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Leprosy study
 Moderated by: Dr Trevor Marshall  

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Deedee
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 Posted: Tue Jan 31st, 2012 12:40

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It would seem the researchers would know that Vitamin D supplementation is contraindicated in diseases like sarcoidosis, TB, lymphoma AND LEPROSY (even by main-stream medicine)! Still, interesting info on how bacteria can cripple our immune system...

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Stealthy Leprosy Pathogen Evades Critical Vitamin D-Dependent Immune Response
ScienceDaily (Jan. 29, 2012) — A team of UCLA scientists has found that the pathogen that causes leprosy has a remarkable ability to avoid the human immune system by inhibiting the antimicrobial responses important to our defenses.
In one of the first laboratory studies of its kind, researchers discovered that the leprosy pathogen Mycobacterium leprae was able to reduce and evade immune activity that is dependent on vitamin D, a natural hormone that plays an essential role in the body's fight against infections.
The pathogen manipulated micro-RNAs, tiny molecules made of ribonucleic acids that carry information and that help regulate genes to direct cell activity, including immune system defenses. Micro-RNAs are short RNAs that do not code information for proteins, which carry out all cell activity; rather, they bind to the RNAs that do code for proteins and block them.
Published in the Jan. 29 online edition of the journal Nature Medicine, the findings demonstrate how an infectious disease pathogen like M. leprae can use micro-RNAs to impact the immune system's fight response.
"We may find that these tiny micro-RNAs can be exploited by pathogens to weaken our immune response," said the study's first author, Dr. Philip T. Liu, an assistant professor of medicine at the Orthopaedic Hospital Research Center and in the department of dermatology at the David Geffen School of Medicine at UCLA. "By better understanding how pathogens can escape our immune cells, we can design more effective therapies to boost our immune responses to these difficult to treat infections like leprosy."
Leprosy, one of the world's oldest known diseases, is a chronic infectious disease that affects the skin, the peripheral nerves, the upper respiratory tract and the eyes and can lead to disfigurement of the hands, face and feet. In 2008, approximately 249,000 new cases of leprosy were reported worldwide, according to the World Health Organization.
For the study, researchers compared the micro-RNAs in human skin lesions from two types of leprosy: tuberloid leprosy, a milder infection that is more easily contained, and lepromatous leprosy, which is more serious and causes widespread infection throughout the body.
In the lab, the scientists identified 13 micro-RNAs that differed between the two types of leprosy. The micro-RNAs that were found to be more common in lepromatous leprosy seemed to target the genes important for directing key immune system cells, including macrophages and T cells.
The team found that a particular micro-RNA, hsa-mir-21, inhibited the gene activity of the vitamin D-dependent immune pathway used to help fight infection. When researchers neutralized the activity of hsa-mir-21 in macrophages, the cells were able to kill the bacteria again.
"The leprosy pathogen was able to effectively evade the host's immune response by regulating critical immune system genes," said senior investigator Dr. Robert Modlin, UCLA's Klein Professor of Dermatology and chief of dermatology at the Geffen School of Medicine. "It's like having the enemy sending a decoy message to your combat troops and telling them to lower their weapons."
To test the significance of this micro-RNA with other infectious diseases, the researchers also introduced hsa-mir-21 to human macrophages that were then infected with tuberculosis in the lab. Researchers found that the micro-RNA similarly blocked the ability of the macrophages to kill the bacteria.
Researchers also demonstrated that immune activation of the leprosy-infected immune cells decreased the leprosy bacteria's viability four-fold -- but only when hsa-mir-21 activity was silenced. In fact, an over-expression of this micro-RNA blocked immune activity, resulting in a five-fold increase in bacterial viability.
"We were surprised at the devastating effects that even a single micro-RNA had on the ability of immune cells to fight the infections," Liu said.
In addition, the team showed that this micro-RNA was found in human immune cells only 18 hours after the onset of leprosy infection. The presence of the micro-RNA so early in the infection suggests it might play a role in actual disease development, the researchers said.
Further investigation of this single micro-RNA in leprosy may provide a framework for analyzing other micro-RNAs to help determine their cumulative role in regulating the immune response.
The micro-RNAs are small, and therefore it is possible to develop treatments which neutralize them, the researchers said.
"We may find that a combination of vitamin D supplementation with a genetically targeted therapy could provide an optimal treatment approach to leprosy and possibly other chronic infectious diseases," said Modlin, who also serves as vice chair for cutaneous medicine and dermatological research at UCLA and is a distinguished professor of medicine and of microbiology, immunology and molecular genetics.
"Vitamin D insufficiency has been associated with a number of infectious and autoimmune diseases, cardiovascular disease and cancers," Modlin added. "Our study indicates that micro-RNAs can alter human vitamin D responses and contribute to disease pathology."
Dr. Barry Bloom of Harvard University, who was not an author of this study but is part of the research team studying this field, agreed.
"Such a novel approach may be especially worth exploring in treatment of drug-resistant pathogens such as some forms of tuberculosis, where antimicrobial therapy is becoming increasingly problematic," Bloom said.
Bloom, the former dean of the faculty at Harvard's School of Public Health, is Harvard's Distinguished University Service Professor and the Jack and Joan Jacobson Professor of Public Health in the School of Public Health's department of immunology and infectious diseases and department of global health and population.
The study was funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Arthritis, Skin and Musculoskeletal Diseases, both parts of the National Institutes of Health.

Last edited on Tue Jan 31st, 2012 12:46 by Deedee



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 Posted: Tue Jan 31st, 2012 12:52

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Interesting article. Would the micro-RNA be the bacterial ligands? I'm not exactly sure how they came to the conclusion of nuking everything with vitamin D though, just when they were doing so well! :P

I found it interesting how quickly the micro-RNA could be detected, only 18 hours. Maybe some of these bacteria are not so slow acting after all?

Deb



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 Posted: Tue Jan 31st, 2012 12:54

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"I found it interesting how quickly the micro-RNA could be detected, only 18 hours. Maybe some of these bacteria are not so slow acting after all?"


Good point, Deb.

Last edited on Tue Jan 31st, 2012 12:54 by Deedee



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 Posted: Tue Jan 31st, 2012 20:00

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Micro RNA is like a protein in some ways - it interacts with RNA transcribed from genes and 'silences' it. There are other interactions, too. MicroRNA provides yet another level of complication we didn't have to deal with at the turn of the century... It is just amazing that Olmesartan just manages to get the Interactome all sorted out - even if it takes a few years :)

Biologists absolutely rely on their physician colleagues with respect to Vit D supplementation, etc. If Doc says to supplement, then they follow that advice blindly.

It is always possible that a peer reviewer asked for the comments on supplementation to be put in the paper, a peer reviewer (John White) tried to do that on my BioEssay, but I refused to modify anything... So the paper was delayed a year before it was eventually published...
 

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 Posted: Wed Feb 1st, 2012 03:14

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Dr Trevor Marshall wrote: It is just amazing that Olmesartan just manages to get the Interactome all sorted out - even if it takes a few years :)

What I find even more amazing is that the designers/creators of Olmesartan weren't even trying to make a drug that did all these things - and presumably still don't know what it's capable of.  They accidentally made the perfect drug, just happened to stumble upon the cure for chronic disease, and they don't even realize it.  Seems like a billion to one shot.  Or perhaps they know more about what Olmesartan does than they let on...



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 Posted: Wed Feb 1st, 2012 07:56

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No, Russ, they don't know, and when told, they don't believe. You see, they tried Pure Olmesartan in mice, and found it didn't work. They know that no benefit is achieved from using Olmesartan more than twice a day, or with a dose greater than 20mg (the maximum they use in Japan) because they tested it, and proved those facts without a doubt :X

One of their papers filed with the FDA says they ran tests of many, many human receptors with Olmesartan, and found it only had affinity for the Angiotensin type II receptor, nothing else...

..Trevor..
 


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