout the experiment and the exposed brain was continuously superfused with artificial CSF buffer at 37°C.
Leukocytes were fluorescently labelled by i.v. administration of rhodamine 6G (5 mg·kg−1 body weight) and visualized by a Zeiss Axioplan 2 imaging microscope (Hertfordshire, UK) connected to an AxioCam MR digital camera using the AxioVision AC imaging software and an Acroplan 20x/0.50W Ph2 lens. Eight different post-capillary venules of diameter between 30 and 70 µm were chosen for observation. Rolling leukocytes were defined as white cells moving at a velocity less than that of erythrocytes. Leukocytes remaining stationary for 30 s or longer were considered adherent to the venular endothelium. Leukocyte adhesion was expressed as cells/mm2 of venular surface area, as shown previously (Martín et al., 2010).
Evaluation of cytokines and MOG-specific antibodies by elisa
Anti-MOG-specific IgM and IgG isotypes were detected in serum samples collected from animals on day 30 after immunization, using elisa. In brief, 96-well polystyrene microtitre plates were coated with 0.5 mg per well of MOG35–55 peptide diluted in PBS overnight in a humidified chamber followed by PBS washing and blocking for 1 h with 5% BSA in PBS. Wells were incubated in duplicate with serum samples diluted 1:60 in PBS for 2 h at room temperature. After washing, HRP-labelled rat anti-mouse IgM, anti-mouse IgG, anti-mouse IgG1 and anti-mouse IgG2a (1:2000) from Serotec (Sigma-Aldrich, St Louis, MO, USA) were subsequently added for 90 min. After another washing, adding the substrate, and arresting the reaction with 0.1N HCl, absorbance was read at 450 nm. Data are expressed as mean optical density at 450 nm.
Leptin levels in serum samples and spinal cord tissue were determined by elisa (RayBiotech, Norcross, GA, USA). For cytokine quantification (IL-4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ), cell culture medium, serum and spinal cord tissue were analysed by elisa according to the manufacturer's protocols (eBioscience, San Diego, CA, USA). Spinal cords were removed on day 30 after immunization or at the severe stage of the disease (score 5), weighed and then frozen at −80°C. SC tissue was homogenized by using a tissue homogenizer (Cole-Parmer Instrument, Vernon Hills, IL, USA) in an ice bath in 0.5 mL ice-cold PBS supplemented with 0.4 M NaCl, 0.05% Tween 20, 0.5% BSA and a protease inhibitor cocktail: 20 µg·mL−1 of leupeptin, 20 KI units of aprotinin, 0.1 mM phenylmethylsulphonyl fluoride (Sigma-Aldrich), and centrifuged at 3000× g for 10 min at 4°C. Supernatant were stored at −80°C until cytokine assays were performed. Total protein was assayed using the Bradford method. A 50 to 100 µL sample of each supernatant was used for tests.
Data were processed and expressed as pg of cytokine per mg of spinal cord wet weight, or pg of cytokine per mL for serum samples.
BBB permeability measurement
To evaluate BBB disruption, we measured the extravasation of Evans blue (EB) dye as a marker of albumin extravasation. At 30–31 days following EAE induction, mice were injected i.p. with 1 mL of 4% w/v EB. After 4 h, mice were killed, perfused, and brain and spinal cords were removed. Dye was extracted for 2–3 days in formamide (4 mL·g−1 of wet tissue) at room temperature. Extracted dye concentration was determined by measuring the absorbance at 650 nm. CNS tissue was dried 24 h at 60°C and weighed. Calculations were based on external standard readings and extravasated dye was expressed as mg of EB per mg dried weight of tissue.
Murine BV-2 cells, an immortalized murine microglia cell line, exhibit phenotypic and functional properties comparable with those of primary microglia and hippocampal neurons (Bocchini et al., 1992). BV-2 cells (a gift from Prof J. Bethea, Miller School of Medicine, Miami, FL, USA) were cultured in Dulbecco's modified Eagle's medium high sucrose, supplemented with 10% fetal bovine serum (FBS), 100 U·mL−1 penicillin and 100 µg·mL−1 streptomycin, and kept at 37°C in 5% CO2. Cells were seeded in 96-well plates (5 × 104 cells per well) or 60 mm culture dishes (3 × 106 cells per well.).
Cell proliferation was quantified by using the Promega kit (Madison, WI, USA), Cell Titer 96® Aqueous One Solution Cell Proliferation Assay, according to the manufacturer's recommendations. Briefly, cells were seeded in 96-well plates and serum starved for 24 h. Then, cells were treated in triplicate with IFN-γ, leptin or LPS, in the presence or absence of the triterpenes. After 24 h of incubation, formazan product formation was assayed by recording the absorbance at 490 nm in a 96-well plate reader (OD value). Formazan is measured as an assessment of the number of metabolically active cells and expressed in percentages relative to FBS-stimulated cells. Cell viability was assessed by Trypan blue exclusion.
Western blot analysis
Cells were washed with PBS and harvested in Laemmli SDS sample buffer. Protein extracts were separated by SDS-PAGE and transferred to polyvinylidene difluoride membranes. Membranes were blocked with 5% BSA-TBST at room temperature and then incubated for 18 h at 4°C with the indicated antibodies including ERK 1/2 (Zymed Laboratories, South San Francisco, CA, USA), rabbit p-ERK1/2, p-rS6 (Cell Signaling Technology, Danvers, MA, USA), COX-2 (sc-1745, Santa Cruz Biotech, Santa Cruz, CA, USA), actin (sc-8432, Santa Cruz Biotech) and iNOS (BD Biosciences, Lexington, KY, USA). After washing with TBST buffer, a 1:2.000 (v/v) dilution of horseradish peroxidase-labelled IgG was added at room temperature for 1 h. The blots were developed using enhanced chemiluminescence.
Cells were stimulated in serum-free media with or without 100 UI·mL−1 of IFN-γ, 1 µg·mL−1 of LPS or 0.5 µM of leptin for 24 h, in the presence or absence of different doses of oleanolic acid or erythrodiol and then exposed to 0.1 mg·mL−1 of FITC-labelled dextran (MW 40 000) for 2 h. Non-internalized particles were removed by vigorous washing with cold PBS (pH 7.4) prior to measuring fluorescence at 480 nm excitation and 520 nm emission on either a Flow Cytometer (Gallios™; Beckman Coulter, Fullerton, CA, USA) or a Fluoroskan multiwell plate reader (TECAN Genios Pro; Tecan Group Ltd, Zurich, Switzerland). Cultures without fluospheres were used (blank wells) as background. Each culture condition was done in triplicate, and three independent experiments were performed. To confirm that the fluospheres were accumulated intracellularly, a Leica TCS SP5X confocal microscope was used with the Leica LAS AF acquisition software (Wetzlar, Germany) and a ×60 oil objective.
Statistical analysis was performed with the GraphPad Prism Version 4 software (San Diego, CA, USA) by anova. Analyses were performed using repeated measures anova (or two-way anova) for comparison of clinical parameters, and one-way anova for comparison of parameters such as cytokines, extravasation, leukocytes and MOG antibodies. A post hoc analysis was made by the Bonferroni's multiple comparison test. P < 0.05 was considered statistically significant.
Effects of preventive treatment with oleanolic acid or erythrodiol on clinical EAE
Female C57BL/6 mice exhibit active EAE after immunization with the MOG35–55 peptide. In this experimental model we compared the effects of two pentacyclic triterpenes, oleanolic acid and erythrodiol given at a dose (50 mg·kg−1) previously proven to be both safe and therapeutically relevant in rodents (Jeong, 1999; Senthil et al., 2007; Martín et al., 2010) in two regimens: 7 days before immunization (day -7; OA-7, ERY-7) or at the day of induction (day 0; OA0, ERY0). The clinical analysis of the different groups of animals is shown in Figure 1. The placebo-treated animals developed neurological symptoms of active EAE after 12 to 31 days, consisting of tail limpness and a mild-to-moderate paraparesis, as well as progressive weight loss. Interestingly, when oleanolic acid or erythrodiol were administered from the day of induction, clinical disease was markedly less severe and mice had a later onset of the clinical signs compared with untreated animals with EAE (Figure 1A). First neurological symptoms (score 1) were observed at day 11 with mean day of onset 13.5 ± 2 in untreated EAE mice, while OA0 or ERY0 animals showed no clinical signs at that time and a similar score (tail atony) was first reached on day 27 (mean values 33 ± 2 and 34 ± 2 days respectively). When the triterpenes were given as a pre-treatment, starting 1 week before EAE induction, clinical disease remained mostly suppressed for the duration of the experiment (until day 30 post-induction)........... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419913/
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Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: a possible strategy for reducing SARS-COV-2 infectivity?
Mirko Baglivo 1, Manuela Baronio 2, Giuseppe Natalini 3, Tommaso Beccari 4, Pietro Chiurazzi 5, Ezio Fulcheri 6, Paolo Pietro Petralia 7, Sandro Michelini 8, Giovanni Fiorentini 9, Giacinto Abele Miggiano 10, Assunta Morresi 11, Gerolamo Tonini 12, Matteo Bertelli 13
PMID: 32191676 PMCID: PMC7569585 DOI: 10.23750/abm.v91i1.9402
Free PMC article
Background: Viral infectivity depends on interactions between components of the host cell plasma membrane and the virus envelope. Here we review strategies that could help stem the advance of the SARS-COV-2 epidemic.
Methods and results: We focus on the role of lipid structures, such as lipid rafts and cholesterol, involved in the process, mediated by endocytosis, by which viruses attach to and infect cells. Previous studies have shown that many naturally derived substances, such as cyclodextrin and sterols, could reduce the infectivity of many types of viruses, including the coronavirus family, through interference with lipid-dependent attachment to human host cells.
Conclusions: Certain molecules prove able to reduce the infectivity of some coronaviruses, possibly by inhibiting viral lipid-dependent attachment to host cells. More research into these molecules and methods would be worthwhile as it could provide insights the mechanism of transmission of SARS-COV-2 and, into how they could become a basis for new antiviral strategies. https://pubmed.ncbi.nlm.nih.gov/32191676/
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Background: This study has been done to analyze the effect of nutritional elements on human immune system. Human body possesses many elements in order to protect itself. In the simplest term, the outer creatine layer on the skin is one of them. Human immune system, along with the cells in peripheries circulation, hormones and solvable immuno modulators is fairly sophisticated and had yet not been resolved completely. Immune system, in human organism detects the molecules which are unfamiliar to its own structure and responds to them in convenient terms. In the event of pathogen factor entrance into human body, immune system steps in to action and creates immune response.
There are many factors that affect immune system functions, one of those is nutrition. There is a significant correlation between immune system and nutrition, furthermore malnutrition shouldn’t be considered as energy and a protein deficiency alone. Due to these reasons, the main aim of nourishment is not merely to gain energy and protein, but to enhance resistance against ailments with some specific nutriment and to turn the inflammatory response in someone’s best interests. The nutriments which show beneficial effects on immune system are called. Immune nutriments and nourishment on these nutriments is called immune diet. The main fields of application of immune diet is
patient undergoing surgery, traumatized, cancer patients, patients who need intensive care and patients with serious infections such as sepsis.
Conclusions: In conclusion, in order to strengthen our immune system, to reduce the risks of ailments and to stay healthy the body defence system in our body should be strengthened. To do so, particular costly medicines can be used; however, regular exercises and having an immune diet will be more economical and natural preference.
Nourishment; Immune system; Nutritional elements; Immunological nourishment
Human beings are in close relation with the microorganisms that were common in nature. Immune system is a means of protection against the damaging effects of noxas, which cause infection in our bodies. Immune system is a form of protection consisting of, thymus, spleen, lymph nodes and some specific immunity cells .
Immunity, on resistance against microorganisms acts both naturally and acquired in a complex mechanism, but they are mostly in collaboration. One of the factors that affect natural resistance is nutrition. Malnutrition breaks down the immune functions by suppressing the immune system .
The dietary factors that cause harm to immunity functions are either deficient intake of macro-nutrient elements (fat, carbohydrate, protein) or deficiency in some specific micronutrient elements (vitamin, mineral, water). Balanced nutrition, especially in terms of adequate vitamin, mineral and protein intake, enhances the resistance against infections. Research’s show that balanced nutrition subsidizes the immune system and Cary out vital importance on the system .
Nutrition has an impact on body resistance and microbes. Excessive strain, Traumas, Ambustions, etc., could cause protein destruction consequently body resistance decreases. Malnutrition, especially in childhood play vital role in catching illness and mortality. Malnutrition paves the way for infections and their complications. This composed infection distorts the nutrition and abates the immunity [2,3].
The effects of nutritional elements on immune system has been a study case for many research’s because there is significant influence on supporting immune system and in deficiency it causes malfunction in immune system [2,3].
Immune system is a common name for structures within our bodies that protects living organisms against harmful substances. Human body possesses many elements in self defence. One of the simplest of those is outer creatine layer on the skin. Another element is biochemical body units .
The substance that stimulates the immune system is generally known as nonspecific substance like macrophage and neutrophils that enhance the defence capability of phagocytes. The many of those substances ad here the surfaces of phagocytes and lymphocyte cells and also stimulates the production of interferon, interleukin and sophisticated compositions, consequently activates the immune system .
Immune system has a structure that consists of similar neurologic system. One of the most significant traits of immune system is, having the ability of recognizing the millions of different threats and distinguishes them. Thanks to this trait, the functionary cells in immune system, detect the unfamiliar object, memorise it and recognise it when coming across later.
These structures are; thymus spleen, lymph nodes and specific immunity cells. Immune system gets down to work as soon as pathogenic factors entering the body. This defence carried out by immune system against pathogenic called “immune response” [1,5,6].
Immune system is a moliminous mechanism in fighting against diseases and sanitation. The possible response of immune system against body cells is called autoimmune reactions and consequently autoimmune disorders occur ...... https://www.omicsonline.org/open-access/the-effect-of-nutritional-elements-on-the-immune-system-2165-7904.1000152.php?aid=10186
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Diet and Immune Function
Caroline E. Childs,1 Philip C. Calder,1,2 and Elizabeth A. Miles1,*
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This article has been cited by other articles in PMC.
A well-functioning immune system is critical for survival. The immune system must be constantly alert, monitoring for signs of invasion or danger. Cells of the immune system must be able to distinguish self from non-self and furthermore discriminate between non-self molecules which are harmful (e.g., those from pathogens) and innocuous non-self molecules (e.g., from food). This Special Issue of Nutrients explores the relationship between diet and nutrients and immune function. In this preface, we outline the key functions of the immune system, and how it interacts with nutrients across the life course, highlighting the work included within this Special Issue. This includes the role of macronutrients, micronutrients, and the gut microbiome in mediating immunological effects. Nutritional modulation of the immune system has applications within the clinical setting, but can also have a role in healthy populations, acting to reduce or delay the onset of immune-mediated chronic diseases. Ongoing research in this field will ultimately lead to a better understanding of the role of diet and nutrients in immune function and will facilitate the use of bespoke nutrition to improve human health.
Keywords: nutrition, immunity, macronutrients, micronutrients, microbiome, life course, probiotic, prebiotic, inflammation
1. Overview of the Immune System
Broadly, cells of the immune system may be divided into those of the innate and those of the adaptive immune response. The innate response is the first response to an invading pathogen. Cells of the innate immune response include phagocytes (e.g., macrophages and monocytes), neutrophils, dendritic cells, mast cells, eosinophils, and others. The innate response is rapid, but not specialised and is generally less effective than the adaptive immune response.
The adaptive immune response has the ability to specifically recognise a pathogen and ‘remember’ it if exposed to it again. T cells are critical in antigen recognition and the co-ordination of the immune response. T cells are present in an array of subtypes that coordinate different types of immune responses. Broadly, they are divided into the cytotoxic T cells (bearing the CD8 receptor), which are involved in direct killing of infected damaged cells and tumour cells, and the T helper cells. T helper (Th) cells bear the CD4 receptor and are important in coordinating the responses of other immune cells. There are a number of subtypes of Th cells, defined by the cytokines they produce. Initial studies identified two subsets, the Th1 cells, which produced interferon gamma (IFN-γ) and interleukin (IL)-2 and were important in antiviral and cellular immune responses, and the Th2 subset producing IL-4, IL-5, and IL-13 and involved in humoral (antibody) and anti-parasitic responses (but also in allergic responses) . It is now apparent that there are a number of other Th subtypes, which do not fall into these categories. This includes Th17 cells, which produce IL-17A, IL-17F, and IL-22 and are important in fighting extracellular pathogens (bacteria and fungi) . There are also T regulatory cells (Treg), which are CD4-bearing T cells vital in maintaining immune tolerance to allow the immune system to ignore non-harmful non-self (such as food, pollen, and environmental antigens such as latex). Thus, the role of T cells is coordinating an appropriate immune response following immune stimulation or challenge.
The other lymphocytes of the adaptive immune system are the B cells, which are responsible for antibody or immunoglobulin (Ig) production. Like T cells, B cells respond specifically to an antigen. They can differentiate into short-lived plasma cells, which produce Igs in the short term, or can become long-lived plasma cells. Igs are pathogen-specific molecules, which help the immune system to recognise and destroy pathogens. The B cells can differentiate into plasma cells, which produce one of five classes of Ig (IgM, IgD, IgG, IgA, and IgE). Each class of Ig has a specialised role . IgM is the first Ig expressed during development, is often found as a multimeric molecule (e.g., pentameric), and can bind an antigen to identify it for destruction by immune cells. IgD is found in low concentrations in the plasma and the specialist role of IgD is not yet clear. IgG is the predominant Ig class and can persist for long periods. It has important roles in antigen labelling, resulting in more effective removal. IgA can be found in the serum (mostly as a monomer) and at mucosal surfaces (normally as a dimer). At the mucosal surface, IgA protects against bacteria and or viruses, preventing infection. IgA also has an important role in neutralising food antigens and helping to maintain immune tolerance to food antigens (preventing the development of food allergy) . IgE has a role in clearance of extracellular parasites (e.g., helminths) but when produced inappropriately to innocuous environmental and food antigens, has an important role in IgE-mediated allergy. B cells go through a process called class switching to set the class of Ig that the plasma cells derived from them will produce. B cell class switching is controlled by the cytokines present, particularly IL-4, IL-6, and IFN-γ secreted from Th cells .
T and B cells can specialise to become memory cells, which persist permanently or for very long periods and are able to recognise the antigen if encountered again and elicit a rapid, pathogen-specific immune response.
The effective deployment of the immune system against pathogens or harmful signals and the swift resolution of the immune response is required for survival. The fighting of infection is only one piece of the puzzle. A fulminating immune response is costly in terms of energy expended and results in damage to the host tissues; thus, rapid and complete resolution of an immune response is also key. Cytokines play a role in resolution of immune responses. IL-10, which is produced by a range of immune cells including Tregs, has anti-inflammatory actions including suppressing inflammatory cytokine production .
The instigation of an immune response and the activities of the immune cells results in inflammation (seen as redness, swelling, and the feeling of heat and pain), which are signs of the damage to the tissue going on whilst the immune system does its work. This is an expected outcome of an effective immune response. Increasingly there is concern that modern lifestyle changes have resulted in the promotion of ongoing, low-grade, whole-body (systemic) inflammation caused by immune and other cells (e.g., adipocytes, the cells that store lipids in fat tissue) . Such exposures may include diet quality and quantity .
2. The Role of Nutrition in Immune Function
Adequate and appropriate nutrition is required for all cells to function optimally and this includes the cells in the immune system. An “activated” immune system further increases the demand for energy during periods of infection, with greater basal energy expenditure during fever for example. Thus, optimal nutrition for the best immunological outcomes would be nutrition, which supports the functions of immune cells allowing them to initiate effective responses against pathogens but also to resolve the response rapidly when necessary and to avoid any underlying chronic inflammation. The immune system’s demands for energy and nutrients can be met from exogenous sources i.e., the diet, or if dietary sources are inadequate, from endogenous sources such as body stores. Some micronutrients and dietary components have very specific roles in the development and maintenance of an effective immune system throughout the life course or in reducing chronic inflammation. For example, the amino acid arginine is essential for the generation of nitric oxide by macrophages, and the micronutrients vitamin A and zinc regulate cell division and so are essential for a successful proliferative response within the immune system.
Undernutrition is well understood to impair immune function, whether as a result of food shortages or famines in developing countries, or as a result of malnutrition arising from periods of hospitalisation in developed countries. The extent of impairment that results will depend upon the severity of the deficiency, whether there are nutrient interactions to consider, the presence of infection, and the age of the subject . A single nutrient can also exert multiple diverse immunological effects, such as in the case of vitamin E, where it has a role as both antioxidant, inhibitor of protein kinase C activity, and potentially interacting with enzymes and transport proteins . For some micronutrients, excessive intake can also be associated with impaired immune responses. For example, supplementation with iron can increase morbidity and mortality of those in malaria endemic regions. As well as nutrition having the potential to effectively treat immune deficiencies related to poor intake, there is a great deal of research interest in whether specific nutrient interventions can further enhance immune function in sub-clinical situations, and so prevent the onset of infections or chronic inflammatory diseases.
3. Gut-Associated Lymphoid Tissue
The majority of immune cells within the human body are found within the gut-associated lymphoid tissue (GALT), reflecting the importance of this immune tissue in maintaining host health. In ingesting food, we expose ourselves to near constant and massive antigenic stimulation, and our immune system must be able to provide strong and protective immunity against invasive pathogens, while tolerating food proteins and commensal bacteria. In order to achieve this, the GALT contains a variety of sensing and effector immune functions. Dendritic cells and M cells sample the gut content, while plasma B cells within the lamina propria produce IgA, providing protection against pathogenic organisms. Specialised immune regions known as Peyer’s patches, rich in immune cells, allow for communication between immune cells resident within the GALT, propagation of signals to the wider systemic immune system, and the recruitment or efflux of immune cells .
Within the gut lumen itself, the human gut microbiome will provide antigens and signals with the potential to interact with resident and systemic immune cells. The composition of the gut microbiome changes over the life course, in response to dietary components, and to environmental factors such as antibiotic exposure. Dietary interventions targeted at the gut microbiome include probiotics and prebiotics. Probiotics are defined as “live microorganisms, which, when consumed in adequate amounts, confer a health benefit of the host”  while prebiotics, “a substrate that is selectively utilized by host microorganisms conferring a health benefit” , tend to be non-digestible oligosaccharides such as fructo-oligosaccharides and galacto-oligosaccharides. Provision of plant-based diets may enhance the diversity of nutrients that reach the gut microbiome, with the indigestibility of plant cell walls enabling peptides and lipids, which may otherwise have been absorbed in the upper digestive tract to reach the microbiome . There may be circumstances in which immune cells of the GALT come into direct contact with nutrients or gut microbiota, such as in the case of reduced epithelial integrity, or ‘leaky gut’ observed in both acute and chronic gut inflammation . Such changes in gut permeability may be influenced by micronutrient status such as that of vitamin D .
A number of nutrients and dietary interventions have demonstrated the capacity to improve measures of gut health or to reduce gut inflammation. Protein hydrolysates have been demonstrated to enhance barrier function and IgA production in animal models, and as a result may have applications for incorporation within hypo-allergenic infant formula and clinical nutrition for those with conditions such as inflammatory bowel disease . Animal models of gut inflammation have identified that providing probiotic bacteria can reduce inflammation, with reductions in proinflammatory Th1 and Th17 cytokines such as IL-17 and IFN-γ, and enhanced production of inflammation resolving cytokine IL-10 . Prebiotics can also enhance barrier function, in addition to their role as substrates for bacterial metabolism . Santiago-Lopez et al. have investigated the effect of fermented milk on a murine model of inflammatory bowel disease  and demonstrated a reduction in serum IL-17 and IFN-γ following fermented milk consumption when compared with the control group.
4. Immune Function Over the Life course
The developing foetus and neonates have an immature immune system, with poor antibody production and a low proliferative response to challenge. In utero, the foetus can gain passive protection from its mother via antibodies, which cross the placenta. This is the basis by which infants in the UK are provided with early protection against whooping cough, with mothers offered vaccination in their third trimester, in order to provide passive immunity to their infants until they reach the age of infant vaccinations. While immature, the foetal immune system can produce antibodies, and allergens can reach the developing foetus, and allergen-specific IgE can be detected in cord blood samples . Another signature of the immaturity of the immune system in early life is the susceptibility of neonates to infections, and the associated higher burden of morbidity and mortality.
The development of the immune system in early life will be influenced by both feeding practices and environmental exposures. Breastfeeding provides further passive immunity to the infant, for example via transfer of antibodies and cytokines. Breast milk components can also stimulate maturation of the gut-associated lymphoid tissue, with breast milk known to be rich in bifidogenic oligosaccharides and to contain its own unique microbiota. Human milk oligosaccharides (HMOs) are synthesised from lactose in the mammary gland, and the specific HMO profile will vary between individuals and across contexts and changes over the time course of lactation . These HMOs have been found to confer health benefits to infants by inhibiting the adhesion of microorganisms to the intestinal mucosa, enhancing the production of short-chain fatty acids by bacteria within the microbiome, and inhibiting inflammation . Other immune active components of breast milk are also likely to be involved in immune system maturation, with studies identifying that the growth factors epidermal growth factor, fibroblast growth factor 21, and transforming growth factor-β2 can change lymphocyte phenotypes in new-born rats when provided as supplements by oral gavage .
In infancy, diverse environmental factors will impact upon immune system development; identified factors include pet ownership, antibiotic use, and the timing of introduction of foods . The opportunity for introduction of prebiotic oligosaccharides during the introduction of foods has been explored, with the suggestion that this could provide a unique opportunity to influence the developing microbiome and thereby interact with the developing immune system . These early years of life are a critical period in the development of the immune system, particularly for T cell function, with the thymus maturing and reaching its maximum size relative to body weight in infancy .
As we move through the life course towards later life, a decline in immune function is observed among older adults. As was the case in infancy, older adults are more susceptible to infections, and have more serious complications as a result than younger people. This declining immune function is known as immunosenescence and reflects deterioration of both the acquired and innate immune systems . Declining T cell function with age arises from thymic involution and decreased thymic output, resulting in fewer naive T cells and more memory cells in the circulation . Ageing is also associated with increased inflammation in the absence of infection and has been found to predict hospitalisation and death . A number of micronutrient deficiencies have been identified as contributors to such declining immunity, and so may provide opportunities for targeted interventions to restore immune function .
5. Chronic Systemic Inflammation
Chronic systemic inflammation is a key underlying feature for a range of chronic non-communicable disease conditions such as cardiovascular disease, stroke, and autoimmune disorders such as rheumatoid arthritis. This chronic inflammation is positively correlated with aging and other co-morbidities (e.g., obesity, cardiovascular disease, insulin resistance). Interestingly, in a study in healthy adults, increasing age was found to be a risk factor for chronic systemic inflammation, independent of other risk factors such as body mass index, blood pressure, and blood lipid profiles .
The rising worldwide prevalence of obesity in children and adults is of grave concern. Obesity and over nutrition are strongly associated with chronic inflammation, metabolic perturbation, and higher risk for a number of chronic diseases including cardiovascular disease, stroke, type 2 diabetes mellitus, and chronic liver disease. This metabolism-induced inflammation associated with obesity is termed metaflammation, and the Western diet is a known risk factor [31,32]. The Western diet is characterised by a diet high in sugar, trans and saturated fats, but low in complex carbohydrates, fibre, micronutrients, and other bioactive molecules such as polyphenols and omega 3 polyunsaturated fatty acids. The mechanisms by which the Western diet predispose individuals to metaflammation are still under investigation. However, one mechanism which has been reported is the increased uptake of lipopolysaccharide (LPS, a constituent of gram-negative bacterial cells walls), from microbes in the gut because of increased gut leakiness. This LPS is sensed by cells of the innate immune system through toll-like receptor 4 (TLR4). Activation of TLR4 by LPS will induce an inflammatory response by the immune cells. Certain nutrients, notably long-chain omega 3 polyunsaturated fatty acids, can interfere with TLR4 activation and, thus, can ameliorate this inflammatory signal. Rogero et al. describe the relationship between obesity and inflammation and explores the immune pathway for this mechanism and the anti-inflammatory roles of omega 3 fatty acids in this process .
Interestingly, in juxtaposition with the review by Rogero et al. on inflammation in obesity, Dalton and colleagues report a study into systemic inflammation in individuals with the serious psychological eating disorder, anorexia nervosa . They show that in a severely undernourished state, there are indications of systemic inflammation with an increased serum concentration of IL-6 when compared with healthy control participants. IL-6 is a classically inflammatory cytokine produced by immune and other cells. Whether this inflammation is the result of the impact of undernutrition or whether the clinical condition is the result of pre-existing inflammation is a matter that remains to be determined. It has been shown that patients with clinical depression have increased systemic inflammation suggesting that inflammation may have a bearing on mental health and wellbeing .
In contrast with the Western diet, the Mediterranean diet is rich in vegetables, fruit, nuts, legumes, fish, and ‘healthy’ dietary fats. The Mediterranean diet is associated with a reduced risk of chronic disease such as cardiovascular disease, cancer, and more recently Alzheimer’s disease . A range of bioactive compounds found in fruits and vegetables have been reported to offer one explanation for the protective effect of diets rich in fruits and vegetables (e.g., Mediterranean diet) on the reduction of risk for developing non-communicable diseases attributed to chronic inflammation (e.g., cardiovascular disease). One family of molecules, which are known to have a role in regulation of inflammation are the dietary polyphenols . Yahfoufi et al. explain the mechanisms by which polyphenols can be immunomodulatory and anti-inflammatory and explore the evidence for the role of dietary polyphenols in reducing the risk of cardiovascular disease, some neurological diseases, and cancer .
6. Nutrition in the Clinical Setting
In clinical settings, acute inflammation may be a sudden, severe, and overwhelming process. If not controlled, this severe systemic inflammation results in sepsis, culminating in multiple organ failure and death. Sepsis is a major global cause of death killing approximately 6 million people per year and is estimated to be the cause of 30% of neonatal deaths . In this Special Issue of Nutrients, the role of zinc in sepsis is discussed . Zinc is known to be an important micronutrient for the immune system. It has a role as a cofactor with both catalytic and structural roles in many proteins . Even a mild deficiency in zinc has been associated with widespread defects in both the adaptive and innate immune response . During sepsis, zinc homeostasis is profoundly altered with zinc moving from the serum into the liver. Alker and Haase consider this phenomenon and the implications for therapeutic options to improve outcomes in patients presenting with sepsis .
Selenium is a trace element that, like zinc, has critical functional, structural, and enzymatic roles, in a range of proteins. Poor selenium status is associated with a higher risk for range of chronic diseases including cancer and cardiovascular disease . In addition to critical roles in many non-immune tissues within the body, selenium is important for optimal immune function. Avery and Hoffman explain the role of selenium in immunobiology and the mechanisms by which selenoproteins regulate immunity. The evidence for the significance of selenium status in infectious diseases including human immunodeficiency virus infection is reviewed .
Glutamine is a nonessential amino acid that provides an important energy source for many cell types including those involved in immune responses. It also serves as a precursor for nucleotide synthesis, particularly relevant for rapidly dividing cells such as the immune cells during an immune response. During infection, the rate of glutamine consumption by immune cells is equivalent or greater than that for glucose. Glutamine has roles in the functions of a number of immune cells including neutrophils, macrophages, and lymphocytes . In catabolic conditions (e.g., infection, inflammation, trauma), glutamine is released into the circulation, an essential process controlled by metabolic organs such as the liver, gut, and skeletal muscles. Despite this adaptation, a significant depletion of glutamine is seen in the plasma and tissues in critical illness, which has provided a rationale for the use of in clinical nutrition supplementation of critically ill patients. How glutamine homeostasis is maintained and when and how to utilise glutamine in the clinical setting is explored in a review by Cruzat et al. .
The vitamin D receptor (VDR) is a nuclear receptor that can directly affect gene expression . The presence of VDR in the majority of immune cells immediately suggests an important role for this micronutrient in immune cell activities . Furthermore, vitamin D-activating enzyme 1-α-hydroxylase (CYP27B1), which results in the active metabolite 1 α,25-dihydroxyvitamin D3 (1,25(OH)2D3), is expressed in many types of immune cells. Ligation of VDR by 1,25(OH)2D3 can elicit the production of antimicrobial proteins and influence cytokine production by immune cells [47,48]. Sassi, Tamone, and d’Amelio have reviewed the evidence for the role of the nutrient vitamin D in the innate and adaptive immune systems .
In this Special Issue of Nutrients, the collected works provide a breadth of reviews and research indicating the key influence of nutrients and nutrition on immune responses in health and disease and across the life course. Nutrients may impact directly or indirectly upon immune cells causing changes in their function or may exert effects via changes in the gut microbiome. A better understanding of the role of nutrients in immune function will facilitate the use of bespoke nutrition to improve human health.
|Posted on December 4, 2020 at 5:40 PM||comments (0)|
Speleotherapy for asthma
S Beamon 1, A Falkenbach, G Fainburg, K Linde
PMID: 11406004 DOI: 10.1002/14651858.CD001741
Background: Speleotherapy, the use of subterranean environments, is a therapeutic measure in the treatment of chronic obstructive airways diseases. It is virtually unknown in the UK or the US, but has considerable widespread use in some Central and Eastern European countries.
Objectives: To review evidence for the efficacy of speleotherapy in the treatment of asthma.
Search strategy: We searched electronic databases (Medline, Embase, Cochrane Airways group database), contacted speleotherapy centres and experts in the field, hand searched proceedings, and checked bibliographies of articles obtained to identify possible relevant publications.
Selection criteria: We included controlled clinical trials (i.e., both randomized and those not reporting the method of allocation) that compared clinical effects of speleotherapy with another intervention or no intervention in patients with chronic asthma.
Data collection and analysis: Information concerning patients, interventions, results, and methodology were extracted in standardized manner by two independent reviewers and summarized descriptively.
Main results: Three trials including a total of 124 asthmatic children met the inclusion criteria, but only one trial had reasonable methodological quality. Two trials reported that speleotherapy had a beneficial short-term effect on lung function. Other outcomes could not be assessed in a reliable manner. A further search was conducted in July 2000. One further paper was excluded (see excluded studies)
Reviewer's conclusions: The available evidence does not permit a reliable conclusion as to whether speleo-therapeutic interventions are effective for the treatment of chronic asthma. Randomized controlled trials with long-term follow-up are necessary.
Speleotherapy for asthma.
Beamon S, Falkenbach A, Fainburg G, Linde K.
Cochrane Database Syst Rev. 2000;(2):CD001741. doi: 10.1002/14651858.CD001741.
PMID: 10796665 Updated. Review.
Speleotherapy for asthma.
Beamon S, Falkenbach A, Fainburg G, Linde K.
Cochrane Database Syst Rev. 2000;(2):CD001741. doi: 10.1002/14651858.CD001741.
PMID: 10796665 Updated. Review.
Weight loss interventions for chronic asthma.
Adeniyi FB, Young T.
Cochrane Database Syst Rev. 2012 Jul 11;(7):CD009339. doi: 10.1002/14651858.CD009339.pub2.
PMID: 22786526 Review.
Manual therapy for asthma.
Hondras MA, Linde K, Jones AP.
Cochrane Database Syst Rev. 2001;(1):CD001002. doi: 10.1002/14651858.CD001002.
PMID: 11279701 Updated. Review.
Is immediate imaging important in managing low back pain?
J Athl Train. 2011 Jan-Feb;46(1):99-102. doi: 10.4085/1062-6050-46.1.99.
PMID: 21214357 Free PMC article.
Yoga for asthma.
Yang ZY, Zhong HB, Mao C, Yuan JQ, Huang YF, Wu XY, Gao YM, Tang JL.
Sao Paulo Med J. 2016 Jul-Aug;134(4):368. doi: 10.1590/1516-3180.20161344T2.
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Freidl J, Huber D, Braunschmid H, Romodow C, Pichler C, Weisböck-Erdheim R, Mayr M, Hartl A.
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|Posted on December 4, 2020 at 5:30 PM||comments (0)|
A human skull that is prominently displayed at the National Museum here has been attracting crowds and controversy in equal measure since it was first unveiled early this month. After two decades in storage, the fossilized cranium has now been identified by Brazilian scientists as the oldest human remains ever recovered in the Western Hemisphere.
The skull is that of a young woman, nicknamed Luzia, who is believed to have roamed the savannah of south-central Brazil some 11,500 years ago. Even more startling, a reconstruction of her cranium undertaken in Britain this year indicates that her features appear to be Negroid rather than Mongoloid, suggesting that the Western Hemisphere may have initially been settled not only earlier than thought, but by a people distinct from the ancestors of today's North and South American Indians.
''We can no longer say that the first colonizers of the Americas came from the north of Asia, as previous models have proposed,'' said Dr. Walter Neves, an anthropologist at the University of Sao Paulo, who made the initial discovery along with an Argentine colleague, Hector Pucciarelli. ''This skeleton is nearly 2,000 years older than any skeleton ever found in the Americas, and it does not look like those of Amerindians or North Asians.''
If the date is confirmed, the find could transform thinking about the peopling of the Americas. It may be some time before that work is completed, but meanwhile, archeologists here and abroad say the find is potentially very important.
The finds, along with recent discoveries in North America like those of the so-called Kennewick Man and Spirit Cave Man, are forcing a reassessment of long-established theories as to the settling of the Americas. Based on such evidence, Dr. Neves suggests that Luzia belonged to a nomadic people who began arriving in the New World as early as 15,000 years ago.
Luzia's Negroid features notwithstanding, Dr. Neves is not arguing that her ancestors came to Brazil from Africa in an early trans-Atlantic migration. Instead, he believes they originated in Southeast Asia, ''migrating from there in two directions, south to Australia, where today's aboriginal peoples may be their descendants, and navigating northward along the coast and across the Bering Straits until they reached the Americas.''
About one-third of Luzia's skeleton has been recovered, enough to indicate that she appears to have perished in an accident or perhaps even from an animal attack. She was in her 20's when she died, stood just under five feet tall, and was part of a group of hunter-gatherers who appear to have subsisted largely on whatever fruits, nuts and berries they came across in their meanderings, plus the occasional piece of meat.
AMER'ICAN, adjective Pertaining to America.
AMER'ICAN, noun A native of America; originally applied to the aboriginals, or copper-colored races, found here by the Europeans; but now applied to the descendants of Europeans born in America.
The name American must always exalt the pride of patriotism. - Washington