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'important points'
 
happyhealthygal Views: 8,663
Published: 13 years ago
 
This is a reply to # 1,219,011

'important points'


I mentioned and linked this article on an answer to a question about CS for HIV a while ago - I suppose it was foolishly optimistic to think that anyone might have followed the link and read it!

Important Points from the article:

1) SIZE MATTERS!

Inhibition of HIV-1 was only seen with nanoparticles that were 1-10ng, and can probably only occur by the presumed mechanism with nanoparticles smaller than 14ng.

Anyone who wants to make silver for ingestion for the purposes of treating HIV should look at the procedure these guys used – it is not just electrolysing silver in water!
Too many silver distributers either do not tell you the size of their particles, or do not provide validation for what they say. Therefore, ask the questions!

2) CONCENTRATION MATTERS!

More effective inhibition with nanoparticle concentration >25 micrograms/mL.

3) CAPPING AGENT MATTERS!

They had to use a capping agent because otherwise, they’d get large silver agglomerations instead of nanoparticles. Choice of capping agent mattered (foamy carbon was best).

4) IF IT’S SMALL ENOUGH TO GUM UP HIV, IT’S SMALL ENOUGH TO GUM UP YOUR CELLS!

This is the problem with metal nanoparticles, and it’s not necessarily because silver was the nanoparticle used here (the author of the paper believes that other nanoparticles should work equally well, although this, of course, remains to be proven). The problem is their non-specificity. If they’re small enough (and it would appear that in order to get inside HIV, they have to be very small indeed), they can get just about anywhere and it can be difficult if not impossible to get them out again. Chronic exposure is probably not a good thing, although to some it may be an acceptable risk.
In the paper, the authors reported that it was cytotoxic (moderately) to the line of T-helper cells they used.

Nanotoxicology is an emerging field, because of the challenges presented by this teeny-tiny particles.

Here’s some data (albeit mostly not the sort of in vivo data you would like, but nobody’s about to go putting these into humans to determine the LD50!)


http://ieeexplore.ieee.org/Xplore/login.jsp?url=/iel5/4160288/4144525/0416053...
(silver nanoparticles toxic to all cell lines tested, and the lethal dose was lower for healthy human cell lines than for tumor lines. LD50 for normal cells was 5-6 ppm)


http://nanoforum.nanonet.info/5th_pdf/17_s4_5.pdf?PHPSESSID=687325935ee1db6d3...
(toxicity in human pulmonary epithelial cells + macrophages: smaller silver particles more toxic than larger ones – 5nm + 20nm vs. 80 nm. Induced synthesis of reactive oxygen species, chemokines IL-8, MIF, RANTES, but not CKs TNF-a, IL-1, IL-6).



http://toxsci.oxfordjournals.org/cgi/content/full/88/2/412
(preliminary study, testing effects of nanoparticles on mammalian germlines. All were toxic in dose-dependent manner, but silver nanoparticles were the most toxic. May therefore impact upon fertility + development of offspring)


http://www.stormingmedia.us/87/8774/A877444.html
(effect on male germlines: Silver, again, most toxic to spermatogonial stem cell proliferation. At 130nm, silver wasn’t toxic to the cells, but smaller particles, even at low concentrations, were toxic – e.g. caused membrane leakage. May therefore impact male fertility – sperm counts – and development of offspring).


http://www.nanowerk.com/spotlight/spotid=3045.php
(dose-dependent toxicity on zebrafish embryos; as concentrations rise, number of normally developed fish lowers, and at critical concentrations (above .19 nM), only dead and deformed fish. Silver nanoparticles can passively diffuse into developing embryos (via chorion pore channels), and have negative effects on embryonic development (especially early).


http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCP-4GYH7NK-1&_use...
(toxicity of silver and other nanoparticles in rat liver cells: silver nanoparticles of two different sizes – 15 and 100 nm – led to a significant decrease in mitochondrial function at concentration of 5-50 micrograms/ml, whereas the other metals studied were only significantly toxic at higher doses. Also saw leakage of LDH even at lower silver concentrations, and at higher concentrations, cells became abnormal in shape and size. Concluded that the silver nanoparticles were “highly toxic” and that other metals were less so. Followup on the silver nanoparticles determined that the cytotoxicity to liver cells was probably mediated through oxidative stress – the silver depleted glutathione, reduced mitochondrial membrane potential, increased levels of reactive oxygen species).


http://www.springerlink.com/content/h2115245g02p6637/
(study of nanoparticle toxicity on pulmonary macrophages. Silver nanoparticles more cytotoxic than chrysotile asbestos or any of the nanoparticles tested at 5µ/ml.


http://www.iop.org/EJ/abstract/0957-4484/19/23/235104
(“However, the induction of reactive oxygen species (ROS), degradation of mitochondrial membrane integrity, disruption of the actin cytoskeleton, and reduction in proliferation after stimulation with nerve growth factor were found after incubation with Ag nanoparticles at concentrations of 25 µg ml-1 or greater”)

Everybody is (rightfully, imo) being very cautious with nanoparticles because they don’t want another thalidomide disaster. At the very least, I would say don’t deliberately ingest or inhale any metallic nanoparticles if you’re planning on becoming pregnant.

I’m not sure if silver nanoparticles actually have that much to do with what is sold under the name Colloidal Silver , but from the data, it would seem that for silver particles to inhibit HIV, they have to be very, very small. However, smaller silver nanoparticles appear to have far greater potential for toxicity.

5) This doesn't relate to HIV, but just wanted to mention that contrary to popular belief, bacteria can and do become resistant to silver nanoparticles and resistance can be spread via plasmids. In some cases, there may be a fitness cost to it, but there is also probably cross-resistance with other Antibiotics . The idea that there is something “special” about silver’s antimicrobial mechanism that makes resistance impossible is just plain wrong.

(HIV has one-up and one-down on bacteria when it comes to the development of resistance. The one-down is obviously that viruses cannot transfer resistance-conferring genes via plasmids. The one-up is that it replicates far faster than any bacteria ever could, and its reverse transcriiption is a very error-prone process, leading to tons of viral mutants every day. In the case of silver, the former disadvantage seems more important than the latter advantage, but this is speculation based on the proposed mechanism of action which is yet to be confirmed)

Examples of bacteria becoming silver-resistant:


http://www.pnas.org/content/96/24/13611.full.pdf


http://www.ncbi.nlm.nih.gov/pubmed/526888


http://www3.interscience.wiley.com/journal/118701549/abstract


http://www.ncbi.nlm.nih.gov/pubmed/46385


http://www.nature.com/nm/journal/v5/n2/full/nm0299_183.html
(on the mechanism by which salmonella become silver-resistant)

http://pubs.acs.org/cgi-bin/abstract.cgi/jprobs/2008/7/i06/abs/pr700646b.html


http://jb.asm.org/cgi/content/abstract/179/19/6127


http://www.springerlink.com/content/7220171q78h3207n/


http://www.ncbi.nlm.nih.gov/pubmed/17334141


It should be easy for someone with HIV to test whether a particular Colloidal Silver product is ‘doing the job’. When the virus is fully inhibited, viral load drops VERY quickly – if it’s not down to undetectable in a couple months (perhaps 90 days if the VL starts high), it’s probably not a great option.

I’ve never been thrilled about the idea of leaving virally infected cells free to replicate as much as they want, while just trying to kill most of the virions as they come out. While this might slowly drive down replication somewhat, as far as I’m concerned, you want replication stopped entirely, and don’t want any virions floating around – regardless of whether they’re non-infectious or ‘inactivated’. With HIV, most virions are not infectious anyways (a small percentage of infectious virions is still enough to keep disease progression going), but non-infectious virions are still able to cause a LOT of damage to neurons and T-cells:

http://jvi.asm.org/cgi/content/abstract/75/3/1152?maxtoshow=&HITS=10&hits=10&...


http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=387714


http://www.retrovirology.com/content/1/1/12


http://www.annalsnyas.org/cgi/content/abstract/1010/1/19


If silver nanoparticles could be made so that they were SPECIFIC to HIV, I think a lot of people, myself included, would have been more excited about this when it came out. Personally, I find the research about catalytic antibodies to a conserved region of gp120 much more interesting
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W8V-4SD1B9V-1&_use...

(popular press piece on this article, for those who prefer less Science terminology:
http://www.eatg.org/news/newsitem.php?pf=1&id=15329)


 

 
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